Exploring the autophagy-related pathogenesis of active ulcerative colitis.

BACKGROUND: The pathogenesis of ulcerative colitis (UC) is complex, and recent therapeutic advances remain unable to fully alleviate the condition. AIM: To inform the development of novel UC treatments, bioinformatics was used to explore the autophagy-related pathogenesis associated with the active phase of UC. METHODS: The GEO database was searched for UC-related datasets that included healthy controls who met the screening criteria. Differential analysis was conducted to obtain differentially expressed genes (DEGs). Autophagy-related targets were collected and intersected with the DEGs to identiy differentially expressed autophagy-related genes (DEARGs) associated with active UC. DEARGs were then subjected to KEGG, GO, and DisGeNET disease enrichment analyses using R software. Differential analysis of immune infiltrating cells was performed using the CiberSort algorithm. The least absolute shrinkage and selection operator algorithm and protein-protein interaction network were used to narrow down the DEARGs, and the top five targets in the Dgree ranking were designated as core targets. RESULTS: A total of 4822 DEGs were obtained, of which 58 were classified as DEARGs. SERPINA1, BAG3, HSPA5, CASP1, and CX3CL1 were identified as core targets. GO enrichment analysis revealed that DEARGs were primarily enriched in processes related to autophagy regulation and macroautophagy. KEGG enrichment analysis showed that DEARGs were predominantly associated with NOD-like receptor signaling and other signaling pathways. Disease enrichment analysis indicated that DEARGs were significantly linked to diseases such as malignant glioma and middle cerebral artery occlusion. Immune infiltration analysis demonstrated a higher presence of immune cells like activated memory CD4 T cells and follicular helper T cells in active UC patients than in healthy controls. CONCLUSION: Autophagy is closely related to the active phase of UC and the potential targets obtained from the analysis in this study may provide new insight into the treatment of active UC patients.

Catalytic efficiency and thermal stability promotion of the cassava linamarase with multiple mutations for better cyanogenic glycoside degradation.

In our previous study, we found that cassava cyanogenic glycosides had an acute health risk. Therefore, to solve this problem, the improvement of specific degradation of cyanogenic glycosides of cassava linamarase during processing is the key. In this study, the catalytic activity and thermal stability of enzymes were screened before investigating the degradation efficiency of cyanogenic glycosides with a cassava linamarase mutant K263P-T53F-S366R-V335C-F339C (CASmut) -controlled technique. The CASmut was obtained with the optimum temperature of 45 °C, which was improved by 10 °C. The specific activity of CASmut was 85.1 ± 4.6 U/mg, which was 2.02 times higher than that of the wild type. Molecular dynamics simulation analysis and flexible docking showed there were more hydrogen bonding interactions at the pocket, and the aliphatic glycoside of the linamarin was partially surrounded by hydrophobic residues. The optimum conditions of degradation reactions was screened with CASmut addition of 47 mg/L at 45 °C, pH 6.0. The CASmut combined with ultrasonication improved the degradation from 478.2 ± 10.4 mg/kg to 86.7 ± 7.4 mg/kg. Those results indicating the great potential of CASmut in applying in the cassava food or cyanogenic food. However, challenges in terms of the catalytic mechanism research is worthy of being noticed in further studies.

Nanoemulsion Co-Loaded with XIAP siRNA and Gambogic Acid for Inhalation Therapy of Lung Cancer.

Lung cancer is a leading cause of cancer mortality worldwide, with a 5-year survival rate of less than 20%. Gambogic acid (GA) is a naturally occurring and potent anticancer agent that destroys tumor cells through multiple mechanisms. According to the literature, one of the most potent inhibitors of caspases and apoptosis currently known is the X-linked Inhibitor of Apoptosis Protein (XIAP). It is highly expressed in various malignancies but has little or no expression in normal cells, making it an attractive target for cancer treatment. Here we report the development of a chitosan (CS)-based cationic nanoemulsion-based pulmonary delivery (p.d.) system for the co-delivery of antineoplastic drugs (GA) and anti-XIAP small interfering RNA (siRNA). The results showed that the chitosan-modified cationic nanoemulsions could effectively encapsulate gambogic acid as well as protect siRNA against degradation. The apoptosis analysis confirmed that the cationic nanoemulsions could induce more apoptosis in the A549 cell line. In addition, most drugs and siRNAs have a long residence time in the lungs through pulmonary delivery and show greater therapeutic effects compared to systemic administration. In summary, this work demonstrates the applicability of cationic nanoemulsions for combined cancer therapy and as a promising approach for the treatment of lung cancer.

Pulmonary delivery of liposomes co-loaded with SN38 prodrug and curcumin for the treatment of lung cancer.

A co-delivery system of SN38 (7-ethyl-10-hydroxyl camptothecin) prodrug and CUR (curcumin) was designed for the treatment of lung cancer by pulmonary delivery. SN38 was linked to cell-penetrating peptide (CPP) TAT via a polyethylene glycol (PEG) linker to form the SN38 prodrug (TAT-PEG-SN38). Liposomes co-loaded with amphiphilic TAT-PEG-SN38 and curcumin (Lip-TAT-PEG-SN38/CUR) were successfully prepared by a microfluidic method for the treatment of lung cancer via pulmonary delivery. Lip-TAT-PEG-SN38/CUR showed nanometer-sized sphericity and a particle size of 171.21 nm. Besides, Lip-TAT-PEG-SN38/CUR exhibited enhanced antiproliferative effect, increased cell apoptosis induction and improved cell cycle arrest compared to the single agents in vitro. The combination induced significant tumor inhibition in a BALB/c mouse lung cancer model. These results indicated that our SN38 prodrug and curcumin co-delivery system was a promising candidate for lung cancer treatment.

Deep learning for aspect-based sentiment analysis: a review.

User-generated content on various Internet platforms is growing explosively, and contains valuable information that helps decision-making. However, extracting this information accurately is still a challenge since there are massive amounts of data. Thereinto, sentiment analysis solves this problem by identifying people's sentiments towards the opinion target. This article aims to provide an overview of deep learning for aspect-based sentiment analysis. Firstly, we give a brief introduction to the aspect-based sentiment analysis (ABSA) task. Then, we present the overall framework of the ABSA task from two different perspectives: significant subtasks and the task modeling process. Finally, challenges are proposed and summarized in the field of sentiment analysis, especially in the domain of aspect-based sentiment analysis. In addition, ABSA task also takes the relations between various objects into consideration, which is rarely discussed in the previous work.

Nanoparticles as Drug Delivery Systems of RNAi in Cancer Therapy.

RNA interference (RNAi) can mediate gene-silencing by knocking down the expression of a target gene via cellular machinery with much higher efficiency in contrast to other antisense-based approaches which represents an emerging therapeutic strategy for combating cancer. Distinct characters of nanoparticles, such as distinctive size, are fundamental for the efficient delivery of RNAi therapeutics, allowing for higher targeting and safety. In this review, we present the mechanism of RNAi and briefly describe the hurdles and concerns of RNAi as a cancer treatment approach in systemic delivery. Furthermore, the current nanovectors for effective tumor delivery of RNAi therapeutics are classified, and the characteristics of different nanocarriers are summarized.

Advanced schistosomiasis reappeared after curing seemingly being cured for over 20 years and without known history of reexposure to Schistosoma japonicum.

Schistosomiasis is an intravascular disease caused by parasitic trematode worms of the genus Schistosoma. It is estimated that more than 200 million people are infected in the world, and 800 million are at risk of infection. The main lesions are due to eggs trapping in tissue which can lead a series of pathogenic effect relative to immune response. Therefore, killing and eradicating eggs in tissue is often the target to treat schistosomiasis. Here, we report 75 patients who being cured for over 20 years developed into advanced schistosomiasis. A total of 90 patients with a diagnosis of schistosomiasis in various periods were enrolled. Of them, all patients have liver fibrosis, splenectomy was performed in 48.0 %, 42.7 % have splenomegaly, and 30.0 % have portal hypertension. No patients were infected with HBV. Moreover, all patients have not been to Schistosoma-endemic regions. Our results showed that there are other factors leading to schistosomiasis progress besides eggs as well as Schistosoma mansoni.