[Molding matrix formulation of hot-melt pressure-sensitive adhesive plaster of personalized traditional Chinese medicine preparations].

This study aims to optimize the matrix formulation for the hot-melt pressure-sensitive adhesive plaster of personalized traditional Chinese medicine(TCM) preparations and verify the applicability of the formulation. The central composite design in JMP Pro 16.1.0 was employed to optimize the dosages of styrene-isoprene-styrene triblock copolymer(SIS), hydrogenated petroleum resin, and lightweight liquid paraffin, with the fine powder of Yipifang as the model drug(drug loading of 10%) and the sensory score and objective evaluation as the comprehensive evaluation indicators. The quality evaluation system of hot-melt pressure-sensitive adhesive plaster of personalized TCM preparations was established. The applicability of the optimized matrix formulation of hot-melt pressure-sensitive adhesive plaster was verified with 16 TCM preparations for external application. Furthermore, the applicability of the matrix formulation was investigated with different drug loadings. The general molding matrix formulation was SIS∶hydrogenated petroleum resin∶lightweight liquid paraffin 3∶3∶5. The optimized matrix formulation showed good molding properties and high quality scores for 16 TCM preparations and were suitable for the plastering of finely powdered decoction pieces with a loading capacity of 10% to 30%. The results suggest that the optimized matrix formulation has good applicability and is suitable for TCM preparations. The findings lay a foundation for the application and promotion of the hot-melt pressure-sensitive adhesive plasters of personalized TCM preparations.

Vitamin C alleviates rheumatoid arthritis by modulating gut microbiota balance.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic and symmetric in-flammation. Our previous research revealed an imbalance in the gut flora of RA patients and showed that certain gut microbiota can accelerate RA progression by enhancing vitamin C degradation. However, it is unclear whether vitamin C supplementation could improve the gut microbiota to prevent the development of arthritis by interfering with the gut-joint axis. In this work, we aimed to evaluate the effects of vitamin C in regulating the gut microbiota and to elucidate its potential role in the onset and progression of RA in a mouse model, thus providing a basis for the development of new intervention strategies and treatments for RA. In this study, collagen-induced arthritis (CIA) mouse models, biochemical, histological and 16S rRNA microbiological methods were used to investigate the role and possible mechanism of vitamin C in rheumatoid arthritis. The results showed that treatment of CIA mice with vitamin C effectively rescued the gut mi-crobiota imbalance and suppressed the inflammatory response associated with RA, and effectively alleviated arthritis symptoms in mice in which levels of the pro-inflammatory cytokines IL-6 and TNF-α were specifi-cally reduced. In conclusion, our results demonstrate the potential of vitamin C as a potential therapeutic choice for RA.

[Identification and visual analysis of ginsenosides in multi-steamed roots of Panax quinquefolium based on UPLC-Q-TOF-MS/MS and MALDI-MSI].

This study aims to investigate the component variations and spatial distribution of ginsenosides in Panax quinquefolium roots during repeated steaming and drying. Ultra performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to identify the ginsenosides in the root extract. Matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI) was employed to visualize the spatial distribution and spatiotemporal changes of prototype ginsenosides and metabolites in P. quinquefolium roots. The UPLC results showed that 90 ginsenosides were identified during the steaming process of the roots, and polar ginsenosides were converted into low polar or non-polar ginsenosides. The content of prototype ginsenosides decreased, while that of rare ginsenosides increased, which included 20(S/R)-ginsenoside Rg_3, 20(S/R)-ginsenoside Rh_2, and ginsenosides Rk_1, Rg_5, Rs_5, and Rs_4. MALDI-MSI results showed that ginsenosides were mainly distributed in the epidermis and phloem. As the steaming times increased, ginsenosides were transported to the xylem and medulla. This study provides fundamental information for revealing the changes of biological activity and pharmacological effect of P. quinquefolium roots that are caused by repeated steaming and drying and gives a reference for expanding the application scope of this herbal medicine.

Integrated component identification, network pharmacology, and experimental verification revealed mechanism of Dendrobium officinale Kimura et Migo against lung cancer.

BACKGROUND: Dendrobium officinale Kimura et Migo (DO), a valuable Chinese herbal medicine, has been reported to exhibit potential effects in the prevention and treatment of lung cancer. However, its material basis and mechanism of action have not been comprehensively analyzed. PURPOSE: The objective of this study was to preliminarily elucidate the active components and pharmacological mechanisms of DO in treating lung cancer, according to UPLC-Q/TOF-MS, HPAEC-PAD, network pharmacology, molecular docking, and experimental verification. METHODS: The chemical components of DO were identified via UPLC-Q/TOF-MS, while the monosaccharide composition of Dendrobium officinale polysaccharide (DOP) was determined by HPAEC-PAD. The prospective active constituents of DO as well as their respective targets were predicted in the combined database of Swiss ADME and Swiss Target Prediction. Relevant disease targets for lung cancer were searched in OMIM, TTD, and Genecards databases. Further, the active compounds and potential core targets of DO against lung cancer were found by the C-T-D network and the PPI network, respectively. The core targets were then subjected to enrichment analysis in the Metascape database. The main active compounds were molecularly docked to the core targets and visualized. Finally, the viability of A549 cells and the relative quantity of associated proteins within the major signaling pathway were detected. RESULTS: 249 ingredients were identified from DO, including 39 flavonoids, 39 bibenzyls, 50 organic acids, 8 phenanthrenes, 27 phenylpropanoids, 17 alkaloids, 17 amino acids and their derivatives, 7 monosaccharides, and 45 others. Here, 50 main active compounds with high degree values were attained through the C-T-D network, mainly consisting of bibenzyls and monosaccharides. Based on the PPI network analysis, 10 core targets were further predicted, including HSP90AA1, SRC, ESR1, CREBBP, MAPK3, AKT1, PIK3R1, PIK3CA, HIF1A, and HDAC1. The results of the enrichment analysis and molecular docking indicated a close association between the therapeutic mechanism of DO and the PI3K-Akt signaling pathway. It was confirmed that the bibenzyl extract and erianin could inhibit the multiplication of A549 cells in vitro. Furthermore, erianin was found to down-regulate the relative expressions of p-AKT and p-PI3K proteins within the PI3K-Akt signaling pathway. CONCLUSIONS: This study predicted that DO could treat lung cancer through various components, multiple targets, and diverse pathways. Bibenzyls from DO might exert anti-lung cancer activity by inhibiting cancer cell proliferation and modulating the PI3K-Akt signaling pathway. A fundamental reference for further studies and clinical therapy was given by the above data.

Integrated metabolome and transcriptome analyses reveal the molecular mechanism underlying dynamic metabolic processes during taproot development of Panax notoginseng.

BACKGROUND: Panax notoginseng (Burk) F. H. Chen is one of the most famous Chinese traditional medicinal plants. The taproot is the main organ producing triterpenoid saponins, and its development is directly linked to the quality and yield of the harvested P. notoginseng. However, the mechanisms underlying the dynamic metabolic changes occurring during taproot development of P. notoginseng are unknown. RESULTS: We carried out metabolomic and transcriptomic analyses to investigate metabolites and gene expression during the development of P. notoginseng taproots. The differentially accumulated metabolites included amino acids and derivatives, nucleotides and derivatives, and lipids in 1-year-old taproots, flavonoids and terpenoids in 2- and 3-year-old taproots, and phenolic acids in 3-year-old taproots. The differentially expressed genes (DEGs) are related to phenylpropanoid biosynthesis, metabolic pathway and biosynthesis of secondary metabolites at all three developmental stages. Integrative analysis revealed that the phenylpropanoid biosynthesis pathway was involved in not only the development of but also metabolic changes in P. notoginseng taproots. Moreover, significant accumulation of triterpenoid saponins in 2- and 3-year-old taproots was highly correlated with the up-regulated expression of cytochrome P450s and uridine diphosphate-dependent glycosyltransferases genes. Additionally, a gene encoding RNase-like major storage protein was identified to play a dual role in the development of P. notoginseng taproots and their triterpenoid saponins synthesis. CONCLUSIONS: These results elucidate the molecular mechanism underlying the accumulation of and change relationship between primary and secondary metabolites in P. notoginseng taproots, and provide a basis for the quality control and genetic improvement of P. notoginseng.

Multi-omics reveals that 5-O-methylvisammioside prevention acute liver injury in mice by regulating the TNF/MAPK/NF-κB/arachidonic acid pathway.

BACKGROUND: The pathogenesis of acute liver injury (ALI) has been a pressing issue in the medical scientific community. We previously found that 5-O-methylvisammioside (MeV) from Saposhnikovia divaricata (Turcz.) Schischk has excellent anti-inflammatory properties. However, the mechanism by which MeV protects against ALI still needs to be deeply investigated. PURPOSE: In the present study, we established an acetaminophen (APAP) -induced ALI mouse model and pre-protected the mice with MeV. METHODS & RESULTS: Our findings indicate that MeV (5 and 10 mg/kg) lowered the blood levels of alanine aminotransferase and aspartate aminotransferase and reduced the infiltration of inflammatory cells in the liver. MeV initially showed an inhibitory effect on ALI. We then analyzed the molecular mechanisms underlying the effects of MeV by transcriptomic and metabolomic analyzes. Through transcriptomic analysis, we identified 4675 differentially expressed genes between the APAP+MeV group and the APAP-induced ALI group, which were mainly enriched in the MAPK pathway, the TNF pathway, and the NF-κB pathway. Through metabolomic analysis, we found that 249 metabolites in the liver were differentially regulated between the APAP+MeV group and the APAP- induced ALI group, which were mainly enriched in the arachidonic acid pathway. The mRNA expression levels of key genes (encoding TNF-α, p38, AP-1, RelB, IL-1ß, and Ptges), as determined by RT-PCR analysis, were consistent with the RNA-seq data. The ELISA results indicate that MeV markedly decreased the serum levels of TNF-α and IL-1ß in mice. Finally, the key proteins in the NF-κB and MAPK pathways were examined using immunoblotting. The results showed that MeV decreased IκB-α phosphorylation and inhibited the nuclear translocation of NF-κB. In addition, MeV reduced the hepatic inflammatory burst mainly by inhibiting the phosphorylation of p38 and JNK in the MAPK pathway. CONCLUSION: The present study demonstrated (i) that MeV could ameliorate APAP-induced ALI by inhibiting arachidonic acid metabolism and the TNF, MAPK, and NF-κB pathways, and (ii) that MeV is a promising drug candidate for the prevention of ALI.

Umbilical Cord Blood Betaine in Infants Born Small for Gestational Age.

Background: Birth weight is of importance due to its relation to fetal health, and it's also a predictor of the subsequent development of the child. Objective: This study aims to assess whether betaine is associated with poor fetal growth. Design: A case-control study was used in this study. Setting: The study took place at the Chongqing Maternal and Child Health Hospital, in Chong Qing, China. Participants: A total of 141mother-infant pairs were recruited from the Department of Obstetrics of our hospital between June 2021 and December 2021. According to gestational age and birth weight, themother-infant pairs were divided into small-for-gestational-age and appropriate-for-gestational-age groups. Primary Outcome Measures: Cord plasma concentrations of betaine were measured by high-performance liquid chromatography tandem mass spectrometry. Plasma levels of triglycerides, low-density lipoprotein, high-density lipoprotein and total cholesterol were determined using commercially available assays on an automatic biochemical analyzer (BS-240 VET, Mindray Medical, Shenzhen, China) using reagent from Mindray Medical company. Results: Cord plasma betaine concentrations were higher in small-for-gestational-age relative to appropriate-for-gestational-age newborns, and were not correlated to lipid levels. Adjusting for maternal and neonatal characteristics, birth weight and birth length were negatively correlated with the levels of betaine. Higher betaine concentrations were associated with increased risks of small-for-gestational-age. Conclusions: Elevated cord blood betaine concentration was independently associated with a higher risk of small-for-gestational-age infants, suggesting that betaine dysregulation may be a risk factor for impaired fetal growth.

The function of chemical folic acid in calibration methods and neurodevelopmental disorders.

Functional molecules have been attracting increasing attention in environmental and physiological studies. In particular, folic acid (FA) could be considered a key factor in estimating, adjusting, and making decisions in the treatment of neurodevelopmental disorders. It promotes the general significance and conceptual for considering FA molecular scientific research detections, which implies related advancement in both of biological structure and detection methods. Among these applications, the FA molecule acts as a coenzyme that incorporates carbon atoms and synthesizes purines and pyrimidines. Therefore, the calibration method has real applications and can be used as a sensing platform and for detection approaches, which conveys the internal relationship between the FA molecule and physiological characterization. This mini review briefly discusses multiple FA application fields and detection pathways and could supplement their utilization in anticipation of the onset of disease.

A multi-center cross-sectional study of Chinese Herbal Medicine-Drug adverse reactions using active surveillance in Singapore's Traditional Chinese Medicine clinics.

BACKGROUND: This study aimed to investigate the rates and causality of patient-reported adverse events (AEs) associated with concomitant Chinese Herbal Medicine (CHM) and Western Medicine prescription drug (WMPD) consumption through active surveillance in Singapore's Traditional Chinese Medicine (TCM) clinics. METHODS: A cross-sectional study was conducted at five TCM clinics across Singapore from 8th May till 8th July 2023. Patients were screened to determine rates of CHM and WMPD consumption, and then interviewed if an AE was reported. An expert committee assessed the AE reports to determine causality. Along with descriptive statistics, odds ratios were calculated to determine AE occurrence likelihoods for patients who consumed both CHM and WMPD compared to CHM consumption alone. RESULTS: 1028 patients were screened and 62.65% of them reported concurrent CHM-WMPD consumption. Patients who consumed CHM and WMPD were 3.65 times more likely to experience an AE as compared to CHM consumption alone. 18 AE reports were adjudicated, with most AEs deemed unlikely due to CHM consumption. CONCLUSIONS: A large proportion of patients consumed CHM and WMPD concurrently, thus increasing their risk of experiencing AEs compared to those consuming CHM only. Active surveillance is applicable for detecting AEs, collecting data for causality assessment, and analysis.

Nutritional Intervention Leads to Successful Re-pregnancy of Pregnant Women with Severe Preeclampsia: A Case Report.

Objective: Preeclampsia is a common and serious pregnancy complication, with a high risk of onset in clinical practice, which seriously affects the physical and mental health of patients. Insufficient nutrition is considered as one of the factors contributing to the occurrence of preeclampsia, but there are few reports on the prevention of preeclampsia through nutritional interventions. This study reports the effects of personalized nutritional support on a second pregnancy in a woman with severe preeclampsia. Methods: A patient with familial inherited nephropathy was followed up postpartum, and nutritional interventions including light diet, avoid spicy food, according to the principle of carbohydrate accounting for 55%-65%, fat accounting for 20%-30%, protein accounting for 10%-15%, were performed according to her individual circumstances after her second pregnancy. Moreover, the kidney function index was detected regularly by quantitative detection of urine protein in the course of pregnancy, and the pregnancy status was observed. Results: After the nutritional intervention, the 24 h urinary protein quantification and plasma albumin were decreased with the increase of gestational age, while urinary occult blood was progressive negative conversion, indicating that the kidney function of the pregnant woman gradually recovered but did not reach the normal level. Moreover, the fetal development was normal. Conclusion: Dietary nutrition treatment during pregnancy and active cooperation during pregnancy can effectively prevent the recurrence of preeclampsia in high-risk pregnant women. However, further research or larger studies are still needed to validate these findings.

Oxymatrine protects articular chondrocytes from IL-1ß-induced damage through autophagy activation via AKT/mTOR signaling pathway inhibition.

BACKGROUND: Osteoarthritis (OA) is a common degenerative joint disease characterized by persistent articular cartilage degeneration and synovitis. Oxymatrine (OMT) is a quinzolazine alkaloid extracted from the traditional Chinese medicine, matrine, and possesses anti-inflammatory properties that may help regulate the pathogenesis of OA; however, its mechanism has not been elucidated. This study aimed to investigate the effects of OMT on interleukin-1ß (IL-1ß)-induced damage and the potential mechanisms of action. METHODS: Chondrocytes were isolated from Sprague-Dawley rats. Toluidine blue and Collagen II immunofluorescence staining were used to determine the purity of the chondrocytes. Thereafter, the chondrocytes were subjected to IL-1ß stimulation, both in the presence and absence of OMT, or the autophagy inhibitor 3-methyladenine (3-MA). Cell viability was assessed using the MTT assay and SYTOX Green staining. Additionally, flow cytometry was used to determine cell apoptosis rate and reactive oxygen species (ROS) levels. The protein levels of AKT, mTOR, LC3, P62, matrix metalloproteinase-13, and collagen II were quantitatively analyzed using western blotting. Immunofluorescence was used to assess LC3 expression. RESULTS: OMT alleviated IL-1ß-induced damage in chondrocytes, by increasing the survival rate, reducing the apoptosis rates of chondrocytes, and preventing the degradation of the cartilage matrix. In addition, OMT decreased the ROS levels and inhibited the AKT/mTOR signaling pathway while promoting autophagy in IL-1ß treated chondrocytes. However, the effectiveness of OMT in improving chondrocyte viability under IL-1ß treatment was limited when autophagy was inhibited by 3-MA. CONCLUSIONS: OMT decreases oxidative stress and inhibits the AKT/mTOR signaling pathway to enhance autophagy, thus inhibiting IL-1ß-induced damage. Therefore, OMT may be a novel and effective therapeutic agent for the clinical treatment of OA.

Modulation of fried spring roll wrapper quality upon treatment of batter with maltogenic amylase, transglutaminase and bromelain.

BACKGROUND: Fried foods are favored for their unique crispiness, golden color and flavor, but they also face great challenge because of their high oil content, high calories and the existence of compounds such as acrylamide and polycyclic aromatic hydrocarbons. Long-term consumption of fried foods may adversely affect health. Therefore, it is necessary to explore fried foods with lower oil contents and a high quality to meet the demand. RESULTS: A method of enzyme treatment was explored to investigate the effects of maltogenic amylase (MA), transglutaminase (TG) and bromelain (BRO) on the physicochemical properties of the batter and the quality of fried spring roll wrapper (FSRW). The results showed that the MA-, TG- or BRO-treated batters had a significant shear-thinning behavior, especially with an increase in viscosity upon increasing TG contents. FSRW enhanced its fracturability from 419.19 g (Control) to 616.50 g (MA-6 U g-1), 623.49 g (TG-0.75 U g-1) and 644.96 g (BRO-10 U g-1). Meanwhile, in comparison with BRO and MA, TG-0.5 U g-1 endowed batter with the highest density and thermal stability. MA-15 U g-1 and TG-0.5 U g-1 displayed FSRW with uniform and dense pores, and significantly reduced its oil content by 18.05% and 25.02%, respectively. Moreover, compared to MA and TG, BRO-50 U g-1 improved the flavor of FSRW. CONCLUSION: MA, TG or BRO played a key role in affecting the physicochemical properties of the batter and the quality of FSRW. TG-0.5 U g-1 remarkly reduced the oil content of FSRW with a great potential in practical application. © 2024 Society of Chemical Industry.

High-dose vitamin D supplementation in patients with COVID-19: A meta-analysis of randomized controlled trials.

The efficacy of administering high doses of vitamin D to patients diagnosed with COVID-19 remains uncertain. We conducted a comprehensive search across multiple databases (PubMed, EMBASE, Cochrane Library, and ISI Web of Science) from inception until August 2022, with no limitations on language, to locate randomized controlled trials (RCTs) that investigated the impact of high-dose vitamin D supplementation (defined as a single dose of ≥100,000 IU or daily dose of ≥10,000 IU reaching a total dose of ≥100,000 IU) on COVID-19 patients. Risk ratios (RR) with 95% confidence intervals (CI) and weighted mean differences (WMD) with 95% CI were calculated. Our meta-analysis included 5 RCTs with a total of 834 patients. High-dose vitamin D supplementation did not show any significant benefits for mortality (I 2 = 0.0%, p = .670; RR 1.092, 95% CI 0.685-1.742, p = .711) or intensive care unit (ICU) admission (I 2 = 0.0%, p = .519; RR 0.707, 95% CI 0.454-1.102, p = .126) in COVID-19 patients compared to the control group. However, it was found to be safe and well-tolerated (I 2 = 0.0%, p = .887; RR 1.218, 95% CI 0.930-1.594, p = .151). Subgroup analysis also showed no benefits in overall mortality, including for patients with vitamin D deficiency (I 2 = 0.0%, p = .452; RR 2.441, 95% CI 0.448-13.312, p = .303) or compared to the placebo (I 2 = 0.0%, p = .673; RR 1.666, 95% CI 0.711-3.902, p = .240). Our research indicates that there is no evidence to support the efficacy of high-dose vitamin D supplementation in improving clinical outcomes among individuals with COVID-19, in line with previous studies focused on contexts including rickets. Considering the limitations of the study, additional research may be required.

Total paeony glycoside relieves neuroinflammation to exert antidepressant effect via the interplay between NLRP3 inflammasome, pyroptosis and autophagy.

BACKGROUND: Depression is a common mental illness characterised by abnormal and depressed emotions. Total paeony glycoside (TPG) is a naturally active saponin extracted from the traditional Chinese medicine Radix Paeoniae rubra. However, the antidepressant and neuroinflammatory effects of TPG have not been thoroughly studied. PURPOSE: To study the therapeutic potential of TGP in depression caused by neuronal injury and neuroinflammation and to explore the mechanism of TGP and the relationship between the NLRP3 inflammasome, pyroptosis, and autophagy. STUDY DESIGN: A chronic unpredictable mild stress (CUMS)-induced depression model and a cell model of corticosterone (CORT)-induced hippocampal neuron injury were established to evaluate the therapeutic effects of TPG. METHODS: The composition of TPG was analysed using high-performance liquid chromatography and mass spectrometry. The effects of TPG and fluoxetine on depression-like behaviour, neuronal injury, neuroinflammation, pyroptosis, and mitochondrial autophagy in the mice models were evaluated. RESULTS: TGP alleviated depression-like behaviours in mice and inhibited hippocampal neuronal apoptosis. The secretion of inflammatory cytokines was significantly reduced in CORT-induced hippocampal neuron cells and in the serum of a mouse model of CUMS-induced depression. In addition, TGP treatment reduced the levels of NLRP3 family pyrin structural domains, including NLRP3, pro-caspase-1, caspase-1, and IL-1ß, and the pyroptosis related proteins such as GSDMD-N. Importantly, TPG attenuated mitochondrial dysfunction, promoted the clearance of damaged mitochondria, and the activation of mitochondrial autophagy, which reduced ROS accumulation and NLRP3 inflammasome activation. An in-depth study observed that the regulatory effect of TPG on autophagy was attenuated by the autophagy inhibitor 3-methyladenine (3-MA) in vitro and in vivo. However, administration of the caspase-1 inhibitor Belnacasan (VX-765) successfully inhibited pyroptosis and showed a synergistic therapeutic effect with TPG. CONCLUSION: These results indicate that TPG can repair neuronal damage by activating autophagy, restoring mitochondrial function, and reducing inflammation-mediated pyroptosis, thereby playing an important role in the alleviation of neuroinflammation and depression. This study suggests new potential drugs and treatment strategies for neuroinflammation-related diseases and depression.

N-3 polyunsaturated fatty acids attenuate amyloid-beta-induced toxicity in AD transgenic Caenorhabditis elegans via promotion of proteasomal activity and activation of PPAR-gamma.

Alzheimer's disease (AD) is a common neurodegenerative disease that causes progressive cognitive decline. A major pathological characteristic of AD brain is the presence of senile plaques composed of ß-amyloid (Aß), the accumulation of which induces toxic cascades leading to synaptic dysfunction, neuronal apoptosis, and eventually cognitive decline. Dietary n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial for patients with early-stage AD; however, the mechanisms are not completely understood. In this study, we investigated the effects of n-3 PUFAs on Aß-induced toxicity in a transgenic AD Caenorhabditis elegans (C. elegans) model. The results showed that EPA and DHA significantly inhibited Aß-induced paralytic phenotype and decreased the production of reactive oxygen species while reducing the levels of Aß in the AD worms. Further studies revealed that EPA and DHA might reduce the accumulation of Aß by restoring the activity of proteasome. Moreover, treating worms with peroxisome proliferator-activated receptor (PPAR)-γ inhibitor GW9662 prevented the inhibitory effects of n-3 PUFAs on Aß-induced paralytic phenotype and diminished the elevation of proteasomal activity by n-3 PUFAs, suggesting that PPARγ-mediated signals play important role in the protective effects of n-3 PUFAs against Aß-induced toxicity.

Structural characterisation of deer sinew peptides as calcium carriers, their promotion of MC3T3-E1 cell proliferation and their effect on bone deposition in mice.

Deer sinew as a by-product has high collagen and nutritional value. This study focuses on its hydrolysate being used as a calcium carrier to develop functional foods. The chelation mechanism was analyzed by SEM, EDS, UV-vis, FTIR, and fluorescence spectroscopy and zeta potential analysis after using peptide-sequenced deer sinew peptides for chelation with calcium ions. The results showed that the chelation of deer sinew peptides with calcium ions occurs mainly at the O and N atoms of carboxyl, amino and amide bonds. In vitro and in vivo studies revealed that deer sinew peptide-calcium chelate (DSPs-Ca) promoted the proliferation of MC3T3-E1 cells without toxic side effects and increased the alkaline phosphatase activity. The DSPs-Ca group improved the bone microstructure induced by low calcium, as well as up-regulated the expression of genes responsible for calcium uptake in the kidneys, as evidenced by serum markers, bone sections, bone parameters, and gene expression analyses in low-calcium-fed mice. From the above, it can be concluded that DSPs-Ca is expected to be a calcium supplement food for promoting bone health.

Three Artemisia pollens trigger the onset of allergic rhinitis via TLR4/MyD88 signaling pathway.

OBJECTIVE: The prevalence of allergic rhinitis is high, making it a relatively common chronic condition. Countless patients suffer from seasonal Allergic rhinitis (AR). The objective of this investigation is to examine the potential involvement of common pollen allergens in seasonal allergic rhinitis, and study the proposed mechanism of Toll-like receptor 4 (TLR4)/Myeloid differentiation primary response gene 88 (MyD88) signaling pathway in the induction of AR. METHOD: A mouse AR model (sensitized group) was constructed with pollen extracts and ovalbumin (OVA) of Artemisia annua (An), Artemisia argyi (Ar) and Artemisia Sieversiana (Si), and thereafter, AR symptom score was performed. After successful modeling, mouse serum and nasal mucosa tissues were extracted for subsequent experiments. The expression levels of immunoglobulin E (IgE), Interleukin (IL)-4, IL-5, IL-13 and Tumor Necrosis Factor-α (TNF-α) in serum were detected using Enzyme-linked immunosorbent assay (ELISA); Hematoxylin-eosin (H&E) staining methods were used to observe the pathological changes of the nasal mucosal tissue; Utilizing immunohistochemistry (IHC) staining, the expression levels of TLR4, MyD88 and Nuclear factor kappa B (NF-κB) p65 in mouse nasal mucosa were quantified; The mRNA and protein expression levels of TLR4, MyD88 and NF-κB p65 in nasal mucosa of sensitized mice were detected with Quantitative reverse transcription PCR (qRT-PCR) and Western Blot. Finally, the in vitro culture of Human nasal mucosal epithelial cells (HNEpC) cells was conducted, and cells were treated with 200 µg/ml Artemisia annua pollen extract and OVA for 24 h. Western Blot assay was used to detect the expression level of TLR4, MyD88 and NF-κB p65 proteins before and after HNEpC cells were treated with MyD88 inhibitor ST-2825. RESULT: On the second day after AR stimulation, the mice showed obvious AR symptoms. H&E results showed that compared to the control group, the nasal mucosal tissue in the sensitized group was significantly more inflamed. Furthermore, ELISA assay showed increased expression levels of IgE, IL-4, IL-5, IL-13 and TNF-α in serum of mice induced by OVA and Artemisia annua pollen, Artemisia argyi pollen and Artemisia Sieversiana pollen than those of the control group. However, the expression level of IL-2 was lower than that of the control group (P < 0.05). Using Immunohistochemistry staining visually observed the expression levels of TLR4, MyD88 and NF-κB p65 in mouse nasal mucosa tissues and quantitatively analyzed. The expression levels of TLR4, MyD88 and NF-κB p65 in the sensitized group were higher than those in the control group, and the differences were statistically significant (P < 0.05). The results from qRT-PCR and Western Blot showed that the mRNA and protein expression levels of TLR4, MyD88 and NF-κB p65 in nasal mucosa of the sensitized group were significantly higher than those in the control group (P < 0.05). Finally, HNEpC cells were cultured in vitro and analyzed using Western Blot. The expression levels of TLR4, MyD88 and NF-κB p65 in OVA and An groups were significantly increased (P < 0.05). After ST-2825 treatment, TLR4 protein expression was significantly increased (P < 0.05) and MyD88 and NF-κB p65 protein expression were significantly decreased (P < 0.05). CONCLUSION: To sum up, the occurrence and development of AR induced by OVA and pollen of Artemisia annua, Artemisia argyi and Artemisia Sieversiana were related to TLR4/MyD88 signal pathway.

Distinguishment of different varieties of rhubarb based on UPLC fingerprints and chemometrics.

Rhubarb, a widely used traditional Chinese medicine (TCM), is primarily used for purging in practice. It is derived from the dried roots and rhizomes of R. tanguticum Maxim. ex Balf. (RT), Rheum officinale Baill. (RO) and R. palmatum L. (RP). To date, although the three varieties of rhubarb have been used as the same medicine in clinical, studies have found that they have different chemical compositions and pharmacological effects. To ensure the stability of rhubarb for clinical use, a simple and effective method should be built to compare and discriminate three varieties of rhubarb. Here, ultra-performance liquid chromatography-diode array detection (UPLC-DAD) fingerprints combined with chemometric methods were developed to evaluate and discriminate 29 batches of rhubarb. Similarity evaluation, hierarchical cluster analysis (HCA) and principal component analysis (PCA) showed that the chemical constituents of the three varieties of rhubarb were significantly different, and the three varieties could be effectively distinguished. Finally, all the 14 common peaks were identified by ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). In this research, the developed UPLC fingerprints offer a simple, reliable and specific approach for distinguishing different varieties of rhubarb. This research aims to promote the scientific and appropriate clinical application of rhubarb from three varieties.

The Effectiveness of Traditional Chinese Medicine in Treating Malignancies via Regulatory Cell Death Pathways and the Tumor Immune Microenvironment: A Review of Recent Advances.

Traditional Chinese Medicine (TCM) has achieved high clinical efficacy in treating malignancies in recent years and is thus gradually becoming an important therapy for patients with advanced tumor for its benefits in reducing side effects and improving patients' immune status. However, it has not been internationally recognized for cancer treatment because TCM's anti-tumor mechanism is not fully elucidated, limiting its clinical application and international promotion. This review traced the mechanism of the TCM-mediated tumor cell death pathway and its effect on remodeling the tumor immune microenvironment, its direct impact on the microenvironment, its anti-tumor effect in combination with immunotherapy, and the current status of clinical application of TCM on tumor treatment. TCM can induce tumor cell death in many regulatory cell death (RCD) pathways, including apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis. In addition, TCM-induced cell death could increase the immune cells' infiltration with an anti-tumor effect in the tumor tissue and elevate the proportion of these cells in the spleen or peripheral blood, enhancing the anti-tumor capacity of the tumor-bearing host. Moreover, TCM can directly affect immune function by increasing the population or activating the sub-type immune cells with an anti-tumor role. It was concluded that TCM could induce a pan-tumor death modality, remodeling the local TIME differently. It can also improve the systemic immune status of tumor-bearing hosts. This review aims to establish a theoretical basis for the clinical application of TCM in tumor treatment and to provide a reference for TCM's potential in combination with immunotherapy in cancer treatment.

Design, Synthesis, and Biological Evaluation of Pierardine Derivatives as Novel Brain-Penetrant and In Vivo Potent NMDAR-GluN2B Antagonists for Ischemic Stroke Treatment.

A series of structurally novel GluN2B NMDAR antagonists were designed, synthesized, and biologically evaluated as anti-stroke therapeutics by optimizing the chemical structure of Pierardine, the active ingredient of traditional Chinese medicine Dendrobium aphyllum (Roxb.) C. E. Fischer identified via in silico screening. The systematic structure-activity relationship study led to the discovery of 58 with promising NMDAR-GluN2B binding affinity and antagonistic activity. Of the two enantiomers, S-58 exhibited significant inhibition (IC50 = 74.01 ± 12.03 nM) against a GluN1/GluN2B receptor-mediated current in a patch clamp assay. In addition, it displayed favorable specificity over other subtypes and off-target receptors. In vivo, S-58 exerted therapeutic efficacy comparable to that of the approved GluN2B NMDAR antagonist ifenprodil and excellent safety profiles. In addition to the attractive in vitro and in vivo potency, S-58 exhibited excellent brain exposure. In light of these merits, S-58 has been advanced to further preclinical investigation as a potential anti-stroke candidate.