Network pharmacology and experimental verification to explore the anti-superficial thrombophlebitis mechanism of Mailuo shutong pill.

ETHNOPHARMACOLOGICAL RELEVANCE: Mailuo shutong pill (MLST) has been widely used in clinical treatment of superficial thrombotic phlebitis (STP). Nevertheless, the major active components of MLST and the mechanism of synergistic action have not been reported. AIM OF THE STUDY: The present study aimed to evaluate the improving effects and the underlying mechanism of MLST on mannitol-induced STP in rabbits. MATERIAL AND METHODS: In this study, Ultrahigh-performance liquid chromatography electrospray ionization quadrupole-exactive orbitrap mass spectrometry (UHPLC-ESI-Q-Exactive-Orbitrap-MS) was used to analyze and identify the chemical composition of MLST and the prototype components absorbed into the blood. Then, according to the prototype components in serum, the targets and mechanisms of MLST were explored by applying network pharmacology. The rabbit model of STP was established by injecting 20% mannitol into bilateral auricular vein. The pathological changes of rabbit ear tissues, inflammatory factors, coagulation function and hemorheology were detected. In addition, molecular docking verified the interaction between the main active ingredient and the key target. Finally, the PI3K/AKT pathway and its regulated downstream pathways were verified by Western blot. RESULTS: A total of 96 MLST components and 53 prototypical components absorbed into the blood were successfully identified. Based on network pharmacology, PI3K/AKT pathway and 10 chemical components closely related to this pathway were obtained. Hematoxylin-eosin (HE) staining results indicated that MLST effectively improved of the pathological damage of ear tissues. MLST decreased levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and C-reactive protein (CRP). The expression of platelets (PLT) and fibrinogen concentration (FIB) was decreased, while prothrombin time (PT) and activated partial thromboplastin time (APTT) were prolonged. In addition, the plasma viscosity and whole blood viscosity in the MLST groups were significantly decreased. The more important discovery was that the expressions of P-PI3K, VEGF, P-AKT, P-IκB-α, P-NF-κB, NLRP3, ASC, Cleaved IL-1ß and Cleaved Caspase-1 were effectively reversed after treatment with MLST. CONCLUSIONS: This study comprehensively analyzed and characterized the chemical composition of MLST and the prototypical components absorbed into the blood. This study strongly confirmed the pharmacodynamic effect of MLST on STP. More importantly, this pharmacodynamic effect was achieved through inhibition of the PI3K/AKT pathway and its regulated NF-κB and NLRP3 pathways.

Supplementation of chestnut tannins in diets can improve meat quality and antioxidative capability in Hu lambs.

Chestnut tannins (CNT), as a source of hydrolyzable tannins, positively affect the antioxidant status of livestock. In the current study, 90 male Hu lambs were used to investigate the effect of dietary CNT intake on growth performance, nutrient digestibility, meat quality and oxidative stability, rumen microbial, and the transcriptomes of muscle and liver. A completely randomized design with three CNT intake levels (0, 0.3%, and 0.6%) was used. Rumen microbial and nutrient digestibility were not significantly altered by CNT intake. Diets with 0.3% CNT intake significantly reduced the shear force, yellowness at 24 h, and C20:2 polyunsaturated fatty acids of lamb meat and malondialdehyde in serum and longissimus thoracis (LT) muscle. Meanwhile, the 0.3% CNT diet significantly increased average daily gain during the 1- 21 days and 64- 90 days, dry matter intake during the 1- 21 days, the slaughter weight, and liver index of lambs. The 0.3% CNT diet significantly increased C26:0 saturated fatty acids, total antioxidant capacity, glutathione peroxidase, superoxide dismutase, and catalase in LT muscle. The meat shelf life of 0.3% CNT and 0.6% CNT groups was prolonged by 8.7 h and 5.4 h, respectively. Transcriptomic analysis revealed that CNT supplementation can induce the expression of antioxidant enzyme gene (CAT, SOD1), and the differentially expressed genes were mainly involved in antioxidant activity, transferase activity, and adenosine triphosphate binding. These results suggest that 0.3% CNT intake can relieve the oxidative stress of lambs, and improve the stability of meat color and meat tenderness, due to the enhanced antioxidative capacity.

Shouhui Tongbian Capsules induce regression of inflammation to improve intestinal barrier in mice with constipation by targeted binding to Prkaa1: With no obvious toxicity.

Constipation arising from the poor bowel movement is a rife enteric health problem. Shouhui Tongbian Capsule (SHTB) is a traditional Chinese medicine (TCM) which effectively improve the symptoms of constipation. However, the mechanism has not been fully evaluated. The purpose of this study was to evaluate the effect of SHTB on the symptoms and intestinal barrier of mice with constipation. Our data showed that SHTB effectively improved the constipation induced by diphenoxylate, which was confirmed by shorter first defecation time, higher internal propulsion rate and fecal water content. Additionally, SHTB improved the intestinal barrier function, which was manifested by inhibiting the leakage of Evans blue in intestinal tissues and increasing the expression of occludin and ZO-1. SHTB inhibited NLRP3 inflammasome signaling pathway and TLR4/NF-κB signaling pathway, reduced the number of proinflammatory cell subsets and increased the number of immunosuppressive cell subsets to relieve inflammation. The photochemically induced reaction coupling system combined with cellular thermal shift assay and central carbon metabolomics technology confirmed that SHTB activated AMPKα through targeted binding to Prkaa1 to regulate Glycolysis/Gluconeogenesis and Pentose Phosphate Pathway, and finally inhibited intestinal inflammation. Finally, no obvious toxicity related to SHTB was found in a repeated drug administration toxicity test for consecutive 13 weeks. Collectively, we reported SHTB as a TCM targeting Prkaa1 for anti-inflammation to improve intestinal barrier in mice with constipation. These findings broaden our knowledge of Prkaa1 as a druggable target protein for inflammation inhibition, and open a new avenue to novel therapy strategy for constipation injury.

Ceftazidime-avibactam-based combination therapy for hospital-acquired central nervous system infections caused by carbapenem-resistant Klebsiella pneumoniae.

OBJECTIVES: Klebsiella pneumoniae (K. pneumoniae) is one of the most common bacteria in the hospital-acquired central nervous system (CNS) infections. Central nervous system infections caused by carbapenem-resistant K. pneumoniae (CRKP) are associated with significant mortality rates and high hospital costs due to limited antibiotic treatment options. This retrospective study aimed to evaluate the clinical efficacy of ceftazidime-avibactam (CZA) for the treatment of CNS infections caused by CRKP. METHODS: Twenty-one patients with hospital-acquired CNS infections caused by CRKP who received treatment with CZA for ≥ 72 hours were enrolled. The primary outcome was to assess the clinical and microbiology efficacy of CZA for the treatment of CNS infections caused by CRKP. RESULTS: A high burden of comorbidity was discovered in 20 of 21 patients (95.2%). Most patients had a history of craniocerebral surgery and 17 (81.0%) of the patients were in the intensive care unit with a median APACHE II score of 16 (IQR 9-20) and SOFA score of 6 (IQR 3-7). Eighteen cases were treated by CZA-based combination therapies, while the remaining three cases were treated with CZA alone. At the end of the treatment, the overall clinical efficacy was 76.2% (16 of 21) with a bacterial clearance rate of 81.0% (17 of 21) and all-cause mortality of 23.8% (five of 21). CONCLUSION: This study showed that CZA-based combination therapy is an effective treatment option for CNS infections caused by CRKP.

Berberine in Sepsis: Effects, Mechanisms, and Therapeutic Strategies.

Sepsis is defined as a dysregulated immune response to infection that leads to multiple organ dysfunction. To date, though a growing body of knowledge has gained insight into the clinical risk factors, pathobiology, treatment response, and recovery methods, sepsis remains a significant concern and clinical burden. Therefore, further study is urgently needed to alleviate the acute and chronic outcomes. Berberine (BBR), a traditional Chinese medicine with multiple actions and mechanisms, has been investigated in cellular and rodent animal models of sepsis mainly based on its anti-inflammatory effect. However, the practical application of BBR in sepsis is still lacking, and it is imperative to systematically summarize the study of BBR in sepsis. This review summarized its pharmacological activities and mechanisms in septic-related organ injuries and the potential BBR-based therapeutic strategies for sepsis, which will provide comprehensive references for scientific research and clinical application.

High throughput-screening of native herbal compounds identifies taccaoside A as a cytotoxic compound that mediates RAS signaling in cancer stem cells.

BACKGROUND: Cancer stem cells (CSCs) are characterized by their ability to self-renew, to differentiate into multiple cell types and also drive tumor formation, altogether making them important cellular targets for therapeutic intervention. However, existing CSC-targeting drugs do not significantly improve clinical outcomes. More recently, preclinical studies of natural product-derived compounds have demonstrated their potential usefulness as a therapeutic cancer treatment through their cytotoxic actions on CSCs. PURPOSE: Here, we identify CSC-specific compounds derived from natural products and characterize their putative mechanisms of action in CSCs. METHODS: Glioblastoma stem cells (GSCs) were labeled with EGFP via homologous recombination and utilized for a high-throughput screen of 8,344 fractions from 386 herbal medicines. The fractions that extinguished EGFP fluorescence signal were then further characterized by LC-MS/MS. Next, several putative cytotoxic compounds were evaluated for their cytotoxic effects on GSCs, cancer cell lines and immortalized cells using a variety of methods to study cell proliferation (EdU incorporation assay), cell death (cleaved-Caspase-3 immunostaining), DNA damage (comet assay), mitochondrial membrane changes (JC-1 immunostaining), and tumor formation in vitro (soft agar colony forming assay). We also performed surface plasmon resonance analysis, western blotting, and immunohistochemistry to characterize the putative mechanisms underlying the cytotoxic effects of putative compounds on GSCs. Finally, we carried out xenograft tumor growth assays to study the cytotoxic potential of several candidates in vivo. RESULTS: Our high throughput screen led to the identification of the furostanol saponin taccaoside A and its two homologs from the rhizomatous geophyte Tacca. subflabellata that were cytotoxic to GSCs. Interestingly, the cytotoxic effect of taccaoside A on cell lines was significantly less compared to its homologs, owing to stereochemical differences of a carbon-carbon double bond between C-20 and C-22. Molecular studies revealed that taccaoside A binds to RAS to inhibit downstream effector signaling. Correspondingly, blockade of the interaction between taccaoside A and RAS abolished the inhibitory effect of this compound on CSCs. Furthermore, taccaoside A treatment was effective in limiting tumor cell growth in vivo. CONCLUSION: Our study yielded an effective approach to screen for CSC-specific agents. Through this approach, we identified taccaoside A from the rhizomatous geophyte Tacca. subflabellata are cytotoxic to CSCs through a molecular mechanism that involves RAS binding and suppression of its downstream signaling. Our findings indicate taccaoside A is a potential lead compound for anti-CSC drug discovery.

Jingfang Granules improve glucose metabolism disturbance and inflammation in mice with urticaria by up-regulating LKB1/AMPK/SIRT1 axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Jingfang Granule (JFG) is a Traditional Chinese Medicine prescription to empirically treat skin disease such as urticaria in clinical practice. However, the potential mechanisms of JFG on urticaria are not fully defined. AIM OF STUDY: The aim of this study is to investigate the mechanisms of JFG in treating urticaria through an OVA/aluminum hydroxide induced urticaria mice model. MATERIALS AND METHODS: KM mice were injected intraperitoneally (i.p.) with OVA/aluminium hydroxide to establish the model with urticaria. After the mice were administered JFG, itching degree and hematoxylin and eosin (H&E) staining were used to assess the protective effect of JFG on mice with urticaria. The regulatory networks were investigated by proteomics and central carbon metabolomics. Spleen T lymphocyte subsets were detected by flow cytometry. Peripheral blood cytokines were detected using ELISA kits or Cytometric Bead Array (CBA) kits. The protein expression of skin tissue was detected by western blot or immunohistochemical staining. RESULTS: JFG significantly relived skin tissue lesions and skin pruritus in mice with urticaria. Meanwhile, JFG significantly decreased IgE, IL-1ß, IL-6, IL-4, TNF-α and IL-17A levels and increased IFN-γ levels in the serum of urticaria mice by inhibiting the expression of inflammation associated proteins including TLR4 and p-NF-κB p65, p-ERK1/2, p-JNK and p-p38, NLRP3, ASC and cleaved caspase-1. The results of proteomics, central carbon metabolomics, western blot and immunohistochemical staining confirmed that JFG inhibited Glycolysis/Gluconeogenesis and Pentose phosphate pathway in the skin tissue of urticaria mice by activating the LKB1/AMPK/SIRT1 axis and then downregulating the protein expressions of Glut1, TORC2, p-CREB, PEPCK, HNF4α and G6Pase. CONCLUSION: The current study demonstrates that JFG is effective in treating OVA/aluminum hydroxide-induced skin lesions and inflammation in mice, and JFG exhibits the clinical benefits via modulating LKB1/AMPK/SIRT1 axis, which in turn inhibits Glycolysis/Gluconeogenesis and Pentose phosphate pathway.

[Intervention effect of Jingfang Mixture on urticaria mice based on NF-κB/NLRP3/IL-1ß signaling pathway].

This study explored the curative effect of Jingfang Mixture on urticaria mice induced by aluminum hydroxide/ovalbumin, and discussed its mechanism. Sixty male Kunming mice were randomly divided into a normal group, a model group, three Jingfang Mixture(low-dose, medium-dose, and high-dose) groups, and a positive drug(cetirizine hydrochloride) group. The urticarial model in mice was induced by the intraperitoneal injection of the mixed solution of ovalbumin and aluminum hydroxide. The degrees of pruritus were observed after the second immunization. Pathological changes were detected by hematoxylin and eosin(HE) staining. Levels of interleukin 1ß(IL-1ß) and tumor necrosis factor α(TNF-α) in the serum were detected by enzyme linked immunosorbent assay(ELISA). Expressions of NOD-like receptor protein 3(NLRP3) and IL-1ß were detected by immunohistochemistry(IHC). Expressions of nuclear factor kappa-B(NF-κB p65), NLRP3, apoptosis-associated speck-like protein containing a CARD(ASC), cysteinyl aspartate-specific proteases 1(caspase-1), and IL-1ß proteins were detected by Western blot. The results showed that, except for the normal group, the mice in all groups had different degrees of pruritus. Compared with the model group, the Jingfang Mixture groups and the positive drug group prolonged the scratching latency of mice(P<0.05), and significantly reduced the number of scratching(P<0.05). In addition, the Jingfang Mixture groups and the positive drug group improved the pathological morphology of skin tissue. The expression levels of IL-1ß and TNF-α in serum were significantly reduced(P<0.05), and the number of NLRP3 and IL-1ß positive cells was decreased(P<0.01). The expressions of p-NF-κB p65, NLRP3, ASC, cleaved caspase-1, and IL-1ß protein were significantly down-regulated(P<0.05). The results of the above study indicate that Jingfang Mixture inhibit the inflammatory response in urticaria mice, and the mechanism may be related to the inhibition of activating NF-κB/NLRP3/IL-1ß signaling pathway.

[Anti-inflammatory mechanism of active ingredients in Jingfang Mixture based on network pharmacology and experimental verification].

The present study aimed to explore the regulatory targets and anti-inflammatory mechanism of Jingfang Mixture based on network pharmacology and animal tests. The active ingredients of Jingfang Mixture and the corresponding targets were screened out by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Inflammation-related targets were searched from GeneCards and DisGeNET, and the targets of active ingredients of Jingfang Mixture against inflammation were obtained. The protein-protein interaction(PPI) network was analyzed by STRING and plotted. Gene ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were carried out based on DAVID. The results of network pharmacology showed 159 active ingredients and 276 targets of Jingfang Mixture and 664 inflammation-related targets were screened out, and 90 targets of active ingredients of Jingfang Mixture against inflammation were obtained. As revealed by the PPI network, protein kinase B1(AKT1), caspase-3(CASP3), interleukin-1ß(IL1 B), prostaglandin-endoperoxide synthase 2(PTGS2), and tumor necrosis factor(TNF) might be the key proteins for the anti-inflammatory effect of Jingfang Mixture. KEGG enrichment analysis demonstrated the pathways involved TNF, nuclear factor-kappa B(NF-κB), and mitogen-activated protein kinase(MAPK). The anti-inflammatory effect of Jingfang Mixture was explored through the mouse model of urticaria. The results indicated that Jingfang Mixture could down-regulate the phosphorylation levels of p38 MAPK, extracellular regulated protein kinases(ERK1/2), and NF-κB. The present study revealed the anti-inflammatory effect of Jingfang Mixture with multi-component and multi-target characteristics, which is expected to provide a scientific basis and important support for further research, development, and application.

[Proteomic study of Jingfang Mixture on urticaria based on label-free quantitative proteomics technology].

This study aims to explore the effect of Jingfang Mixture on the protein expression of urticaria in mice and explain the mechanism of Jingfang Mixture in the treatment of urticaria. Twenty-seven male Kunming mice were randomly divided into a normal group, a model group and a Jingfang Mixture group according to body weight. Except for the normal group, mice in the model group and the Jingfang Mixture group were injected with the mixture of ovalbumin and Al(OH)_3 gel for the first immunization, and the second immunization was performed on the 10 th day to induce the urticaria model. Mice in the Jingfang Mixture group started to be administered on the 6 th day after the initial immunization, and was administered continuously for 21 days. The normal group and the model group were replaced with the same amount of purified water. Twenty-four hours after the last administration, an appropriate amount of skin was taken, and label-free quantitative proteomics technology was used to detect the differences in protein expression in skin tissue. The signaling pathways involved in the differential proteins was further analyzed. The results of proteomics indicated that seventy-six proteins were involved in the intervention of Jingfang Mixture on mice with urticaria, and the differential proteins were mainly enriched in biological process(BP), molecular function(MF), and cellular component(CC). Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis showed that the signaling pathways regulated by Jingfang Mixture mainly involved carbon metabolism, metabolic pathways, glucagon signaling pathway, glycolysis/gluconeogenesis, pentose phosphate pathway, hypoxia inducible factor-1(HIF-1) signaling pathway, purine metabolism, adherens junction, calcium signaling pathway, leukocyte transendothelial migration, and inflammatory mediator regulation of transient receptor potential(TRP) channels, which were involved in skin tissue energy metabolism and immune regulation. The findings of this study showed that the protective effect of Jingfang Mixture on mice with urticaria was closely related to the regulation of immune disorders, and the regulatory effect on immune system may be achieved through the regulation of energy metabolism by Jingfang Mixture.

[Effect of Jingfang Granules on carrageenan-induced tail thrombosis in mice based on ERK/p38 MAPK signaling pathway].

The present study explored the anti-inflammatory and anti-thrombotic mechanism of Jingfang Granules on tail thrombosis induced by carrageenan in mice. Thirty-two male ICR mice were randomly divided into a control group, a model group, a Jingfang Granules group, and a positive drug(aspirin) group, with eight mice in each group. The thrombosis model was induced by intraperitoneal injection of carrageenan(45 mg·kg~(-1)) combined with low-temperature stimulation, and the mice were treated with drugs for 7 days before modeling. Twenty-four hours after modeling, blood was detected for four blood coagulation indices in each group. The enzyme-linked immunosorbent assay(ELISA) was used to detect the activity of plasma interleukin-6(IL-6), interleukin-1ß(IL-1ß), tumor necrosis factor-α(TNF-α), and other inflammatory factors. The tails of mice in each group were cut off to observe tail lesions and measure the length of the thrombus. The protein expression and phosphorylation level of extracellular signal-regulated kinase 1/2(ERK1/2) and p38 mitogen-activated protein kinase(p38 MAPK) in spleen tissues were detected by Western blot. The results showed that dark red thrombus appeared in the tails of mice in each group. The length of the black part accounted for about 40% of the total tail in the model group. Additionally, the model group showed prolonged prothrombin time(PT), increased fibrinogen(FIB) content, and shortened activated partial thromboplastin time(APTT). Compared with the model group, the groups with drug intervention displayed shortened black parts in the tail and improved four blood coagulation indices(P<0.05). As revealed by ELISA, the expression levels of TNF-α, IL-1ß, and IL-6 in the mouse plasma were significantly up-regulated in the model group, and those in the groups with drug intervention were reduced as compared with the model group(P<0.05). As demonstrated by Western blot, the protein expression and phosphorylation levels of ERK1/2 and p38 MAPK in the spleen tissues were significantly elevated in the model group, while those in the Jingfang Granules group were down-regulated as compared with the model group with a significant difference. Jingfang Granules can inhibit tail thrombosis of mice caused by carrageenan presumedly by inhibiting the activation of ERK1/2 and p38 MAPK signaling pathways.

XCHD Inhibits C6 Cell Growth Primarily via the p53/Caspase Pathway.

The effects of XCHD on the proliferation of C6 cells and on factors associated with the microRNA-34a (miR-34a)/p53/caspase-3 signaling pathway in vitro were investigated. Methods. XCHD was purchased too much to complete the study. CCK-8 assay was used to measure the XCHD concentration, and qPCR was used to quantify miR-34a expression at the mRNA level. Apoptosis was assessed using TUNEL. Western blots were used to determine the p53, caspase-3, caspase-8, and Bcl-2 expression levels. Results. The optimal XCHD concentration and time effect for C6 cells were observed after 36 h of exposure to a concentration of 100 µg/ml XCHD. miR-34a expression increased 8 and 12 h after the addition of XCHD. The presence of XCHD decreased Bcl-2 expression but increased p53, cleaved caspase-3, Bax, and caspase-8 expression. When p53 was inhibited, miR-34a expression was unaffected by the addition of XCHD, Bcl-2 expression was low, and cleaved caspase-3, Bax, and caspase-8 expression increased. The inhibition of p53 promoted C6 cell growth when compared with C6 cells exposed to XCHD and with no inhibition of p53. Conclusions. XCHD inhibits C6 cell growth which was influenced by the p53/caspase pathway.

Isocostunolide inhibited glioma stem cell by suppression proliferation and inducing caspase dependent apoptosis.

Glioblastoma multiform (GBM) is a highly aggressive brain tumor with poor life expectancy, and glioma stem cells (GSCs) are a small population of tumor cells existed in GBM, in which GSCs response to drive GBM recurrence, invasion and contribute to the anti-cancer resistance. GSCs have been identified and developed as a therapeutic target for GBM and can be used in drugs screening. Isocostunolide is a natural sesquiterpenoid and contained abundant resource in medicinal plants, but the anti-cancer efficacies of it against GSCs are still unexplored. In this investigation, the anti-tumor activity of isocostunolide against GSCs was investigated and the result demonstrated that it inhibited the growth of GSCs (GSC-3#, GSC-12#, GSC-18#) significantly with an IC50 value of 2.80µg/ml, 2.61µg/ml, 1.07µg/ml, respectively. In further mechanism study, isocostunolide inhibited GSCs cell proliferation, induced GSCs apoptosis significantly, as well as increased the proportion of the cleavage of caspase-3. The result suggested that isocostunolide induced GSCs apoptosis via the caspase dependent apoptotic pathway. Moreover, isocostunolide damaged GSCs colony formation capacity significantly and exhibited the anti-cancer efficacy against GSCs in vitro.

A Selenium-Enriched Ziyang Green Tea Polysaccharide Induces Bax-Dependent Mitochondrial Apoptosis and Inhibits TGF-ß1-Stimulated Collagen Expression in Human Keloid Fibroblasts via NG2 Inactivation.

Keloids are fibroproliferative disorders characterized by the overabundant deposition of extracellular matrix (ECM), especially collagen and overgrowth of scar tissue in response to cutaneous injury. In this study, we isolated a selenium (Se)-containing polysaccharide (Se-ZGTP-I) from Ziyang green tea and explored its potential therapeutic effects on keloid fibroblasts formation. 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and annexin V/propidium iodide (PI) staining assays demonstrated that Se-ZGTP-I or neuron-glia 2 (NG2) short hairpin RNA (shRNA) significantly inhibited proliferation of human keloid fibroblasts via induction of apoptosis. Besides, the activation of caspase-3 and the subsequent cleavage of poly (ADP-ribose) polymerase (PARP) were observed in keloid fibroblasts following Se-ZGTP-I (200 and 400 µg/ml) or NG2 shRNA treatment. Moreover, Western blotting analysis showed that treatment of keloid fibroblasts with Se-ZGTP-I (200 and 400 µg/ml) or NG2 shRNA resulted in an increase of pro-apoptotic protein Bax expression and a decrease in expression levels of anti-apoptotic protein Bcl-2 and NG2. In addition, type I collagen biosynthesis and protein expression in keloid fibroblasts following TGF-ß1 stimulation were decreased by Se-ZGTP-I (200 and 400 µg/ml) or NG2 shRNA management. Current findings imply that Se-ZGTP-I has a therapeutic potential to intervene and prevent keloid formation and other fibrotic diseases.

[Efficacies of lactulose plus live combined Bacillus subtilis and Enterococcus faecium capsules in the treatment of functional constipation: a multicenter, randomized, double blind, controlled trial].

OBJECTIVE: To explore the efficacies of live combined Bacillus subtilis (B. subtilis) and Enterococcus faecium (E. faecium) capsules plus lactulose in the treatment of functional constipation. METHODS: A total of 216 patients fulfilling the diagnostic criteria of functional constipation (slow transit pattern) were randomly enrolled from 9 participating hospitals and allocated into treatment group and control group. The patients of treatment group received lactulose plus live combined B. subtilis and E. faecium capsules for 14 days and only took the latter during the following 14 days. The patients of control group received lactulose plus placebo for 2 weeks and then only took placebo continually for the following 2 weeks. RESULTS: A total of 216 patients were analyzed (treatment group n = 104, control group n = 112). The effective rates of 7-day treatment were 88.46% (n = 92) and 84.82% (n = 95) for treatment and control groups respectively. And those of 28-day treatment were 87.50% (n = 91) and 81.25% (n = 91)respectively. And the inter-group differences were not statistically significant (all P > 0.05). Fecal form, frequency, difficulty, urgency, distension, abdominal pain and expelling rates of barium enema were not statistically significant (all P > 0.05). Comparing the effective rates of 28-day with that of 14-day, differences were not statistically significant in A group (S = 0.5, P = 0.4795), but in B group the effective rates of 28-day were lower than that of 14-day statistically(S = 11, P = 0.0009). CONCLUSION: The regiment of live combined B. subtilis and E. faecium capsules plus lactulose offers better efficacies in the treatment of functional constipation.

[Effect of qishen huoxue granule combined with fluconazole on survival rate of mice with systemic C. albaicans infection].

OBJECTIVE: To observe the effect of Qishen Huoxue Granule (QHG) combined with Fluconazole on the survival rate of mice with systemic C. albaicans (CA) infection. METHODS: Deep CA infection model mice, with normal and low immunity, were established separately by injecting standard strain of CA via caudal vein, and were divided into 4 groups at random, treated by gastrogavage with normal saline (Group A), QHG (Group B) Fluconazole (FCZ, Group C) and QHG + FCZ (Group D) respectively, and a blank group was set up with normal mice for control. The survival time and the total survival rate in 30 days in various groups were recorded. RESULTS: For mice with normal immunity, the survival rate in Group D and C was 79% and 78% respectively, showing no difference between them (P > 0.05). But for those with low immunity, it was 36% and 7% respectively, and the survival rate significantly higher in Group D than in Group C (P < 0.05). CONCLUSION: As compared with those treated with FCZ alone, QHG combined with FCZ can raise the survival rate of the immuno-suppressed mice with systemic CA infection.