Polyphyllin I induces rapid ferroptosis in acute myeloid leukemia through simultaneous targeting PI3K/SREBP-1/SCD1 axis and triggering of lipid peroxidation.

Acute myeloid leukemia (AML) is a malignant disease that is difficult to completely cure. Polyphyllin I (PPI), a steroidal saponin isolated from Paris polyphylla, has exhibited multiple biological activities. Here, we discovered the superior cytotoxicity of PPI on AML cells MOLM-13 with an IC50 values of 0.44 ± 0.09 µM. Mechanically, PPI could cause ferroptosis via the accumulation of intracellular iron concentration and triggering lipid peroxidation. Interestingly, PPI could induced stronger ferroptosis in a short time of about 6 h compared to erastin. Furthermore, we demonstrate that PPI-induced rapid ferroptosis is due to the simultaneous targeting PI3K/SREBP-1/SCD1 axis and triggering lipid peroxidation, and PI3K inhibitor Alpelisib can enhance the activity of erastin-induced ferroptosis. Molecular docking simulations and kinase inhibition assays demonstrated that PPI is a PI3K inhibitor. In addition, PPI significantly inhibited tumor progression and prolonged mouse survival at 4 mg/kg with well tolerance. In summary, our study highlights the therapeutic potential of PPI for AML and shows its unique dual mechanism.

TaoHe ChengQi decoction ameliorates sepsis-induced cardiac dysfunction through anti-ferroptosis via the Nrf2 pathway.

BACKGROUND: Sepsis-induced cardiac dysfunction (SICD) is a serious complication of sepsis that is associated with increased mortality. Ferroptosis has been reported in the SICD. TaoHe ChengQi decoction (THCQD), a classical traditional Chinese medicinal formula, has multiple beneficial pharmacological effects. The potential effects of THCQD on the SICD remain unknown. PURPOSE: To investigate the effect of THCQD on SICD and explore whether this effect is related to the regulation of myocardial ferroptosis through nuclear factor erythroid 2-related factor 2 (Nrf2) activation. METHODS: We induced sepsis in a mouse model using cecal ligation and puncture (CLP) and administered THCQD (2 and 4 g/kg) and dexamethasone (40 mg/kg). Mice mortality was recorded and survival curves were plotted. Echocardiography, hematoxylin and eosin staining, and analysis of serum myocardial injury markers and inflammatory factors were used to evaluate cardiac pathology. Myocardial ferroptosis was detected by quantifying specific biomarker content and protein levels. Through HPLC-Q-Exactive-MS analysis, we identified the components of the THCQD. Network pharmacology analysis and Cellular Thermal Shift Assay (CETSA) were utilized to predict the targets of THCQD for treating SICD. We detected the expression of Nrf2 using Western blotting or immunofluorescence. An RSL3-induced ferroptosis model was established using neonatal rat cardiomyocytes (NRCMs) to further explore the pharmacological mechanism of THCQD. In addition to measuring cell viability, we observed changes in NRCM mitochondria using electron microscopy and JC-1 staining. NRF2 inhibitor ML385 and Nrf2 knockout mice were used to validate whether THCQD exerted protective effects against SICD through Nrf2-mediated ferroptosis signaling. RESULTS: THCQD reduced mortality in septic mice, protected against CLP-induced myocardial injury, decreased systemic inflammatory response, and prevented myocardial ferroptosis. Network pharmacology analysis and CETSA experiments predicted that THCQD may protect against SICD by activating the Nrf2 signaling pathway. Western blotting and immunofluorescence showed that THCQD activated Nrf2 in cardiac tissue. THCQDs consistently mitigated RSL3-induced ferroptosis in NRCM, which is related to Nrf2. Furthermore, the pharmacological inhibition of Nrf2 and genetic Nrf2 knockout partially reversed the protective effects of THCQD on SICD and ferroptosis. CONCLUSION: The effect of THCQD on SICD was achieved by activating Nrf2 and its downstream pathways.

1H-NMR-based metabolomics to dissect the traditional Chinese medicine promotes mesenchymal stem cell homing as intervention in liver fibrosis in mouse model of Wilson's disease.

BACKGROUND: We administered Bushen Huoxue Huazhuo Formula (BSHXHZF) and transplanted bone marrow mesenchymal stem cells (BMSCs) into mice with Wilson's disease (WD)-related liver fibrosis to evaluate the liver-protecting mechanism of this prescription. METHODS: Mice, randomly divided into different treatment groups, showed histopathological changes and degree of hepatocyte apoptosis. For hepatic hydroxyproline (Hyp) determination, transforming growth factor-ß1 (TGF-ß1) and bone morphogenetic protein-7 (BMP-7) mRNA and protein were measured. Chemical profiling of the extract of BSHXHZF using The liquid chromatography-mass spectrometry (LC-MS/MS) and revealing its antifibrosis mechanism using metabolomics. RESULTS: TCM+BMSC group livers exhibited few inflammatory cells. TUNEL revealed abundant brown apoptotic cells in model control groups, while the TCM+BMSC groups showed a significant increase in blue negative expression of liver cells. Hyp in toxic milk (TX) mice groups was significantly lower than that in model control groups (MG). Compared with MG, TGF-ß1 expression was significantly lower than all other groups, while BMP-7 expression was significantly higher. Metabolic analysis identified 20 potential biomarkers and 10 key pathways, indicating that BSHXHZF+BMSC intervention has a significant regulatory effect on metabolic disorders of these small molecule substances. CONCLUSION: BSHXHZF combined with BMSCs can inhibit liver fibrosis and hepatocyte apoptosis by improving related metabolic disorders, and achieving therapeutic effects in WD-related liver fibrosis.

Isobavachalcone, a natural sirtuin 2 inhibitor, exhibits anti-triple-negative breast cancer efficacy in vitro and in vivo.

Triple-negative breast cancer (TNBC) is the most aggressive and lethal clinical subtype and lacks effective targeted therapies at present. Isobavachalcone (IBC), the main active component of Psoralea corylifolia L., has potential anticancer effects. Herein, we identified IBC as a natural sirtuin 2 (SIRT2) inhibitor and characterized the potential mechanisms underlying the inhibition of TNBC. Molecular dynamics analysis, enzyme activity assay, and cellular thermal shift assay were performed to evaluate the combination of IBC and SIRT2. The therapeutic effects, mechanism, and safety of IBC were analyzed in vitro and in vivo using cellular and xenograft models. IBC effectively inhibited SIRT2 enzyme activity with an IC50 value of 0.84 ± 0.22 µM by forming hydrogen bonds with VAL233 and ALA135 within its catalytic domain. In the cellular environment, IBC bound to and stabilized SIRT2, consequently inhibiting cellular proliferation and migration, and inducing apoptosis and cell cycle arrest by disrupting the SIRT2/α-tubulin interaction and inhibiting the downstream Snail/MMP and STAT3/c-Myc pathways. In the in vivo model, 30 mg/kg IBC markedly inhibited tumor growth by targeting the SIRT2/α-tubulin interaction. Furthermore, IBC exerted its effects by inducing apoptosis in tumor tissues and was well-tolerated. IBC alleviated TNBC by targeting SIRT2 and triggering the reactive oxygen species ROS/ß-catenin/CDK2 axis. It is a promising natural lead compound for future development of SIRT2-targeting drugs.

Pachymaran Alleviates Acute Gouty Arthritis by Inhibiting NLRP3 Inflammasome Activation and Pyroptosis.

Objective: Acute gouty arthritis is the most common rheumatic diseases, and leads to a heavy clinical burden, thereby to explore the treatment effects of pachymaran on acute gouty arthritis and elucidate its mechanism are meaningful. Methods: Eighteen SPF C57BL/6 mice were randomly divided into three groups: the sham group, model group, and pachymaran group (200mg/kg), with 6 mice in each group. The acute gouty arthritis model of mice was established by injecting 0.025 mL sodium urate solution into the right ankle cavity of the mice. The pachymaran group was given 200mg/kg of pachymaran intragastrically, in the sham group and model group were given the same volume of normal saline, respectively, for 7 consecutive days. Blood samples were collected from the orbital venous plexus 1 h after the last administration, all mice were killed, and ankle tissue samples were collected. The pathological changes of mouse ankle synovial tissue were observed by HE staining. The expression levels of IL-1ß and IL-18 inflammatory factors in the serum of mice were determined by ELISA. The ultrastructure of the synovial tissue of the mouse ankle joint was observed by transmission electron microscope. The protein expression levels of NLRP3, ASC, IL-1ß, IL-18, GSDMD, and Caspase-1 in synovial tissue of mouse ankle were detected by Western blot assay. Mouse chondrocytes were cultured and divided into groups I, II, III, and IV. Group I was the control group without any drug intervention. The cells in groups II, III, and IV were stimulated with sodium urate solution (100µg/mL), and groups III and IV were intervened by pachymaran (200µg/mL), among which the NLRP3 agonist Nigericin sodium salt intervened group IV. The expression levels of NLRP3, IL-1ß, GSDMD, and Caspase-1 proteins were detected by Western blot assay, and the apoptosis rate was detected by flow cytometry. Results: Compared with the sham group, the pathological injury of mice ankle synovial tissue in the model group was significantly aggravated, as the membrane was incomplete, mitochondria were swollen, the ridge was unclear or even disappeared, and the pathological injury of mice ankle synovial tissue in the pachymaran group was significantly improved vs model group; the serum levels of IL-1ß and IL-18 were increased in model group vs sham group, and pachymaran decreased these index vs model group; Compared with the sham group, protein expression levels of NLRP3, ASC, IL-1ß, IL-18, GSDMD, and Caspase-1 were significant increased in model group, and pachymaran suppressed these proteins vs model group. The TEM results showed that in model group the wide swelling of mitochondria accompanied by disappearance of mitochondrial cristae vs sham group, and the mitochondrial ridge was slightly damaged, or the mitochondria were only swollen, and the ridge was still clearly visible in pachymaran group. In vitro experiments, Compared with group I, the protein expression levels of NLRP3, IL-1ß, GSDMD, Caspase-1, and the apoptosis rate of chondrocytes in group II were significantly increased. Compared with group II, the protein expression levels of NLRP3, IL-1ß, GSDMD, Caspase-1, and the apoptosis rate of chondrocytes in group III were significantly decreased. Compared with group III, the protein expression levels of NLRP3, IL-1ß, GSDMD, Caspase-1, and the apoptosis rate of chondrocytes in group IV were significantly increased. Conclusion: Pachymaran maintain the structural integrity of joints and alleviate the progression of acute gouty arthritis by inhibiting NLRP3 inflammasome activation and pyroptosis, pachymaran may be used and applied to clinical treatment.

Qingfei Tongluo Mixture Attenuates Bleomycin-Induced Pulmonary Inflammation and Fibrosis through mTOR-Dependent Autophagy in Rats.

As an interstitial fibrosis disease characterized by diffuse alveolitis and structural alveolar disorders, idiopathic pulmonary fibrosis (IPF) has high lethality but lacks limited therapeutic drugs. A hospital preparation used for the treatment of viral pneumonia, Qingfei Tongluo mixture (QFTL), is rumored to have protective effects against inflammatory and respiratory disease. This study aims to confirm whether it has a therapeutic effect on bleomycin-induced IPF in rats and to elucidate its mechanism of action. Male SD rats were randomly divided into the following groups: control, model, CQ + QFTL (84 mg/kg chloroquine (CQ) + 3.64 g/kg QFTL), QFTL-L, M, H (3.64, 7.28, and 14.56 g/kg, respectively) and pirfenidone (PFD 420 mg/kg). After induction modeling and drug intervention, blood samples and lung tissue were collected for further detection. Body weight and lung coefficient were examined, combined with hematoxylin and eosin (H&E) and Masson staining to observe lung tissue lesions. The enzyme-linked immunosorbent assay (ELISA) and the hydroxyproline (HYP) assay kit were used to detect changes in proinflammatory factors (transforming growth factor-ß (TGF-ß), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß)) and HYP. Immunohistochemistry and Western blotting were performed to observe changes in proteins related to pulmonary fibrosis (α-smooth muscle actin (α-SMA) and matrix metalloproteinase 12 (MMP12)) and autophagy (P62 and mechanistic target of rapamycin (mTOR)). Treatment with QFTL significantly improved the adverse effects of bleomycin on body weight, lung coefficient, and pathological changes. Then, QFTL reduced bleomycin-induced increases in proinflammatory mediators and HYP. The expression changes of pulmonary fibrosis and autophagy marker proteins are attenuated by QFTL. Furthermore, the autophagy inhibitor CQ significantly reversed the downward trend in HYP levels and α-SMA protein expression, which QFTL improved in BLM-induced pulmonary fibrosis rats. In conclusion, QFTL could effectively attenuate bleomycin-induced inflammation and pulmonary fibrosis through mTOR-dependent autophagy in rats. Therefore, QFTL has the potential to be an alternative treatment for IPF in clinical practice.

Exploring the relations of NLR, hsCRP and MCP-1 with type 2 diabetic kidney disease: a cross-sectional study.

Type 2 diabetic kidney disease (T2DKD) is a common microvascular complication of type 2 diabetes mellitus (T2DM), and its incidence is significantly increasing. Microinflammation plays an important role in the development of T2DKD. Based on this, this study investigated the value of inflammatory markers including neutrophil-lymphocyte ratio (NLR), high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1) in the prediction of T2DKD. This was a cross-sectional survey study. A total of 90 patients with T2DM, who were hospitalized in the nephrology and endocrinology departments of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from June 2021 to January 2022, were included and divided into three groups (A1, A2, A3) according to the urinary albumin-to-creatinine ratio (UACR). Observe and compare the basic information, clinical and laboratory data, and the inflammatory markers NLR, hs-CRP, MCP-1. Results revealed that high levels of NLR (OR = 6.562, 95% CI 2.060-20.902, P = 0.001) and MCP-1 (OR = 1.060, 95% CI 1.026-1.095, P < 0.001) were risk factors in the development of T2DKD. Receiver operating characteristic curve analysis showed that the area under curve of NLR and MCP-1 in diagnosing T2DKD were 0.760 (95% CI 0.6577-0.863, P < 0.001) and 0.862 (95% CI 0.7787-0.937, P < 0.001). Therefore, the inflammatory markers NLR and MCP-1 are risk factors affecting the development of T2DKD, which of clinical value may be used as novel markers of T2DKD.

Ferroptosis: a new mechanism of traditional Chinese medicine for cancer treatment.

Ferroptosis, distinct from apoptosis, is a novel cellular death pathway characterized by the build-up of lipid peroxidation and reactive oxygen species (ROS) derived from lipids within cells. Recent studies demonstrated the efficacy of ferroptosis inducers in targeting malignant cells, thereby establishing a promising avenue for combating cancer. Traditional Chinese medicine (TCM) has a long history of use and is widely used in cancer treatment. TCM takes a holistic approach, viewing the patient as a system and utilizing herbal formulas to address complex diseases such as cancer. Recent TCM studies have elucidated the molecular mechanisms underlying ferroptosis induction during cancer treatment. These studies have identified numerous plant metabolites and derivatives that target multiple pathways and molecular targets. TCM can induce ferroptosis in tumor cells through various regulatory mechanisms, such as amino acid, iron, and lipid metabolism pathways, which may provide novel therapeutic strategies for apoptosis-resistant cancer treatment. TCM also influence anticancer immunotherapy via ferroptosis. This review comprehensively elucidates the molecular mechanisms underlying ferroptosis, highlights the pivotal regulatory genes involved in orchestrating this process, evaluates the advancements made in TCM research pertaining to ferroptosis, and provides theoretical insights into the induction of ferroptosis in tumors using botanical drugs.

Efficient removal and transformation of Cr(VI) from alkaline wastewater to form a ferrochromium spinel multiphase via a modified ferrite process.

Chromium-containing wastewater causes serious environmental pollution due to the harmfulness of Cr(VI). The ferrite process is typically used to treat chromium-containing wastewater and recycle the valuable chromium metal. However, the current ferrite process is unable to fully transform Cr(VI) into chromium ferrite under mild reaction conditions. This paper proposes a novel ferrite process to treat chromium-containing wastewater and recover valuable chromium metal. The process combines FeSO4 reduction and hydrothermal treatment to remove Cr(VI) and form chromium ferrite composites. The Cr(VI) concentration in the wastewater was reduced from 1040 mg L-1 to 0.035 mg L-1, and the Cr(VI) leaching toxicity of the precipitate was 0.21 mg L-1 under optimal hydrothermal conditions. The precipitate consisted of micron-sized ferrochromium spinel multiphase with polyhedral structure. The mechanism of Cr(VI) removal involved three steps: 1) partial oxidation of FeSO4 to Fe(III) hydroxide and oxy-hydroxide; 2) reduction of Cr(VI) by FeSO4 to Cr(III) and Fe(III) precipitates; 3) transformation and growth of the precipitates into chromium ferrite composites. This process meets the release standards of industrial wastewater and hazardous waste and can improve the efficiency of the ferrite process for toxic heavy metal removal.

An electrochlorination process integrating enhanced oxidation of phosphonate to orthophosphate and elimination: Verification of matrix chloridion-induced oxidation mechanism.

Phosphonate used as scale inhibitor is a non-negligible eutrophic contaminant in corresponding polluted waters. Besides, its conversion to orthophosphate (ortho-P) is a precondition for realizing bioavailable phosphorus recovery. Due to the feeble degradation efficiency with less than 30 % from classical Fenton commonly used in industrial wastewater treatment and itself vulnerable to strong inhibition interference of matrix chloride ions, we proposed an electrochemical approach to transform the native salt in the solution into oxidizing substances, sort of achieving beneficial utilization of matrix waste, and enhanced the ortho-P conversion rate of 1-Hydroxyethane-1,1-diphosphonic acid (HEDP) to 89.2 % (± 3.6 %). In electrochlorination system, it was found that HEDP rapidly complexed with Fe(II) and then coordinated in-situ Fe(III) to release free HEDP via intramolecular metal-ligand electron transfer reaction. The subsequent degradation mainly rooted in the oxidation of pivotal reactive species HClO, FeIVO2+ and 1O2, causing C-P and CC bonds to fracture in sequence. Eventually the organically bound phosphorus of HEDP was recovered as ortho-P. This study acquainted the audiences with the rare mechanism of chloridion-triggered HEDP degradation under electrochemical way, as well as offered a feasible technology for synchronous transformation of organically bound phosphorus to ortho-P and elimination from phosphonates.

Prognostic Impact of Serum Homocysteine-Lowering Therapy on Patients with Hemorrhagic Stroke and Its Influence on National Institutes of Health Stroke Scale and China Stroke Scale Scores.

Objective: This study aimed to investigate the prognostic impact of serum homocysteine-lowering therapy on patients with hemorrhagic stroke (HS) and its influence on their National Institutes of Health Stroke Scale (NIHSS) and China Stroke Scale (CSS) scores. Methods: A double-blind study involving 120 patients with HS and hyperhomocysteinemia (Hhcy) who were admitted to our hospital was conducted in 2021. They were evenly divided into two groups: the control group (n=60) received low-dose folic acid, methylcobalamin, and vitamin B6 as part of serum homocysteine-lowering therapy, while the study group (n=60) received high-dose folic acid, methylcobalamin, and vitamin B6. The prognosis of each group was compared using the NIHSS and CSS to assess the neurological function of the patients. Results: Before treatment, the levels of oxidative stress markers and vascular endothelial function markers were comparable between the two groups (t = 0.051, 0.015, 0.010, 0.011, 0.013, 0.022, P = .960, .988, .992, 0.991, .989, 0.982). However, after treatment, the study group exhibited higher levels of MDA and ET-1 compared to the control group (t = 3.418, 1.978, P < .001). Additionally, SOD, GSH-Px, and PON1 levels were lower in the study group (t = 3.435, 3.783, 2.735, 3.893, P < .001). The NIHSS scores before treatment were comparable among patients (t = 0.058, P = 0.954), but after treatment, the study group showed significantly lower NIHSS scores (t = 20.105, P < .001). Similarly, the CSS scores before treatment were comparable (t = 0.046, P = .963), but the CSS scores in the study group after treatment were significantly lower (t = 5.027, P < .001). Conclusions: High-dose folic acid, methylcobalamin, and vitamin B6 as part of serum homocysteine-lowering therapy can improve oxidative stress and vascular endothelial function in HS patients. This treatment also enhances prognosis and ameliorates neurological deficits. Therefore, it holds significant clinical potential and should be considered for broader adoption.

Functions and targets of miRNAs in pharmacological and toxicological effects of major components of Tripterygium wilfordii Hook F.

Tripterygium wilfordii Hook F (TwHF) has a long history of use as a traditional Chinese medicine and has been widely administered to treat various inflammatory and autoimmune diseases. MicroRNAs (miRNAs) are endogenous, short, non-coding RNAs that regulate gene expression post-transcriptionally. They participate in the efficacies and even toxicities of the components of TwHF, rendering miRNAs an appealing therapeutic strategy. This review summarizes the recent literature related to the roles and mechanisms of miRNAs in the pharmacological and toxicological effects of main components of TwHF, focusing on two active compounds, triptolide (TP) and celastrol (CEL). Additionally, the prospects for the "You Gu Wu Yun" theory regarding TwHF nephrotoxicity are presented.

Traditional Chinese medicine alleviating neuropathic pain targeting purinergic receptor P2 in purinergic signaling: A review.

Past studies have suggested that Chinese herbal may alleviate neuropathic pain, and the mechanism might target the inhibition of purinergic receptor P2. This review discusses whether traditional Chinese medicine target P2 receptors in neuropathic pain and its mechanism in order to provide references for future clinical drug development. The related literatures were searched from Pubmed, Embase, Sinomed, and CNKI databases before June 2023. The search terms included"neuropathic pain", "purinergic receptor P2", "P2", "traditional Chinese medicine", "Chinese herbal medicine", and "herb". We described the traditional Chinese medicine alleviating neuropathic pain via purinergic receptor P2 signaling pathway including P2X2/3 R, P2X3R, P2X4R, P2X7R, P2Y1R. Inhibition of activating glial cells, changing synaptic transmission, increasing painful postsynaptic potential, and activating inflammatory signaling pathways maybe the mechanism. Purine receptor P2 can mediate the occurrence of neuropathic pain. And many of traditional Chinese medicines can target P2 receptors to relieve neuropathic pain, which provides reasonable evidences for the future development of drugs. Also, the safety and efficacy and mechanism need more in-depth experimental research.

Influence of Lactose Supplementation on Regulation of Streptococcus thermophilus on Gut Microbiota.

It has been found that Streptococcus thermophilus (S. thermophilus) influenced the gut microbiota and host metabolism with strain specificity in C57BL/6J mice in the previous study, though it remains unclear whether lactose as a dietary factor associated with dairy consumption is involved as the mediator in the interaction. In the present study, integrated analysis of 16S rRNA gene sequencing and untargeted metabolomics by liquid chromatography-mass spectrometry of fecal samples in C57BL/6J mice was applied to evaluate the effect of lactose on the regulation of gut microbiota by two S. thermophilus strains (4M6 and DYNDL13-4). The results showed that the influence of lactose supplementation on gut microbiota induced by S. thermophilus ingestion was strain-specific. Although two S. thermophilus strains ingestion introduced similar perturbations in the fecal microbiota and gut microbial metabolism, the regulation of DYNDL13-4 on the gut microbiota and metabolism was more affected by lactose than 4M6. More specifically, lactose and 4M6 supplementation mainly enriched pathways of d-glutamine and d-glutamate metabolism, alanine, aspartate, and glutamate metabolism, and tryptophan and phenylalanine metabolism in the gut, whereas 4M6 only enriched tryptophan and phenylalanine metabolism. DYNDL13-4-L (DYNDL13-4 with lactose) had significant effects on sulfur, taurine, and hypotaurine metabolism in the gut and on phenylalanine, tyrosine, tryptophan biosynthesis, and linoleic acid metabolism in serum relative to the DYNDL13-4. Our study demonstrated the strain-specific effect of lactose and S. thermophilus supplementation on gut microbiota and host metabolism. However, considering the complexity of the gut microbiota, further research is necessary to provide insights to facilitate the design of personalized fermented milk products as a dietary therapeutic strategy for improving host health.

[Serum metabolomics study of Psoraleae Fructus in improving learning and memory ability of APP/PS1 mice].

This study aimed to investigate the mechanism of Psoraleae Fructus in improving the learning and memory ability of APP/PS1 mice by serum metabolomics, screen the differential metabolites of Psoraleae Fructus on APP/PS1 mice, and reveal its influence on the metabolic pathway of APP/PS1 mice. Thirty 3-month-old APP/PS1 mice were randomly divided into a model group and a Psoraleae Fructus extract group, and another 15 C57BL/6 mice of the same age were assigned to the blank group. The learning and memory ability of mice was evaluated by the Morris water maze and novel object recognition tests, and metabolomics was used to analyze the metabolites in mouse serum. The results of the Morris water maze test showed that Psoraleae Fructus shortened the escape latency of APP/PS1 mice(P<0.01), and increased the number of platform crossing and residence time in the target quadrant(P<0.01). The results of the novel object recognition test showed that Psoraleae Fructus could improve the novel object recognition index of APP/PS1 mice(P<0.01). Eighteen differential metabolites in serum were screened out by metabolomics, among which the levels of arachidonic acid, tryptophan, and glycerophospholipid decreased after drug administration, while the levels of glutamyltyrosine increased after drug administration. The metabolic pathways involved included arachidonic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism, linoleic acid metabolism, α-linolenic acid metabolism, and glycerolipid metabolism. Therefore, Psoraleae Fructus can improve the learning and memory ability of APP/PS1 mice, and its mechanism may be related to the effects in promoting energy metabolism, reducing oxidative damage, protecting central nervous system, reducing neuroinflammation, and reducing Aß deposition. This study is expected to provide references for Psoraleae Fructus in the treatment of Alzheimer's disease(AD) and further explain the mechanism of Psoraleae Fructus in the treatment of AD.

The frontline of alternatives to animal testing: novel in vitro skin model application in drug development and evaluation.

The FDA Modernization Act 2.0 has brought nonclinical drug evaluation into a new era. In vitro models are widely used and play an important role in modern drug development and evaluation, including early candidate drug screening and preclinical drug efficacy and toxicity assessment. Driven by regulatory steering and facilitated by well-defined physiology, novel in vitro skin models are emerging rapidly, becoming the most advanced area in alternative testing research. The revolutionary technologies bring us many in vitro skin models, either laboratory-developed or commercially available, which were all built to emulate the structure of the natural skin to recapitulate the skin's physiological function and particular skin pathology. During the model development, how to achieve balance among complexity, accessibility, capability, and cost-effectiveness remains the core challenge for researchers. This review attempts to introduce the existing in vitro skin models, align them on different dimensions, such as structural complexity, functional maturity, and screening throughput, and provide an update on their current application in various scenarios within the scope of chemical testing and drug development, including testing in genotoxicity, phototoxicity, skin sensitization, corrosion/irritation. Overall, the review will summarize a general strategy for in vitro skin model to enhance future model invention, application, and translation in drug development and evaluation.

Association between weight loss agents and elevated liver enzymes: a population-based cross-sectional study.

The widespread use of body weight control agents might be related to liver enzyme elevation, but this potential association has only been documented in a few case reports. This study aimed to investigate the associations between weight loss agents and elevated liver enzymes at the population-level. We conducted a cross-sectional study using Korea National Health and Nutrition Examination Survey (KNHANES) data from 2013 to 2019. This study included 36,259 participants over 20 years of age who completed the questionnaire and had no history of hepatitis, cancer, or renal failure. In these participants, we analyzed associations between weight loss agents and elevated liver enzymes by constructing multiple logistic regression models with adjustment for confounding factors and stratified by sex, age, and body mass index. The use of weight loss agents related to liver enzyme elevation in men (adjusted odds ratio (aOR): 1.36, 95% confidence interval (CI): 1.08-1.71) and participants aged less than 40 years (aOR: 1.44, 95% CI: 1.12-1.87). Using more types of weight loss agents was associated with liver enzyme elevation (aOR: 1.31, 95% CI: 1.03-1.67 for 1 weight loss agent, aOR: 1.93, 95% CI: 0.93-3.99 for ≥ 2 weight loss agents). Elevated liver enzymes were associated with the use of traditional medicines (aOR: 1.96, 95% CI: 1.14-3.34) and dietary supplements (aOR: 1.33, 95% CI: 1.02-1.72) in men. We observed an association between weight loss agents and liver enzyme elevation in men, particularly for traditional herbal medicines and dietary supplements. To confirm the observed associations, studies higher on the evidence hierarchy are needed.

Genetic Authentication of the Medicinal Plant Portulaca oleracea Using a Quick, Precise, and Sensitive Isothermal DNA Amplification Assay.

Portulaca oleracea (PO) is a commonly known medicinal crop that is an important ingredient for traditional Chinese medicine (TCM) due to its use as a vegetable in the diet. PO has been recorded to be frequently adulterated by other related species in the market of herbal plants, distorting the PO plant identity. Thus, identification of the botanical origin of PO is a crucial step before pharmaceutical or functional food application. In this research, a quick assay named "loop-mediated isothermal amplification (LAMP)" was built for the specific and sensitive authentication of PO DNA. On the basis of the divergences in the internal transcribed spacer 2 (ITS2) sequence between PO and its adulterant species, the LAMP primers were designed and verified their specificity, sensitivity, and application for the PO DNA authentication. The detection limit of the LAMP assay for PO DNA identification specifically was 100 fg under isothermal conditions at 63 °C for 30 min. In addition, different heat-processed PO samples can be applied for use in PO authentication in the LAMP assay. These samples of PO were more susceptible to the effect of steaming in authentication by PCR than boiling and drying treatment. Furthermore, commercial PO samples pursued from herbal markets were used to display their applicability of the developed LAMP analysis for PO postharvest authentication, and the investigation found that approximately 68.4% of PO specimens in the marketplace of herbal remedies were adulterated. In summary, the specific, sensitive, and rapid LAMP assay for PO authentication was first successfully developed herein, and its practical application for the inspection of adulteration in PO samples from the herbal market was shown. This LAMP assay created in this study will be useful to authenticate the botanical origin of PO and its commercial products.

Effects of Doctor-Nurse Integrated Care Combined with Health Education on Hip Function, Incidence of Deep Vein Thrombosis and Nursing Satisfaction in Patients with Hip Arthroplasty.

Objective: The aim of our study was to investigate the effect of implementing doctor-nurse integrated care combined with health education on joint function recovery, incidence of deep vein thrombosis, coping style, self-efficacy and nursing care satisfaction in patients undergoing hip arthroplasty. Methods: This is a clinical prospective randomized study with 83 patients who underwent total hip arthroplasty in the orthopedic department of our hospital between May 2019 and May 2022 selected by a random number table. They were divided into 2 groups: the observation group (n = 42) and the control group (n = 41). Both groups used the integrated care model during the perioperative period. Patients in the observation group were also given health education and the differences in the incidence of lower limb deep vein thrombosis, hip function score, coping style, self-efficacy and nursing satisfaction in the 2 groups were compared. Results: Preoperatively, there was no statistically significant difference between the Harris Hip Score (HHS) in the observation group and the control group (P > .05); the HHS in the observation group was higher than in the control group at 2 weeks and 1 month after surgery, and the difference was statistically significant (P < .05); there was no statistically significant difference between the confrontation, avoidance and submission scores of the 2 groups the first day after surgery (P > .05); while the confrontation and avoidance scores in the observation group were higher than in the control group at 2 weeks after surgery, with statistical significance. There was no statistically significant difference between role function, emotional control, symptom management and nurse-patient communication scores in the 2 groups the first day after surgery (P > .05); while the emotional control, symptom management and nurse-patient communication scores in the observation group were higher than in the control group at 2 weeks after surgery, and the differences were statistically significant (P < .05). Overall patient satisfaction in the observation group was better than in the control group, and the difference was statistically significant (P < .05). There was no statistically significant difference in the incidence of lower limb deep vein thrombosis in the 2 groups (P > .05). Conclusion: The implementation of an integrated care model combined with health education in patients with hip arthroplasty is beneficial to improving self-efficacy, patient trauma coping style, promoting early hip function recovery and improving nursing care satisfaction.

Mechanism of action of Asparagus officinalis extract against multiple myeloma using bioinformatics tools, in silico and in vitro study.

Introduction: Asparagus (Asparagus officinalis) is a perennial flowering plant species. Its main components have tumor-prevention, immune system-enhancement, and anti-inflammation effects. Network pharmacology is a powerful approach that is being applied increasingly to research of herbal medicines. Herb identification, study of compound targets, network construction, and network analysis have been used to elucidate how herbal medicines work. However, the interaction of bioactive substances from asparagus with the targets involved in multiple myeloma (MM) has not been elucidated. We explored the mechanism of action of asparagus in MM through network pharmacology and experimental verification. Methods: The active ingredients and corresponding targets of asparagus were acquired from the Traditional Chinese Medicine System Pharmacology database, followed by identification of MM-related target genes using GeneCards and Online Mendelian Inheritance in Man databases, which were matched with the potential targets of asparagus. Potential targets were identified and a target network of traditional Chinese medicine was constructed. The STRING database and Cytoscape were utilized to create protein-protein interaction (PPI) networks and further screening of core targets. Results: The intersection of target genes and core target genes of the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway was enriched, the top-five core target genes were selected, and the binding affinity of corresponding compounds to the top-five core targets was analyzed using molecular docking. Network pharmacology identified nine active components of asparagus from databases based on oral bioavailability and drug similarity, and predicted 157 potential targets related to asparagus. Enrichment analyses showed that "steroid receptor activity" and the "PI3K/AKT signaling pathway" were the most enriched biological process and signaling pathway, respectively. According to the top-10 core genes and targets of the PPI pathway, AKT1, interleukin (IL)-6, vascular endothelial growth factor (VEGF)A, MYC, and epidermal growth factor receptor (EGFR) were selected for molecular docking. The latter showed that five core targets of the PI3K/AKT signaling pathway could bind to quercetin, among which EGFR, IL-6, and MYC showed strong docking, and the diosgenin ligand could bind to VEGFA. Cell experiments showed that asparagus, through the PI3K/AKT/NF-κB pathway, inhibited the proliferation and migration of MM cells, and caused retardation and apoptosis of MM cells in the G0/G1 phase. Discussion: In this study, the anti-cancer activity of asparagus against MM was demonstrated using network pharmacology, and potential pharmacological mechanisms were inferred using in vitro experimental data.