Volume 100 Issue 3, March 2020

Bone marrow mesenchymal stem cells (BMSC) or BMSC-derived exosome transplantation improves rat ovarian function after chemotherapy-induced ovarian failure. Furthermore, transfer of miR-144-5p using BMSC-derived exosomes decreases granulosa cell (GCs) apoptosis via the PTEN pathway. Thus, a cell-free therapeutic strategy may be possible for ovarian failure.

The authors investigated global analysis coupled shotgun proteomics and in silico metabolic pathway analyses in malignant lymphoma and normal lymphocytes. Trifunctional protein subunit alfa (HADHA) was detected as a lymphoma-specific protein and a prognostic predictor. In vitro, downregulation of HADHA inhibited cell growth and increase susceptibility of cell death stimuli. Therefore, HADHA may be a potential therapeutic target in refractory malignant lymphoma cases.

This study reveals that adhesion molecule ICAM-1 is markedly upregulated in the aorta after angiotensin II infusion. Blockage of soluble ICAM-1 prevents Ang II-induced arterial hypertension and vascular remodeling by reducing macrophage adhesion, suggesting that targeting ICAM-1 may represent a new therapeutic target for hypertension.

This study suggests a potential mechanism wherein microRNA-21-5p (miR-21-5p) inhibition downregulates autophagy, migration ability, and LC3B expression via PTEN/AKT signaling in electron beam (EB)-irradiated keloid fibroblasts, effectively preventing local invasion and recurrence. Therefore, miR-21-5p could be a new therapeutic target, to replace EB irradiation, and control keloid relapse.

While the transcription factor TBX3 is widely studied in tumorigenesis, the functionality of the two isoforms (TBX3iso1 and TBX3iso2) which differ in their DNA-binding domain is not well understood. By utilizing a nude mouse xenograft model, the authors identified differential tumorigenic potential between TBX3 isoforms, with TBX3iso1 (but not TBX3iso2) promoting invasive carcinoma in vivo through induction of angiogenesis. This process is moderated by downstream mediators osteopontin (OPN) and hyaluronan synthase 2 (HAS2).

The role of the prostaglandin E1 receptor EP₁ in hypertensive kidney disease remains controversial. EP₁ mediates thick ascending limb chloride transport response to prostaglandin E2 and inhibits vasopressin-mediated water transport in the inner medullary collecting duct (IMCD). Though the IMCD transport is unaltered by hypertension, its responsiveness to vasopressin is reduced in diabetes. Moreover, EP1 is protective against glomerular and endothelial injury in hypertensive kidney disease, unlike its harmful role in diabetic kidney disease. This highlights the importance of carefully examining disease state (diabetes vs hypertension) when characterizing underlying disease processes.

Most of the cancer-associated genes mutated only in high-grade gastrointestinal stromal tumors (GISTs) are mainly involved in cell cycle control. High-grade GISTs had more MYC copy number gains than matched low-grade tumors. The authors show that alterations in cell cycle regulation-associated genes, may promote primary progression from low-grade GISTs to high-grade tumors by regulating tumor cell proliferation.

High expression of the transcription factor ETS2 plays important role in a mouse model of renal fibrosis and in TGF-β1-treated human tubular epithelial cells (HK2). ETS2 promotes TGF-β1-induces epithelial-to-mesenchymal transition (EMT) phenotypic inversion and the expression of EMT markers in HK2 cells by enhancing transcription of JUNB. These findings suggest that ETS2 could be a novel target for the prevention the progression of renal fibrosis.

The endocannabinoid (EC) system has been implicated in the pathogenesis nonalcoholic fatty liver diseases (NAFLD). Here the authors demonstrate that endocannabinoid receptor 1 (CB1) receptor knockout in vivo and pharmacologic antagonization of CB1 in cell culture decreases expression of lipid droplet binding protein perilipin 2, which might be an essential step in lipid breakdown. Thus, pharmacologic modulation of the CB1-perilipin 2 axis might represent a novel therapeutic approach for the treatment of steatosis.

The expression of HIP/PAP and its mouse counterpart, Reg3B, is markedly unregulated in fibrotic livers. Ectopic HIP/PAP potently protects from CCl₄- and BDL-induced liver fibrosis in mice. This study shows that downregulation of TGF-βRII expression is one of the important underlying mechanisms for HIP/PAP in suppression of hepatic fibrosis.

The two Na⁺ and water pore-forming claudins, claudin-2 and claudin-15, are reciprocally regulated during human development. This study shows that expression of these claudins is altered in celiac disease, graft-versus-host disease, and common variable immunodeficiency, but that the specific claudin affected differed between children and adults, suggesting distinct contributions to diarrheal pathophysiology.

The authors investigated the potential mechanisms of interleukin-33 (IL-33) in the pathogenesis of ulcerative colitis. IL-33 was found to sustain mucosal inflammation by down-regulation of protective ABCG5/8 during recovery from colitis. These results may help to increase understanding regarding the IL-33-mediated pathogenesis of ulcerative colitis and potentially contribute to creation of a novel therapeutic strategy.

In this study, the authors show that RIP1/RIP3/MLKL-mediated necroptosis is activated in a mouse model of Parkinson’s disease. Blockade of necroptosis through pharmacological intervention by Nec-1 or deletion of RIP3/MLKL gene increased dopamine levels and the number of dopaminergic neurons in mice. Moreover, necroptosis enhanced the expression of pro-inflammatory genes, which may have initiated neuroinflammation and in turn aggravated dopaminergic neuron necroptosis.

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