Explore the vast range of titles available.

Adipose-derived mesenchymal stem cells (ADSCs) are promising candidate for regenerative medicine to repair non-healing bone defects due to their high and easy availability. However, the limited osteogenic differentiation potential greatly hinders the clinical application of ADSCs in bone repair. Accumulating evidences demonstrate that circular RNAs (circRNAs) are involved in stem/progenitor cell fate determination, but their specific role in stem/progenitor cell osteogenesis, remains mostly undescribed. Here, we show that circRNA-vgll3 originating from the vgll3 locus markedly enhances osteogenic differentiation of ADSCs; nevertheless, silencing of circRNA-vgll3 dramatically attenuates ADSC osteogenesis. Furthermore, we validate that circRNA-vgll3 functions in ADSC osteogenesis through a circRNA-vgll3/miR-326-5p/integrin α5 (Itga5) pathway. Itga5 promotes ADSC osteogenic differentiation and miR-326-5p suppresses Itga5 translation. CircRNA-vgll3 directly sequesters miR-326-5p in the cytoplasm and inhibits its activity to promote osteogenic differentiation. Moreover, the therapeutic potential of circRNA-vgll3-modified ADSCs with calcium phosphate cement (CPC) scaffolds was systematically evaluated in a critical-sized defect model in rats. Our results demonstrate that circRNA-vgll3 markedly enhances new bone formation with upregulated bone mineral density, bone volume/tissue volume, trabeculae number, and increased new bone generation. This study reveals the important role of circRNA-vgll3 during new bone biogenesis. Thus, circRNA-vgll3 engineered ADSCs may be effective potential therapeutic targets for bone regenerative medicine.

Retinal degeneration (RD) is one of the dominant causes of irreversible vision impairment and blindness worldwide. However, the current effective therapeutics for RD in the ophthalmologic clinic are unclear and controversial. In recent years, extensively investigated stem/progenitor cells—including retinal progenitor cells (RPCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and mesenchymal stromal cells (MSCs)—with proliferation and multidirectional differentiation potential have presented opportunities to revolutionise the ultimate clinical management of RD. Herein, we provide a comprehensive overview on the progression of clinical trials for RD treatment using four types of stem/progenitor cell-based transplantation to replace degenerative retinal cells and/or to supplement trophic factors from the aspects of safety, effectiveness and their respective advantages and disadvantages. In addition, we also discuss the emerging role of stem cells in the secretion of multifunctional nanoscale exosomes by which stem cells could be further exploited as a potential RD therapy. This review will facilitate the understanding of scientists and clinicians of the enormous promise of stem/progenitor cell-based transplantation for RD treatment, and provide incentive for superior employment of such strategies that may be suitable for treatment of other diseases, such as stroke and ischaemia–reperfusion injury.

Parkinson’s disease (PD) is a progressively debilitating neurodegenerative condition that leads to motor and cognitive dysfunction. At present, clinical treatment can only improve symptoms, but cannot effectively protect dopaminergic neurons. Several reports have demonstrated that human umbilical cord mesenchymal stem cells (hucMSCs) afford neuroprotection, while their application is limited because of their uncontrollable differentiation and other reasons. Stem cells communicate with cells through secreted exosomes (Exos), the present study aimed to explore whether Exos secreted by hucMSCs could function instead of hucMSCs. hucMSCs were successfully isolated and characterized, and shown to contribute to 6-hydroxydopamine (6-OHDA)-stimulated SH-SY5Y cell proliferation; hucMSC-derived Exos were also involved in this process. The Exos were purified and identified, and then labeled with PKH 26, it was found that the Exos could be efficiently taken up by SH-SY5Y cells after 12 h of incubation. Pretreatment with Exos promoted 6-OHDA-stimulated SH-SY5Y cells to proliferate and inhibited apoptosis by inducing autophagy. Furthermore, Exos reached the substantia nigra through the blood–brain barrier (BBB) in vivo, relieved apomorphine-induced asymmetric rotation, reduced substantia nigra dopaminergic neuron loss and apoptosis, and upregulated the level of dopamine in the striatum. These results demonstrate that hucMSCs-Exos have a treatment capability for PD and can traverse the BBB, indicating their potential for the effective treatment of PD.

Environmental pollution with toxic heavy metals can lead to the possible contamination of the rice. Selected metals (As, Cd, Hg and Pb) and their accumulation in rice collected from Zhejiang, China were analyzed to evaluate the potential health risk to the local adults and children. The mean levels found in rice were as follows: As, 0.080 mg/kg; Cd, 0.037 mg/kg; Hg, 0.005 mg/kg; Pb, 0.060 mg/kg. The estimated daily intakes (EDIs) were calculated in combination of the rice consumption data. The mean intakes of As, Cd, Hg and Pb through rice were estimated to be 0.49, 0.23, 0.03 and 0.37 µg/kg bw/day for adults, and 0.34, 0.29, 0.04 and 0.47 µg/kg bw/day for children. The 97.5th percentile (P97.5) daily intakes of As, Cd, Hg and Pb were 1.02, 0.64, 0.37 and 1.26 µg/kg bw/day for adults, and 0.63, 0.83, 0.47 and 1.63 µg/kg bw/day for children. The risk assessment in mean levels showed that health risk associated with these elements through consumption of rice was absent. However, estimates in P97.5 level of Cd and Pb for children, and Hg for adults have exceeded the respective safe limits.

Intrinsic shortcomings associated with conventional therapeutic strategies often compromise treatment efficacy in clinical ophthalmology, prompting the rapid development of versatile alternatives for satisfactory diagnostics and therapeutics. Given advances in material science, nanochemistry, and nanobiotechnology, a broad spectrum of functional nanosystems has been explored to satisfy the extensive requirements of ophthalmologic applications. In the present review, the recent progress in nanosystems, both conventional and emerging nanomaterials in ophthalmology from state‐of‐the‐art studies, are comprehensively examined and the role of their fundamental physicochemical properties in bioavailability, tissue penetration, biodistribution, and elimination after interacting with the ophthalmologic microenvironment emphasized. Furthermore, along with the development of surface engineering of nanomaterials, emerging theranostic methodologies are promoted as potential alternatives for multipurpose ocular applications, such as emerging biomimetic ophthalmology (e.g., smart electrochemical eye), thus provoking a holistic review of “ocular nanomedicine.” By affording insight into challenges encountered by ocular nanomedicine and further highlighting the direction of future studies, this review provides an incentive for enriching ocular nanomedicine‐based fundamental research and future clinical translation. The distinctive functional ocular nanomedicine as potential alternatives for satisfying the requirements of abundant ophthalmologic applications has been comprehensively overviewed. In this comprehensive review, the authors summarize, discuss and highlight the fundamental principles on the design, fabrication, and ophthalmologic application of distinctive ocular nanomedicine, and provide an overview and deep discussion on the nano‐enabled amalgamation of ophthalmology, material chemistry, biology, and medicine.

There is a close anatomical and functional relationship between adipose tissue and blood vessels. The crosstalk between these two organs is vital to both metabolic and vascular homeostasis. On the one hand, adipose tissue is highly vascularized, and maintenance of ample supply of blood flow is essential for both expansion and metabolic functions of adipose tissue. Vascular endothelium also secretes many factors to regulate adipogenesis and adipose tissue remodeling. On the other hand, almost all blood vessels are surrounded by perivascular adipose tissue (PVAT), which regulates vascular function by producing a large number of “vasocrine” molecules. Under the normal conditions, PVAT exerts its anti-contractile effects by release of vasorelaxants (such as adipocyte-derived relaxation factors and adiponectin) that promote both endothelium-dependent and –independent relaxations of blood vessels. However, PVAT in obesity becomes highly inflamed and induces vascular dysfunction by augmented secretion of vasoconstriction factors (such as the major components of renin-angiotensinogen-aldosterone system and superoxide) and pro-inflammatory adipokines (such as TNF-α and adipocyte fatty acid binding protein), the latter of which are important contributors to endothelial activation, vascular inflammation and neointimal formation. Furthermore, several adipocyte-derived adipokines impair vascular function indirectly, by acting in the brain to activate sympathetic nerve system (such as leptin) or by exerting their actions in major metabolic organs to induce vascular insulin resistance, which in turn aggravates endothelial dysfunction. Aberrant secretion of adipokines and other vasoactive factors in adipose tissue is a major contributor to the onset and progression of obesity-related metabolic and vascular complications.

Callus browning, a common trait derived from the indica rice cultivar ( Oryza sativa L.), is a challenge to transformation regeneration. Here, we report the map-based cloning of BROWNING OF CALLUS1 ( BOC1 ) using a population derived from crossing Teqing, an elite indica subspecies exhibiting callus browning, and Yuanjiang, a common wild rice accession ( Oryza rufipogon Griff.) that is less susceptible to callus browning. We show that BOC1 encodes a SIMILAR TO RADICAL-INDUCED CELL DEATH ONE (SRO) protein. Callus browning can be reduced by appropriate upregulation of BOC1 , which consequently improves the genetic transformation efficiency. The presence of a Tourist -like miniature inverted-repeat transposable element ( Tourist MITE) specific to wild rice in the promoter of BOC1 increases the expression of BOC1 in callus. BOC1 may decrease cell senescence and death caused by oxidative stress. Our study provides a gene target for improving tissue culturability and genetic transformation. Callus browning heavily affects indica rice transformation regeneration. Here, the authors show transposon insertion in the promoter of BOC1 gene, encoding a SIMILAR TO RADICAL-INDUCED CELL DEATH ONE protein, can upregulate its expression and decrease callus browning in cultivated rice by releasing oxidative stress.

The present study analyzed 5785 vegetables for concentrations of As, Cd, Cr, Pb, Ni and Hg and estimated the health risk to local consumers by deterministic (point estimates) approaches. Levels of elements varied in different vegetables. Average levels of As, Cd, Cr, Ni, Hg and Pb were 0.013, 0.017, 0.057, 0.002, 0.094 and 0.034 mg/kg (fresh weight), respectively. The samples with 0.25% for Cd and 1.56% for Pb were exceeding the maximum allowable concentrations (MACs) set by the Chinese Health Ministry. No obvious regular geographical distribution for these metals in vegetables was found in areas of Zhejiang, China. The mean and 97.5 percentile levels of heavy metal and metalloid were used to present the mean and high exposure assessment. The health indices (HIs) were less than the threshold of 1 both in mean and high exposure assessment. It indicates that for the general people there is very low health risk to As, Cd, Cr, Pb, Ni and Hg by vegetable intake.

Background Gasdermin D (GSDMD)-mediated pyroptotic cell death is implicated in the pathogenesis of cognitive deficits in sepsis-associated encephalopathy (SAE), yet the underlying mechanisms remain largely unclear. Dynamin-related protein 1 (Drp1) facilitates mitochondrial fission and ensures quality control to maintain cellular homeostasis during infection. This study aimed to investigate the potential role of the GSDMD/Drp1 signaling pathway in cognitive impairments in a mouse model of SAE. Methods C57BL/6 male mice were subjected to cecal ligation and puncture (CLP) to establish an animal model of SAE. In the interventional study, mice were treated with the GSDMD inhibitor necrosulfonamide (NSA) or the Drp1 inhibitor mitochondrial division inhibitor-1 (Mdivi-1). Surviving mice underwent behavioral tests, and hippocampal tissues were harvested for histological analysis and biochemical assays at corresponding time points. Haematoxylin-eosin staining and TUNEL assays were used to evaluate neuronal damage. Golgi staining was used to detect synaptic dendritic spine density. Additionally, transmission electron microscopy was performed to assess mitochondrial and synaptic morphology in the hippocampus. Local field potential recordings were conducted to detect network oscillations in the hippocampus. Results CLP induced the activation of GSDMD, an upregulation of Drp1, leading to associated mitochondrial impairment, neuroinflammation, as well as neuronal and synaptic damage. Consequently, these effects resulted in a reduction in neural oscillations in the hippocampus and significant learning and memory deficits in the mice. Notably, treatment with NSA or Mdivi-1 effectively prevented these GSDMD-mediated abnormalities. Conclusions Our data indicate that the GSDMD/Drp1 signaling pathway is involved in cognitive deficits in a mouse model of SAE. Inhibiting GSDMD or Drp1 emerges as a potential therapeutic strategy to alleviate the observed synaptic damages and network oscillations abnormalities in the hippocampus of SAE mice.

Adipose tissue macrophage (ATM) inflammation is involved with meta-inflammation and pathology of metabolic complications. Here we report that in adipocytes, elevated lactate production, previously regarded as the waste product of glycolysis, serves as a danger signal to promote ATM polarization to an inflammatory state in the context of obesity. Adipocyte-selective deletion of lactate dehydrogenase A ( Ldha ), the enzyme converting pyruvate to lactate, protects mice from obesity-associated glucose intolerance and insulin resistance, accompanied by a lower percentage of inflammatory ATM and reduced production of pro-inflammatory cytokines such as interleukin 1β (IL-1β). Mechanistically, lactate, at its physiological concentration, fosters the activation of inflammatory macrophages by directly binding to the catalytic domain of prolyl hydroxylase domain-containing 2 (PHD2) in a competitive manner with α-ketoglutarate and stabilizes hypoxia inducible factor (HIF-1α). Lactate-induced IL-1β was abolished in PHD2-deficient macrophages. Human adipose lactate level is positively linked with local inflammatory features and insulin resistance index independent of the body mass index (BMI). Our study shows a critical function of adipocyte-derived lactate in promoting the pro-inflammatory microenvironment in adipose and identifies PHD2 as a direct sensor of lactate, which functions to connect chronic inflammation and energy metabolism. Adipocyte tissue macrophages (ATM) are recruited and activated in obesity. The authors show that adipocytes release lactate as a signal of inflammation and that this metabolite can enhance obesity associated inflammation through stimulation of ATM by direct binding with PHD2.