Associations between somatic symptoms and remission of major depressive disorder: A longitudinal study in China.

Previous studies have documented negative associations between somatic symptoms and remission of major depressive disorder (MDD). However, the correlations of specific somatic symptoms with remission remain uncertain. We aimed to explore the associations between specific somatic symptoms and remission focusing on sex differences among patients with MDD. We used data from patients with MDD in the Depression Cohort in China. At baseline, total somatic symptoms were evaluated using the 28-item Somatic Symptoms Inventory and were categorized into pain, autonomic, energy, and central nervous system (CNS) symptoms. To measure remission of MDD, depressive symptoms were evaluated using the Patient Health Questionnaire-9 after 3 months of treatment. We ultimately included 634 patients. Compared with quartile 1 of total somatic symptom scores, the full-adjusted ORs (95% CIs) for remission from quartile 2 to quartile 4 were 0.52 (0.30, 0.90), 0.44 (0.23, 0.83), and 0.36 (0.17, 0.75), respectively (P-value for trend = 0.005). The restricted cubic spline showed no non-linear associations between total somatic symptoms with remission (P-value for non-linear = 0.238). Pain, autonomic, and CNS symptoms showed similar results. Sex-stratified analysis showed that total somatic symptoms, pain symptoms, and autonomic symptoms were negatively correlated with remission in females, whereas CNS symptoms were negatively associated with remission in males. Our findings indicate that specific somatic symptoms exert differential effects on remission of MDD. Therapeutic interventions that target pain, autonomic, and CNS symptoms may increase the probability of remission. Furthermore, interventions for somatic symptoms should be tailored by sex, and females deserve more attention.

Associations of rumination with suicidal ideation and suicide attempts amongst individuals with major depressive disorder: A 12-month longitudinal study in China.

BACKGROUND: This study aimed to explore the longitudinal associations of rumination with suicidal ideation and suicide attempts in individuals with major depressive disorder (MDD). METHODS: Participants were derived from the Depression Cohort in China study (DCC). Those who completed at least one follow-up visit during the 12 months were included in the analysis. Dimensions of rumination including brooding and reflection were each measured using five items of the Ruminative Responses Scale. Suicidal ideation was assessed using the Beck Scale for Suicide Ideation. Suicide attempts were also assessed and all were analyzed with generalized estimating equations. RESULTS: Our final sample included 532 participants aged 18 to 59 years (mean [SD], 26.91 [6.94] years) consisting of 148 (27.8%) males and 384 (72.2%) females. After adjusting for temporal trend and potential confounders, individuals with higher levels of reflection were more likely to report suicidal ideation (AOR =1.11, 95% CI:1.01-1.22). However, no statistically significant association was found between brooding and suicidal ideation (AOR =1.06, 95% CI:0.96-1.17). Conversely, individuals with higher levels of brooding were more likely to report suicide attempts (AOR =1.13, 95% CI:1.02-1.24), while no statistically significant association was observed between reflection and suicide attempts (AOR =0.91, 95% CI:0.82-1.01). CONCLUSION: Rumination reflects a disturbance in cognitive emotional processing and manifests in different dimensions. Our findings suggest that high levels of reflection and brooding may be associated with a higher likelihood of having suicidal ideation and suicide attempts, respectively. However, it should be interpreted with caution, given that effect sizes are small.

Evaluation of a novel instrument for detecting bipolar disorders in China: The Rapid Mood Screener (RMS).

OBJECTIVE: Bipolar disorder is easily misdiagnosed with major depressive disorder (MDD). The Rapid Mood Screener (RMS) was developed to address this unmet clinical need. This study aims to translate and evaluated the reliability and validity of the RMS in Chinese adults with bipolar I/II disorder (BD-I/II). METHODS: Brislin's translation and Delphi method were conducted to formulate the RMS-Chinses version (RMS-C). Patients with MDD (N = 99), BD-I (N = 77) and BD-II (N = 78) were included to assess the validity and reliability of RMS-C. The area under the curve (AUC) was computed to ascertain the ability of the Mood Disorder Questionnaire (MDQ) and RMS-C to distinguish BD-I and BD-II from MDD. The optimal cut-off scores for classification were also calculated by the maximum sensitivity and specificity. RESULTS: The intraclass correlation coefficient of the RMS-C was 0.82 (95%CI, 0.71-0.89). The content validity index by six items were 0.71, 0.86, 1.00, 0.86, 1.00, and 1.00 in turn, and by scales was 0.90. The AUCs of the RMS-C in both BD-I/II, BD-I alone and BD-II alone were 0.83 (95 % CI, 0.78-0.89), 0.82 (95 % CI, 0.75-0.89) and 0.85 (95 % CI, 0.79-0.91), respectively, and were comparably to the MDQ. The optimal RMS-C values of the presence of BD-I and BD-II were >4 and 3, respectively. CONCLUSION: The RMS-C is a valid, simple self-administer screening tool to help identify BD-I or BD-II in persons experiencing a depressive episode. Validating the impact of screening with the RMS-C on health outcomes and health economics is warranted.

Chemical constituents from the roots of Dolomiaea souliei.

A new benzofuran-type neolignan (1), two new phenylpropanoids (2 - 3), and one new C21 steroid (4) were isolated from the ethyl acetate extract of the roots of Dolomiaea souliei by chromatographic methods, including silica gel, ODS column chromatography, MPLC, and semi-preparative HPLC. Their structures were identified as dolosougenin A (1), (S)-3-isopropylpentyl (E)-3-(4-hydroxy-3-methoxyphenyl) acrylate (2), (S)-3-isopropylpentyl (Z)-3-(4-hydroxy-3-methoxyphenyl) acrylate (3) and dolosoucin A (4) through various spectroscopic techniques including 1D NMR, 2D NMR, IR, UV, HR ESI MS, ORD, and computational ORD methods.

Pinellia ternata (Thunb.) Breit. attenuates the allergic airway inflammation of cold asthma via inhibiting the activation of TLR4-medicated NF-kB and NLRP3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Pinellia ternata (Thunb.) Breit. (PT) has been demonstrated to be effective against the allergic airway inflammation (AAI) in clinical practices, especially in cold asthma (CA). Until now, the active ingredients, protective effect, and possible mechanism of PT against CA remain unknown. AIM OF THE STUDY: The aim of this investigation was to examine the therapeutic impact and elucidate the underlying mechanism of PT on the AAI of CA. METHODS: The compositions of PT water extract were determined via the UPLC-Q-TOF-MS/MS. The ovalbumin (OVA) and cold-water baths were used to induce CA in female mice. Morphological characteristic observations, expectorant effect, bronchial hyperreactivity (BHR), excessive mucus secretion, and inflammatory factors were used to uncover the treatment effect of PT water extract. In addition, the mucin 5AC (MUC5AC) mRNA and protein levels and the aquaporin 5 (AQP5) mRNA and protein levels were detected via qRT-PCR, immunohistochemistry (IHC), and western blotting. Moreover, the protein expressions associated with the TLR4, NF-κB, and NLRP3 signaling pathway were monitored by western blot analysis. RESULTS: Thirty-eight compounds were identified from PT water extract. PT showed significant therapeutic effects on mice with cold asthma in terms of expectorant activity, histopathological changes, airway inflammation, mucus secretion, and hyperreactivity. PT exhibited good anti-inflammatory effects in vitro and in vivo. The expression levels of MUC5AC mRNA and protein decreased significantly, while AQP5 expression levels increased significantly in the lung tissues of mice after administration with PT as compared to mice induced by CA. Furthermore, the protein expressions of TLR4, p-iκB, p-p65, IL-1ß, IL-18, NLRP3, cleaved caspase-1, and ASC were markedly reduced following PT treatment. CONCLUSIONS: PT attenuated the AAI of CA by modulating Th1- and Th2-type cytokines. PT could inhibit the TLR4-medicated NF-kB signaling pathway and activate the NLRP3 inflammasome to reduce CA. This study provides an alternative therapeutic agent of the AAI of CA after administration with PT.

Exploring the pharmacological mechanisms and key active ingredients of total flavonoids from Lamiophlomis rotata (Benth.) Kudo against rheumatoid arthritis based on multi-technology integrated network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Lamiophlomis rotata (Benth.) Kudo (LR, Lamiaceae) is a traditional Tibetan medicinal material in China. Tibetan medicine classic and research report suggested that LR could be used to cure rheumatoid arthritis (RA). However, the anti-RA active ingredients and pharmacological mechanisms of LR have not been elucidated. AIM OF THE STUDY: To explore the mechanisms and key active ingredients of total flavonoids from LR (TFLR) against RA. MATERIALS AND METHODS: First, the mechanisms of TFLR against RA were investigated on collagen-induced arthritis (CIA) rat model by analyzing paw appearance, paw swelling, arthritis score, spleen index, thymus index, inflammatory cytokine (TNF-α, IL-1ß, IL-6 and IL-17) levels in serum, histopathology of ankle joint and synovium from knee joint (hematoxylin-eosin, safranin O-fast green and DAB-TUNEL staining), and apoptosis-related protein (PI3K, Akt1, p-Akt, Bad, p-Bad, Bcl-xL and Bcl-2) levels in the synovium of ankle joints (Western blot). Then, the crucially active ingredients of TFLR against RA were explored by network pharmacology, ingredient analysis, in vitro metabolism and TNF-α-induced human RA synovial fibroblast MH7A proliferation assays. Network pharmacology was applied to predict the key active ingredients of TFLR against RA. The ingredient analysis and in vitro metabolism of TFLR were performed on HPLC, and MH7A proliferation assay were applied to evaluate the predicted results of network pharmacology. RESULTS: TFLR shown excellently anti-RA effect by reducing paw swelling, arthritis score, spleen index, thymus index and inflammatory cytokine (IL-1ß, IL-6 and IL-17) levels, and improving the histopathological changes of ankle joint and synovium from knee joint in CIA rats. Results of Western blot indicated that TFLR reversed the changes of PI3K, p-Akt, p-Bad, Bcl-xL and Bcl-2 levels in the ankle joint synovium of CIA rats. Results of network pharmacology exhibited that luteolin was identified as the pivotal active ingredient of TFLR against RA. The ingredient analysis of TFLR indicated that the main ingredient in TFLR was luteoloside. The in vitro metabolism study of TFLR suggested that luteoloside could be converted to luteolin in artificial gastric juice and intestinal juice. Results of MH7A proliferation assay showed that there was no significant difference between TFLR and equal luteoloside on the viability of MH7A cells, indicating that luteoloside was the key active ingredient of TFLR against RA. Additionally, the luteolin (same mol as luteoloside) showed better inhibitory effect on the viability of MH7A cells than luteoloside. CONCLUSION: TFLR showed anti-RA effect, and the mechanism was related to promoting synovial cell apoptosis mediated by PI3K/Akt/Bad pathway. Meanwhile, this work indicated that luteoloside was the key active ingredient of TFLR against RA. This work lays a foundation for providing TFLR product with clear mechanism and stable quality to treat RA.

Driving factors of soil organic carbon sequestration under straw returning across China's uplands.

Straw returning is suggested as a sustainable agricultural practice to promote soil organic carbon (SOC) sequestration, whose magnitude can be influenced by climatic, edaphic and agronomic factors simultaneously. However, the driving factors regulating straw returning-induced SOC increase in China's uplands remain uncertain. This study conducted a meta-analysis by collecting data from 238 trials at 85 field sites. The results showed that straw returning significantly increased SOC content by an average of 16.1% ± 1.5% with an average sequestration rate of 0.26 ± 0.02 g kg-1 yr-1. The improvement effects were significantly better in the northern China (NE-NW-N) than in the eastern and central (E-C). SOC increases were more pronounced in C-rich and alkaline soils, in cold and dry climates, and under larger amounts of straw-C and moderate nitrogen fertilizer inputs. Longer experimental period resulted in higher SOC increase rates but lower SOC sequestration rates. Furthermore, partial correlation analysis and structural equation modelling revealed that total straw-C input was the key driving factor of SOC increase rate whereas straw returning duration was the dominant limiting factor of SOC sequestration rate across China. Climate conditions were potential limiting factors of SOC increase rate in NE-NW-N and SOC sequestration rate in E-C. It was suggested that straw returning with large application amounts should be more strongly recommended in uplands in NE-NW-N especially in the straw applications at the beginning, from the perspective of SOC sequestration.

Association of emotional and behavioral problems with sleep disturbance among Chinese adolescents: The moderation effect of academic performance.

BACKGROUND: This study aimed to explore the association of emotional and behavioral problems with sleep disturbance among Chinese adolescents, and to test whether these associations vary with adolescents' academic performance. METHODS: Data were from the 2021 School-based Chinese Adolescents Health Survey using a multistage, stratified-cluster, and random-sampling method to collect information from 22,684 middle school students in Guangdong Province, China. RESULTS: Emotional problems (aOR = 1.34, 95 % CI = 1.32-1.36), conduct problems (aOR = 1.19, 95 % CI = 1.16-1.21), hyperactivity (aOR = 1.35, 95 % CI = 1.33-1.37), and peer problems (aOR = 1.06, 95 % CI = 1.04-1.09) were significantly associated with the increased risk of sleep disturbance among middle school students in Guangdong Province. The prevalence of sleep disturbance among adolescents was 29.4 %. There were significant interactions of emotional problems/conduct problems/peer problems/prosocial behavior with academic performance on sleep disturbance. Further stratification analyses by academic performance showed that adolescents with self-reported good academic performance had a higher risk of sleep disturbance than those students with self-reported average or poor academic performance. LIMITATIONS: This study only included school students and used the cross-sectional design to preclude causality determination. CONCLUSIONS: Our findings suggest that emotional and behavioral problems elevate the risk of sleep disturbance in adolescents. Adolescent academic performance plays a modulating role in these above-mentioned significant associations for sleep disturbance.

Effects of Sedi Herba (Sedum sarmentosum) on attenuating cholestasis by the activation of the farnesoid x receptor (FXR)-mediated signaling.

Sedum sarmentosum (Sedi Herba) has traditionally been used to treat jaundice and various types of liver disease. This study aimed to clarify the anti-cholestatic efficacy and the mechanism of S. sarmentosum ethyl acetate extract (SDEAE), as well as to screen the potential compounds with FXR activation. SDEAE effectively ameliorated ANIT-induced cholestasis in rats, as evidenced by the ameliorative histopathology of the liver and the significant decrease in biochemical markers (ALT, AST, ALP, GGT, TBIL, DBIL and TBA). The analysis of bile acid profile by LC-MS indicated that SDEAE decreased the toxic bile acid levels (TCA, TMCA and CA). Western blotting indicated that SDEAE activated FXR-associated pathway, thereby upregulating FXR, SHP, BSEP and UGT2B4 expression, and downregulating CYP7A1 and NTCP expression. Twenty-three compounds (7 nor-sesquiterpenoids, 13 flavonoids, 1 lignin, 1 sterol and 1 anthraquinone) were isolated and identified from SDEAE by comparing NMR data with the literature. The HPLC profiles of SDEAE and isolated compounds were also compared. High-content analysis showed that eight compounds (6, 7, 8, 11, 12, 13, 14 and 23) could activate FXR and compound 8 exhibited the most potent activity (p < 0.01). Molecular docking suggested that the main binding modes between these active compounds and FXR were hydrogen bonding and van der Waals forces, and compound 8 had the highest docking score 6.34. The activation of compound 8 on FXR-mediated signaling was validated in L02 cells. After siRNA down-regulation of FXR, compound 8 significantly elevated FXR, SHP, BSEP and UGT2B4 expression, and reduced CYP7A1 and NTCP expression.

Effects of Fruit Storage Temperature and Time on Cloud Stability of Not from Concentrated Apple Juice.

Apple juice that is designated 'Not from concentrated' (NFC) is now increasingly popular with consumers due to its unique taste and rich nutritional value. However, layered precipitation and instability have emerged as serious technical problems that restrict the viability of the NFC apple juice industry. This study researched the influence of water-cored 'Fuji' apple fruit storage under different temperatures (0, 20 °C) and times (0, 9, 18, 30, 60 days) on the turbidity stability of NFC apple juice. Changes in the physicochemical properties (juice yield, pH, total soluble solids and titratable acid), turbidity stability (turbidity and particle size) and precipitation sensitive substances (insoluble starch, total phenolics, soluble protein and pectin) of NFC apple juice were determined, combined with the respiratory rates and ethylene release of apples, in order to study post-harvest regulation and control of processed fruit. Results indicated that fruit storage temperature and time significantly guided the turbidity stability of NFC apple juice. As a typical respiratory climacteric fruit, apple fruit stored 45 days at 0 °C and 15 days at 20 °C gained the best juice stability, respectively. This is basically consistent with the respiratory peak of fruit when processing raw materials. During the post-ripening process, the insoluble starch in apple gradually hydrolyzed into fructose and glucose, while total phenolics diminished and water-soluble pectin content increased. On the other hand, the amounts of pectin, soluble protein and phenolics in fruit juice declined as the fruit aged in the late storage period (stored 75 days at 0 °C and 40 days at 20 °C). Meanwhile particle size became larger and the turbidity stability of cloudy juices also decreased. This study's results will provide a sound theoretical basis for improving the turbidity stability of NFC apple juice by regulating the physiological state of processed raw materials.

Lecithin-Polysaccharide Self-Assembled Microspheres for Resveratrol Delivery.

Poor water solubility and low chemical stability, seriously limit the efficient bioavailability of resveratrol. Here, we propose encapsulating resveratrol in lecithin-polysaccharide self-assembled microspheres (LPSM). An LPSM was designed with a lecithin core, and alginate-carboxymethyl chitosan biolayer shell. The LPSM had a spherical shape with 12.171 ± 0.960 µm of particle size and -30.86 ± 1.37 mV of zeta potential. The introduce of lecithin remarkably increased the encapsulation efficiency of resveratrol to 92.78 ± 0.82%. The LPSM elevated the antioxidant capacity and ultraviolet resistance of resveratrol. Moreover, LPSM inhibited release in a simulated gastric environment, promoted sustained release in simulated intestinal environment, and elevated the bioavailability of resveratrol during in vitro simulated digestion. Results indicate that LPSM is promising as a carrier for resveratrol delivery to enhance stability and bioaccessibility.

Integrated strategy of network pharmacology, molecular docking, HPLC-DAD and mice model for exploring active ingredients and pharmacological mechanisms of Penthorum chinense Pursh against alcoholic liver injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Penthorum chinense Pursh (PCP, Saxifragaceae) is an edible plant and frequently-used Chinese herbal medicine, and is commonly used as Miao medicine in China. It showed well effect on alcoholic liver injury (ALI), but studies on its active ingredients and mechanisms against ALI remain at the starting stage. AIM OF THE STUDY: This work aims to explore the active ingredients and pharmacological mechanisms of PCP against ALI. MATERIALS AND METHODS: First, network pharmacology was applied to decipher the potential active ingredients and pharmacological mechanisms of PCP against ALI by ingredient identification, ADMET evaluation, target identification, network construction and analysis, protein-protein interaction (PPI) analysis, and gene enrichment analysis. Second, molecular docking was used to explore the interaction between key active ingredient and hub protein of PCP against ALI. Then, the ingredient analysis of PCP aqueous extract and semiquantitative analysis of key active ingredient were carried out on HPLC-DAD. Subsequently, mice with ALI were used to investigate the therapeutic effect or verify the predicted mechanisms of PCP or key active ingredient against ALI by analyzing body weight, liver index, ALT and AST activities in serum and liver tissues, oxidation related indices (SOD activity, GSH level and MDA level) in liver tissues, histopathology of liver tissues (oil red O, hematoxylin-eosin and DAB-TUNEL staining), and changes of related proteins (PI3K, Akt, p-Akt, Bax and Bcl-2) in liver tissues with the aid of Western blot. RESULTS: Network pharmacology showed that the active ingredients and related genes of PCP against ALI comprised 10 ingredients and 52 genes. Based on the result of ingredient analysis of PCP aqueous extract, quercitrin was identified as the key active ingredient of PCP against ALI. PPI analysis indicated that AKT1 was the hub gene of PCP against ALI, and molecular docking suggested that there were good interaction between quercetin and Akt1 protein. Gene enrichment analysis showed that the pivotal molecular mechanism of PCP against ALI might be to inhibit hepatocyte apoptosis via activation of PI3K-Akt signaling pathway. PCP and quercitrin showed anti-ALI effect by offsetting weight loss and increase of liver index, and reversing the imbalance of oxidative stress and histopathological changes of liver tissues (abnormal fatty acid metabolism, hepatic cord swelling and inflammatory cell infiltration) in mice with ALI. PCP caused the decrease of DAB-TUNEL-positive cells, upregulated the anti-apoptotic proteins (PI3K, Akt and p-Akt) levels and the ratio of p-Akt/Akt, and downregulated pro-apoptotic protein (Bax) level and the ratio of Bax/Bcl-2 in liver tissues of mice with ALI, indicating that the mechanism of PCP against ALI involved in inhibiting hepatocyte apoptosis via activation of PI3K-Akt signaling pathway. CONCLUSION: PCP and quercitrin showed well anti-ALI effect. The key active ingredient of PCP against ALI was identified as quercitrin. The underlying pharmacological mechanisms of PCP against ALI may be related to PI3K-Akt signaling pathway-mediated inhibition of hepatocyte apoptosis. This work provided new evidence to support the application of PCP in treatment of ALI, and a research basis for the research and development of functional foods or drugs against ALI from PCP.

[Two new triterpeneoids from roots of Dolomiaea souliei].

The present study analyzed the chemical constituents in dried roots of Dolomiaea souliei. Chromatographic methods, such as normal-phase, and reversed-phase column chromatography, TLC, and preparative HPLC, were applied to separate and purify the petroleum ether extract of D. souliei. The structures of the purified constituents were identified by multiple spectroscopic methods including 1 D NMR, 2 D NMR, IR, UV, and HR-ESI-MS. Fourteen triterpenoids were obtained and identified as bauer-8-ene-3,11-dione-7α-ol(1), bauer-8-ene-3-one-7α,11α-diol(2), 3-oxo-11α-hydroxy-urs-12-ene(3), 3-oxour-12-ene-1ß,11α-diol(4), 3ß,11α-dihydroxy-urs-12-ene(5), taraxast-20-ene-3ß,30-diol(6), 28-hydroxy-3-oxo-12-ursene(7), 3ß-hydroxytaraxast-20-ene-30-aldehyde(8), urs-12-ene-2α,3ß,28-triol(9), 20-hydroxylupan-3-one(10), monogynol A(11), obtusalin(12), 3-oxo, 11α-hydroxy-olean-12-ene(13), and isocabralealactone(14). Among them, compounds 1 and 2 were new compounds. Compounds 4-10, 12, and 14 were isolated from this genus for the first time. Compounds 3 and 11 were obtained from D. souliei for the first time.

Trait-based comparison of transgenic Bt rice and its non-Bt counterpart in response to soil copper pollution.

Transgenic Bacillus thuringiensis (Bt) rice can provide economic and environmental benefits under the current increasing demand for food and socioeconomic pressures for sustainability. However, information about the ecological adaptation of Bt rice under nontarget environmental stress is still lacking. This study compared the adaptability of one Bt rice and its nontransgenic counterpart to soil copper (Cu) pollution in terms of agronomic and physiological traits. With Cu addition, grain yield and biomass of both cultivars were significantly decreased. Within the same Cu treatment, Bt rice exhibited higher biomass and close plant height, chlorophyll content, grain yield, and grain quality compared with non-Bt rice, except for the grain yield with a 35 mg kg-1 Cu addition with respect to which Bt rice was significantly lower by 22%. The Cu content in Bt rice was generally lower, whereas the antioxidant enzyme activity and lipid peroxidation were stronger than the non-Bt. These results demonstrated that Bt rice exhibited close adaptability but higher Cu tolerance compared with the non-Bt under Cu stress.

[Network pharmacological analysis and experimental verification of anti-inflammatory and analgesic effect of Zanthoxyli Pericarpium].

To explore the mechanism of anti-inflammatory and analgesic effect of Zanthoxyli Pericarpium based on network pharmacology and inflammatory or pain mouse models. The effective components of Zanthoxyli Pericarpium were screened out by TCMSP database. And their potential corresponding targets were predicted by PharmMapper software. The possible targets relating to inflammation and pain were mainly collected through DrugBank, TTD and DisGeNET databases. The "active ingredient-gene-disease" network diagram was constructed by Cytoscape 3.7.0 software. The network pharmacology results showed 5 potential effective compounds, which were related to 29 targets; 132 targets relating to inflammation and pain were screened out in the DrugBank, TTD and DisGeNET databases. The network analysis results indicated that the phosphatidylinositol 3-kinase catalytic subunit gamma isoform(PIK3 CG) gene may be the key to the anti-inflammatory and analgesic effect of Zanthoxyli Pericarpium. The anti-inflammatory and analgesic effects of essential oil extract and dichloromethane extract of Zanthoxyli Pericarpium were explored through the mouse model of inflammation induced by xylene or carrageenan and the mouse model of pain induced by acetic acid or formalin. The experimental results showed that essential oil extract and dichloromethane extract of Zanthoxyli Pericarpium could reduce xylene-induced ear swelling and carrageenan-induced paw swelling and decrease the number of writhing responses in mice induced by acetic acid and the licking foot time of mice in phase Ⅱ induced by formalin. Western blot results showed that Zanthoxyli Pericarpium extract could inhibit the expressions of PIK3 CG, phosphonated nuclear factor kappaB(p-NF-κB) and phosphonated p38(p-p38 MAPK) protein. The present study showed the anti-inflammatory and analgesic effect of Zanthoxyli Pericarpium through multiple components and targets, so as to provide a pharmacodynamic basis for the study of Zanthoxyli Pericarpium and its mechanism.

A supramolecular nanocarrier for efficient cancer imaging and therapy by targeting at matriptase.

Human serum albumin (HSA), a versatile protein carrier for endogenous and exogenous compounds, is a proven macromolecule to form nanoparticles for drug delivery. To render HSA carrier specificity toward tumors, we designed a recombinant HSA protein fused with Kunitz domain 1 (KD1) of hepatocyte growth factor activator inhibitor type 1, which targets to matriptase, a type II transmembrane serine protease overexpressed on tumor cell surface. The carrier was thus named matriptase targeting carrier (MTC). In this study, we showed that MTC displayed the same inhibitory potency as the KD1 againast matriptase, demonstrating the HSA fusion did not affect the KD1 targeting potency. For tumor optical imaging and ablation, MTC was prepared as nanoparticle drug carrier by a novel method via denaturation and refolding to incorporate photosensitizer, CPZ. This matriptase targeting nanoparticles, CPZ:MTC@NPs, showed high specificity and cytotoxicity for matriptase-overexpressing cancer cells in vitro. In tumor-bearing mice, CPZ:MTC@NPs demonstrated selective accumulation and high retention in matriptase-overexpressing tumor. Under illumination, the nanoparticles significantly reduced tumor volumes (79.6%) as compared to saline control. These findings showed that this supramolecular nanocarrier, a new type of tumor targeting self-assembly nanoparticle, had potential as a highly efficient tumor targeting drug carrier for imaging and therapy.

Elucidation of the active ingredients of Lamiophlomis herba against hemorrhage based on network pharmacology and tail snipping model in mice.

This study aimed to elucidate the active ingredients of Lamiophlomis herba (LH), the overground part of Lamiophlomis rotata (Benth.) Kudo, against hemorrhage based on network pharmacology and tail snipping model in mice. A total of 118 hemorrhage-related target genes were identified by retrieving public databases, and 39 genes were identified as the hub genes of hemorrhage based on protein-protein interaction and module analyses. The interactions between 67 potentially active ingredients in LH and 7 genes in the 39 hub genes were established and analyzed through molecular docking and Cytoscape. A total of 21 ingredients were involved in the interactions, and were divided into three categories: iridoid (15 ingredients), flavonoid (2 ingredients) and other category (4 ingredients). Based on the "multi-ingredient, multi-target" characteristic of traditional Chinese medicines (TCMs), the results of network pharmacology indicated that iridoid might be the key active ingredient group of LH against hemorrhage. The contribution of iridoid to the hemostatic effect of LH was investigated by the tail snipping model in mice. The results showed that iridoid was the key active ingredient group of LH against hemorrhage, which confirmed the prediction in network pharmacology. Additionally, the previous reports also supported this prediction. In conclusion, the finding of the present study indicates that iridoid is the key hemostatic ingredient group of LH. This work provides valuable references for investigation of the hemostatic ingredients of LH based on the holistic theory of TCMs. Meanwhile, this work also provides further insight into the development of hemostatic drugs based on LH.

Crystal Structures of Human C4.4A Reveal the Unique Association of Ly6/uPAR/α-neurotoxin Domain.

Ly6/uPAR/α-neurotoxin domain (LU-domain) is characterized by the presence of 4-5 disulfide bonds and three flexible loops that extend from a core stacked by several conversed disulfide bonds (thus also named three-fingered protein domain). This highly structurally stable protein domain is typically a protein-binder at extracellular space. Most LU proteins contain only single LU-domain as represented by Ly6 proteins in immunology and α-neurotoxins in snake venom. For Ly6 proteins, many are expressed in specific cell lineages and in differentiation stages, and are used as markers. In this study, we report the crystal structures of the two LU-domains of human C4.4A alone and its complex with a Fab fragment of a monoclonal anti-C4.4A antibody. Interestingly, both structures showed that C4.4A forms a very compact globule with two LU-domain packed face to face. This is in contrast to the flexible nature of most LU-domain-containing proteins in mammals. The Fab combining site of C4.4A involves both LU-domains, and appears to be the binding site for AGR2, a reported ligand of C4.4A. This work reports the first structure that contain two LU-domains and provides insights on how LU-domains fold into a compact protein and interacts with ligands.

Improvement of quantitative solution 31P NMR analysis of soil organic P: a study of spin-lattice relaxation responding to paramagnetic ions.

Solution 31P nuclear magnetic resonance (NMR) spectroscopy has been widely applied to analyze the speciation of soil organic P; however, this time-consuming technique suffers from a low analytical efficiency, because of the lack of fundamental information such as the spin-lattice relaxation (T1) of 31P nucleus for model P compounds. In this study, we for the first time determined the T1 values of twelve typical soil organic P compounds using the inversion recovery method. Furthermore, we examined the effect of co-existing paramagnetic ions (e.g., Fe3+ and Mn2+) on the reduction of the T1 values of these compounds. Without the addition of paramagnetic ions, the T1 values of twelve model P compounds ranged from 0.61 s for phytic acid to 9.65 s for orthophosphate. In contrast, the presence of paramagnetic ion significantly shortened the T1 values of orthophosphate, pyrophosphate, and phytic acid to 1.29, 1.26, and 0.07 s, respectively, except that of deoxyribonucleic acid (DNA) remaining unchanged. Additionally, we evaluated the feasibility of improving the efficiency of quantitative 31P NMR analysis via addition of paramagnetic ion. Results show that, after an addition of 50 mg L-1 paramagnetic ions, 31P NMR measurement can be 3 times more efficient, attributed to the reduced T1 and the corresponding recycle delay.

Deciphering the Active Ingredients and Molecular Mechanisms of Tripterygium hypoglaucum (Levl.) Hutch against Rheumatoid Arthritis Based on Network Pharmacology.

Tripterygium hypoglaucum (Levl.) Hutch (THH) shows well clinical effect on rheumatoid arthritis (RA), but the active ingredients and molecular mechanisms remain unclear. This work was designed to explore these issues by network pharmacology. Compounds from THH were gathered by retrieving literatures. Compound-related and RA-related genes were identified using databases, and the overlapping genes were identified by Venn diagram. The active ingredients and genes of THH against RA were confirmed by dissecting interactions between overlapping genes and compounds using Cytoscape. SystemsDock website was used to further verify the combining degree of key genes with active ingredients. Pathway enrichment analysis was performed to decipher the mechanisms of THH against RA by Database for Annotation, Visualization and Integrated Discovery. A total of 123 compounds were collected, and 110 compounds-related and 1871 RA-related genes were identified, including 64 overlapping genes. The target genes and active ingredients of THH against RA comprised 64 genes and 17 compounds, the focus of which was PTGS2, triptolide, and celastrol. SystemsDock website indicated that the combing degree of PTGS2 with triptolide or celastrol was very good. The mechanisms of THH against RA were linked to 31 signaling pathways, and the key mechanism was related to inhibition of inflammation response through inactivating TNF and NF-kappa B signaling pathways. This work firstly explored the active ingredients and mechanisms of THH against RA by network pharmacology and provided evidence to support clinical effects of THH on RA.