Tianma-Gouteng pair ameliorates the cognitive deficits on two transgenic mouse models of Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a progressive neurodegenerative disease. Tianma-Gouteng Pair (TGP), commonly prescribed as a pair-herbs, can be found in many Chinese medicine formulae to treat brain diseases. However, the neuroprotective effects and molecular mechanisms of TGP remained unexplored. AIM OF THE STUDY: This study investigated the difference between the TgCRND8 and 5 × FAD transgenic mice, the anti-AD effects of TGP, and underlying molecular mechanisms of TGP against AD through the two mouse models. METHODS: Briefly, three-month-old TgCRND8 and 5 × FAD mice were orally administered with TGP for 4 and 6 months, respectively. Behavioral tests were carried out to determine the neuropsychological functions. Moreover, immunofluorescence and western blotting assays were undertaken to reveal the molecular mechanisms of TGP. RESULTS: Although TgCRND8 and 5 × FAD mice had different beta-amyloid (Aß) burdens, neuroinflammation status, and cognition impairments, TGP exerted neuroprotective effects against AD in the two models. In detail, behavioral tests revealed that TGP treatment markedly ameliorated the anxiety-like behavior, attenuated the recognition memory deficits, and increased the spatial learning ability as well as the reference memory of TgCRND8 and 5 × FAD mice. Moreover, TGP treatment could regulate the beta-amyloid precursor protein (APP) processing by inhibiting the Aß production enzymes such as ß- and γ-secretases and activating Aß degrading enzyme to reduce Aß accumulation. In addition, TGP reduced the Aß42 level, the ratio of Aß42/Αß40, Aß accumulation, and tau hyperphosphorylation in both the 5 × FAD and TgCRND8 mouse models. Furthermore, TGP ameliorated neuroinflammation by decreasing the densities of activated microglia and astrocytes, and inhibiting the production of inflammatory cytokines. TGP upregulated the SIRT1 and AMPK, and downregulated sterol response element binding protein 2 (SREBP2) in the brain of TgCRND8 mice and deactivation of the EPhA4 and c-Abl in the brain tissues of 5 × FAD mice. CONCLUSION: Our experiments for the first time revealed the neuroprotective effects and molecular mechanism of TGP on 5 × FAD and TgCRND8 transgenic mouse models of different AD stages. TGP decreased the level of Aß aggregates, improved the tauopathy, and reduced the neuroinflammation by regulation of the SIRT1/AMPK/SREBP2 axis and deactivation of EPhA4/c-Abl signaling pathway in the brains of TgCRND8 and 5 × FAD mice, respectively. All these findings unequivocally confirmed that the TGP would be promising in developing into an anti-AD therapeutic pharmaceutical.

Clinical Predictive Value of Phospholipase A2 Receptor Gene Polymorphism Combined with Subclass of Immunoglobulin G in Renal Tissues for Membranous Nephropathy.

Context: Idiopathic membranous nephropathy (IMN) is a common pathologic type of nephrotic syndrome, and the level of the M-type phospholipase A2 receptor (PLA2R) antibody can serve as one index for predicting its progression and prognosis. However, patients with the same level can show great differences in their responses and prognoses. Objectives: The study aimed to explore the relationship between a PLA2R gene polymorphism combined with an immunoglobulin G (IgG) subclass in renal tissues and patients' responses to immunosuppressive therapy, to determine the clinical prognosis for IMN patients. Design: This is a prospective study. Patients with new onset membranous nephropathy who need treatment were selected and grouped according to the curative effect after 6 months of treatment. Setting: The study took place at the First Affiliated Hospital of Ningbo University, Ningbo, China. Participants: Participants were 60 patients with IMN, who had been admitted in the hospital between January 1, 2021 and June 30, 2022. Intervention: Participants first received standard immunosuppressive therapy for six months. The research team then clinically divided participants into two groups: (1) a remission group with 32 participants and (2) a nonremission group with 28 participants. Outcome Measures: The research team: (1) compared the groups, summarizing the demographic and clinical differences between the groups, (2) compared the PLA2R antibody titers at baseline and postintervention between the groups, (3) analyzed the genotyping of the PLA2R single nucleotide polymorphisms (SNPs) rs35771982 and rs4664308 loci as well as the human leukocyte antigen (HLA)-DQA1 SNP rs2187668 locus, and (4) compared the subclass IgG and PLA2R depositions in the renal tissues between the groups. Results: Compared with the remission group, the nonremission group included significantly more males (P < .05), was significantly older (P < .05), had significantly more participants with a BMI of >25 (P < .05), and included significantly more participants with a positive IgG3 (P < .01) than the remission group. The remission group's PLA2R antibody titers at baseline and postintervention weren't significantly different from those of the nonremission group. Postintervention, 24 participants in the remission group had a negative conversion of PLA2R antibodies, and 22 in the nonremission group had a negative conversion. The genotyping of the PLA2R SNP rs4664308 and the HLA-DQA1 SNP rs2187668 loci showed no relationship to the remission rate. The GC genotype on the PLA2R SNPrs35771982 locus may be a risk factor for a poor prognosis for IMN patients. Moreover, the patients with a positive IgG3 in the renal tissues and the GC genotype on the PLA2R SNPrs35771982 locus exhibited a poor response to immunosuppressive therapy and could need intensive treatment. Conclusions: The PLA2R gene polymorphism combined with the IgG subclass can predict the sensitivity of IMN patients to immunosuppressive therapy.

Influence of Proteins on Bioaccessibility of α-Tocopherol Encapsulation within High Diacylglycerol-Based Emulsions.

α-Tocopherol has been widely used in medicine, cosmetics, and food industry as a nutritional supplement and antioxidant. However, α-tocopherol showed low bioaccessibility, and there is a widespread α-tocopherol deficiency in society today. The preparation of oil-in-water emulsions with high safety and low-calorie property is necessary. The aim of this research was to investigate the effects of different protein emulsifiers (whey protein isolate (WPI), soy protein isolate (SPI), and sodium casein (SC)) on the properties of emulsions delivery system, and diacylglycerol (DAG) was picked as a low-accumulated lipid. The interfacial changes, microstructural alterations, and possible interactions of the protein-stabilized DAG emulsions were investigated during the in vitro digestion. The results show that different proteins affect the degree of digestibility and α-tocopherol bioaccessibility of the emulsions. Both WPI- and SPI-coated emulsions showed good digestibility and α-tocopherol bioaccessibility (77.64 ± 2.93%). This might be due to the strong hydrolysis resistance of WPI (ß-lactoglobulin) and the good emulsification ability of SPI. The SC-coated emulsion showed the lowest digestibility and α-tocopherol bioaccessibility, this might be due to the emulsification property of hydrolysis products of SC and the potential interaction with calcium ions. This study provides new possibilities for the application of DAG emulsions in delivery systems.

Exposure to herbicides mixtures in relation to type 2 diabetes mellitus among Chinese rural population: Results from different statistical models.

BACKGROUND: Although it has been reported that herbicides exposure is related to adverse outcomes, available evidence on the associations of quantitatively measured herbicides with type 2 diabetes mellitus (T2DM) and prediabetes is still scant. Furthermore, the effects of herbicides mixtures on T2DM and prediabetes remain unclear among the Chinese rural population. AIMS: To assess the associations of plasma herbicides with T2DM and prediabetes among the Chinese rural population. METHODS: A total of 2626 participants were enrolled from the Henan Rural Cohort Study. Plasma herbicides were measured with gas chromatography coupled to triple quadrupole tandem mass spectrometry. Generalized linear regression analysis was employed to assess the associations of a single herbicide with T2DM, prediabetes, as well as indicators of glucose metabolism. In addition, the quantile g-computation and environmental risk score (ERS) structured by adaptive elastic net (AENET), and Bayesian kernel machine regression (BKMR) were used to estimate the effects of herbicides mixtures on T2DM and prediabetes. RESULTS: After adjusting for covariates, positive associations of atrazine, ametryn, and oxadiazon with the increased odds of T2DM were obtained. As for prediabetes, each 1-fold increase in ln-transformed oxadiazon was related to 8.4% (95% confidence interval (CI): 1.033, 1.138) higher odds of prediabetes. In addition, several herbicides were significantly related to fasting plasma glucose, fasting insulin, and HOMA2-IR (false discovery rates adjusted P value < 0.05). Furthermore, the quantile g-computation analysis showed that one quartile increase in multiple herbicides was associated with T2DM (OR (odds ratio): 1.099, 95%CI: 1.043, 1.158), and oxadiazon was assigned the largest positive weight, followed by atrazine. In addition, the ERS calculated by the selected herbicides from AENET were found to be associated with T2DM and prediabetes, and the corresponding ORs and 95%CIs were 1.133 (1.108, 1.159) and 1.065 (1.016, 1.116), respectively. The BKMR analysis indicated a positive association between mixtures of herbicides exposure and the risk of T2DM. CONCLUSIONS: Exposure to mixtures of herbicides was associated with an increased risk of T2DM among Chinese rural population, indicating that the impact of herbicides exposure on diabetes should be paid attention to and measures should be taken to avoid herbicides mixtures exposure.

Jingfang granules exert anti-psoriasis effect by targeting MAPK-mediated dendritic cell maturation and PPARγ-mediated keratinocytes cell cycle progression in vitro and in vivo.

BACKGROUND: Jingfang granules (JFG), derived from JingFangBaiDu San (JFBDS), are a traditional herbal formulas used for the treatment of respiratory tract infections. They were initially prescribed to treat skin disease, such as psoriasis in Chinese Taiwan, but are not widely used for psoriasis treatment in mainland China because of the lack of anti-psoriasis mechanism research. PURPOSES: The present study was designed to evaluate the anti-psoriasis effect of JFG and reveal the correlated mechanisms of JFG in vivo and in vitro using network pharmacology, UPLC-Q-TOF-MS technology and molecular biotechnology methods. RESULTS: An imiquimod-induced psoriasis-like murine model was used to verify the anti-psoriasis effect in vivo, with inhibition of lymphocytosis and CD3+CD19+B cell proliferation in the peripheral blood and prevention of the activation of CD4+IL17+T cells and CD11c+ MHC Ⅱ+ dendritic cells (DCs) in the spleen. Network pharmacology analysis demonstrated that the targets of the active components were significantly enriched in pathways involved in cancer, inflammatory bowel disease and rheumatoid arthritis, which were closely related to cell proliferation and immune regulation. The drug-component-target networks and molecular docking analysis demonstrated the active ingredients to be luteolin, naringin and 6'-feruloylnodakenin, which had a good binding affinity to PPARγ, p38a MAPK and TNF-a. Finally, UPLC-Q-TOF-MS analysis to validate the active ingredients in drug-containing serum and in vitro experiments showed that JFG inhibited the maturation and activation of BMDCs via the p38a MAPK signaling pathway and translocation of the agonist PPARγ into the nuclei to reduce the activity of NF-κB/STAT3 inflammatory signaling pathway in keratinocytes. CONCLUSIONS: Our study demonstrated that JFG improved psoriasis by inhibiting the maturation and activation of BMDCs and proliferation and inflammation of keratinocytes, which may facilitate the applications of JFG in anti-psoriasis therapy in clinical settings.

Baicalin can enhance odonto/osteogenic differentiation of inflammatory dental pulp stem cells by inhibiting the NF-κB and ß-catenin/Wnt signaling pathways.

BACKGROUND: Scutellaria baicalensis Georgi is a famous traditional Chinese medicine, which is widely used in treating fever, upper respiratory tract infection and other diseases. Pharmacology study showed it can exhibit anti-bacterial, anti-inflammation and analgesic effects. In this study, we investigated the effect of baicalin on the odonto/osteogenic differentiation of inflammatory dental pulp stem cells (iDPSCs). METHODS AND RESULTS: iDPSCs were isolated from the inflamed pulps collected from pulpitis. The proliferation of iDPSCs was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2,5-tetrazolium bromide (MTT) assay and flow cytometry. Alkaline phosphatase (ALP) activity assay, alizarin red staining, Real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assay were conducted to examine the differentiation potency along with the involvement of nuclear factor kappa B(NF-κB) and ß-catenin/Wnt signaling pathway. MTT assay and cell-cycle analysis demonstrated that baicalin had no influence on the proliferation of iDPSCs. ALP activity assay and alizarin red staining demonstrated that baicalin could obviously enhance ALP activity and calcified nodules formed in iDPSCs. RT-PCR and Western blot showed that the odonto/osteogenic markers were upregulated in baicalin-treated iDPSCs. Moreover, expression of cytoplastic phosphor-P65, nuclear P65, and ß-catenin in iDPSCs was significantly increased compared with DPSCs, but the expression in baicalin-treated iDPSCs was inhibited. In addition, 20 µM Baicalin could accelerate odonto/osteogenic differentiation of iDPSCs via inhibition of NF-κB and ß-catenin/Wnt signaling pathways. CONCLUSION: Baicalin can promote odonto/osteogenic differentiation of iDPSCs through inhibition of NF-κB and ß-catenin/Wnt pathways, thus providing direct evidence that baicalin may be effective in repairing pulp with early irreversible pulpitis.

A two-pronged strategy to alleviate tumor hypoxia and potentiate photodynamic therapy by mild hyperthermia.

The application of photodynamic therapy (PDT) is limited by tumor hypoxia. To overcome hypoxia, catalase-like nanozymes are often used to catalyze endogenous H2O2 enriched in tumor tissues to O2. Nonetheless, the catalase activity may not be optimal at body temperature and the O2 supply may not meet the rapid O2 consumption of PDT. Herein, we provide a two-pronged strategy to alleviate tumor hypoxia based on hollow mesoporous Prussian blue nanoparticles (HMPB NPs). HMPB NPs can efficiently load the photosensitizer chlorin e6 (Ce6) and exhibit photothermal capability and temperature-dependent catalase activity. Under 808 nm laser irradiation, the photothermal effect of HMPB NPs elevated the catalase activity of HMPB NPs for O2 production. Furthermore, mild hyperthermia reduced cancer associated fibroblasts (CAFs) and induced extracellular matrix (ECM) degradation. The reduction of CAFs and the ECM decreased the solid stress of tumor tissues and normalized the tumor vasculature, which was beneficial for the external supplementation of O2 to tumors. Thereafter, under 606 nm laser irradiation, Ce6-mediated PDT generated excessive reactive oxygen species (ROS) that induced tumor cell apoptosis and achieved a high tumor inhibition rate of 92.2% in 4T1 breast tumors. Our work indicated that the alleviation of tumor hypoxia from both internal and external pathways significantly enhanced Ce6-mediated PDT against breast cancers.

Patchouli alcohol ameliorates the learning and memory impairments in an animal model of Alzheimer's disease via modulating SIRT1.

BACKGROUND: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases. Patchouli alcohol (PA), a major active ingredient isolated from Pogostemonis Herba, exhibits extensive bioactivity in the central nervous system (CNS) and exerts neuroprotective effects. PURPOSE: This study aimed to investigate the anti-AD effects of PA in an animal model of AD and to elucidate the underlying molecular mechanisms. METHODS: The gas chromatography (GC) was used to determine the ability of PA to pass the blood-brain barrier (BBB) in rats after oral administration. The sporadic AD rat model was established by intracerebroventricularly (ICV) injection with streptozotocin (STZ). PA (25 and 50 mg/kg) was given to rat orally once daily for 42 consecutive days. Morris water maze (MWM) test was performed to determine the learning and memory functions of the STZ-induced AD rats. EX527, a silent information regulator 1 (SIRT1) selective inhibitor, was used to investigate the involvement of SIRT1 in the anti-AD effects of PA in rats. RESULTS: PA could penetrate the BBB. MWM test results showed that PA could significantly ameliorate the learning and memory deficits induced by STZ in rats. Meanwhile, PA enhanced the expression of SIRT1, and markedly alleviated the tau pathology by inhibiting the hyperacetylation (at the site of Lys174) and hyperphosphorylation (at the sites of Thr181, Thr205, Ser396 and Ser404) of tau protein. PA also efficiently suppressed the activation of microglia and astrocytes, and the beta-amyloid (Aß) expression and the deacetylation of nuclear factor-kappa B (NF-κB) at Lys 310 (K310) in the STZ-treated AD rats. EX527, a SIRT1 selective inhibitor, could partially abolish the cognitive deficits improving effect of PA and inhibit the down-regulation of acetylated tau and acetylated NF-κB p65, suggesting that PA exhibited neuroprotective effects against AD via upregulating SIRT1. CONCLUSION: This study reported for the first time that PA could penetrate the BBB to exert its protective effects on the brain after a single-dose oral administration. The current experimental findings also amply demonstrated that PA could improve the cognitive and memory impairments in the STZ-induced AD rat model. The underlying mechanisms involve the alleviations of neuroinflammation, tau pathology and Aß deposition via modulating of SIRT1 and NF-κB pathways. All these findings strongly suggest that PA is a promising naturally occurring compound worthy of further development into an anti-AD pharmaceutical.

Exploring midwifery students' experiences of professional identity development during clinical placement: A qualitative study.

BACKGROUND: Healthy China 2030 has proposed to strengthen the investment in midwifery education to prepare more qualified midwives to address the shortage of midwifery workforce in China. The formation of a strong professional identity has been demonstrated to be a vital enabler for successfully transitioning from university to work. As midwifery is a practice-based profession, clinical placement is a key period for midwifery students' professional identity development, where they can be part of the profession and exposed to professional behaviour and interaction in the real world. However, it has not yet been explored in terms of the professional identity development of midwifery students in China during clinical placement. AIM: To gain insight into the professional identity development experiences of midwifery students in China during clinical placement. DESIGN: A qualitative study using a descriptive phenomenological approach. METHODS: Semi-structured interviews were conducted with fourteen final-year midwifery students who were undertaking clinical placement in four public hospitals in central China between March 2021 and May 2021. The transcribed data were analyzed following the Colaizzi's phenomenological analysis method. RESULTS: A total of one category, two theme clusters and seven themes emerged. The overarching category "conflicting experiences of professional identity development" was identified from the interaction of two theme clusters, "positive experiences motivating professional identity development" and "negative experiences impeding professional identity development". Four themes including "feeling the sense of accomplishment for facilitating smooth births", "developing professional competence", "positive role models of clinical mentors", and "cooperative inter-professional relationships" fell into the theme cluster of "positive experiences motivating professional identity development"; while the other three themes including "high-intensity working state", "emotional instability of birthing women", and "feeling insufficient in professional competence" fell into the theme cluster of "negative experiences impeding professional identity development". CONCLUSIONS: The conflicting experiences of professional identity development among midwifery students might lead to the emergence of confusion and further decrease their retention intention in the profession. Thus, intervention strategies should be adopted to promote midwifery students' professional identity development during clinical placement, so as to prepare confident and motivated midwives to provide high-quality maternal care and address the shortage of midwifery workforce in China.

Water-in-oil emulsions enriched with alpha-linolenic acid in diacylglycerol form: Stability, formation mechanism and in vitro digestion analysis.

This study developed an alpha-linolenic acid (ALA) supplement with emulsion form using ALA-rich diacylglycerol (ALA-DAG) and ALA-DAG stearin (DAG-SF) as a new source of ALA and emulsifier. Stable, commercial surfactant-free W/O emulsions with 90 wt% oil phase (including DAG-SF and ALA-DAG with 10:90 - 20:80 wt ratio) was fabricated. Microstructure and Raman spectra revealed that the compact crystal networks and high amounts of solid acyl chains were responsible for high emulsion stability. These emulsions exhibited good potential in improving the ALA nutritional status (with ALA release level of 60.49% - 62.98%). Furthermore, the emulsifier-to-oil ratio greatly impacted the emulsion texture (solid-like or liquid-like) and emulsions showed great oxidation stability (2.80 - 3.09 meq/kg lipid of peroxide value at 6th week). The tunable texture and high oxidation stability make this emulsion system useful for a wide range of food products. This developed emulsion system could provide valuable information for other important fatty acids supplement.

YY1 Oligomerization Is Regulated by Its OPB Domain and Competes with Its Regulation of Oncoproteins.

Yin Yang 1 (YY1) plays an oncogenic role through regulating the expression of various cancer-related genes and activating key oncoproteins. Previous research reported that YY1 protein formed dimers or oligomers without definite biological implications. In this study, we first demonstrated the oncoprotein binding (OPB) and zinc finger (ZF) domains of YY1 as the regions involved in its intermolecular interactions. ZFs are well-known for protein dimerization, so we focused on the OPB domain. After mutating three hydrophobic residues in the OPB to alanines, we discovered that YY1(F219A) and YY1(3A), three residues simultaneously replaced by alanines, were defective of intermolecular interaction. Meanwhile, the OPB peptide could robustly facilitate YY1 protein oligomerization. When expressed in breast cancer cells with concurrent endogenous YY1 knockdown, YY1(F219A) and (3A) mutants showed better capacity than wt in promoting cell proliferation and migration, while their interactions with EZH2, AKT and MDM2 showed differential alterations, especially with improved EZH2 binding affinity. Our study revealed a crucial role of the OPB domain in facilitating YY1 oligomerization and suggested a mutually exclusive regulation between YY1-mediated enhancer formation and its activities in promoting oncoproteins.

Effective Treatment of Small Uncomplicated Skin Abscesses with Fire Needle: A Case Series.

BACKGROUND: Uncomplicated skin abscesses are collections of pus within the skin structure and are usually caused by bacterial infections. Clinically, they are quite common and inevitably affect people of any age. The current management strategies comprise prompt initiation of antibiotics and incision and drainage. However, pain and the long healing process of skin lesions can cause distress to a lot of patients. Fire needling is a characteristic treatment in traditional Chinese medicine (TCM) and has proven effective in treating skin abscesses. Moreover, fire needle therapy has a more desirable cosmetic outcome in contrast to surgical debridement. The purpose of the study is to demonstrate the rapid, effective, minimally invasive, and better cosmetic outcomes of fire needles in the treatment of uncomplicated skin abscesses. METHODS: A total of 10 patients, aged between 1 and 45 years, with skin abscesses, were recruited. All patients who fulfilled the inclusion criteria with lesions less than 4 cm in diameter were topically treated with mupirocin ointment twice a day after fire needle therapy. If the lesion was still purulent after 2 days, it was treated again with fire needle therapy. The efficacy was assessed by a 4-grade scale at 2 days, 1 week, 2 weeks, 4 weeks and 12 weeks post-fire needling. RESULTS: Lesions with a diameter of less than 2 cm achieved significant remission (SR) or partial remission (PR), after 2 days post-treatment and reached complete remission (CR) or significant remission (SR) after 1 week following treatment. Meanwhile, lesions with a diameter of 2-4 cm achieved PR after 2 days and were assessed as CR or SR 1 week after post-fire needle therapy. None of the patients had a recurrence within 12 weeks after treatment. CONCLUSION: Fire needle therapy is a promising treatment method for uncomplicated skin abscesses smaller than 4 cm, which warrants further in-depth and more large-scale studies.

The permeability characteristics and interaction of main components from Si-Ni-San in a MDCK epithelial cell monolayer model.

1. Si-Ni-San (SNS) possesses extensive therapeutic effects, however, the extent to which main components are absorbed and the mechanisms involved are controversial. 2. In this study, MDCK cell model was used to determine the permeability characteristics and interaction between the major components of Si-Ni-San, including saikosaponin a, paeoniflorin, naringin and glycyrrhizic acid. 3. The transport of the major components was concentration-dependent in both directions. Moreover, the transport of paeoniflorin, naringin and glycyrrhizic acid was significantly reduced at 4 °C or in the presence of NaN3. Additionally, the efflux of paeoniflorin and naringin were apparently reduced in the presence of P-gp inhibitor verapamil. The transport of glycyrrhizic acid was clearly inhibited by the inhibitors of MRP2, indicating that MRP2 may be involved in the transport of glycyrrhizic acid. However, the results indicated that saikosaponin a was absorbed mainly by passive diffusion. Furthermore, the combined incubation of four major components had a powerful sorbefacient effect than a single drug used alone which may be regulated by tight junctions. 4. Taken together, our study provides useful information for pharmacological applications of Si-Ni-San and offers new insights into this ancient decoction for further researches, especially in drug synergism.

Effect of perennial dust mites allergy on symptom severity of autumn allergic rhinitis in adults.

Background: Multiple immunoglobulin E (IgE) mediated sensitizations and/or allergies often coexist in patients with allergic rhinitis (AR). Several simultaneous allergen exposures in multiple IgE-mediated sensitizations and/or allergies may increase the allergen load and be related to disease severity. No study has verified whether positive allergen serum IgE levels and allergen categories together are associated with AR severity in adults. Objective: To investigate the effects of perennial dust mites (DMs) allergy and multiple serum sIgE-mediated autumn pollen allergy coexistence on symptom severity in adult patients with AR in autumn. Methods: In total, 153 patients with AR and with autumn pollen allergy (Artemisia argyi, ragweed, and hop) with or without DMs allergy were recruited in the autumn pollen season. Symptom severity was assessed by using the Chinese version of the visual analog scale (VAS): four rhinitis symptoms (sneezing, rhinorrhea, nasal pruritus, and nasal congestion) and two ocular symptoms (ocular itching and/or grittiness and/or redness, and ocular tearing) were scored at approximately the same period. We measured allergen serum sIgE levels for the inhaled allergens. The effects of DMs allergy and multiple autumn pollen allergy coexistence on symptom severity were analyzed. Results: Neither the sum of the autumn pollen allergens categories (total number of positive autumn pollen allergens, i.e., Artemisia argyi or ragweed or hop positive: 1; Artemisia argyi and ragweed positive: 2; Artemisia argyi, ragweed, and hop positive: 3) nor serum sIgE levels( total sIgE levels of positive autumn pollen allergens) exerted any influence on the severity of nasal and ocular symptoms (p > 0.05). When the concomitant DMs allergy status was considered, the sum of the positive autumn pollen allergen categories and accumulated positive autumn pollen and DMs serum sIgE levels (total levels of serum sIgE of positive autumn pollen allergens plus the levels of serum sIgE of DMs) had no influence on patients' symptom severity (p > 0.05). Conclusion: The coexistence of perennial DMs allergy and multiple autumn pollen allergy did not affect the severity of symptoms among adult patients with AR and with autumn pollen allergy in autumn.

Effect of Green Tea and (-)-Epigallocatechin Gallate on the Pharmacokinetics of Rosuvastatin.

BACKGROUND: Green tea can inhibit OATPs, so it may interact with the substrate of OATPs, such as rosuvastatin. OBJECTIVE: This study aimed to investigate the effects of green tea on the pharmacokinetics of rosuvastatin and its mechanism. METHODS: Male Sprague-Dawley rats received different doses of green tea extract (GTE) and (-)- epigallocatechin-3- gallate (EGCG). Caco-2 cells and OATP1B1-HEK293T cells were used in drug uptake and transport assay. The matrix concentrations of rosuvastatin and catechins were determined by ultra-performance liquid chromatographytandem mass spectrometry (UPLC-MS/MS). RESULTS: GTE and EGCG were both found to increase the area under the plasma concentration-time curve (AUC0-∞) of rosuvastatin ((p<0.050). In the Caco-2 cell model, the uptake and transport of rosuvastatin in the GTE groups were 1.94-fold (p<0.001) and 2.11-fold (p<0.050) higher, respectively, than those of the control group. However, in the EGCG group, the uptake and transport of rosuvastatin were decreased by 22.62% and 44.19%, respectively (p<0.050). In the OATP1B1- HEK293T cell model, the OATP1B1-mediated rosuvastatin uptake was decreased by GTE to 35.02% of that in the control (p<0.050) and was decreased by EGCG to 45.61% of that in the control (p<0.050). CONCLUSION: GTE increased the systemic rosuvastatin exposure in rats. The mechanism may include an increase in rosuvastatin absorption and a decrease in liver distribution by inhibiting OATP1B1. EGCG may be the main ingredient of green tea that affects the pharmacokinetic parameters of rosuvastatin. Our results showed the importance of conducting green tea-rosuvastatin study.

Effects of Different Selenium Sources on Meat Quality and Shelf Life of Fattening Pigs.

The aim of this study was to evaluate the effects of different Se sources on the meat quality and shelf life of fattening pigs. The control diet was supplemented with 0.3 mg/kg of Se from sodium selenite (SS), and experimental diets included 0.3, 0.3 and 0.15 + 0.15 mg/kg of Se from Se-enriched yeast (SY), selenomethionine (Se-Met) and SS + Se-Met, respectively. The results showed that using organic Se or Se + Se-Met in fattening pigs' diet could increase average daily gain (ADG) (p < 0.05), decrease F/G (p < 0.05), reduce (p < 0.01) moisture, drip loss and cooking loss of longissimus thoracis, as well as increase (p < 0.05) protein and fat contents of longissimus thoracis. Diet supplementation with SY or Se + Se-Met could increase (p < 0.01) back fat thickness and skin thickness, and SY could increase (p < 0.01) belly fat rat. Adding SY or Se + Se-Met could reduce (p < 0.01) L value (45 min, 24 h). Adding Se-Met could decrease (p < 0.01) b value (45 min, 24 h), adding Se + Se-Met could reduce b value (45 min), and adding SY could reduce the b value (24 h). However, there were no (p < 0.05) significant effects on dressing percentage, carcass sloping length, eye muscle area, pH, a value (45 min) and a value (24 h) of longissimus thoracis. Moreover, the TVB-N contents of longissimus thoracis on the first and fifth days, the numbers of Lactobacillus on the third to seventh days and the numbers of E. coli in in the fifth to seventh days of longissimus thoracis were reduced (p < 0.01) by diet supplementation with organic Se. In conclusion, all the results indicate that replacing inorganic Se in diet with organic Se could improve meat quality of fattening pigs. In addition, organic Se could reduce the total volatile basic nitrogen (TVB-N) contents of longissimus thoracis and reduce the numbers of E. coli and Lactobacillus in longissimus thoracis, prolonging the shelf life of pork. These results demonstrated that organic Se supplementation was more effective than SS supplementation for meat quality and the shelf life of fattening pigs.

Herbal Compatibility of Ginseng and Rhubarb Exerts Synergistic Neuroprotection in Cerebral Ischemia/Reperfusion Injury of Rats.

OBJECTIVE: Ischemic stroke is a complex multifactorial disease caused by interactions among polygenetic, environmental, and lifestyle factors with limited effective treatments. Multi-herbal formulae have long been used for stroke through herbal compatibility in traditional Chinese medicine (TCM); however, there is still a lack of evidence due to their unimaginable complexity. Herbal pairs represent the simplest and basic features of multi-herbal formulae, which are of great significance in clarifying herbal compatibility. Here, we aim to investigate the neuroprotective effects of the herbal compatibility of Ginseng and Rhubarb on a cerebral ischemia/reperfusion (I/R) injury model of rats. METHODS: Male adult SD rats were randomly divided into a sham group, a normal saline (NS) group, a Ginseng group, a Rhubarb group, and a Ginseng + Rhubarb (GR) group, a Carbenoxolone [CBX, gap junction (GJ) specific inhibitor] group, and a GR + CBX group. Each group was further assigned into four subgroups according to ischemic time (6 h, 1 day, 3 days, and 7 days). The cerebral I/R injury model was established according to the modified Zea Longa method. The Neurological Deficiency Score (NDS) was assessed by the Zea-Longa scale; the cerebral infarction area was detected by TTC (2,3,5-triphenyltetrazolium chloride) staining; and the expression of connexin-43 (Cx43) and aquaporin-4 (AQP4) were detected based on an immunofluorescence technique and quantitative real-time-PCR. RESULTS: Compared to the I/R group, both the independent and combined use of Ginseng and Rhubarb can significantly improve NDS (P < 0.05), decrease the percentage of the cerebral infarction area around the infarction penumbra (P < 0.05) and down-regulate the expression of Cx43 and AQP4 after I/R injury (P < 0.05). The GR had more significant effects than that of Ginseng and Rhubarb (P < 0.05). Compared with the GR group, the GR + CBX group significantly improved in NDS (P < 0.05), and decreased the percentage of the cerebral infarction area (P < 0.05) and expression of Cx43 and AQP4 protein (P < 0.05). CONCLUSION: The herbal compatibility of Ginseng and Rhubarb synergistically exerts neuroprotective function during acute cerebral I/R injury, mainly through reducing the expression of Cx43 and AQP4.

Comparative effects of dietary supplementations with sodium butyrate, medium-chain fatty acids, and n-3 polyunsaturated fatty acids in late pregnancy and lactation on the reproductive performance of sows and growth performance of suckling piglets.

This study was conducted to compare the effects of adding sodium butyrate (SB), medium-chain fatty acids (MCFAs), or n-3 polyunsaturated fatty acids (n-3 PUFAs) to the diet of sows during late gestation and lactation on the reproductive performance of sows and the growth performance and intestinal health of suckling piglets. Twenty-four sows (Landrace × Large-White hybrid; third parity; 200 ± 15 kg) were randomly assigned to receive 1 of 4 diets: basal diet (control group), basal diet + 1 g SB/kg (SB group), basal diet + 7.75 g MCFA/kg (MCFA group), or basal diet + 68.2 g n-3 PUFA/kg (n-3 PUFA group). The experiment began on day 85 of gestation and ended day 22 of lactation. Colostrum samples were collected from each sow. After the experiment, blood and tissue samples were collected from 1 randomly selected piglet. The results showed that the weaning-to-estrus interval of sows in the SB, MCFA, and n-3 PUFA groups was shorter than that of sows in the control group (P < 0.05). The incidence of diarrhea in suckling piglets in the SB, MCFA, and n-3 PUFA groups was lower than that of piglets in the control group (P < 0.05). The fat, protein, IgA, IgG, and IgM concentration in colostrum from sows increased following dietary supplementation with SB, MCFA, or n-3 PUFA (P < 0.05). Comparison with the control group, the mRNA expression of claudin-1, zona occludens 1, and interleukin-10 increased in the jejunum mucosa of suckling piglets in the SB, MCFA, and n-3 PUFA groups, while that of TLR4 decreased (P < 0.05). Compared with the control group, the Chao1 and ACE indexes of microbial flora in the colon contents of piglets in the SB, MCFA, and MCFA groups increased (P < 0.05), while the relative abundance of Firmicutes, Actinobacteria, and Synergistetes decreased at the phylum level (P < 0.05). In conclusion, during late pregnancy and lactation, dietary SB supplementation had a greater effect on intestinal health and caused a greater decrease in preweaning mortality of suckling piglets than did dietary MCFA or n-3 PUFA supplementation; dietary MCFA supplementation shortened the weaning-to-estrus interval of sows to a greater extent than did dietary SB or n-3 PUFA supplementation; and dietary n-3 PUFA supplementation increased the fat and protein content in the colostrum to the greatest extent.

Wogonin attenuates liver fibrosis via regulating hepatic stellate cell activation and apoptosis.

Liver fibrosis is the representative features of liver chronic inflammation and the characteristic of early cirrhosis. To date, effective therapy for liver fibrosis is lacking. Recently, Traditional Chinese Medicine (TCM) has attracted increasing attention due to its wide pharmacological effects and more uses in clinical. Wogonin, as one major active constituent of Scutellaria radix, has been reported it plays an important role in anti-inflammatory, anti-cancer, anti-viral, anti-angiogenesis, anti-oxidant and neuro-protective effects. However, the anti-fibrotic effect of wogonin is never covered in liver. In this study, we evaluated the protect effect of wogonin in liver fibrosis. Wogonin significantly attenuated liver fibrosis both in CCl4-induced mice and TGF-ß1 activated HSCs. Meanwhile, wogonin can enhances apoptosis of TGF-ß1 activated HSC-T6 cell from rat and LX-2 cell from human detected by flow cytometry. Additionally, wogonin can largely enhances cle-caspase3, cle-caspase9 expression and the ratio of Bax/Bcl-2 in T6 cells. Pro-apoptosis effect of wogonin in vivo was further verified in situ. In conclusion, wogonin can attenuate liver fibrosis via regulating the activation and apoptosis of hepatic stellate cells, and may be an effective drug to treat and prevent liver fibrosis.

Borneol for Regulating the Permeability of the Blood-Brain Barrier in Experimental Ischemic Stroke: Preclinical Evidence and Possible Mechanism.

Borneol, a natural product in the Asteraceae family, is widely used as an upper ushering drug for various brain diseases in many Chinese herbal formulae. The blood-brain barrier (BBB) plays an essential role in maintaining a stable homeostatic environment, while BBB destruction and the increasing BBB permeability are common pathological processes in many serious central nervous system (CNS) diseases, which is especially an essential pathological basis of cerebral ischemic injury. Here, we aimed to conduct a systematic review to assess preclinical evidence of borneol for experimental ischemic stroke as well as investigate in the possible neuroprotective mechanisms, which mainly focused on regulating the permeability of BBB. Seven databases were searched from their inception to July 2018. The studies of borneol for ischemic stroke in animal models were included. RevMan 5.3 was applied for data analysis. Fifteen studies investigated the effects of borneol in experimental ischemic stroke involving 308 animals were ultimately identified. The present study showed that the administration of borneol exerted a significant decrease of BBB permeability during cerebral ischemic injury according to brain Evans blue content and brain water content compared with controls (P < 0.01). In addition, borneol could improve neurological function scores (NFS) and cerebral infarction area. Thus, borneol may be a promising neuroprotective agent for cerebral ischemic injury, largely through alleviating the BBB disruption, reducing oxidative reactions, inhibiting the occurrence of inflammation, inhibiting apoptosis, and improving the activity of lactate dehydrogenase (LDH) as well as P-glycoprotein (P-GP) and NO signaling pathway.