Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease. Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes. With the development of immunological technology, many studies have shown that diabetic nephropathy is an immune complex disease, and that most patients have immune dysfunction. However, the immune response associated with diabetic nephropathy and autoimmune kidney disease, or caused by ischemia or infection with acute renal injury, is different, and has a com-plicated pathological mechanism. In this review, we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism, to provide guidance and advice for early intervention and treatment of diabetic nephropathy.

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There are about 14,000 pseudogenes that are mutated or truncated sequences resembling functional parent genes. About two-thirds of pseudogenes are processed, while others are duplicated. Although initially thought dead, emerging studies indicate they have functional and regulatory roles. We study 14-3-3ζ, an adaptor protein that regulates cytokine signaling and inflammatory diseases, including rheumatoid arthritis, cancer, and neurological disorders. To understand how 14-3-3ζ (gene symbol YWHAZ) performs diverse functions, we examined the human genome and identified nine YWHAZ pseudogenes spread across many chromosomes. Unlike the 32 kb exon-to-exon sequence in YWHAZ, all pseudogenes are much shorter and lack introns. Out of six, four YWHAZ exons are highly conserved, but the untranslated region (UTR) shows significant diversity. The putative amino acid sequence of pseudogenes is 78-97% homologous, resulting in striking structural similarities with the parent protein. The OMIM and Decipher database searches revealed chromosomal loci containing pseudogenes are associated with human diseases that overlap with the parent gene. To the best of our knowledge, this is the first report on pseudogenes of the 14-3-3 family protein and their implications for human health. This bioinformatics-based study introduces a new insight into the complexity of 14-3-3ζ\'s functions in biology.

Depression is a serious public health problem, and adolescence is an \'age of risk\' for the onset of Major Depressive Disorder. Recently, we and others have proposed neuroimmune network models that highlight bidirectional communication between the brain and the immune system in both mental and physical health, including depression. These models draw on research indicating that the cellular actors (particularly monocytes) and signaling molecules (particularly cytokines) that orchestrate inflammation in the periphery can directly modulate the structure and function of the brain. In the brain, inflammatory activity heightens sensitivity to threats in the cortico-amygdala circuit, lowers sensitivity to rewards in the cortico-striatal circuit, and alters executive control and emotion regulation in the prefrontal cortex. When dysregulated, and particularly under conditions of chronic stress, inflammation can generate feelings of dysphoria, distress, and anhedonia. This is proposed to initiate unhealthy, self-medicating behaviors (e.g. substance use, poor diet) to manage the dysphoria, which further heighten inflammation. Over time, dysregulation in these brain circuits and the inflammatory response may compound each other to form a positive feedback loop, whereby dysregulation in one organ system exacerbates the other. We and others suggest that this neuroimmune dysregulation is a dynamic joint vulnerability for depression, particularly during adolescence. We have three goals for the present paper. First, we extend neuroimmune network models of mental and physical health to generate a developmental framework of risk for the onset of depression during adolescence. Second, we examine how a neuroimmune network perspective can help explain the high rates of comorbidity between depression and other psychiatric disorders across development, and multimorbidity between depression and stress-related medical illnesses. Finally, we consider how identifying neuroimmune pathways to depression can facilitate a \'next generation\' of behavioral and biological interventions that target neuroimmune signaling to treat, and ideally prevent, depression in youth and adolescents.

Immune disorders caused by sepsis have recently drawn much attention. We sought to dynamically monitor the expression of small extracellular vesicle (sEV) miRNAs in peripheral blood during sepsis to explore these miRNAs as potential biomarkers for monitoring immune function in sepsis patients. This study included patients with sepsis. Blood samples were obtained from 10 patients on the first through 10th days, the 12th day and the 14th day since sepsis onset, resulting in 120 collected samples. Serum sEVs were extracted from peripheral venous blood, and levels of MIR497HG, miR-195, miR-497, and PD-L1 in serum sEVs were detected by qPCR, and clinical information was recorded. Our study revealed that the levels of MIR497HG, miR-195, miR-497 and PD-L1 in serum sEVs showed periodic changes; the time from peak to trough was approximately 4-5 days. The levels of sEV MIR497HG and miR-195 had a positive linear relationship with SOFA score (r values were -0.181 and -0.189; p values were 0.048 and 0.039, respectively). The recorded quantities of sEV MIR497HG, miR-195 and PD-L1 showed a substantial correlation with ARDS. ROC curve analysis revealed that sEV MIR497HG, miR-195 and miR-497 could predict the 28-day mortality of sepsis patients with an AUC of 0.66, 0.68 and 0.72, respectively. Levels of sEVs MIR497HG, miR-195, miR-497 and PD-L1 showed periodic changes with the immune status of sepsis, which provides a new exploration direction for immune function biomarkers and immunotherapy timing in sepsis patients.

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UNASSIGNED: Acute respiratory distress syndrome (ARDS) is caused by severe pulmonary inflammation and the leading cause of death in the intensive care unit.
UNASSIGNED: We used single-cell RNA sequencing to compare peripheral blood mononuclear cells from sepsis-induced ARDS (SEP-ARDS) and pneumonic ARDS (PNE-ARDS) patient. Then, we used the GSE152978 and GSE152979 datasets to identify molecular dysregulation mechanisms at the transcriptional level in ARDS.
UNASSIGNED: Markedly increased CD14 cells were the predominant immune cell type observed in SEP-ARDS and PNE-ARDS patients. Cytotoxic cells and natural killer (NK) T cells were exclusively identified in patients with PNE-ARDS. An enrichment analysis of differentially expressed genes (DEGs) suggested that Th1 cell differentiation and Th2 cell differentiation were enriched in cytotoxic cells, and that the IL-17 signaling pathway, NOD receptor signaling pathway, and complement and coagulation cascades were enriched in CD14 cells. Furthermore, according to GSE152978 and GSE152979, 1939 DEGs were identified in patients with ARDS and controls; they were mainly enriched in the Kyoto Encyclopedia of Genes and Genomes pathways. RBP7 had the highest area under the curve values among the 12 hub genes and was mainly expressed in CD14 cells. Additionally, hub genes were negatively correlated with NK cells and positively correlated with neutrophils, cytotoxic cells, B cells, and macrophages.
UNASSIGNED: A severe imbalance in the proportion of immune cells and immune dysfunction were observed in SEP-ARDS and PNE-ARDS patients. RBP7 may be immunologically associated with CD14 cells and serve as a potential marker of ARDS.

Nucleotides are the foundational elements of life. Proliferative cells acquire nutrients for energy production and the synthesis of macromolecules, including proteins, lipids, and nucleic acids. Nucleotides are continuously replenished through the activation of the nucleotide synthesis pathways. Despite the importance of nucleotides in cell physiology, there is still much to learn about how the purine and pyrimidine synthesis pathways are regulated in response to intracellular and exogenous signals. Over the past decade, evidence has emerged that several signaling pathways [Akt, mechanistic target of rapamycin complex I (mTORC1), RAS, TP53, and Hippo-Yes-associated protein (YAP) signaling] alter nucleotide synthesis activity and influence cell function. Here, we examine the mechanisms by which these signaling networks affect de novo nucleotide synthesis in mammalian cells. We also discuss how these molecular links can be targeted in diseases such as cancers and immune disorders.

Fever has a complicated etiology, and diagnosing its causative factor is clinically challenging. Human cytomegalovirus (HCMV) infection causes various diseases. However, the clinical relevance, prevalence, and significance of HCMV microRNAs (miRNA) in association with fever remain unclear. In the present study, we analyzed the HCMV miRNA expression pattern in the serum of patients with fever and evaluate its clinical associations with occult HCMV infection status in immune disorders.
We included serum samples from 138 patients with fever and 151 age-gender-matched controls in this study. First, the serum levels of 24 HCMV miRNAs were determined using a hydrolysis probe-based stem-loop quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay in the training set. The markedly altered miRNAs were verified in the validation and testing sets. The serum HCMV IgG/IgM and DNA titers in the testing cohort were also assessed using enzyme-linked immunosorbent assay (ELISA) and RT-qPCR, respectively.
The majority of HCMV miRNAs were markedly upregulated in the serum of fever patients. We selected the five most significantly altered HCMV miRNAs: hcmv-miR-US4-3p, hcmv-miR-US29-3p, hcmv-miR-US5-2-3p, hcmv-miR-UL112-3p, and hcmv-miR-US33-3p for validation. These miRNAs were also significantly elevated in the serum of fever patients in the validation and testing sets compared with the controls. Logistic regression analysis revealed that the five miRNAs were novel potential risk factors for fever. Notably, the serum levels of four of the five confirmed HCMV miRNAs were significantly associated with blood C-reaction protein concentrations. Moreover, the five HCMV miRNA levels were closely correlated with the HCMV DNA titers in the testing cohort.
HCMV infection and activation are common in fever patients and could be novel risk factors for fever. These differentially expressed HCMV miRNAs could enable HCMV activation status monitoring in immune disorders.

Cholesterol gallstones are very common in hepatobiliary surgery and have been studied to a certain extent by doctors worldwide for decades. However, the mechanism of cholesterol gallstone formation is not fully understood, so there is currently no completely effective drug for the treatment and prevention of cholesterol gallstones. The formation and development of cholesterol gallstones are caused by a variety of genetic and environmental factors, among which genetic susceptibility, intestinal microflora disorders, impaired gallbladder motility, and immune disorders are important in the pathogenesis of cholesterol gallstones. This review focuses on recent advances in these mechanisms. We also discuss some new targets that may be effective in the treatment and prevention of cholesterol gallstones, which may be hot areas in the future.