A bibliometric analysis of immune-related adverse events in cancer patients and a meta-analysis of immune-related adverse events in patients with hepatocellular carcinoma.

Background and Objectives: Immunotherapy has become the standard treatment for hepatocellular carcinoma (HCC), but it carries a risk of immune-related adverse events (irAEs) that can be life-threatening. This study employs bibliometric analysis to understand global scientific research on irAEs in cancer, focusing on characteristics and areas of interest. Additionally, a meta-analysis provides a comprehensive overview of irAEs in HCC patients receiving immune checkpoint inhibitor (ICI)-based therapies. Methods: We conducted a thorough search of Web of Science Core Collection (WoSCC) publications from 1999 to 2022. R and VOSviewer software were used for analysis. A meta-analysis was performed using data from PubMed, Embase, and the Cochrane Library databases up to March 22, 2022. Trials with HCC patients reporting irAE incidence were included. Quality assessment followed Cochrane risk of bias, Newcastle-Ottawa Scale (NOS), and Methodological Index for Non-Randomized Studies (MINORS). We used random-effects or fixed-effects models based on I2 values. Primary outcomes included any-grade irAEs and grade ≥ 3 irAEs. This review and meta-analysis are registered in PROSPERO as CRD42022318885. Results: In bibliometric analysis, we included 2946 papers, showing a consistent rise in annual publications on irAEs in cancer research. Frequent keywords were "nivolumab", "immune checkpoint inhibitor", and "immune-related adverse event". "Hepatocellular carcinoma" emerged as a prominent research focus linked to irAEs. We conducted a comprehensive meta-analysis on irAE incidence in HCC patients, including 29 studies. The overall incidence of any-grade irAEs was 61.0% (95% CI 38.5%-81.3%), and grade ≥ 3 irAEs was 13.2% (95% CI 7.9%-19.6%). Treatment-related mortality occurred in 3.1% (95% CI 0.8%-6.3%), with treatment discontinuation at 10.7% (95% CI 6.3%-16.0%). Reactive cutaneous capillary endothelial proliferation (RCCEP) was the most common any-grade irAE, while elevated aspartate aminotransferase (AST) was the most common grade ≥ 3 irAE. Treatment strategies were independently associated with specific irAEs, as indicated by multivariable analysis. Conclusion: This study provides valuable insights into the current research landscape of irAEs in cancer and ofers a comprehensive overview of irAEs in HCC patients undergoing ICI-based therapy. The relatively high incidence of irAEs and their association with treatment strategies emphasize the need for careful management by clinicians when treating HCC patients. These findings offer significant guidance for optimizing care and treatment for HCC patients.

Development and characterization of an antibody that recognizes influenza virus N1 neuraminidases.

Influenza A viruses (IAVs) continue to pose a huge threat to public health, and their prevention and treatment remain major international issues. Neuraminidase (NA) is the second most abundant surface glycoprotein on influenza viruses, and antibodies to NA have been shown to be effective against influenza infection. In this study, we generated a monoclonal antibody (mAb), named FNA1, directed toward N1 NAs. FNA1 reacted with H1N1 and H5N1 NA, but failed to react with the NA proteins of H3N2 and H7N9. In vitro, FNA1 displayed potent antiviral activity that mediated both NA inhibition (NI) and blocking of pseudovirus release. Moreover, residues 219, 254, 358, and 388 in the NA protein were critical for FNA1 binding to H1N1 NA. However, further validation is necessary to confirm whether FNA1 mAb is indeed a good inhibitor against NA for application against H1N1 and H5N1 viruses.

Serine hydroxymethyltransferase 2 knockdown induces apoptosis in ccRCC by causing lysosomal membrane permeabilization via metabolic reprogramming.

Serine hydroxymethyltransferase 2 (SHMT2) plays an important role in converting serine to glycine and supplying carbon to one-carbon metabolism to sustain cancer cell proliferation. However, the expression, function, and underlying mechanisms of SHMT2 in clear cell renal cell carcinoma (ccRCC) remain largely unknown. In this study, we demonstrated that SHMT2 was upregulated in ccRCC tissues compared with controls and associated with patient survival. SHMT2 knockdown inhibited proliferation, migration, and invasion in ccRCC cells. Overexpression of SHMT2 promoted tumor progression. Mechanistically, SHMT2 depletion disrupted one-carbon metabolism, increased reactive oxygen species (ROS) levels, and decreased ATP levels via metabolic reprogramming, which destroyed cell homeostasis. The SHMT2 knockdown-induced stress activated autophagy. A mass of autophagosomes fused with lysosomes, resulting in lysosomal membrane permeabilization (LMP) and leakage of lysosomal contents into the cytoplasm, which eventually led to apoptosis. Our work reveals that SHMT2 functions as an oncogenic gene to promote ccRCC progression. SHMT2 depletion induces apoptosis by causing LMP through excessive activation of the autophagy-lysosome pathway via metabolic reprogramming.