Peroxiredoxins (PRDXs), a ubiquitous family of redox‐regulating proteins, are reported of potential to eliminate various reactive oxygen species (ROS). As a major member of the antioxidant enzymes, ...PRDX1 can become easily over‐oxidized on its catalytically active cysteine induced by a variety of stimuli in vitro and in vivo. In nucleus, oligomeric PRDX1 directly associates with p53 or transcription factors such as c‐Myc, NF‐κB and AR, and thus affects their bioactivities upon gene regulation, which in turn induces or suppresses cell death. Additionally, PRDX1 in cytoplasm has anti‐apoptotic potential through direct or indirect interactions with several ROS‐dependent (redox regulation) effectors, including ASK1, p66Shc, GSTpi/JNK and c‐Abl kinase. PRDX1 is proven to be a versatile molecule regulating cell growth, differentiation and apoptosis. Recent studies have found that PRDX1 and/or PRDX1‐regulated ROS‐dependent signalling pathways play an important role in the progression and metastasis of human tumours, particularly in breast, oesophageal and lung cancers. In this paper, we review the structure, effector functions of PRDX1, its role in cancer and the pivotal role of ROS in anticancer treatment.
Gastric cancer (GC) is one of the most common tumors worldwide and the leading cause of tumor-related mortality. Endoscopy and serological tumor marker testing are currently the main methods of GC ...screening, and treatment relies on surgical resection or chemotherapy. However, traditional examination and treatment methods are more harmful to patients and less sensitive and accurate. A minimally invasive method to respond to GC early screening, prognosis monitoring, treatment efficacy, and drug resistance situations is urgently needed. As a result, liquid biopsy techniques have received much attention in the clinical application of GC. The non-invasive liquid biopsy technique requires fewer samples, is reproducible, and can guide individualized patient treatment by monitoring patients' molecular-level changes in real-time. In this review, we introduced the clinical applications of circulating tumor cells, circulating free DNA, circulating tumor DNA, non-coding RNAs, exosomes, and proteins, which are the primary markers in liquid biopsy technology in GC. We also discuss the current limitations and future trends of liquid biopsy technology as applied to early clinical biopsy technology.
The hybridization chain reaction (HCR) is widely used for biosensing. However, HCR does not provide the required sensitivity. In this study, we reported a method to improve the sensitivity of HCR by ...dampening the cascade amplification. First, we designed a biosensor based on HCR, and an initiator DNA was used to trigger the cascade amplification. Optimization of the reaction was then performed, and the results showed that the limit of detection (LOD) for the initiator DNA was about 2.5 nM. Second, we designed a series of inhibitory DNAs to dampen the HCR cascade amplification, and DNA dampeners (50 nM) were applied in the presence of the DNA initiator (50 nM). One of the DNA dampeners (D5) showed the best inhibitory efficiency of greater than 80%. This was further applied at concentrations ranging from 0 nM to 10 nM to prohibit the HCR amplification caused by a 2.5 nM initiator DNA (the limit of detection for this initiator DNA). The results showed that 0.156 nM of D5 could significantly inhibit the signal amplification (p<0.05). Additionally, the limit of detection for the dampener D5 was 16 times lower than that for the initiator DNA. Based on this detection method, we achieved a detection limit as low as 0.625 nM for HCV-RNAs. In summary, we developed a novel method with improved sensitivity to detect the target designed to prohibit the HCR cascade. Overall, this method could be used to qualitatively detect the presence of single-stranded DNA/RNA.
An effective biomarker for the diagnosis of breast cancer (BC) and benign breast diseases (BBD) is crucial for improving the prognosis. We investigated whether N6-methyladenosine (m6A) can be a ...diagnostic biomarker of BC.
We detected the contents of peripheral blood m6A in 62 patients with BC, 41 patients with BBD, and 41 normal controls (NCs) using the colorimetric method. The relative expression of the m6A regulated genes methyltransferase-like 14 (METTL14) and fat mass and obesity-associated (FTO) was analyzed using quantitative real-time polymerase chain reaction.
m6A in peripheral blood RNA was significantly higher in patients with BC than that in patients with BBD (p < 0.001) or the NCs (p < 0.001). m6A was closely associated with the disease stage (from stage 0 to stage I-IV, p=0.003). The receiver operating characteristic curve of m6A contained an area under the curve (AUC) value of 0.887 in BC, which was greater than that of carcinoembryonic antigen (CEA) or carbohydrate antigen 153 (CA153). The combination of m6A, CEA, and CA153 improved the AUC to 0.914. The upregulated and downregulated mRNA expression of METTL14 and FTO, respectively, might contribute to the increase of m6A in patients with BC. m6A combined with METTL14 and FTO improved the AUC to 0.929 with a specificity of 97.4% in the peripheral blood of patients with BC.
The peripheral blood RNA of m6A might be a valuable biomarker for the diagnosis of BC.
Recently, the long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) was reported to be involved in the pathogenesis of several cancers, including human colorectal cancer (CRC). ...However, the molecular basis for cancer initiation, development, and progression remains unclear. In this study, we observe that upregulated PVT1 is associated with poor prognosis and bad clinicopathological features of CRC patients. In vitro means of PVT1 loss in a CRC cell line inhibit cell proliferation, migration, and invasion. Furthermore, dual-luciferase reporter and RNA pull-down assays indicated that PVT1 binds to miR-16-5p, which has been shown to play strong tumor suppressive roles in CRC. Targeted loss of miR-16-5p partially rescues the suppressive effect induced by PVT1 knockdown. Vascular endothelial growth factor A (VEGFA), a direct downstream target of miR-16-5p, was suppressed by PVT1 knockdown in CRC cells. Overexpression of VEGFA is known to modulate the AKT signaling cascade by activating vascular endothelial growth factor receptor 1 (VEGFR1). We, therefore, show that PVT1 loss combined with miR-16-5p overexpression reduces tumor volume maximally when propagated within a mouse xenograft model. We conclude that the PVT1-miR-16-5p/VEGFA/VEGFR1/AKT axis directly coordinates the response in CRC pathogenesis and suggest PVT1 as a novel target for potential CRC therapy.
The monkeypox virus (MPXV) is a zoonotic DNA virus that belongs to the poxvirus family. Conventional laboratory methods for detecting MPXV are complex and expensive, making them unsuitable for ...detecting the virus in regions with limited resources. In this study, we using the Helicase dependent amplification (HDA) method and the Recombinase polymerase amplification (RPA) technique in combination with the lateral flow test (LFT), together with a self-designed qPCR technique for the detection of the MPXV specific conserved fragment F3L, to compare the sensitivity and specificity of the three assays. By analyzing the sensitivity detection results using Probit, it can be seen that the limit of detection (LOD) of the HDA-LFT detection target is 9.86 copies/µL (95% confidence interval, CI 7.52 copies/µL lower bound), the RPA-LFT detection target is 6.97 copies/µL (95% CI 3.90 copies/µL lower bound), and the qPCR detection target is 479.24 copies/mL (95% CI 273.81 copies/mL lower bound). The specificity test results showed that the specificity of the three methods mentioned above was higher than 90% in detecting pseudoviruses of the same genus of MPXV. The simple, highly sensitive, and specific MPXV assay developed in this study is anticipated to provide a solid foundation for future applications in the early screening, diagnosis, and evaluation of the efficacy of MPXV. This is the first time the HDA-LFT assay has been utilized to detect MPXV infection.
Treponema phagedenis
, a human commensal spirochete, has been reported world-wide as a key factor in the pathogenesis of bovine digital dermatitis. Here we report a case of
T. phagedenis
sequence ...detection in the cerebrospinal fluid (CSF) of a patient. The patient was diagnosed with neurosyphilis, and
T. phagedenis
was detected as the only microorganism in his CSF by metagenomic sequencing. The patient went through a round of penicillin therapy previously (2.4 million units of Benzathine Penicillin intramuscularly once a week for three weeks) that did not resolve the symptoms; after the diagnosis of neurosyphilis he was treated with Penicillin G Sodium 4.0 million units q4h intravenous for 14 days then his symptoms resolved. To the best of our knowledge,
T. phagedenis
has never been reported to be detected in a human’s CSF before. This was also the first time it was detected by metagenomic next-generation sequencing. We propose that more etiological tests should be performed including culture and sequencing for more patients with syphilis, which will contribute to a deeper understanding of the pathogenicity of the spirochete.
The emergence of drug-resistant bacteria emphasizes the urgent need for novel antibiotics. The antimicrobial peptide TS shows extensive antibacterial activity in vitro and in vivo, especially in ...gram-negative bacteria; however, its antibacterial mechanism is unclear. Here, we find that TS without hemolytic activity disrupts the integrity of the outer bacterial cell membrane by displacing divalent cations and competitively binding lipopolysaccharides. In addition, the antimicrobial peptide TS can inhibit and kill
by disintegrating the bacteria from within by interacting with bacterial DNA. Thus, antimicrobial peptide TS's multiple antibacterial mechanisms may not easily induce bacterial resistance, suggesting use as an antibacterial drug to be for combating bacterial infections in the future.
Pseudopodium-enriched atypical kinase 1 (PEAK1), a novel non-receptor tyrosine kinase, has been demonstrated to act as an oncogenic regulator in breast and pancreatic cancers. However, the role of ...PEAK1 in the progression and metastasis of lung cancer is still unknown. Here, we observed that ectopic PEAK1 expression promoted lung cancer cell migration and invasion, while PEAK1 knockout resulted in suppressed cell migration and invasion. Interestingly, cell proliferation did not significantly increase or decrease in either the PEAK1 overexpression or knockout groups compared with the corresponding control cells. In addition, PEAK1 overexpression could induce epithelial-to-mesenchymal transition (EMT) and the expression of matrix metalloproteinase-2 (MMP2) and MMP9 both in vitro and in vivo, whereas PEAK1 knockout had the opposite effects. Then, we had confirmed that PEAK1 was significantly upregulated in lung cancer tissues, and correlated with a higher tumor node metastasis stage. Moreover, PEAK1 upregulation markedly enhanced the activation of extracellular signal-regulated kinase-1/2 (ERK1/2) and Janus kinase-2 (JAK2) signaling in lung cancer cells. Further work demonstrated that the combination of PD98059 with AZD1480 could reverse the effects of PEAK1-induced EMT, cell migration and invasion. Our findings highlight a newer mechanism for PEAK1 in regulating EMT and metastasis in lung cancer, which might serve as a therapeutic target for lung cancer patients.
Systemic lupus erythematosus (SLE) is an auto-immune disease, the pathogenesis of which remains to be fully addressed. Metrnβ is a novel cytokine involved in the pathogenesis of inflammatory disease, ...but its regulatory roles in SLE are unclear. We aimed to comprehensively investigate the clinical value of Metrnβ in SLE. A massive elevation of circulating Metrnβ levels was observed in SLE, and patients with an active phase displayed higher Metrnβ concentrations than those with inactive phases. Additionally, we found that Metrnβ expression was positively correlated with clinical indicators of SLE. Longitudinal cytokine and chemokine profiles revealed a disturbed immune response in SLE, with high activity profiles displayed severe pathogenic inflammation, and a positive correlation of the serum Metrnβ with CXCL9, IL10, IL18 and IL1RA was observed as well. Moreover, Metrnβ expressions exhibited an inverse correlation with Treg and B10. Of note, a significant decrease of ILC2 was found in SLE, and there was a negative correlation of Metrnβ with ILC2 as well. Further ROC analysis showed that the area under the curve (AUC) for Metrnβ was 0.8250 (95% CI: 0.7379–0.9121), with a cutoff value of 1131 pg/mL to effectively distinguish SLE patients from healthy controls. Our study herein demonstrated for the first time that Metrnβ values were increased and were immunologically correlated with SLE activity, which could be utilized as an alternative biomarker for the early identification and predicting of the immuno-response of SLE.
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