Therapeutic administration of type I IFN (IFN-I) is a common treatment option for individuals suffering from hepatitis B virus (HBV) infection. IFN-I therapy, however, has a relatively low response rate in HBV-infected patients and can induce serious side-effects, limiting its clinical efficacy. There is, thus, a clear need to understand the molecular mechanisms governing the influence of IFN-I therapy in HBV treatment in order to improve patient outcomes. In this study, we explored the interactions between HBV and IFITs (IFN-induced proteins with tetratricopeptide repeats), which are classical IFN-inducible genes. Specifically, we found that HBV patients undergoing IFN-I therapy exhibited elevated expression of IFITs in their peripheral blood mononuclear cells (PBMCs). We further observed upregulation in the expressions of IFIT1, IFIT2, and IFIT3 in cells transfected with the pHBV1.3 plasmid, which yields infectious virions in hepatic cells. We additionally found that HBx, which is the only regulatory protein encoded within the HBV genome, activates NF-κB, which in turn directly drives IFIT3 transcription. When IFIT3 was overexpressed in HepG2 cells, HBV replication was enhanced. Together, these results suggest that IFIT genes may unexpectedly enhance viral replication, thus making these genes potential therapeutic targets in patients with HBV.
Rationale:
Foreign body ingestion is often encountered in clinical practice; however, intestinal perforation owing to foreign body ingestion is rare.
Patient concerns:
Here, we present the cases of 2 patients who accidentally swallowed foreign bodies and later presented with pain in the right lower abdominal quadrant.
Diagnoses:
Both patients were initially diagnosed with acute appendicitis and underwent immediate emergency laparotomy.
Interventions:
During the operation, the appendix was found to be only mildly inflamed. On transection of the appendix, the mucosa was found to be inflamed, and yellow-white exudate was noted. We, therefore, decided to explore the entire bowel. The bowel examination revealed small bowel perforations, and palpation of the adjacent bowel revealed a hard, sharp object. The object was removed through the perforation site, the perforation was repaired, and the abdomen was closed in layers.
Outcome:
The postoperative recovery, in both cases, was uneventful.
Lessons:
Patients who swallow sharp or large foreign bodies should undergo endoscopy as soon as possible to avoid intestinal perforation. Clinicians should inquire about a history of foreign body ingestion. The preoperative diagnosis of intestinal perforation secondary to foreign body ingestion requires a high degree of clinical suspicion and awareness.
Cbp/P300 interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2) is a transcription co-factor that interacts with several other transcription factors and co-factors, and serves critical roles in fundamental cell processes, including proliferation, apoptosis, differentiation, migration and autophagy. The interacting transcription factors or co-factors of CITED2 include LIM homeobox 2, transcription factor AP-2, SMAD2/3, peroxisome proliferator-activated receptor γ, oestrogen receptor, MYC, Nucleolin and p300/CBP, which regulate downstream gene expression, and serve important roles in the aforementioned fundamental cell processes. Emerging evidence has demonstrated that CITED2 serves an essential role in embryonic and adult tissue stem cells, including hematopoietic stem cells and tendon-derived stem/progenitor cells. Additionally, CITED2 has been reported to function in different types of cancer. Although the functions of CITED2 in different tissues vary depending on the interaction partner, altered CITED2 expression or altered interactions with transcription factors or co-factors result in alterations of fundamental cell processes, and may affect stem cell maintenance or cancer cell survival. The aim of this review is to summarize the molecular mechanisms of CITED2 function and how it serves a role in stem cells and different types of cancer based on the currently available literature.
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