Assessing the ecological impacts of polycyclic aromatic hydrocarbons petroleum pollutants using a network toxicity model.

Polycyclic aromatic hydrocarbons (PAHs) are significant petroleum pollutants that have long-term impacts on human health and ecosystems. However, assessing their toxicity presents challenges due to factors such as cost, time, and the need for comprehensive multi-component analysis methods. In this study, we utilized network toxicity models, enrichment analysis, and molecular docking to analyze the toxicity mechanisms of PAHs at different levels: compounds, target genes, pathways, and species. Additionally, we used the maximum acceptable concentration (MAC) value and risk quotient (RQ) as an indicator for the potential ecological risk assessment of PAHs. The results showed that higher molecular weight PAHs had increased lipophilicity and higher toxicity. Benzo[a]pyrene and Fluoranthene were identified as core compounds, which increased the risk of cancer by affecting core target genes such as CCND1 in the human body, thereby influencing signal transduction and the immune system. In terms of biological species, PAHs had a greater toxic impact on aquatic organisms compared to terrestrial organisms. High molecular weight PAHs had lower effective concentrations on biological species, and the ecological risk was higher in the Yellow River Delta region. This research highlights the potential application of network toxicity models in understanding the toxicity mechanisms and species toxicity of PAHs and provides valuable insights for monitoring, prevention, and ecological risk assessment of these pollutants.

Sanguisorba officinalis ethyl acetate extract attenuates ulcerative colitis through inhibiting PI3K-AKT/NF-κB/ STAT3 pathway uncovered by single-cell RNA sequencing.

BACKGROUND: Ulcerative colitis (UC) accounts for the untreatable illness nowadays. Bloody stools are the primary symptom of UC, and the first-line drugs used to treat UC are associated with several drawbacks and negative side effects. S. officinalis has long been used as a medicine to treat intestinal infections and bloody stools. However, what the precise molecular mechanism, the exact etiology, and the material basis of the disease remain unclear. PURPOSE: This work aimed to comprehensively explore pharmacological effects as well as molecular mechanisms underlying the active fraction of S. officinalis, and to produce a comprehensive and brand-new guideline map of its chemical base and mechanism of action. METHODS: First, different polarity S. officinalis extracts were orally administered to the DSS-induced UC model mice for the sake of investigating its active constituents. Using the UPLC-orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap-HRMS) technique, the most active S. officinalis (S. officinalis ethyl acetate fraction, SOEA) extract was characterized. Subsequently, the effectiveness of its active fraction on UC was evaluated through phenotypic observation (such as weight loss, colon length, and stool characteristics), and histological examination of pathological injuries, mRNA and protein expression. Cell profile, cell-cell interactions and molecular mechanisms of SOEA in different cell types of the colon tissue from UC mice were described using single-cell RNA sequencing (scRNA-seq). As a final step, the molecular mechanisms were validated by appropriate molecular biological methods. RESULTS: For the first time, this study revealed the significant efficacy of SOEA in the treatment of UC. SOEA reduced DAI and body weight loss, recovered the colon length, and mitigated colonic pathological injuries along with mucosal barrier by promoting goblet cell proliferation. Following treatment with SOEA, inflammatory factors showed decreased mRNA and protein expression. SOEA restored the dynamic equilibrium of cell profile and cell-cell interactions in colon tissue. All of these results were attributed to the ability of SOEA to inhibit the PI3K-AKT/NF-κB/STATAT pathway. CONCLUSIONS: By integrating the chemical information of SOEA derived from UPLC-Q-Orbitrap-HRMS with single-cell transcriptomic data extracted from scRNA-seq, this study demonstrates that SOEA exerts the therapeutic effect through suppressing PI3K-AKT/NF-B/STAT3 pathway to improve clinical symptoms, inflammatory response, mucosal barrier, and intercellular interactions in UC, and effectively eliminates the interference of cellular heterogeneity.

TMT-based quantitative proteomics revealed protective efficacy of Icariside II against airway inflammation and remodeling via inhibiting LAMP2, CTSD and CTSS expression in OVA-induced chronic asthma mice.

BACKGROUND: Asthma is a chronic inflammatory disorder in airways with typical pathologic features of airflow limitation, airway inflammation and remodeling. Icariside II (IS), derived from herbal medicine Herba Epimedii, exerts an anti-inflammatory property. However, underlying mechanisms with specifically targeted molecular expression by IS in asthma have not been fully understood, and whether IS could inhibit remodeling and EMT still remains unclear. PURPOSE: The study aimed to clarify therapeutic efficacy of IS for attenuating airway inflammation and remodeling in asthma, and illustrate IS-regulated specific pathway and target proteins through TMT-based quantitative proteomics. STUDY DESIGN AND METHODS: Murine model of chronic asthma was constructed with ovalbumin (OVA) sensitization and then challenge for 8 weeks. Pulmonary function, leukocyte count in bronchoalveolar lavage fluid (BALF), lung histopathology, inflammatory and fibrotic cytokines, and markers of epithelial-mesenchymal transition (EMT) were evaluated. TMT-based quantitative proteomics were performed on lung tissues to explore IS-regulated proteins. RESULTS: IS contributed to alleviative airway hyperresponsiveness (AHR) evidenced by declined RL and increased Cdyn. After IS treatment, we observed a remarked down-regulation of leukocyte count, inflammatory cytokines in BALF, and peribronchial inflammation infiltration. Goblet cell hyperplasia, mucus secretion and peribronchial collagen deposition were attenuated, with the level of TGF-ß and MMP-9 in BALF declined. Furthermore, IS induced a rise of Occludin and E-cadherin and a decline of N-cadherin and α-SMA in lung tissues. These results proved the protective property of IS against airway inflammation, remodeling and EMT. To further investigate underlying mechanisms of IS in asthma treatment, TMT-based quantitative proteomics were performed and 102 overlapped DEPs regulated by IS were identified. KEGG enrichment exhibited these DEPs were enriched in lysosome, phagosome and autophagy, in which LAMP2, CTSD and CTSS were common DEPs. WB, q-PCR and IHC results proofed expressional alteration of these proteins. Besides, IS could decrease Beclin-1 and LC3B expression with increasing p62 expression thus inhibiting autophagy. CONCLUSIONS: The study demonstrated IS could ameliorate AHR, airway inflammation, remodeling and EMT in OVA-induced chronic asthma mice. Our research was the first to reveal that inhibition of LAMP2, CTSD and CTSS expression in autophagy contributed to the therapeutic efficacy of IS to asthma.

Amelioration of alcohol-induced acute liver injury in C57BL/6 mice by a mixture of TCM phytochemicals and probiotics with antioxidative and anti-inflammatory effects.

Background: There are many causes of acute liver injury (ALI), such as alcohol, drugs, infection, and toxic materials, which have caused major health problems around the world. Among these causes, alcohol consumption induced liver injury is a common alcoholic liver disease, which can further lead to liver failure even liver cancer. A number of traditional Chinese medicine (TCM) and TCM derived compounds have been used in treating the liver-associated diseases and combination use of probiotics with TCM phytochemicals has attracted interests for enhanced biological effects. Methods: This study investigated the hepatoprotective effect of TCM-probiotics complex (TCMPC) and its underlying mechanism for the treatment of ALI in mice. The TCMPC is composed of TCM phytochemicals puerarin, curcumin, ginsenosides, and 5 lactobacteria strains. We first established a mouse model of alcohol-induced ALI, then the therapeutic effects of TCMPC on alcohol-induced ALI were monitored. A series of measurements have been performed on antioxidation, anti-inflammation, and lipid metabolism regulation. Results: The results showed that TCMPC can reduce the level of liver injury biomarkers and regulate oxidative stress. Histopathological results indicated that TCMPC could ameliorate ALI in mice. In addition, it can also significantly reduce the production of inflammatory cytokines caused by ALI. Conclusion: Our research has proved the therapeutic effect of TCMPC on alcohol-induced ALI. The potential mechanism of hepatoprotective effects of TCMPC may be related to its antioxidative and anti-inflammatory effects. Our research might provide a new way for liver disease treatment.

Current Status of Objectification of Four Diagnostic Methods on Constitution Recognition of Chinese Medicine.

Chinese medicine (CM) has thousands of years of experience in prevention of diseases. As for CM, people's constitution is closely related to their health status, thus recognition of CM constitution is the fundamental and core content of research on constitution types. With development of technologies such as sensors, artificial intelligence and big data, objectification of the four diagnostic methods of CM has gradually matured, bringing changes in the mindset and innovations in technical means for recognition of CM constitution. This paper presents a systematic review of the latest research trends in constitution recognition based on objectification of diagnostic methods in CM.

Lonicera rupicola Hook.f.et Thoms flavonoids ameliorated dysregulated inflammatory responses, intestinal barrier, and gut microbiome in ulcerative colitis via PI3K/AKT pathway.

BACKGROUND: Lonicera rupicola Hook.f.et Thoms (LRH) is used as a customary medicinal herb in Tibetans. And LRH flavonoids have excellent anti-inflammatory and antioxidant pharmacological activities. However, the specific effects of LRH and its mechanism remain unknown, and there is a deficiency of systematic research, leading to the waste of LRH as a medicinal resource. PURPOSE: In this study, in an attempt to rationalize the development and utilization of Tibetan herbal resources, the therapeutic efficacy and the underlying molecular mechanisms of LRH flavonoids on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) were investigated, establishing the favorable basis for the pharmacodynamic material basis of LRH and providing a scientific basis for the discovery of new drugs for the treatment of UC. METHODS: Firstly, ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was used for identification and detection of the flavonoid components of LRH. Meanwhile, their potential targets, biological functions and signaling pathways were predicted with the assistance of network pharmacology analysis. Subsequently, pharmacological efficacy of LRH were evaluated by body weight loss, colon length, disease activity index (DAI), histology observation and the expression levels of inflammatory mediators, messenger RNA (mRNA) and tight junction proteins. Moreover, in the present investigation, we also profiled the gut microbiome via high-throughput sequencing of the V3-V4 region of 16S ribosomal DNA (rDNA) for bacterial community composition and diversity by Illumina MiSeq platforms. Finally, the key regulatory proteins in the PI3K/AKT pathways were measured to investigate their underlying molecular mechanisms. RESULTS: A total of 37 LRH flavonoid components were identified and detected by UPLC-MS/MS, and 12 potential active components were obtained after screening. 137 of their common targets with UC were further predicted. GO and KEGG pathway enrichment analysis and molecular docking experiments demonstrated that LRH flavonoids could interfere with UC through "multi-component-multi-target-multi-pathway". In the animal experiments, LRH flavonoids could significantly attenuate UC as demonstrated by reducing the body weight loss and DAI, restoring colon length, decreasing oxidative stress, and improving the intestinal epithelial cell barrier. The mRNA and proteins expression levels of inflammatory mediators were returned to dynamic balance following LRH flavonoids treatment. 16S rDNA sequence analysis indicated that LRH flavonoids promoted the recovery of gut microbiome. And the PI3K/AKT pathway was significantly suppressed by LRH flavonoids. CONCLUSIONS: LRH flavonoids exhibited multifaceted protective effects against DSS-induced UC in mice through mitigating colon inflammation and oxidative stress, restoring epithelial barrier function, and improving the gut microenvironment potentially through modulation of the PI3K/AKT pathway. This finding demonstrated that LRH flavonoids possessed great potential for becoming an excellent drug for the treatment of UC.

Intersex goats show different gene expression levels in the hypothalamus and pituitary compared with non-intersex goats based on RNA-Seq.

The conditions for sex reversal in vertebrate species have been extensively studied, and the results highlighted numerous key factors involved in sex differentiation. However, the transcriptomes in hypothalamic and pituitary tissues from intersex goats have rarely been studied. The aim of this study was to screen candidate genes and signalling pathways related to sex reversal in Huai goats by analyzing gene expression in hypothalamic and pituitary tissues via transcriptome sequencing and bioinformatics analyses. In total, 612 and 139 differentially expressed genes (DEGs) were identified between the intersex and non-intersex groups in the hypothalamus and pituitary, respectively. The DEGs in the hypothalamus and pituitary were significantly enriched in 41 and 16 signalling pathways, respectively, including the calcium signalling pathway, neuroactive ligand-receptor interaction signalling pathway, and oestrogen signalling pathway, which might be related to intersex sex development disorders. A candidate gene from the tachykinin family (TACR1) was significantly enriched in the calcium signalling pathway. Thirty-one DEGs were shared between these two comparisons and were enriched in several acetyl-CoA-related processes and the oestrogen signalling pathway. The results of the real-time PCR analysis show that the transcriptome sequencing results were reliable. The transcriptome data indicate that the regulation of various physiological systems is involved in intersex goat development. Therefore, these results provide helpful data enhancing our understanding of the molecular mechanisms underlying intersex syndrome in goats.

Cyclodextrin metal-organic framework as vaccine adjuvants enhances immune responses.

It is urgently needed to develop novel adjuvants for improving the safety and efficacy of vaccines. Metal-organic frameworks (MOFs), with high surface area, play an important role in drug delivery. With perfect biocompatibility and green preparation process, the γ-cyclodextrin metal-organic framework (γ-CD-MOF) fabricated with cyclodextrin and potassium suitable for antigen delivery. In this study, we modified γ-CD-MOF with span-85 to fabricate the SP-γ-CD-MOF as animal vaccine adjuvants. The ovalbumin (OVA) as the model antigen was encapsulated into particles to investigate the immune response. SP-γ-CD-MOF displayed excellent biocompatibility in vitro and in vivo. After immunization, SP-γ-CD-MOF loaded with OVA could induce high antigen-specific IgG titers and cytokine secretion. Meanwhile, SP-γ-CD-MOF also significantly improved the proliferation of spleen cells and activated and matured the bone marrow dendritic cells (BMDCs). The study showed the potential of SP-γ-CD-MOF in vaccine adjuvants and provided a novel idea for the development of vaccine adjuvants.

[Optimization of extraction of flavonoids from Lonicera rupicola and analysis of its effects in resisting inflammation, relieving pain, enhancing immunity, and inhibiting pyroptosis].

The present study optimized the extraction of flavonoids from Lonicera rupicola Hook. f. et Thoms(LRH) and explored its pharmacological effects, such as resisting inflammation, relieving pain, enhancing immunity, and inhibiting pyroptosis, aiming to provide data support and scientific basis for the development and utilization of LRH. Response surface methodology(RSM) was applied to optimize the extraction of flavonoids from LRH based on the results of single-factor experiments. Anti-inflammatory and analgesic effects of LRH flavonoids were evaluated via inflammation and pain models in mice, such as xylene-induced ear swelling, carrageenan-induced footpad swelling, writhing caused by acetic acid, and paw licking. The effect of LRH flavonoids on the carbon clearance index of monocytes and serum immunoglobulin A(IgA) and IgM levels was analyzed on the immunosuppression model induced by cyclophosphamide in mice. The anti-oxidative effect in vivo of LRH flavonoids on liver superoxide dismutase(SOD), catalase(CAT), and malondialdehyde(MDA) levels was determined based on the chronic/subacute aging model in mice induced by D-galactose. The levels of cysteinyl aspartate specific proteinase-1(caspase-1), interleukin-1ß(IL-1ß), and IL-18 in the supernatant of J774 A.1 mononuclear phagocytes were detected to evaluate the effect of LRH flavonoids on the pyroptosis of mononuclear phagocytes in mice induced by the combination of lipopolysaccharide(LPS) and adenosine triphosphate(ATP). Meanwhile, the effect of LRH flavonoids on the cAMP-PKA signaling pathway was also explored. The optimum conditions for the extraction of LRH flavonoids are listed below: extraction temperature of 65 ℃, the ethanol concentration of 50%, extraction time of 60 min, a material-liquid ratio at 1∶25, and the yield of LRH flavonoids of 0.553%. RSM determined the multiple quadratic regression equation model of response value and variables as follows: the yield of LRH flavonoids=0.61-0.48A+0.1B+0.029C-0.014D+0.32AB+0.04AC-0.012AD-0.02BC+0.037BD-0.031CD-0.058A~2-0.068B~2-0.069C~2-0.057D~2. LRH flavonoids could effectively inhibit ear swelling and footpad swelling, reduced acetic acid-induced writhing, and delayed the paw licking response time in mice. Additionally, LRH flavonoids could improve the carbon clearance index in immunosuppressed mice, potentiate the activities of SOD and CAT and reduce MDA levels in the liver of aging mice induced by D-galactose, and effectively inhibit macrophage pyroptosis by decreasing the levels of caspase-1, IL-1ß, and IL-18. The results reveal that LRH flavonoids possess excellent pharmacological activities such as resisting inflammation and oxidation, relieving pain, and enhancing immunity. They can inhibit pyroptosis by enhancing the cAMP-PKA signaling pathway. The results of this study can underpin the pharmacological research, development, and utilization of LRH.

Cycloastragenol alleviates airway inflammation in asthmatic mice by inhibiting autophagy.

Cycloastragenol (CAG), a secondary metabolite from the roots of Astragalus zahlbruckneri, has been reported to exert anti­inflammatory effects in heart, skin and liver diseases. However, its role in asthma remains unclear. The present study aimed to investigate the effect of CAG on airway inflammation in an ovalbumin (OVA)­induced mouse asthma model. The current study evaluated the lung function and levels of inflammation and autophagy via measurement of airway hyperresponsiveness (AHR), lung histology examination, inflammatory cytokine measurement and western blotting, amongst other techniques. The results demonstrated that CAG attenuated OVA­induced AHR in vivo. In addition, the total number of leukocytes and eosinophils, as well as the secretion of inflammatory cytokines, including interleukin (IL)­5, IL­13 and immunoglobulin E were diminished in bronchoalveolar lavage fluid of the OVA­induced murine asthma model. Histological analysis revealed that CAG suppressed inflammatory cell infiltration and goblet cell secretion. Notably, based on molecular docking simulation, CAG was demonstrated to bind to the active site of autophagy­related gene 4­microtubule­associated proteins light chain 3 complex, which explains the reduced autophagic flux in asthma caused by CAG. The expression levels of proteins associated with autophagy pathways were inhibited following treatment with CAG. Taken together, the results of the present study suggest that CAG exerts an anti­inflammatory effect in asthma, and its role may be associated with the inhibition of autophagy in lung cells.

[Compatibility characteristics of Bufei Yishen formula III in regulating chronic obstructive pulmonary disease mucus hypersecretion].

OBJECTIVE: To evaluate the compatibility laws of effective-component compatibility of Bufei Yishen formula III (ECC-BYF III) in regulating mucus hypersecretion of chronic obstructive pulmonary disease (COPD). METHODS: According to the efficacy of the original Chinese medicine, the components of ECC-BYF III were divided into four categories: Buqi (Ginsenoside Rh1+Astragaloside), Bushen (Icariin), Huatan (Nobiletin), and Huoxue (Paeonol). The four categories were divided into 14 groups based on the method of mathematical permutation. (1) The rats were divided into control group, model group, ECC-BYF III, and different components compatibility groups according to the random number table, totaling 17 groups. COPD rat model in stable phase was established by cigarette smoke exposure combined with repeated bacterial infections. The corresponding drugs were given by gavage at the 9th week of modeling, and the samples were collected at the end of the 16th week. The levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinase 1 (TIMP-1) in serum and bronchoalveolar lavage fluid (BALF), and the levels of mucin (MUC) 5AC in lung tissue and BALF were detected by enzyme linked immunosorbent assay (ELISA). (2) Human lung epithelial cells BEAS-2B were divided into blank group, model group, and different components compatibility groups. Hypoxia-induced mucus hypersecretion model of human lung epithelial cells BEAS-2B was established 4 hours after corresponding drug pretreatment. The mRNA expressions of MUC5AC, MUC5B, and MUC1 were detected by quantitative polymerase chain reaction (PCR). The mucus secretion indexes of rats and BEAS-2B cells were evaluated by Region (R) value comprehensive evaluation method. RESULTS: (1) Compared with the control group, MMP-9 in serum and BALF from the model group were significantly increased, the level of TIMP-1 was significantly decreased, and MUC5AC in lung tissue and BALF were significantly increased. The results of R value comprehensive evaluation showed that except for the Buqi and Bushen groups, ECC-BYF III and other components compatibility groups significantly corrected mucus hypersecretion in COPD rats, ECC-BYF III, Bushen Quxie, Fuzheng Huatan, and Quxie groups were much better (R values were 2.15±0.42, 2.11±0.23, 2.16±0.23 and 2.16±0.55, respectively), compared with the model group (R value: 3.00±0.00), the differences were statistically significant (all P < 0.05). (2) Compared with the blank group, the mRNA expressions of MUC5AC, MUC5B, and MUC1 increased in the model group. But different components compatibility groups had no significant effects on the mucus secretion of BEAS-2B cells. (3) The comprehensive evaluation results of R value about each in vivo and in vitro index showed that ECC-BYF III, Huoxue, Quxie, Bushen Huoxue, Fuzheng Huatan, Buqi Quxie groups significantly corrected the mucus hypersecretion (R values were 2.30±0.43, 2.33±0.44, 2.12±0.68, 2.27±0.64, 2.24±0.27 and 2.29±0.47, respectively), compared with the model group (R value: 3.00±0.00), the difference was statistically significant (all P < 0.01). The order was: Quxie > Fuzheng Huatan > Bushen Huoxue > Buqi Quxie > ECC-BYF III > Huoxue. CONCLUSIONS: Different components compatibility of ECC-BYF III had different effects on COPD mucus secretion. The components containing Huatan (Nobiletin) or Huoxue (Paeonol) showed a better inhibitory effect on mucus secretion.

Metallothionein-2 is associated with the amelioration of asthmatic pulmonary function by acupuncture through protein phosphorylation.

BACKGROUND: Acupuncture has long been used for asthma treatment but the underlying mechanism remains unclear. Previous study showed that metallothionein-2 (MT-2) was significantly decreased in asthmatic lung tissue. However, the relationship between acupuncture treatment and MT-2 expression during asthma is still unknown, and the detailed effect analysis of MT-2 on phosphorylation in airway smooth muscle cells (ASMCs) is also unclear. METHODS: The acupuncture effect on pulmonary resistance (RL) was investigated in a rat model of asthma, and the mRNA and protein levels of MT-2 in lung tissue were detected. Primary ASMCs were isolated and treated with MT-2 recombinant protein to study the MT-2 effects on ASMC relaxation. A Phospho Explorer antibody microarray was applied to detect protein phosphorylation changes associated with MT-2-induced ASMC relaxation. Bioinformatic analysis were performed with PANTHER database, DAVID and STRING. Phosphorylation changes in key proteins were confirmed by Western blot. RESULTS: Acupuncture significantly reduced RL at 2-5 min (P < 0.05 vs asthma) in asthmatic rats. Acupuncture continued to increase MT-2 mRNA expression in lung tissue for up to 14 days (P < 0.05 vs asthma). The MT-2 protein expression was significantly decreased in the asthmatic rats (P < 0.05 vs control), while MT-2 protein expression was significantly increased in the asthmatic model group treated with acupuncture (P < 0.05 vs asthma). Primary ASMCs were successfully isolated and recombinant MT-2 protein (100, 200, 400 ng/ml) significantly relaxed ASMCs (P < 0.05 vs control). MT-2 induced phosphorylation changes in 51 proteins. Phosphorylation of 14 proteins were upregulated while 37 proteins were downregulated. PANTHER classification revealed eleven functional groups, and the phosphorylated proteins were identified as transferases (27.8 %), calcium-binding proteins (11.1 %), etc. DAVID functional classification showed that the phosphorylated proteins could be attributed to eight functions, including protein phosphorylation and regulation of GTPase activity. STRING protein-protein interaction network analysis showed that Akt1 was one of the most important hubs for the phosphorylated proteins. The phosphorylation changes of Akt1 and CaMK2ß were consistent in both the Phospho Explorer antibody microarray and Western blot. CONCLUSION: Acupuncture can significantly ameliorate RL, and the MT-2 mRNA and protein levels in lung tissue are increased during treatment. MT-2 significantly relaxes ASMCs and induces a series of protein phosphorylation. These phosphorylation changes, including Akt1 and CaMK2ß, may play important roles in the therapeutic effects of acupuncture on asthma.

Combining Chemical Profiling and Network Analysis to Investigate the Pharmacology of Complex Prescriptions in Traditional Chinese Medicine.

We present a paradigm, combining chemical profiling, absorbed components detection in plasma and network analysis, for investigating the pharmacology of combination drugs and complex formulae. On the one hand, the composition of the formula is investigated comprehensively via mass spectrometry analysis, followed by pharmacological studies of the fractions as well as the plasma concentration testing for the ingredients. On the other hand, both the candidate target proteins and the effective ingredients of the formula are predicted via analyzing the corresponding networks. The most probable active compounds can then be identified by combining the experimental results with the network analysis. In order to illustrate the performance of the paradigm, we apply it to the Danggui-Jianzhong formula (DJF) from traditional Chinese medicine (TCM) and predict 4 probably active ingredients, 3 of which are verified experimentally to display anti-platelet activity, i.e., (Z)-Ligustilide, Licochalcone A and Pentagalloylglucose. Moreover, the 3-compound formulae composed of these 3 chemicals show better anti-platelet activity than DJF. In addition, the paradigm predicts the association between these 3 compounds and COX-1, and our experimental validation further shows that such association comes from the inhibitory effects of the compounds on the activity of COX-1.

Phytochemical and Pharmacological Studies on the Genus Psoralea: A Mini Review.

The genus Psoralea, which belongs to the family Fabaceae, comprises ca. 130 species distributed all over the world, and some of the plants are used as folk medicine to treat various diseases. Psoralea corylifolia is a typical example, whose seeds have been widely used in many traditional Chinese medicine formulas for the treatment of various diseases such as leucoderma and other skin diseases, cardiovascular diseases, nephritis, osteoporosis, and cancer. So, the chemical and pharmacological studies on this genus were performed in the past decades. Here, we give a mini review on this genus about its phytochemical and pharmacological studies from 1910 to 2015.

Analysis of risk factors for medication-overuse headache relapse: a clinic-based study in China.

BACKGROUND: Medication overuse headache (MOH) is the third most prevalent headache type after migraine and tension-type headache. A large number of studies on the long-term prognosis have shown that MOH has a high relapse rate after treatment. Although MOH relapse-related risk factors have been reported, no related research has been performed in China. Therefore, the purpose of this study was to analyze and evaluate the risk factors for MOH relapse in China. METHODS: Eighty-six out-patients of Shandong Provincial Hospital who were initially diagnosed with MOH, and who had successful withdrawal treatment within 2 months, were chosen from March 2012 to July 2013. All subjects were followed up by the investigators of this study. Of the 86 subjects, 27 who had relapsed were compared with 59 who had not relapsed (i.e. the controls). Based on a standardized questionnaire, a database was created (with Microsoft Excel 2010). The data, which included 38 indexes, were analyzed by univariate analysis with chi-square test, Fisher's exact test, t-test, or paired rank test. The statistically correlated (P<0.05) variables were chosen as the independent variables, thereby enabling the calculation of the non-conditional multivariate stepwise logistic regression. RESULTS: The independent risk factors for medication-overuse headache relapse were determined as headache frequency before drug withdrawal, duration of primary headache, and headache frequency after drug withdrawal. CONCLUSION: Headache frequency before drug withdrawal, duration of primary headache, and headache frequency after drug withdrawal may be the independent risk factors for MOH relapse in China.

Enteral Immunomodulatory Diet (Omega-3 Fatty Acid, γ-Linolenic Acid and Antioxidant Supplementation) for Acute Lung Injury and Acute Respiratory Distress Syndrome: An Updated Systematic Review and Meta-Analysis.

UNLABELLED: Enteral immunomodulatory nutrition is considered as a promising therapy for the treatment of acute lung injury and acute respiratory distress syndrome (ALI/ARDS). However, there are still some divergences, and it is unclear whether this treatment should be recommended for patients with ALI/ARDS. Therefore, we conducted this systematic review and meta-analysis to assess the efficacy and safety of an enteral immunomodulatory diet on the clinical outcomes of ALI/ARDS patients. METHODS: We retrieved potentially relevant clinical trials though electronic databases. All trials of enteral immunomodulatory diet for ALI/ARDS were included. Analyses of the overall all-cause mortality, 28-day ventilator-free days and 28-day intensive care unit (ICU) free days were conducted. RESULTS: In total six controlled trials were evaluated. The pooled results did not show a significant reduction in the risk of all-cause mortality (M-H RR (the overall Mantel-Haenszel relative risk), 0.81 (95% CI, 0.50-1.31); p = 0.38; 6 trials, n = 717) in ALI/ARDS patients treated with the immunomodulatory diet. This treatment also did not extend the ventilator-free days and ICU-free days. However, patients with high mortality might benefit from this treatment. CONCLUSIONS: The enteral immunomodulatory diet could not reduce the severity of the patients with ALI/ARDS. Whereas, for ALI/ARDS patients with high mortality, this treatment might reduce the all-cause mortality, but its use should be treated with discretion.

Identification of two novel mutations in SLC12A3 gene in two Chinese pedigrees with Gitelman syndrome and review of literature.

OBJECTIVE: Gitelman syndrome (GS) is one of the most common causes of inherited hypokalaemia. As it was caused by mutations in the SLC12A3 gene, GS is a highly heterogeneous disease. Here, we aimed to investigate the clinical and genetic characteristics of two Chinese pedigrees and summarize the advance in GS genetics, diagnosis and management. SUBJECTS AND METHODS: Two three-generation families with GS were identified and screened for mutations in the SLC12A3 gene. Genotype-phenotype correlations were analysed. RESULTS: The two probands (A and B) were characterized by hypokalaemia, hypomagnesaemia and hypocalciuria without hypertension. Complete DNA sequencing of the SLC12A3 gene revealed two novel compound heterozygous mutations (c.179C>T and c.234delG; c.486-490delTACGGinsA and c.1925G>A), which are predicted to drastically affect normal protein structure. The female members of the pedigrees showed mild-to-no phenotype, although they carried the same mutations as the probands. Moreover, proband B presented with more severe symptoms than did proband A, which might be related to a lower serum magnesium level. During the 1-year follow-up, both probands showed satisfactory symptom improvement following the use of potassium and magnesium supplements. CONCLUSION: Our findings strongly suggested that the two novel mutations in the SLC12A3 gene are the causative agents of GS, which may provide further insights into the function of this gene and help clinicians better understand this disorder.

Tanshinone IIA attenuates bleomycin-induced pulmonary fibrosis via modulating angiotensin-converting enzyme 2/ angiotensin-(1-7) axis in rats.

Pulmonary fibrosis (PF) is a common complication in those interstitial lung diseases patients, which will result in poor prognosis and short survival. Traditional therapeutic methods such as glucocorticoid and cytotoxic drugs are insufficient for treating PF and may cause severe side effects. Recent studies showed that traditional Chinese herbal abstraction such as Tanshinone IIA (TIIA) was displayed significant anti-PF effects in animal models. However, the exact mechanisms underlying the protective effects of TIIA were not fully understood. Here we further investigated the protective effects of TIIA and its mechanisms underlying. PF models of rat were induced by bleomycin (BLM); TIIA was administered subsequently. The PF changes were identified by histopathological analyses. The results showed that BLM resulted in severe PF and alveolar inflammation; together with significant elevation of transforming growth factor-ß 1 (TGF-ß1). Angiotensin-converting enzyme 2 (ACE-2) together with angiotensin-(1-7) [ANG-(1-7)] were both greatly reduced after BLM administration. TIIA treatment notably attenuated BLM induced PF and inflammation, decreased expression of TGF-ß1 and reversed ACE-2 and ANG-(1-7) production in rat lungs. Thus we may draw the conclusion that TIIA may exert protective effects on BLM induced PF in rats, and the ACE-2/ANG-(1-7) axis may ascribe to those protective effects.