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Sepsis is now defined as a life-threatening syndrome of organ dysfunction triggered by a dysregulated host response to infection, posing significant challenges in critical care. The main objective of this review is to evaluate the potential of emerging biomarkers for early diagnosis and accurate prognosis in sepsis management, which are pivotal for enhancing patient outcomes. Despite advances in supportive care, traditional biomarkers like C-reactive protein and procalcitonin have limitations, and recent studies have identified novel biomarkers with increased sensitivity and specificity, including circular RNAs, HOXA distal transcript antisense RNA, microRNA-486-5p, protein C, triiodothyronine, and prokineticin 2. These emerging biomarkers hold promising potential for the early detection and prognostication of sepsis. They play a crucial role not only in diagnosis but also in guiding antibiotic therapy and evaluating treatment effectiveness. The introduction of point-of-care testing technologies has brought about a paradigm shift in biomarker application, enabling swift and real-time patient evaluation. Despite these advancements, challenges persist, notably concerning biomarker variability and the lack of standardized thresholds. This review summarizes the latest advancements in sepsis biomarker research, spotlighting the progress and clinical implications. It emphasizes the significance of multi-biomarker strategies and the feasibility of personalized medicine in sepsis management. Further verification of biomarkers on a large scale and their integration into clinical practice are advocated to maximize their efficacy in future sepsis treatment.
Assuntos
Biomarcadores , Sepse , Humanos , Sepse/diagnóstico , Sepse/sangue , PrognósticoRESUMO
Chronic hepatitis B virus (HBV) infection is a primary cause for liver cancer. And the main challenge of curing hepatitis B is the elimination of the stable covalently closed circular DNA (cccDNA) of the viral genome. The formation of HBV cccDNA requires the filling of single-stranded region and the ligation of nicks in relaxed circular DNA (rcDNA) strands. Previously, our group reported that proliferating cell nuclear antigen (PCNA) was involved in the formation of HBV cccDNA. However, the underlying mechanism of the conversion of HBV rcDNA to cccDNA is poorly understood. In the present study, we aim to explore the mechanism by which PCNA contributes to the conversion of HBV rcDNA to cccDNA. Our data showed that PCNA was involved in the process of HBV rcDNA repair. The knockout of PCNA by the CRISPR/Cas9 system remarkably blocked the conversion of HBV rcDNA to cccDNA, while the ectopic expression of PCNA could effectively rescue the event (P<0. 001). Knockout of PCNA significantly slowed down the conversion kinetics of HBV rcDNA to cccDNA (P<0. 01). Mechanically, the DNA binding domain of PCNA was required for the process of HBV rcDNA repair to cccDNA (P<0. 01). Thus, we conclude that PCNA confers the conversion of HBV rcDNA to cccDNA by its DNA binding domain. Clinically, PCNA might serve as a novel target for antiviral therapy.
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To explain biological function of protein CCL15 in HCC cell lines. The different expression level of CCL15 among HCC cell lines was validated by RT-PCR and Western blot. The expression recombinant plasmid of siRNA-CCL15 was constructed successfully and transfected into high metastasis cell lines HCCML3 to observe the alteration of biological function of HCCML3. The overexpression of CCL15 in high metastasis HCC cell lines was confirmed by validation tests. After transfected with siRNA-CCL15, the average amounts of invaded cells in cell invasion assay were 657.9 (HCCML3) and 148.4(HCCML3-siCCL15) (t=19.34, P less than 0.05). And in the scratch assay, the migrating distance were (0.35+/-0.02) mm (HCCML3) and (0.82+/-0.03)mm (HCCML3-siCCL15) (t=15.67, P less than 0.05). The expression of MMP-9 in HCCML3 was higher than HCCML3-siCCL15 through Western blot. Some biological properties (migration, invasion, MMP-9) of HCCML3 transfected with siRNA-CCL15 were decreased. The results suggest CCL15 might play an important role in HCC cell invasion and metastasis through two paths of MMPs regulation and invasion potential strengthening.