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Sepsis-associated acute kidney injury (SA-AKI) is common in patients with severe sepsis, and has a high incidence rate and high mortality rate in ICU patients. Most patients progress to AKI before drug treatment is initiated. Early studies suggest that the main mechanism of SA-AKI is that sepsis leads to vasodilation, hypotension and shock, resulting in insufficient renal blood perfusion, finally leading to renal tubular cell ischemia and necrosis. Research results in recent years have shown that programmed cell death such as apoptosis, necroptosis, pyroptosis and autophagy play important roles. In the early stage of sepsis-related AKI, autophagy bodies form and inhibit various types of programmed cell death. With the progress of disease, programmed cell death begins. Apoptosis promoter represents caspase-8-induced apoptosis and apoptosis effector represents caspase-3-induced apoptosis, however, caspase-11 and caspase-1 regulate gasdermin D-mediated pyroptosis. Caspase-8 and receptor interacting kinase 1 bodies mediate necroptosis. This review focuses on the pathophysiological mechanisms of various programmed cell death in sepsis-related AKI.

Identifying better predictive and prognostic biomarkers for the diagnosis and treatment of triple negative breast cancer (TNBC) is complicated by tumor heterogeneity ranging from responses to therapy, mutational burden, and clonal evolution. To overcome the gap in our understanding of tumor heterogeneity, we hypothesized that isolating and studying the gene expression profile of invasive tumor cell subpopulations would be a crucial step towards achieving this goal. In this report, we utilized a fluidic device previously reported to be capable of supporting long-term three-dimensional growth and invasion dynamics of cancer cells. Live invading and matched non-invading SUM149 inflammatory breast cancer cells were enriched using this device and these two functionally distinct subpopulations were tested for differences in gene expression using a gene expression microarray. 305 target genes were identified to have altered expression in the invading cells compared to the non-invading tumoroid cells. Gene ontology analysis of the gene panel identified multiple biological roles ranging from extracellular matrix reorganization to modulation of the immune response and Rho signaling. Interestingly, the genes associated with the invasion front differ between different samples, consistent with inter- and intra-tumor heterogeneity. This work suggests the impact of heterogeneity in biomarker discovery should be considered as cancer therapy increasingly heads towards a personalized approach.

At present, there is no effective drug for the treatment of renal fibrosis; in particular, a safe and effective treatment for renal fibrosis should be established. Cordyceps has several medical effects, including immunoregulatory, antitumor, anti-inflammatory, and antioxidant effects, and may prevent kidney, liver, and heart diseases. Cordyceps has also been reported to be effective in the treatment of renal fibrosis. In this paper, we review the potential mechanisms of Cordyceps against renal fibrosis, focusing on the effects of Cordyceps on inflammation, oxidative stress, apoptosis, regulation of autophagy, reduction of extracellular matrix deposition, and fibroblast activation. We also discuss relevant published clinical trials and meta-analyses. Available clinical studies support the possibility that Cordyceps and related products provide benefits to patients with chronic kidney diseases as adjuvants to conventional drugs. However, the existing clinical studies are limited by low quality and significant heterogeneity. The use of Cordyceps and related products may be a potential strategy for the treatment of renal fibrosis. Randomized controlled trial studies with good methodological quality, favorable experimental design, and large sample size are needed to evaluate the efficacy and safety of Cordyceps.

Although recent studies have reported that long non-coding RNA (lncRNA) is involved in the development of ischemic acute kidney injury (AKI), the exact function and regulatory mechanism of lncRNAs in ischemic AKI remain largely unknown. Herein, we found that ischemic injury promoted the expression of lncRNA 148400 in mouse proximal tubule-derived cell line (BUMPT) and C57BL/6J mice. Furthermore, the lncRNA148400 mediates ischemic injury-induced apoptosis of BUMPT cells. Mechanistically, lncRNA 148400 sponged miR−10b−3p to promote apoptosis via GRK4 upregulation. Finally, knockdown of lncRNA 148400 alleviated the I/R-induced deterioration of renal function, renal tubular injury, and cell apoptosis. In addition, cleaved caspase−3 is increased via targeting the miR−10b−3p/GRK4 axis. Collectively, these results showed that lncRNA 148400/miR−10b−3p/GRK4 axis mediated the development of ischemic AKI.

Tanshinone IIA (Tan IIA), a bioactive compound derived from the traditional Chinese herb , is well-known for its protective effects in various kidney diseases. However, its role in obstructive nephropathy has not been thoroughly investigated. This study aimed to explore the protective effects of Tan IIA in a mouse model of unilateral ureteral obstruction (UUO) and to elucidate the cellular and molecular mechanisms underlying these effects. Gasdermin D (GSDMD) knockout mice and their wild-type (WT) littermates underwent UUO surgery, with Tan IIA treatment administered 24 h prior. Human proximal tubular cells (HK-2 cells) were treated with TGF-β1 to induce fibrosis (50 ng/mL for 24 h), followed by Tan IIA treatment (5 μM) for an additional 3 h. Tan IIA significantly reduced the expression of extracellular matrix (ECM) components, including collagen I, α-smooth muscle actin (α-SMA), vimentin and fibronectin, in UUO mice. Tan IIA attenuated GSDMD-mediated pyroptosis. However, in GSDMD knockout mice subjected to UUO, the protective effects of Tan IIA on ECM gene expression and collagen deposition in the tubular interstitium were reduced. studies showed that Tan IIA reduced GSDMD activation and fibronectin protein expression in HK-2 cells. Tan IIA may mitigate GSDMD-mediated pyroptosis in renal tubular epithelial cells (RTECs) and reduce kidney fibrosis, highlighting its potential as a therapeutic strategy to prevent the progression of kidney disease after ureteral obstruction.

Hemodialysis patients frequently experience chronic inflammation and malnutrition, while C-reactive protein to prealbumin ratio (CP ratio) is a comprehensive assessment approach of inflammatory and nutritional status. Howerer, there is limited research on the prognostic value of the CP ratio specifically in hemodialysis patients infected with the Omicron variant. Data from 847 hemodialysis patients, diagnosed with Omicron across 6 hemodialysis centers between December 2022 and February 2023, were analyzed. Hazard ratios were estimated using univariate and multivariable Cox regression, and receiver operating characteristic curves were used to evaluate the predictive abilities. Survival rate differences between higher and lower CP ratio groups were analyzed using the Kaplan-Meier method. From the total, 98 patients (11.6%) succumbed, with a majority (80/98) within a month post-infection. C-reactive protein, prealbumin, and CP ratio were all associated with all-cause mortality in the crude model. After adjusting for other confounding factors, the CP ratio remained an independent risk factor for all-cause mortality (HR 1.97; 95% CI 1.07-3.63;  = 0.029). In addition, we also found that the CP ratio has better discriminatory ability, than the C-reactive protein to albumin ratio (areas under the curve; 0.84 vs. 0.80; Z-test;  = 0.001). This study underscores that CP ratio substantially influence the mortality rates in hemodialysis patients following Omicron infection. Careful monitoring and consideration of the CP ratio could inform more effective patient management strategies, potentially leading to reduced mortality rates in this vulnerable group.

Background Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a critical pathological mechanism in acute kidney injury (AKI). While pharmacologic targeting of ferroptosis holds therapeutic potential, clinically applicable inhibitors remain elusive, with even the classical inhibitor ferrostatin-1 (Fer-1) demonstrating limitations. Ginsenoside Rb1 (Rb1), a major active component of Panax ginseng, has recently been shown to inhibit ferroptosis in non-renal tissues. This study aimed to investigate the role and mechanism of Rb1 in treating AKI. Methods The protective and anti-ferroptotic effects of Rb1 on AKI were evaluated by assessing renal function, tissue damage, inflammation, ferrous iron, glutathione, malondialdehyde, and ferroptosis markers in C57BL/6 mice, as well as cell viability and ferroptosis-related indicators in HK-2 cells. Network pharmacology and molecular docking were employed to identify Rb1's target proteins. Transcriptome sequencing predicted further mechanisms underlying its anti-ferroptotic effects, which were subsequently validated through in vivo and in vitro experiments. Results The experimental results demonstrated that Rb1 administration significantly ameliorated renal dysfunction, attenuated tubular necrosis and inflammatory responses, while markedly suppressing ferroptosis-related indicators. Strikingly, Rb1 exhibited superior efficacy to Fer-1 in preventing ferroptosis in proximal tubular epithelial cells (PTECs) in vitro. Nuclear factor erythroid 2-related factor 2 (NRF2) was verified as a direct target for Rb1's ferroptosis-inhibitory effect. Mechanistic studies revealed that Rb1 selectively inhibits lipid peroxidation—the biochemical hallmark of ferroptosis—by activating the NRF2-PPARγ-ACSL4 axis.  Conclusion Given its established safety profile in human use, Rb1 represents a potential therapeutic agent for preventing and treating AKI, providing scientific evidence for its application in anti-ferroptosis therapy.

A growing number of studies have confirmed that immune cells play various key roles in the pathophysiology of acute kidney injury (AKI) development. After the resident immune cells and intrinsic renal cells are damaged by ischemia and hypoxia, drugs and toxins, more immune cells will be recruited to infiltrate through the release of chemokines, while the intrinsic cells promote macrophage polarity conversion, and the immune cells will promote various programmed deaths, phenotypic conversion and cycle arrest of the intrinsic cells, ultimately leading to renal impairment and fibrosis. In the complex and dynamic immune microenvironment of AKI, the bidirectional interaction between immune cells and intrinsic renal cells affects the prognosis of the kidney and the progression of fibrosis, and determines the ultimate fate of the kidney.

There is ample evidence to suggest that patients infected with SARS-CoV-2 Omicron variant may experience liver dysfunction. However, the impact of pre-infection liver function on postinfection mortality rates remains inadequately researched. Data from 847 hemodialysis (HD) patients, diagnosed with Omicron across six HD centers between December 2022 and February 2023, were analyzed. Initial liver function assessments were conducted, following which patients were monitored for mortality outcomes. The stepwise multivariable Cox regression analysis and receiver operating characteristic (ROC) curves were utilized to identify the predictors of mortality. From the total, 98 patients (11.6%) succumbed, with a majority (80/98) within a month postinfection. The deceased patients were observed to be mostly older males with an increased prevalence of diabetes and tumors, signifying higher AST and C-reactive protein levels. These patients also exhibited lower hemoglobin, albumin, and prealbumin levels. An elevated AST [per 1 IU increment; HR 1.04 (95% CI 1-1.04),  = 0.026], AST/ALT ratio [per 1 increment; HR 1.52 (95% CI 1.27-2.36),  = 0.004], and reduced prealbumin [per 10 mg/L increment; HR 0.93 (95% CI 0.9-0.96),  < 0.001] were discovered to be independent indicators of an increased mortality risk. Notably, AST, AST/ALT ratio, and prealbumin proved significant predictors of mortality (AUC values were 0.59, 0.65, and 0.79 respectively). This study underscores that pre-infection liver function, specifically AST, AST/ALT ratio, and prealbumin levels, substantially influence the mortality rates in HD patients following Omicron infection. Therefore, careful consideration of these liver function parameters could guide superior patient management strategies and potentially decrease mortality rates within this at-risk population.

Trivalent lanthanide (Ln 3+ )-doped luminescent nanoparticles (NPs) have been extensively investigated as deep-tissue-penetration visual bioimaging agents owing to their exceptional upconversion and near-infrared (NIR) luminescence upon irradiation of NIR light. However, in most cases, the power density of irradiation used for in vivo biological imaging is much higher than that of the reported maximum permissible exposure (MPE) value of NIR light, which inevitably does great damage to the living organisms under study and thus impedes the plausible clinical applications. Herein, by using a facile syringe pump-aided shell epitaxial growth method, we construct for the first time a new class of Ln 3+ -doped KMgF 3 :Yb/Er@KMgF 3 core-shell NPs that can be activated by utilizing a 980-nm xenon lamp or diode laser with an ultralow excitation power density down to 0.08 mW cm −2 , a value that is approximately 4 orders of magnitude lower than the MPE value set by the American National Standards Institute (ANSI) for safe bioimaging in vivo. By combining the comparative spectroscopic investigations with atomic-resolved spherical aberration corrected transmission electron microscopy (AC-TEM) characterization, we find that the reduced crystallographic defects are the primary cause underlying such an ultralow-power-excitable feature of the KMgF 3 : Yb/Er@KMgF 3 core-shell NPs. And, by the same token, the resultant KMgF 3 :Yb/Er@KMgF 3 core-shell NPs also exhibit an anomalous thermo-enhanced photoluminescence (PL) behavior coupled with an excellent photothermal stability that cannot occur in other Ln 3+ -doped core-shell NPs. These findings described here unambiguously pave a new way to prepare high-quality Ln 3+ -doped luminescent NPs with desirable ultralow-power-excitable capability and photothermal stability for future biomedical applications.