[Tetrapeptide repeat domain 36 (TTC36) inhibits the inflammatory response of HK2 cells by enhancing the expression of IκBα to inhibit the activation of NF-κB signaling pathway].

Objective To investigate the effects and underlying mechanisms of tetratricopeptide repeat domain 36 (TTC36) on injury of HK2 renal tubular epithelial cell. Methods HK2 stable cell lines expressing either TTC36 and an empty vector control-CMV-Flag were generated with lentivirus . The mRNA expression level of tumor necrosis factor α (TNF-α), inducible nitric oxide synthase(iNOS), interleukin 6(IL-6), C-C motif chemokine ligand 2(CCL2), IL-1β, inhibitor of nuclear factor κB α(IκBα) and nuclear factor κB p65(NF-κB p65) were analyzed by real time quantitative PCR (qRT-PCR).

Inhibits Cell Proliferation and the Warburg Effect in Bladder Cancer by Blocking PDHK1.

Background: Cancer treatment has recently shifted towards metabolic approaches aimed at enhancing therapeutic efficacy. Somewhat surprisingly, a known regulator of energy metabolism in normal tissues, , is down-regulated in bladder cancer. This suggests that could exert an inhibitory effect on bladder cancer through its role in energy metabolism.

Temporary impact on medical system and effectiveness of mitigation strategies after COVID-19 policy adjustment in China: a modeling study.

Background: As China amends its "zero COVID" strategy, a sudden increase in the number of infections may overwhelm medical resources and its impact has not been quantified. Specific mitigation strategies are needed to minimize disruption to the healthcare system and to prepare for the next possible epidemic in advance.

Method: We develop a stochastic compartmental model to project the burden on the medical system (that is, the number of fever clinic visits and admission beds) of China after adjustment to COVID-19 policy, which considers the epidemiological characteristics of the Omicron variant, age composition of the population, and vaccine effectiveness against infection and severe COVD-19.

Biofabricated macrophage and fibroblast membranes synergistically promote skin wound healing.

Effective skin wound healing is a complex process involving anti-inflammation, fibrosis, matrix reconstruction, and angiogenesis. This work aimed to integrate the macrophage-mediated anti-inflammation and fibroblast-assisted matrix reconstruction for enhanced skin wound healing. Herein, we utilized the cytomembranes derived from repolarized M2 macrophages and fibroblasts to prepare the natural biologics.

Tetratricopeptide repeat domain 36 protects renal tubular cells from cisplatin-induced apoptosis potentially via maintaining mitochondrial homeostasis.

The apoptosis of proximal tubule epithelial cells (PTECs) is a critical event of acute kidney injury (AKI). Tetratricopeptide repeat domain 36 (TTC36) with three tetratricopeptide repeats is evolutionarily conserved across mammals, which functions as a chaperone for heat shock protein 70. We have revealed that TTC36 is specifically expressed in PTECs in our previous work.

mA Regulator-Mediated Methylation Modification Patterns and Characteristics of Immunity in Blood Leukocytes of COVID-19 Patients.

Both RNA N6-methyladenosine (mA) modification of SARS-CoV-2 and immune characteristics of the human body have been reported to play an important role in COVID-19, but how the mA methylation modification of leukocytes responds to the virus infection remains unknown. Based on the RNA-seq of 126 samples from the GEO database, we disclosed that there is a remarkably higher mA modification level of blood leukocytes in patients with COVID-19 compared to patients without COVID-19, and this difference was related to CD4 T cells. Two clusters were identified by unsupervised clustering, mA cluster A characterized by T cell activation had a higher prognosis than mA cluster B.

Macrophage-derived implantable vaccine prevents postsurgical tumor recurrence.

Immunotherapy emerges as a potential therapeutic strategy against tumor relapse. However, immunosuppressive tumor microenvironment poses an obstacle to immunotherapy. Of particular note is that macrophages are abundant in solid tumors and tumor-associated macrophages (TAMs) are mainly anti-inflammatory and protumoral.

Tetratricopeptide repeat domain 36 deficiency mitigates renal tubular injury by inhibiting TGF-β1-induced epithelial-mesenchymal transition in a mouse model of chronic kidney disease.

The damage of proximal tubular epithelial cells (PTECs) is considered a central event in the pathogenesis of chronic kidney disease (CKD) and deregulated repair processes of PTECs result in epithelial-mesenchymal transition (EMT), which in turn aggravates tubular injury and kidney fibrosis. In this study, we firstly revealed that the reduction of TTC36 is associated with unilateral ureteral obstruction (UUO)-induced CKD; besides, ablation of TTC36 attenuated tubular injury and subsequent EMT in UUO-treated mice kidneys. Consistently, TTC36 overexpression promoted EMT in TGF-β1-induced HK2 cells.

ID1 As a Prognostic Biomarker and Promising Drug Target Plays a Pivotal Role in Deterioration of Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most common cancers in the world. Our aim is to identify prognostic biomarkers that contribute to the progression of early stage ccRCC and clarify the mechanism. Here, the mRNA microarray expression profile of ccRCC samples was obtained from Gene Expression Omnibus (GEO) (GSE68417).

[PPP3CA silence regulates MET process, cell apoptosis, proliferation and migration in metanephric mesenchyme cells].

Kidney is one of the most important organs of the body and the mammalian kidney development is essential for kidney unit formation. The key process of kidney development is metanephric development, where mesenchymal-epithelial transition (MET) plays a crucial role. Here we investigated the biological function of PPP3CA in metanephric mesenchyme (MM) cells.

A Derivate of Benzimidazole-Isoquinolinone Induces SKP2 Transcriptional Inhibition to Exert Anti-Tumor Activity in Glioblastoma Cells.

We have previously shown that compound-7g inhibits colorectal cancer cell proliferation and survival by inducing cell cycle arrest and PI3K/AKT/mTOR pathway blockage. However, whether it has the ability to exert antitumor activity in other cancer cells and what is the exact molecular mechanism for its antiproliferation effect remained to be determined. In the present study, compound-7g exhibited strong activity in suppressing proliferation and growth of glioblastoma cells.

Negatively Modulates in Tumor Formation of Clear Cell Renal Cell Carcinoma.

Substantial research has revealed that peroxisome proliferator-activated receptor-gamma (PPARG) plays a critical role in glucose homeostasis and lipid metabolism, and recent studies have shown different effects in the progression of different tumors. However, the role of PPARG and its target gene in clear cell renal cell carcinoma (ccRCC) are incompletely understood. Clinical data revealed abnormal glucolipid metabolism in primary ccRCC samples.

PPP3CB Inhibits Migration of G401 Cells via Regulating Epithelial-to-Mesenchymal Transition and Promotes G401 Cells Growth.

PPP3CB belongs to the phosphoprotein phosphatases (PPPs) group. Although the majority of the PPP family play important roles in the epithelial-to-mesenchymal transition (EMT) of tumor cells, little is known about the function of PPP3CB in the EMT process. Here, we found PPP3CB had high expression in kidney mesenchymal-like cells compared with kidney epithelial-like cells.

PPARγ maintains the metabolic heterogeneity and homeostasis of renal tubules.

Background: The renal tubules, which have distant metabolic features and functions in different segments, reabsorb >99% of approximately 180 l of water and 25,000 mmol of Na  daily. Defective metabolism in renal tubules is involved in the pathobiology of kidney diseases. However, the mechanisms underlying the metabolic regulation in renal tubules remain to be defined.

Gulo regulates the proliferation, apoptosis and mesenchymal-to-epithelial transformation of metanephric mesenchyme cells via inhibiting Six2.

During kidney development, the balance between self-renewal and differentiation of metanephric mesenchyme (MM) cells, mainly regulated by Sine oculis-related homeobox 2 (Six2), is critical for forming mature kidney. L-gulono-γ-lactone oxidase (Gulo), a crucial enzyme for vitamin C synthesis, reveals a different expression at various stages during kidney development, but its function in the early renal development remains unknown. In this work, we aim to study the role of Gulo in MM cells at two differentiation stages.

Apobec-1 complementation factor regulates cell migration and apoptosis through Dickkopf1 by acting on its 3' untranslated region in MCF7 cells.

A1CF (apobec-1 complementation factor) acts as a component of the apolipoprotein-B messenger RNA editing complex. Previous researches mainly focused on its post-transcriptional cytidine to uridine RNA editing. However, few study reported its role in progression of breast carcinoma cells.

Blockade of Y177 and Nuclear Translocation of Bcr-Abl Inhibits Proliferation and Promotes Apoptosis in Chronic Myeloid Leukemia Cells.

The gradual emerging of resistance to imatinib urgently calls for the development of new therapy for chronic myeloid leukemia (CML). The fusion protein Bcr-Abl, which promotes the malignant transformation of CML cells, is mainly located in the cytoplasm, while the c-Abl protein which is expressed in the nucleus can induce apoptosis. Based on the hetero-dimerization of FKBP (the 12-kDa FK506- and rapamycin-binding protein) and FRB (the FKBP-rapamycin binding domain of the protein kinase, mTOR) mediated by AP21967, we constructed a nuclear transport system to induce cytoplasmic Bcr-Abl into nuclear.

MiR542-3p Regulates the Epithelial-Mesenchymal Transition by Directly Targeting BMP7 in NRK52e.

Accumulating evidence demonstrated that miRNAs are highly involved in kidney fibrosis and Epithelial-Eesenchymal Transition (EMT), however, the mechanisms of miRNAs in kidney fibrosis are poorly understood. In this work, we identified that miR542-3p could promote EMT through down-regulating bone morphogenetic protein 7 (BMP7) expression by targeting BMP7 3'UTR. Firstly, real-time PCR results showed that miR542-3p was significantly up-regulated in kidney fibrosis in vitro and in vivo.

MiR-30a Inhibits the Epithelial--Mesenchymal Transition of Podocytes through Downregulation of NFATc3.

MicroRNAs (miRNAs) possess an important regulating effect among numerous renal diseases, while their functions in the process of epithelial-to-mesenchymal transition (EMT) after podocyte injury remain unclear. The purpose of our study is to identify the potential functions of miR-30a in EMT of podocytes and explore the underlying mechanisms of miR-30a in the impaired podocytes. The results revealed that downregulation of miR-30a in podocyte injury animal models and patients, highly induced the mesenchymal markers of EMT including Collagen I, Fibronectin and Snail.

miR-135 family members mediate podocyte injury through the activation of Wnt/β-catenin signaling.

The upregulation of Wnt/β-catenin signaling occurs in virtually all types of kidney disease and is associated with podocyte injury. However, the precise mechanisms involved in the development of kidney disease remain to be elucidated. MicroRNAs (miRNAs or miRs) are a class of short non-coding RNAs and they have been shown to be regulators of gene expression, mainly by binding to the untranslated region (UTR) of mRNAs.

Down-regulated Six2 by knockdown of neurofibromin results in apoptosis of metanephric mesenchyme cells in vitro.

Embryonic Six2-positive nephron progenitor cells adjacent to ureteric bud tips ultimately give rise to nephron structures, including proximal and distal tubules, podocytes, Bowman's capsules, and the glomeruli. This process requires an internal balance between self-renew and differentiation of the nephron progenitor cells, which is mediated by numerous molecules. Recent studies have shown that the neurofibromin (Nf1) null mutant mouse embryos have an 18- to 24-h developmental delay in metanephros manifesting retardation in its cephalad repositioning and reduction number of glomeruli.

Induction of apoptosis by directing oncogenic Bcr-Abl into the nucleus.

The chimeric Bcr-Abl oncoprotein, which causes chronic myeloid leukemia, mainly localizes in the cytoplasm, and loses its ability to transform cells after moving into the nucleus. Here we report a new strategy to convert Bcr-Abl to be an apoptotic inducer by altering its subcellular localization. We show that a rapalog nuclear transport system (RNTS) containing six nuclear localization signals directs Bcr-Abl into the nucleus and that nuclear entrapped Bcr-Abl induces apoptosis and inhibits proliferation of CML cells by activating p73 and shutting down cytoplasmic oncogenic signals mediated by Bcr-Abl.