Macrophage metalloelastase (matrix metalloproteinase MMP-12) is upregulated in atherosclerotic lesions and aneurysm; thus, increased MMP-12 activity may play an important role in the pathogenesis of ...atherosclerosis. However, the pathological roles of MMP-12 in the initiation and progression of atherosclerosis have not been defined.
We compared the susceptibility of MMP-12 transgenic (Tg) rabbits to cholesterol-rich diet-induced atherosclerosis with that of non-Tg littermate rabbits. The rabbits were maintained at either relatively lower levels of hypercholesterolemia for shorter periods or higher levels of hypercholesterolemia for longer periods through a diet containing different amounts of cholesterol. We found no significant difference in the aortic atherosclerotic lesion size or quality between Tg and non-Tg rabbits at lower hypercholesterolemia. At higher hypercholesterolemia for longer periods, however, Tg rabbits developed more extensive atherosclerosis in the aortas and coronary arteries than did non-Tg rabbits. Histological examinations revealed that atherosclerotic lesions of Tg rabbits contained prominent macrophage infiltration associated with marked disruption of the elastic lamina in the tunica media with occasional formation of aneurysm-like lesions. Furthermore, increased expression of MMP-12 derived from macrophages was associated with elevated expression of MMP-3, suggesting that MMP-12 may play a pivotal role in the cascade activation of other MMPs, thereby exacerbating extracellular matrix degradation during the progression of atherosclerosis.
Overexpression of MMP-12 causes accelerated atherosclerosis in Tg rabbits. These results suggest that macrophage-derived MMP-12 participates in the progression of atherosclerosis.
Increased proteolytic activity of matrix metalloproteinases (MMPs) may promote articular destruction such as occurs in rheumatoid arthritis and osteoarthritis. Recently, we reported that synovial ...tissue and fluid obtained from patients with rheumatoid arthritis contained higher activity of macrophage elastase (MMP-12). To examine the hypothesis that MMP-12 may potentially enhance the progression of arthritis, we investigated the effects of overexpression of MMP-12 on inflammatory arthritis in transgenic rabbits that express the human MMP-12 transgene in the macrophage lineage. Inflammatory arthritis was produced by articular injection of carrageenan solution and the degree of inflammatory arthritis in transgenic rabbits was compared with that in control rabbits. We found that overexpression of MMP-12 in transgenic rabbits significantly enhanced the arthritic lesions, resulting in severe synovial thickening, pannus formation, and prominent macrophage infiltration at an early stage and a marked destruction of articular cartilage associated with loss of proteoglycan at a later stage. These results demonstrate that excessive MMP-12 expression exacerbates articular connective tissue and cartilage degradation and thus plays a critical role in the development of inflammatory joint disease.
The individual toxicity of sodium fluoride (NaF) and microplastics (MPs) has been extensively documented. Owing to their high specific surface area, widespread presence and durability, MPs can adsorb ...a broad spectrum of environmental contaminants into the organism. However, the combined toxicity of NaF and MPs has not been investigated. This study aimed to assess the effects of combined exposure to NaF and MPs on the function of testicular Sertoli cells (SCs) in male mice, and to investigate the underlying molecular mechanisms. The study revealed that combined exposure to NaF and MPs resulted in a decrease in the negative surface charge of MPs, along with an increase in the number of MPs entering the SCs. Through in vivo observation of the testicular pathological structure, spermatogenesis, and cell apoptosis in 180-day-old male mice, we discovered that combined exposure to NaF (80 mg/L) and MPs (10 mg/L) heightened reproductive toxicity compared to the individual exposure groups. This was evidenced by testicular structural defects, impaired spermatogenesis, and increased testicular cell apoptosis. Our in vitro studies showed that NaF (21 μg/mL) and MPs (100 μg/mL) synergistically induced SCs apoptosis and ferroptosis, leading to a reduction in SCs number and dysfunction. This ultimately resulted in structural and functional damage to the testes. Our findings demonstrate, for the first time, the synergistic effects of NaF and MPs on reproductive toxicity in mammals. These insights may provide valuable contributions to co-toxicity studies involving MPs and other environmental pollutants.
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•Co-exposure to NaF and MPs exacerbates testicular injury in mice.•Co-exposure to NaF and MPs induced ferroptosis and apoptosis in Sertoli cells (SCs).•Co-exposure to NaF and MPs increases dysfunction in SCs.•Co-exposure to NaF and MPs exacerbates dysfunction in SCs via ferroptosis and apoptosis pathways.
Various assaults on mitochondria occur during the human aging process, contributing to mitochondrial dysfunction. This mitochondrial dysfunction is intricately connected with aging and diseases ...associated with it. In vivo, the accumulation of defective mitochondria can precipitate inflammatory and oxidative stress, thereby accelerating aging. Mitophagy, an essential selective autophagy process, plays a crucial role in managing mitochondrial quality control and homeostasis. It is a highly specialized mechanism that systematically removes damaged or impaired mitochondria from cells, ensuring their optimal functioning and survival. By engaging in mitophagy, cells are able to maintain a balanced and stable environment, free from the potentially harmful effects of dysfunctional mitochondria. An ever-growing body of research highlights the significance of mitophagy in both aging and age-related diseases. Nonetheless, the association between mitophagy and inflammation or oxidative stress induced by mitochondrial dysfunction remains ambiguous. We review the fundamental mechanisms of mitophagy in this paper, delve into its relationship with age-related stress, and propose suggestions for future research directions.
Diabetic kidney disease (DKD) poses a severe threat to human health. Compound Xiancao Granule (CXCG), a classic Zhuang medicinal formula, is reported as highly effective in treating DKD. However, the ...mechanisms underlying the action of CXCG in DKD remain unclear.
This study aimed to investigate the mechanisms of action of CXCG against DKD using multi-omics analysis, including 16s rRNA sequencing, metabolomics, and transcriptomics.
The chemical compounds of CXCG were identified using ultra-high- performance liquid chromatography quadrupole/electrostatic field orbital trap high-resolution mass spectrometry analysis. A rat model of DKD was established by combining nephrectomy of the left kidney, high-fat diet, and streptozotocin. The therapeutic effects of CXCG on DKD were assessed based on body weight, blood glucose level, renal function, inflammatory cytokine levels, and histological staining. Subsequently, 16s rRNA sequencing, liquid chromatography-tandem mass spectrometry untargeted metabolomic profiling, and RNA sequencing analysis were used to investigate the mechanisms of action of CXCG in DKD. Spearman's correlation analysis was performed to elucidate the correlations between efficacy indicators, gut microbiota, metabolites, and inflammation-related genes.
A total of 118 compounds were identified in CXCG. CXCG significantly ameliorated glucose metabolism disorders, improved renal function, attenuated inflammation, and delayed renal pathological changes in DKD rats. CXCG modulated gut microbiota dysbiosis, including Alloprevotella, Oscillibacter, Anaeroplasma, Anaerotruncus, and Faecalibacterium. In addition, metabolic disruption in DKD rats was regulated by CXCG, which is involved in the metabolism of carbohydrates and amino acids. Transcriptome analysis showed that CXCG affected DKD mainly by regulating inflammation-related genes and pathways, such as the PI3K/Akt and MAPK signaling pathways. Furthermore, there were significant correlations between efficacy indicators, gut microbiota, metabolites, and genes.
This multi-omics association study provides novel insights into the effects of CXCG on DKD by remodeling the gut microbiota structure and restoring the metabolic homeostasis through the regulation of carbohydrate metabolism, amino acid metabolism, and inflammation-related pathways, highlighting a potential therapeutic strategy for DKD.
Telenursing is receiving extensive attention from scholars and medical staff. However, there are few studies on the knowledge structure of telenursing for elderly individuals with chronic diseases. ...This study aims to demonstrate current research status and development trend of telenursing for elderly individuals with chronic diseases through a visual analysis of CiteSpace, so as to provide a more comprehensive perspective for future researches.
Literature about telenursing for elderly patients with chronic diseases from 2002 to 2022 was retrieved from the Web of Science Core Collection using CiteSpace 6.1.R3.
A total of 375 records were obtained. Annual publication and citation frequency gradually increased over the investigated period, reaching a peak in 2022. Journal of Telemedicine and Telecare was the most prolific and the most cited journal. The United States was the most productive country, the University of Melbourne was the most productive institution, and the author CHEN C ranked the highest in the number of publications. The most popular keywords were "care," "telemedicine," "management," "older adult," "chronic disease," "health," and "heart failure," which had a high frequency and centrality. The keywords "telehealth," "randomized controlled trail," "chronic obstructive pulmonary disease," "implementation" and "time" showed the strongest citation burst. The keywords were clustered to form 10 labels. The article published in 2010 by Chaudhry SI was cited the most. The top 3 cited journals were all special journal of telemedicine.
This study revealed current research status and development trend of telenursing for elderly individuals with chronic diseases. The bibliometric analysis of telenursing expands the knowledge field of telemedicine and provides new insights into the management of elderly patients with chronic diseases.
Health information literacy (HIL) is a significant concept that has gradually become known to the broader public in recent years. Although the definitions of HIL and health literacy seem to overlap, ...as an independent subconcept, HIL still shows a unique influence on improvements in people's health and health education. Remarkable evidence indicates that online health information (OHI) can effectively enrich people's knowledge and encourage patients to actively join the medical process, which is also accompanied by the emergence of various assessment tools. Although the current assessment tools, to a certain extent, can help people identify their shortcomings and improve their HIL, many studies have indicated that the deficiencies of the scales induce incomplete or unreal results of their HIL. In addition, continuing research has revealed an increasing number of influencing factors that have great effects on HIL and even regulate the different trends in doctor-patient relationships. Simultaneously, most of the uncensored OHI broadcasts have also affected the improvement in HIL in various ways. Thus, this review aims to summarize the assessment tools, influencing factors and current situations and challenges related to HIL. Further studies are required to provide more trusted and deeper references for the development of HIL.
Lipoprotein lipase (LPL) produced by macrophages is upregulated in the atherosclerotic lesions; however, it is not fully understood whether increased macrophage-derived LPL is pro-atherogenic. To ...examine the hypothesis that macrophage-derived LPL in the arterial wall enhances atherosclerotic lesion formation, we generated transgenic (Tg) rabbits that express the human LPL transgene under the control of the human scavenger receptor enhancer/promoter, which drives macrophage-specific expression of the human LPL gene. We fed Tg and non-Tg littermate rabbits a diet containing 0.3% cholesterol for 16 weeks and compared their lipoproteins and aortic atherosclerosis. We found that there was no difference in plasma lipid or lipoprotein profiles between Tg and non-Tg rabbits; however, atherosclerotic lesions were significantly increased in Tg compared to non-Tg rabbits. There was a 1.4-fold increase in total aortic
en face lesions and a 2-fold increase in intimal lesions evaluated by image analysis system. Furthermore, immunohistochemical staining revealed that the increased atherosclerotic lesions present in Tg rabbits were characterized by marked accumulation of macrophage-derived foam cells and frequently associated with the deposition of oxidized LDL. These results support the notion that macrophage-derived LPL in the arterial wall is pro-atherogenic, possibly via the enhancement of foam cell formation during atherogenesis.
Ischemic stroke is characterized by cute onset and high mortality. The suppression of neuroinflammation is crucial in the treatment of ischemic stroke. Exosomes derived from mesenchymal stem cell ...(MSC) have attracted extensive research attention due to their wide origin, small size, and containing large number of active components. Recent studies have shown that MSC-derived exosomes can inhibit the proinflammatory activity of microglia and astrocytes and stimulate their neuroprotective activity; also can inhibit neuroinflammation by regulating immune cells and inflammatory mediators. This article reviews the roles and related mechanism of MSC-derived exosomes in neuroinflammation after ischemic stroke, hoping to provide ideas and references for the development of a novel approach for the treatment of ischemic stroke diseases.
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