Epidemiological insights into seasonal, sex­specific and age­related distribution of bacterial pathogens in urinary tract infections.

Urinary tract infections (UTIs) are prevalent and recurrent bacterial infections that affect individuals worldwide, posing a significant burden on healthcare systems. The present study aimed to explore the epidemiology of UTIs, investigating the seasonal, gender-specific and age-related bacterial pathogen distribution to guide clinical diagnosis. Data were retrospectively collected from electronic medical records and laboratory reports of 926 UTIs diagnosed in Fuding Hospital (Fujian University of Traditional Chinese Medicine, Fuding, China). Bacterial isolates were identified using standard microbiological techniques. χ2 tests were performed to assess associations between pathogens and the seasons, sex and age groups. Significant associations were found between bacterial species and seasons. Enterococcus faecium exhibited a substantial prevalence in spring (χ2, 12.824; P=0.005), while Acinetobacter baumannii demonstrated increased prevalence in autumn (χ2, 16.404; P=0.001). Female patients showed a higher incidence of UTIs. Gram-positive bacteria were more prevalent in males, with Staphylococcus aureus showing significant male predominance (χ2, 14.607; P<0.001). E. faecium displayed an age-related increase in prevalence (χ2, 17.775; P<0.001), whereas Escherichia coli tended to be more prevalent in younger patients (χ2, 12.813; P=0.005). These findings highlight the complex nature of UTIs and offer insights for tailored diagnostic and preventive strategies, potentially enhancing healthcare outcomes.

Targeted inhibition of the HNF1A/SHH axis by triptolide overcomes paclitaxel resistance in non-small cell lung cancer.

Paclitaxel resistance is associated with a poor prognosis in non-small cell lung cancer (NSCLC) patients, and currently, there is no promising drug for paclitaxel resistance. In this study, we investigated the molecular mechanisms underlying the chemoresistance in human NSCLC-derived cell lines. We constructed paclitaxel-resistant NSCLC cell lines (A549/PR and H460/PR) by long-term exposure to paclitaxel. We found that triptolide, a diterpenoid epoxide isolated from the Chinese medicinal herb Tripterygium wilfordii Hook F, effectively enhanced the sensitivity of paclitaxel-resistant cells to paclitaxel by reducing ABCB1 expression in vivo and in vitro. Through high-throughput sequencing, we identified the SHH-initiated Hedgehog signaling pathway playing an important role in this process. We demonstrated that triptolide directly bound to HNF1A, one of the transcription factors of SHH, and inhibited HNF1A/SHH expression, ensuing in attenuation of Hedgehog signaling. In NSCLC tumor tissue microarrays and cancer network databases, we found a positive correlation between HNF1A and SHH expression. Our results illuminate a novel molecular mechanism through which triptolide targets and inhibits HNF1A, thereby impeding the activation of the Hedgehog signaling pathway and reducing the expression of ABCB1. This study suggests the potential clinical application of triptolide and provides promising prospects in targeting the HNF1A/SHH pathway as a therapeutic strategy for NSCLC patients with paclitaxel resistance. Schematic diagram showing that triptolide overcomes paclitaxel resistance by mediating inhibition of the HNF1A/SHH/ABCB1 axis.

Angucyclinones with IDO and TDO inhibitory activities isolated from the actinomycetes Umezawaea beigongshangensis.

Four previously undescribed angucyclinones umezawaones A-D (1-4) were isolated from the liquid cultures of Umezawaea beigongshangensis. Their structures were determined by spectroscopic analyses, single crystal X-ray diffraction, quantum chemical 13C NMR and electronic circular dichroism calculations. All compounds displayed strong inhibitory activities against indoleamine 2,3-dioxygenase and tryptophan-2,3-dioxygenase in enzymatic assay, especially compound 2.

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.

Screening of phosphate-solubilizing bacteria and their abilities of phosphorus solubilization and wheat growth promotion.

BACKGROUND: Phosphate-solubilizing bacteria (PSB) can enhance plant growth and phosphorus (P) solubilization, it also has been reported to reduce the negative effects of overused agricultural fertilizer in farmland and protect the soil environment. However, the mechanism behind this interaction has not been fully elucidated. RESULTS: In this study, we screened out Pseudomonas moraviensis, Bacillus safensis, and Falsibacillus pallidus which can both solubilize P efficiently and produce indole-3-acetic acid (IAA) from sandy fluvo-aquic soils. The yield of wheat (Triticum aestivum) under PSB inoculation significantly increased up to 14.42% (P < 0.05) compared with the control treatment in phosphate fertilizer-used farmland. Besides promoting wheat growth, we found the labile P fraction in soil was significantly increased by over 122.04% (P < 0.05) under PSB inoculation compared with it in soils without, in parallel, the stable P fraction was significantly reduced by over 46.89% (P < 0.05). Furthermore, PSB inoculation increased the soil microbial biomass and activity, indicating that PSB screened out in this work performed a remarkable ability to colonize the soils in the wheat field. CONCLUSION: PSB from sandy fluvo-aquic soil improve wheat growth and crop productivity by increasing the labile P fraction and IAA content in the greenhouse and wheat field. Our work provides an environment and economy-friendly bacterial resource that potentially promotes sustainable agricultural development in the long term.

Study on the effect and mechanism of quercetin in treating gout arthritis.

Quercetin is widely found in natural plants, especially Chinese herbal plants. It has been used to treat arthritis in China for thousands of years. However, the effects and mechanisms of quercetin in the treatment of gout arthritis (GA) remain unclear. We aimed to verify the treatment of GA with quercetin and investigate the underlying mechanism. A combination of network pharmacology and experiments was used to reveal the mechanism of quercetin in the treatment of GA. Potential targets of quercetin and gout were identified. Then, the protein-protein interaction network for the common targets between quercetin and gout was constructed and the core targets were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses for the common targets were performed to elucidate the pharmacological functions and mechanisms associated with quercetin treatment in GA. Finally, a monosodium urate-induced GA rat model was used to validate the predicted mechanisms in network pharmacology. Seventy-two common targets were identified. KEGG analysis revealed that treatment of GA with quercetin predominantly involved the interleukin (IL)-17, tumor necrosis factor (TNF), mitogen-activated protein kinase, and phosphoinositide 3-kinase-Akt signaling pathways. In an experimental validation, quercetin attenuated ankle joint inflammation-induced bone destruction and histological lesions. It also diminished the expression of IL-6, IL-17A, and IL-17F in the IL-17 pathway, and regulated the release of RAR-related orphan receptor gamma t,IL-17E, IL-1ß, IL-6, TNF-α, Foxp3, and transforming growth factor-beta 1. The collective findings implicate quercetin as a valuable alternative drug for the treatment of GA.

[Impact of Land Use Types at Different Scales on Surface Water Environment Quality and Its Driving Mechanism].

As an important carrier of human activities, the spatial type of land use has an important impact on the surface water environment. Taking the Ruoergai wetland as an example, based on object-oriented remote sensing interpretation of land use types combined with water quality examination data, this study analyzed the impact and driving mechanism of land use types at different scales on the surface water environment at the small watershed and buffer scale. ① It was found that the water quality of the Ruoergai wetland could been classified as water grade V, and it was slightly eutrophic as a whole. The main pollutants were total nitrogen(TN) and phosphorus(TP), and the pollution originated from domestic sewage and grazing. ② The environmental quality of surface water was closely related to land use types. There was a negative correlation between chemical oxygen demand(COD) and the proportion of water area, a positive correlation between TN and the proportion of swamp area, and a negative correlation between total TP. ③ There was a significant correlation between spatial land use types at different scales and surface water environment. The land use type within a buffer of 1000 m had the highest interpretation degree for all factors, the land use type within a buffer of 200 m had the greatest interpretation degree for COD, the land use type within a buffer of 500 m zone had the greatest interpretation degree for TP and TN, and the land use type within a buffer of 800 m had the greatest explanation for Chl-a. The results of this study showed that the Ruoergai wetland wetland had a certain purification effect on pollutants and eutrophication. However, different land use types had different effects on different pollutants. The water body had a purification effect on Fe2+, COD, and Chl-a, and the swamp had a purification effect on TP but a cumulative effect on TN. Thus, the small-buffer zone(≤ 1000 m) land use type should be controlled, the water body and swamp areas should be controlled, the self-purification capacity of wetland waters should be improved, and the surface water environment of the Ruoergai wetland should be further protected and repaired.

Antibiotics prescription for targeted therapy of pediatric invasive pneumococcal diseases in China: a multicenter retrospective study.

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) is a major cause of bacterial meningitis, septicemia and pneumonia in children. Inappropriate choice of antibiotic can have important adverse consequences for both the individual and the community. Here, we focused on penicillin/cefotaxime non-susceptibility of S. pneumoniae and evaluated appropriateness of targeted antibiotic therapy for children with IPD (invasive pneumococcal diseases) in China. METHODS: A multicenter retrospective study was conducted in 14 hospitals from 13 provinces in China. Antibiotics prescription, clinical features and resistance patterns of IPD cases from January 2012 to December 2017 were collected. Appropriateness of targeted antibiotics therapy was assessed. RESULTS: 806 IPD cases were collected. The non-susceptibility rates of S. pneumoniae to penicillin and cefotaxime were 40.9% and 20.7% respectively in 492 non-meningitis cases, whereas those were 73.2% and 43.0% respectively in 314 meningitis cases. Carbapenems were used in 21.3% of non-meningitis cases and 42.0% of meningitis cases for targeted therapy. For 390 non-meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were used in 17.9% and 8.7% of cases respectively for targeted therapy. For 179 meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were prescribed in 55.3% and 15.6% of cases respectively. Overall, inappropriate targeted therapies were identified in 361 (44.8%) of 806 IPD cases, including 232 (28.8%) cases with inappropriate use of carbapenems, 169 (21.0%) cases with inappropriate use of vancomycin and 62 (7.7%) cases with inappropriate use of linezolid. CONCLUSIONS: Antibiotic regimens for IPD definite therapy were often excessive with extensive prescription of carbapenems, vancomycin or linezolid in China. Antimicrobial stewardship programs should be implemented to improve antimicrobial use.

[Effect of Nrf2/HO-1 signaling pathway in intestinal protection by Sishen Pills against ulcerative colitis in mice].

The present study aimed to explore the effect of nuclear factor erythroid 2 related factor 2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway in intestinal protection by Sishen Pills against ulcerative colitis(UC). After the UC model was induced by 3% dextran sodium sulfate(DSS), experimental animals were randomly divided into control group, model group, salazosulfapyridine(SASP) group, and low-and high-dose Sishen Pills groups. Drug intervention(ig) was performed for seven consecutive days during modeling. On the 7 th day, the mice were euthanized. The body weight and colon length were recorded, and the histopathological changes of the colon were observed by HE staining. Serum interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and reactive oxygen species(ROS) were detected by ELISA. The protein and mRNA expression of Nrf2, HO-1, and NADPH quinine oxidoreductase-1(NQO-1) was determined by Western blot and reverse transcription-polymerase chain reaction(RT-PCR). Compared with the normal group, the model group exhibited reduced body weight, colon length, and T-AOC, increased IL-6, TNF-α, MDA, and ROS, and diminished protein and mRNA expression of Nrf2, HO-1, and NQO-1 in the colon tissues. Compared with the model group, the SASP group and high-dose Sishen Pills group showed elevated body weight, colon length, and T-AOC, lowered IL-6, TNF-α, MDA, and ROS levels, and increased protein and mRNA expression of Nrf2, HO-1, and NQO-1 in the colon tissues. As assessed by HE staining, Sishen Pills could improve the pathological changes of the colon. The findings suggested that Sishen Pills could protect the colon against UC induced by 3% DSS. The specific mechanism of action may be related to the anti-inflammatory and anti-oxidative stress effects by the activation of the Nrf2/HO-1 signaling pathway.

Bufalin-induced cardiotoxicity: new findings into mechanisms.

Bufalin is one of the main pharmacological and toxicological components of Venenum Bufonis and many traditional Chinese medicine preparations. The cardiotoxicity clearly limits its application to patients living in countries. Hence, an investigation of its toxicological mechanism is helpful for new drug development and treatment of the related clinical adverse reactions. We investigate the cardiotoxicity of bufalin using human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) (0.003-0.1 µmol·L-1), human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) (0.03-0.3 µmol·L-1) and eight human cardiac ion channel currents (0.01-100 µmol·L-1) combined with an impedance-based bioanalytical and patch clamp method. Biphasic effect of bufalin on the contractility in hiPSC-CMs, which has been shown to strengthen myocardial contractility, accelerate conduction, and increase beating rate at the earlier stage of administration, whereas weakened myocardial contractility, abolished conduction, and ceased beating rate at the later stage of administration. Bufalin decreased the action potential duration (Action potential duration at 30%, 50% and 90% repolarization), cardiac action potential amplitude, and maximal depolarization rate and depolarized the resting membrane potential of hiPSC-CMs. Spontaneous beating rates of hiPSC-CMs were markedly increased at 0.03 µmol·L-1, while were weakened at 0.3 µmol·L-1 after application. Bufalin blocks INav1.5 in a concentration-dependent manner with half maximal inhibitory concentration of 74.5 µmol·L-1. Bufalin respectively increased the late sodium current and Na+-Ca2+ exchange current with a concentration for 50% of maximal effect of 2.48 and 66.06 µmol·L-1 in hiPSC-CMs. Whereas, bufalin showed no significant effects on other cardiac ion channel currents. The enhancement of the late sodium current is one of the main mechanism for cardiotoxicity of bufalin.

Effects of various oil extraction methods on the gelatinization and retrogradation properties of starches isolated from tigernut (Cyperus esculentus) tuber meals.

Gelatinization and retrogradation characteristics of starches from tigernut (Cyperus esculentus) tuber before and after various oil extraction processes were studied in this investigation. The results indicated that starches isolated from tigernut tuber after the various oil extraction processes varied significantly in gelatinization and retrogradation properties. The starches isolated from the cakes of tigernut tuber after hot press extraction exhibited higher retrogradation tendency and relatively less shear-thinning than other starch samples. The results of FT-IR, XRD, and NMR analysis indicated that oil extraction had an unfavorable influence on starch retrogradation, which may be due to structural changes caused by oil extraction processes. In particular, oil extraction led to more efficient packing of double helices in the crystalline lamella of the starches during storage. Retrogradation of the starch gels also reduced the water holding capacities of the starches. The starch sample isolated from the cake after cold press extraction exhibited the highest water absorption capacity among the five samples for all storage times. This investigation provides valuable novel information for the industrial utilization of tigernut tuber starches isolated from meals and cakes after oil extraction.

[Analysis of nine antioxidants in vegetable oils by high performance liquid chromatography].

A method was developed for the determination of nine antioxidants in vegetable oils by high performance liquid chromatography (HPLC). The samples were extracted with methanol, and the fat in the samples was degreased by freezing. Separation of the targeted compounds was performed on an XBridge C18 column in gradient elution mode using methanol-0.1% (v/v) formic acid aqueous solution as the mobile phase. The analytes were detected using a diode-array detector by the external standard method. The stability and storage conditions for the nine antioxidants were systematically investigated. Ascorbyl palmitate (AP) was introduced into the preparation and pre-treatment of the targets. The concentration of AP was optimized to improve the stability and recovery of the targets. The effects of different extraction solvents and purification methods on the extraction efficiencies were discussed. The results showed that the nine antioxidants could be separated well under the optimized conditions. Good linear relationships in the linear range were obtained, and the correlation coefficients (R2) were greater than 0.999. The average recoveries of the nine antioxidants ranged from 85.3% to 104.1%, with RSDs of the method ≤5.0%. The limits of quantitation (LOQs) for the nine synthetic antioxidants were in the range of 0.6-3.0 mg/kg. The method is simple, rapid, sensitive, and it shows good recovery and reproducibility.

Taurine Supplementation Reverses Diabetes-Induced Podocytes Injury via Modulation of the CSE/TRPC6 Axis and Improvement of Mitochondrial Function.

BACKGROUND: The protective effects of taurine supplementation on diabetic kidney disease (DKD) have been defined, but the mechanisms are not quite clear yet. TRPC6 has been shown to function in the homeostasis of podocytes, but whether TRPC6-modulated mitochondrial dysfunctions participating in taurine-induced renal protection during diabetes are unclear. METHODS: A DKD model was constructed using streptozocin (STZ), and an immortalized mouse podocytes cell line MPC-5 was used. Renal histology and western blot were used to analyze the expression levels of certain proteins. Cell proliferation assays, apoptosis assays, calcium influx, and mitochondrial functions were evaluated. RESULTS: In this study, taurine intervention improved STZ-induced DKD injuries, while it decreased both 24-h urinary protein and podocytes apoptosis. In detail, this study showed that taurine treatment decreased mitochondrial ROS productions by suppressing calcium overload and improving mitochondrial respiratory functions. Furthermore, the upregulation of TRPC6 is partially responsible for the calcium overload during high glucose treatment, whereas taurine treatment inhibited TRPC6 expression and partially attenuated high glucose-induced podocytes injuries. In addition, we demonstrated that taurine could upregulate CSE expression and inhibits TRPC6 expression via promoting the synthesis of H2S. CONCLUSION: Our study reveals that taurine intervention could partially attenuate the lesions of DKD by modulating the CSE/TRPC6 axis.

Bufalin-induced cardiotoxicity: new findings into mechanisms / 中国天然药物

Bufalin is one of the main pharmacological and toxicological components of Venenum Bufonis and many traditional Chinese medicine preparations. The cardiotoxicity clearly limits its application to patients living in countries. Hence, an investigation of its toxicological mechanism is helpful for new drug development and treatment of the related clinical adverse reactions. We investigate the cardiotoxicity of bufalin using human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) (0.003-0.1 μmol·L), human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) (0.03-0.3 μmol·L) and eight human cardiac ion channel currents (0.01-100 μmol·L) combined with an impedance-based bioanalytical and patch clamp method. Biphasic effect of bufalin on the contractility in hiPSC-CMs, which has been shown to strengthen myocardial contractility, accelerate conduction, and increase beating rate at the earlier stage of administration, whereas weakened myocardial contractility, abolished conduction, and ceased beating rate at the later stage of administration. Bufalin decreased the action potential duration (Action potential duration at 30%, 50% and 90% repolarization), cardiac action potential amplitude, and maximal depolarization rate and depolarized the resting membrane potential of hiPSC-CMs. Spontaneous beating rates of hiPSC-CMs were markedly increased at 0.03 μmol·L, while were weakened at 0.3 μmol·L after application. Bufalin blocks I in a concentration-dependent manner with half maximal inhibitory concentration of 74.5 μmol·L. Bufalin respectively increased the late sodium current and Na-Ca exchange current with a concentration for 50% of maximal effect of 2.48 and 66.06 μmol·L in hiPSC-CMs. Whereas, bufalin showed no significant effects on other cardiac ion channel currents. The enhancement of the late sodium current is one of the main mechanism for cardiotoxicity of bufalin.

Suppression of the NF­κB signaling pathway in colon cancer cells by the natural compound Riccardin D from Dumortierahirsute.

Colorectal cancer (CRC) is a major cause of mortality and morbidity. Chronic inflammation is closely associated with the development, progression and prognosis of the majority of intestinal malignancies. In recent years, targeting the nuclear factor (NF)­κB signaling pathway for CRC therapy has become an attractive strategy. Riccardin D, a novel macrocyclicbis (bibenzyl) compound, was isolated from the Chinese liverwort plant. Previous studies have suggested that Riccardin D exerted chemo­preventative effects against the intestinal malignancy formation. In the present study, cell counting kit­8, Hochest 33258 staining, mitochondria membrane permeability assay, western blotting analysis, reverse transcription­polymerase chain reaction, luciferase reporter gene assay and molecular modeling analysis were performed to detect the effect and mechanisms of Riccardin D on human colon cancer cells. The results demonstrated that Riccardin D significantly inhibited the growth of HT­29 cells. In addition, the cDNA expression of cyclooxygenase­2, and the protein expression and activity of NF­κB and tumor necrosis factor­α were downregulated; however, the protein expression of cleaved caspase­3 and ­9, and cleaved poly (adenosine diphosphate­ribose) polymerase, and the B­cell lymphoma (Bcl)­2: Bcl­2­associated X protein ratio were upregulated. Furthermore, Auto Dock analysis identified binding sites between Riccardin D and NF­κB. These results indicated that Riccardin D may inhibit cell proliferation and induce apoptosis in HT­29 cells, which may be associated with the blocking of the NF­κB signaling pathway. Thus, Riccardin D should be investigated as an NF­κB inhibitor in cancer therapy.

[Effect of Saposhnikoviae Radix on pharmacokinetics and tissue distributions of active components in Tongxie Yaofang in rats].

Tongxie Yaofang (TXYF) is a famous formula that has been used for treating gastrointestinal diseases in traditional Chinese medicine(TCM). Saposhnikoviae Radix is considered as a meridian guiding drug in TXYF and could enhance the effectiveness of prescription. However, the scientific evidence for this effect is still not clear. To reveal the interactions of Saposhnikoviae Radix with other herbs, we conducted this study on the pharmacokinetic profile and tissue distribution of active ingredients of TXYF in rats. The concentrations of four components in blood and tissues were determined by UPLC-MS/MS after oral administration with TXYF. The detection was carried out by electrospray ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. The positive and negative ion switching technique was performed in the same analysis. The results revealed that Saposhnikoviae Radix could enhance Cmax, AUC0-t, and AUC0-∞ of paeoniflorin and hesperidin, and increase the distribution of atractylenolide-I, paeoniflorin and hesperidin in liver, spleen, brain and small intestine. Saposhnikoviae Radix increased the ratio of brain to blood concentrations of atractylenolide-I, paeoniflorin and hesperidin. Meanwhile, it reduced the ratio of lung to blood concentrations of atractylenolide-I and paeoniflorin. Saposhnikoviae Radix, and may enhance the effectiveness of prescriptions by promoting distribution of other herbs in brain.

Effect of Saposhnikoviae Radix on pharmacokinetics and tissue distributions of active components in Tongxie Yaofang in rats / 中国中药杂志

Tongxie Yaofang (TXYF) is a famous formula that has been used for treating gastrointestinal diseases in traditional Chinese medicine(TCM). Saposhnikoviae Radix is considered as a meridian guiding drug in TXYF and could enhance the effectiveness of prescription. However, the scientific evidence for this effect is still not clear. To reveal the interactions of Saposhnikoviae Radix with other herbs, we conducted this study on the pharmacokinetic profile and tissue distribution of active ingredients of TXYF in rats. The concentrations of four components in blood and tissues were determined by UPLC-MS/MS after oral administration with TXYF. The detection was carried out by electrospray ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. The positive and negative ion switching technique was performed in the same analysis. The results revealed that Saposhnikoviae Radix could enhance Cmax, AUC0-t, and AUC0-∞ of paeoniflorin and hesperidin, and increase the distribution of atractylenolide-I, paeoniflorin and hesperidin in liver, spleen, brain and small intestine. Saposhnikoviae Radix increased the ratio of brain to blood concentrations of atractylenolide-I, paeoniflorin and hesperidin. Meanwhile, it reduced the ratio of lung to blood concentrations of atractylenolide-I and paeoniflorin. Saposhnikoviae Radix, and may enhance the effectiveness of prescriptions by promoting distribution of other herbs in brain.

Tetramethypyrazine inhibits renal cell carcinoma cells through inhibition of NKG2D signaling pathways.

Tetramethypyrazine (TMP), one of the active compounds extracted from the traditional Chinese medicinal herb (Chuanxiong), has been verified as an anticancer compound against several types of cancer. However, understanding of the molecular mechanisms have not been fully elucidated. In the present study, the anticancer efficacy of TMP was investigated in human clear cell renal cell carcinoma (ccRCC) cells. We showed that TMP significantly inhibited ccRCC cell viability, proliferation, apoptosis, invasion and migration through the methods of MTT, flow cytometry, wound healing and transwell assays. Furthermore, reverse transcription polymerase chain reaction (RT-PCR), western blotting and immunofluorescence results demonstrated TMP upregulation of the expression of NKG2D ligands (NKG2DLs) MHC class I chain-related molecules A and B (MICA/B) and epithelial cell expression marker of E-cadherin, and downregulation of mesenchymal cell expression markers of vimentin and fibronectin. Taken together, the inhibition of TMP on ccRCC cells might be mediated via inhibition of NKG2D related signaling pathway to further suppress epithelial-mesenchymal transition (EMT) progression. The binding of NKG2D to its ligands activates NK cells, giving the rationale for studies on the utilization of TMP as a potential cancer therapeutic compound to increase NK cells-mediated cytotoxicity against high MICA/B expression in cancer cells.

The protective effects of paeonol against epirubicin-induced hepatotoxicity in 4T1-tumor bearing mice via inhibition of the PI3K/Akt/NF-kB pathway.

Epirubicin is widely used for the treatment of various breast cancers; however, it has serious adverse side effects, such as hepatotoxicity, which require dose-adjustment or therapy substitution. Paeonol, an active component from Moutan Cortex, has a variety of biological activities, including preventing or reducing various toxicities induced by antineoplastics. Protection by paeonol against hepatotoxicity induced by epirubicin and the underlying mechanism of action were investigated in this study. Cytosolic enzymes in the serum and oxidative stress indices in the liver were determined. The protective effects were determined using the MTT assay in vitro or by evaluating the expression of apoptotic factors and crucial proteins in the PI3K/Akt/NF-kB pathway using western blot analysis. It is concluded that paeonol alleviates epirubicin-induced hepatotoxicity in 4T1-tumor bearing mice by inhibiting the PI3K/Akt/NF-kB pathway.

[Astragalus Granule Combined Auricular Point Sticking for Cough Variant Asthma in Children].

Objective To observe the clinical efficacy and effect of Astragalus Granule (AG) , auricular point sticking combined with aerosol inhalation on the levels of tumor necrosis factor-α (TNF- a), interleukin-4 (IL-4), interleukin-10 (IL-10), eosinophil cell count (EOS), and immunoglobulin E (IgE) in cough variant asthma (CVA) children. Methods Totally 150 CVA children patients were ran- domly assigned to three group, the Western medicine group (WM) , the Chinese medicine group (CM) , and the combined group, 50 in each group. All patients received basic treatment of aerosol inhalation with Budesonide suspension and Terbutaline Sulphate Solution. Patients in the WM group received basic treatment alone. Those in the CM group additionally took AG. Those in the combined group additionally took AG and received auricular point sticking. The therapeutic course for all was 8 weeks. Expression levels of TNF-α, IL-4, and IL-10 were detected in each group using ELISA before and after treatment. Levels of EOS and IgE were detected using hematology analyzer. Results Compared with before treatment in the same group, the expression levels of TNF-α and IgE decreased in the WM group after treatment (P < 0. 05) ; the expression levels of TNF-α, IL-4, EOS, and IgE decreased, but the level of IL-10 increased in the CM group and the combined group after treatment (P <0. 05). Compared with the WM group at the same time, the expression level of IL-10 increased, and the level of IgE decreased in the CM group (P < 0. 05). The control rate, the markedly effective rate, and the total effective rate were elevated (P < 0. 05), and the ineffective rate was lowered (P <0. 05) in the CM group. In the combined group the expression levels of TNF-α, IL-4, EOS, and IgE decreased, and the level of IL-10 increased after treatment (P <0. 05). The cough alleviation time and the disappearance time were shortened in the combined group after treatment (P <0. 05). The control rate, the markedly effective rate, and the total effective rate were elevated (P <0. 05), and the ineffective rate was lowered (P <0. 05) in the combined group after treatment. Compared with the CM group at the same time point, the expression level of IL-10 increased (P < 0. 05), the levels of IgE and EOS were lowered (P <0. 05), the cough alleviation time and the disappear- ance time were shortened (P <0. 05) , the control rate and the total effective rate were elevated in the combined group after treatment (P <0. 05). Conclusion AG, auricular point sticking combined with aerosol inhalation could significantly reduce the levels of TNF-α, IL-4, EOS, and IgE, and improve the level of IL-10 in CVA children patients, with significant clinical effects.