High level of C3 is associated with Th2 immune response and liver fibrosis in patients with schistosomiasis.

Long-term infection of schistosomiasis will seriously affect the liver health of patients. The serum of 334 chronic Schistosoma japonicum patients and 149 healthy volunteers was collected. Compared with heathy people, the level of C4 (complement 4) was increased, and the level of C3 (complement 3) was in an obvious skewed distribution. ELISA was performed to detect the serum cytokines, the results showed that the levels of IFN-γ (interferon-γ), IL (interleukin)-2 and TNF-α (tumour necrosis factor-α) were reduced, while the levels of Th2 cytokines (IL-4, IL-6 and IL-10) were increased. In the serum of patients with high C3, the secretion of HA (hyaluronic acid), LN (laminin), IV-C (type IV collagen) and PCIII (type III procollagen) were increased, the activation of hepatic stellate cells was promoted. Exogenous human recombinant C3 made mice liver structure of the mice damaged and collagen deposition. IFN-γ and IFN-γ/IL-4 were decreased, while HA, LN, PCIII and IV-C were increased, and the expressions of α-SMA and TGF-ß1 in liver tissues were up-regulated. However, the addition of IFN-γ partially reversed the effect of C3 on promoting fibrosis. High level of C3 is associated with Th2 immune response and liver fibrosis in patients with schistosomiasis.

A novel "off-on" fluorescent probe for the detection of nickel ions and its clinical application.

Nickel serves as an essential micronutrient for the human body, playing a vital role in various enzymatic processes. However, excessive nickel entering the environment can cause pollution and pose serious risks to animals, plants, and human health. High concentrations of nickel ions in the human body increase the risk of various diseases, highlighting the need for accurate measurement of nickel ions levels. In this study, we designed a sequence-specific cleavage probe for nickel (II) ion called SSC-Ni. Similar to the TaqMan probe, SSC-Ni is an off-on fluorescent probe with an exceptionally low background fluorescence signal. It exhibits high detection specificity, making it highly selective for nickel ions, and the detection limit of the probe towards Ni2+ is as low as 82 nM. The SSC-Ni probe can be utilized for convenient and cost-effective high-throughput quantitative detection of nickel ions in serum. Its user-friendly operation and affordability make it a practical solution. By addressing the lack of simple and effective nickel ion detection methods, this probe has the potential to contribute significantly to environmental monitoring and the protection of human health.

Simultaneous detection of human norovirus GI, GII and SARS-CoV-2 by a quantitative one-step triplex RT-qPCR.

Background: There are many similarities in the clinical manifestations of human norovirus and SARS-CoV-2 infections, and nucleic acid detection is the gold standard for diagnosing both diseases. In order to expedite the identification of norovirus and SARS-CoV-2, a quantitative one-step triplex reverse transcription PCR (RT-qPCR) method was designed in this paper. Methods: A one-step triplex RT-qPCR assay was developed for simultaneous detection and differentiation of human norovirus GI (NoV-GI), GII (NoV-GII) and SARS-CoV-2 from fecal specimens. Results: The triplex RT-qPCR assay had high detection reproducibility (CV < 1%) and sensitivity. The lower limits of detection (LLOD95) of the triplex RT-qPCR assay for each target site were 128.5-172.8 copies/mL, and LLOD95 of the singleplex RT-qPCR assay were 110.3-142.0 copies/mL. Meanwhile, among the detection of clinical oropharyngeal swabs and fecal specimens, the results of the singleplex and triplex RT-qPCR assay showed high agreement. Conclusion: The triplex RT-qPCR assay for simultaneous detection of NoV-GI, NoV-GII and SARS-CoV-2 from fecal specimens has high clinical application value.

Circ_0000284 Promoted Acute Pancreatitis Progression through the Regulation of miR-10a-5p/Wnt/ß-Catenin Pathway.

Circular RNAs (circRNAs) have been found to be involved in the progression of acute pancreatitis (AP). The objective of our study was to investigate the effects of circ_0000284 on caerulein-induced AR42J cell injury. To mimic AP in vitro, rat pancreatic acinar AR42J cells were treated with caerulein. The expression of circ_0000284 and miR-10a-5p was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Enzyme-linked immunosorbent assay (ELISA) was employed to determine the content of inflammatory cytokines interleukin (IL)-1ß, IL-6, IL-8 and tumor necrosis factor α (TNF-α). Western blotting was applied to analyze the levels of Wnt/ß-catenin pathway-related and apoptosis-related proteins. Cell viability and apoptosis were monitored by Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. The target connection between circ_0000284 and miR-10a-5p was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. AP induced inflammation in patients, and caerulein treatment increased apoptosis and inflammation in AR42J cells. Circ_0000284 was upregulated in serum of AP patients and caerulein-induced AR42J cells, while Wnt/ß-catenin pathway was inactivated. Knockdown of circ_0000284 could decrease apoptosis and inflammation in caerulein-induced AR42J cells, which was attenuated by miR-10a-5p inhibition or Wnt signaling pathway antagonist Dickkopf-related protein 1 (DKK1). MiR-10a-5p was sponged by circ_000028 and was downregulated in caerulein-induced AR42J cells. Circ_0000284 depletion could protect caerulein-induced AR42J cells from apoptosis and inflammation by upregulating miR-10a-5p expression and activating Wnt/ß-catenin pathway, underscoring a potential target for AP therapy.

Comprehensive Analysis Identified ASF1B as an Independent Prognostic Factor for HBV-Infected Hepatocellular Carcinoma.

Purpose: Hepatitis B (HBV)-infected hepatocellular carcinoma is one of the most common cancers, and it has high incidence and mortality rates worldwide. The incidence of hepatocellular carcinoma has been increasing in recent years, and existing treatment modalities do not significantly improve prognosis. Therefore, it is important to find a biomarker that can accurately predict prognosis. Methods: This study was analyzed using the The Cancer Genome Atlas (TCGA) database and validated by the International Cancer Genome Consortium (ICGC) database. The STRING database was used to construct a gene co-expression network and visualize its functional clustering using Cytoscape. A prognostic signature model was constructed to observe high and low risk with prognosis, and independent prognostic factors for HBV-infected hepatocellular carcinoma were identified by Cox regression analysis. The independent prognostic factors were then analyzed for expression and survival, and their pathway enrichment was analyzed using gene set enrichment analysis (GSEA). Results: 805 differentially expressed genes (DEGs) were obtained by differential analysis. Protein-protein interaction (PPI) showed that DEGs were mostly clustered in functional modules, such as cellular matrix response, cell differentiation, and tissue development. Prognostic characterization models showed that the high-risk group was associated with poor prognosis, while Cox regression analysis identified ASF1B as the only independent prognostic factor. As verified by expression and prognosis, ASF1B was highly expressed in HBV-infected hepatocellular carcinoma and led to a poor prognosis. GSEA showed that high ASF1B expression was involved in cell cycle-related signaling pathways. Conclusion: Bioinformatic analysis identified ASF1B as an independent prognostic factor in HBV-infected hepatocellular carcinoma, and its high expression led to a poor prognosis. Furthermore, it may promote hepatocellular carcinoma progression by affecting cell cycle-related signaling pathways.

Role of Wnt/ß-catenin pathway agonist SKL2001 in Caerulein-induced acute pancreatitis.

The goal of this study was to clarify the protective role of the Wnt/ß-catenin pathway agonist SKL2001 in a rat model of Caerulein-induced acute pancreatitis. AR42J cells and rats were divided into 4 groups: control, Caerulein, SKL2001 + Caerulein, and SKL2001 + control. Cell apoptosis was examined using flow cytometry. Hematoxylin-eosin staining was performed to observe pathological changes in pancreatic and small intestinal tissues. Inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA), while genes related to the Wnt/ß-catenin pathway were quantified using quantitative real-time PCR. In vitro results showed that Caerulein promoted cell necrosis, inhibited the Wnt/ß-catenin pathway, and increased the level of inflammatory cytokines. However, SKL2001 reduced cell necrosis and inflammatory cytokines and activated the Wnt/ß-catenin pathway. Additionally, in vivo results demonstrated the accumulation of fluid (i.e., edema), hemorrhage, inflammation and necrosis of the pancreatic acini occurred 6 h after the final Caerulein induction, with the damage reaching a maximal level 12 h after the final Caerulein induction; meanwhile, the Wnt/ß-catenin pathway was evidently inhibited with an enhanced level of inflammatory cytokines. The aforementioned damage was further aggravated 12 h later. Nevertheless, the pancreatic and small intestinal tissue damages were alleviated in Caerulein-induced rats treated with SKL2001. In conclusion, activation of the Wnt/ß-catenin pathway could inhibit Caerulein-induced cell apoptosis and inflammatory cytokine release, thus improving pancreatic and intestinal damage in rats with acute pancreatitis.

Highly selective peripheral nerve radio frequency ablation for the treatment of severe knee osteoarthritis.

The objective of the present study was to investigate the effect of highly selective peripheral nerve radiofrequency (RF) ablation for the pain caused by severe knee osteoarthritis (OA). A total of 96 patients with knee OA were randomly divided into two groups. The 49 patients in group A were treated with highly selective peripheral nerve RF ablation group and the 47 patients in group B were treated with sodium hyaluronate injection. Visual analogue scale (VAS), Lysholm knee score (LKS), and pain relief before treatment and at 3 days and 3, 6, 9, and 12 months after treatment were compared. At each time point after treatment in group A, both VAS and LKS scores were significantly different compared with before treatment (P<0.05). At 3 days, and at 3 and 6 months after treatment in group B, VAS scores were significantly different from before treatment (P<0.05) and at 9 and 12 months after treatment, the scores were not significantly different from those before treatment. In addition, LKS scores were only significantly different at 3 months after treatment compared with before treatment (P<0.05) and not significantly different after that time point. Furthermore, compared with group B, the rates of effective pain relief in group A were significantly higher at each time point after treatment (P<0.05). Compared with sodium hyaluronate injection, highly selective peripheral nerve RF ablation of the knee was more effective, easy to operate and had no significant adverse effects for the treatment of knee OA.

TNFSF15 is likely a susceptibility gene for systemic lupus erythematosus.

We aim to explore the correlation of TNFSF15 genetic polymorphisms with susceptibility to systemic lupus erythematosus (SLE). This study enrolled SLE patients and healthy individuals to detect three single nucleotide polymorphisms (SNPs) of TNFSF15 (rs3810936, rs6478108 and rs4979462) through using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to analyze the possible association of these three SNPs with the risk of SLE and the mRNA level of TNFSF15 was quantified by real-time PCR. The rs3810936 T allele carrier greatly decreased risk of SLE (OR = 0.620, 95% CI = 0.454-0.849, P = 0.003), while the risk of SLE for rs4979462 T allele carrier was significantly increased (OR = 1.66, 95% CI = 1.243-2.218, P < 0.001). The mRNA level of TNFSF15 was obviously higher in SLE patients, and specifically, the patients who carried the CC genotype of TNFSF15 rs3810936 had a higher TNFSF15 mRNA, but the rs4979462 CC genotype carriers appeared to be associated with the decreased TNFSF15 mRNA (all P < 0.05). Besides, the genotypes of rs3810936 and rs4979462 of TNFSF15 were significantly associated with butterfly rash, arthritis, serositis, renal nephritis, hematological disorder, immunological disorder and positive antinuclear antibody (ANA) of SLE patients (all P < 0.05). CCT and CTT haplotypes were risk factors of SLE, but CCC and TTT were protective factors of SLE (all P < 0.05). Logistic regression analysis showed that rs3810936 and rs4979462 of TNFSF15, histories of chilblain and wet living environment were independently associated with the risk of SLE (all P < 0.05).The current results suggested that TNFSF15 (rs3810936 and rs4979462) SNPs may confer susceptibility to SLE risk, which were significantly associated with the clinical phenotypes of SLE.

Long-term streptozotocin-induced diabetes in rats leads to severe damage of brain blood vessels and neurons via enhanced oxidative stress.

The aim of this study was to investigate pathophysiological alterations and oxidative stress in various stages of streptozotocin (STZ)­induced diabetes mellitus (DM) in rats. Male Sprague-Dawley rats (120) were randomized into DM and control groups. Body mass, plasma glucose, glycated hemoglobin (HbA1c), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels, as well as aldose reductase (AR) activities, in brain tissue and serum were determined. Electron microscopy was used to observe neuron and vessel changes in the brain. In STZ­treated rats, blood glucose, low density lipoproteins, triglycerides and total cholesterol levels increased 1.43­3.0­fold and high density lipoprotein, HbA1c and insulin sensitivity index increased 1.1­1.23­fold compared with control. At week 16 following treatment, DM rat serum H2O2 concentration was increased, indicating oxidative stress and mRNA levels of GPx and SOD were 2­fold higher than the control. Protein GPx and SOD levels were reduced (P<0.01). DM rats were identified to exhibit early irregular glomerular capillary basement membrane thickening and vacuolization in the mitochondria and epithelial cells. Neuron cells and blood vessels in the DM rat brains became increasingly abnormal over time with altered Golgi bodies, mitochondria and endoplasmic reticulum cisterns, concurrent with SOD inactivation and AR protein accumulation. Disease progression in rats with STZ­induced DM included brain pathologies with vascular and neuron cell abnormalities, associated with the reduction of SOD, CAT and GPx activities and also AR accumulation.