Xianglian Pill combined with 5-fluorouracil enhances antitumor activity and reduces gastrointestinal toxicity in gastric cancer by regulating the p38 MAPK/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Perioperative or postoperative adjuvant chemotherapy based on 5-fluorouracil (5-FU) is a common first-line adjuvant therapy for gastric cancer (GC). However, drug resistance and the side effects of 5-FU have reduced its efficacy. Among these side effects, gastrointestinal (GI) toxicity is one of the most common. Xianglian Pill (XLP) is a Chinese patent medicine that is commonly used for the treatment of diarrhoea. It can reduce inflammation and has a protective effect on the intestinal mucosa. Recent studies have shown that many components of XLP can inhibite tumor cell growth. However, the therapeutic effect of XLP in combination with 5-FU on GC is unclear. AIM OF THE STUDY: To investigate whether the combination of XLP and 5-FU can enhance anti-GC activity while reducing GI toxicity. MATERIALS AND METHODS: XLP was administered orally during intraperitoneal injection of 5-FU in GC mice model. Mice were continuously monitored for diarrhea and xenograft tumor growth. After 2 weeks, the mice were sacrificed and serum was collected to determine interleukin-6 levels. Pathological changes, the expression of pro-inflammatory factors and p38 mitogen-activated protein kinase (MAPK) in GI tissue were determined by Western blot analysis. Pathological changes, apoptosis levels and p38 MAPK expression levels in xenograft tissues were also determined. RESULTS: The results showed that XLP could alleviate GI mucosal injury caused by 5-FU, alleviated diarrhea, and inhibited the expression of nuclear factor (NF)-κB and myeloid differentiation primary response-88. Besides, XLP could promote the 5-FU-induced apoptosis of GC cells and enhance the inhibitory effect of 5-FU on tumor xenografts. Further study showed that XLP administration could regulate the expression of p38 MAPK. CONCLUSIONS: XLP in combination with 5-FU could alleviate its GI side effects and enhance its inhibitory effect on xenograft tumor. Moreover, these effects were found to be related to the regulation of the p38 MAPK/NF-κB pathway.

Bioactive solanidane steroidal alkaloids from Solanum lyratum.

Six previously unreported solanidane steroidal alkaloids, namely lyrasolanosides A-F, were isolated from Solanum lyratum. In addition, five known steroidal alkaloids were also identified. The structures of these compounds were determined through the use of NMR, HRESIMS,UV, IR and ECD analysis. To assess their bioactivities, the cytotoxic effects of the six previously unreported compounds were evaluated on A549 cells. The results revealed that lyrasolanoside B (2) exhibited the highest potency among them. Lyrasolanoside B (2) exhibited significant inhibition of cell migration, invasion, and adhesion dramatically. Mechanistically, it was found to suppress the activity of JAK2/STAT3 signaling pathway by downregulating the expression of phosphorylated JAK2/STAT3 in an exosome-dependent manner. In addition, lyrasolanoside B (2) was found to significantly upregulate the expression of E-cadherin and downregulate the expression of N-cadherin and vimentin. These findings indicate that lyrasolanoside B (2) inhibits the metastasis of A549 cells by suppressing exosome-mediated EMT. These findings suggest that lyrasolanoside B (2) may inhibit the metastasis of lung cancer by regulating A549-derived exosomes.

Eudesmane sesquiterpenoids with inhibitory effects on NO production from Artemisia princeps.

Five undescribed eudesmane methyl esters (1-5), three undescribed eudesmane-12,6-olides (6-8), and 21 known analogues (9-29) were isolated from the aerial part of Artemisia princeps Pamp. Their structures were established by detailed analysis of the NMR and HRESIMS data. The absolute configurations of 1-8 were determined based on single-crystal X-ray diffraction analysis and ECD calculations. Moreover, the inhibitory effects on LPS-induced NO production in BV-2 microglial cells of all the isolated compounds were assessed. Except for compounds 2, 4, 10, and 11, the others showed significant inhibitory activities, with IC50 values of 0.73-18.66 µM, wherein the potential structure-activity relationship was also discussed.

Use of Real-World Evidence in Regulatory Decisions for Traditional Chinese Medicine: Current Status and Future Directions.

Traditional Chinese medicine (TCM) is a valuable resource unique to China with a long history of human use and clinical practice, which can be analyzed to generate real-world evidence (RWE). The Chinese government has been actively promoting regulatory reform that is in line with the characteristics of TCM, optimizing the clinical evidence system for TCM, and exploring the important role of RWE in supporting the development of new drugs and regulatory decision-making for TCM. This article aims to provide a comprehensive review of the use of RWE in regulatory decisions for TCM. Based on the characteristics of TCM, this study focuses on the application scenarios, challenges, and opportunities of RWE in TCM. And some suggestions are put forward to promote the wider application of RWE in TCM development and supervision.

Revealing the mechanism of quartz sand seeding in accelerating phosphorus recovery from anaerobic fermentation supernatant through vivianite crystallization.

The recovery of phosphorus (P) through vivianite crystallization offers a promising approach for resource utilization in wastewater treatment plants. However, this process encounters challenges in terms of small product size and low purity. The study aimed to assess the feasibility of using quartz sand as a seed material to enhance P recovery and vivianite crystal characteristics from anaerobic fermentation supernatant. Various factors, including seed dosage, seed size, Fe/P ratio, and pH, were systematically tested in batch experiments to assess their influence. Results demonstrated that the effect of seed enhancement on vivianite crystallization was more pronounced under higher seed dosages, smaller seed sizes, and lower pH or Fe/P ratio. The addition of seeds increased P recovery by 4.43% in the actual anaerobic fermentation supernatant and also augmented the average particle size of the recovered product from 19.57 to 39.28 µm. Moreover, introducing quartz sand as a seed material effectively reduced co-precipitation, leading to a notable 12.5% increase in the purity of the recovered vivianite compared to the non-seeded process. The formation of an ion adsorption layer on the surface of quartz sand facilitated crystal attachment and growth, significantly accelerating the vivianite crystallization rate and enhancing P recovery. The economic analysis focused on chemical costs further affirmed the economic viability of using quartz sand as a seed material for P recovery through vivianite crystallization, which provides valuable insights for future research and engineering applications.

Phosphorus recovery from synthetic anaerobic fermentation supernatant via vivianite crystallization: Coupling effects of various physicochemical process parameters.

Recovery of phosphorus (P) via vivianite crystallization is an effective strategy to recycle resources from the anaerobic fermentation supernatant. However, the presence of different components in the anaerobic fermentation supernatant (e.g., polysaccharides and proteins) might alter conditions for optimal growth of vivianite crystals, resulting in distinct vivianite characteristics. In the present study, the effect of different components on vivianite crystallization was explored. Then, the reaction parameters (pH, Fe/P, and stirring speed) for P recovery from synthetic anaerobic fermentation supernatant as vivianite were optimized using response surface methodology, and the relationship between crystal properties and supersaturation was elucidated using a thermodynamic equilibrium model. The optimized values for pH, Fe/P, and stirring speed were found to be 7.8, 1.74, and 500 rpm respectively, resulting in 90.54 % P recovery efficiency. Moreover, the variation of reaction parameters did not change the crystalline structure of the recovered vivianite but influenced its morphology, size, and purity. Thermodynamic analysis suggested the saturation index (SI) of vivianite increased with increasing pH and Fe/P ratio, leading to a facilitative effect on vivianite crystallization. However, when the SI was >11, homogenous nucleation occurred so that the nucleation rate was much higher than the crystal growth rate, causing a smaller crystal size. The findings presented herein will be highly valued for the future large-scale application of the vivianite crystallization process for wastewater treatment.

The association between the essential metal mixture and fasting plasma glucose in Chinese community-dwelling elderly people.

BACKGROUND: Epidemiological studies about the effect of essential metal mixture on fasting plasma glucose (FPG) levels among elderly people are sparse. The object of this study was to examine the associations of single essential metals and essential metal mixture with FPG levels in Chinese community-dwelling elderly people. METHODS: The study recruited 2348 community-dwelling elderly people in total. Inductively coupled plasma-mass spectrometry was adopted to detect the levels of vanadium (V), selenium (Se), magnesium (Mg), cobalt (Co), calcium (Ca), and molybdenum (Mo) in urine. The relationships between single essential metals and essential metal mixture and FPG levels were evaluated by linear regression and Bayesian kernel machine regression (BKMR) models, respectively. RESULTS: In multiple-metal linear regression models, urine V and Mg were negatively related to the FPG levels (ß = - 0.016, 95 % CI: - 0.030 to - 0.003 for V; ß = - 0.021, 95 % CI: - 0.033 to - 0.009 for Mg), and urine Se was positively related to the FPG levels (ß = 0.024, 95 % CI: 0.014-0.034). In BKMR model, the significant relationships of Se and Mg with the FPG levels were also found. The essential metal mixture was negatively associated with FPG levels in a dose-response pattern, and Mg had the maximum posterior inclusion probability (PIP) value (PIP = 1.0000), followed by Se (PIP = 0.9968). Besides, Co showed a significant association with decreased FPG levels in older adults without hyperlipemia and in women. CONCLUSIONS: Both Mg and Se were associated with FPG levels, individually and as a mixture. The essential metal mixture displayed a linear dose-response relationship with reduced FPG levels, with Mg having the largest contribution to FPG levels, followed by Se. Further prospective investigations are necessary to validate these exploratory findings.

Determinants affecting the blood mercury levels of preschool children in Shanghai, China: A cross-sectional study.

Infants and children are vulnerable to mercury (Hg)-induced toxicity, which has detrimental effects on their neurological development. This study measured blood Hg levels (BMLs) and identified potential factors influencing BMLs, including demographic and socioeconomic factors, lifestyle, and daily dietary habits, among 0 to 7-year-old children in Shanghai. Our study recruited 1474 participants, comprising 784 boys and 690 girls. Basic demographic and lifestyle information were obtained and blood Hg were analyzed using the Direct Mercury Analyzer 80. The blood Hg concentrations of children in Shanghai ranged from 0.01 to 17.20 µg/L, with a median concentration of 1.34 µg/L. Older age, higher familial socioeconomic status, higher residential floors, and a higher frequency of consuming aquatic products, rice, vegetables, and formula milk were identified as risk factors. Other potential influencing factors including the mother's reproductive history (gravidity and parity), smoking (passive smoking), supplementation of fish oil and calcium need to be further investigated. These findings can be useful in establishing appropriate interventions to prevent children's high blood Hg concentrations in Shanghai and other similar metropolitan cities.

Effects of food-borne cholesterol supplementation on lead-induced neurodevelopmental impairments of rats based on BDNF signaling pathway and cholesterol metabolism.

Despite the ubiquity and prevalence of lead (Pb) in the environment and industry, the mechanism of lead-induced neurotoxicity in the brain remains unclear, let alone its prevention and treatment. In this study, we hypothesized that exogenous cholesterol supplementation acts as an effective remedy for lead-induced neurodevelopmental impairments caused by lead. Forty 21-day-old male rats were randomly divided into four groups and administered 0.1 % lead water and/or 2 % cholesterol-containing feed for 30 d. Ultimately, rats in the lead group lost weight, accompanied by spatial learning and memory impairments as verified by the Morris water maze test, in which the escape latency of rats was prolonged, and the number of crossings in the target platform and the residence time in the target quadrant were significantly diminished compared to the control group. Hematoxylin-Eosin (H&E) staining and Nissl staining illustrated that typical pathological morphology occurred in the brain tissue of the lead group, where the tissue structure was loose, the number of hippocampal neurons and granulosa cells decreased significantly and were arranged loosely, along with enlarged intercellular space, light matrix staining, and decline in Nissl bodies. In addition, inflammatory response and oxidative stress were significantly induced by lead. Immunofluorescence experiments showed apparent activation of astrocytes and microglia, followed by the enhancement of TNF-α and IL-ß levels. Moreover, the MDA content in the lead group was elevated dramatically, whereas the activities of SOD and GSH were significantly inhibited. As for the mechanism, western blot and qRT-PCR experiments were performed, where lead could significantly inhibit the BDNF-TrkB signaling pathway, lowering the protein expression of BDNF and TrkB. Cholesterol metabolism was also affected by lead exposure, in which cholesterol metabolism-related protein expression and gene transcription, including SREBP2, HMGCR, and LDLR, were downregulated. However, cholesterol supplementation efficiently detoxified the negative effects of lead-induced neurotoxicity, reversing the inflammatory response, oxidative stress, inactivation of the BDNF signaling pathway, and imbalance of cholesterol metabolism, thus improving the learning and memory ability of rats. In brief, our study demonstrated that cholesterol supplementation could ameliorate the deficiency of learning and memory induced by lead, which is closely associated with the initiation of the BDNF/TrkB signaling pathway and regulation of cholesterol metabolism.

Recovery of phosphorus from wastewater containing humic substances through vivianite crystallization: Interaction and mechanism analysis.

Vivianite crystallization has been regarded as a suitable option for recovering phosphorus (P) from P-containing wastewater. However, the presence of humic substances (HS) would inevitably affect the formation of vivianite crystals. Therefore, the influences of HS on vivianite crystallization and the changes in the harvested vivianite crystals were investigated in this study. The results suggested the inhibition effect of 70 mg/L HS on vivianite crystallization reached 12.24%, while it could be attenuated by increasing the pH and Fe/P ratio of the solution. Meanwhile, the addition of HS altered the size, purity, and morphology of recovered vivianite crystals due to the blockage of the growth sites on the crystal surface. Additionally, the formation of phosphate ester group, hydrogen bonding, and COOH-Fe2+ complexes are the potential mechanisms of HS interaction with vivianite crystals. The results obtained herein will help to elucidate the underlying mechanism of HS on vivianite crystallization from P-containing wastewater.

Unusual N-pyridinium amino acid-type alkaloids from roots and rhizomes of Sophora tonkinensis Gagnep.

Two previously undescribed amino acid-type alkaloids with unusual N-pyridinium cation (1-2) and six known alkaloids (3-8), were isolated from the roots and rhizomes of Sophora tonkinensis Gapnea. Their structures were characterized by UV, IR, NMR, and HRESIMS spectroscopic data. The absolute configurations of compounds 1 and 2 were established through comparison of their experimental ECD spectra to the theoretical spectra of 2 calculated by TDDFT method. The plausible biosynthetic pathway of pyridinium was also proposed. Moreover, compound 4 exhibited weak XOD inhibitory activity with the inhibition rate of 65.8% at concentration of 10 µM.

Rapid fabrication of the Au hexagonal cone arrays for SERS applications.

This study performed trace detection using surface-enhanced Raman scattering (SERS) on Au hexagonal cone arrays (Au-HCAs). Uniform porous anodized aluminum oxide (AAO) templates were used, and an Ag film with a cone cavity was prepared using a thermal deposition technique. Next, a series of homogeneous Au-HCAs were prepared controllably via electrodeposition growth technology. The prepared Au-HCAs were used as SERS substrates, and according to the experimental results, the optimal electrodeposition time is 600 s. At this time, Au-HCAs had the highest SERS activity. The detection limit of R6G was 10-9 M, exhibiting high reproducibility and high uniformity at 10-6 M, indicating that Au-HCAs had good stability. Moreover, a good linear correlation between the Raman intensity and the molecular concentration endowed Au-HCAs with good quantitative analysis ability. Therefore, the Au-HCAs exhibited great potential for qualitative and quantitative detection.

Selenium attenuates the association of co-exposure to arsenic, cadmium, and lead with cognitive function among Chinese community-dwelling older adults.

The effects of interactions between the toxic and essential metal mixtures on cognitive function are poorly understood. This study aims to identify the joint association of arsenic (As), cadmium (Cd), and lead (Pb) with cognitive function in older adults and the moderating role of selenium (Se), zinc (Zn), and copper (Cu) in this association. This study included 1000 community-dwelling older adults. Cognitive function was assessed by the Mini-Mental State Examination (MMSE). Blood concentrations of As, Cd, Pb, Se, Zn, and Cu were measured using inductively coupled plasma mass spectrometry. Linear regression and Bayesian kernel machine regression (BKMR) models were applied to assess the individual and joint associations of As, Cd, and Pb with cognitive function and to examine whether Se, Zn, and Cu (individually and as a mixture) modified these associations. In the adjusted single-metal models, both Cd (ß = - 0.37, 95% CI: - 0.73 to - 0.01) and Pb (ß = - 0.44, 95% CI: - 0.86 to - 0.02) were associated with MMSE scores, while Se (ß = 0.71, 95% CI: 0.30 to 1.13) exhibited a positive relationship with MMSE scores. Univariate exposure-response functions from BKMR models showed similar results. Moreover, the toxic metal mixture (As, Cd, and Pb) exhibited a significant negative association with MMSE scores in a dose-response pattern, with Pb being the greatest contributor within the mixture. The negative association of Pb alone or the toxic metal mixture with MMSE scores became weaker at higher concentrations of Se within its normal range, especially when Se levels were greater than the median (89.18 µg/L). Our findings support that Se can attenuate the negative associations of exposure to single Pb or the As, Cd, and Pb mixtures with cognitive function. Future prospective studies are needed to replicate our findings.

Effect of hyperbaric oxygen on symptoms of dementia in patients with delayed encephalopathy after acute carbon monoxide poisoning. / é«˜åŽ‹æ°§å¯¹æ€¥æ€§ä¸€æ°§åŒ–ç¢³ä¸­æ¯’è¿Ÿå‘æ€§è„‘ç— æ‚£è€ ç—´å‘†ç—‡çŠ¶çš„å½±å“ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is the most severe complication of carbon monoxide poisoning, which seriously endangers patients' quality of life. This study aims to investigate the efficacy of hyperbaric oxygen (HBO2) on improving dementia symptoms in patients with DEACMP. METHODS: A retrospective analysis was performed on DEACMP patients, who visited Xiangya Hospital, Central South University from June 2014 to June 2020. Among them, patients who received conventional drug treatment combined with HBO2 treatment were included in an HBO2 group, while those who only received conventional drug treatment were included in a control group. HBO2 was administered once daily. Patients in the HBO2 group received 6 courses of treatment, with each course consisting of 10 sessions. The Hasegawa Dementia Scale (HDS) was used to diagnose dementia, and the Clinical Dementia Rating (CDR) was used to grade the severity of dementia for DEACMP. The Alzheimer's Disease Assessment Scale-Cognitive Section (ADAS-Cog), the Functional Activities Questionnaire (FAQ), the Neuropsychiatric Inventory (NPI), and the Clinician's Interview-Based Impression of Change-Plus Caregiver Input (CIBIC-Plus) were performed to assess cognitive function, ability to perform activities of daily living (ADL), behavioral and psychological symptoms, and overall function. The study further analyzed the results of objective examinations related to patients' dementia symptoms, including magnetic resonance imaging detection of white matter lesions and abnormal electroencephalogram (EEG). The changes of the above indicators before and after treatment, as well as the differences between the 2 groups after treatment were compared. RESULTS: There was no significant difference in the HDS score and CDR grading between the 2 groups before treatment (both P>0.05). After treatment, the score of ADAS-Cog, FAQ, NPI, and CIBIC Plus grading of the 2 groups were significantly improved, and the improvement of the above indicators in the HBO2 group was greater than that in the control group (all P<0.05). The effective rate of the HBO2 group in treating DEACMP was significantly higher than that of the control group (89.47% vs 65.87%, P<0.05). The objective examination results (white matter lesions and abnormal EEG) showed that the recovery of patients in the HBO2 group was better than that in the control group. CONCLUSIONS: Hyperbaric oxygen can significantly relieve the symptoms of dementia in patients with DEACMP.

Inhibition of Synaptic Glutamate Exocytosis and Prevention of Glutamate Neurotoxicity by Eupatilin from Artemisia argyi in the Rat Cortex.

The inhibition of synaptic glutamate release to maintain glutamate homeostasis contributes to the alleviation of neuronal cell injury, and accumulating evidence suggests that natural products can repress glutamate levels and associated excitotoxicity. In this study, we investigated whether eupatilin, a constituent of Artemisia argyi, affected glutamate release in rat cortical nerve terminals (synaptosomes). Additionally, we evaluated the effect of eupatilin in an animal model of kainic acid (KA) excitotoxicity, particularly on the levels of glutamate and N-methyl-D-aspartate (NMDA) receptor subunits (GluN2A and GluN2B). We found that eupatilin decreased depolarization-evoked glutamate release from rat cortical synaptosomes and that this effect was accompanied by a reduction in cytosolic Ca2+ elevation, inhibition of P/Q-type Ca2+ channels, decreased synapsin I Ca2+-dependent phosphorylation and no detectable effect on the membrane potential. In a KA-induced glutamate excitotoxicity rat model, the administration of eupatilin before KA administration prevented neuronal cell degeneration, glutamate elevation, glutamate-generating enzyme glutaminase increase, excitatory amino acid transporter (EAAT) decrease, GluN2A protein decrease and GluN2B protein increase in the rat cortex. Taken together, the results suggest that eupatilin depresses glutamate exocytosis from cerebrocortical synaptosomes by decreasing P/Q-type Ca2+ channels and synapsin I phosphorylation and alleviates glutamate excitotoxicity caused by KA by preventing glutamatergic alterations in the rat cortex. Thus, this study suggests that eupatilin can be considered a potential therapeutic agent in the treatment of brain impairment associated with glutamate excitotoxicity.

Undescribed protolimonoids from the root bark of Dictamnus dasycarpus Turcz.

Nine undescribed protolimonoids, including two apotirucallane and seven tirucallane triterpenoids, as well as five known compounds, were isolated from the root bark of Dictamnus dasycarpus Turcz. Their structures were elucidated by extensive spectroscopic analysis. Compounds 4-8, with an undescribed 22,25-epoxytirucallene part, were established their absolute configuration by single-crystal X-ray diffraction of 4. Such compounds might provide evidence for the degradation of protolimonoids to limonoids, bridging an oxidative cleavage biogenetic pathway between these structurally diverse triterpenoids. None of them showed anti-inflammatory, hepatoprotective, or monoamine oxidase B inhibitory activity.

Rutin prevents seizures in kainic acid-treated rats: evidence of glutamate levels, inflammation and neuronal loss modulation.

Rutin, a naturally derived flavonoid molecule with known neuroprotective properties, has been demonstrated to have anticonvulsive potential, but the mechanism of this effect is still unclear. The current study aimed to investigate the probable antiseizure mechanisms of rutin in rats using the kainic acid (KA) seizure model. Rutin (50 and 100 mg kg-1) and carbamazepine (100 mg kg-1) were administered daily by oral gavage for 7 days before KA (15 mg kg-1) intraperitoneal (i.p.) injection. Seizure behavior, neuronal cell death, glutamate concentration, excitatory amino acid transporters (EAATs), glutamine synthetase (GS), glutaminase, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits GluA1 and GluA2, N-methyl-D-aspartate (NMDA) receptor subunits GluN2A and GluN2B, activated astrocytes, and inflammatory and anti-inflammatory molecules in the hippocampus were evaluated. Supplementation with rutin attenuated seizure severity in KA-treated rats and reversed KA-induced neuronal loss and glutamate elevation in the hippocampus. Decreased glutaminase and GluN2B, and increased EAATs, GS, GluA1, GluA2 and GluN2A were observed with rutin administration. Rutin pretreatment also suppressed activated astrocytes, downregulated the protein levels of inflammatory molecules [interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high mobility group Box 1 (HMGB1), interleukin-1 receptor 1 (IL-1R1), and Toll-like receptor-4 (TLR-4)] and upregulated anti-inflammatory molecule interleukin-10 (IL-10) protein expression. Taken together, the results indicate that the preventive treatment of rats with rutin attenuated KA-induced seizures and neuronal loss by decreasing glutamatergic hyperactivity and suppressing the IL-1R1/TLR4-related neuroinflammatory cascade.

Effects of Acupuncture Combined with Exercise on Expression of Immune Factors in Aging Rats and Its Significance in Antiaging Intervention.

Background: With the improvement of people's living standards, how to maintain health and delay aging to improve the quality of life and achieve longevity has become a hot topic of concern. objective. To investigate the effect of acupuncture combined with exercise on the expression of immune factors in aging rats and its significance in antiaging intervention. Materials and Methods: Forty-three SD rats included 12 rats in the control group, and the remaining rats were injected intraperitoneally with D-galactose 500 mg/kg to prepare a subacute aging rat model. The 24 rats that were successfully modeled were divided into acupuncture exercise groups and exercise groups according to the random number table method, with 12 rats in each group. After the modeling, the comparison group did not do any intervention, the exercise group was given aerobic exercise intervention, and the acupuncture exercise group was given acupuncture combined with exercise intervention. The effect of immune factor expression in rats was compared. Results: The levels of IgM, IgA, and IgG in the acupuncture exercise group were significantly higher than those in the exercise group (P < 0.05). The IL-10 content in the acupuncture exercise group was significantly higher than that in the exercise group (P < 0.05) and was significantly reduced in the acupuncture exercise group compared with the comparison group (P < 0.05). The level of IL-6 in the acupuncture exercise group was significantly lower than that in the exercise group, and the level of IL-6 in the acupuncture exercise group was significantly increased compared with the comparison group (P < 0.05). The C3 and C4 levels in the acupuncture exercise group were significantly higher than those in the exercise group (P < 0.05). The levels of IFN-γ and TNP-α were significantly lower in the acupuncture exercise group than in the exercise group and significantly increased in the acupuncture exercise group compared with the comparison group (P < 0.05). Conclusion: Ling turtle eight method acupuncture combined with exercise promoted the development of immune organ spleen, enhances the body's immune function and complement system, inhibits the immune inflammatory response and regulates immune balance, reduces the inflammatory response caused by the aging of D-type galactose, and achieves the effect of delaying aging.

GPX4 Plays a Crucial Role in Fuzheng Kang'ai Decoction-Induced Non-Small Cell Lung Cancer Cell Ferroptosis.

Background: Fuzheng Kang'ai decoction (FZKA) has been widely used to treat Non-Small Cell Lung Cancer (NSCLC) patients in China for decades, showing definitively curative effects in clinic. Recently, we found that FZKA could induce NSCLC cell ferroptosis, another type of programmed cell death (PCD), which is totally different from cell apoptosis. Therefore, in the present study, we aim to discover the exact mechanism by which FZKA induces NSCLC cell ferroptosis, which is rarely studied in Traditional Chinese Medicine (TCM). Methods: Cell proliferation assay were performed to detect the cell viability. Cell ferroptosis triggered by FZKA was observed by performing lipid peroxidation assay, Fe2+ Ions assay, and mitochondrial ultrastructure by transmission electron microscopy. Ferroptosis inhibitors including liproxstatin-1 and UAMC 3203 were used to block ferroptosis. The ratio of GSH/GSSG was done to measure the alteration of oxidative stress. Western blot and qRT-PCR were carried out to detect the expression of solute carrier family 7 member 11 (SLC7A11), solute carrier family 3 member 2 (SLC3A2) and glutathione peroxidase 4 (GPX4) at protein and mRNA levels, respectively. Lentivirus transfection was performed to overexpress GPX4 stably. Animal model was done to verify the effect of FZKA-induced ferroptosis in NSCLC in vivo and immunohistochemistry was done to detect the expression of SLC7A11, SLC3A2 and GPX4 at protein level. Results: First of all, in vitro experiments confirmed the inhibition effect of FZKA on NSCLC cell growth. We then, for the first time, found that FZKA induced NSCLC cell ferroptosis by increasing lipid peroxidation and cellular Fe2+ Ions. Moreover, characteristic morphological changes of NSCLC cell ferroptosis was observed under transmission electron microscopy. Mechanistically, GPX4, as a key inhibitor of lipid peroxidation, was greatly suppressed by FZKA treatment both at protein and mRNA levels. Furthermore, system xc- (SLC7A11 and SLC3A2) were found to be suppressed and a decreased GSH/GSSG ratio was observed at the same time when treated with FZKA. Notably, overexpressing GPX4 reversed the effect of FZKA-induced NSCLC cell ferroptosis significantly. Finally, the above effect was validated using animal model in vivo. Conclusion: Our findings conclude that GPX4 plays a crucial role in FZKA-induced NSCLC cell ferroptosis, providing a novel molecular mechanism by which FZKA treats NSCLC.

Anticonvulsive and Neuroprotective Effects of Eupafolin in Rats Are Associated with the Inhibition of Glutamate Overexcitation and Upregulation of the Wnt/ß-Catenin Signaling Pathway.

Several plant compounds have been found to possess neuroactive properties. The aim of this study was to investigate the anticonvulsant effect of eupafolin, a major active component extracted from Salvia plebeia, a herb used in traditional medicine for its anti-inflammatory properties. To this end, we assessed the anticonvulsant effects of eupafolin in rats intraperitoneally (i.p.) injected with kainic acid (KA) to elucidate this mechanism. Treatment with eupafolin (i.p.) for 30 min before KA administration significantly reduced behavioral and electrographic seizures induced by KA, similar to carbamazepine (i.p.), a widely used antiepileptic drug. Eupafolin treatment also significantly decreased KA seizure-induced neuronal cell death and glutamate elevation in the hippocampus. In addition, eupafolin notably reversed KA seizure-induced alterations in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluR2, glutamate decarboxylase 67 (GAD67, GABAergic enzyme), and Wnt signaling-related proteins, including porcupine, Wnt1, phosphorylated-glycogen synthase kinase-3ß, ß-catenin, and Bcl-2 in the hippocampus. Furthermore, the increased level of Dickkopf-related protein 1 (Dkk-1, a Wnt signaling antagonist) and the decreased level of Disheveled1 (Dvl-1, a Wnt signaling activator) in the hippocampus of KA-treated rats were reversed by eupafolin. This study provides evidence of the anticonvulsant and neuroprotective properties of eupafolin and of the involvement of regulation of glutamate overexcitation and Wnt signaling in the mechanisms of these properties. These findings support the benefits of eupafolin in treating epilepsy.