The human gut microbiota is a complex cluster composed of 100 trillion microorganisms, which holds a symbiotic relationship with the host under normal circumstances. Intestinal flora can facilitate the treatment of human metabolic dysfunctions and interact with the intestinal tract, which could influence intestinal tolerance, immunity, and sensitivity to inflammation. In recent years, significant interests have evolved on the association of intestinal microbiota and kidney diseases within the academic circle. Abnormal changes in intestinal microbiota, known as dysbiosis, can affect the integrity of the intestinal barrier, resulting in the bacterial translocation, production, and accumulation of dysbiotic gut-derived metabolites, such as urea, indoxyl sulfate (IS), and p-cresyl sulfate (PCS). These processes lead to the abnormal activation of immune cells; overproduction of antibodies, immune complexes, and inflammatory factors; and inflammatory cell infiltration that can directly or indirectly cause damage to the renal parenchyma. The aim of this review is to summarize the role of intestinal flora in the development and progression of several renal diseases, such as lupus nephritis, chronic kidney disease, diabetic nephropathy, and renal ischemia-reperfusion injury. Further research on these mechanisms should provide insights into the therapeutic potential of regulating intestinal flora and intervening related molecular targets for the abovementioned nephropathy.

Systemic lupus erythematosus (SLE) is an archetype autoimmune disease characterized by a myriad of immunoregulatory abnormalities that drives injury to multiple tissues and organs. Due to the involvement of various immune cells, inflammatory cytokines, and related signaling pathways, researchers have spent a great deal of effort to clarify the complex etiology and pathogenesis of SLE. Nevertheless, current understanding of the pathogenesis of SLE is still in the early stages, and available nonspecific treatment options for SLE patients remain unsatisfactory. First discovered in 1993, microRNAs (miRNAs) are small RNA molecules that control the expression of 1/3 of human genes at the post-transcriptional level and play various roles in gene regulation. The aberrant expression of miRNAs in SLE patients has been intensively studied, and further studies have suggested that these miRNAs may be potentially relevant to abnormal immune responses and disease progression in SLE. The aim of this review was to summarize the specific miRNAs that have been observed aberrantly expressed in several important pathogenetic processes in SLE, such as DCs abnormalities, overactivation and autoantibody production of B cells, aberrant activation of CD4+ T cells, breakdown of immune tolerance, and abnormally increased production of inflammatory cytokines. Our summary highlights a novel perspective on the intricate regulatory network of SLE, which helps to enrich our understanding of this disorder and ignite future interest in evaluating the molecular regulation of miRNAs in autoimmunity SLE.

Kidney disease is a general term for heterogeneous damage that affects the function and the structure of the kidneys. The rising incidence of kidney diseases represents a considerable burden on the healthcare system, so the development of new drugs and the identification of novel therapeutic targets are urgently needed. The pathophysiology of kidney diseases is complex and involves multiple processes, including inflammation, autophagy, cell-cycle progression, and oxidative stress. Heme oxygenase-1 (HO-1), an enzyme involved in the process of heme degradation, has attracted widespread attention in recent years due to its cytoprotective properties. As an enzyme with known anti-oxidative functions, HO-1 plays an indispensable role in the regulation of oxidative stress and is involved in the pathogenesis of several kidney diseases. Moreover, current studies have revealed that HO-1 can affect cell proliferation, cell maturation, and other metabolic processes, thereby altering the function of immune cells. Many strategies, such as the administration of HO-1-overexpressing macrophages, use of phytochemicals, and carbon monoxide-based therapies, have been developed to target HO-1 in a variety of nephropathological animal models, indicating that HO-1 is a promising protein for the treatment of kidney diseases. Here, we briefly review the effects of HO-1 induction on specific immune cell populations with the aim of exploring the potential therapeutic roles of HO-1 and designing HO-1-based therapeutic strategies for the treatment of kidney diseases.

Kidney disease encompasses a complex set of diseases that can aggravate or start systemic pathophysiological processes through their complex metabolic mechanisms and effects on body homoeostasis. The prevalence of kidney disease has increased dramatically over the last two decades. CD4+CD25+ regulatory T (Treg) cells that express the transcription factor forkhead box protein 3 (Foxp3) are critical for maintaining immune homeostasis and preventing autoimmune disease and tissue damage caused by excessive or unnecessary immune activation, including autoimmune kidney diseases. Recent studies have highlighted the critical role of metabolic reprogramming in controlling the plasticity, stability, and function of Treg cells. They are also likely to play a vital role in limiting kidney transplant rejection and potentially promoting transplant tolerance. Metabolic pathways, such as mitochondrial function, glycolysis, lipid synthesis, glutaminolysis, and mammalian target of rapamycin (mTOR) activation, are involved in the development of renal diseases by modulating the function and proliferation of Treg cells. Targeting metabolic pathways to alter Treg cells can offer a promising method for renal disease therapy. In this review, we provide a new perspective on the role of Treg cell metabolism in renal diseases by presenting the renal microenvironment、relevant metabolites of Treg cell metabolism, and the role of Treg cell metabolism in various kidney diseases.

Immunosenescence is the deterioration of the innate and adaptive immune systems associated with aging and is primarily characterized by a reduction in T cell production and accumulation of atypical subsets. Age-related immunological dysfunction leads to impaired immune protection and persistent low-grade chronic inflammation, resulting in a decreased vaccination response and increased vulnerability to infection, cancer, cardiovascular disease, and autoimmune disease in the elderly. As the elderly constitute a growing proportion of the population with renal disease, immunosenescence is a normal aging process that is prevalent among older people. In addition, immunosenescence seems to be more pronounced in patients with kidney diseases than in healthy controls, as shown by severe chronic inflammation, accumulation of immune cells with the senescent phenotype (CD28− T cells, CD14+CD16+ monocytes), and proinflammatory cytokine production. Immunosenescence inhibits immunological clearance and renal tissue regeneration, thereby increasing the risk of permanent renal damage, infection, and cardiovascular events in patients with kidney disease, lowering the prognosis, and even influencing the efficacy of renal replacement treatment. Biological drugs (senomorphics and senolytics) target the aging immune system and exert renoprotective effects. This review aims to emphasize the features of immunosenescence and its influence on kidney diseases and immunotherapy, highlighting the future directions of kidney disease treatment using senescence-focused techniques.

Small‐for‐size syndrome (SFSS) is a common complication following partial liver transplantation and extended hepatectomy. SFSS is characterized by postoperative liver dysfunction caused by insufficient regenerative capacity and portal hyperperfusion and is more frequent in patients with preexisting liver disease. We explored the effect of the Mesenchymal‐epithelial transition factor (MET)‐agonistic antibody 71D6 on liver regeneration and functional recovery in a mouse model of SFSS. Male C57/BL6 mice were exposed to repeated carbon tetrachloride injections for 10 weeks and then randomized into 2 arms receiving 3 mg/kg 71D6 or a control immunoglobulin G (IgG). At 2 days after the randomization, the mice were subjected to 70% hepatectomy. Mouse survival was recorded up to 28 days after hepatectomy. Satellite animals were euthanized at different time points to analyze liver regeneration, fibrosis, and inflammation. Serum 71D6 administration significantly decreased mouse mortality consequent to insufficient regeneration of the cirrhotic liver. Analysis of liver specimens in satellite animals revealed that 71D6 promoted powerful activation of the extracellular signal‐regulated kinase pathway and accelerated liver regeneration, characterized by increased liver‐to‐body weight, augmented mitotic index, and higher serum albumin levels. Moreover, 71D6 accelerated the resolution of hepatic fibrosis as measured by picrosirius red, desmin, and α–smooth muscle actin staining, and suppressed liver infiltration by macrophages as measured by CD68 and F4/80 staining. Analysis of gene expression by reverse‐transcription polymerase chain reaction confirmed that 71D6 administration suppressed the expression of key profibrotic genes, including platelet‐derived growth factor, tissue inhibitor of metalloproteinase 3, and transforming growth factor‐β1, and of key proinflammatory genes, including tumor necrosis factor‐α, interleukin‐1β, chemokine (C‐C motif) ligand 3, and chemokine (C‐C motif) ligand 5. These results suggest that activating the MET pathway via an hepatocyte growth factor–mimetic antibody may be beneficial in patients with SFSS and possibly other types of acute and chronic liver disorders.

Hematopoietic stem cell transplantation (HSCT), also known as bone marrow transplantation, has curative potential for various hematologic malignancies but is associated with risks such as graft-versus-host disease (GvHD), severe bloodstream infection, viral pneumonia, idiopathic pneumonia syndrome (IPS), lung fibrosis, and sinusoidal obstruction syndrome (SOS), which severely deteriorate clinical outcomes and limit the wide application of HSCT. Recent research has provided important insights into the effects of gut microbiota and oxidative stress (OS) on HSCT complications. Therefore, based on recent studies, we describe intestinal dysbiosis and OS in patients with HSCT and review recent molecular findings underlying the causal relationships of gut microbiota, OS, and transplant-related complications, focusing particularly on the involvement of gut microbiota-mediated OS in postengraftment complications. Also, we discuss the use of antioxidative and anti-inflammatory probiotics to manipulate gut microbiota and OS, which have been associated with promising effects in improving HSCT outcomes.

The most extensively and well-investigated sequences in the human genome are protein-coding genes, while large numbers of non-coding sequences exist in the human body and are even more diverse with more potential roles than coding sequences. With the unveiling of non-coding RNA research, long-stranded non-coding RNAs (lncRNAs), a class of transcripts >200 nucleotides in length primarily expressed in the nucleus and rarely in the cytoplasm, have drawn our attention. LncRNAs are involved in various levels of gene regulatory processes, including but not limited to promoter activity, epigenetics, translation and transcription efficiency, and intracellular transport. They are also dysregulated in various pathophysiological processes, especially in diseases and cancers involving genomic imprinting. In recent years, numerous studies have linked lncRNAs to the pathophysiology of various kidney diseases. This review summarizes the molecular mechanisms involved in lncRNAs, their impact on kidney diseases, and associated complications, as well as the value of lncRNAs as emerging biomarkers for the prevention and prognosis of kidney diseases, suggesting their potential as new therapeutic tools.