Patent Foramen Ovale Closure for Migraineurs with Massive Right-to-Left Shunt and White Matter Lesions: An Exploration on Curative Effects.

Objective: This study aims to investigate the therapeutic efficacy of patent foramen ovale (PFO) closure in migraine patients with a massive right-to-left shunt (RLS) and white matter lesions (WMLs). Methods: The research focused on migraine patients with a massive RLS who underwent PFO closure in our hospital from June 2020 to June 2021. The study included 51 patients without WMLs (control group, CG) and 27 patients with WMLs (observation group, OG). A 12-month postoperative follow-up survey was conducted to assess headache episodes (frequency and duration), evaluated using the Headache Impact Test-6 (HIT-6) and the Pain Intensity Visual Analog Scale (VAS). The psychological state was also evaluated using the Hamilton Anxiety and Depression Scale (HAMA, HAMD). Adverse reactions during the follow-up were recorded. Results: No significant differences in perioperative and prognostic adverse reactions were observed between OG and CG (P > .05). Both groups showed a reduction in postoperative headache episodes and pain intensity. However, the OG exhibited higher frequency and duration of headache episodes and elevated HIT-6 and VAS scores, resulting in lower clinical efficacy (P < .05). Postoperatively, both groups demonstrated reductions in HAMA and HAMD, with CG showing lower scores compared to OG (P < .05). Logistic regression analysis identified the course of the disease, HIT-6 score, and the presence of WMLs as independent risk factors for the efficacy of PFO closure (P < .05). Conclusions: PFO closure proves effective and safe in treating migraine patients with RLS. However, for those with WMLs, clinical attention should be directed toward the treatment of WMLs.

Nobiletin, an active component of Wenyang Yiqi formula, alleviates constipation associated depression through targeting MAPT to inhibit the MAPK signaling pathway.

BACKGROUND: Slow transit constipation (STC) is a common gastrointestinal disorder that is often accompanied by depression. Nobiletin is a natural compound that has been shown to have anti-inflammatory and anti-depressant effects. PURPOSE: To study the effects of nobiletin extracted from Wenyang Yiqi Formula 19 (WYF) on STC accompanied by depression and the related mechanism in STC mouse models. METHODS: In this study, the effects of nobiletin on STC accompanied by depression were investigated in both an STC animal model and an in vitro study. The animal model was induced by loperamide, and the in vitro study used Interstitial cells of Cajal (ICCs) isolated from STC mice. The efficacy of nobiletin was assessed by comparing various parameters, including stool particle counts, moisture content, intestinal propulsive rate, colon histopathology, microtubule-associated protein-tau (MAPT) expression in colon tissue, serum levels of TNF-α, IL-1ß, IL-6, IFN-γ, and the levels of MAPK pathway-related proteins among three experimental groups. RESULTS: Nobiletin treatment significantly improved stool particle counts, moisture content, intestinal propulsive rate, and colon histopathology in the STC animal model. Nobiletin also decreased MAPT expression in colon tissue and serum levels of TNF-α, IL-1ß, IL-6, IFN-γ, and the levels of MAPK pathway-related proteins. In the in vitro study, nobiletin treatment reversed the increased cell proliferation and cell apoptosis observed in ICC isolated from the STC model. CONCLUSION: The findings of this study indicate that nobiletin exhibits promising therapeutic potential in addressing STC accompanied by depression. This potential may be attributed to its ability to regulate the function of ICC by targeting MAPT.

New cassane-type alkaloids and diterpenoids from the pericarps of Caesalpinia bonduc.

The phytochemical investigation of the pericarps of Caesalpinia bonduc led to the isolation and identification of five new cassane-type alkaloids: caesalminines C - G (1-5) and six new diterpenoids: caesalbonducin K - P (6-11), along with seven known compounds (12-18). Compounds 1-5 were identified as a group of rare alkaloids possessing a tetracyclic cassane-type diterpenoid skeleton with a lactam D-ring instead of a typical furan or lactone moiety. The structures of 1-11 were elucidated on the basis of 1D and 2D NMR including HSQC, HMBC, COSY and NOESY, and other spectroscopic analyses. The cytotoxic activities of the isolated compounds were evaluated in the A431, A549 and U87MG cancer cell lines.

UPLC-Q-TOF/MS-Based Serum Metabolomics Reveals Potential Anti-tumor Mechanism of Banxia Xiexin Decoction in Colorectal Cancer Mice.

OBJECTIVE: To clarify the potential mechanism of Banxia Xiexin Decoction (BXD) on colorectal cancer (CRC) from the perspective of metabolomics. METHODS: Forty male C57BL/6 mice were randomly divided into normal control (NC), azoxymethane/dextran sulfate sodium (AOM/DSS) model, low-dose BXD (L-BXD), high-dose BXD (H-BXD) and mesalamine (MS) groups according to a random number table, 8 mice in each group. Colorectal cancer model was induced by AOM/DSS. BXD was administered daily at doses of 3.915 (L-BXD) and 15.66 g/kg (H-BXD) by gavage for consecutive 21 days, and 100 mg/kg MS was used as positive control. Following the entire modeling cycle, colon length of mice was measured and quantity of colorectal tumors were counted. The spleen and thymus index were determined by calculating the spleen/thymus weight to body weight. Inflammatory cytokine and changes of serum metabolites were analyzed by enzyme-linked immunosorbent assay kits and ultra performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS), respectively. RESULTS: Notably, BXD supplementation protected against weight loss, mitigated tumor formation, and diminished histologic damage in mice treated with AOM/DSS (P<0.05 or P<0.01). Moreover, BXD suppressed expression of serum inflammatory enzymes, and improved the spleen and thymus index (P<0.05). Compared with the normal group, 102 kinds of differential metabolites were screened in the AOM/DSS group, including 48 potential biomarkers, involving 18 main metabolic pathways. Totally 18 potential biomarkers related to CRC were identified, and the anti-CRC mechanism of BXD was closely related to D-glutamine and D-glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arginine biosynthesis, nitrogen metabolism and so on. CONCLUSION: BXD exerts partial protective effects on AOM/DSS-induced CRC by reducing inflammation, protecting organism immunity ability, and regulating amino acid metabolism.

Polysaccharides from Chinese herbs as natural weapons against colorectal cancer.

Colorectal cancer (CRC) ranks third and second among the most widespread cancers worldwide and the most common causes of human death due to cancer, respectively. Furthermore, for unknown reasons, numbers of young patients diagnosed with colon cancer has increased. Polysaccharides are important functional phytochemicals reported to have anti-CRC effects. Moreover, CRC development and progression is closely related to the gut microbiome. Although approaches for treating CRC have been the subject of some review papers, research into traditional Chinese medicine (TCM) treatments for CRC and the underlying mechanisms involving polysaccharides have not been reviewed. Here, we reviewed the mechanisms underlying treatment of CRC using TCM polysaccharides, based on the etiology of CRC, and common treatment methods applied. The relationship between intestinal microbes and CRC, the mechanism by which TCM polysaccharides induce CRC cell apoptosis, and how TCM polysaccharides promote immune responses are discussed, as well as TCM polysaccharide use in combination with chemotherapy. TCM polysaccharides provide options for CRC treatment, due to their advantages of having multiple targets, eliciting modest adverse reactions, and wide range of available sources.

Association between blood selenium levels and gestational diabetes mellitus: A systematic review and meta-analysis.

Introduction: The association between blood (serum or plasma) selenium concentrations and gestational diabetes mellitus (GDM) has been evaluated in some studies. However, the reported findings are debatable, and only case-control and cross-sectional studies were included. Objective: This research aimed to assess the association between blood selenium levels and GDM by analyzing existing literature. To provide a reference for the prevention and treatment of GDM, we included prospective studies which are not included in previous studies to collate more high-quality evidence and better test the etiological hypothesis between blood Se concentrations and GDM. Methods: The PubMed, EMBASE, and Web of Science databases were retrieved for literature up to September 2022, and relevant references were manually searched. Raw data from relevant studies were extracted, and a random effect model was adopted for meta-analysis. The total effects were reported as weighted mean differences. All data were analyzed using Stata 16.0 software. Results: Fourteen studies involving 890 pregnant women with GDM and 1618 healthy pregnant women were incorporated in the meta-analysis. Pregnancies with GDM had significantly lower blood selenium levels than those with normal glucose tolerance (weighted mean difference = -8.11; 95% confidence interval: -12.68 to -3.54, P = 0.001). Subgroup analyses showed that the association between blood selenium levels and GDM was consistent in the residents of Asia and Africa, but not in European. This trend was significant in the second and third trimester subgroups, but not in the first trimester subgroup. Articles published in 2006-2015 also showed this trend, but those published before 2005 and 2016-2019 did not show significant results. This difference was evident in non-prospective studies, but not significant in prospective studies. Studies using the Carpenter and Coustan diagnostic criteria were consistent with this trend, whereas studies using other diagnostic criteria found no differences. In addition, in terms of blood selenium measurement methods, atomic absorption spectrometry showed more significant differences than other methods. In the subgroup analysis based on the sample size of included studies and the quality of the studies, each subgroup showed statistical differences. Conclusion: Lower blood selenium concentrations are associated with GDM as shown in our study. Therefore, supplementing an appropriate amount of selenium may be helpful for GDM prevention and treatment.

Evaluation of Peroxidase in Herbal Medicines Based on an Electrochemical Sensor.

Peroxidases are species-specific. Differences in peroxidase can objectively reflect the genetics among species. The use of peroxidase to assist in species identification is relatively simple and effective. In this work, we proposed a graphene-modified electrode. This electrode can amplify the signal of electrocatalytic reduction of hydrogen peroxide. Since peroxidase can catalyze the reduction of hydrogen peroxide, this signal can be used as an indicator to demonstrate the content of peroxidase in different plant tissues. Twelve herbal medicines were selected for our study. The results show that this electrochemical-based detection technique was comparable to colorimetric method in terms of accuracy.

[Gene cloning, heterologous expression and activity identification of latroeggtoxin-â ¥].

One of the distinct characters of Latrodectus tredecimguttatus is that its toxic components exist not only in the venomous glands, but also in the tissues outside the venomous glands and even in the eggs. Investigation on the toxins outside the venomous glands can deepen our understanding of spider toxins and discover new lead molecules with important application prospects. In order to explore the low-abundance proteinaceous toxins in the L. tredecimguttatus eggs, we used bioinformatic strategies to mine a gene sequence encoding a peptide toxin from the transcriptome of L. tredecimguttatus eggs, and then heterologously expressed the gene successfully with a 3'-RACE combined with nest PCR strategy. Biological activity analyses indicated that the expressed peptide toxin, named latroeggtoxin-Ⅵ (LETX-Ⅵ), could inhibit Na⁺ channel currents in ND7/23 cells and promote dopamine release from PC12 cells, without obvious toxicity against Periplaneta americana and bacteria as well as fungi including Staphylococcus aureus and Candida albicans, demonstrating that LETX-Ⅵ is a mammal-specific neurotoxin with a potential application prospect in development of the tool reagents for neurobiological study and the drugs for treating related diseases.

Development of Electrochemical Oscillation Method for Identification of Prunus persica, Prunus davidiana, and Prunus armeniaca Nuts.

In this work, an electrochemical oscillation system has been developed using the Belousov-Zhabotinsky reaction. The effect of the combination of each reagent, reaction temperature, and stirring speed on the induction period, oscillating period, and oscillating life were optimized. The nuts of Prunus persica, Prunus davidiana, and Prunus armeniaca have been widely used for medical purposes. The proposed electrochemical oscillation system was then used for the identification of P. persica, P. davidiana, and P. armeniaca. Three nuts exhibited very different electrochemical oscillation profiles. The dendrogram was divided into three main principal infrageneric clades. Each cluster only contains one species, suggesting that no outlier was observed in this study. Based on the discussed results, we proposed a simple method for herbal medicine identification.

Metabolomics study on the therapeutic effect of the Chinese herb pair Fructus Aurantii Immaturus and Rhizoma Atractylodis Macrocephalae in constipated rats based on UPLC-Q/TOF-MS analysis.

BACKGROUND: In China, Zhishi (Aurantii Fructus Immaturus) - Baizhu (Atractylodis Macrocephalae Rhizoma) is a well-known herb pair used to treat gastrointestinal motility disorders for thousands of years, and it has especially shown a definite advantage in the treatment of slow transit constipation (STC). However, the mechanism of Zhishi-Baizhu (ZSBZ) in the treatment of STC remains unclear. In this study, plasma metabolomics research combined with metabolic pathway analysis has been used to illuminate the potential mechanism of its effects against STC. METHODS: Parameters of intestinal transit ratio, plasma motilin (MTL), substance P (SP), adenosine triphosphate (ATP), histological alteration of the colon and MLCK expression in the colon were detected to evaluate the effects with respect to STC. Principal component analysis (PCA) was used to investigate the global metabolite alterations, while orthogonal partial least squares discriminant analysis (OPLS-DA) and t-test were used to filter potential metabolite markers. Moreover, metabolic pathway analysis was employed. RESULTS: Oral administration of ZSBZ significantly prevented the development of STC. It increased the expression of MTL and SP in serum, as well as the expression of ATP and MLCK in the colon. ZSBZ administration alleviated symptoms in loperamide-induced constipated rats, evidenced by the increase of intestinal transit ratio. Futhermore, 9 potential biomarkers of STC were screened, and the levels were all reversed to different degrees after ZSBZ administration. Metabolic pathway analysis showed that the improvement of STC by ZSBZ was mainly related to caffeine and vitamin B6 metabolism. CONCLUSIONS: Our study identifies the metabolic networks of constipated rats and demonstrates the efficacy of this metabolomics approach to systematically study the therapeutic effects of ZSBZ on constipation.

Suppressive effect of Aurantii Fructus Immaturus and Atractylodis Macrocephalae Rhizoma on glutamic acid-induced autophagy of interstitial cells of Cajal.

OBJECTIVE: To investigate the effects of Aurantii Fructus Immaturus (Zhishi, ZS) and Atractylodis Macrocephalae Rhizoma (Baizhu, BZ)-containing serum on glutamate-induced autophagy in rat colonic interstitial cells of Cajal (ICCs) and to analyze the underlying mechanism. METHODS: Rat colonic ICCs cultured in vitro were identified by fluorescence and then stimulated with glutamic acid (5 mmol/L) for 24 h to establish a cell model of autophagy. The cells were then treated with different concentrations of ZSBZ-containing serum or rat serum. The viability of the ICCs was detected with cell counting kit-8 assays, and cell apoptosis rates were examined with flow cytometry. The ultrastructure and autophagosomes in the ICCs were observed using transmission electron microscopy. The effects of ZSBZ-containing serum on apoptosis-associated mediators were assessed by Western blotting and real-time quantitative polymerase chain reaction. In addition, microtubule-associated protein light chain 3 (LC3), p-phosphoinositide 3-kinase (p-PI3K), p-Akt and p-mammalian target of rapamycin (p-mTOR) expression was detected via Western blotting analysis. RESULTS: Compared to those in the model group, ICC viability and apoptosis rates were significantly increased by ZSBZ-containing serum (P < 0.05). In addition, the expression levels of Beclin-1, LC3, p-PI3K, p-Akt and p-mTOR were significantly lower (P < 0.05) and Bcl-2 expression was higher in the ZSBZ-containing serum treatment groups than in the model group (P < 0.05). CONCLUSION: Our findings demonstrated that ZSBZ protects glutamic acid-stimulated ICCs, and this beneficial effect may be mediated by a reduction in autophagy via inhibition of the PI3K/Akt/mTOR pathway.

Establishment of HPLC fingerprint and determination method of three index components of classical herbal formula substance benchmarks of Xiebai Powder / 中草药

Objective: To establish the HPLC fingerprint and the determination method of three index components of the classical herbal formula substance benchmarks of Xiebai Powder. Methods: Fingerprint chromatographic conditions were as following: detection wavelength 254 nm/325 nm, column temperature 35 ℃; flow rate 0.8 mL/min; injection volume 25 μL; mobile phase consisting of 0.1% aqueous formic acid (A) and acetonitrile (B); binary gradient elution: 0-20 min, 5%-10% B; 20-33 min, 10%-15% B; 33-50 min, 15%-20% B; 50-95 min, 20%-58% B. Ten batches of substance benchmarks of Xiebai Powder fingerprints were collected and evaluated by the Chinese Pharmacopoeia Committee "Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System 2012 Edition" software. Chromatographic conditions of content determination: detection wavelength 237 nm, column temperature 30 ℃; flow rate 1.0 mL/min; injection volume 5 μL; mobile phase consisting of 0.1% aqueous phosphoric acid (A) and acetonitrile (B) for binary gradient elution: 0-10 min, 5%-20% B; 10-18 min, 20%-60% B; 18-26 min, 60%-100% B; 26-38 min, 100% B; 38-41 min, 100%-5% B; 41-45 min, 5% B. Results: Based on the matching results, 55 common peaks were determined at a wavelength of 254 nm, and 57 common peaks were determined at a wavelength of 325 nm. Three substances, mulberroside A (S), liquiritin and ammonium glycyrrhizinate, were identified in the common peaks. After methodological research, its precision, stability and reproducibility were good. Ten batches of substance benchmarks of Xiebai Powder fingerprints were evaluated with reference fingerprints, and their similarities were greater than 0.9. The average recovery rates of mulberroside A (S), liquiritin and ammonium glycyrrhizinate were 97.82%, 97.40% and 105.81%, respectively. The RSD (n = 6) was 4.41%, 2.51% and 1.19%, respectively, which met the require of 2015 edition of the Chinese Pharmacopoeia. The three components had good linearity in the range of 25.25-2525 ng, 25-2 500 ng and 8.5-850 ng, respectively. The method had good precision, stability and repeatability. The contents of 10 batches of substance benchmarks of Xiebai was determined. The content of mulberry A was 11.6-35.5 mg/g, the content of liquiritin was 0.1-1.6 mg/g, and the content of glycyrrhizic acid was 0.3-2.5 mg/g. The range of the contents of these ingredients was large, which indicated that the quality of mulberry husks and licorice herbs from different places was quite different. Conclusion: The establishment of the HPLC fingerprint and the determination method of three index components of the classical herbal formula substance benchmarks of Xiebai Powder provided some bases for the study of the quality standard of substance benchmarks of Xiebai Powder.

Banxia Xiexin decoction, a traditional Chinese medicine, alleviates colon cancer in nude mice.

BACKGROUNDS: Banxia Xiexin decoction (BXD) is widely used in the treatment of acute and chronic gastritis, peptic ulcer, dyspepsia, gastrointestinal dysfunction, chronic hepatitis, oral ulcer and other diseases, but there are few reports on its treatment of colon cancer. The current study was designed to investigate the effect of BXD on colon cancer and its possible molecular mechanisms. METHODS: Fifty SPF BALB/c nude mice were selected to establish an animal model of colon cancer bearing nude mice. Establishment of nude mice intestinal cancer model by subcutaneous injection of intestinal cancer cells. Serum superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by commercial kits. Pro-inflammatory cytokines in serum were detected. Western blotting was used to demonstrate the expression levels of related apoptosis proteins, inflammation and oxidative stress proteins. RESULTS: Our results showed that BXD could decrease SOD and increased MDA in nude mice bearing tumors. BXD increased pro-inflammatory cytokines in serum in nude mice bearing tumors. Western blotting revealed that the protein expressions of Bax, Caspase-3, Caspase-9 were increased by different concentrations of BXD, while Bcl-2 was decreased. BXD also decreased Nrf-2 and HO-1, and increased the levels of MAPK/NF-κB pathway in tumor tissue. CONCLUSIONS: BXD has an obvious tumor inhibiting effect on SW 480 colon cancer transplanted tumor in nude mice via apoptotic pathway and MAPK/NF-κB pathway.

Tetramethylpyrazine Improves Postoperative Tissue Adhesion: A Drug Repurposing.

Plants are known to possess plenty of pharmacological activities as a result of various phytoconstituents. Tetramethylpyrazine (TMP), one of the most widely used medicinal compound isolated from traditional Chinese herb, is usually employed for anti-oxidation, anti-inflammation, anti-platelet aggregation, anti-lipid, anti-fibrosis, as well as activating blood, removing stasis, dilating small arteries, improving microcirculation and antagonizing calcium. In the present paper, the anti-adhesion effect of TMP were reviewed. TMP was found to play a multi-target and muti-link role in anti-adhesion by inhibiting hyperplasia of collagen and overexpression of adhesion-related factors and reducing the concentration of white blood cells and fibrin in plasma. Because previous studies mostly focused on in vitro experiments and animal experiments, there is an urgent need for clinical research with abundant indicators to further prove its anti-adhesion potency. Future basic research should concentrate on the development of TMP as a biological material.

Identification of metabolites in human and rat urine after oral administration of Xiao-Qing-Long-Tang granule using ultra high performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry.

Xiao-Qing-Long-Tang is a traditional Chinese formula used for the treatment of cold syndrome, bronchitis, and nasal allergies for thousands of years. However, the in vivo integrated metabolism of its multiple components and the active chemical constituents of Xiao-Qing-Long-Tang remain unknown. In this study, a method using ultra high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was established for the detection and identification of the metabolites in human and rat urine after oral administration of Xiao-Qing-Long-Tang. A total of 19 compounds were detected or tentatively identified in human urine samples, including eight prototypes and 11 metabolites. Also, a total of 50 compounds were detected or tentatively identified in rat urine samples, including 15 prototypes and 35 metabolites detected with either a highly sensitive extracted ion chromatogram method or the MSE determination using Mass Fragment software. Our results indicated that phase Ⅱ reactions (e.g. glucuronidation and sulfation) were the main metabolic pathways of flavones, while phase I reactions (e.g. demethylation and hydroxylation) were the major metabolic reaction for alkaloids, lignans, and ginger essential oil. This investigation provided important structural information on the metabolism of Xiao-Qing-Long-Tang and provided evidence to obtain a more comprehensive metabolic profile.

Aqueous Extracts of Herba Cistanche Promoted Intestinal Motility in Loperamide-Induced Constipation Rats by Ameliorating the Interstitial Cells of Cajal.

Traditional Chinese medicine was reported to have good effects in treating functional constipation. This work attempted to prove the effects of aqueous extracts of Herba Cistanche (AEHC) on STC treatment and to determine the possible mechanisms by a loperamide-induced slow transit constipation (STC) model. HPLC was performed for identification and confirmation of the bioactive components in the AEHC. It was found that AEHC attenuated STC responses based on increased fecal quantity, moisture content, and intestinal transit rate, as well as serum levels of GAS, MTL, SS, and CGRP. The protein and mRNA levels of c-kit, a labeling of interstitial cells of Cajal (ICC), also increased. Meanwhile, only the protein level of SCF, a ligand of c-kit, increased. The analysis of our data suggested that AEHC could obviously improve the function of ICC via a signaling pathway involving PI3K, SCF, and c-kit and enhance colonic motility indices such as GAS, MTL, SS, and CGRP. It is interesting to note that AEHC appeared to be effective on constipation, so further experiments are necessary to clarify the exact mechanisms involved.

Effect of ligustrazine nanoparticles nano spray on transforming growth factor-ß/Smad signal pathway of rat peritoneal mesothelial cells induced by tumor necrosis factor-α.

OBJECTIVE: To study the effect of ligustrazine nanoparticles nano spray (LNNS) on transforming growth factor ß (TGF-ß)/Smad signal protein of rat peritoneal mesothelial cells (RPMC) induced by tumor necrosis factor α (TNF-α), and the anti-adhesion mechanism of LNNS in the abdominal cavity. METHODS: The primary culture and subculture of rat peritoneal mesothelial cells (RPMC) was processed by trypsin digestion method in vitro. The third generation was identifified for experiment and divided into 5 groups: a blank group: RPMC without treatment; a control group: RPMC stimulated with TNF-α; RPMC treated by a low-dosage LNNS group (2.5 mg/L); RPMC treated by a medium-dosage LNNS group (5 mg/L); and RPMC treated by a high-dosage LNNS group (10 mg/L). Reverse transcription-polymerase chain reaction was applied to test the expression of fifibronectin, collagen I (COL-I), TGF-ß mRNA, and Western blot method to test the Smad protein 7 expression of RPMC. RESULTS: Compared with the blank group, a signifificant elevation in fifibronectin (FN), COL-I and TGF-ß mRNA expression of RPMC were observed in the control group (P<0.05). Compared with the control group, LNNS suppressed the expressions of FN, COL-I and TGF-ß mRNA in a concentrationdependent manner (P<0.05). The expression of Smad7 protein of RPMC was down-regulated by TNF-α stimulation, and up-regulated with the increase of LNNS dose (P<0.05). CONCLUSIONS: TNF-α may induce changes in RPMC's viability, leading to peritoneal injury. LNNS could reverse the induction of fifibrosis related cytokine FN, COL-I and TGF-ß, up-regulating the expression of Smad7 by TNF-α in RPMC, thus attenuate peritoneal injury by repairing mesothelial cells.

Recent Advances in Research on Widow Spider Venoms and Toxins.

Widow spiders have received much attention due to the frequently reported human and animal injures caused by them. Elucidation of the molecular composition and action mechanism of the venoms and toxins has vast implications in the treatment of latrodectism and in the neurobiology and pharmaceutical research. In recent years, the studies of the widow spider venoms and the venom toxins, particularly the α-latrotoxin, have achieved many new advances; however, the mechanism of action of the venom toxins has not been completely clear. The widow spider is different from many other venomous animals in that it has toxic components not only in the venom glands but also in other parts of the adult spider body, newborn spiderlings, and even the eggs. More recently, the molecular basis for the toxicity outside the venom glands has been systematically investigated, with four proteinaceous toxic components being purified and preliminarily characterized, which has expanded our understanding of the widow spider toxins. This review presents a glance at the recent advances in the study on the venoms and toxins from the Latrodectus species.

Isolation and preliminary characterization of proteinaceous toxins with insecticidal and antibacterial activities from black widow spider (L. tredecimguttatus) eggs.

The eggs of black widow spider (L. tredecimguttatus) have been demonstrated to be rich in toxic proteinaceous components. The study on such active components is of theoretical and practical importance. In the present work, using a combination of multiple biochemical and biological strategies, we isolated and characterized the proteinaceous components from the aqueous extract of the black widow spider eggs. After gel filtration of the egg extract, the resulting main protein and peptide peaks were further fractionated by ion exchange chromatography and reversed-phase high performance liquid chromatography. Two proteinaceous components, named latroeggtoxin-III and latroeggtoxin-IV, respectively, were purified to homogeneity. Latroeggtoxin-III was demonstrated to have a molecular weight of about 36 kDa. Activity analysis indicated that latroeggtoxin-III exhibited neurotoxicity against cockroaches but had no obvious effect on mice, suggesting that it is an insect-specific toxin. Latroeggtoxin-IV, with a molecular weight of 3.6 kDa, was shown to be a broad-spectrum antibacterial peptide, showing inhibitory activity against all five species of bacteria tested, with the highest activity against Staphylococcus aureus. Finally, the implications of the proteinaceous toxins in egg protection and their potential applications were analyzed and discussed.

Proanthocyanidins from Grape Seeds Modulate the NF-κB Signal Transduction Pathways in Rats with TNBS-Induced Ulcerative Colitis.

To elucidate the molecular mechanisms involved in the therapeutic effects of proanthocyanidins from grape seeds (GSPE), we explore whether GSPE regulates the inflammatory response of TNBS-induced colitis in rats at the levels of NF-κB signal transduction pathway. Rats were intragastrically administered of different doses of GSPE (100, 200 and 400 mg·kg-1) per day for seven days after ulcerative colitis (UC) was induced by intracolonic injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS) dissolved in 50% ethanol. Sulfasalazine (SASP) at 400 mg/kg was used as a positive control drug. The expression of nuclear factor-kappa B (NF-κB), phospho-I kappaB-alpha (pIκBα), inhibitor kappa B kinase (IκK) in the colon tissues were all measured by enzyme-linked immunosorbent assay (ELISA) methods. Treatment with GSPE reduced the expression of NF-κB, pIκBα and IκK in the colon. The results of this study show that GSPE exerts beneficial effects in inflammatory bowel disease by inhibition of NF-κB signal transduction pathways.