DNAJC12 downregulation induces neuroblastoma progression via increased histone H4K5 lactylation.

Neuroblastoma (NB) is the most common extracranial solid tumor in children. Despite treatment advances, the survival rates of high-risk NB patients remain low. This highlights the urgent need for a deeper understanding of the molecular mechanisms driving NB progression to support the development of new therapeutic strategies.

Cardiac-specific renalase overexpression alleviates CKD-induced pathological cardiac remodeling in mice.

Introduction: CKD-induced pathological cardiac remodeling is characterized by myocardial hypertrophy and cardiac fibrosis. The available therapeutic options are limited, it is thus urgently needed to identify novel therapeutic targets. Renalase (RNLS) is a newly discovered protein secreted by the kidney and was found beneficial in many renal diseases.

Pifithrin-α ameliorates glycerol induced rhabdomyolysis and acute kidney injury by reducing p53 activation.

Objectives: Rhabdomyolysis is a series of symptoms caused by the dissolution of striped muscle, and acute kidney injury (AKI) is a potential complication of severe rhabdomyolysis. The underlying causes of AKI are remarkably complex and diverse. Here, we aim to investigate whether pifithrin-α protected against rhabdomyolysis-induced AKI and to determine the involved mechanisms.

Nicotinamide retains Klotho expression and ameliorates rhabdomyolysis-induced acute kidney injury.

Objectives: Acute kidney injury (AKI) is a severe complication of rhabdomyolysis that significantly increases mortality. Unfortunately, the therapeutic approach is limited. Inflammation plays a critical role in the pathogenesis of rhabdomyolysis-induced AKI, which is a potential therapeutic target.

Dl-3-n-butylphthalide pretreatment attenuates renal ischemia/reperfusion injury.

Background: Renal ischemia reperfusion injury (IRI) has become a growing concern in clinical practice with high morbidity and mortality rates. There is currently no effective prophylactic regimen available to prevent its occurrence and to improve its clinical prognosis. Dl-3-n-butylphthalide (NBP) has been used for stroke treatment in China for years.

Wnt5a promotes renal tubular inflammation in diabetic nephropathy by binding to CD146 through noncanonical Wnt signaling.

Immune and inflammatory factors have emerged as key pathophysiological mechanisms in the progression of diabetic renal injury. Noncanonical Wnt5a signaling plays an essential role in obesity- or diabetes-induced metabolic dysfunction and inflammation, but its explicit molecular mechanisms and biological function in diabetic nephropathy (DN) remain unknown. In this study, we found that the expression of Wnt5a and CD146 in the kidney and the level of soluble form of CD146 (sCD146) in serum and urine samples were upregulated in DN patients compared to controls, and this alteration was correlated with the inflammatory process and progression of renal impairment.

Sitagliptin ameliorates renal tubular injury in diabetic kidney disease via STAT3-dependent mitochondrial homeostasis through SDF-1α/CXCR4 pathway.

Mitochondrial abnormalities play critical roles in diabetic tubular injury progression. Dipeptidyl peptidase-4 (DPP4) inhibitors are widely used antihyperglycemic agents that exert renal protective and positive effects against mitochondrial dysfunction in diabetic kidney disease (DKD). However, their underlying mechanism remains unclear.

Comparison of Kidney Transcriptomic Profiles of Early and Advanced Diabetic Nephropathy Reveals Potential New Mechanisms for Disease Progression.

To identify the factors mediating the progression of diabetic nephropathy (DN), we performed RNA sequencing of kidney biopsy samples from patients with early DN, advanced DN, and normal kidney tissue from nephrectomy samples. A set of genes that were upregulated at early but downregulated in late DN were shown to be largely renoprotective, which included genes in the retinoic acid pathway and glucagon-like peptide 1 receptor. Another group of genes that were downregulated at early but highly upregulated in advanced DN consisted mostly of genes associated with kidney disease pathogenesis, such as those related to immune response and fibrosis.

Ischemic Duration and Frequency Determines AKI-to-CKD Progression Monitored by Dynamic Changes of Tubular Biomarkers in IRI Mice.

Ischemia reperfusion injury (IRI) is one of the most common causes of acute kidney injury (AKI). However, the pathogenesis and biomarkers predicting the progression of IRI-induced AKI to chronic kidney disease (CKD) remain unclear. A side-by-side comparison between different IRI animal models with variable ischemic duration and episodes was performed.

Expression of Endothelial Cell Injury Marker Cd146 Correlates with Disease Severity and Predicts the Renal Outcomes in Patients with Diabetic Nephropathy.

Background/aims: Glomerular endothelial cell injury plays a crucial role in the development of diabetic nephropathy (DN). CD146, an endothelial marker, was shown to increase in chronic kidney disease (CKD), but its role in DN remains unknown. We aim to assess whether CD146 could be used to evaluate disease severity and predict renal outcomes in DN at early stages.

Febuxostat attenuates ER stress mediated kidney injury in a rat model of hyperuricemic nephropathy.

Hyperuricemia contributes to kidney tubular injury and kidney fibrosis. However, the underlying mechanism remains unclear. Here we examined the role of RTN1A, a novel endoplasmic reticulum (ER)-associated protein and ER stress in hyperuricemic nephropathy.

Rtn1a-Mediated Endoplasmic Reticulum Stress in Podocyte Injury and Diabetic Nephropathy.

We previously reported a critical role of reticulon (RTN) 1A in mediating endoplasmic reticulum (ER) stress in kidney tubular cells and the expression of RTN1A correlates with the renal function and the severity of kidney injury in patients with diabetic nephropathy (DN). Here, we determined the roles of RTN1A and ER stress in podocyte injury and DN. We used db/db mice with early unilateral nephrectomy (Unx) as a murine model of progressive DN and treated mice with tauroursodeoxycholic acid (TUDCA), a specific inhibitor of ER stress.

Inhibition of Reticulon-1A-Mediated Endoplasmic Reticulum Stress in Early AKI Attenuates Renal Fibrosis Development.

Several animal studies have shown an important role for endoplasmic reticulum (ER) stress in AKI, whereas human studies are lacking. We recently reported that Reticulon-1A (RTN1A) is a key mediator of ER stress and kidney cell injury. Here, we investigated whether modulation of RTN1A expression during AKI contributes to the progression to CKD.

Co-delivery of LIGHT expression plasmid enhances humoral and cellular immune responses to HIV-1 Nef in mice.

The immunogenicity and efficacy of a DNA vaccine can be greatly enhanced when a gene adjuvant is used. LIGHT, a member of TNF superfamily, can function as a costimulatory molecule for human naïve T cells to proliferate and can be a potential gene adjuvant. In the current study, the eukaryotic expression plasmid pcDNA-nef was constructed by inserting a full-length nef gene into pcDNA3.

Improvement in efficacy of DNA vaccine encoding HIV-1 Vif by LIGHT gene adjuvant.

DNA vaccine can induce the prolonged immune responses against the encoded antigen with the appropriate adjuvant. To study the immunogenicity of the HIV-1 vif DNA vaccine in inducing the humoral and cellular immune responses and the immunoadjuvant effect of LIGHT, which is a member of TNF superfamily and can stimulate the proliferation of naïve T cells as a co-stimulatory molecule, DNA vaccine plasmid pcDNA-Vif was constructed by inserting HIV-1 vif gene into the downstream of CMV promoter in eukaryotic expression vector pcDNA3.1(+).

[Expression of VP0 protein of enterovirus 71 in Escherichia coli and generation of the corresponding polyclonal antibodies in guinea pigs].

Aim: To obtain recombinant VP0 protein of enterovirus 71, and generate the corresponding VP0-specific polyclonal antibodies, for molecular detection and characterization of EV71.

Methods: The VP0 gene was amplified by PCR and cloned into vector pET26b to make pET-VP0 for the prokaryotic expression of VP0. The recombinant VP0 protein was expressed in E.

[Cloning and expression of the extracellular region of human LIGHT gene in E.coli.].

Aim: To construct a recombinant prokaryotic expression vector containing the extracellular region of human LIGHT gene and perform the express in E.coli.

Methods: Total RNA was extracted from human immature bone marrow-derived dendritic cells.

B7-DC-silenced dendritic cells induce stronger anti-HBV immunity in transgenic mice.

Hepatitis B virus (HBV) is a noncytopathic DNA virus and is the pathogen of acute and chronic hepatitis. Interferon and nucleotide analogues such as lamivudine and adefovir are the current treatment strategies of HBV infection; however, it is still a serious disease. Therefore, the development of new therapeutic options against HBV is needed.

Engineering enhancement of the immune response to HBV DNA vaccine in mice by the use of LIGHT gene adjuvant.

DNA vaccines could induce protective immune responses in several animal models. Many strategies have been employed to improve the effect of nucleic acid vaccines. LIGHT is a member of the TNF superfamily and functions as a co-stimulatory molecule for T cell proliferation.

[Construction and expression of prokaryotic vector encoding extracellular region of murine B7-DC].

Aim: To construct a prokaryotic expression vector for the extracellular domain of murine B7-DC(B7-DC(ECD)) gene, and to express the gene in E.coli BL21.

Methods: The total RNA was extracted from murine immature bone marrow-derived dendritic cells and the extracellular fragment of B7-DC cDNA was amplified by RT-PCR.

Therapeutic potential of dendritic cell-based immunization against HBV in transgenic mice.

Hepatitis B virus (HBV) transgenic mice that express HBV envelope proteins represent a model of chronic HBV infection suitable for the development of therapeutic immunization strategies. To address immunologically therapeutic effects induced by peptide-pulsed DCs, HBV transgenic mice were immunized with peptide-pulsed DCs, and the mice were killed after three times of immunization and the splenocytes were stimulated in vitro and detected by IFN-gamma ELISPOT and cytotoxic T lymphocyte (CTL) activity. The data demonstrated that HBV-specific CD8+ T cell response could be induced and CD8+ T cells had specific CTL activity.