Calmodulin-dependent protein kinase II activation promotes kidney mesangial expansion in streptozotocin-induced diabetic mice

Mikhailov, Alexei; Liu, Yixi; Cheng, Heng-Jie; Lin, Jen-Jar; Cheng, Che Ping

doi:10.1016/j.heliyon.2022.e11653

Cited by 4 publications

(1 citation statement)

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“…After selecting the image field, the tissue image of the corresponding area was extracted using slide‐reading software (Figure 1C ). In a further step, the binarization transformation of the tissue image was implemented through the TWS plug‐in 19 , 20 , 21 of ImageJ software (Figure 1D–F ). In short, the area of the tumor cells was measured on brown‐stained paraffin slides using a trainable segmentation method based on the WEKA TWS plug‐in.…”

Section: Methodsmentioning

confidence: 99%

Multiperspective quantitative tumor–stroma ratio reveals histological areas associated with poor outcomes in oral squamous cell carcinoma

Wang

Yan

et al. 2023

Cancer Medicine

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Aims Different regions of oral squamous cell carcinoma (OSCC) have particular histopathological characteristics, and the individual histological characteristics of the tumors are poorly understood. Therefore, calculating the proportion of tumor cells in different regions that allow assessment of the prognostic outcomes for OSCC patients would be of great clinical significance. Methods and Results We established an open‐source software‐based analytic pipeline that defines the inner tumor and invasive tumor front (ITF) in pancytokeratin‐stained whole slide images (WSIs) and quantifies the tumor‐stroma ratio (TSR) within the two regions. We applied this method to 114 patients with OSCC and predicted patient prognosis by the TSR. The proportion of tumor area in the inner tumor was generally higher than that in the ITF (p < 0.0001). TSR was an independent prognostic factor for overall survival (OS) (p = 0.016), disease‐free survival (DFS) (p = 0.026), and relapse‐free survival (RFS) (p = 0.037) in inner tumor, and TSR was an independent prognostic factor for OS (p = 0.00052), DFS (p = 0.035), and metastasis‐free survival (MFS) (p = 0.038) in the ITF. Tumor‐low status was associated with poorer prognosis. There was a significant correlation between the TSR and perineural invasion (PNI) in the inner tumor (p = 0.009). Conclusions The histopathological characteristics of different regions of OSCC may be used to develop the potential prognostic markers. The TSR of the inner tumor is more targeted in predicting prognosis and accurately assesses the risk of PNI+.

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Section: Methodsmentioning

confidence: 99%

Multiperspective quantitative tumor–stroma ratio reveals histological areas associated with poor outcomes in oral squamous cell carcinoma

Wang

Yan

et al. 2023

Cancer Medicine

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Podocyte-specific KLF6 primes proximal tubule CaMK1D signaling to attenuate diabetic kidney disease

Gujarati,

Frimpong,

Zaidi

et al. 2024

Nat Commun

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Diabetic kidney disease (DKD) is the main cause of chronic kidney disease worldwide. While injury to the podocytes, visceral epithelial cells that comprise the glomerular filtration barrier, drives albuminuria, proximal tubule (PT) dysfunction is the critical mediator of DKD progression. Here, we report that the podocyte-specific induction of human KLF6, a zinc-finger binding transcription factor, attenuates podocyte loss, PT dysfunction, and eventual interstitial fibrosis in a male murine model of DKD. Utilizing combination of snRNA-seq, snATAC-seq, and tandem mass spectrometry, we demonstrate that podocyte-specific KLF6 triggers the release of secretory ApoJ to activate calcium/calmodulin dependent protein kinase 1D (CaMK1D) signaling in neighboring PT cells. CaMK1D is enriched in the first segment of the PT, proximal to the podocytes, and is critical to attenuating mitochondrial fission and restoring mitochondrial function under diabetic conditions. Targeting podocyte-PT signaling by enhancing ApoJ-CaMK1D might be a key therapeutic strategy in attenuating the progression of DKD.

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The Effect of Selected Nitric Oxide Synthase Polymorphisms on the Risk of Developing Diabetic Nephropathy

Król-Kulikowska,

Banasik,

Kepinska

2024

Antioxidants

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Background: Nitric oxide synthase (NOS) is an enzyme that catalyzes the formation of nitric oxide (NO), the altered production of which is characteristic of diabetic nephropathy. NOS exists in three isoforms: NOS1, NOS2, and NOS3. Moreover, there are reports about the potential role of NOS3 polymorphisms in the development of diabetes complications. The aim of this study was to assess the role of selected NOS polymorphisms—rs3782218 (NOS1), rs1137933 (NOS2), rs1799983, rs2070744, and rs61722009 (NOS3)—in the risk of developing diabetic nephropathy and in the likelihood of renal replacement therapy. Methods: The studied polymorphisms were analyzed in a group of 232 patients divided into three groups. Four polymorphisms (rs3782218, rs1137933, rs1799983, rs2070744) were genotyped using the PCR-RFLP, while the rs61722009 polymorphism was genotyped using the PCR. Results: The C/C genotype and the C allele of the rs3782218 polymorphism (NOS1) were associated with an increased risk of developing diabetic nephropathy and an increased likelihood of renal replacement therapy. In turn, the G allele of the rs1137933 polymorphism (NOS2) reduces the likelihood of renal replacement therapy. Conclusions: The specific genotypes or alleles of the rs3782218 (NOS1) and rs1137933 (NOS2) polymorphisms seem to be potential risk factors for diabetic nephropathy and renal replacement therapy.

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Calmodulin-dependent protein kinase II activation promotes kidney mesangial expansion in streptozotocin-induced diabetic mice

Cited by 4 publications

References 50 publications

Multiperspective quantitative tumor–stroma ratio reveals histological areas associated with poor outcomes in oral squamous cell carcinoma

Multiperspective quantitative tumor–stroma ratio reveals histological areas associated with poor outcomes in oral squamous cell carcinoma

Podocyte-specific KLF6 primes proximal tubule CaMK1D signaling to attenuate diabetic kidney disease

The Effect of Selected Nitric Oxide Synthase Polymorphisms on the Risk of Developing Diabetic Nephropathy

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