Effects of folate-chicory acid liposome on macrophage polarization and TLR4/NF-κB signaling pathway in ulcerative colitis mouse.

BACKGROUND: Chichoric acid (CA) is a major active ingredient found in chicory and Echinacea. As a derivative of caffeic acid, it has various pharmacological effects. PURPOSE: Due to the unclear etiology and disease mechanisms, effective treatment methods for ulcerative colitis (UC) are currently lacking. The study investigated the therapeutic effects of the folate-chicory acid liposome on both LPS-induced macrophage inflammation models and dextran sulfate sodium (DSS)-induced mouse UC models. METHODS: Folate-chicory acid liposome was prepared using the double emulsion ultrasonic method with the aim of targeting folate receptors specifically expressed on macrophages. The study investigated the therapeutic effects of the folate-chicory acid liposome on both LPS-induced macrophage inflammation models and DSS -induced mouse UC models. Furthermore, the effects of the liposomes on macrophage polarization and their underlying mechanisms in UC were explored. RESULTS: The average particle size of folate-chicory acid liposome was 120.4 ± 0.46 nm, with an encapsulation efficiency of 77.32 ± 3.19 %. The folate-chicory acid liposome could alleviate macrophage apoptosis induced by LPS, decrease the expression of inflammatory factors in macrophages, enhance the expression of anti-inflammatory factors, inhibit macrophage polarization towards the M1 phenotype, and mitigate cellular inflammation in vetro. In vivo test, folate-chicory acid liposome could attenuate clinical symptoms, increased colon length, reduced DAI scores, CMDI scores, and alleviated the severity of colonic histopathological damage in UC mice. Furthermore, it inhibited the polarization of macrophages towards the M1 phenotype in the colon and downregulated the TLR4/NF-κB signaling pathway, thereby ameliorating UC in mice. CONCLUSION: Folate-chicory acid liposome exhibited a uniform particle size distribution and high encapsulation efficiency. It effectively treated UC mice by inhibiting the polarization of macrophages towards the M1 phenotype in the colon and downregulating the TLR4/NF-κB signaling pathway.

Discrimination of opium from Afghanistan and Myanmar by infrared spectroscopy coupled with machine learning methods.

Afghanistan and Myanmar are two overwhelming opium production places. In this study, rapid and efficient methods for distinguishing opium from Afghanistan and Myanmar were developed using infrared spectroscopy (IR) coupled with multiple machine learning (ML) methods for the first time. A total of 146 authentic opium samples were analyzed by mid-IR (MIR) and near-IR (NIR), within them 116 were used for model training and 30 were used for model validation. Six ML methods, including partial least squares discriminant analysis (PLS-DA), orthogonal PLS-DA (OPLS-DA), k-nearest neighbour (KNN), support vector machine (SVM), random forest (RF), and artificial neural networks (ANNs) were constructed and compared to get the best classification effect. For MIR data, the average of precision, recall and f1-score for all classification models were 1.0. For NIR data, the average of precision, recall and f1-score for different classification models ranged from 0.90 to 0.94. The comparison results of six ML models for MIR and NIR data showed that MIR was more suitable for opium geography classification. Compared with traditional chromatography and mass spectrometry profiling methods, the advantages of MIR are simple, rapid, cost-effective, and environmentally friendly. The developed IR chemical profiling methodology may find wide application in classification of opium from Afghanistan and Myanmar, and also to differentiate them from opium originating from other opium producing countries. This study presented new insights into the application of IR and ML to rapid drug profiling analysis.

The History of Controlling and Treating Infectious Diseases in Ancient China.

Infectious diseases are the common enemies of mankind. In the course of historical development, they persistently threaten human health and safety. Even today, despite the developments in medical science, we cannot escape the fear and suffering caused by infectious diseases. Whether in ancient or modern times, the source of infection, route of transmission, and a susceptible population are the three key conditions for the prevalence and spread of infectious diseases. All factors closely related to these three conditions can affect the prevalence of infectious diseases. China is one of the cradles of world civilization. The ancient people accumulated a great deal of experience and lessons in the long struggle against infectious diseases. In the face of the current threat posed by widespread infectious disease, it is imperative to review and summarize ancient Chinese ideas and health policies on epidemic prevention and control to inspire contemporary efforts in the prevention and control of infectious disease. The combination of prevention-oriented epidemic prevention ideology and traditional medicine provides valuable insights, especially for impoverished and medically underserved regions.

A Study of Elderly Patients' Preference for "Internet + Nursing Service" Based on Discrete Choice Experiments.

Objective: To investigate the preference of elderly patients for "Internet + Nursing Service", so as to provide reference for accurately matching their service needs. Methods: Based on discrete choice experiments, the elderly patients' "Internet + Nursing Service" choice preference questionnaire was prepared, and 410 elderly patients were interviewed face-to-face. The Conditional Logit Model was used for quantitative analysis of the experimental data. Results: The six attributes included in the study had a significant impact on the elderly patients' preference for "Internet + Nursing Service" (P < .05). Among non-economic attributes, "medical insurance reimbursement ratio -70%" has the highest utility (.263, P < .001), with "hospital size - larger (.205, P < .05)" and "medical insurance reimbursement ratio -50%" (.188, P < .05) ranking second and third, respectively. The relative importance of the attribute of medical insurance reimbursement proportion is the highest (26.44%), and the relative importance of service content is the lowest (9.78%). If the proportion of medical insurance reimbursement increases from 30% to 70%, patients are willing to pay 202.9 yuan, and the probability of choosing "Internet + Nursing Service" increases by 6.1%. Conclusion: Patients prefer to choose a higher proportion of medical insurance reimbursement, a larger medical institution, a higher level of nurses, low single service costs, a basic package, and "Internet + Nursing Service" led by the government and hospitals. Improvement of the price and medical insurance payment policy is recommended, along with the enhancement of the ability of primary nursing services, strengthening of the management of Internet enterprise platforms, and scientific assessment of the needs of patients for personalized nursing services.

Multiomics of HER2-low triple-negative breast cancer identifies a receptor tyrosine kinase-relevant subgroup with therapeutic prospects.

To provide complementary information and reveal the molecular characteristics and therapeutic insights of HER2-low breast cancer, we performed this multiomics study of hormone receptor-negative (HR-) and HER2-low breast cancer, also known as HER2-low triple-negative breast cancer (TNBC), and identified 3 subgroups: basal-like, receptor tyrosine kinase-relevant (TKR), and mesenchymal stem-like. These 3 subgroups had distinct features and potential therapeutic targets and were validated in external data sets. Interestingly, the TKR subgroup (which exists in both HR+ and HR- breast cancer) had activated HER2 and downstream MAPK signaling. In vitro and in vivo patient-derived xenograft experiments revealed that pretreatment of the TKR subgroup with a tyrosine kinase inhibitor (lapatinib or tucatinib) could inhibit HER2 signaling and induce accumulated expression of nonfunctional HER2, resulting in increased sensitivity to the sequential HER2-targeting, Ab-drug conjugate DS-8201. Our findings identify clinically relevant subgroups and provide potential therapeutic strategies for HER2-low TNBC subtypes.

Effects of Different Dietary Selenium Sources on the Meat Quality and Antioxidant Capacity of Yellow Catfish (Pelteobagrus fulvidraco).

To assess the effect of dietary selenium (Se) sources on the meat quality and antioxidant capacity of yellow catfish (Pelteobagrus fulvidraco), sodium selenite (Na2SeO3), Se yeast, and selenium-enriched Spirulina platensis (Se-SP) were supplemented in the control diet at 0.30 mg Se/kg feed to formulate four diets. The experimental period lasted 50 days. The results showed that Se levels in the plasma, liver, muscle, and whole body were significantly increased by dietary Se yeast supplementation (P < 0.05) but showed no change in response to Na2SeO3 (P > 0.05). The three types of Se all increased the firmness and decreased the fracturability of the muscles (P < 0.05), but only Na2SeO3 resulted in higher springiness, flexibility, stringiness, and stickiness (P < 0.05). In addition, the muscle n-3 polyunsaturated fatty acid (PUFA) content was increased by Se yeast (P < 0.05). Regarding antioxidant capacity, dietary Se yeast and Se-SP supplementation improved hepatic glutathione peroxidase activity but decreased hepatic malondialdehyde content (P < 0.05). Given these results, Se yeast was found to be the optimal source of Se for yellow catfish for higher tissue retention, antioxidant capacity, and PUFA levels. Dietary Se is an effective way to regulate the meat quality and antioxidant capacity of yellow catfish.

Mechanism underlying the action of Duanteng-Yimu Tang in regulating Treg/Th17 imbalance and anti-rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is a chronic immune disease characterised by synovitis and cartilage destruction. Currently, many patients experience poor remission after new antirheumatic drug treatments. Duanteng-Yimu Tang (DTYMT), a traditional Chinese medicine, is effective in the treatment of RA. In this research, we designed to investigate the anti-RA effects of DTYMT and explore its potential mechanisms. Methods: Network pharmacology was adopted to explore the main pathways of DTYMT in patients with RA. Collagen-induced arthritis models of male DBA/1 mice were established, and their histopathological changes were observed by hematoxylin-eosin staining and micro-CT. qRT-PCR was performed to detect the expression of Foxp3 and RORγt in the serum and synovial tissue and IL-17, IL-1ß, TNF-α, and IL-10 mRNA in vivo. The proliferation and invasion of synovial cells were analyzed using Cell Counting Kit-8 and transwell assays, respectively. The ratio of T helper 17 (Th17) to regulatory T (Treg) cells was analyzed by flow cytometry. Results: Network pharmacology analysis revealed that Th17 cell differentiation may be the key pathway of DTYMT in RA. DTYMT ameliorated joint damage, inhibited RORγt expression, and increased Foxp3 expression in CIA mice. DTYMT significantly decreased IL-1ß, IL-17, and TNF-α mRNA levels, and increased IL-10 mRNA levels in IL-6-induced cells. Additionally, DTYMT inhibited Th17 cell differentiation and promoted Treg cell production, thus improving the Treg/Th17 imbalance. DTYMT also inhibited the proliferation, migration, and invasion of RA fibroblast-like synovial cells. Conclusions: These results indicate that DTYMT could regulate the Treg/Th17 cell balance, which is a possible mechanism of DTYMT in treating RA.

[Effect of heat-reinforcing needling on the inflammation and necrotizing apoptosis of synovial cells in synovial tissues of knee joint in rabbits with cold syndrome rheumatoid arthritis].

OBJECTIVE: To observe the effect of heat-reinforcing needling (HRN) on inflammatory factors and necrotizing apoptosis of synovial cells in synovial tissues of knee joint in rabbits with cold syndrome rheumatoid arthritis (RA), so as to explore its underlying mechanisms in treating RA. METHODS: By using the random number table method, 40 New Zealand rabbits were randomly divided into normal, model, antagonist(AG), twist-reinforceing needling (TRN) and HRN groups, with 8 rabbits in each group. The model of cold syndrome RA was established by ovalbumin induction combined with Freund's complete adjuvant injection and cryogenic freezing method. In the AG group, the antagonist TAK-632 (25 mg/kg) was administered intragastrically, once every 2 days, for a total of 7 times. Rabbits of TRN and HRN groups were treated with corresponding acupuncture techniques on bilateral "Zusanli" (ST36) for 30 min, once a day for 14 days. After intervention, the changes of knee skin temperature and circumference were measured. Color Doppler ultrasound was used to observe the joint cavity effusion, synovial thickness and internal blood flow signal. The histomorphological changes of synovial tissues were observed after HE staining. ELISA was used to detect the contents of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 in serum. Transmission electron microscope was used to observe the ultrastructure, necrosis and apoptosis of synovial cells. Western blot was used to detect the protein expressions of receptor-interacting protein kinase1 (RIPK1), RIPK3, mixed lineage kinase domain-like protein (MLKL), and phosphorylation （p）-MLKL in synovial tissues. RESULTS: Compared with the normal group, the synovial was diffusely hyperplasia, joint cavity effusion and abnormal blood flow signal were obvious, inflammatory cells were clustered, arranged closely and disordered in the model group. The findings of transmission electron microscopy showed disruption of cell membrane integrity, swollen or ruptured mitochondria, obviously ruptured nucleus, condensed and pyknotic chromatin and nucleolus in the model group. Also, the skin temperature of the knee joint was significantly decreased (P<0.01), while the circumference of the knee joint, the contents of TNF-α, IL-1ß and IL-6 in serum, the protein expressions of RIPK1, RIPK3, p-MLKL and MLKL in synovial tissues were significantly increased (P<0.01) in the model group. Compared with the model group, synovial tissue hyperplasia, joint cavity effusion, abnormal blood flow signals, synovial cell proliferation, inflammatory cell infiltration, disruption of cell membrane integrity, cell swelling, cell rupture, and nuclear pyknosis were reduced to different degrees in the AG, TRN and HRN groups. Additionally, the skin temperature of the knee joint was increased (P<0.01, P<0.05), while the circumference of the knee joint, the contents of TNF-α, IL-1ß and IL-6 in serum, the expressions of RIPK1, RIPK3, p-MLKL and MLKL in synovial tissues were decreased (P<0.01, P<0.05) in the AG, TRN and HRN groups. The effects of HRN and AG were notably superior to that of TRN in up-regulating skin temperature of the knee joint, and down-regulating the circumference of the knee joint, the contents of TNF-α, IL-1ß and IL-6 in serum, the expressions of RIPK1, RIPK3, p-MLKL and MLKL in synovial tissues (P<0.01, P<0.05). CONCLUSION: HRN can reduce synovial inflammation of knee joint in rabbits with cold syndrome RA, which may be related to its function in inhibiting the necrotizing apoptosis of synovial cells.

[Effects of heat-reinforcing needling on synovial inflammation and miR-155/TLR4/NF-κB signaling axis in rheumatoid arthritis rabbits with cold syndrome].

OBJECTIVE: To observe the effects of heat-reinforcing needling on synovial inflammation and microRNA-155 (miR-155)/Toll-like receptor 4 (TLR4)/nuclear transcription factor-κB (NF-κB) signaling axis, so as to investigate its anti-inflammatory mechanism in rabbits with cold syndrome of rheumatoid arthritis (RA). METHODS: A total of 36 rabbits were randomly divided into normal, model, agonist, inhibitor, heat-reinforcing needling (HRN) and agonist+heat-reinforcing needling (A+HRN) groups, with 6 rabbits in each group. The RA with cold syndrome model was induced by injecting ovalbumin dry powder and Freund's complete adjuvant combined with cold freezing. Rabbits in agonist group were intraperitoneally injected with miR-155 agomir 4.5 OD; rabbits in the inhibitor group were intraperitoneally injected with miR-155 antagomir 6.1 OD; rabbits in HRN group received heat-reinforcing needling at bilateral "Zusanli" (ST36) for 30 min；rabbits in A+HRN group received the same treatment as agonist group, and 30 min later, received the same treatment as the HRN group; rabbits in the normal and model groups were grasped and fixed in the same way, all groups received continuous treatment once a day for 7 d. After modeling, the knee joints of rabbits were examined by ultrasound, the pain threshold and the circumference were determined. After the interventions, the pain threshold and knee circumference were measured; the pathological morphology of synovial tissue of the knee joints were observed by HE staining; the mRNA levels of miR-155 and suppressor of cytokine signaling protein 1 (SOCS1), the expression levels of SOCS1, TLR4, NF-κB p65, interleukin (IL)-1ß and IL-17A proteins in synovial tissue of knee joints were detected by real-time PCR and Western blot respectively. RESULTS: Compared with the normal group, the pain threshold was significantly decreased (P<0.05), and the knee circumference was significantly increased (P<0.05); the synovial tissue of knee joints showed significant hyperplasia, abundant blood flow signal, joint cavity effusion and obvious inflammatory invasion, the pathological score was significantly increased (P<0.05), the expressions of miR-155 mRNA and IL-1ß, IL-17A, TLR4, NF-κB p65 proteins were significantly increased (P<0.05), the expressions of SOCS1 mRNA and protein were significantly decreased (P<0.05) in the model group. Compared with model group, the pain threshold was significantly increased (P<0.05), the circumference of knee joint was significantly decreased (P<0.05); in synovial tissue, the pathological score was decreased (P<0.05), the expression levels of miR-155 mRNA and IL-1ß, IL-17A, TLR4, NF-κB p65 proteins were significantly decreased (P<0.05), and the expressions of SOCS1 mRNA and protein were significantly increased (P<0.05) in inhibitor group and HRN group, while the above changes in agonist group were reversed (P<0.05). Compared with the agonist group, the pain threshold was significantly increased (P<0.05), the knee circumference was significantly decreased (P<0.05), the synovial pathological score was significantly decreased (P<0.05), the expressions of miR-155 mRNA and IL-1ß, IL-17A, TLR4, NF-κB proteins in synovial tissue were significantly decreased (P<0.05), and the expression levels of SOCS1 mRNA and protein were significantly increased (P<0.05) in A+HRN group. CONCLUSION: The heat-reinforcing needling can increase the pain threshold, reduce the knee circumference and inhibit the inflammatory response in rabbits with RA cold syndrome. The possible mechanism is related to the regulation of miR-155/TLR4/NF-κB signaling axis.

Echinacea purpurea (L.) Moench extract suppresses inflammation by inhibition of C3a/C3aR signaling pathway in TNBS-induced ulcerative colitis rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Echinacea purpurea (L.) Moench (EP) is a perennial herbaceous flowering plant, commonly known as purple conical flower. It was widely used to treat skin inflammation and gastrointestinal diseases. AIM OF STUDY: Ulcerative colitis (UC) is a chronic and nonspecific inflammatory disease. Recent evidence shows that immune disorders are involved in the pathogenesis of UC. To evaluate the protective effect of Echinacea purpurea (L.) Moench exact (EE) on UC and explore the role of complement system in the treatment of UC. MATERIALS AND METHODS: UC model was induced in rats by 2,4,6-trinitrobenzene sulfonic acid (TNBS), and then rats were administered with EE for 10 days. Collect colon tissues for analysis of relevant mechanisms. RESULTS: EE could reduce the weight loss and diarrhea of UC rats. In addition, EE could improve the integrity of intestinal epithelial barrier in UC rats. EE inhibited the level of proinflammatory cytokines and promoted the antioxidation. Furthermore, EE suppressed the expression of C3aR, CFB, CD55, TLR4 and NLRP3. CONCLUSION: These results indicate that EE may achieve therapeutic effect by inhibiting C3a/C3aR signal pathway, suggesting that EE may be used as a medicinal plant to alleviate UC.

Photothermal and Concus Finn capillary assisted superhydrophobic fibrous network enabling instant viscous oil transport for crude oil cleanup.

Rapid and effective removal of highly viscous oil spills from the sea remains a great challenge globally. Superhydrophobic materials are attractive candidates for handling oil spills, but they are restrained to recover oils with low viscosity exclusively. Herein, we report a novel polypyrrole wrapped superhydrophobic fibrous network using cross-shaped polyester fibers as starting blocks. The polypyrrole coating enables the absorbent to convert light to heat, ensuring that the viscosity of heavy oils in the proximity can be easily controlled. In the meanwhile, the special structure of the starting fibers initiates Concus Finn (CFin) capillary allowing instant oil transport in the network. When the absorbent is exposed to light oils (0-500 mPa.s), the oils can be transported instantly via CFin capillary. Interestingly, under synergistic effect of light-to-heat conversion and CFin capillary, a drawing-sticking crude oil strip (105 mPa.s) is sucked instantly against gravity by the absorbent. The absorbent is successfully applied to efficiently separate both oil/water mixtures and oil/water emulsions (efficiency > 99%). Such absorbent can absorb 62.99-74.23 g/g light oils on average and up to 123.3 g/g crude oil under 0-2 sun illumination, holding a huge potential in managing oil spills.

Optimization of κ-Selenocarrageenase Production by Pseudoalteromonas sp. Xi13 and Its Immobilization.

The bioenzymatic production of selenium oligosaccharides addresses the problems resulting from high molecular weight and poor water solubility of κ-selenocarrageenan, and lays foundation for its application as adjuvant drugs for cancer treatment and food additive. κ-selenocarrageenase extracted from Pseudoalteromonas sp. Xi13 can degrade κ-selenocarrageenan to selenium oligosaccharides. The maximum optimized κ-selenocarrageenase activity using Response Surface Methodology (RSM) was increased by 1.4 times, reaching 8.416 U/mL. To expand applications of the κ-selenocarrageenase in industry, the preparation conditions of it in either lyophilized or immobilized form were investigated. The activity recovery rate of the lyophilized enzyme was >70%, while that of the immobilized enzyme was 62.83%. However, the immobilized κ-selenocarrageenase exhibits good stability after being reused four times, with 58.28% of residual activity. The selenium content of κ-selenocarrageenan oligosaccharides degraded by the immobilized κ-selenocarrageenase was 47.06 µg/g, 8.3% higher than that degraded by the lyophilized enzyme. The results indicate that the immobilized κ-selenocarrageenase is suitable for industrial applications and has commercial potential.

Effect of Traditional Chinese Medicine on the Gut Microbiota in Heat-Stressed Laying Hens.

Gut microbiota plays an important role in health and disease. To determine whether the traditional Chinese formula Zi Huang Huo Xiang San (ZHHXS) modulates gut microbiota under heat stress, a heat stress model was prepared in Roman layer hens by housing them at temperatures of 32-36°C and administering ZHHXS for 4 weeks. The Roman egg layers were randomly divided into three groups with 10 hens in each: a ZHHXS treatment group (ZHHXS-HS), a heat-stressed group (HS), and a blank control group (BC). The ZHHXS-HS and HS groups were housed in a 34 ± 2°C environment, while the BC group was housed at 25 ± 1°C. The ZHHXS-HS hens were fed a diet supplemented with 1% ZHHXS from 1 to 28 days, while the other groups were not. Gut microbiota in the hens' feces was assessed through 16S rRNA high-throughput sequencing on days 1, 3, 7, 14, and 28. A plot of the PCA scores showed that the gut microbiota composition in the BC group was a similar trend in the ZHHXS-HS group on days 1 and 3. The principal coordinate analysis (PCoA) unweighted distribution showed that the gut microbiota composition had no significant differences between the BC and ZHHXS-HS groups on days 1 and 7. The PCoA weighted distribution showed that the gut microbiota composition had no significant differences between the BC and ZHHXS-HS groups on days 1 and 3. This study showed that the composition of gut microbiota in layer hens with heat stress was modulated by ZHHXS treatment. ZHHXS treatment caused key phylotypes of gut microbiota to match the BC group, particularly Actinobacteria, Bacteroidetes, Bacteroides, and Enterococcus. The effect of ZHHXS in alleviating heat stress could be achieved by altering the composition of gut microbiota and regulating some key phylotypes.

Oral administration of turmeric-derived exosome-like nanovesicles with anti-inflammatory and pro-resolving bioactions for murine colitis therapy.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by diffuse inflammation of the colonic mucosa and a relapsing and remitting course. The current therapeutics are only modestly effective and carry risks for unacceptable adverse events, and thus more effective approaches to treat UC is clinically needed. RESULTS: For this purpose, turmeric-derived nanoparticles with a specific population (TDNPs 2) were characterized, and their targeting ability and therapeutic effects against colitis were investigated systematically. The hydrodynamic size of TDNPs 2 was around 178 nm, and the zeta potential was negative (- 21.7 mV). Mass spectrometry identified TDNPs 2 containing high levels of lipids and proteins. Notably, curcumin, the bioactive constituent of turmeric, was evidenced in TDNPs 2. In lipopolysaccharide (LPS)-induced acute inflammation, TDNPs 2 showed excellent anti-inflammatory and antioxidant properties. In mice colitis models, we demonstrated that orally administrated of TDNPs 2 could ameliorate mice colitis and accelerate colitis resolution via regulating the expression of the pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1ß, and antioxidant gene, HO-1. Results obtained from transgenic mice with NF-κB-RE-Luc indicated that TDNPs 2-mediated inactivation of the NF-κB pathway might partially contribute to the protective effect of these particles against colitis. CONCLUSION: Our results suggest that TDNPs 2 from edible turmeric represent a novel, natural colon-targeting therapeutics that may prevent colitis and promote wound repair in colitis while outperforming artificial nanoparticles in terms of low toxicity and ease of large-scale production.

The neuroprotective effects of icariin on ageing, various neurological, neuropsychiatric disorders, and brain injury induced by radiation exposure.

Epimedium brevicornum Maxim, a Traditional Chinese Medicine, has been used for the treatment of impotence, sinew and bone disorders, "painful impediment caused by wind-dampness," numbness, spasms, hypertension, coronary heart disease, menopausal syndrome, bronchitis, and neurasthenia for many years in China. Recent animal experimental studies indicate that icariin, a major bioactive component of epimedium may effectively treat Alzheimer's disease, cerebral ischemia, depression, Parkinson's disease, multiple sclerosis, as well as delay ageing. Our recent study also suggested that epimedium extract could exhibit radio-neuro-protective effects and prevent ionizing radiation-induced impairment of neurogenesis. This paper reviewed the pharmacodynamics of icariin in treating different neurodegenerative and neuropsychiatric diseases, ageing, and radiation-induced brain damage. The relevant molecular mechanisms and its anti-neuroinflammatory, anti-apoptotic, anti-oxidant, as well as pro-neurogenesis roles were also discussed.

[Therapeutic effect of Baimai Ointment on peripheral sensitization of chronic inflammatory pain in mice].

Chronic inflammatory pain is mainly manifested by peripheral sensitization. Baimai Ointment(BMO), a classical Tibetan medicine for external use, has good clinical efficacy in the treatment of chronic inflammatory pain, while its pharmacodynamics and mechanism for relieving peripheral sensitization remain unclear. This study established an animal model of chronic inflammatory pain induced by complete Freund's adjuvant to explore the mechanism of BMO in the treatment of chronic inflammatory pain by behavioral test, side effect assessment, network analysis, and experimental verification. The pharmacodynamics experiment showed that BMO increased the thresholds of mechanical pain sensitivity and thermal radiation pain sensitivity of chronic inflammatory pain mice in a dose-dependent manner, and had inhibitory effect on foot swelling, inflammatory mediator, and the expression of transient receptor potential vanilloid-1(TRPV1) and transient receptor potential A1(TRPA1). The results of body weight monitoring, pain sensitivity threshold detection in normal mice, rotarod performance test, and forced swimming test showed that BMO had no obvious toxic or side effect. The network analysis of 51 candidate active molecules selected according to the efficacy of BMO, content of main components, and ADME parameters showed that the inhibitory effect of BMO on chronic inflammatory pain was associated with the core regulatory elements of tumor necrosis factor(TNF) and T cell receptor signaling pathways. BMO down-regulated the protein levels of mitogen-activated protein kinase 14(MAPK14), MAPK1, and prostaglandin-endoperoxide synthase 2(PTGS2), and up-regulated the phosphorylation le-vel of glycogen synthase kinase 3 beta(GSK3 B) in the plantar tissue of mice. In conclusion, BMO can effectively relieve peripheral sensitization of chronic inflammatory pain without inducing tolerance and obvious toxic and side effects. The relevant mechanism may be related to the regulation of BMO on core regulatory elements of TNF and T cell receptor signaling pathways in surrounding tissues.

Effects of ShenLing BaiZhu San Supplementation on Gut Microbiota and Oxidative Stress in Rats with Ulcerative Colitis.

The aim of this study was to evaluate the effect of gut microbiota and antioxidation of Shenling Baizhu San (SLBZS) as a supplement in a rat model of ulcerative colitis (UC) induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Acute intestinal inflammation was induced in 40 male SD rats aged 4 weeks with 100 mg/kg TNBS, and then three dosages of SLBZS (0.5 g/kg, 1 g/kg, and 1.5 g/kg) were administered for eight days, respectively. Faecal microbiome composition was assessed by 16S rRNA high-throughput sequencing. The result indicated that SLBZS could reduce the diversity of gut microbiota and increased its abundance. At the genus level, the relative abundance of SCFAs producing bacteria including Prevotella and Oscillospira increased, while the relative abundance of opportunistic pathogens including Desulfovibrio and Bilophila decreased. Meanwhile, SLBZS could improve the lesions of colon and significantly reduce the level of MPO, increase the levels of SOD and CAT in rats' serum. These findings revealed that SLBZS was effective and possessed anticolitic activities in a rat model of UC by reducing macroscopical and microscopical colon injury, enhancing antioxidant capacity, and regulating gut microbiota.

Digestion-Promoting Effects and Mechanisms of Dashanzha Pill Based on Raw and Charred Crataegi Fructus.

Emerging evidence suggests that a high-fat diet (HFD) can influence endoplasmic reticulum (ER) stress and gut microbiota. Crataegi Fructus is a traditional Chinese herb widely used in formulas for dyspepsia, with Dashanzha Pill composed of raw Crataegi Fructus (DR) being a representative drug. Processing products of Crataegi Fructus, however, have a stronger pro-digestive effect, and we hypothesized that Dashanzha Pill composed of charred Crataegi Fructus (DC) is more effective. We found that the contents of glucose 1-phosphate and luteolin in DR and DC were substantially different via ultra-high performance liquid chromatography-hybrid quadrupole-Orbitrap high-resolution mass spectrometry. DC outperformed DR in improving histopathological changes, increasing gastrin and motilin, and decreasing vasoactive intestinal peptides in rats with HFD induced dyspepsia. Fecal microbiota analysis revealed that DC could restore the disturbed intestinal microbiota composition, including that of Bacteroides, Akkermansia, and Intestinimonas to normal levels. Furthermore, DC significantly reduced the mRNA and protein levels of glucose-regulated protein 78, protein kinase R-like ER kinase, and eukaryotic initiation factor 2α. Taken together, DC outperformed DR in relieving dyspepsia by regulating gut microbiota and alleviating ER stress.

Theory of the exterior-interior relationship between the lungs and the large intestine to explore the mechanism of Eriobotrya japonica leaf water extract in the treatment of cough variant asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Eriobotrya japonica (Thunb.) Lindl leaf (EJL) is used as a traditional Chinese medicine. E. japonica is a member of the Rosaceae family. EJL suppresses cough and relieves asthma and is widely used to treat lung diseases. In the present study, guided by the traditional Chinese medicine theory of the exterior-interior relationship between the lungs and the large intestine, the pathogenesis of cough variant asthma (CVA) and the treatment mechanism of EJL on CVA were explored. AIM OF THE STUDY: This study aimed to explore the airway remodeling effects of EJL in CVA from the perspective of the intestinal flora and the matrix metallopeptidase 9/tissue inhibitor of metalloproteinases-1 (MMP-9/TIMP-1) pathway. MATERIALS AND METHODS: The oleanolic acid and ursolic acid contents in EJL were measured by high-performance liquid chromatography (HPLC) to ensure the quality of EJL. BALB/c mice were used to establish a CVA model through ovalbumin (OVA) sensitization and atomization. EJL (at 5, 10, or 20 g/kg/day) was intragastrically administered. The body weight, ratio of total bronchial wall area (WAt) to bronchial basement membrane perimeter (Pbm) (WAt/Pbm), the number of coughs, and cough latency were measured. The pathological changes of the lung tissue were analyzed by hematoxylin and eosin (HE) staining. The expression of α-smooth muscle actin (α-SMA) was measured by immunohistochemistry (IHC). The expressions of MMP-9 and TIMP-1 were detected in the lung tissue by reverse transcription quantitative polymerase chain reaction (RT-PCR) and Western blot analysis. Additionally, an Illumina Hiseq platform was used for 16S ribosomal DNA (16S rDNA) high-throughput sequencing to detect the intestinal flora in feces samples. RESULTS: The results confirmed the positive effects of EJL on CVA. After administration of EJL, the number of coughs and the WAt/Pbm ratio decreased, the cough latency was prolonged, body weight was increased, and the general status was better than that of the CVA model mice. HE staining revealed that EJL decreased inflammatory cell infiltration and improved the histopathological structure of the lung tissue. EJL also showed significant inhibitory effects on the expression of α-SMA, MMP-9, and TIMP-1 and normalized the intestinal flora to a certain extent. CONCLUSIONS: The results demonstrated that EJL alleviated airway remodeling of CVA mice, which might be related to the inhibition of the MMP-P/TIMP-1 pathway and the regulation of intestinal flora.

Identification and quantification of 10 indole/indazole carboxamide synthetic cannabinoids in 36 herbal blends by gas chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy.

Herbal blends containing synthetic cannabinoids have become popular alternatives to marijuana. The number of synthetic cannabinoids and speed of their emergence enable this group of compounds particularly challenging in terms of detection, monitoring, and responding. In this work, both gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR) methods were developed for the identification and quantification of synthetic cannabinoids in herbal blends. Ten types of indole/indazole carboxamide synthetic cannabinoids, which showed different types of substitutions connected to nitrogen of the indole/indazole carboxamide, were detected in 36 herbal blends. The GC-MS fragmentation routes of indole/indazole carboxamide synthetic cannabinoids were discussed in detail for structure identification purpose. The concentration range of synthetic cannabinoid in 36 herbal blends was 1.9-50.6 mg/g using GC-MS method, while 1.5-49.0 mg/g by NMR method. Nicotine in herbal blends was quantified by NMR method without using reference material, and showed a variation of 5.3-44.7 mg/g. For quantitative analysis, NMR method showed great advantage in the absence of reference material, while GC-MS method showed great merit for multiple-compound analysis when reference material was available. Therefore, for the quantitative analysis of new emerged synthetic cannabinoid in herbal blends, different methods could be chosen by considering whether reference material is available, as well as the number and types of synthetic cannabinoids detected in a single sample.