Glucagon-like peptide-1 receptor agonists （GLP-1RAs） have been widely used in diabetes and obese people in recent years， and they have also caused a series of adverse reactions， the most important of which is digestive system-related adverse reactions. The adverse reactions of the digestive system associated with GLP-1RAs involve the gastrointestinal， pancreatic， and biliary tracts； among them， nausea， vomiting， constipation， and diarrhea are the most common adverse reactions， which are the main reasons for drug withdrawal. The incidence of pancreatic and biliary system diseases is low， but there is no research evidence to exclude their association with GLP-1RAs. Tirzepatide appears on the market relatively late， and its safety still lacks sufficient real-world data. Medical staff should adopt active dietary guidance strategies for patients and strengthen medication education to help patients actively prevent and scientifically respond to adverse reactions in the digestive system.

Secretory anti-gp96 scFv fragment was expressed in Pichia pastoris to obtain a small molecule antibody that specifically recognizes heat shock protein gp96. The gp96-scFv fragment gene was synthesized and cloned to Pichia pastoris expression plasmid pPICZa-A. Pichia pastoris X33 was electroporated with the linearized recombinant expression vector, and expression of gp96-scFv fragment was induced by methanol. The His-tagged recombinant protein was then purified by affinity chromatography and analyzed with SDS-PAGE and Western blotting assays. The biological activities of recombinant gp96-scFv fragment were determined by Western blotting, Immunofluorescence, ELISA and FACS assays. The gp96-scFv fragment was expressed successfully in Pichia pastoris. About 50 mg of recombinant protein could be purified from 1 liter of the Pichia pastoris culture supernatant. Its molecular weight was about 15 kDa. The gp96-scFv fragment could specifically bind to gp96 protein by Western blotting, immunofluorescence, ELISA and FACS analyses. Pichia pastoris-expressed gp96-scFv fragment specifically recognizes gp96 protein, which could be used for Western blotting, Immunofluorescence, ELISA and FACS analyses.
Blotting, Western ; Chromatography, Affinity ; Electrophoresis, Polyacrylamide Gel ; Enzyme-Linked Immunosorbent Assay ; Membrane Glycoproteins ; immunology ; Pichia ; metabolism ; Plasmids ; Recombinant Proteins ; biosynthesis ; Single-Chain Antibodies ; biosynthesis

During virus infection, viral RNAs and mRNAs function as blueprints for viral protein synthesis and possibly as pathogen-associated molecular patterns (PAMPs) in innate immunity. Here, considering recent research progress in microRNAs (miRNAs) and competitive endogenous RNAs (ceRNAs), we speculate that viral RNAs act as sponges and can sequester endogenous miRNAs within infected cells, thus cross-regulating the stability and translational efficiency of host mRNAs with shared miRNA response elements. This cross-talk and these reciprocal interactions between viral RNAs and host mRNAs are termed "competitive viral and host RNAs" (cvhRNAs). We further provide recent experimental evidence for the existence of cvhRNAs networks in hepatitis B virus (HBV), as well as Herpesvirus saimiri (HVS), lytic murine cytomegalovirus (MCMV) and human cytomegalovirus (HCMV) infections. In addition, the cvhRNA hypothesis also predicts possible cross-regulation between host and other viruses, such as hepatitis C virus (HCV), HIV, influenza virus, human papillomaviruses (HPV). Since the interaction between miRNAs and viral RNAs also inevitably leads to repression of viral RNA function, we speculate that virus may evolve either to employ cvhRNA networks or to avoid miRNA targeting for optimal fitness within the host. CvhRNA networks may therefore play a fundamental role in the regulation of viral replication, infection establishment, and viral pathogenesis.
Animals ; DNA Viruses ; genetics ; physiology ; Host-Pathogen Interactions ; physiology ; Humans ; MicroRNAs ; metabolism ; RNA Viruses ; genetics ; physiology ; RNA, Messenger ; metabolism ; RNA, Viral ; metabolism ; Virus Diseases ; immunology ; physiopathology ; virology ; Virus Replication