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Biomaterials with osteoinductivity are widely used for bone defect repair due to their unique structures and functions. Machine learning (ML) is pivotal in analyzing osteoinductivity and accelerating new material design. However, challenges include creating a comprehensive database of osteoinductive materials and dealing with low-quality, disparate data. As a standard for evaluating the osteoinductivity of biomaterials, ectopic ossification has been used. This paper compiles research findings from the past thirty years, resulting in a robust database validated by experts. To tackle issues of limited data samples, missing data, and high-dimensional sparsity, a data enhancement strategy is developed. This approach achieved an area under the curve (AUC) of 0.921, a precision of 0.839, and a recall of 0.833. Model interpretation identified key factors such as porosity, bone morphogenetic protein-2 (BMP-2), and hydroxyapatite (HA) proportion as crucial determinants of outcomes. Optimizing pore structure and material composition through partial dependence plot (PDP) analysis led to a new bone area ratio of 14.7 ± 7 % in animal experiments, surpassing the database average of 10.97 %. This highlights the significant potential of ML in the development and design of osteoinductive materials. This study leverages machine learning to analyze osteoinductive biomaterials, addressing challenges in database creation and data quality. Our data enhancement strategy significantly improved model performance. By optimizing pore structure and material composition, we increased new bone formation rates, showcasing the vast potential of machine learning in biomaterial design. [Display omitted] [ABSTRACT FROM AUTHOR]

Spinal cord compression is a source of pathology routinely seen in clinical practice. However, there remain unanswered questions surrounding both the understanding of pathogenesis and the best method of treatment. This arises from limited real-life testing of the mechanical properties of the spinal cord, either through cadaveric human specimens or animal testing, both of which suffer from methodological, as well as ethical, issues. To conduct a review of the literature on the mechanical properties of the spinal cord. A systematic review of the literature on the mechanical properties of the spinal cord is undertaken. All literature reporting the testing of the mechanical properties of the spinal cord. Reported physiological mechanical properties of the spinal cord. The methodological quality of the studies has been assessed within the ARRIVE guidelines using the CAMARADES framework and SYRCLE's risk of bias tool. This paper details the methodologies and results of the reported testing. We show that (1) the research quality of previous work does not follow published guidelines on animal treatment or risk of bias, (2) no standard protocol has been employed for sample preparation or mechanical testing, (3) this leads to a wide distribution of results for the tested mechanical properties, not applicable to the living human or animal, and (4) animal testing is not a good proxy for human application. The findings summarize the sum of current knowledge inherent to the mechanical properties of the spinal cord and may contribute to the development of a physical model which is applicable to the living human for analysis and testing in a controlled and repeatable fashion. Such a model would be the basis for further clinical research to improve outcomes from spinal cord compression. [ABSTRACT FROM AUTHOR]

[Display omitted] • We reviewed the literature on isolation of Toxoplasma gondii directly in cell culture. • Four experiments were reported to isolate T. gondii from different animals in Vero and HFF cell cultures. • We recommend an in vitro protocol to isolate T. gondii. • This method is simpler, more cost-effective, ethically more acceptable, and less time-sensitive. Toxoplasma gondii is an apicomplexan protozoan parasite that can infect mammals and birds. The infection can cause acute toxoplasmosis and death in susceptible hosts. Bioassay using cats and mice has been the standard for the isolation of T. gondii from infected hosts for the past several decades. However, bioassay is labor-intensive, expensive, and involves using laboratory animals. To search alternative approaches and o work towards replacement of animal experiments, we summarized the key literature and conducted four experiments to isolate T. gondii in vitro by cell culture. A few heart tissue samples from animals with the highest antibody titers in a given collection were used for T. gondii isolation. These experiments included samples from five out of 51 wild ducks, four of 46 wild turkeys, six of 24 white-tailed deer, as well as from six kangaroos that had died with acute toxoplasmosis in a zoo. These experiments resulted in three isolates from five chronically infected wild ducks (60%), four isolates from four chronically infected wild turkeys (100%), one isolate from six chronically infected white-tailed deer (17%), and four isolates from six kangaroos with acute toxoplasmosis (67%). In addition, five isolates from the five chronically infected wild ducks were obtained by bioassay in mice, showing a 100% success rate, which is higher than the 60% rate by direct cell culture. These T. gondii isolates were successfully propagated in human foreskin fibroblast (HFF) or Vero cells, and genotyped by multilocus PCR-RFLP markers. The results showed that it is practical to isolate T. gondii directly in cell culture. Although the cell culture approach may not be as sensitive as the bioassay, it does provide an alternative that is simple, cost-effective, ethically more acceptable, and less time-sensitive to isolate T. gondii. In this paper we propose a procedure that may be applied and further optimized for isolation of T. gondii. [ABSTRACT FROM AUTHOR]

• Evidence-based analysis of peri‑implant gas accumulation (PIGA). • Postoperative PIGA: common for musculoskeletal Mg implants. • Clinical relevance: potentially associated surgical complications. • Radiological techniques: for quantitative and longitudinal analysis. • Standardized evaluation needed for developing Mg implants. Historically, the rapid degradation and massive gas release from magnesium (Mg) implants resulted in severe emphysema and mechanical failure. With the advent of new alloys and surface treatment methods, optimized Mg implants have re-entered clinics since last decade with reliable performance. However, the optimization aims at slowing down the degradation process, rather than exemption of the gas release. This study involved a systematic evaluation of current preclinical and clinical evidence, regarding the physical signs, symptoms, radiological features, pathological findings and complications potentially associated with peri‑implant gas accumulation (PIGA) after musculoskeletal Mg implantation. The literature search identified 196 potentially relevant publications, and 51 papers were enrolled for further analysis, including 22 preclinical tests and 29 clinical studies published from 2005 to 2023. Various Mg-based materials have been evaluated in animal research, and the application of pure Mg and Mg alloys have been reported in clinical follow-ups involving multiple anatomical sites and musculoskeletal disorders. Soft tissue and intraosseous PIGA are common in both animal tests and clinical follow-ups, and potentially associated with certain adverse events. Radiological examinations especially micro-CT and clinical CT scans provide valuable information for quantitative and longitudinal analysis. While according to simulation tests involving Mg implantation and chemical processing, tissue fixation could lead to an increase in the volume of gas cavity, thus the results obtained from ex vivo imaging or histopathological evaluations should be interpreted with caution. There still lacks standardized procedures or consensus for both preclinical and clinical evaluation of PIGA. However, by providing focused insights into the topic, this evidence-based study will facilitate future animal tests and clinical evaluations, and support developing biocompatible Mg implants for the treatment of musculoskeletal disorders. [ABSTRACT FROM AUTHOR]

Wuji Wan (WJW) is a traditional Chinese medicine formula that can be found in the "Prescriptions of Taiping Benevolent Dispensary" that has been employed in treating gastric discomfort, burning epigastric pain, and gastric reflux for hundreds of years and has shown promise for treating gastric ulcers (GUs). However, the active components and mechanism of action against GUs remain unclear. The aim of this study was to explore the active components of WJW and elucidate the underlying mechanism involved in treating GUs. Initially, cell viability was measured by a cell counting kit 8 (CCK-8) assay to evaluate the efficacy of WJW-containing serum in vitro. The gastric ulcer index, ulcer inhibition rate, hematoxylin and staining (H&E), and periodic acid-Schiff (PAS) staining were used to evaluate the therapeutic effect of WJW in vivo. Subsequently, the levels of inflammatory factors and oxidative stress factors were determined using an enzyme-linked immunosorbent assays (ELISA) on in vitro and in vivo samples. Additionally, UPLC-Q Exactive Plus Orbitrap HRMS was used to analyze the components that were absorbed into the blood of WJW and its metabolites. Network pharmacology and metabolomics were subsequently used to identify the targets and pathways. Real-time quantitative PCR (RT‒qPCR) and Western blotting were used to verify the mRNA and protein levels of the key targets and pathways. Finally, the active components were identified by molecular docking to verify the binding stability of the components and key targets. WJW-containing serum ameliorated ethanol-induced damage in GES-1 cells and promoted cell healing. WJW-containing serum reduced IL-6, TNF-α, MDA, and LDH levels while increasing IL-10, SOD, and T-AOC levels in the cells. Moreover, WJW treatment resulted in decreased IL-6, TNF-α, and MDA levels and increased IL-10, SOD, PGE 2, and NO levels in GUs rats. In addition, eight components of WJW were absorbed into the blood. The network pharmacology results revealed 192 common targets for blood entry components and GUs, and KEGG analysis revealed that apoptosis signaling pathways were the main pathways involved in WJW activity against GUs. Metabolomic screening was used to identify 13 differential metabolites. There were 23 common targets for blood entry components, GUs, and differential metabolites, with the key targets TNF (TNF-α), AKT1, PTGS2 (COX2) and MAPK1. WJW significantly inhibited the expression of Bax, Caspase-9, Caspase-3, cleaved Caspase-9, cleaved Caspase-3, TNF-α, COX2, and p-p44/42 MAPK while promoting the expression of Bcl-2 and p-AKT1. Molecular docking revealed that the active components of WJW for the treatment of GUs are berberine, palmatine, coptisine, evodiamine, rutaecarpine, evocarpine, and paeoniflorin. WJW treatment reduces inflammation and oxidative stress injury and inhibits apoptosis signaling pathways. The main active components are berberine, palmatine, coptisine, evodiamine, rutaecarpine, evocarpine, and paeoniflorin. In this paper, we provide a new strategy for exploring the active components of traditional Chinese medicine formulas for the treatment of diseases based on target mechanisms. [Display omitted] • WJW treatment GUs potential mechanism is by inhibiting inflammation, oxidative stress injury and apoptosis signaling pathways. • Integrated network pharmacology and metabolomics identified the key targets of WJW in the treatment of GUs, namely TNF, AKT1, PTGS2 and MAPK1. • The active components in WJW for the treatment of GUs are berberine, palmatine, coptisine, evodiamine, rutaecarpine, evocarpine, and paeoniflorin. • This paper provides a new strategy for exploring the active components of traditional Chinese medicine formulas for the treatment of diseases based on target mechanisms. [ABSTRACT FROM AUTHOR]

The Shenlian formula (SL) is a Chinese medicine formula used to curb the development of atherosclerosis (AS) and cardiovascular disease in clinical practice. However, owing to the complexity of compounds and their related multiple targets in traditional Chinese medicine (TCM), it remains difficult and urgent to elucidate the underlying mechanisms at a holistic level. To investigate the intrinsic mechanisms by which SL suppresses AS progression and to gain new insight into its clinical use. We proposed a network pharmacology-based workflow to evaluate the mechanism by which SL affects AS via data analysis, target prediction, PPI network construction, GO and KEGG analyses, and a "drug-core ingredient-potential target-key pathway" network. Then, non-targeted lipidomic analysis was performed to explore the differential lipid metabolites in AS rats, revealing the possible mechanism by which SL affects atherosclerotic progression. Moreover, an AS rabbit model was constructed and gavaged for SL intervention. Serum lipid profiles and inflammatory cytokine indices were tested as an indication of the mitigating effect of SL on AS. A total of 89 bioactive compounds and 298 targets related to SL and AS, which play essential roles in this process, were identified, and a component-target-disease network was constructed. GO and KEGG analyses revealed that SL regulated metabolic pathway, lipids and atherosclerosis, the PI3K-Akt pathway, the MAPK pathway and so on. In vivo experimental validation revealed that a total of 43 different lipid metabolites regulated by SL were identified by non-targeted lipidomics, and glycerophospholipid metabolism was found to be an important mechanism for SL to interfere with AS. SL reduced the plaque area and decreased the levels of inflammatory cytokines (TNF-α and IL-4) and blood lipids (TC, TG, LDL-C, and ApoB) in HFD-induced AS models. In addition, HDL and ApoA 1 levels are increased. PLA2 and Lipin1 are highly expressed in AS model, indicating their role in destabilizing glycerophosphatidylcholine metabolism and contributing to the onset and progression of ankylosing spondylitis. Moreover, SL intervention significantly reduced the level of pro-inflammatory cytokines; significantly down-regulated NF-kB/p65 expression, exhibiting anti-inflammatory activity. The Shenlian formula (SL) plays a pivotal role in the suppression of AS progression by targeting multiple pathways and mechanisms. This study provides novel insights into the essential genes and pathways associated with the prognosis and pathogenesis of AS. [Display omitted] • The innovation of this paper lies in clarifying the therapeutic effect of SL on atherosclerosis, especially the prediction of anti-atherosclerosis active ingredients and related targets by network pharmacology tools. • The network pharmacology prediction and lipid metabolism pathway were verified by In vivo experiments, in atherosclerosis model. • SL formula intervention significantly reduced the level of pro-inflammatory cytokines; significantly down-regulated NF-kB/p65 expression, exhibiting anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

The essential oil (EO) obtained from hemp (Cannabis sativa L.) biomass is rich of bioactive constituents and its oral administration can be valuable. In this paper two different hemp EOs were orally administered to CD1 mice. One EO, obtained from the fresh plant material, resulted rich in monoterpenes (monoterpene rich oil, MRO) and the other, obtained from the dried biomass, contained mainly sesquiterpenes and CBD (sesquiterpene rich oil, SRO). The blood levels of the most abundant constituents were evaluated in the animals 30 and 90 min after oral administration of hemp EOs. Furthermore, compounds were also measured in brain, liver, kidney, spleen, and cecum content to evaluate their tissue distribution at the same times. Results showed the easy absorption and the ability of the major hemp EOs constituents to reach brain, liver, and kidney. Oral administration of MRO resulted in blood levels of monoterpenes in the range 45–115 ng/g at 30 min and significant tissue distribution with the detection of monoterpenes in brain, liver, and kidney. Oral administration of SRO resulted in blood levels, at 30 min, in the range 70–80 ng/g of sesquiterpenes and 139 ng/g of CBD. The compounds are still detectable in blood and brain 90 min after oral administration and significant concentrations of terpenoids are observed in liver and kidney. MRO and SRO can be considered as valuable sources of these bioactive compounds and further investigations are needed to evaluate the potential uses of hemp EO as constituent of innovative drug formulations. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • We propose a decision logic to identify thyroid disruption in aquatic vertebrates. • The decision logic is evidence-based and includes internationally agreed guidelines. • Thyroid-mediated effect patterns must consider consistency and directions of changes. • The weight-of-evidence considers mode-of-action and population relevance assessments. • The decision logic supports regulatory assessments while minimising animal testing. According to the World Health Organisation and European Commission definitions, substances shall be considered as having endocrine disrupting properties if they show adverse effects, have endocrine activity and the adverse effects are a consequence of the endocrine activity (using a weight-of-evidence approach based on biological plausibility), unless the adverse effects are not relevant to humans or non-target organisms at the (sub)population level. To date, there is no decision logic on how to establish endocrine disruption via the thyroid modality in non-mammalian vertebrates. This paper describes an evidence-based decision logic compliant with the integrated approach to testing and assessment (IATA) concept, to identify thyroid-mediated effect patterns in aquatic vertebrates using amphibians as relevant models for thyroid disruption assessment. The decision logic includes existing test guidelines and methods and proposes detailed considerations on how to select relevant assays and interpret the findings. If the mammalian dataset used as the starting point indicates no thyroid concern, the Xenopus Eleutheroembryonic Thyroid Assay allows checking out thyroid-mediated activity in non-mammalian vertebrates, whereas the Amphibian Metamorphosis Assay or its extended, fixed termination stage variant inform on both thyroid-mediated activity and potentially population-relevant adversity. In evaluating findings, the response patterns of all assay endpoints are considered, including the direction of changes. Thyroid-mediated effect patterns identified at the individual level in the amphibian tests are followed by mode-of-action and population relevance assessments. Finally, all data are considered in an overarching weight-of-evidence evaluation. The logic has been designed generically and can be adapted, e.g. to accommodate fish tests once available for thyroid disruption assessments. It also ensures that all scientifically relevant information is considered, and that animal testing is minimised. The proposed decision logic can be included in regulatory assessments to facilitate the conclusion on whether substances meet the endocrine disruptor definition for the thyroid modality in non-mammalian vertebrates. [ABSTRACT FROM AUTHOR]

In this paper, the co-pyrolysis of blends of animal manure (AM) and high-density polyethylene (HDPE) waste was investigated using micro-thermal analysis techniques. Thermogravimetry coupled with Fourier-transform infrared spectroscopy was used to study the process kinetics and potential synergistic effects during co-pyrolysis. Dynamic co-pyrolysis experiments of animal manure (AM) and polyethylene (PE) blends in proportions of (90:10 %) and (80:20 %) were conducted at heating rates of 5, 10, 15, and 20 °C/min under an N 2 atmosphere. The process was analyzed and compared to the results obtained in the pyrolysis of pure components. AM and PE co-pyrolysis exhibited a synergic effect on the pyrolysis process, leading to a favorable change in the CPI pyrolysis initiation index. This was observed in the FTIR, shifting maximum devolatilization peaks by 14 °C towards lower temperatures and a lower activation energy of the main pyrolysis stage, with a decrease from 341.49±4.65 kJ/mol to 273.04±6.93 kJ/mol after the addition of 20 wt% PE to the blend. During co-pyrolysis, the main compounds observed in the FTIR absorption spectra were CO 2 , CO, CH 4 , NH 3 , and aromatic hydrocarbons from AM pyrolysis. Additionally, there was an increase in CH 4 and short-chain hydrocarbons due to the PE pyrolysis. • Co-processing of animal and plastic waste via pyrolysis using TG-FTIR was examined. • Addition of plastics to the animal waste changed CPI over 40 %. • 20 % addition of plastic lower energy activation of main pyrolysis stage by 25 %. • Four independent reaction kinetic models of the AM-PE co-pyrolysis were observed. [ABSTRACT FROM AUTHOR]

• In this paper, we found that senescent mice develop pathologies such as obesity lipid metabolism disorders. • The expression of miR-743b-3p was elevated in senescent mice, which inhibited the expression of PPM1K. • MiR-743b-3p regulates BCAA levels in senescent hepatocytes by targeting PPM1K causing abnormal lipid deposition. Lipid metabolism disorders appear to play an important role in the ageing process, thus understanding the cellular and molecular mechanisms underlying the association of ageing with elevated vulnerability to lipid metabolism related diseases is crucial towards promoting quality of life in old age. MicroRNAs (miRNAs) have emerged as crucial regulators of lipid metabolism, and some miRNAs have key roles in ageing. In this study, we investigated changes in liver lipid metabolism of ageing mice and the mechanisms of the altered expression of miRNAs in the ageing liver which contributes to the age-dependent increase in lipid synthesis. Here we found that miR-743b-3p was higher expressed in the liver tissues of ageing mice through the small RNA sequencing and bioinformatics analysis, and its target PPM1K was predicted and confirmed the target relationship of miR-743b-3p with PPM1K in the aged mouse liver tissues and the cultured senescent hepatocytes in vitro. Moreover, using the transfected miR-743b-3p mimics/inhibitors into the senescent hepatocyte AML12. We found that miR-743b-3p inhibition reversed the hepatocyte senescence, and finally decreased the expression of genes involved in lipid synthesis(Chrebp, Fabp4, Acly and Pparγ) through increasing the target gene expression of PPM1K which regulated the expression of branched-chain amino acids (BCAA) metabolism-related genes (Bckdhα, Bckdk, Bcat2, Dbt). These results identify that age-induced expression of miR-743b-3p inhibits its target PPM1K which induces BCAA metabolic disorder and regulates hepatocyte lipid accumulation during ageing. [Display omitted] [ABSTRACT FROM AUTHOR]

Animal experimentation has long been an integral part of biomedical and cosmetics research, with historical roots dating back to ancient Greece. During that period, physicians constrained by cultural taboos that forbade the use of human cadavers, turned to the dissection of animals for their anatomical studies. The use of specific animal models in research has often been justified by the remarkable biological similarities between animals and humans. However, there are instances where animal models, such as fish and frogs, are used, despite significant disparities in their anatomy and physiology compared to humans. In herbal medicine research, animal experimentation has found various applications. Numerous plant species from diverse global regions, including the United Kingdom, United States, China, India, and Africa, have been studied to identify their pharmacological properties and therapeutic indications. Nevertheless, the use of animals in these studies, while offering undeniable advantages, remains a subject of intense debate and contention, mainly arising from the ethical challenges it presents, as well as the substantial financial burden it imposes, and its inability to reliably predict human responses. This paper, therefore, proposes a comprehensive list of research methodologies that are ethical, practical, cost-effective, and consistent with the real ethos of herbal medicine. These alternative methods, which include in vitro studies, human cell cultures, computational modelling, culturally sensitive clinical trials, and ethnobotanical surveys, have the potential to provide cost-effective healthcare solutions, without subjecting animals to unnecessary suffering. [ABSTRACT FROM AUTHOR]

Stable delivery of liquids to microfluidic systems is essential for their reproducible functioning, especially when supplying flows to organs-on-chips – delicate living models that recreate human physiology on the microscale and thus can be used to reduce the need for animal testing. Most flow control systems are unable to sustain a robust and stable flow in longer experiments (>1 week), particularly those based on the ubiquitous syringe pump. Though easy to use, syringe pumps have no mechanism for actually measuring flow, let alone flow regulation with sensor feedback. We have developed a liquid delivery system based on the generation of flow by applying a constant air pressure to liquids in sealed containers. A flow of liquid is monitored by accurate measurement of mass flows (mg/min) using downstream Coriolis-based mass flow sensors. Measured mass flows provide fast feedback to integrated valves, with valves opening or closing slightly to increase or decrease solution flows to the organs-on-chips as required. This mass flow sensing principle is not affected by changes in the density, temperature, and viscosity of the liquids being displaced. This is in contrast to systems that use volumetric flow sensors, which require recalibration when these parameters change. The rationale behind using this principle for organs-on-chips, is that the stability provided by this flow control system allows for more control over growth of these mini-organs. We demonstrate the functionality of this system with three examples: 1) Fast stabilization (within seconds) under changing physical conditions; 2) Short-term stability (minutes to hours) of delivered flows in a microreactor with interconnected inlets; and 3) Long-term stability (>1 week) of cell medium flows to a living organ-on-a-chip. Two categories of organs-on-chips (OOCs) can be distinguished: 1) solid OOC are designed for three-dimensional cell or tissue constructs that interact with each other and their surroundings, and 2) barrier-type OOC contain a selective cellular barrier between two compartments as do many barriers in the body. The latter of these two types is the most challenging to culture and maintain as they are very sensitive to variations in flow and pressure surges. The flow control system presented in this work provides a great improvement compared to the use of syringe pumps and volumetric flow sensors in OOC studies. The novelty of this work lies in the long-term stability use of this system for organs-on-chips, maintaining stability for short to very long periods of time without compromising the barrier function of the organ-on-chip by pressure surges, bacterial contamination, or other undesired effects from the flow delivery system. • Stable flows are required for long-term (>1 week) organ-on-chip experiments. • This paper describes a flow control system based on Coriolis mass flow sensors. • Stable flows for long operation times, with varying conditions (viscosity, density). • Flow stability needed for optimal control of cell culture conditions. [ABSTRACT FROM AUTHOR]

• Proposed a parallel tapered seven-core fiber biosensor based on the vernier effect for AKT protein detection. • Ultra-low limit of detection of 44 pg/mL is achieved. • Detection of AKT protein in human embryonic kidney cell lysate compared with western blotting method. • The PTSCF biosensor has great stability, ultrahigh sensitivity and excellent specificity. The AKT protein is closely related to the cancer and diabetes. Rapid detection of AKT is very important in medical diagnosis. This paper proposed a parallel connected tapered seven-core fiber (PTSCF) biosensor to utilize vernier effect to improve sensitivity. Experimental results showed that 5.99 times improvements have been achieved in the refractive index sensing in the ranges of 1.333–1.337. By functionalizing AKT-Ab on the PTSCF sensor surface, a fast detection (<40 min) and an ultra-low limit of detection (LoD) of 0.044 ng/mL have been achieved for AKT protein solutions. The proposed PTSCF biosensor has been applied to detect AKT proteins in human embryonic kidney cell lysates and compared with those obtained by the western blotting (WB) method. Experimental results showed that the LoD of the PTSCF biosensor is 400-fold less than that of WB method. The proposed PTSCF biosensor holds great potential for applications in various medical fields, including intra-operative rapid detection, animal experiments, and pathological research. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cell metabolomics is a reliable and efficient tool to study PFAS toxicity. • Diverse cell types show non-specific and specific responses to PFAS. • Cell metabolomics approach revealed pathways associated with PFAS effects. • Cell metabolomics studies identified potential biomarkers linked to PFAS effects. Per- and polyfluoroalkyl substances (PFAS), ubiquitous environmental contaminants, pose significant challenges to ecosystems and human health. While cell cultures have emerged as new approach methodologies (NAMs) in ecotoxicity research, metabolomics is an emerging technique used to characterize the small-molecule metabolites present in cells and to understand their role in various biological processes. Integration of metabolomics with cell cultures, known as cell culture metabolomics, provides a novel and robust tool to unravel the complex molecular responses induced by PFAS exposure. In vitro testing also reduces reliance on animal testing, aligning with ethical and regulatory imperatives. The current review summarizes key findings from recent studies utilizing cell culture metabolomics to investigate PFAS toxicity, highlighting alterations in metabolic pathways, biomarker identification, and the potential linkages between metabolic perturbations. Additionally, the paper discusses different types of cell cultures and metabolomics methods used for studies of environmental contaminants and particularly PFAS. Future perspectives on the combination of metabolomics with other advanced technologies, such as single-cell metabolomics (SCM), imaging mass spectrometry (IMS), extracellular flux analysis (EFA), and multi-omics are also explored, which offers a holistic understanding of environmental contaminants. The synthesis of current knowledge and identification of research gaps provide a foundation for future investigations that aim to elucidate the complexities of PFAS-induced cellular responses and contribute to the development of effective strategies for mitigating their adverse effects on human health. [ABSTRACT FROM AUTHOR]

Sophora flavescens Ait.- Angelica sinensis (Oliv.) Diels drug pairing (SA) is a transformed drug pairing from Shengui pill, a traditional Chinese medicine prescription in the ninth volume of Traditional Chinese Medicine classic "Gu Jin Yi Jian", which is famous for clearing heat, moistening dryness, and promoting blood circulation. It is commonly used in the treatment of eczema, a skin condition that causes itching and inflammation. Despite its widespread use, there is still limited research on the mechanism of how SA treats eczema. This paper aims to fill this gap by conducting animal experiments to uncover the mechanism behind SA's therapeutic effects on eczema. Our findings provide a solid foundation for the clinical use of this TCM prescription. The basic purpose of this study is to clarify the therapeutic mechanism of Sophora flavescens-Angelica sinensis (SA) in the treatment and control of eczema. The chemical compositions of SA were analyzed using HPLC-Q-Orbitrap-MS. In vivo, a mouse model of eczema was created, and the serum levels of TNF-α and IL-1β were quantified using an enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (HE) staining was performed to assess the pathological state of the mouse skin, and immunohistochemical technique (IHC) was employed to estimate the contents of TNF-α, TLR4, and NF-κB semi-quantitatively. The expression levels of TLR4, MyD88, and NF-κB mRNA were determined through real-time quantitative polymerase chain reaction (qRT-PCR). Western Blotting was utilized to identify the protein levels of TLR4, MyD88, and NF-κB in mouse skin tissue. SA identified 18 active chemicals, some of which were shown in vivo to inhibit the TLR4/MyD88/NF-κB signaling pathway while reducing serum levels of TNF-α and IL-1β, making them ideal agents for the treatment of eczema. SA's anti-inflammatory properties are attributed to its ability to reduce serum levels of TNF-α and IL-1β, likewise inhibit the TLR4/MyD88/NF-κB signaling pathway. [Display omitted] • Application of SG in the treatment of acute eczema. • Study on the mechanism of SG in the treatment of acute eczema for the first time. • The experiments were carried out in vivo. • The results showed that SG could reduce the expression of IL-1β and TNF-α. • The anti-inflammation effect of SG is mediated by TLR4/MyD88/NF-κB signal pathway. [ABSTRACT FROM AUTHOR]

Cholestatic liver injury (CLI) is a pathologic process with the impairment of liver and bile secretion and excretion, resulting in an excessive accumulation of bile acids within the liver, which leads to damage to both bile ducts and hepatocytes. This process is often accompanied by inflammation. Cucumis melo L is a folk traditional herb for the treatment of cholestasis. Cucurbitacin B (CuB), an important active ingredient in Cucumis melo L, has significant anti-inflamamatory effects and plays an important role in diseases such as neuroinflammation, skin inflammation, and chronic hepatitis. Though numerous studies have confirmed the significant therapeutic effect of CuB on liver diseases, the impact of CuB on CLI remains uncertain. Consequently, the objective of this investigation is to elucidate the therapeutic properties and potential molecular mechanisms underlying the effects of CuB on CLI. The aim of this paper was to investigate the potential protective mechanism of CuB against CLI. First, the corresponding targets of CuB were obtained through the SwissTargetPrediction and SuperPre online platforms. Second, the DisGeNET database, GeneCards database, and OMIM database were utilized to screen therapeutic targets for CLI. Then, protein-protein interaction (PPI) was determined using the STRING 11.5 data platform. Next, the OmicShare platform was employed for the purpose of visualizing the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The molecular docking technique was then utilized to evaluate the binding affinity existing between potential targets and CuB. Subsequently, the impacts of CuB on the LO2 cell injury model induced by Lithocholic acid (LCA) and the CLI model induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) were determined by evaluating inflammation in both in vivo and in vitro settings. The potential molecular mechanism was explored by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) techniques. A total of 122 CuB targets were collected and high affinity targets were identified through the PPI network, namely TLR4, STAT3, HIF1A, and NFKB1. GO and KEGG analyses indicated that the treatment of CLI with CuB chiefly involved the inflammatory pathway. In vitro study results showed that CuB alleviated LCA-induced LO2 cell damage. Meanwhile, CuB reduced elevated AST and ALT levels and the release of inflammatory factors in LO2 cells induced by LCA. In vivo study results showed that CuB could alleviate DDC-induced pathological changes in mouse liver, inhibit the activity of serum transaminase, and suppress the liver and systemic inflammatory reaction of mice. Mechanically, CuB downregulated the IL-6, STAT3, and HIF-1α expression and inhibited STAT3 phosphorylation. By combining network pharmacology with in vivo and i n vitro experiments, the results of this study suggested that CuB prevented the inflammatory response by inhibiting the IL-6/STAT3/HIF-1α signaling pathway, thereby demonstrating potential protective and therapeutic effects on CLI. These results establish a scientific foundation for the exploration and utilization of natural medicines for CLI. [Display omitted] • Targets of CuB treatment for cholestasis are enriched in the inflammatory pathway. • STAT3 and HIF-1α are key targets. • CuB alleviates cholestasis-induced liver damage and inflammatory reactions. • CuB prevents cholestasis by inhibiting the IL-6/STAT3/HIF-1α signaling pathway. [ABSTRACT FROM AUTHOR]

Erigeron breviscapus is a common medicine of eight ethnic minorities, including Miao, Naxi, and Yi. As early as the Ming Dynasty (AD 1368–1644), Lanmao's Materia Medica of Southern Yunnan (AD 1436) recorded that the medicine is used for the treatment of "Zuo tan you huan." In modern pharmacological research, Erigeron breviscapus injection is the most commonly used preparation in the treatment of ischemic stroke caused by acute cerebral infarction, but its mechanism of action in the treatment of ischemic stroke is not well understood. In this study, a metabonomics study based on ultraperformance liquid chromatography–quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) was used in investigating the effect of a traditional Chinese medicine preparation Erigeron breviscapus injection on the rat model of focal cerebral ischemia-reperfusion and the affinity of its main components with the targets of mitochondrial apoptotic pathways. This study used molecular docking technology to verify the effective binding ability of main effective components of Erigeron breviscapus injection to target proteins related to mitochondrial apoptosis pathway. This study developed a metabonomics method based on the ultra-performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry (UPLC Q-TOF MS) to evaluate the efficacy and study the mechanism of traditional Chinese medicine preparation. With pattern recognition analysis (principal component analysis and partial least squares-discriminate analysis) of urinary metabolites, a clear separation of focal cerebral ischemia-reperfusion model group and healthy control group was achieved. Erigeron breviscapus injection can significantly reduce the area of cerebral infarction, improve tissue morphological lesion in rats, and can increase the number of Nissl bodies. It may be a promoting factor by inhibiting hippocampal nerve cell apoptosis and Bax protein expression and by exerting effects against ischemia reperfusion after the induction of apoptosis. Thus, it plays a role in brain protection. Moreover, it can considerably promote the recovery of neurological deficiency signs in advance. Meanwhile, Erigeron breviscapus decreased malondialdehyde content and T-NOS activity. Its curative effect from strong to weak order: low dose > high dose > medium dose. The representative components of Erigeron breviscapus have good affinity with the active sites of mitochondrial apoptosis-related proteins. Metabolomics found that the potential biomarkers regulated by breviscapine are kynurequinolinic acid, succinylornithine, and leucine proline. It is speculated that it may participate in TRP–kynurequinolinic acid and succinylornithine–urea cycle–NO metabolic pathways. This paper revealed the potential biomarkers and metabolic pathways regulated by Erigeron breviscapus. It was speculated that the mechanism is related to its inhibition of mitochondrion-mediated apoptosis. Erigeron breviscapus could restore the metabolic profiles of the model animals to normal animal levels. The mechanism may be related to the potential biomarkers of quinolinic acid, succinylornithine, and leucine proline and the metabolic pathways involved. However, the exact mechanism by which Erigeron breviscapus inhibits mitochondrion-mediated apoptosis remains to be further explored. [Display omitted] • The metabolic profile of cerebral ischemia-reperfusion injury model rats regulated by Breviscapus injection were revealed. • A new method of metabolomics combined with pharmacodynamics to evaluate the effectiveness of ethnomedicine was explored. • Erigeron breviscapus has high research value. • Erigeron breviscapus is a common medicine of eight ethnic minorities, such as the Miao, Naxi and Yi nationalities. [ABSTRACT FROM AUTHOR]

Licorice can nourish Pi (spleen) and thereby strengthening the digestive system according to the theory of traditional Chinese medicine. Licorice has been generally used in the compound prescription to treat intestinal inflammatory disease. Licochalcone A (Lico A) is one of the characteristic molecules from licorice. T-UCRs, which are transcribed from ultraconserved regions, are a new class of long noncoding RNAs related to the renewal of intestinal epithelial renewal. This study aimed to investigate the effect and the uc.173-related mechanism of Lico A on intestinal epithelial renewal. IE-6 and Caco-2 cells were used to evaluate the effect of Lico A on apoptosis, proliferation, and migration of IECs. The intestinal organoid was used to investigate ex vivo effect and mechanism of Lico A promoting intestinal organoid development. C57BL/6J mice (both normal and uc.173-deficient ones) were used to examine the in vivo effect of Lico A on the renewal of intestinal mucosa. The expression of three T-UCRs related to the intestinal mucosa renewal was altered in Lico A-treated IECs. Lico A promoted the proliferation and inhibited the apoptosis of IECs through uc.173/miR-195 pathway. The development of intestinal organoids and the renewal of intestinal mucosa of mice subjected to the 48-h FAST were all promoted by the treatment of Lico A. Moreover, the growth arrest of uc.173-deficient intestinal organoids and the atrophy of intestinal mucosa in uc.173-deficient mice could be rescued by the Lico A administration. Results in this paper suggest that targeting T-UCRs may be the novel therapeutic approach for the promotion of epithelial regeneration, and through stimulating the regeneration of intestinal mucosa, Lico A may become a new therapeutic agent for the maintenance of intestinal epithelial integrity. Licochalcone A promotes intestinal epithelial renewal through uc.173. [Display omitted] • Licochalcone A from licorice affects the expression of three T-UCRs related to the regeneration of intestinal mucosa. • Licochalcone A promotes the development of intestinal organoids and in vivo renewal of intestinal mucosa. • Licochalcone A reverses uc. 173-induced delay in intestinal epithelial renewal both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Tight control of systemic oxygenation is a key component of mechanical ventilation of critically ill patients. Yet, closed-loop control remains challenging due to the non-linear, uncertain, and time-varying relationship between the inspired oxygen and the resulting patient's oxygen saturation, especially in cases of acute lung injury. This paper uses a Hammerstein model to combine a clinically validated static model incorporating ventilation-to-perfusion mismatch with uncertain linear dynamics to synthesize a robust closed-loop controller for regulating systemic oxygenation in subjects with acute lung injury. Data from an experimental lung injury model in five pigs, in combination with data augmentation, allowed modeling of the uncertainty in the system. Subsequently, gain-scheduled proportional–integral controllers were designed using the mixed-sensitivity H ∞ approach. The resulting closed-loop systems were analyzed for robust stability, and the performance was evaluated in a thousand synthetically generated subjects spanning the overall parameter space in various combinations. A mean rise time of less than three minutes was achieved for recovering from the severely hypoxemic state for simulated subjects with a range of ventilation-to-perfusion mismatch and arterial acid–base status. Furthermore, the results from a pilot animal experiment matched the simulated results well, and the system could respond to significant disturbances. The system was safe and reliable in both simulations and the pilot animal experiment. The methodological approach for uncertainty modeling and controller synthesis is an essential step toward the practical deployment of closed-loop control of systemic oxygenation in the acutely injured lung. [Display omitted] • Development of a Hammerstein model for systemic oxygenation in an acutely injured lung. • Parameter estimation and data augmentation to model the uncertainty of the system. • Robust controller synthesis and analysis of closed-loop oxygenation control. • Large uncertainties in open-loop gain and time constants limit controller performance, but stable controllers can be synthesized for the proposed subject populations. [ABSTRACT FROM AUTHOR]

Radiotherapy for massive tumors is a major problem in tumor radiotherapy today. Our research group found that partial stereotactic ablation (P-SABR) with local high-dose irradiation and whole low-dose irradiation has achieved ideal clinical results, but its specific mechanism is still unclear. In recent years, this study aimed to explore the immunological explanation of the therapeutic effect of P-SABR. Using C57BL/6j mouse MC38 subcutaneous tumor model, the clinical treatment was simulated by giving P-SABR or SBRT. The tumor center was given 9Gy/f, 3 fractions, and the tumor periphery was given 3Gy/f, 6 fractions. The tumor growth curve and mouse survival curve were drawn to evaluate the similarity of animal experiments to clinical efficacy. We designed and made a new type of lead box to complete P-SABR on subcutaneous tumor of mice and protect normal tissues at the same time, and explored whether animal experiments can complete the central dose of P-SABR in dose distribution by using X-ray imaging film. The distribution of NETosis and CD8+T cells was explored by immunofluorescence of tumor specimen slices after radiotherapy. Whether P-SABR is CD8+T cell-dependent was explored by immune cell deletion experiment, we further investigated the in vivo distribution of 68Ga grazytracer in MC38 tumor–bearing mice pretreated with P-SABR. 68Ga-grazytracer uptake was highest 1 hour after injection. P-SABR has similar curative effect to SBRT in animal model. P-SABR produced a large number of NETs in the tumor center, and CD8+T cells were distributed around the NETs. CD8+T cell deletion significantly reduced the efficacy of P-SABR, while NK cell or CD4+T cell deletion did not produce significant effects. P-SABR increased granzyme B levels during in tumor. In conclusion, animal experiments well restored the clinical efficacy of P-SABR. P-SABR produced a large number of NETs in tumor and hindered the infiltration of CD8+T cells. The therapeutic effect of P-SABR depends on the existence and activation of CD8+T cells. [ABSTRACT FROM AUTHOR]