Monotropein is a compound classified into iridoid which is found in herbaceous plants Morindae officinalis. It possesses anti-inflammatory, antioxidant, and anti-osteoarthritic activities. Previous study indicates that monotropein may have the potential to combat cardiovascular disease, although the related mechanism remains unclear. In this study, we constructed the model of atherosclerosis by oxidized low density lipoprotein-induced vascular smooth muscle cells and LDLR –/–mice given high-fat diet to investigate the effects of monotropein on atherosclerosis.Our results showed that monotropein treatment significantly reduced the area of atherosclerotic plaques and necrotic cores in mice, inhibited the proliferation and migration of vascular smooth muscle cells, and reduced inflammatory responses and oxidative stress, which in turn alleviated atherosclerosis. In addition, we found that monotropein reduced the expression levels of P-NF-κB and P-AP-1. In conclusion, our data suggest that monotropein inhibited the proliferation and migration of vascular smooth muscle cells by mediating the activity of NF-κB, AP-1, reducing the level of inflammation and oxidative stress, and thus resisting the development of atherosclerosis. These findings demonstrate the efficacious therapeutic impact of monotropein on atherosclerosis and elucidate its specific target.

Monotropein is a compound classified into iridoid which is found in herbaceous plants Morindae officinalis. It possesses anti-inflammatory, antioxidant, and anti-osteoarthritic activities. Previous study indicates that monotropein may have the potential to combat cardiovascular disease, although the related mechanism remains unclear. In this study, we constructed the model of atherosclerosis by oxidized low density lipoprotein-induced vascular smooth muscle cells and LDLR –/–mice given high-fat diet to investigate the effects of monotropein on atherosclerosis.Our results showed that monotropein treatment significantly reduced the area of atherosclerotic plaques and necrotic cores in mice, inhibited the proliferation and migration of vascular smooth muscle cells, and reduced inflammatory responses and oxidative stress, which in turn alleviated atherosclerosis. In addition, we found that monotropein reduced the expression levels of P-NF-κB and P-AP-1. In conclusion, our data suggest that monotropein inhibited the proliferation and migration of vascular smooth muscle cells by mediating the activity of NF-κB, AP-1, reducing the level of inflammation and oxidative stress, and thus resisting the development of atherosclerosis. These findings demonstrate the efficacious therapeutic impact of monotropein on atherosclerosis and elucidate its specific target.

Monotropein is a compound classified into iridoid which is found in herbaceous plants Morindae officinalis. It possesses anti-inflammatory, antioxidant, and anti-osteoarthritic activities. Previous study indicates that monotropein may have the potential to combat cardiovascular disease, although the related mechanism remains unclear. In this study, we constructed the model of atherosclerosis by oxidized low density lipoprotein-induced vascular smooth muscle cells and LDLR –/–mice given high-fat diet to investigate the effects of monotropein on atherosclerosis.Our results showed that monotropein treatment significantly reduced the area of atherosclerotic plaques and necrotic cores in mice, inhibited the proliferation and migration of vascular smooth muscle cells, and reduced inflammatory responses and oxidative stress, which in turn alleviated atherosclerosis. In addition, we found that monotropein reduced the expression levels of P-NF-κB and P-AP-1. In conclusion, our data suggest that monotropein inhibited the proliferation and migration of vascular smooth muscle cells by mediating the activity of NF-κB, AP-1, reducing the level of inflammation and oxidative stress, and thus resisting the development of atherosclerosis. These findings demonstrate the efficacious therapeutic impact of monotropein on atherosclerosis and elucidate its specific target.

Monotropein is a compound classified into iridoid which is found in herbaceous plants Morindae officinalis. It possesses anti-inflammatory, antioxidant, and anti-osteoarthritic activities. Previous study indicates that monotropein may have the potential to combat cardiovascular disease, although the related mechanism remains unclear. In this study, we constructed the model of atherosclerosis by oxidized low density lipoprotein-induced vascular smooth muscle cells and LDLR –/–mice given high-fat diet to investigate the effects of monotropein on atherosclerosis.Our results showed that monotropein treatment significantly reduced the area of atherosclerotic plaques and necrotic cores in mice, inhibited the proliferation and migration of vascular smooth muscle cells, and reduced inflammatory responses and oxidative stress, which in turn alleviated atherosclerosis. In addition, we found that monotropein reduced the expression levels of P-NF-κB and P-AP-1. In conclusion, our data suggest that monotropein inhibited the proliferation and migration of vascular smooth muscle cells by mediating the activity of NF-κB, AP-1, reducing the level of inflammation and oxidative stress, and thus resisting the development of atherosclerosis. These findings demonstrate the efficacious therapeutic impact of monotropein on atherosclerosis and elucidate its specific target.

Objective To identify the pathogenic gene and variant for a family with branchio-otic syndrome.Methods The clinical data of this family were collected,and the peripheral blood was extracted for deafness gene NGS panel analysis.Pathogenic variation detected was verified by Sanger sequencing.Results The family contained 17 members in three-generations,3 of whom exhibited autosomal dominant,hearing loss,preauricular fistula and branchial cleft fistula,which were in accordance with the clinical diagnosis criteria of branchio-otic syndrome.A no-vel heterozygous variant c.963dupT(p.E322X)in EYA1 gene was identified,which co-segregated with the branchi-o-otic syndrome phenotype in the family.The variant was a nonsense variant resulting in the premature appearance of the stop codon.According to the American College of Medical Genetics and Genomics(ACMG)guidelines and the criteria,the variant was classified as pathogenic.Conclusion We identified a novel pathogenic variant EYA1:c.963dupT(p.E322X)in a family with branchio-otic syndrome.

Monotropein is a compound classified into iridoid which is found in herbaceous plants Morindae officinalis. It possesses anti-inflammatory, antioxidant, and anti-osteoarthritic activities. Previous study indicates that monotropein may have the potential to combat cardiovascular disease, although the related mechanism remains unclear. In this study, we constructed the model of atherosclerosis by oxidized low density lipoprotein-induced vascular smooth muscle cells and LDLR –/–mice given high-fat diet to investigate the effects of monotropein on atherosclerosis.Our results showed that monotropein treatment significantly reduced the area of atherosclerotic plaques and necrotic cores in mice, inhibited the proliferation and migration of vascular smooth muscle cells, and reduced inflammatory responses and oxidative stress, which in turn alleviated atherosclerosis. In addition, we found that monotropein reduced the expression levels of P-NF-κB and P-AP-1. In conclusion, our data suggest that monotropein inhibited the proliferation and migration of vascular smooth muscle cells by mediating the activity of NF-κB, AP-1, reducing the level of inflammation and oxidative stress, and thus resisting the development of atherosclerosis. These findings demonstrate the efficacious therapeutic impact of monotropein on atherosclerosis and elucidate its specific target.

Objective:To explore effect and potential mechanism of disulfiram on necrotizing apoptosis of renal podocytes and macrophages.Methods:Mouse renal podocyte MPC-5 and macrophages J774A.1 and BMDM cells were cultured in vitro and treated with TNF-α,Smac mimetic LCL-161 and pan-caspase inhibitor IDN-6556(TSI)to induce necroptosis.Cell necrosis was detected by propi-dium iodide staining.Western blot was used to detect protein levels of necroptosis markers MLKL,RIPK3 and RIPK1.Immuno-fluorescence microscopy was used to observe the subcellular distribution of RIPK3 and p-MLKL in MPC-5 cells.Results:TSI treat-ment induced significant necroptosis in both MPC-5 cells and macrophages.Disulfiram was able to inhibit necroptosis in these cells in a dose-dependent manner.Moreover,disulfiram markedly blocked the phosphorylation of RIPK1,RIPK3 and MLKL.The aggregation of RIPK3 and p-MLKL were also suppressed by disulfiram.Conclusion:Disulfiram inhibits necroptosis in podocytes and macrophages by suppressing RIPK1/RIPK3/MLKL signaling pathway.

Objective:To explore effect and potential mechanism of disulfiram on necrotizing apoptosis of renal podocytes and macrophages.Methods:Mouse renal podocyte MPC-5 and macrophages J774A.1 and BMDM cells were cultured in vitro and treated with TNF-α,Smac mimetic LCL-161 and pan-caspase inhibitor IDN-6556(TSI)to induce necroptosis.Cell necrosis was detected by propi-dium iodide staining.Western blot was used to detect protein levels of necroptosis markers MLKL,RIPK3 and RIPK1.Immuno-fluorescence microscopy was used to observe the subcellular distribution of RIPK3 and p-MLKL in MPC-5 cells.Results:TSI treat-ment induced significant necroptosis in both MPC-5 cells and macrophages.Disulfiram was able to inhibit necroptosis in these cells in a dose-dependent manner.Moreover,disulfiram markedly blocked the phosphorylation of RIPK1,RIPK3 and MLKL.The aggregation of RIPK3 and p-MLKL were also suppressed by disulfiram.Conclusion:Disulfiram inhibits necroptosis in podocytes and macrophages by suppressing RIPK1/RIPK3/MLKL signaling pathway.

Objective To identify the pathogenic gene and variant for a family with branchio-otic syndrome.Methods The clinical data of this family were collected,and the peripheral blood was extracted for deafness gene NGS panel analysis.Pathogenic variation detected was verified by Sanger sequencing.Results The family contained 17 members in three-generations,3 of whom exhibited autosomal dominant,hearing loss,preauricular fistula and branchial cleft fistula,which were in accordance with the clinical diagnosis criteria of branchio-otic syndrome.A no-vel heterozygous variant c.963dupT(p.E322X)in EYA1 gene was identified,which co-segregated with the branchi-o-otic syndrome phenotype in the family.The variant was a nonsense variant resulting in the premature appearance of the stop codon.According to the American College of Medical Genetics and Genomics(ACMG)guidelines and the criteria,the variant was classified as pathogenic.Conclusion We identified a novel pathogenic variant EYA1:c.963dupT(p.E322X)in a family with branchio-otic syndrome.

italic>Platycodon grandiflorum (Jacq.) A. DC is one of the most commonly used bulk medicinal herbs. It has important value in the fields of medicine, food and cosmetics, and its market demand is increasing year by year, and it has a good development prospect. In this study, based on 403 distribution records and 8 environmental variables, we used Maxent model to predict the potential distribution of P. grandiflorum under climate change. The results showed that the model simulation effect was the best when the Maxent parameter was FC (feature combination) = LQPH (L: linear features; Q: quadratic features; P: product features; H: hinge features) and RM (regularization multiplier) = 2.1, AUC (area under curve) = 0.901, and the model prediction showed that P. grandiflorum was widely distributed in 28 provinces of China under the current climate conditions, with a suitable area of 2 337 419.98 km². Under the influence of climate change in the future, the area of suitable habitat of P. grandiflorum showed a decreasing trend, and the distribution center as a whole showed a trend of northward and eastward shift. The distribution area of P. grandiflorum in the three main producing areas is affected by climate change, and the overall trend is that the future suitable distribution area of Chifeng in Inner Mongolia increases, while the future suitable distribution area of Zibo in Shandong and Taihe, Bozhou in Anhui decreases or even disappears under the SSP5-8.5 scenario (shared socioeconomic pathways). It is suggested to maintain and protect the ecological environment and germplasm resources of the reserved area suitable for the growth of P. grandiflorum, and increase the cultivation research in the expansion area of P. grandiflorum, so as to lay a foundation for the subsequent expansion of P. grandiflorum planting and to promote the protection and sustainable development of P. grandiflorum resources.