Mesenchymal stem cells inhibited the inflammation and oxidative stress in LPS-activated microglial cells through AMPK pathway.

Microglia are the resident mononuclear immune cells of the central nervous system (CNS) and the activation of microglia contributes to the production of excessive neurotoxic factors. In particular, the overproduction of neurotoxic factors has critical effects on the development of brain injuries and neurodegenerative diseases. The human bone marrow-derived mesenchymal stem cells (hBM-MSCs) have blossomed into an effective approach with great potential for the treatment of neurodegenerative diseases and gliomas. The present study aimed to investigate the mechanism behind the therapeutic effect of hBM-MSCs on the activation of microglia in vitro. Specifically, the hBM-MSCs significantly inhibited the proliferation of lipopolysaccharide-activated microglial cells (LPS)-activated microglial cells. Additionally, we investigated whether the adenosine-monophosphate-activated protein kinase signaling (AMPK) pathway was involved in this process. Our data demonstrated that hBM-MSCs significantly increased the phosphorylated AMPK in LPS-activated microglial cells. In addition, our study indicated the inhibitory effect of hBM-MSCs on the pro-inflammatory mediators and oxidative stress by the AMPK pathway in LPS-activated microglial cells. These results could shed light on the understanding of the molecular basis for the inhibition of hBM-MSCs on LPS-activated microglial cells and provide a molecular mechanism for the hBM-MSCs implication in brain injuries and neurodegenerative diseases.

Successful Removal and Replacement of a Stuck Hemodialysis Catheter via Thoracotomy: Report of Two Cases and Literature Review.

Introduction: Stuck tunneled central venous catheters (CVCs) have been increasingly reported. In rare cases, the impossibility of extracting the CVC from the central vein after regular traction is the result of rigid adhesions to the surrounding fibrin sheath. Forced traction during catheter removal can cause serious complications, including cardiac tamponade, hemothorax, and hemorrhagic shock. Knowledge and experience on how to properly manage the stuck catheter are still limited. Case Presentation: Here, we present two cases that highlight the successful removal of the stuck tunneled CVC via thoracotomy through the close collaboration of multidisciplinary specialists in the best possible way. Both patients underwent an unsuccessful attempt at thrombolytic therapy with urokinase, catheter traction under the guidance of digital subtraction angiography and intraluminal balloon dilation. And we reviewed the literature on stuck catheters in the hope of providing knowledge and effective approaches to attempted removal of stuck catheters. Conclusion: There is no standardized procedure for dealing with stuck catheters. Intraluminal percutaneous transluminal angioplasty should be considered as the first-line treatment, while open surgery represents a second option only in the event of failure. Care must be taken that forced extubation can cause patients life-threatening.

The Emerging Roles of Exosomal miRNAs in Breast Cancer Progression and Potential Clinical Applications.

Breast cancer remains the leading malignancy in terms of morbidity and mortality today. The tumor microenvironment of breast cancer includes multiple cell types, secreted proteins, and signaling components such as exosomes. Among these, exosomes have a lipid bilayer structure. Exosomes can reflect the biological traits of the parent cell and carry a variety of biologically active components, including proteins, lipids, small molecules, and non-coding RNAs, which include miRNA, lncRNA, and circRNA. MiRNAs are a group of non-coding RNAs of approximately 20-23 nucleotides in length encoded by the genome, triggering silencing and functional repression of target genes. MiRNAs have been shown to play a significant role in the development of cancer owing to their role in the prognosis, pathogenesis, diagnosis, and treatment of cancer. MiRNAs in exosomes can serve as effective mediators of information transfer from parental cells to recipient cells and trigger changes in biological traits such as proliferation, invasion, migration, and drug resistance. These changes can profoundly alter the progression of breast cancer. Therefore, here, we systematically summarize the association of exosomal miRNAs on breast cancer progression, diagnosis, and treatment in the hope of providing novel strategies and directions for subsequent breast cancer treatment.

Ferroptosis: the emerging player in remodeling triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly heterogeneous breast tumor type that is highly malignant, invasive, and highly recurrent. Ferroptosis is a unique mode of programmed cell death (PCD) at the morphological, physiological, and molecular levels, mainly characterized by cell death induced by iron-dependent accumulation of lipid peroxides, which plays a substantial role in a variety of diseases, including tumors and inflammatory diseases. TNBC cells have been reported to display a peculiar equilibrium metabolic profile of iron and glutathione, which may increase the sensitivity of TNBC to ferroptosis. TNBC possesses a higher sensitivity to ferroptosis than other breast cancer types. Ferroptosis also occurred between immune cells and tumor cells, suggesting that regulating ferroptosis may remodel TNBC by modulating the immune response. Many ferroptosis-related genes or molecules have characteristic expression patterns and are expected to be diagnostic targets for TNBC. Besides, therapeutic strategies based on ferroptosis, including the isolation and extraction of natural drugs and the use of ferroptosis inducers, are urgent for TNBC personalized treatment. Thus, this review will explore the contribution of ferroptosis in TNBC progression, diagnosis, and treatment, to provide novel perspectives and therapeutic strategies for TNBC management.

TOFA induces cell cycle arrest and apoptosis in ACHN and 786-O cells through inhibiting PI3K/Akt/mTOR pathway.

Cancer cells usually have a high requirement for fatty acids in order to meet the rapid proliferation and metabolism. Acetyl-CoA carboxylase-α(ACCA) catalyzes the carboxylation of acetyl-CoA to malonyl-CoA and has been a rate-limiting enzyme in the synthesis of long chain fatty acid and cellular energy storage. 5-tetradecyloxy-2-furoic acid (TOFA) is well known as an allosteric inhibitor of ACCA. In this study, we examined the functions of TOFA in human renal cell carcinoma (RCC) cell lines ACHN and 786-O. According to the results, TOFA inhibited ACHN and 786-O cell growth in a concentration and time dependent manner. The IC50 values of ACHN and 786-O cells were 6.06 and 5.36 µg/ml by the treatment of TOFA for 48 h, respectively. Flow cytometry analysis showed that TOFA markedly arrest cell cycle at G2/M phase and lead to cell apoptosis. In addition, Western blot results revealed that TOFA decreased the phosphorylation of proteinkinaseB(Akt), Mammalian target of rapamycin (mTOR) and p70 ribosomal protein S6 kinase (p70S6K). What's more, specific phosphoinositide 3-kinases (PI3K) phosphorylation inhibitor LY294002 potentiated TOFA anti-cancer activity. These results suggested that TOFA induces growth restraint and apoptosis via inhibiting the PI3K/Akt/mTOR pathway and TOFA may be a novel therapeutic strategy for RCC treatment.