Host Factors Modulate Virus-Induced IFN Production via Pattern Recognition Receptors.

Innate immunity is the first line of defense in the human body, and it plays an important role in defending against viral infection. Viruses are identified by different pattern-recognition receptors (PRRs) that activate the mitochondrial antiviral signaling protein (MAVS) or transmembrane protein 173 (STING), which trigger multiple signaling cascades that cause nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3) to produce inflammatory factors and interferons (IFNs). PRRs play a pivotal role as the first step in pathogen induction of interferon production. Interferon elicits antiviral activity by inducing the transcription of hundreds of IFN-stimulated genes (ISGs) via the janus kinase (JAK) - signal transducer and activator of transcription (STAT) pathway. An increasing number of studies have shown that environmental, pathogen and host factors regulate the IFN signaling pathway. Here, we summarize the mechanisms of host factor modulation in IFN production via pattern recognition receptors. These regulatory mechanisms maintain interferon levels in a normal state and clear viruses without inducing autoimmune disease.

PLAU and GREM1 are prognostic biomarkers for predicting immune response in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a common malignant tumor. Identification of biomarkers and understanding their potential functions will facilitate the treatment and diagnosis in LUAD patients. The yellow module (cor = 0.31, P = 2e-6) was selected as the core module based on weighted gene co-expression network analysis (WGCNA) by integrating RNA-seq data and tumor stage. Two upregulated genes (PLAU and GREM1) in yellow module were identified to be biomarkers. Kaplan-Meier curve analysis displayed that high expression levels of them had a poor overall survival (OS). And, their high expression levels revealed higher tumor stage and relapse possibility in LUAD patients, and could be a prognostic parameter. Both biomarkers showed similar immune cell expression profiles in low- and high-expression groups. Strongly positive correlation between both biomarkers and biomarkers of tumor-infiltrating lymphocytes were also clarified in TCGA-LUAD cohort. Importantly, single gene GSEA showed that transcriptional mis-regulation in cancer and microRNAs in cancer were enriched in LUAD patients. Therefore, a miRNA-mRNA-transcription factors (TFs) co-expression regulatory networks was constructed for each biomarker, various miRNAs and TFs were related to PLAU and GREM1. Among which, 6 downstream TFs were overlapped genes for both biomarkers. Notably, 2 of these TFs (FOXF1 and TFAP2A) exhibited significantly abnormal expression levels. Among which, FOXF1 was downregulated and TFAP2A was upregulated in TCGA-LUAD cohort. Both TFs showed a significantly positive correlation with the expression level of PLAU. In conclusion, we identified 2 biomarkers related to immune response and achieved a good accuracy in predicting OS in patients with LUAD.

ABO Blood Group and the Risk and Prognosis of Lymphoma.

ABO blood group antigens exhibit alternative phenotypes and genetically derived structures that are located on the red cell surface. The role of ABO blood group in cancer biology has been intensely reported by several studies, and it is now widely recognized that ABO antigens are associated with the risk and prognosis of several types of tumors, namely gastric cancer and pancreatic cancer. However, there have been contentious limited issues with the association between the ABO blood group and lymphoma. In this narrative review, based on literature data, we discuss the role of ABO blood group in the risk and prognosis of lymphoma and summarize the current knowledge of the underlying pathogenic mechanisms of the association. The possible association of ABO blood group with racial disparities and pathological classification in lymphoma patients is also discussed.

Key signal transduction pathways and crosstalk in cancer: Biological and therapeutic opportunities.

Several different signaling pathways and molecular mechanisms have been identified as responsible for controlling critical functions in human cancer cells, such as selective growth and proliferative advantage, altered stress response favoring overall survival, vascularization, invasion and metastasis, metabolic rewiring, an abetting microenvironment, and immune modulation. This concise summary will provide a selective review of recent studies of key signal transduction pathways, including mitogen-activated protein kinase (MAPK) pathway, Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling, and Wnt/ß-catenin signaling pathway, which are altered in cancer cells, as the novel and promising therapeutic targets.

Energy metabolism pathways in breast cancer progression: The reprogramming, crosstalk, and potential therapeutic targets.

Breast cancer (BC) is a malignant tumor that seriously endangers health in women. BC, like other cancers, is accompanied by metabolic reprogramming. Among energy metabolism-related pathways, BC exhibits enhanced glycolysis, tricarboxylic acid (TCA) cycle, pentose phosphate pathway (PPP), glutamate metabolism, and fatty acid metabolism activities. These pathways facilitate the proliferation, growth and migration of BC cells. The progression of BC is closely related to the alterations in the activity or expression level of several metabolic enzymes, which are regulated by the intrinsic factors such as the key signaling and transcription factors. The metabolic reprogramming in the progression of BC is attributed to the aberrant expression of the signaling and transcription factors associated with the energy metabolism pathways. Understanding the metabolic mechanisms underlying the development of BC will provide a druggable potential for BC treatment and drug discovery.

Microfluidic Chip for Detection of Drug Resistance at the Single-cell Level.

Drug-resistant bacterial strains seriously threaten human health. Rapid screening of antibiotics is urgently required to improve clinical treatment. Conventional methods of antimicrobial susceptibility testing rely on turbidimetry that is evident only after several days of incubation. The lengthy time of the assay can delay clinical treatment. Here, we proposed a single-cell level rapid system based on a microfluidic chip. The detection period of 30 min to 2 h was significantly shorter than the conventional turbidity-based method. To promote detection efficiency, 16 independent channels were designed, permitting the simultaneous screening of 16 drugs in the microfluidic chip. Prepositioning of drugs in the chip permitted prolonged transportation and storage. This may allow for the widespread use of the novel system, particularly in the regions where medical facilities are scarce. The growth curves were reported rapidly through a custom code in Matlab after tracking and photographing the bacteria during microscopy examination. The capability of the proposed system was validated by antimicrobial susceptibility testing trials with standard strains. The system provides a potentially useful detection tool for drug-resistant bacteria.

Cyanobacteria-derived peptide antibiotics discovered since 2000.

Members of cyanobacteria, including Moorea spp., Okeania spp., Lyngbya spp., Schizothrix spp., Leptolyngbya spp., Microcystis spp., Symploca spp., Hassallia sp., Anabaena spp., Planktothrix sp., Tychonema spp., Oscillatoria spp., Tolypothrix sp., Nostoc sp., and Hapalosiphon sp. produce an enormously diverse range of peptide antibiotics with huge potential as pharmaceutical drugs and biocontrol agents following screening of structural analogues and analysis of structure-activity relationships (SAR). The need for novel antibiotic lead compounds is urgent, and this review summarizes 78 cyanobacteria-derived compounds reported since 2000, including 32 depsipeptides, 18 cyclic lipopeptides, 13 linear lipopeptides, 14 cyclamides, and one typical cyclic peptide. The current and potential therapeutic applications of these peptides are discussed, including for SAR, antituberculotic, antifungal, antibacterial, antiviral, and antiparasitic (anti-plasmodial, antitrypanosomal and antileishmanial) activities.

Gram-negative bacilli-derived peptide antibiotics developed since 2000.

Gram-negative bacilli such as Pseudomonas spp., Pseudoalteromonas sp., Angiococcus sp., Archangium sp., Burkholderia spp., Chromobacterium sp., Chondromyces sp., Cystobacter sp., Jahnella sp., Janthinobacterium sp., Lysobacter spp., Paraliomyxa sp., Photobacterium spp., Photorhabdus sp., Pontibacter sp., Ruegeria sp., Serratia sp., Sorangium sp., Sphingomonas sp., and Xenorhabdus spp. produce an enormous array of short peptides of 30 residues or fewer that are potential pharmaceutical drugs and/or biocontrol agents. The need for novel lead antibiotic compounds is urgent due to increasing drug resistance, and this review summarises 150 Gram-negative bacilli-derived compounds reported since 2000, including 40 cyclic lipopeptides from Pseudomonas spp.; nine aromatic peptides; eight glycopeptides; 45 different cyclic lipopeptides; 24 linear lipopeptides; eight thiopeptides; one lasso peptide; ten typical cyclic peptides; and five standard linear peptides. The current and potential therapeutic applications of these peptides, including structures and antituberculotic, anti-cyanobacterial, antifungal, antibacterial, antiviral, insecticidal, and antiprotozoal activities are discussed.

Actinobacteria-Derived peptide antibiotics since 2000.

Members of the Actinobacteria, including Streptomyces spp., Kutzneria sp. Actinoplanes spp., Actinomycete sp., Nocardia sp., Brevibacteriumsp.,Actinomadura spp., Micromonospora sp., Amycolatopsis spp., Nonomuraea spp., Nocardiopsis spp., Marinactinospora sp., Rhodococcus sp., Lentzea sp., Actinokineospora sp., Planomonospora sp., Streptomonospora sp., and Microbacterium sp., are an important source of structurally diverse classes of short peptides of ∼30 residues or fewer that will likely play an important role in new antibiotic development and discovery. Additionally, many have unique structures that make them recalcitrant to traditional modes of drug resistance via novel mechanisms, and these are ideal therapeutic tools and potential alternatives to current antibiotics. The need for novel antibiotic is urgent, and this review summarizes 199 Actinobacteria compounds published since 2000, including 35 cyclic lipopeptides containing piperazic or pipecolic acids, eight aromatic peptides, five glycopeptides, 21 bicyclic peptides, 44 other cyclic lipopeptides, five linear lipopeptides, six 2,5-diketopiperazines, one dimeric peptide, four nucleosidyl peptides, two thioamide-containing peptides, 25 thiopeptides, nine lasso peptides, and 34 typical cyclic peptides. The current and potential therapeutic applications of these peptides, including their structure, antituberculotic, antibacterial, antifungal, antiviral, anti-brugia, anti-plasmodial, and anti-trypanosomal activities, are discussed.

Bacillaceae-derived peptide antibiotics since 2000.

Members of the Bacillaceae family, including Bacillus spp., Brevibacillus spp., Paenibacillus spp., Aneurinibacillus sp., and Halobacillus sp., are an important source of structurally diverse classes of short peptides of ∼ 30 residues or fewer possessing peculiar and rapid killing activity against various pathogens. Additionally, many have unique structures that enhance resistance to hydrolysis by proteases, and these are ideal therapeutic tools and potential alternatives to current antibiotics. The need for novel antibiotic lead compounds is urgent, and this review summarises 119 Bacillaceae compounds published since 2000, including 12 surfactin-like lipopeptides, 16 iturinic lipopeptides, fengycin C, 33 other cyclic lipopeptides, 26 linear lipopeptides, two thiopeptides, four 2,5-diketopiperazines, 20 typical cyclic peptides, and five standard linear peptides. The current and potential therapeutic applications of these peptides, including structure, antibacterial, antifungal, and antiviral activities, are discussed.