C6orf15 promotes liver metastasis via WNT/ß-catenin signalling in colorectal cancer.

BACKGROUND: Colon cancer ranks third among global tumours and second in cancer-related mortality, prompting an urgent need to explore new therapeutic targets. C6orf15 is a novel gene that has been reported only in Sjogren's syndrome and systemic lupus erythematosus patients. We found a close correlation between increased C6orf15 expression and the occurrence of colon cancer. The aim of this study was to explore the potential of C6orf15 as a therapeutic target for colorectal cancer. METHOD: RNA-seq differential expression analysis of the TCGA database was performed using the R package 'limma.' The correlation between target genes and survival as well as tumour analysis was analysed using GEPIA. Western blot and PCR were used to assess C6orf15 expression in colorectal cancer tissue samples. Immunofluorescence and immunohistochemistry were used to assess C6orf15 subcellular localization and tissue expression. The role of C6orf15 in liver metastasis progression was investigated via a mouse spleen infection liver metastasis model. The association of C6orf15 with signalling pathways was assessed using the GSEA-Hallmark database. Immunohistochemistry (IHC), qPCR and western blotting were performed to assess the expression of related mRNAs or proteins. Biological characteristics were evaluated through cell migration assays, MTT assays, and Seahorse XF96 analysis to monitor fatty acid metabolism. RESULTS: C6orf15 was significantly associated with liver metastasis and survival in CRC patients as determined by the bioinformatic analysis and further verified by immunohistochemistry (IHC), qPCR and western blot results. The upregulation of C6orf15 expression in CRC cells can promote the nuclear translocation of ß-catenin and cause an increase in downstream transcription. This leads to changes in the epithelial-mesenchymal transition (EMT) and alterations in fatty acid metabolism, which together promote liver metastasis of CRC. CONCLUSION: Our study identified C6orf15 as a marker of liver metastasis in CRC. C6orf15 can activate the WNT/ß-catenin signalling pathway to promote EMT and fatty acid metabolism in CRC.

Switchable surface and loading/release of target molecules in hierarchically porous PLA nonwovens based on shape memory effect.

In this work, hierarchically porous PLA (polylactic acid) shape memory nonwovens were prepared by electrospinning its blend solution with PEO (polyethylene oxide) and subsequent water etching. Based on shape memory effect resulting from tiny crystals and the amorphous matrix of PLA, the switch between compact and porous surfaces has been achieved via cyclical hot-pressing and recovery in a hot water bath. After hot-pressing, the disappearance of hierarchical pores contributes to compact surface, enabling embedding of the target molecule in PLA nonwoven (i.e., CLOSE state). Upon exposure to heat, PLA nonwoven recovers to its permanent shape and exhibits a porous surface, providing a penetrative diffusion pathway for small molecules (i.e., OPEN state). The hierarchically porous structure and shape memory effect endow PLA nonwoven with the capability of rapid release. Our results provide a good candidate for some potential applications, such as temperature-controlled quick-release of catalysts and drugs.

Antibacterial, antidiarrheal, anti-inflammatory and analgesic activities of compound Shikuqin powder.

The MIC and MBC values of Shikuqin (SKQ) against 5 bacteria that readily cause diarrhea were measured by the broth micro dilution method. The castor oil-induced diarrhea method was used to evaluate the antidiarrheal activity. Intestinal transit and gastric emptying were also evaluated with normal and neostigmine-induced intestinal transit in rodents. In addition, the antidiarrheal activity of SKQ was assessed in vivo with isolated rabbit ileum. Xylene-induced ear edema was used to evaluate the anti-inflammatory activities in mice, while hot plate and writhing tests were performed to assess the analgesic effects. Senna decoction (0.3g/mL) was administered intragastrically to induce a rat model of diarrhea. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect AQP4 mRNA, and Western blot was performed to quantify the protein level of AQP4 in the colon. SKQ exhibits remarkable antidiarrheal, anti-inflammatory and analgesic effects in the gastrointestinal tract disorders, and can therefore be developed as a promising antidiarrheal agent.

Protective effects and immunomodulation on piglets infected with rotavirus following resveratrol supplementation.

Rotavirus (RV), belonging to Reoviridae family, is the leading cause of acute severe viral diarrhea in children (under 5 years old) and infant animals worldwide. Although vaccines are commonly used to prevent infection, episodes of diarrhea caused by RV frequently occur. Thus, this study was conducted to determine whether resveratrol had protective effects against RV infection in piglets. Following pretreatment with resveratrol dry suspension through adding into the basal diet for 3 weeks, the piglets were orally challenged with RV. We found that resveratrol could alleviate diarrhea induced by RV infection. Resveratrol-treatment inhibited the TNF-α production, indicating that the anti-RV activity of resveratrol may be achieved by reducing the inflammatory response. The IFN-γ level was elevated in 10mg/kg/d resveratrol-treated group and 30mg/kg/d resveratrol-treated group after RV infection. The ratios of CD4+/CD8+ in resveratrol-treated groups were the same as that in mock infected group, suggesting that resveratrol could maintain the immune function in RV-infected piglets. It was found that resveratrol could alleviate diarrhea induced by RV infection. These results revealed that resveratrol dry suspension could be a new control measure for RV infection.

Acute and subchronic toxicity and the evaluation of safety pharmacology of Chinese herbal compound preparation "Shikuqin".

"Shikuqin" (SKQ) powder consists of three Chinese herbs: Punica granatum L, Sophora flavescens Ait, and Fraxinus rhynchophylla Hance. SKQ has been used for the treatment of diarrhea. In order to provide a comprehensive understanding of toxicity, the acute and sub-chronic toxicity and safety pharmacology of SKQ were evaluated in the present study. The result of the acute toxicity revealed that the LD50 of the valve was 28,379mg/kg.b.w, which was more than 5,000 mg/kg b.w. The 30-day sub-chronic toxicity test results revealed that compared with the control group, the clinical signs, hematology parameters and body weight of rats in each group had no significant differences. The viscera coefficient and histopathological examination results revealed that the SKQ powder could cause kidney and liver damage. In the safety pharmacology test, SKQ did not exhibit any toxicity to the central nervous system, cardiovascular system and respiratory system. In conclusion, SKQ powder could be considered safe for veterinary use.

In Vivo Evaluation of Galla chinensis Solution in the Topical Treatment of Dermatophytosis.

AIM: Dermatophytosis is one of the main fungal diseases in humans and animals all over the world. Galla chinensis, a traditional medicine, has various pharmacological effects. The goal of this study was to evaluate the treatment effect of Galla chinensis solution (GCS) on dermatophytosis-infected dogs (Microsporum canis, Microsporum gypseum, and Trichophyton mentagrophytes, resp.). METHODS: The treatment effects of GCS were evaluated by mycological cure rates and clinical score comprised of three indices, including inflammation, hair loss, and lesion scale. RESULTS: The results showed that, in the three models of dermatophytosis, GCS significantly (P < 0.05) improved skin lesions and fungal eradication. GCS (10% and 5%) had higher efficacy compared to the positive control (Tujingpi Tincture). The fungal eradication efficacy exceeds 85% after treatment with GCS (10%, 5%, and 2.5%) on day 14. CONCLUSION: The GCS has antidermatophytosis effect in dogs, which may be a candidate drug for the treatment of dermatophytosis.

Effect of Modified Pulsatilla Powder on Enterotoxigenic Escherichia coli O101-Induced Diarrhea in Mice.

MPP can be effective in the treatment of E. coli O101-induced diarrhea in mice. MPP can improve the weight loss caused by diarrhea, increase spleen and thymus indices, and reduce the diarrhea index. MPP can reduce the number of WBC, regulate the level of cytokines, and regulate the intestinal microbial flora. These data suggest that MPP is a promising candidate for treatment of E. coli-induced diarrhea in humans and animals.

iTRAQ-based quantitative proteomic analysis reveals multiple effects of Emodin to Haemophilus parasuis.

Haemophilus parasuis, a symbiotic bacteria of upper respiratory tract of swine, is the etiological agent of Glässer's disease, which is characterized by fibrinous polyserositis. Emodin, exhibits antibacterial activity against H. parasuis, yet the action mode has not been fully understood. In present study, isobaric tag for relative and absolute quantification (iTRAQ) method was applied to analyze the global protein alteration of H. parasuis in response to 16µg/mL Emodin. In total, 338 proteins exhibiting significant differential expressions were identified. It was speculated that, through application of bioinformatics analysis to theses differentially expressed proteins, Emodin mainly inhibited some key proteins expression of ABC transport system, carbohydrate metabolism pathway and bacterial cell division by inhibiting the ribosome synthesis, resulting in the growth inhibition of H. parasuis. Remarkably, nine virulence-associated proteins were detected differently expressed, further experiments revealed that after treatment with Emodin, H. parasuis could be inhibited to adhere to and invade into porcine kidney epithelial cells (PK-15 line) and exhibited increased sensitivity to serum complement in a concentration-dependent manner. Phagocytosis assay showed Emodin also could enhance phagocytic activity of porcine alveolar macrophages PAM to H. parasuis. These results indicated that Emodin also can attenuate virulence of H. parasuis and reduce infection. BIOLOGICAL SIGNIFICANCE: The Glässer's disease caused by H. parasuis has become a typical bacterial disease and cause serious economic loss to the swine industry around the world. Antibiotics are extensively used to control the infection, but increasing antibiotic resistance has been a severe problem. Hence, novel treatment agents are needed. So far, few antibacterial agents were reported that could control H. parasuis infection. In the present study, the state-of-the-art quantitative proteomic technology was applied to uncover underlying action mechanism of Emodin. This study extends understanding of antibacterial effect of Emodin to H. parasuis at molecular level and provides useful information for further investigations. Moreover, our results provide theoretical foundation for the practical application of Emodin.

Theoretical study of photodissociation dynamics on the lowest-lying Rydberg state of ketene.

In the present study, an attempt is made to reveal the main mechanism of photodissociation on the lowest-lying Rydberg state (1)B(1) of ketene, referred to as the second singlet excited state S(2), by means of the complete active space self-consistent field and the second-order multiconfigurational perturbation theory methods. The located S(2)S(1)T(1) three-surface intersection plays an important role in the dissociation process. It is shown that the intersection permits an efficient internal conversion from S(2) to S(1) state, but prohibits the intersystem crossing from S(2) to T(1) state because of the small spin-orbital coupling value of 0.136 cm(-1). The main photodissociation process could be described as follows: after one photon absorption to the S(2) state, ketene preferentially relaxes to the minimum S(2)C(2v), and undergoes a transition state S(2)TS with small potential barrier along the C(s)-I (out-of-plane bent) symmetry, and passes through the S(2)S(1)T(1) intersection to reach S(1) surface, then arrives at the transition state S(1)TS along the minimum energy path. As is well known, S(1)-->S(0) internal conversion around the Franck-Condon region is expected to be very efficient, and eventually the hot S(0) molecule has accumulated enough energy to yield the CH(2) (a (1)A(1)) and CO (X (1)Sigma(+)) products.

Si2CN: a stable nitrogen-containing radical with cyclic ground state.

The structures and isomerization of Si(2)CN species are explored at density functional theory and ab initio levels. Fourteen minimum isomers are located connected by 23 interconversion transition states. At the coupled-cluster single double (CCSD)(T)/6-311+G(2df)//QCISD/6-311G(d) +zero-point vibrational energies level, the thermodynamically most stable isomer is a four-membered ring form cSiSiCN 1 with Si-C cross bonding. Isomer 1 has very strong C-N multiple bonding characters, formally suggestive of a radical adduct between Si(2) and CN. Such a highly pi-electron localization can effectively stabilize isomer 1 to be the ground state. The second low-lying isomer is a linear form SiCNSi 5 (9.8 kcal/mol above 1) with resonating structure among [Si=C-*N=Si], *[Si=C=N=Si], and [Si=C=N-Si*]* with the former two bearing more weight. The species 1 and 5 have very high kinetic stability stabilized by the barriers of at least 25 kcal/mol. Both isomers should be experimentally or astrophysically observable. In light of the fact that no cyclic nitrogen-containing species have been detected in space, the cyclic species 1 could be a very promising candidate. The calculated results are compared to those of the analogous molecules C(3)N, C(3)P, SiC(2)N, and SiC(2)P. Implications of Si(2)CN in interstellar and N-doped SiC vaporization processes are also discussed.