Influenza virus contains three integral membrane proteins: haemagglutinin, neuraminidase, and matrix protein (M1 and M2). Among them, M2 protein functions as an ion channel, important for virus uncoating in endosomes of virus-infected cells and essential for virus replication. In an effort to explore potential new functions of M2 in the virus life cycle, we used yeast two-hybrid system to search for M2-associated cellular proteins. One of the positive clones was identified as human Hsp40/Hdj1, a DnaJ/Hsp40 family protein. Here, we report that both BM2 (M2 of influenza B virus) and A/M2 (M2 of influenza A virus) interacted with Hsp40 in vitro and in vivo. The region of M2-Hsp40 interaction has been mapped to the CTD1 domain of Hsp40. Hsp40 has been reported to be a regulator of PKR signaling pathway by interacting with p58(IPK) that is a cellular inhibitor of PKR. PKR is a crucial component of the host defense response against virus infection. We therefore attempted to understand the relationship among M2, Hsp40 and p58(IPK) by further experimentation. The results demonstrated that both A/M2 and BM2 are able to bind to p58(IPK) in vitro and in vivo and enhance PKR autophosphorylation probably via forming a stable complex with Hsp40 and P58(IPK), and consequently induce cell death. These results suggest that influenza virus M2 protein is involved in p58(IPK) mediated PKR regulation during influenza virus infection, therefore affecting infected-cell life cycle and virus replication.
HSP40 Heat-Shock Proteins ; genetics ; metabolism ; Humans ; Orthomyxoviridae ; genetics ; metabolism ; Phosphorylation ; Protein Binding ; genetics ; Signal Transduction ; genetics ; Two-Hybrid System Techniques ; Viral Matrix Proteins ; metabolism ; Virus Replication ; genetics ; Virus Uncoating ; eIF-2 Kinase ; metabolism

Human NUDT16 (hNUDT16) is a decapping enzyme initially identified as the human homolog to the Xenopus laevis X29. As a metalloenzyme, hNUDT16 relies on divalent cations for its cap-hydrolysis activity to remove m⁷GDP and m²²⁷GDP from RNAs. Metal also determines substrate specificity of the enzyme. So far, only U8 small nucleolar RNA (snoRNA) has been identified as the substrate of hNUDT16 in the presence of Mg²(+). Here we demonstrate that besides U8, hNUDT16 can also actively cleave the m⁷GDP cap from mRNAs in the presence of Mg²(+) or Mn²(+). We further show that hNUDT16 does not preferentially recognize U8 or mRNA substrates by our cross-inhibition and quantitative decapping assays. In addition, our mutagenesis analysis identifies several key residues involved in hydrolysis and confirms the key role of the REXXEE motif in catalysis. Finally an investigation into the subcellular localization of hNUDT16 revealed its abundance in both cytoplasm and nucleus. These findings extend the substrate spectrum of hNUDT16 beyond snoRNAs to also include mRNA, demonstrating the pleiotropic decapping activity of hNUDT16.
Amino Acid Motifs ; Biocatalysis ; Cell Nucleus ; enzymology ; Consensus Sequence ; Cytoplasm ; enzymology ; metabolism ; Guanosine Diphosphate ; metabolism ; Histidine ; metabolism ; Humans ; Hydrolysis ; Luciferases ; genetics ; Magnesium ; metabolism ; Manganese ; metabolism ; Mutagenesis ; Mutation ; Pyrophosphatases ; antagonists & inhibitors ; chemistry ; genetics ; metabolism ; RNA Caps ; chemistry ; metabolism ; pharmacology ; RNA, Small Nucleolar ; chemistry ; metabolism ; pharmacology

The aim of the present study is to explore the association between abdominal obesity and chronic kidney disease (CKD) through a systematic review of published studies. Databases including Wanfang data, CNKI, VIP, CBM, Cochrane Library, PubMed, Web of science and Embase were searched up to July 2021 to collect longitudinal studies published in Chinese and English on the association between abdominal obesity and CKD. In order to avoid omission, reference lists of related articles were also checked manually. After literature selection, data were extracted and study quality was evaluated by the Newcastle-Ottawa scale. Statistical analysis of this study was conducted using Stata 11.0 software. Finally, five studies were included in this study. The results showed that abdominal obesity defined by waist circumference was not associated with CKD (OR=1.17,95% CI:0.93-1.48). According to the results of subgroup analyses, whether adjusted body mass index might be part of the reason of heterogeneity. Based on results of this study, the association between abdominal obesity defined by waist hip ratio and CKD, as well as the association between abdominal obesity and CKD in different genders, remains unknown. In conclusion, abdominal obesity might not be associated with incident CKD. However, more studies are needed in the future to explore this association.

Objective:To retrieve and summarize the evidence for postoperative observation time and bed rest time in patients undergoing percutaneous renal biopsy, so as to provide evidence-based basis for postoperative nursing of patients undergoing percutaneous renal biopsy.Methods:Using search terms such as "renal biopsy" and "renal puncture", based on the "6S" evidence resource pyramid model, evidence on postoperative observation time and bed rest time of percutaneous renal biopsy patients, including guidelines, best practice information books, evidence summaries, systematic reviews, expert consensus, and original research, was systematically searched on various guideline websites, evidence-based databases, original research databases, and professional association websites both domestically and internationally. The search period was from database establishment to July 1, 2023. After independent evaluation of the included literature by two researchers, evidence was extracted and summarized from the literature that met the quality standards.Results:A total of nine articles were included, including one guideline, five cohort studies, and three cross-sectional studies. This study summarized six best pieces of evidence from two aspects, namely postoperative observation time and postoperative bed rest time. For patients with low risk of complications after percutaneous renal biopsy, it was recommended to observe for 6 to 8 hours after surgery, but further shortening the observation time to 4 to 5 hours may also be safe and sufficient. For patients with high risk of complications after percutaneous renal biopsy, those living far from the hospital, those living alone, or those who may experience significant psychological stress after biopsy, it was recommended to extend the observation time to up to 24 hours.Conclusions:Based on existing evidence, it seems feasible to shorten the bed rest time after percutaneous renal biopsy. A large amount of high-quality research is still needed to explore the optimal postoperative bed rest time.