The emerging roles of IFIT3 in antiviral innate immunity and cellular biology.

The interferon-inducible protein with tetrapeptide repeats 3 (IFIT3) is one of the most important members in both the IFIT family and interferon-stimulated genes family. IFIT3 has typical features of the IFIT family in terms of gene and protein structures, and is able to be activated through the classical PRRs-IFN-JAK/STAT pathway. A variety of viruses can induce the expression of IFIT3, which in turn inhibits the replication of viruses, with the underlying mechanism showing its crucial role in antiviral innate immunity. Emerging studies have also identified that IFIT3 is involved in cellular biology changes, including cell proliferation, apoptosis, differentiation, and cancer development. In this review, we summarize the characteristics of IFIT3 with respect to molecular structure and regulatory pathways, highlighting the role of IFIT3 in antiviral innate immunity, as well as its diverse biological roles. We also discuss the potential of IFIT3 as a biomarker in disease diagnosis and therapy.

The implications of cell-free DNAs derived from tumor viruses as biomarkers of associated cancers.

Cancer is still ranked as a leading cause of death according to estimates from the World Health Organization (WHO) and the strong link between tumor viruses and human cancers have been proved for almost six decades. Cell-free DNA (cfDNA) has drawn enormous attention for its dynamic, instant, and noninvasive advantages as one popular type of cancer biomarker. cfDNAs are mainly released from apoptotic cells and exosomes released from cancer cells, including those infected with viruses. Although cfDNAs are present at low concentrations in peripheral blood, they can reflect tumor load with high sensitivity. Considering the relevance of the tumor viruses to the associated cancers, cfDNAs derived from viruses may serve as good biomarkers for the early screening, diagnosis, and treatment monitoring. In this review, we summarize the methods and newly developed analytic techniques for the detection of cfDNAs from different body fluids, and discuss the implications of cfDNAs derived from different tumor viruses in the detection and treatment monitoring of virus-associated cancers. A better understanding of cfDNAs derived from tumor viruses may help formulate novel antitumoral strategies to decrease the burden of cancers that attributed to viruses.

Synthesis of direct ß-to-ß linked porphyrin arrays with large electronic interactions: branched and cyclic oligomers.

Direct ß-to-ß linked branched and cyclic porphyrin trimers and pentamers have been synthesized by the Suzuki-Miyaura coupling of ß-borylporphyrins and ß-bromoporphyrins. The cyclic porphyrin trimer, the smallest directly linked cyclic porphyrin wheel to date, and its twined pentamer, exhibit small electrochemical HOMO-LUMO gaps, broad nonsplit Soret bands, and red-shifted Q-bands, thus indicating large electronic interactions between the constituent porphyrin units.

The Antitumor Effects of α-Linolenic Acid.

α-linolenic acid (ALA), which is a member of the n-3 polyunsaturated fatty acid (n-3 PUFA) family, has often been ignored due to a lack of information. ALA has gradually attracted increased attention due to its nutritional and medicinal advantages. Studies have shown that ALA exerts beneficial effects on a variety of diseases, including cancer. In this review, we summarize the antitumor effects of ALA in the context of cell biology, including the inhibition of proliferation, the induction of apoptosis, the inhibition of metastasis and angiogenesis, and antioxidant effects. In addition, studies have shown that ALA can be used as a drug carrier or exert positive clinical effects when combined with drugs. Therefore, the use of ALA in clinical treatments is very promising and valuable.

Insight into LncRNA- and CircRNA-Mediated CeRNAs: Regulatory Network and Implications in Nasopharyngeal Carcinoma-A Narrative Literature Review.

Nasopharyngeal carcinoma (NPC) is a kind of head-and-neck malignant tumor, and distant metastasis treatment resistance is the leading cause of patient death. In-depth understanding of NPC progression and treatment failure remains to be explored. Long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) are noncoding RNAs that play key regulatory role in shaping tumor cell activities. Recent studies have revealed that lncRNA and circRNA function as competitive endogenous RNAs (ceRNAs) by regulating the posttranscriptional expression of genes as miRNA baits. The imbalanced ceRNA networks derived from lncRNA/circRNA-miRNA-mRNA interaction are widely found to contribute to NPC development. Herein, we summarize typical examples of lncRNA/circRNA-associated ceRNAs in recent years, which involved the potential molecular mechanisms in the regulation of proliferation, apoptosis, treatment resistance and metastasis of NPC, and discuss their potential clinical significance in the prognosis and treatment of NPC. Interpreting the involvement of ceRNAs networks will provide new insight into the pathogenesis and treatment strategies of NPC. However, ceRNA regulatory mechanism has some limitations currently. Screening the most effective ceRNA targets and the clinical application of ceRNA still has many challenges.

Plasma Exosomal Proteomic Pattern of Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis.

Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a life-threatening syndrome, which is caused by EBV infection that is usually refractory to treatment and shows relapse. The development of new biomarkers for the early diagnosis and clinical treatment of EBV-HLH is urgently needed. Exosomes have been shown to mediate various biological processes and are ideal non-invasive biomarkers. Here, we present the differential plasma exosomal proteome of a patient with EBV-HLH before vs. during treatment and with that of his healthy twin brother. A tandem mass tag-labeled LC-MS technique was employed for proteomic detection. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that differential proteomic profiles were related to virus infection, coagulopathy, nervous system dysfunction, imbalance of immune response, and abnormal liver function. The candidate biomarkers were first identified in the patient's plasma exosomes at different treatment and follow-up time points. Then, 14 additional EBV-HLH exosome samples were used to verify six differentially expressed proteins. The upregulation of C-reactive protein, moesin, galectin three-binding protein, and heat shock cognate 71 kDa protein and the downregulation of plasminogen and fibronectin 1 could serve as potential biomarkers of EBV-HLH. This plasma exosomal proteomic analysis provides new insights into the diagnostic and therapeutic biomarkers of EBV-HLH.

Corrigendum: Plasma Exosomal Proteomic Pattern of Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis.

[This corrects the article DOI: 10.3389/fmicb.2022.821311.].

Cellular Deubiquitylating Enzyme: A Regulatory Factor of Antiviral Innate Immunity.

Deubiquitylating enzymes (DUBs) are proteases that crack the ubiquitin code from ubiquitylated substrates to reverse the fate of substrate proteins. Recently, DUBs have been found to mediate various cellular biological functions, including antiviral innate immune response mediated by pattern-recognition receptors (PRRs) and NLR Family pyrin domain containing 3 (NLRP3) inflammasomes. So far, many DUBs have been identified to exert a distinct function in fine-tuning antiviral innate immunity and are utilized by viruses for immune evasion. Here, the recent advances in the regulation of antiviral responses by DUBs are reviewed. We also discussed the DUBs-mediated interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and antiviral innate immunity. The understanding of the mechanisms on antiviral innate immunity regulated by DUBs may provide therapeutic opportunities for viral infection.

IGFBP7-AS1 is a p53-responsive long noncoding RNA downregulated by Epstein-Barr virus that contributes to viral tumorigenesis.

Epstein-Barr virus (EBV) is closely related to the development of several malignancies, such as B-cell lymphoma (B-CL), by the mechanism through which these malignancies develop remains largely unknown. We previously observed downregulation of the long noncoding RNA (lncRNA) IGFBP7-AS1 in response to EBV infection. However, the role of IGFBP7-AS1 in EBV-associated cancers has not been clarified. Here, we found that expression of IGFBP7-AS1, as well as its sense gene IGFBP7, is decreased in EBV-positive B-CL cells and clinical tissues. IGFBP7-AS1 stabilizes IGFBP7 mRNA by forming a duplex based on their overlapping regions. The tumour suppressor p53 transcriptionally activates IGFBP7-AS1 expression by binding to the promoter region of the lncRNA gene. The IGFBP7-AS1 expression is able to be rescued in EBV-positive cells in wild-type (wt) p53-dependent manner. IGFBP7-AS1 inhibits the proliferation and promotes the apoptosis of B-CL cells. Moreover, tumorigenic properties due to the depletion of IGFBP7-AS1 were restored by exogenous expression of IGFBP7 or wt-p53. Furthermore, the functional p53/IGFBP7-AS1/IGFBP7 axis facilitates apoptosis by suppressing the production and secretion of the NPPB signal peptide and further regulating the cGMP-PKG signalling pathway. This study demonstrates that EBV promotes tumorigenesis, particularly in B-CL progression, by downregulating the novel p53-responsive lncRNA IGFBP7-AS1.

meso-to-meso 2,5-Pyrrolylene bridged zig-zag porphyrin arrays.

meso-to-meso 2,5-Pyrrolylene bridged zig-zag porphyrin arrays have been synthesized via a stepwise Suzuki-Miyaura cross coupling reaction. Both the dimeric and trimeric structures of ZnII porphyrin were confirmed by X-ray diffraction analysis. DFT calculations indicate that the porphyrin oligomers are all in zig-zag conformations. The UV/Vis absorption and emission spectra of these porphyrin oligomers were red-shifted as the number of their porphyrin units increased.

Female sex worker social networks and STI/HIV prevention in South China.

BACKGROUND: Reducing harm associated with selling and purchasing sex is an important public health priority in China, yet there are few examples of sustainable, successful programs to promote sexual health among female sex workers. The limited civil society and scope of nongovernmental organizations circumscribe the local capacity of female sex workers to collectively organize, advocate for their rights, and implement STI/HIV prevention programs. The purpose of this study was to examine social networks among low-income female sex workers in South China to determine their potential for sexual health promotion. METHODS/PRINCIPAL FINDINGS: Semi-structured interviews with 34 low-income female sex workers and 28 health outreach members were used to examine how social relationships affected condom use and negotiation, STI/HIV testing and health-seeking behaviors, and dealing with violent clients. These data suggested that sex worker's laoxiang (hometown social connections) were more powerful than relationships between women selling sex at the same venue in establishing the terms and risk of commercial sex. Female sex workers from the same hometown often migrated to the city with their laoxiang and these social connections fulfilled many of the functions of nongovernmental organizations, including collective mobilization, condom promotion, violence mitigation, and promotion of health-seeking behaviors. Outreach members observed that sex workers accompanied by their laoxiang were often more willing to accept STI/HIV testing and trust local sexual health services. CONCLUSIONS/SIGNIFICANCE: Organizing STI/HIV prevention services around an explicitly defined laoxiang social network may provide a strong foundation for sex worker health programs. Further research on dyadic interpersonal relationships between female sex workers, group dynamics and norm establishment, and the social network characteristics are needed.