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LncRNA H19-mediated M2 polarization of macrophages promotes myofibroblast differentiation in pulmonary fibrosis induced by arsenic exposure
2021
Xiao, Tian | Zou, Zhonglan | Xue, Junchao | Syed, Binafsha Manzoor | Sun, Jing | Dai, Xiangyu | Shi, Ming | Li, Junjie | Wei, Shaofeng | Tang, Huanwen | Zhang, Aihua | Liu, Qizhan
Arsenic is a potent toxicant, and long-term exposure to inorganic arsenic causes lung damage. M2 macrophages play an important role in the pathogenesis of pulmonary fibrosis. However, the potential connections between arsenic and M2 macrophages in the development of pulmonary fibrosis are elusive. C57BL/6 mice were fed with drinking water containing 0, 10 and 20 ppm arsenite for 12 months. We have found that, in lung tissues of mice, arsenite, a biologically active form of arsenic, elevated H19, c-Myc, and Arg1; decreased let-7a; and caused pulmonary fibrosis. For THP-1 macrophages (THP-M) and bone-marrow-derived macrophages (BMDMs), 8 μM arsenite increased H19, c-Myc, and Arg1; decreased let-7a; and induced M2 polarization of macrophages, which caused secretion of the fibrogenic cytokine, TGF-β1. Down-regulation of H19 or up-regulation of let-7a reversed the arsenite-induced M2 polarization of macrophages. Arsenite-treated THP-M and BMDMs co-cultured with MRC-5 cells or primary lung fibroblasts (PLFs) elevated levels of p-SMAD2/3, SMAD4, α-SMA, and collagen I in lung fibroblasts and resulted in the activation of lung fibroblasts. Knockout of H19 or up-regulation of let-7a in macrophages reversed the effects. The results indicated that H19 functioned as an miRNA sponge for let-7a, which was involved in arsenite-induced M2 polarization of macrophages and induced the myofibroblast differentiation phenotype by regulation of c-Myc. In the sera of arseniasis patients, levels of hydroxyproline and H19 were higher, and levels of let-7a were lower than levels in the controls. These observations elucidate a possible mechanism for arsenic exposure-induced pulmonary fibrosis.
Показать больше [+] Меньше [-]Platelet-rich plasma and/or sildenafil topical applications accelerate and better repair wound healing in rats through regulation of proinflammatory cytokines and collagen/TGF-β1 pathway
2020
Gad, Shereen B. | Hafez, Mona H. | El-Sayed, Yasser S.
Platelet-rich plasma (PRP) composites of various cytokines and growth factors which have the potential to activate and speed the process of wound repair. Sildenafil also is a potent stimulator of angiogenesis which favors its potential effects on wound healing in several models. Existing work planned to examine the effectiveness of topical application of PRP and/or sildenafil citrate hydrogel (SCH) in a non-splinted excision skin wound model. Adult male rats were allocated into control, PRP, SCH, and PRP/SCH groups. On the 7th and 14th days, blood and tissue samples were collected for hematobiochemical, histopathological, and immunohistochemistry analyses. PRP and/or SCH topical treatments caused an enhancement of wound healing parameters, including a rapid switch from inflammatory phase to connective tissue stage evident by less systemic hematological changes and decreased values of proinflammatory cytokines (IL-6, TNF-α, and IL-1β) and C-reactive protein (CRP) on the 7th or 14th days post-wounding. Also, tissue hydroxyproline, collagen, nitrite, and total protein contents were higher in therapeutically handled wounded rats. Histologically, PRP- and/or SCH-treated wounded rats exhibited less necrosis, inflammation, and fibrin with a higher level of granulation tissue formation on the 7th day post-wounding and abundant collagen remodeling, epithelization, and vascularization on the 14th day relative to control. Interestingly, combined PRP and SCH treatment was more efficient in wound healing scoring with less inflammation, more collagen remodeling, and more epithelization. Our findings confirm the effectiveness of PRP and/or SCH as a topical wound healing treatment, with better skin wound healing with their combination.
Показать больше [+] Меньше [-]Vegetable wastes as a bio-additive for low-salt preservation of raw goat skin: An attempt to reduce salinity in leather manufacture
2022
Preservation or curing of hides/skins is performed as the primary step of leather processing to conserve them from putrefaction. Normally preservation is carried out using common salt (NaCl), which is discharged in the soak liquor contributing to ~ 70%, of total dissolved solids (TDS) load of entire leather manufacturing. In an attempt to reduce the TDS and chlorides, phyto-based preservation using garlic peel (Allium sativum) and white onion peel (Allium cepa) was carried out. Different concentrations of salt in combination with garlic peel and white onion peel were applied on freshly flayed goat skins based on its green weight and compared to control (40% salt). Sensory evaluation of the preserved skin was done by assessing different parameters like hair slip, putrefaction and odour. Estimation of hydroxyproline (HP) release, moisture content and microbial load were carried out at regular intervals. Skins that remained in good condition for 14 days were further processed into leather and properties were examined which were found comparable to the conventionally cured skins. Hence, this cleaner curing technique helps in reducing the TDS and chlorides in the effluent, thus controlling the pollution caused by tanneries through sustainable leather processing.
Показать больше [+] Меньше [-]Characterization and application of dried neem leaf powder as a bio-additive for salt less animal skin preservation for tanneries
2022
Velappan, Brindha | Gnanasekaran, Sandhiya | Victor, John Sundar | Alagumuthu, Tamilselvi | Nagarajan, Vedaraman | Chinnaraj, Velappan Kandukalpatti | Chellappa, Muralidhran
Sodium chloride (NaCl) is commonly used as a curing/preservative agent for raw hides and skins in tanneries and is removed through a soaking process with total dissolved solids (TDS) and other organic pollutants in effluent, causing significant pollution load to the environment. Hence, the present study evaluated to apply dried neem leaf powder (DNL) as an additive to reduce the usage of salt in skin processing and preservation. To make certain of DNL antimicrobial properties, solvent extracts were performed against proteolytic bacteria isolated from raw skins. Initial characterization of DNL revealed the presence of bioactive compounds nimbolide and dehydro salannol and acetone extract with 16.9-mm, 10-mm and 8-mm zone of inhibition against Salmonella sp., E. coli sp. and Bacillus sp. identified using phenotypic conventional biochemical screening method. Further, skin curing experiments were carried out using four different treatments of DNL (10% 15%, 20% and 25% w/w) along with 15% w/w of conventional salt to obtain an optimum concentration for pilot-scale studies. Thus, the application of optimal DNL (15%) and salt (15%) resulted in no physical changes such as smell and hair slip and was taken for further studies for hydroxyproline activity, pollution load and organoleptic properties along compared with control 40% salt. DNL-aided salt less preservation of freshly flayed goat skins at ambient condition showed no hair slip or putrefaction during the preservation period with significant reduction of TDS (86%) and chloride (71%) in soak liquors compared to conventional salt preservation and enhanced organic load requiring additional treatment. However, the application of the organoleptic, physical and hydrothermal properties of resulting leathers produced from the DNL applied skins was on par with results of leather obtained from conventional salt. Thus, our results demonstrate DNL-aided salt less preservation method is able to reduce the amount of salt for preservation of goat skins significantly, leading to reduced salinity issues during leather processing.
Показать больше [+] Меньше [-]Krill oil and low-dose aspirin combination mitigates experimentally induced silicosis in rats: role of NF-κB/TGF-β1/MMP-9 pathway
2021
Abd Elhameed, Ahmed G.
This study is an attempt to assess pulmonary protective and antifibrotic potentials of a combination of aspirin, a widely used anti-inflammatory and cardioprotective agent, and krill oil, a naturally occurring omega-3 fatty acid source, against silica-induced pulmonary injury. For silicosis induction, silica particles (50 mg/rat, 0.1 mL 0.9% NaCl) were instilled intranasally into rats. Aspirin (10 mg/kg/day), krill oil (40 mg/kg/day), or their combination was administered orally for 56 days following silica exposure. Results showed that oral aspirin and krill oil combination significantly mitigated silica-induced pulmonary injury. Bronchoalveolar lavage fluid examination showed a decreased lactate dehydrogenase activity, total protein content, and accumulation of total and differential inflammatory cells. Oral aspirin and krill oil combination significantly attenuated silica-induced oxidative stress through the restoration of reduced glutathione concentration and catalase activity in addition to alleviation of elevated malondialdehyde and total nitric oxide contents. Moreover, aspirin and krill oil combination revealed considerable mitigation of silica-induced upregulated expression of the inflammatory and fibrotic mediators: nuclear factor kappa-B, transforming growth factor-β1, and matrix metalloproteinase-9. The antifibrotic effect was also evidenced through the decreased hydroxyproline content and the obvious restoration of lung architecture, as demonstrated upon histopathological examination. In conclusion, oral aspirin and krill oil combination can confer pulmonary protective, anti-inflammatory, and antifibrotic potentials against silica-induced pulmonary injury. This impact could be credited to the ability of this combination to activate resolution mechanisms, which, in turn, suppress the expression of inflammatory and fibrotic biomarkers and replenish antioxidant stores.
Показать больше [+] Меньше [-]Ameliorative role of bosentan, an endothelin receptor antagonist, against sodium arsenite–induced renal dysfunction in rats
2021
Sharma, A. K. (Ashwani Kumar) | Kaur, Japneet | Kaur, Tajpreet | Singh, Balbir | Yadav, Harlokesh Narayan | Pathak, Devendra | Singh, Amrit Pal
Arsenic exposure is well documented to cause serious health hazards, such as cardiovascular abnormalities, neurotoxicity and nephrotoxicity. In the present study, we intended to explore the role of bosentan, an endothelial receptor antagonist, against sodium arsenite-induced nephrotoxicity and hepatotoxicity in rats. Sodium arsenite (5 mg/kg, oral) was administered for 4 weeks to induce renal dysfunction in rats. Sodium arsenite intoxicated rats were treated with bosentan (50 and 100 mg/kg, oral) for 4 weeks. Arsenic led renal damage was demonstrated by significant increase in serum creatinine, urea, uric acid, potassium, fractional excretion of sodium, microproteinuria and decreased creatinine clearance in rats. Sodium arsenite resulted in marked oxidative stress in rat kidneys as indicated by profound increase in lipid peroxides, and superoxide anion generation alongwith decrease in reduced glutathione levels. Hydroxyproline assay highlighted arsenic-induced renal fibrosis in rats. Hematoxylin-eosin staining indicated glomerular and tubular changes in rat kidneys. Picrosirius red staining highlighted collagen deposition in renal tissues of arsenic treated rats. Immunohistological results demonstrated the reduction of renal eNOS expression in arsenic treated rats. Notably, treatment with bosentan attenuated arsenic-induced renal damage and resisted arsenic-led reduction in renal eNOS expression. In addition, sodium arsenite–induced alteration in hepatic parameters (serum aspartate aminotransferase, alanine transferase, alkaline phosphatase, bilirubin), oxidative stress and histological changes were abrogated by bosentan treatment in rats. Hence, we conclude that bosentan treatment attenuated sodium arsenite–induced oxidative stress, fibrosis and reduction in renal eNOS expression in rat kidneys. Moreover, bosentan abrogated arsenic led hepatic changes in rats.
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