期刊,IUBMB life 2022年74卷11期_国家学术搜索

期刊信息/Journal information

IUBMB life

Taylor & Francis, Inc

主办单位：Taylor & Francis, Inc

国际刊号：1521-6543

IUBMB life/Journal IUBMB lifeSCIISTPAHCI

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1页

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NSTL

Desaturases: Structural and mechanistic insights into the biosynthesis of unsaturated fatty acids

Michela CeroneTerry K. Smith

16页

查看更多>>摘要：Abstract This review highlights the key role of fatty acid desaturases in the synthesis of naturally occurring, more common and not unsaturated fatty acids. The three major classes of fatty acid desaturases, such as acyl‐lipid, acyl‐acyl carrier protein and acyl‐coenzyme A, are described in detail, with particular attention to the cellular localisation, the structure, the substrate and product specificity and the expression and regulation of desaturase genes. The review also gives an insight into the biocatalytic reaction of fatty acid desaturation by covering the general and more class‐specific mechanistic studies around the synthesis of unsaturated fatty acids Finally, we conclude the review by looking at the numerous novel applications for desaturases in order to meet the very high demand for polyunsaturated fatty acids, taking into account the opportunity for the development of new, more efficient, easily reproducible, sustainable bioengineering advances in the field.

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NSTL
Wiley

Iron overload‐induced ferroptosis of osteoblasts inhibits osteogenesis and promotes osteoporosis: An in vitro and in vivo study

Zengxin JiangHao WangGuobin QiChang Jiang...

18页

查看更多>>摘要：Abstract Growing evidence indicates that iron overload is an independent risk factor for osteoporosis. However, the mechanisms are not fully understood. The purpose of our study was to determine whether iron overload could lead to ferroptosis in osteoblasts and to explore whether ferroptosis of osteoblasts is involved in iron overload‐induced osteoporosis in vitro and in vivo. Ferric ammonium citrate was used to mimic iron overload conditions, while deferoxamine and ferrostatin‐1 were used to inhibit ferroptosis of MC3T3‐E1 cells in vitro. The ferroptosis, osteogenic differentiation and mineralization of MC3T3‐E1 cells were assessed in vitro. A mouse iron overload model was established using iron dextran. Immunohistochemical analysis was performed to determine ferroptosis of osteoblasts in vivo. Enzyme‐linked immunosorbent assays and calcein–alizarin red S labelling were used to assess new bone formation. Dual x‐ray absorptiometry, micro‐computed tomography and histopathological analysis were conducted to evaluate osteoporosis. The results showed that iron overload reduced cell viability, superoxide dismutase and glutathione levels, increased reactive oxygen species generation, lipid peroxidation, malondialdehyde levels and ferroptosis‐related protein expression, and induced ultrastructural changes in mitochondria. Iron overload could also inhibit osteogenic differentiation and mineralization in vitro. Inhibiting ferroptosis reversed the changes described above. Iron overload inhibited osteogenesis, promoted the ferroptosis of osteoblasts and induced osteoporosis in vivo, which could also be improved by deferoxamine and ferrostatin‐1. These results demonstrate that ferroptosis of osteoblasts plays a crucial role in iron overload‐induced osteoporosis. Maintaining iron homeostasis and targeting ferroptosis of osteoblasts might be potential measures of treating or preventing iron overload‐induced osteoporosis.

原文链接:

NSTL
Wiley

Inhibition of endoplasmic reticulum stress and the downstream pathways protects CD4+ T cells against apoptosis and immune dysregulation in sepsis

Gang LuQingqing LiJianjun LiuYanan Jia...

11页

查看更多>>摘要：Abstract Immunosuppression mediated by CD4+ T cell apoptosis and dysfunction is a key factor in promoting the progression of sepsis. Endoplasmic reticulum (ER) stress participates in the apoptosis and dysfunction of immune cells. We aimed to investigate the role of ER stress inhibition in CD4+ T cells in both in vitro and in vivo models of sepsis. In vitro model of sepsis was established with lipopolysaccharide (LPS) and the rat model of sepsis was established using cecal ligation and puncture (CLP). After the LPS treatment or CLP, ER stress inhibitors including 4‐PBA, SNJ‐1945, and SP600125 were used to treat cells or rats, and the CD4+ T cells were obtained by magnetic bead sorting. The effects of ER stress inhibitors on apoptosis and the function of CD4+ T cells were evaluated. After the LPS stimulation or CLP, the levels of ER stress and downstream markers (PERK, eIF2α, IRE‐1α, ATF6, ATF4, XBP‐1?s, GRP78, CHOP, and p‐JNK) were increased in CD4+ T cells at the beginning of sepsis. Meanwhile, the number of apoptotic CD4+ T cells markedly increased. In addition, sepsis impaired the function of CD4+ T cells, manifested by the increased population of Th1, Th2, Th17, and Treg, as well as the production of TNF‐α, interleukin (IL)‐6, IL‐4, and IL‐10. However, inhibitors of ER stress, JNK, and calpain all decreased the induction of Th1 and Th17, enhanced the increase of Th2 and Treg, decreased the production of TNF‐α and IL‐6, and enhanced the production of IL‐4 and IL‐10. Our findings indicate that ER stress inhibitors may play a protective role by reducing CD4+ T cell apoptosis and maintaining CD4+ T cell function, which may be useful for enhancing the immune function and poor prognosis of patients with sepsis.

原文链接:

NSTL
Wiley

Human osteoprogenitor cells obtained from traumatic heterotopic ossification samples showed enhanced osteogenic differentiation potential and ERK/hedgehog signaling than that from normal bone

Cunyi FanWei WangTongtong ZhangJuehong Li...

13页

查看更多>>摘要：Abstract Traumatic heterotopic ossification (HO) refers to the abnormal ectopic osteogenesis following trauma, causing limb dysfunction and seriously lowering the life quality of patients. Aberrant osteogenic behavior of progenitor cells that ectopically accumulated within the soft tissues are believed to be responsible for HO formation. However, the detailed mechanism still remained to be clarified. Here in this study, we successfully isolated osteoprogenitors from human heterotopic ossification tissues (HO‐ops) and identified their stemness and multi‐directional differentiation potential. Using alkaline phosphatase staining together with alizarin red staining, we confirmed that the HO‐ops in the heterotopic ossified tissues gained greater osteogenic potential than the normal human bone marrow mesenchymal stem cells (HBMSCs). RT‐qPCR also indicated that HO‐ops obtained more gene transcriptions of critical osteogenic determinators than HBMSCs. In addition, through Western blot, we proved that ERK signaling pathway and hedgehog signaling pathway were significantly activated in the HO‐ops. When U0126 and cyclopamine were used to inhibit ERK signaling and hedgehog signaling respectively, the osteogenic potential of HO‐ops decreased significantly. The hedgehog signaling and ERK signaling also showed cross‐talk in HO‐ops during osteogenic differentiation in HO‐ops during osteogenic differentiation. The elevated ERK signaling and hedgehog signaling were further confirmed in the human traumatic HO sample sections by immunohistochemical staining. In sum, our results showed that the activation of ERK and hedgehog signaling pathway jointly enhanced the osteogenic potential of HO‐ops to induce the formation of traumatic HO, which provides novel insights into the molecular basis of HO formation and offers promising targets for future therapeutic strategy.

原文链接:

NSTL
Wiley

iTRAQ‐based proteomic analysis of 17β‐Estradiol‐induced anti‐proliferation and apoptosis in mouse thymic epithelial cells by disturbing ribosomal biogenesis

Yameng LiuZilong LiDongguang GuoYongjiang Ma...

21页

查看更多>>摘要：Abstract Many evidences have suggested that estrogen was associated with thymic atrophy and suppressed thymocyte functions. Thymic epithelial cells (TECs), as a crucial constituent of thymic stroma support a unique microenvironment for thymocyte maturation, but the effects of estrogen on TECs were poorly understood. In our study, we found that 17β‐Estradiol (17β‐E2), one of the primary estrogens, could significantly inhibit cell proliferation, and cause cell cycle arrest in G2/M phase and apoptosis in mouse thymic epithelial cell line 1 (MTEC1 cells) with time‐ and dose‐ dependent. Above all, we provided the systemic and sufficient proteomic profiling of 17β‐E2 (50?nmol/L) acting on MTEC1 cells through isobaric tags for relative and absolute quantitation and LC–MS/MS (Liquid Chromatography Mass Spectrometry/Mass Spectrometry). A total of 71 differentially expressed proteins were identified, of which 61 were up‐regulated and 10 were down‐regulated. Particularly, the differential expression of abundant ribosomal proteins (RPs) was drawing our attention, including RPL3, RPL4, RPS11, RPL17, RPL5, RPS9, RPL13, RPL23A, RPLP2, RPS15A, and RPL29. Most of these proteins have been widely reported exerting extra‐ribosomal function associated with the proliferation and apoptosis of distinct cell types, but not yet observed in TECs. Moreover, bioinformatics analysis revealed that disturbance of ribosomal biogenesis was closely related to the anti‐proliferation and apoptosis in MTEC1 cells upon 17β‐E2. These data highlighted the possible mechanisms of 17β‐E2 on MTEC1 cells through showing adequate differential protein expression profiles. We inferred that 17β‐E2 induced anti‐proliferation and apoptosis in MTEC1 cells in response to alterations of ribosome biogenesis and RPs expression, which will contribute to gaining insight into the internal mechanism of thymic degeneration and exploiting to treat autoimmune diseases in the future.

原文链接:

NSTL
Wiley

Retraction

1页

原文链接:

NSTL
Wiley