Role of circular RNAs in visceral organ fibrosis.

Circular RNAs (circRNAs) are a novel class of noncoding RNAs produced during pre-mRNA splicing and are emerging as new members of the gene regulatory network. Unlike linear RNAs, circRNAs have a unique structure with a covalently closed loop formed from the ligation of exons, introns, or both. CircRNAs are widely expressed in various organisms in a species-, tissue-, developmental stage- and disease-specific manner; circRNAs have been demonstrated to play a vital role in the pathogenesis and progression of human diseases.

CircHECTD1 mediates pulmonary fibroblast activation HECTD1.

Background: Circular RNA (circRNA), a new class of noncoding RNA, has been shown to be important in silicosis due to its unique role as a transcription regulator or as a sponge of small RNA regulators. Here, the mechanisms underlying circHECTD1/HECTD1 in fibroblast activation and subsequent fibrosis induced by SiO were investigated.

Methods: Primary human pulmonary fibroblasts (HPF-a) were utilized, combined with quantitative real-time PCR (qRT-PCR) and fluorescence in situ hybridization (FISH) assays.

circDLPAG4/HECTD1 mediates ischaemia/reperfusion injury in endothelial cells via ER stress.

: Vascular endothelial cell dysfunction, characterized by cell apoptosis and migration, plays a crucial role in ischaemia/reperfusion (I/R) injury, a common aspect of cardiovascular diseases. Recent studies have suggested that non-coding RNAs, such as circular RNAs (circRNA), play a role in cell dysfunction in I/R injury, although the detailed mechanism is unclear.: Human umbilical vein endothelial cells (HUVECs) were used for I/R model.

SPIO nanoparticle-labeled bone marrow mesenchymal stem cells inhibit pulmonary EndoMT induced by SiO.

Endothelial-mesenchymal transition (EndoMT) is a key step during lung fibrosis. Studies have shown that bone marrow mesenchymal stem cells (BMSCs) may act as therapeutic candidates for lung fibrosis. However, the effects of BMSCs on EndoMT induced by SiO have not been elucidated, and means to label and track grafted cells have been lacking.

CircRNA-012091/PPP1R13B-mediated Lung Fibrotic Response in Silicosis via Endoplasmic Reticulum Stress and Autophagy.

Silicosis is a progressive fibrotic disease of lung tissue caused by long-term inhalation of SiO. However, relatively few studies of the direct effects of SiO on lung fibroblasts have been performed. PPP1R13B is a major member of the apoptosis-stimulating proteins of the p53 family, but its role in pulmonary fibrosis is unclear.

circHIPK2-mediated σ-1R promotes endoplasmic reticulum stress in human pulmonary fibroblasts exposed to silica.

Silicosis is characterized by fibroblast accumulation and excessive deposition of extracellular matrix. Although the roles of SiO-induced chemokines and cytokines released from alveolar macrophages have received significant attention, the direct effects of SiO on protein production and functional changes in pulmonary fibroblasts have been less extensively studied. Sigma-1 receptor, which has been associated with cell proliferation and migration in the central nervous system, is expressed in the lung, but its role in silicosis remains unknown.

Protective Effects of Cerium Oxide Nanoparticles on MC3T3-E1 Osteoblastic Cells Exposed to X-Ray Irradiation.

Background/aims: Exposure to ionizing radiation can result in bone damage, including decreased osteocyte number and suppressed osteoblastic activity. However, molecular mechanisms remain to be elucidated, and effective prevention strategies are still limited. This study was to investigate whether cerium oxide nanoparticles (CeO2 NP) can protect MC3T3-E1 osteoblast-like cells from damaging effects of X-ray irradiation, and to study the underpinning mechanism(s).

MCPIP1 Regulates Alveolar Macrophage Apoptosis and Pulmonary Fibroblast Activation After in vitro Exposure to Silica.

Background: Silicosis is a fatal and fibrotic pulmonary disease caused by the inhalation of silica. After arriving at the alveoli, silica is ingested by alveolar macrophages (AMOs), in which monocyte chemotactic protein-induced protein 1 (MCPIP1) plays an essential role in controlling macrophage-mediated inflammatory responses. However, the mechanism of action of MCPIP1 in silicosis is poorly understood.

MCPIP1 mediates silica-induced cell migration in human pulmonary fibroblasts.

Silicosis is a systemic disease caused by inhaling silicon dioxide (SiO2). Phagocytosis of SiO2 in the lungs initiates an inflammatory cascade that results in fibroblast proliferation and migration followed by fibrosis. According to previous data from our laboratory, monocyte chemotactic protein-1 (MCP-1) plays a critical role in fibroblast proliferation and migration in conventional two-dimensional (2D) monolayer cultures.

p53/PUMA expression in human pulmonary fibroblasts mediates cell activation and migration in silicosis.

Phagocytosis of SiO2 into the lung causes an inflammatory cascade that results in fibroblast proliferation and migration, followed by fibrosis. Clinical evidence has indicated that the activation of alveolar macrophages by SiO2 produces rapid and sustained inflammation characterized by the generation of monocyte chemotactic protein 1, which, in turn, induces fibrosis. However, the details of events downstream of monocyte chemotactic protein 1 activity in pulmonary fibroblasts remain unclear.

MCPIP1 Regulates Fibroblast Migration in 3-D Collagen Matrices Downstream of MAP Kinases and NF-κB.

The fibroblast-populated three-dimensional (3-D) collagen matrix has been used to model matrix contraction, cell motility, and general fibroblast biology. MCPIP1 (monocyte chemotactic protein-induced protein 1) has been shown to regulate inflammation, angiogenesis, and cellular motility. In the present study, we demonstrated induction of MCPIP1 in human fibroblasts embedded in the stress-released 3-D collagen matrix, which occurred through activation of mitogen-activated protein kinases, phosphoinositide 3-kinase, and NF-κB.

Role of human pulmonary fibroblast-derived MCP-1 in cell activation and migration in experimental silicosis.

Background: Silicosis is a systemic disease caused by inhaling silicon dioxide (SiO2). Phagocytosis of SiO2 in the lung initiates an inflammatory cascade that results in fibroblast proliferation and migration and subsequent fibrosis. Clinical evidence indicates that the activation of alveolar macrophages by SiO2 produces rapid and sustained inflammation that is characterized by the generation of monocyte chemotactic protein 1 (MCP-1), which induces fibrosis.

Exposure to soil, house dust and decaying plants increases gut microbial diversity and decreases serum immunoglobulin E levels in BALB/c mice.

To assess the impact of sanitation of a living environment on gut microbiota and development of the immune system, we raised BALB/c mice under three distinct environmental conditions: a specific pathogen-free animal room (SPF), a general animal room (XZ) and a farmhouse (JD). All other variables like diet, age, genetic background, physiological status and original gut microbiota were controlled for in the three groups. Using high-throughput sequencing of the 16S rRNA gene, we found that each mouse group had a specific structure of the gut microbial community.

Acetaminophen attenuates glomerulosclerosis in obese Zucker rats via reactive oxygen species/p38MAPK signaling pathways.

Focal segmental glomerulosclerosis is a critical pathological lesion in metabolic syndrome-associated kidney disease that, if allowed to proceed unchecked, can lead to renal failure. However, the exact mechanisms underlying glomerulosclerosis remain unclear, and effective prevention strategies against glomerulosclerosis are currently limited. Herein, we demonstrate that chronic low-dose ingestion of acetaminophen (30 mg/kg/day for 6 months) attenuates proteinuria, glomerulosclerosis, podocyte injury, and inflammation in the obese Zucker rat model of metabolic syndrome.

Involvement of PPARγ in emodin-induced HK-2 cell apoptosis.

Emodin, a major compound in total rhubarb anthraquinones (TRAs), has exhibited nephrotoxicity in Sprague Dawley rats and cytotoxicity to HK-2 cells, a human proximal tubular epithelial cell line, in our previous study. However, the exact molecular mechanisms underlying emodin-induced cytotoxicity remain undefined. In this study, the exposure of HK-2 cells to emodin led to decreased cell viability, caspase 3 cleavage and activation, loss of mitochondrial membrane potential (DWm), and cytochrome c release from mitochondria to cytosol.

Acetaminophen attenuates obesity-related renal injury through ER-mediated stress mechanisms.

Background/aims: Obesity is an independent risk factor for the development of kidney disease. The purpose of this study was to determine how obesity may contribute to renal damage and whether acetaminophen ingestion can diminish obesity-associated renal cell injury in the obese Zucker rat model.

Methods: Male obese Zucker rats (4 weeks old, n=6) were treated with acetaminophen (30 mg / kg body weight / day) for 26 weeks.

Possible roles of astrocytes in estrogen neuroprotection during cerebral ischemia.

17β-Estradiol (E2), one of female sex hormones, has well-documented neuroprotective effects in a variety of clinical and experimental disorders of the central cerebral ischemia, including stroke and neurodegenerative diseases. The cellular mechanisms that underlie these protective effects of E2 are uncertain because a number of different cell types express estrogen receptors in the central nervous system. Astrocytes are the most abundant cells in the central nervous system and provide structural and nutritive support of neurons.

Metabolic syndrome-induced tubulointerstitial injury: role of oxidative stress and preventive effects of acetaminophen.

The prevalence of metabolic syndrome persistently increases and affects over 30% of U.S. adults.

Effects of estrogen on neuronal KCNQ2/3 channels expressed in PC-12 cells.

We previously reported that 17β-estradiol (E2) improves long term potentiation (LTP) in hippocampal neurons after global ischemia in rat. In the present study, we investigated if E2 can directly modulate the activity of neuronal KCNQ2/3 channels, the molecular entity of neuronal M-current in hippocampus, expressed in the PC-12 cells. We found that exogenous E2 inhibits the KCNQ2/3 channels in a dose-dependent fashion.

Neurosteroid estradiol rescues ischemia-induced deficit in the long-term potentiation of rat hippocampal CA1 neurons.

Increasing evidence indicates that neurosteroid 17beta-Estradiol (E2), a type of female sex hormone, has a neuroprotective effect against cerebral injury. However, it remains unknown whether E2 can also protect the hippocampal CA1 neurons from functional deficits in synaptic transmission and plasticity caused by ischemia. To address this issue, adult male Wistar rats were subjected to mild global cerebral ischemia created by four-vessel occlusion (4VO) for 10min, and the effects of E2 administration against the ischemic injury were investigated.

Chronic DHEAS administration facilitates hippocampal long-term potentiation via an amplification of Src-dependent NMDA receptor signaling.

Dehydroepiandrosterone sulfate (DHEAS) has well characterized effects on memory and cognitive performances. Recently we have reported that repetitive administration of DHEAS lowers the threshold pulse number in inducing activity-dependent long-term potentiation (LTP) in rat hippocampal Schaffer collateral-CA1 synapses, in which a sub-threshold high frequency stimulation (HFS, 30 pulses at 100 Hz) for normal rats could induce robust LTP in DHEAS-treated rats (Chen et al., 2006).

Chronic administration of dehydroepiandrosterone sulfate (DHEAS) primes for facilitated induction of long-term potentiation via sigma 1 (sigma1) receptor: optical imaging study in rat hippocampal slices.

Dehydroepiandrosterone sulfate (DHEAS), one of the most abundant neurosteroids synthesized de novo in the nervous system, has well characterized effects on memory and cognitive performances. However, little is known about the underlying synaptic mechanisms. In this study, we investigated the effects of chronic administration of DHEAS (20 mg/kg for 7 days) on the plasticity of Schaffer collateral-CA1 synapses by applying an optical recording technique on the hippocampal slices stained with voltage-sensitive dyes.