Exosome is a Fancy Mobile Sower of Ferroptosis.

Exosomes, nano-sized small extracellular vesicles, have been shown to serve as mediators between intercellular communications by transferring bioactive molecules, such as non-coding RNA, proteins, and lipids from secretory to recipient cells, modulating a variety of physiological and pathophysiological processes. Recent studies have gradually demonstrated that altered exosome charges may represent a key mechanism driving the pathological process of ferroptosis. This review summarizes the potential mechanisms and signal pathways relevant to ferroptosis and then discusses the roles of exosome in ferroptosis. As well as transporting iron, exosomes may also indirectly convey factors related to ferroptosis. Furthermore, ferroptosis may be transmitted to adjacent cells through exosomes, resulting in cascading effects. It is expected that further research on exosomes will be conducted to explore their potential in ferroptosis and will lead to the creation of new therapeutic avenues for clinical diseases.

Effect of Exosomes From Bone Marrow-Derived Mesenchymal Stromal Cells and Adipose-Derived Stromal Cells on Bone-Tendon Healing in a Murine Rotator Cuff Injury Model.

Background: Bone-tendon injury is characterized by poor self-healing. It is established that exosomes are favorable for tissue repair and regeneration. However, their effect on bone-tendon healing has not yet been determined. Purpose: To compare the effectiveness of exosomes derived from adipose-derived mesenchymal stromal cells (ADSC-Exos) and bone marrow-derived mesenchymal stromal cells (BMSC-Exos) on bone-tendon interface healing in murine rotator cuff injury model and explore the underlying mechanisms thereof. Study Design: Controlled laboratory study. Methods: A total of 63 male C57BL6 mice with rotator cuff injuries underwent surgery and were randomly assigned to a control group treated without exosomes (n = 21), an ADSC-Exos group (n = 21), or a BMSC-Exos group (n = 21). The mice were sacrificed 4 or 8 weeks after surgery, and tissues were collected for histologic examination and radiographic and biomechanical testing. For exosome tracing in vivo, mice were sacrificed 7 days after surgery. A series of functional assays (radiographic evaluation, proliferation assay, Alizarin Red staining, alkaline phosphatase staining and activity, Alcian blue staining, quantitative polymerase chain reaction analyses, and glycosaminoglycans quantification) were conducted to evaluate the effect of exosomes on the cellular behaviors of the BMSCs in vitro. A statistical analysis of multiple-group comparisons was performed by 1-way analysis of variance, followed by the Bonferroni post hoc test to assess the differences between the 2 groups. Results: The ADSCs and BMSCs were positive for surface markers CD29 and CD90 and negative for surface markers CD34 and CD45 and could differentiate into osteoblasts, chondrocytes, and adipocytes. Exosomes showed a cup- or sphere-shaped morphology and were positive for CD63 and TGS101. Local injection of ADSC-Exos and BMSC-Exos could recruit BMSCs and promote osteogenesis, chondrogenesis, and bone-tendon healing. In vitro, ADSC-Exos and BMSC-Exos could significantly promote the proliferation, migration, osteogenic differentiation, and chondrogenic differentiation ability of BMSCs. In vivo, ADSC-Exos and BMSC-Exos significantly accelerated bone-tendon injury healing, with no significant statistical difference between them. Conclusion: ADSC-Exos and BMSC-Exos exhibited similar therapeutic effects on bone-tendon healing in our murine animal model. Clinical Relevance: ADSC-Exos and BMSC-Exos may be used to develop a new cell-free therapy method for promoting rotator cuff injury repair.

P53: A Key Target in the Development of Osteoarthritis.

Osteoarthritis (OA), a chronic degenerative disease characterized mainly by damage to the articular cartilage, is increasingly relevant to the pathological processes of senescence, apoptosis, autophagy, proliferation, and differentiation of chondrocytes. Clinical strategies for osteoarthritis can only improve symptoms and even along with side effects due to age, sex, disease, and other factors. Therefore, there is an urgent need to identify new ideas and targets for current clinical treatment. The tumor suppressor gene p53, which has been identified as a potential target for tumor therapeutic intervention, is responsible for the direct induction of the pathological processes involved in OA modulation. Consequently, deciphering the characteristics of p53 in chondrocytes is essential for investigating OA pathogenesis due to p53 regulation in an array of signaling pathways. This review highlights the effects of p53 on senescence, apoptosis, and autophagy of chondrocytes and its role in the development of OA. It also elucidates the underlying mechanism of p53 regulation in OA, which may help provide a novel strategies for the clinical treatment of OA.

Synergistic antibacterial attributes of copper-doped polydopamine nanoparticles: an insight into photothermal enhanced antibacterial efficacy.

Antibiotic-resistant bacteria and associated infectious diseases pose a grave threat to human health. The antibacterial activity of metal nanoparticles has been extensively utilized in several biomedical applications, showing that they can effectively inhibit the growth of various bacteria. In this research, copper-doped polydopamine nanoparticles (Cu@PDA NPs) were synthesized through an economical process employing deionized water and ethanol as a solvent. By harnessing the high photothermal conversion efficiency of polydopamine nanoparticles (PDA NPs) and the inherent antibacterial attributes of copper ions, we engineered nanoparticles with enhanced antibacterial characteristics. Cu@PDA NPs exhibited a rougher surface and a higher zeta potential in comparison to PDA NPs, and both demonstrated remarkable photothermal conversion efficiency. Comprehensive antibacterial evaluations substantiated the superior efficacy of Cu@PDA NPs attributable to their copper content. These readily prepared nano-antibacterial materials exhibit substantial potential in infection prevention and treatment, owing to their synergistic combination of photothermal and spectral antibacterial features.

The suppression of hyperlipid diet-induced ferroptosis of vascular smooth muscle cells protests against atherosclerosis independent of p53/SCL7A11/GPX4 axis.

Ferroptosis as a novel programmed cell death that involves metabolic dysfunction due to iron-dependent excessive lipid peroxidation has been implicated in atherosclerosis (AS) development characterized by disrupted lipid metabolism, but the atherogenic role of ferroptosis in vascular smooth muscle cells (VSMCs), which are principal components of atherosclerotic plaque fibrous cap, remains unclear. The aim of this study was to determine the effects of ferroptosis on AS induced by lipid overload, and the effects of that on VSMCs ferroptosis. We found intraperitoneal injection of Fer-1, a ferroptosis inhibitor, ameliorated obviously high-fat diet-induced high plasma levels of triglycerides, total cholesterol, low-density lipoprotein, glucose and atherosclerotic lesions in ApoE-/- mice. Moreover, in vivo and in vitro, Fer-1 reduced the iron accumulation of atherosclerotic lesions through affecting the expression of TFR1, FTH, and FTL in VSMCs. Interestingly, Fer-1 did augment nuclear factor E2-related factor 2/ferroptosis suppressor protein 1 to enhance endogenous resistance to lipid peroxidation, but not classic p53/SCL7A11/GPX4. Those observations indicated inhibition of VSMCs ferroptosis can improve AS lesions independent of p53/SLC7A11/GPX4, which preliminarily revealed the potential mechanism of ferroptosis in aortic VSMCs on AS and provided new therapeutic strategies and targets for AS.

The interaction of ZnO nanoparticles, Cr(VI), and microorganisms triggers a novel ROS scavenging strategy to inhibit microbial Cr(VI) reduction.

Cr(VI) contaminated water usually contains other contaminants like engineered nanomaterials (ENMs). During the process of microbial treatment, the inevitable interaction of Cr(VI), ENMs, and microorganisms probably determines the efficiency of Cr(VI) biotransformation, however, the corresponding information remains elusive. This study investigated the interaction of ZnO nanoparticles (NPs), Cr(VI), and Pannonibacter phragmitetus BB (hereafter BB), which changed the process of microbial Cr(VI) reduction. ZnO NPs inhibited Cr(VI) reduction, but had no effect on bacterial viability. In particular, Cr(VI) induced BB to produce organic acids and to drive Zn2+ dissolution from ZnO NPs inside and outside of cells. The dissolved Zn2+ not only promoted Cr(VI) reduction to Cr(V)/Cr(IV) by strengthening sugar metabolism and inducing increase in NAD(P)H production, but also hindered Cr(V)/Cr(IV) transformation to Cr(III) through down-regulating Cr(VI) reductase genes. A novel bacterial driven ROS scavenging mechanism leading to the inhibition of Cr(VI) reduction was elucidated. Specifically, the accumulated Cr(VI) and Cr(V)/Cr(IV) formed a redox dynamic equilibrium, which triggered the disproportionation of superoxide radicals mimicking superoxide dismutase through the flip-flop of Cr(VI) and Cr(V)/Cr(IV) in bacterial cells. This study provided a realistic insight into design the applicability of biological remediation technology for Cr(VI) contaminant and evaluating environmental risks of ENMs.

First report of leaf blight caused by Alternaria alternata on Platanus acerifolia in China.

Platanus acerifolia Willd. is widely planted in cities in China due to its strong adaptability to different environmental conditions. In August 2021, light brown, oval to circular, sunken spots were observed on leaves of P. acerifolia trees with 8-35% incidence, leading to severe necrosis and abscission of leaves on a street in Haidian district of Beijing (116°29'84''E, 39°95'93''N). Small pieces (5 mm×5 mm) were taken from the margin of diseased tissues, disinfected with 0.3% sodium hypochlorite for 2 min and 70% ethanol for 40 s, rinsed with sterile water, then plated on potato dextrose agar (PDA) and incubated at 28°C. After 4 days, representative isolates were transferred to new PDA plates. Four isolates with similar morphological characteristics were obtained and deposited in the culture collection (ID: DAA3, DAA5, DAA6 and DAA7) of our laboratory. Colonies on PDA were dense, fluffy, and light to dark gray, with a prominent white margin. Conidia formed in chains on the branched conidiophores, and were obpyriform to ellipsoid, 19.5-32.3×5.5-10.2 µm (average=26.4×7.1 µm, n=30) in size, with 3 to 5 transversal and 1 to 3 longitudinal septa. These morphological characteristics matched those of Alternaria spp. (Simmons 2007). Genomic DNA was extracted with modified CTAB method and the internal transcribed spacer (ITS) region, translation elongation factor 1-α (EF1-α), RNA polymerase II largest subunit (RPB2), glyceraldehyde 3 - dehydrogenase (GPD), endopolygalacturonase (EndoPG), as well as Alternaria major allergen (Alt a1) genes were amplified with primer pairs ITS1/ITS4 (White et al. 1990), EF1-728F/EF1-986R (Carbone and Kohn 1999), RPB2-5F/RPB2-7cR (Liu et al. 1999), gpd1/gpd2 (Berbee et al. 1999), PG3/PG2b (Andrew et al. 2009), and Alt-for/Alt-rev (Hong et al. 2005), respectively. The obtained sequences were deposited in GenBank (accession numbers: OM228653-OM228656, OM221523-OM221542). In a BLAST search, the sequences were 100% identical with corresponding sequences of A. alternata. Phylogenetic analysis based on combined sequences using maximum parsimony method showed that the four isolates clustered together with the type strain CBS 916.96 of A. alternata. For pathogenicity test, three healthy leaves of three one-year-old P. acerifolia plants were wounded with a sterile needle and inoculated with 20 µl of spore suspension (106 conidia/ml). Plants inoculated with sterile water were treated as control. The pathogenicity test was also conducted on the unwounded leaves. After 8 days of inoculation at 25°C and 90% RH with a 12-h photoperiod, the symptoms on spore suspension-inoculated leaves were similar to those observed on trees in the street, whereas the control leaves remained symptomless. Lesions on wounded leaves were larger than those on unwounded leaves. The assay was repeated twice with consistent results. The pathogen was re-isolated from symptomatic leaf tissues and identified based on morphological and rDNA-ITS sequencing, thus, fulfilling Koch's postulates. Examples of other tree species where Alternaria alternata has been reported to cause leaf blight were Ophiopogon japonicas in China (Wang et al. 2021) and Pistacia terebinthus in Spain (López-Moral et al. 2018). To our knowledge, this is the first report of A. alternata causing leaf blight on P. acerifolia in China. The identification could provide information for developing effective disease management strategies.

Two Novel Lasiodiplodia Species from Blighted Stems of Acer truncatum and Cotinus coggygria in China.

The Lasiodiplodia are major pathogens or endophytes living on a wide range of plant hosts in tropical and subtropical regions, which can cause stem canker, shoot blight, and rotting of fruits and roots. During an exploration of the stem diseases on Acer truncatum and Cotinus coggygria in northern China, two novel species of Lasiodiplodia, L. acerina G.H. Qiao & W.T. Qin and L. cotini G.H. Qiao & W.T. Qin, were discovered based on integrated studies of the morphological characteristics and phylogenetic analyses of the internal transcribed spacer region (ITS), translation elongation factor 1-α (TEF1-α), beta-tubulin (TUB2) and RNA polymerase II subunit b genes (RPB2). Lasiodiplodia acerina is a sister taxon of L. henannica and distinguishable by smaller paraphysis and larger conidiomata. Lasiodiplodia cotini is closely related to L. citricola but differs in the sequence data and the size of paraphyses. Distinctions between the two novel species and their close relatives were compared and discussed in details. This study updates the knowledge of species diversity of the genus Lasiodiplodia. Furthermore, this is the first report of Lasiodiplodia associated with blighted stems of A. truncatum and C. coggygria in China.

First report of Diaporthe eres causing leaf spot on Platanus acerifolia in China.

Platanus acerifolia Willd. is one of the world famous urban greening trees, known as "the king of street trees" (Loretta et al. 2020). In August 2021, severe leaf spot disease was observed on P. acerifolia with 15% incidence on a street of Haidian district (116°29'E, 39°95'N), Beijing municipality, China. Typical symptoms were small and irregular brown spots with or without yellow haloes, which gradually expanded, coalesced and became necrotic lesions. For pathogen isolation, the leaf lesions were cut into small tissue pieces, disinfected by 0.3% sodium hypochlorite for 2 min and 70% ethanol for 40 s, rinsed in sterile distilled water, and then incubated on potato dextrose agar (PDA) plates. After incubation at 28°C for 4 days, three fungal isolates (FTDX2, FTDX3, and FTDX6) with similar colony characteristics were obtained after single spore isolation. Colonies were white with fluffy aerial mycelia, abundant pycnidia with black stomata appeared and cream-white liquid oozed after 20 days. Alpha conidia were 7.9 ± 0.6 × 2.5 ± 0.3 µm (n = 30), aseptate, hyaline, fusiform to ellipsoidal, and often biguttulate, while beta conidia were 22.7 ± 1.3 × 1.1 ± 0.1 µm (n = 30), aseptate, hyaline, linear, curved or hamate. The morphological characteristics were consistent with those of Diaporthe sp. (Udayanga et al. 2014). For further identification, total DNA was extracted from the three isolates. The internal transcribed spacer (ITS) region, translation elongation factor 1-α (EF1-α), beta-tubulin (TUB), calmodulin (CAL) and histone (HIS) genes were amplified and sequenced with primers ITS1/ITS4 (White et al. 1990), EF1-728F/EF1-986R (Carbone and Kohn 1999), BT2a/BT2b (Glass and Donaldson 1995), CL1/CL2A (O'Donnell et al. 2000) and CYLH3F/H3-1b (Crous et al. 2014), respectively. The sequences were all deposited in GenBank (accession nos. OL870615 - OL870617 for ITS, OL870618 - OL870620 for EF1-α, OL870621 - OL870623 for TUB, OL870624 - OL870626 for CAL, and OL870627 - OL870629 for HIS) and aligned using BLASTn, obtaining 99-100% homology with the corresponding sequences of known Diaporthe eres strains in NCBI. Phylogenetic analysis of the combined sequences attributed the three isolates to the Diaporthe eres clade. Pathogenicity tests were performed on three healthy one-year-old P. acerifolia plants using the randomly selected isolate FTDX2. The leaves were inoculated with 20 µl of spore suspension (106 conidia/ml), with or without wound pretreatment, sterilized water inoculation under the same condition was used as control. All the treated plants were incubated in the greenhouse at 25°C and 90% RH with a 12-h photoperiod. After 8 days, the inoculated plants showed spot symptoms on leaves similar to those previously observed, whereas the control leaves remained symptomless. Lesions on the wounded leaves were much larger in size compared with those unwounded. The same pathogen was re-isolated and identified based on morphological characteristics and gene sequencing data, fulfilling Koch's postulates. Diaporthe eres has been reported to cause leaf spot on many horticultural plants, such as Photinia fraseri (Song et al. 2019) and Podocarpus macrophyllus (Zheng et al. 2020). To our knowledge, this is the first report of D. eres causing leaf spot on Platanus acerifolia in China. This finding is a valuable contribution to the knowledge on leaf spot disease development in horticultural plants.

Focus on ferroptosis, pyroptosis, apoptosis and autophagy of vascular endothelial cells to the strategic targets for the treatment of atherosclerosis.

Vascular endothelial cells (VECs), which are lined up in the inner surface of blood vessels, are in direct contact with the metabolite-related endogenous danger signals in the circulatory system. Moreover, VECs death impairs vasodilation and increases endothelium-dependent permeability, which is strongly correlated with the development of atherosclerosis (AS). Among several forms of cell death, regulatory death of endothelial cells frequently occurs in AS, mainly including ferroptosis, pyroptosis, apoptosis and autophagy. In this review, we summarize regulatory factors and signaling mechanisms of regulatory death in endothelial cells, discussing their effects in the context of the atherosclerotic procession.

Ferroptosis: the potential value target in atherosclerosis.

In advanced atherosclerosis (AS), defective function-induced cell death leads to the formation of the characteristic necrotic core and vulnerable plaque. The forms and mechanisms of cell death in AS have recently been elucidated. Among them, ferroptosis, an iron-dependent form of necrosis that is characterized by oxidative damage to phospholipids, promotes AS by accelerating endothelial dysfunction in lipid peroxidation. Moreover, disordered intracellular iron causes damage to macrophages, vascular smooth muscle cells (VSMCs), vascular endothelial cells (VECs), and affects many risk factors or pathologic processes of AS such as disturbances in lipid peroxidation, oxidative stress, inflammation, and dyslipidemia. However, the mechanisms through which ferroptosis initiates the development and progression of AS have not been established. This review explains the possible correlations between AS and ferroptosis, and provides a reliable theoretical basis for future studies on its mechanism.

Cloning, Expression, Characterization, and Tissue Distribution of Cystatin C from Silver Carp (Hypophthalmichthys molitrix).

Cystatins are proteins, which inhibit cysteine proteases, such as papain. In this study, the 336-bp cystatin C gene (family II, HmCysC) of silver carp (Hypophthalmichthys molitrix) was cloned and expressed in Escherichia coli BL21 (DE3). HmCysC encodes the mature peptide of cystatin C (HmCystatin C), with 111 amino acids. A typical QXXXG motif was found in HmCystatin C and it formed a cluster with Cyprinus carpio and Danio rerio cystatin C in the phylogenetic tree. Quantitative real-time polymerase chain reaction analysis indicated that HmCysC was transcribed at different levels in five tested tissues of silver carp. Following purification with Ni2+- nitrilotriacetic acid agarose affinity chromatography, HmCystatin C displayed a molecular weight of 20 kDa in sodium dodecyl sulfate polyacrylamide gel electrophoresis. Purified HmCystatin C had strong inhibitory effects toward the proteolytic activity of papain. Immunochemical staining with anti-HmCystatin C antibody showed that HmCystatin C was widely distributed in silver carp tissues. These results collectively demonstrated the properties of HmCystatin C, providing information for further studies of cystatins from fish organisms.

Relationship between postoperative complications and fibular integrity in congenital pseudarthrosis of the tibia in children.

BACKGROUND: This study aimed to investigate the relationship between postoperative complications and fibular integrity in congenital pseudarthrosis of the tibia (CPT) in children. METHODS: A retrospective study was performed in 59 patients with Crawford type IV CPT who were treated with combined surgical technique from 2007 to 2011. The patients were divided into two groups, the CPT with fibular pseudarthrosis (group A) and CPT with intact fibula groups (group B), on the basis of fibula status after the union of CPT. The incidence rates of refracture, ankle valgus, tibial valgus, and limb length discrepancy in the two groups were investigated. RESULTS: In group A, 14 (36.8%) cases had refracture, 30 (78.9%) had ankle valgus; 27 (71%) exhibited tibial valgus with an average tibial valgus of 7° (6°-20°), and 24 (63.2%) had limb length discrepancy with an average limb length of 1.26 cm (0.6-4.4 cm). In group B, 2 (9.5%) cases had refracture, 11 (52.4%) had ankle valgus, 8 (42.9%) had tibial valgus with an average tibial valgus deformity of 2.9° (6°-13°), and 13 (61.9%) had limb length discrepancy with an average limb length of 1.48 cm (0.5-5 cm). Significant difference in refracture and ankle valgus was found between groups A and B (P<0.05). CONCLUSIONS: After the union of CPT, patients with fibular pseudarthrosis showed higher incidence of refracture and ankle valgus than those with intact fibula. Attention should be paid to the presence of fibular pseudarthrosis when managing CPT.