Circulating B Cell-Derived Small RNA Delivered by Extracellular Vesicles: A Dialogue Mechanism for Long-Range Targeted Renal Mitochondrial Injury in Obesity.

The intricate processes that govern the interactions between peripatetic immune cells and distal renal injury in obesity are not fully understood. Employing transcriptomic analysis of circulating extracellular vesicles (EVs), a marked amplification of small RNA (miR-3960) is discerned within CD3-CD19+ B cells. This RNA is found to be preferentially augmented in kidney tissues, contrasting with its subdued expression in other organs. By synthesizing dual-luciferase reporter assay with co-immunoprecipitation analysis, it is pinpointed that miR-3960 specifically targets the nuclear gene TRMT5, a pivotal actor in the methylation of mitochondrial tRNA. This liaison instigates aberrations in the post-transcriptional modifications of mitochondrial tRNA, engendering deficiencies within the electron respiratory chain, primarily attributable to the diminution of the mitochondrial bioenergetic compound (NDUFA7) complex I. Such perturbations lead to a compromised mitochondrial respiratory capacity in renal tubular cells, thereby exacerbating tubular injury. In contrast, EV blockade or miR-3960 depletion markedly alleviates renal tubular injury in obesity. This investigation unveils a hitherto unexplored pathway by which obesity-induced circulating immune cells remotely manipulate mitochondrial metabolism in target organs. The strategic targeting of obese EVs or infiltrative immune cells and their specifically secreted RNAs emerges as a promising therapeutic avenue to forestall obesity-related renal afflictions.

The polarization of M2 macrophages can be adjusted to alleviate renal injury by methylprednisolone in sepsis-AKI.

Acute kidney injury in sepsis patients has an extreme mortality rate in clinical. It obviously seems that immune cells, for example, macrophages are involved with this process. Macrophages, as highly important immune cells, play a significant role in the development of human kidney diseases. But the specific role of macrophages in this process is still unclear. Under different timeline points, we surprisingly found that macrophages had the most dynamic changes in acute kidney injury immune cells. Based on macrophages' functions, they are primarily classified into M1 macrophages (pro-inflammatory) and M2 macrophages (anti-inflammatory). The polarization of M2 macrophages is closely associated with the seriousness of sepsis-induced kidney injury, but how to modulate their polarization to alleviate sepsis-associated renal damage remains unknown. We discovered that the polarization of M2 macrophages after methylprednisolone injection can significantly alleviate acute kidney injury by reducing secreted cytokine. This study suggests that the proportion of macrophage subtypes can be regulated by methylprednisolone to alleviate acute kidney injury in sepsis to provide a new sight for a clinical to provide a promising strategy for renal injury caused.

Natural Killer Cells, as the Rising Point in Tissues, Are Forgotten in the Kidney.

Natural killer (NK) cells are members of a rapidly expanding family of innate lymphoid cells (ILCs). NK cells play roles in the spleen, periphery, and in many tissues, such as the liver, uterine, lung, adipose, and so on. While the immunological functions of NK cells are well established in these organs, comparatively little is known about NK cells in the kidney. Our understanding of NK cells is rapidly rising, with more and more studies highlighting the functional significance of NK cells in different types of kidney diseases. Recent progress has been made in translating these findings to clinical diseases that occur in the kidney, with indications of subset-specific roles of NK cells in the kidney. For the development of targeted therapeutics to delay kidney disease progression, a better understanding of the NK cell with respect to the mechanisms of kidney diseases is necessary. In order to promote the targeted treatment ability of NK cells in clinical diseases, in this paper we demonstrate the roles that NK cells play in different organs, especially the functions of NK cells in the kidney.

Pathogenesis of Chronic Kidney Disease Is Closely Bound up with Alzheimer's Disease, Especially via the Renin-Angiotensin System.

Chronic kidney disease (CKD) is a clinical syndrome secondary to the definitive change in function and structure of the kidney, which is characterized by its irreversibility and slow and progressive evolution. Alzheimer's disease (AD) is characterized by the extracellular accumulation of misfolded ß-amyloid (Aß) proteins into senile plaques and the formation of neurofibrillary tangles (NFTs) containing hyperphosphorylated tau. In the aging population, CKD and AD are growing problems. CKD patients are prone to cognitive decline and AD. However, the connection between CKD and AD is still unclear. In this review, we take the lead in showing that the development of the pathophysiology of CKD may also cause or exacerbate AD, especially the renin-angiotensin system (RAS). In vivo studies had already shown that the increased expression of angiotensin-converting enzyme (ACE) produces a positive effect in aggravating AD, but ACE inhibitors (ACEIs) have protective effects against AD. Among the possible association of risk factors in CKD and AD, we mainly discuss the RAS in the systemic circulation and the brain.

NEAT1 siRNA Packed with Chitosan Nanoparticles Regulates the Development of Colon Cancer Cells via lncRNA NEAT1/miR-377-3p Axis.

This study was for verifying that transfecting colon cancer cells (CCCs) with lncRNA NEAT1 packed with siRNA chitosan nanoparticles (CNPs) can suppress lncRNA NEAT1 and biological behaviors of the cells. siRNA targeting lncRNA NEAT1 expression vector was constructed and then transfected into CCCs after being packed with CNPs. Subsequently, the impact of the transfection on biological behaviors of the cells was evaluated. As a result, with high expression in CCCs, NEAT1 was negatively bound up with miR-377-3p in cases with colon cancer (CC), and dual luciferase reporter assay confirmed the potential binding region. Additionally, after downregulating NEAT1 in CCCs, transfection of NEAT1 siRNA packed with CNPs brought a great inhibition on cell proliferation and a promotion on apoptosis, and inhibiting miR-377-3p was able to offset the role of silencing NEAT1 in CCCs. Therefore, in our opinion, NEAT1 siRNA packed with CNPs can hinder the growth and metastasis of CCCs by knocking down NEAT1 in CC, and its mechanism may be achieved by targeting miR-377-3p, which offers a novel direction for treating CC.