Acetylenic spiroketal enol ethers from Artemisia rupestris and their synergistic antibacterial effects on methicillin-resistant Staphylococcus aureus.

Synergistic bioassay-guided isolation of the extracts of Artemisia rupestris L, which belongs to the family Asteraceae, afforded two acetylenic spiroketal enol ethers, namely rupesdiynes A (1) and B (2). Their structures were determined based on spectroscopic analysis and experimental and calculated ECD investigations. The two compounds exhibited synergistic activity and were able to reduce the minimum inhibitory concentration (MIC) of oxacillin four-fold, with a fractional inhibitory concentration index (FICI) of 0.5 in combination with oxacillin against the oxacillin-resistant EMRSA-16. Biofilm formation inhibitory and Ethidium bromide (EtBr) efflux assay were further employed to verify the possible mechanism of the synergistic antibacterial effect. Additionally, molecular docking studies were conducted to investigate the binding affinities of the two compounds with penicillin-binding protein 2a (PBP2a) of EMRSA-16. Taken together, rupesdiynes A (1) and rupesdiyne B (2) showed moderate synergistic activity against EMRSA-16 with oxacillin via inhibiting biofilm formation and efflux pump activity, respectively.

Simultaneous determination of six α-dicarbonyl compounds in traditional Chinese medicines using high-performance liquid chromatography-fluorescence detector with pre-column derivatization.

A reliable method for determination of six α-dicarbonyl compounds in traditional Chinese medicines was first developed and validated by high-performance liquid chromatography-fluorescence detector with pre-column derivatization. α-Dicarbonyl compounds in traditional Chinese medicines were extracted and derivatized with 2,3-diaminaphthalene. The derivatization procedure of six α-dicarbonyl compounds was confirmed by high-resolution mass spectrometry. The limits of quantitation for six α-dicarbonyl compounds ranged from 3.70 × 10-3 to 2.21 × 10-2  µM. The established method showed good linearity (regression coefficient > 0.9990), precision (relative standard deviation < 3.37%), and high recovery (97.8%∼113.1%). The developed method was successfully applied to detect the six α-dicarbonyl compounds in traditional Chinese medicines. The result exhibited six α-dicarbonyl compounds was found in the 15 kinds of traditional Chinese medicines, which suggested us that the determination of α-dicarbonyl compounds should be paid more attention in the quality control of traditional Chinese medicines.

Integrated serum pharmacochemistry and investigation of the anti-gastric ulcer effect of Zuojin pill in rats induced by ethanol.

CONTEXT: Zuojin Pill (ZJP) has been used to treat gastrointestinal problems in China for hundreds of years. OBJECTIVE: To discover more potential active ingredients and evaluate the gastroprotective mechanisms of ZJP. MATERIALS AND METHODS: An approach involving UPLC-Q-Orbitrap HRMS and serum pharmacochemistry was established to screen the multiple chemical constituents of ZJP. Male Sprague-Dawley (SD) rats were divided into six groups: normal control, ulcer control, omeprazole (30 mg/kg), and three ZJP groups (1.0, 2.0 and 4.0 g/kg). After oral treatment with ZJP or omeprazole for 7 days, all groups except the normal control group were orally administered 5 mL/kg ethanol to induce gastric ulceration. Histopathological assessment of gastric tissue was performed by haematoxylin and eosin staining. Antioxidant parameters and inflammatory mediators were determined using ELISA Kit and immunohistochemical analysis. RESULTS: Ninety components were identified in ZJP. Among them, 23 prototypes were found in rat serum after oral administration of ZJP. The ulcer inhibition was over 90.0% for all the ZJP groups. Compared with the ulcer control rats, ZJP (4.0 g/kg) enhanced the antioxidant capacity of gastric tissue: superoxide dismutase (1.33-fold), catalase (2.61-fold), glutathione (2.14-fold), and reduced the malondialdehyde level (0.48-fold). Simultaneously, the ZJP meaningfully lowered the content of tumour necrosis factor-α (0.76-fold), interleukin-6 (0.66-fold), myeloperoxidase (0.21-fold), and nuclear factor kappa B (p65) (0.62-fold). DISCUSSION AND CONCLUSIONS: This study showed ZJP could mitigate ethanol-induced rat gastric ulcers, which might benefit from the synergistic actions of multiple ingredients. The findings could support the quality control and clinical trials of ZJP.

Risk Factors for Worsening of Bone Loss in Patients Newly Diagnosed with Inflammatory Bowel Disease.

Background: Bone loss is common in patients with inflammatory bowel disease (IBD). The aim of the present study was to determine the prevalence of metabolic bone disease in patients newly diagnosed with IBD and to identify the risk factors for bone loss over time. Methods: We performed a retrospective, both cross-sectional and longitudinal, study to extract the risk factors of bone loss (including osteopenia and osteoporosis) in patients newly diagnosed with IBD, using dual-energy X-ray absorptiometry (DXA). Results: A total of 639 patients newly diagnosed with IBD that had at least one DXA were included in the cross-sectional study. Osteopenia and osteoporosis were diagnosed in 24.6% and 5.4% of patients, respectively. Age at diagnosis, body mass index, and serum phosphorus were identified as independent factors associated with bone loss at baseline. A total of 380 of the 639 IBD patients (including 212 CD patients and 168 UC patients) with at least a second DXA scan were included in the longitudinal study. 42.6% of the patients presented a worsening of bone loss in the follow-up study. Menopause, albumin, and use of corticosteroids were identified as independent factors associated with worsening of bone loss. Conclusions: Metabolic bone disease is common in IBD patients, and there is a significant increase in prevalence of bone loss over time. Postmenopausal female, malnourished patients, and those requiring corticosteroid treatment are at risk for persistent bone loss. Therefore, BMD measurements and early intervention with supplementation of calcium and vitamin D are recommended in IBD patients with high-risk factors.

Synergistic Inhibitory Effect of Polymyxin B in Combination with Ceftazidime against Robust Biofilm Formed by Acinetobacter baumannii with Genetic Deficiency in AbaI/AbaR Quorum Sensing.

Carbapenem resistance of Acinetobacter baumannii poses challenges to public health. Biofilm contributes to the persistence of A. baumannii cells. This study was designed to investigate the genetic relationships among carbapenem resistance, polymyxin resistance, multidrug resistance, biofilm formation, and surface-associated motility and evaluate the antibiofilm effect of polymyxin in combination with other antibiotics. A total of 103 clinical A. baumannii strains were used to determine antibiotic susceptibility, biofilm formation capacity, and motility. Enterobacterial repetitive intergenic consensus (ERIC)-PCR fingerprinting was used to determine the genetic variation among strains. The distribution of 17 genes related to the resistance-nodulation-cell division (RND)-type efflux, autoinducer-receptor (AbaI/AbaR) quorum sensing, oxacillinases (OXA)-23, and insertion sequence of ISAba1 element was investigated. The representative strains were chosen to evaluate the gene transcription and the antibiofilm activity by polymyxin B (PB) in combination with merapenem, levofloxacin, and ceftazidime, respectively. ERIC-PCR-dependent fingerprints were found to be associated with carbapenem resistance and multidrug resistance. The presence of blaOXA-23 was found to correlate with genes involved in ISAba1 insertion, AbaI/AbaR quorum sensing, and AdeABC efflux. Carbapenem resistance was observed to be negatively correlated with biofilm formation and positively correlated with motility. PB in combination with ceftazidime displayed a synergistic antibiofilm effect against robust biofilm formed by an A. baumannii strain with deficiency in AbaI/AbaR quorum sensing. Our results not only clarify the genetic correlation among carbapenem resistance, biofilm formation, and pathogenicity in a certain level but also provide a theoretical basis for clinical applications of polymyxin-based combination of antibiotics in antibiofilm therapy. IMPORTANCE Deeper explorations of molecular correlation among antibiotic resistance, biofilm formation, and pathogenicity could provide novel insights that would facilitate the development of therapeutics and prevention against A. baumannii biofilm-related infections. The major finding that polymyxin B in combination with ceftazidime displayed a synergistic antibiofilm effect against robust biofilm formed by an A. baumannii strain with genetic deficiency in AbaI/AbaR quorum sensing further provides a theoretical basis for clinical applications of antibiotics in combination with quorum quenching in antibiofilm therapy.

Enhancement of the anticoagulant capacity of polyvinyl chloride tubing for cardiopulmonary bypass circuit using aluminum oxide nanoscale coating applied through atomic layer deposition.

For cardiopulmonary bypass, the polyvinyl chloride (PVC) circuit which can initiate the activation of platelets and the coagulation cascade after blood cell contacting is the possible detrimental effect. Surface coating of the PVC tubing system can be an effective approach to enhance circuit's hemocompatibility. In this study, aluminum oxide (Al2 O3 ) thin films were deposited through thermal atomic layer deposition (T-ALD) or plasma-enhanced ALD (PE-ALD) on PVC samples, and the anticoagulation of the Al2 O3 -coated PVC samples was demonstrated. The results revealed that Al2 O3 deposition through ALD increased surface roughness, whereas T-ALD had a relative hydrophilicity compared with blank PVC and PE-ALD. Whole blood immersion tests showed that blood clots formed on blank PVC and that a large amount of red blood cells was found on PE-ALD substrates, whereas less blood cells were noted in T-ALD samples. Both T-ALD and PE-ALD Al2 O3 films did not cause activation of blood cells, as evidenced in CD3+ /CD4+ /CD8+ , CD61+ /CD62P+ , and CD45+ /CD42b+ populations. Analysis of serum coagulation factors showed that a lower amount of prothrombin was absorbed on T-ALD Al2 O3 samples than that on blank PVC. For albumin and fibrinogen immersion tests, immunostaining and scanning electron microscopy further revealed that a thin albumin layer was absorbed on T-ALD Al2 O3 substrates but not on PVC samples. This study revealed that deposition of Al2 O3 films by T-ALD can improve anticoagulation of the PVC tubing system.

Adjunctive Chinese Herbal Medicine Treatment is Associated With an Improved Survival Rate in Patients With Cervical Cancer in Taiwan: A Matched Cohort Study.

BACKGROUND: Cervical cancer is one of the most common cancers in Taiwan. Some patients take Chinese herbal medicine (CHM). However, very few current studies have ascertained the usage and efficacy of CHM in patients with cervical cancer. The aim of this study was to investigate the benefits of complementary CHM among patients with cervical cancer in Taiwan. METHODS: We included the newly diagnosed cervical cancer patients who were registered in the Taiwanese Registry for Catastrophic Illness Patients Database between 2000 and 2010. The end of follow-up period was December 31, 2011. Patients who were less than 20 years old, had missing information for age, withdrew from the National Health Insurance (NHI) program during the follow-up period, or only received other TCM interventions such as acupuncture or tuina massage were excluded from our study. After performing 1:1 frequency matching by age and index date, we enrolled 7521 patients in both CHM and non-CHM user groups. A Cox regression model was used to compare the hazard ratios (HRs) of the risk of mortality. The Kaplan-Meier curve was used to compare the difference in survival time. RESULTS: According to the Cox hazard ratio model mutually adjusted for CHM use, age, comorbidity, treatment, and chemotherapeutic agents used, we found that CHM users had a lower hazard ratio of mortality risk (adjusted HR = 0.29, 95%CI = 0.27-0.31). The survival probability was higher for patients in the CHM group. Bai-Hua-She-She-Cao (Herba Oldenlandiae, synonym Herba Hedyotis diffusae) and Jia-Wei-Xiao-Yao-San were the most commonly prescribed single herb and Chinese herbal formula, respectively. CONCLUSIONS: Adjunctive CHM may have positive effects of reducing mortality rate and improving the survival probability for cervical cancer patients. Further evidence-based pharmacological investigations and clinical trials are warranted to confirm the findings in our study.

[Biosynthesis and metabolism regulation of terpenoids in Pogostemon cablin: a review].

The terpenoids in Pogostemon cablin have complex structures and abundant pharmacological effects. Patchouli alcohol(PA) and pogostone(PO) have a high medicinal value by virtue of anti-tumor, anti-inflammatory, antibacterial, antioxidant, and other biological activities. Due to the low content of terpenoid metabolites in P. cablin, the study of biosynthesis and metabolism regulation can provide a biosynthetic basis for obtaining high-content terpenoids. In this study, key enzyme genes in biosynthesis, transcription factors in metabolism regulation, spatio-temporal expression of terpene synthase were reviewed, aiming to provide a reference for the development, protection, and utilization of P. cablin resources.

High Color Purity and Efficient Green Light-Emitting Diode Using Perovskite Nanocrystals with the Size Overly Exceeding Bohr Exciton Diameter.

Lead halide perovskite nanocrystals (PNCs) are emerging as promising light emitters to be actively explored for high color purity and efficient light-emitting diodes. However, the most reported lead halide perovskite nanocrystal light-emitting diodes (PNCLEDs) encountered issues of emission line width broadening and operation voltage elevating caused by the quantum confinement effect. Here, we report a new type of PNCLED using large-size CsPbBr3 PNCs overly exceeding the Bohr exciton diameter, achieving ultranarrow emission line width and rapid brightness rise around the turn-on voltage. We adopt calcium-tributylphosphine oxide hybrid ligand passivation to produce highly dispersed large-size colloidal CsPbBr3 PNCs with a weak size confinement effect and also high photoluminescence quantum yield (∼85%). Utilizing these large-size PNCs as emitters, we manifest that the detrimental effects caused by the quantum confinement effect can be avoided in the device, thereby realizing the highest color purity in green PNCLED, with a narrow full width at half-maximum of 16.4 nm and a high corrected maximum external quantum efficiency of 17.85%. Moreover, the operation half-life time of the large-size PNCLED is 5-fold of that based on smaller-size PNCs. Our work provides a new avenue for improving the performance of PNCLEDs based on unconventional large-size effects.

Observation of an electronic order along [110] direction in FeSe.

Multiple ordered states have been observed in unconventional superconductors. Here, we apply scanning tunneling microscopy to probe the intrinsic ordered states in FeSe, the structurally simplest iron-based superconductor. Besides the well-known nematic order along [100] direction, we observe a checkerboard charge order in the iron lattice, which we name a [110] electronic order in FeSe. The [110] electronic order is robust at 77 K, accompanied with the rather weak [100] nematic order. At 4.5 K, The [100] nematic order is enhanced, while the [110] electronic order forms domains with reduced correlation length. In addition, the collective [110] order is gaped around [-40, 40] meV at 4.5 K. The observation of this exotic electronic order may shed new light on the origin of the ordered states in FeSe.

Chylomicrons-Simulating Sustained Drug Release in Mesenteric Lymphatics for the Treatment of Crohn's-Like Colitis.

BACKGROUND AND AIMS: Alteration to both the structures and functions of mesenteric lymphatic vessels is a typical hallmark of Crohn's disease [CD]. Dysfunctional lymphatics was observed in patients with both CD and experimental colitis, suggesting mesenteric lymphatics could be potential therapeutic targets. This study aimed to develop a nano-delivery system which can enhance drug delivery in mesenteric lymphatic tissue [MLT] and evaluate the therapeutic effects in Crohn's colitis. METHODS: We designed a mesoporous silica nanoparticle [MSN] conjugated with long-chain fatty acid [LMSN] and covered with enteric coating [ELMSN] which can be specifically transported via the mesenteric lymphatic system. The therapeutic efficacy of laquinimod-loaded nanoparticles [LAQ@ELMSN] was evaluated in the well-established interleukin [IL]-10-/- spontaneous experimental colitis. RESULTS: ELMSNs induced sustainable drug release that markedly increased drug concentration in MLT. In experimental colitis, the lymphatics-targeting drug delivery system suppressed lymphangitis and promoted lymphatic drainage. The downregulation of pro-inflammatory cytokines and the downstream NF-κB-related proteins efficiently inhibited lymphangiogenesis and restored tight junctions of mesenteric lymphatic vessels [MLVs]. LAQ@ELMSN showed a superior therapeutic effect in ameliorating intestinal inflammation compared with free drug administration. Alteration of gut microbiota and metabolites in experimental colitis was also reversed by LAQ@ELMSN. CONCLUSION: Our study demonstrates a convenient, orally administered drug delivery system which enhances drug release in MLT. The results confirm the contribution of the mesenteric lymphatic system to the pathogenesis of gut inflammation and shed light on the application of lymphatics-targeting drug delivery therapy as a potential therapeutic strategy for CD treatment.

Mesopore to Macropore Transformation of Metal-Organic Framework for Drug Delivery in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic relapsing autoimmune disease that is characterized by segmental intestinal inflammation. There is an urgent need for more efficient inflammation-targeting strategies to improve therapeutic effect and reduce systemic drug exposure. Herein, an oxidation-responsive metal-organic framework material (Ce-MOF@PSS) is reported that preferentially adheres to inflamed intestine via enema. The overproduced reactive oxygen species (ROS) at inflammatory sites induces transformation of Ce-MOF@PSS from mesopore to macropore with local drug release. In experimental colitis, the Ce-MOF@PSS delivery system exhibits excellent inflammation-targeting efficacy and superior therapeutic effect over free drug on suppressing inflammation and repairing intestinal barrier function. Accordingly, by targeting intestinal inflammation, increasing local drug concentrations, scavenging ROS, reducing systemic exposure, and exhibiting excellent safety profiles, it is considered that the Ce-MOF drug delivery platform can be intensively developed as a translational nanomedicine for the management of IBD and other inflammatory diseases.

Association between oophorectomy and depression in patients with comorbidities: A nationwide cohort study in Taiwan.

OBJECTIVE: This study investigated the long-term rates of depression after oophorectomy for benign gynecological conditions with or without comorbidities. MATERIALS AND METHODS: This retrospective cohort study examined data from the National Health Insurance Research Database (NHIRD) involving 8199 women aged ≥20 years who underwent unilateral or bilateral oophorectomy for benign gynecological conditions (cases) between 2000 and 2013 (index date). A second cohort consisted of 32,796 women who did not undergo oophorectomy (controls) who were matched 4:1 to cases by age and index year. The follow-up time was more than 10 years. For all participants, the analysis accounted for comorbidities including hypertension, diabetes mellitus, hyperlipidemia, stroke, chronic obstructive pulmonary disease (COPD), chronic liver disease and cirrhosis, chronic kidney disease, and anxiety. Crude hazard ratios, adjusted hazard ratios, and 95% confidence intervals (CIs) were calculated according to multivariable Cox proportional hazard regression models adjusting for age, comorbidity, and the combination of oophorectomy with one comorbidity. RESULTS: Our results show that unilateral or bilateral oophorectomy, whether performed by laparotomy or laparoscopy, increases the overall risk of depression (aHR: 1.36, 95%CI: 1.19-1.55). Compared with controls, women aged <50 years had a significantly higher incidence of depression. Having diabetes (aHR: 1.66, 95%CI: 1.09-2.51), hypertension (aHR:1.56, 95%CI:1.14-2.14), hyperlipidemia (aHR: 1.46, 95%CI: 1.04-2.05), stroke (aHR: 1.91, 95%CI: 1.01-3.60), COPD (aHR: 2.06, 95%CI: 1.3-3.26), chronic liver cirrhosis (aHR: 1.99, 95%CI:1.52-2.61), or anxiety (aHR: 5.01, 95%CI: 3.74-6.70) increased higher risk of depression compared with not having these comorbidities after oophorectomy. The likelihood of depression was highest within the first 6 years following oophorectomy (3-5years:aHR:1.26, 95%CI:1.00-1.58). CONCLUSIONS: Oopherectomy increases the overall risk of depression. We offer useful information for surgical decision-making and preoperative assessments of women undergoing oophorectomy. It is concluded that a synergistic effect exists between oophorectomy and the comorbidities. Post-surgery, physicians should carefully evaluate the risk of depression developing amongst women with comorbidities. A postoperative follow-up time of at least 6 years is recommended, as this period was associated with a significantly higher rate of depression during our over 10-year follow-up.

[Evaluation of taste changes of Scutellariae Radix before and after wine-frying based on electronic ongue technology and its application in identification of Scutellariae Radix pieces].

Scutellariae Radix(Huangqin) is a well-known traditional Chinese medicine(TCM) used for the treatment of clearing heat in clinical application. It is bitter-cold by using directly, but the bitter-cold property can be relieved after wine-frying. The study of taste changes before and after wine-frying of Scutellariae Radix is of great significance in identifying Scutellariae Radix and wine-processed Scutellariae Radix and clarifying the traditional theory of wine-processing. In this experiment, 10 batches of Scutellariae Radix and wine-processed Scutellariae Radix were prepared. The contents of 5 flavonoids were determined by high performance liquid chromatography(HPLC), and principal component analysis(PCA) was performed with 5 flavonoids as variables. As a result, the contents were different in different batches of Scutellariae Radix, but Scutellariae Radix and wine-processed Scutellariae Radix could not be distinguished. Five sensory attributes(sour, salty, fresh, sweet, and bitter) were evaluated by artificial tasting, and the response values of 7 sensors(AHS, AHS, PKS, CTS, NMS, CPS, ANS, SCS) representing the taste of pieces were detected by electronic tongue. The correlation between sensory evaluation and response values of the electronic tongue were analyzed, and the results showed that the sensory evaluation of sour, salty, fresh, sweet, bitter and AHS, CTS, NMS, ANS, SCS sensors had different degrees of correlation, indicating that the electronic tongue technology can be used as an alternative to artificial taste and can serve as a means for quantifying the taste, and it can be used to evaluate the taste of TCM pieces. The taste method was used to analyze the response values of the electronic tongue, and the results showed that the bitterness of wine-processed Scutellariae Radix decreased and the salty taste increased. PCA was used to analyze taste changes before and after wine-processed Scutellariae Radix, and the results showed that taste differences between 2 pieces were divided into 2 categories. PCA loading scattering plots showed that response of saltiness and bitterness were the major factors to affect overall taste in Scutellariae Radix and wine-processed Scutellariae Radix. Based on electronic tongue response values, the Fisher discriminant model for Scutellariae Radix and wine-processed Scutellariae Radix was established, which showed that it could effectively discriminate them with a recognition rate of 100%. The experimental results showed that the electronic tongue combined with multivariate statistical analysis can be used to evaluate taste of TCM, at the same time, it could provide a fast and simple method for identifying different processed products.

A Potential Herbal Adjuvant Combined With a Peptide-Based Vaccine Acts Against HPV-Related Tumors Through Enhancing Effector and Memory T-Cell Immune Responses.

Viral infection is associated with many types of tumorigenesis, including human papillomavirus (HPV)-induced cervical cancer. The induction of a specific T-cell response against virus-infected cells is desired to develop an efficient therapeutic approach for virus-associated cancer. Chinese herbal medicine (CHM) has a long history in the treatment of cancer patients in Asian countries. Hedyotis diffusa Willd (Bai Hua She She Cao, BHSSC) is frequently used clinically and has been shown to inhibit tumor growth in vitro. However, in vivo data demonstrating the antitumor efficacy of BHSSC are still lacking. We showed that BHSSC induces murine and human antigen-presenting cell (APC) activation via the MAPK signaling pathway and enhances antigen presentation in bone marrow-derived dendritic cells (BMDCs) in vitro. Furthermore, we identified that treatment with BHSSC leads to improved specific effector and memory T-cell responses in vivo. Variant peptide-based vaccines combined with BHSSC improved antitumor activity in preventive, therapeutic, and recurrent HPV-related tumor models. Furthermore, we showed that rutin, one of the ingredients in BHSSC, induces a strong specific immune response against HPV-related tumors in vivo. In summary, we demonstrated that BHSSC extract and its active compound, rutin, can be used as adjuvants in peptide-based vaccines to increase immunogenicity and to bypass the requirement of a conditional adjuvant.

[Effect and mechanism of total flavonoids of Lichi Semen on CCl_4-induced liver fibrosis in rats, and prediction of Q-marker].

This paper was to investigate the effect of total flavonoids of Lichi Semen(TFL) on carbon tetrachloride(CCl_4)-induced liver fibrosis in rats, analyze and predict its mechanism of action and potential quality markers(Q-marker). Firstly, male SD rats were taken and injected subcutaneously with a 40% CCl_4-vegetable oil solution twice a week for 8 consecutive weeks to establish a rat model of liver fibrosis. The rats with liver fibrosis were randomly divided into model group, silybin group(43.19 mg·kg~(-1)), Fuzheng Huayu Capsules group(462.75 mg·kg~(-1)), and TFL groups(100 mg·kg~(-1) and 25 mg·kg~(-1)), with normal rats as a blank group, 10 rats in each group. Except for the blank group, the rats in the other groups were subcutaneously injected with 40% CCl_4-vegetable oil solution of a maintenance dose, once a week. The rats in various treatment groups received corresponding doses of drugs, while the rats in the blank group and model group received the same volume of normal saline once a day for 4 weeks. At the end of the experiment, blood was collected from the abdominal aorta and the liver tissues were collected. The levels of total bilirubin(TBiL), direct bilirubin(DBiL), indirect bilirubin(IBiL), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) in serum were detected by using an automatic biochemical detector. Masson staining was used to observe the histopathological changes of rat liver. Then, the chemical compositions of TFL were collected, and the action targets of these chemical compositions were predicted through SWISS database and reverse molecular docking server(DRAR-CPI). After screening of disease targets of liver fibrosis by Gene Cards database, the protein-protein interaction was analyzed with use of STRING database, and GO(gene ontology) analysis and KEGG(Kyoto encyclopedia of genes and genomes) enrich analysis were also carried out. Moreover, an iTRAQ proteomics technology was used to determine protein expression in liver tissues of rats in TFL, model and blank groups to verify the targets. Furthermore, Cytoscape software was used to establish and visualize the network of chemical components, targets and pathways, and predict the potential Q-marker of TFL. The results showed that the levels of TBiL, DBiL, IBiL, ALT, and AST in the model group were significantly higher than those in the blank normal group(P<0.05), and the above levels in the treatment groups were lower than those in the model group, but with no significant differences. Masson staining showed that the liver damage and the degree of fibrosis were severe in the model group, and were relieved to different degrees in the treatment groups. Then, 74 chemical components were screened, which could act on 865 targets such as EGFR and SRC, participating in the regulation of cancer pathways, PI3 K-Akt signaling pathway, HIF-1 signaling pathway and other signaling pathways closely related to liver fibrosis. Pinocembrin, quercetin, epicatechin, procyanidin A2, naringenin, nobiletin, phlorizin and rutin showed the highest correlation with liver fibrosis-related targets and pathways. Proteomics results showed that a total of 18 proteins among the 45 proteins predicted by internet pharmacology were identified, among which 6 proteins were significantly expressed, including 5 up-regulated proteins and 1 down-regulated protein. The protein expression of ALB, PLG, HSP90 AA1, EGFR and MAP2 K1 was significantly returned to a normal state in the TFL treatment groups. In conclusion, TFL may demonstrate the anti-hepatic fibrosis and potential hepatoprotective effects by regulating the expression of ALB, PLG, HSP90 AA1, EGFR and MAP2 K1, which may be associated with the regulation of multiple signaling pathways related to liver fibrosis such as PI3 K-Akt pathway. Pinocembrin, quercetin, epicatechin, procyanidin A2, naringenin, nobiletin, phlorizin and rutin could be regarded as potential Q-markers of TFL for quality control.

Therapeutic Opportunities in Colorectal Cancer: Focus on Melatonin Antioncogenic Action.

Colorectal cancer (CRC) influences individual health worldwide with high morbidity and mortality. Melatonin, which shows multiple physiological functions (e.g., circadian rhythm, immune modulation, and antioncogenic action), can be present in almost all organisms and found in various tissues including gastrointestinal tract. Notably, melatonin disruption is closely associated with the elevation of CRC incidence, indicating that melatonin is effective in suppressing CRC development and progression. Mechanistically, melatonin favors in activating apoptosis and colon cancer immunity, while reducing proliferation, autophagy, metastasis, and angiogenesis, thereby exerting its anticarcinogenic effects. This review highlights that melatonin can be an adjuvant therapy and be beneficial in treating patients suffering from CRC.

Risk of major autoimmune diseases in female breast cancer patients: A nationwide, population-based cohort study.

BACKGROUND: Breast cancer is one of the most common malignancies among women. However, there remains no consensus in current literature on the incidence of autoimmune diseases among breast cancer patients. The purpose of this study was to evaluate the risks of major autoimmune diseases (MAD) including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's syndrome (SS) and dermatomyositis (DMtis)/polymyositis (PM) in female breast cancer patients. METHODS: Using the Taiwanese National Health Insurance Research Database (NHIRD) records from 2003 to 2013, we identified newly-diagnosed female breast cancer patients and randomly selected females without breast cancer in the period 2007 to 2013 into a control group. We matched the two cohorts using a 1:4 ratio based on age, and the year of index date for comparison of the risk of major autoimmune diseases. We estimated and compared the relative risks of autoimmune diseases in female breast cancer patients and females without breast cancer. RESULTS: A total of 54,311 females with breast cancer and 217,244 matched females without breast cancer were included in this study. For SLE, the incidence rates were 2.3 (breast cancer group) vs. 10.0 (control group) per 100,000 women years; for RA rates were 19.3 (breast cancer group) vs. 42.7 (control group) per 100,000 women years; and for SS rates were 20.5 (breast cancer group) vs. 38.2 (control group) per 100,000 women years. After adjusting for potential confounders, the hazard ratios (95% confidence intervals) for female breast cancer patients vs. control group were 0.04 (0.01-0.24) for SLE; 0.03 (0.02-0.04) for RA; and 0.21 (0.09-0.48) for SS. CONCLUSION: Female breast cancer patients had lower risks of SLE, RA and SS when compared to female individuals without breast cancer. However, there was no significant difference in the risk of developing DMtis/PM between both groups.

Effects of Gegen Dingxuan Capsule on behavior, X-Ray Signs of the Cervical Spine, and Humoral Factor Levels in a Rat Model of Cervical Vertigo.

OBJECTIVE: To investigate the effects of Gegen Dingxuan capsule on behavior, X-ray signs of the cervical spine, and levels of norepinephrine (NE), nitric oxide (NO), endothelin (ET-1), and calcitonin gene-related peptide (CGRP) in the plasma of a rat model of cervical vertigo and additionally to clarify the underlying mechanisms of action. METHOD: A total of 40 male SPF Sprague-Dawley rats were randomly assigned to blank control, model, Sibelium, and Gegen Dingxuan capsule groups, with 10 rats in each group. A rat model of cervical vertigo was produced by physically damaging the cervical spine, thereby perturbing its stability. After cervical spine surgery, rats in the Sibelium and Gegen Dingxuan capsule groups were administered Sibelium and Gegen Dingxuan capsule, respectively. After 4 and 8 weeks of administration, balance beam test was used to assess behavior, lateral X-ray images of the cervical spine were taken and scored, and the plasma levels of NE, NO, ET-1, and CGRP were measured. RESULTS: After 4 and 8 weeks of drug administration, the balance beam test scores in the Gegen Dingxuan capsule group were significantly higher than those in the Sibelium group. The radiographic scores were significantly lower in the Gegen Dingxuan capsule group than those in the Sibelium group at 8 weeks. Plasma NE, NO, ET-1 levels, and ET-1/CGRP ratio were significantly decreased in the Gegen Dingxuan capsule group compared with the model group. No significant difference was found between the Sibelium and Gegen Dingxuan capsule groups. Plasma CGRP levels were significantly increased in the Gegen Dingxuan capsule group compared with the model group and were significantly decreased compared with the Sibelium group. CONCLUSIONS: Gegen Dingxuan capsule improves behavior, radiographic scores, reduces plasma levels of NE, NO, ET-1, and the ET-1/CGRP ratio, and increases plasma CGRP levels. Gegen Dingxuan capsule may improve outcome in the rat model of cervical vertigo by ameliorating cervical facet joint disorder, relieving cervical muscle spasm and vasospasm, increasing blood supply, and regulating humoral factor levels.

Effects of Acupressure on Sleep Quality and Psychological Distress in Nursing Home Residents: A Randomized Controlled Trial.

OBJECTIVE: To compare the efficacy of acupressure with sham acupressure in older-adult nursing home residents presenting with poor sleep quality and psychological distress. DESIGN: Prospective, randomized, double-blind, sham-controlled trial. SETTING AND PARTICIPANTS: Sixty-two nursing home residents with poor sleep quality and psychological distress participated in this study. Participants were randomly assigned to an experimental group (n = 31) receiving acupressure at true acupoints (Baihui, Juque, Neiguan, Tianzhu, and Yongchung) or control group (n = 31) receiving acupressure at sham points. All participants received 20 minutes of acupressure before sleeping 3 times a week for 8 weeks. All participants were blinded to group allocation. MEASURES: Sleep quality and psychological distress were measured using the Pittsburgh Sleep Quality Index and the Kessler Psychological Distress scale, respectively. Both groups' outcomes were assessed by assessors blinded to group allocation at the baseline, the end of the intervention, and 1 month after the intervention. RESULTS: The experimental group demonstrated significantly more improvement in sleep quality than did the control group at the end of the intervention (10.5 vs 13.3) and 1 month after the intervention (8.3 vs 14.2; both P ≤ .001). Moreover, the experimental group had lower psychological distress levels than did the control group at 1 month after the intervention (14.6 vs 17.9, P = .05). Furthermore, significant differences in mean sleep quality (F = 60.8, P < .001) and psychological distress (F = 24.6, P < .001) were observed in the experimental group between the measurements at baseline and after the intervention. CONCLUSIONS: Acupressure at true acupoints improves sleep quality, reduces psychological distress, and provides more clinically beneficial effects compared with that at sham points. Future studies should examine whether these effects are maintained in the long term.