Growth factors play a crucial role in regulating a broad variety of biological processes and are regarded as powerful therapeutic agents in tissue engineering and regenerative medicine in the past ...decades. However, their application is limited by their short half‐lives and potential side effects in physiological environments. Hydrogels are identified as having the promising potential to prolong the half‐lives of growth factors and mitigate their adverse effects by restricting them within the matrix to reduce their rapid proteolysis, burst release, and unwanted diffusion. This review discusses recent progress in the development of growth factor‐containing hydrogels for various biomedical applications, including wound healing, brain tissue repair, cartilage and bone regeneration, and spinal cord injury repair. In addition, the review introduces strategies for optimizing growth factor release including affinity‐based delivery, carrier‐assisted delivery, stimuli‐responsive delivery, spatial structure‐based delivery, and cellular system‐based delivery. Finally, the review presents current limitations and future research directions for growth factor‐delivering hydrogels.
A comprehensive review on the progress of hydrogel‐based growth factor delivery systems for biomedical applications and the strategies utilized for growth factor delivery optimization is presented, with an emphasis on the ways the hydrogels facilitate the delivery and improve the therapeutic efficacy of growth factors. The current limitations and future research directions in this field are also discussed.
Although great achievements have been made in the synthesis of giant lanthanide clusters, novel structural models are still scarce. Herein, we report a giant lanthanide cluster Dy76, constructed from ...Dy3(μ3‐OH)4 and Dy5(μ4‐O)(μ3‐OH)8 building blocks. As the largest known Dy cluster, the structure of Dy76 can be seen as arising from the fusion of two Dy48 clusters; these clusters can be isolated under various synthetic conditions and were characterized by single‐crystal X‐ray diffraction. This new, fused structural model of the pillar motif has not been found in Ln clusters. Furthermore, the successful conversion of Dy76 back into Dy48 in a retrosynthetic manner supports the proposed fusion formation mechanism of Dy76. Electrospray ionization mass spectrometry (ESI‐MS) analysis suggests that the metal cluster skeleton of Dy76 shows good stability in various solvents. This work not only reveals a new structural type of Ln clusters but also provides insight into the novel fusion assembly process.
We go together: Two dysprosium clusters with 48 and 76 metal atoms, respectively, were generated under solvothermal conditions by using 3‐furancarboxylic acid. The bi‐nanopillar Dy76 was formed by the fusion of two Dy48 nanopillars.
The Vaginal Microecology Evaluation System (VMES) is a technical and economically feasible tool to assess the vaginal microbiomes of gynecological outpatients. The aim of this review was to introduce ...knowledge on the potential changes that can occur in the vaginal microbiome and how to use the Evaluation System to diagnose and manage a broad range of vaginal infections.
This review was based on data in articles published in PubMed up to December 10, 2018, with the following keywords: "Vaginal microecosystem", "vaginal microbiome", "vaginal microbiota", and "vaginal flora".
Original articles and critical reviews on VMES and vaginal microbiota selected for this review. References of the retrieved articles were also screened to search for potentially relevant papers.
Any imbalance in the naturally occurring vaginal bacterial flora may result in infections such as bacterial vaginitis, aerobic vaginitis, vulvovaginal candidiasis, or Trichomonas vaginalis. VMES is mainly composed of morphological and functional microecological indicators. The former diagnostic modality includes bacterial density, flora diversity, dominant bacterial flora, indicators of inflammation, pathogenic microorganisms, Nugent score, and AV score. Functional indicators consist of two main components: metabolites and microbial enzymes.
The establishment of VMES has a high clinical value in the treatment of vaginal infections. It opens up new opportunities for the comprehensive management of dysbacteriosis when such infections occur.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.
Farnesol is a Candida-secreted quorum-sensing molecule of great interest as a potential antifungal agent for serious and hardly curable infections--candidiasis, especially vulvovaginal candidiasis ...(VVC). The effect of farnesol on cellular morphology and viability and evaluated the production of Th1 (IL-2), Th2 (IL-4), proinflammatory (IL-6), chemotactic (IL-8), and Th17 (IL-17) cytokines in the culture supernatants of vaginal epithelial cell line (VK2) were evaluated. Moreover, we tested the inhibitory effect of farnesol on C. albicans adhesion. Scanning electron microscopy was conducted to observe any VK2 cell ultrastructural changes. Only low concentrations (less than or equal to 50 micromol/L) of farnesol did not affect the morphology and viability of the VK2 cells (P > 0.05). Farnesol reduced the adhesion of C. albicans to the VK2 cells. When treated with farnesol, statistical elevated levels of both IL-4 and IL-17 secreted by the infected VK2 cells were present in the culture supernatants (P < 0.05). Farnesol acts as a stimulator to up-regulate the Th17-type innate immune response, as well as Th2-type humoral immunity following C. albicans infection. Further research is required to select the optimal therapeutic dose to develop efficacious and safe mucosal immune adjuvant for treating VVCs.
The crosstalk between vascular pericytes and endothelial cells (ECs) is critical for microvascular stabilization and remodeling; however, the crosstalk is often disrupted by diabetes, leading to ...severe and even lethal vascular damage. Circular RNAs are a class of endogenous RNAs that regulate several important physiological and pathological processes. Here we show that diabetes-related stress up-regulates cPWWP2A expression in pericytes but not in ECs. In vitro studies show that cPWWP2A directly regulates pericyte biology but indirectly regulates EC biology via exosomes carrying cPWWP2A. cPWWP2A acts as an endogenous miR-579 sponge to sequester and inhibit miR-579 activity, leading to increased expression of angiopoietin 1, occludin, and SIRT1. In vivo studies show that cPWWP2A overexpression or miR-579 inhibition alleviates diabetes mellitus-induced retinal vascular dysfunction. By contrast, inhibition of cPWWP2A-mediated signaling by silencing cPWWP2A or over-expressing miR-579 aggravates retinal vascular dysfunction. Collectively, this study unveils a mechanism by which pericytes and ECs communicate. Intervention of cPWWP2A or miR-579 expression may offer opportunities for treating diabetic microvascular complications.
Background： Vulvovaginal candidiasis （WC） was a common infection associated with lifelong harassment of woman＇s social and sexual life. The purpose of this study was to describe the species ...distribution and in vitro antifungal susceptibility of Candida species （Candida spp.） isolated from patients with VVC over 8 years. Methods： Species which isolated from patients with VVC in Peking University First Hospital were identified using chromogenic culture media. Susceptibility to common antifungal agents was determined using agar diffusion method based on CLSI M44-A2 document. SPSS software （version 14.0, Inc., Chicago, IL, USA） was used for statistical analysis, involving statistical description and Chi-square test. Results： The most common strains were Candida （C.） albicans, 80.5% （n = 1775） followed by C. glabrata, 18.1% （n = 400）. Nystatin exhibited excellent activity against all species （〈4% resistant JR）. Resistance to azole drugs varied among different species. C. albicans： clotrimazole （3.1% R） 〈 fluconazole （ 16.6% R） 〈 itraconazole （51.5% R） 〈 mieonazole （54.0% R）, C. glabrata： miconazole （25.6% R） 〈 clotrimazole （50.5% R） 〈 itraconazole （61.9% R） 〈 fluconazole （73.3% R）; Candida krusei： clotrimazole （0 R） 〈 fluconazole （57.7% R） 〈 miconazole （73.1% R） 〈 itraconazole （83.3% R）. The susceptibility of fluconazole was noticeably decreasing among all species in the study period. Conclusions： Nystatin was the optimal choice for the treatment of VVC at present. The species distribution and in ~＇itro antifungal susceptibility of Candida spp. isolated from patients with VVC had changed over time.
To reveal the expression profile and clinical significance of circular RNAs (circRNAs) in diabetic retinopathy (DR).
Circular RNA microarrays were performed to identify DR-related circRNAs. Gene ...ontology (GO) enrichment and KEGG analysis was performed to determine the biologic modules and signaling pathway. TargetScan and miRana program was used to predict circRNA/miRNA interaction. Quantitative PCR assays were performed to detect circRNA expression pattern in clinical samples. Ki67 staining, Transwell, tube formation, and spheroid sprouting assays were performed to investigate the role and mechanism of circRNA in endothelial angiogenic function.
A total of 529 circRNAs were aberrantly expressed in diabetic retinas. The host genes of differentially expressed circRNAs were targeted to ATP binding (biologic process); extracellular exosome (cellular component); and intracellular signal transduction (molecular function). Circ_0005015 was verified to be upregulated in the plasma, vitreous sample, and fibrovascular membranes of DR patients. Circ_0005015 facilitated retinal endothelial angiogenic function via regulating endothelial cell proliferation, migration, and tube formation. Circ_0005015 acted as miR-519d-3p sponge to inhibit miR-519d-3p activity, leading to increased MMP-2, XIAP, and STAT3 expression.
circRNAs are involved in DR pathogenesis, and thus serve as potential biomarkers of DR diagnosis.
The 3-N-butylphthalide (NBP) comprises one of the chemical constituents of celery oil. It has a series of pharmacologic mechanisms including reconstructing microcirculation, protecting mitochondrial ...function, inhibiting oxidative stress, inhibiting neuronal apoptosis, etc. Based on the complex multi-targets of pharmacologic mechanisms of NBP, the clinical application of NBP is increasing and more clinical researches and animal experiments are also focused on NBP. The aim of this review was to comprehensively and systematically summarize the application of NBP on neurologic diseases and briefly summarize its application to non-neurologic diseases. Moreover, recent progress in experimental models of NBP on animals was summarized.
Literature was collected from PubMed and Wangfang database until November 2018, using the search terms including "3-N-butylphthalide," "microcirculation," "mitochondria," "ischemic stroke," "Alzheimer disease," "vascular dementia," "Parkinson disease," "brain edema," "CO poisoning," "traumatic central nervous system injury," "autoimmune disease," "amyotrophic lateral sclerosis," "seizures," "diabetes," "diabetic cataract," and "atherosclerosis."
Literature was mainly derived from English articles or articles that could be obtained with English abstracts and partly derived from Chinese articles. Article type was not limited. References were also identified from the bibliographies of identified articles and the authors' files.
NBP has become an important adjunct for ischemic stroke. In vascular dementia, the clinical application of NBP to treat severe cognitive dysfunction syndrome caused by the hypoperfusion of brain tissue during cerebrovascular disease is also increasing. Evidence also suggests that NBP has a therapeutic effect for neurodegenerative diseases. Many animal experiments have found that it can also improve symptoms in other neurologic diseases such as epilepsy, cerebral edema, and decreased cognitive function caused by severe acute carbon monoxide poisoning. Moreover, NBP has therapeutic effects for diabetes, diabetes-induced cataracts, and non-neurologic diseases such as atherosclerosis. Mechanistically, NBP mainly improves microcirculation and protects mitochondria. Its broad pharmacologic effects also include inhibiting oxidative stress, nerve cell apoptosis, inflammatory responses, and anti-platelet and anti-thrombotic effects.
The varied pharmacologic mechanisms of NBP involve many complex molecular mechanisms; however, there many unknown pharmacologic effects await further study.
One hallmark of cancer cells is aberrant glucose metabolism. By desperately consuming glucose, cancer cells grow quickly and form a hypoxic core in the tumor, which severely limits the efficacy of ...oxygen‐dependent therapeutic strategies. Herein, a cell metabolism regulation strategy is adopted to reallocate cell respiration substrates for fueling the processes for cancer therapy by constructing a metabolism nanoregulator (denoted as ATO/GOx PLP). To be specific, a protoporphyrin IX (PpIX, the intermembrane‐translocatable accessory)‐doped liposome is employed for direct intracellular delivery of GOx and atovaquone (ATO, a mitochondrial complex III inhibitor). The PpIX‐doped liposome can efficiently avoid the cargo leakage in blood circulation. Benefiting from the translocation of PpIX from the liposome to the cancer cell membrane, ATO and GOx can be rapidly released upon encountering the plasma membrane and internalized by the cancer cell. By inhibiting mitochondrial oxidative phosphorylation and regulating mitochondrial function, ATO reduces both oxygen consumption and glucose metabolism, sparing more substrates for GOx to kill cancer cells. As a result, ATO/GOx PLP presents outstanding anticancer efficacies both in vitro and in vivo. In addition, the ATO/GOx PLP exhibits excellent biosafety, showing its clinical translation potential. Overall, this study provides a new approach to achieve efficacious metabolism regulation‐based cancer therapy.
A cell metabolism regulation strategy to reallocate the cell respiration substrates for fueling the glucose oxidase (GOx) catalysis process for cancer therapy is developed by constructing a metabolism nanoregulator. More importantly, it is also demonstrated that the carrier of the nanoregulator, the protoporphyrin IX (PpIX)‐doped liposome, can directly and responsively release the encapsulated cargoes via an interesting PpIX translocation process.
Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults. Vascular pericyte degeneration is the predominant clinical manifestation of DR, yet the mechanism governing pericyte ...degeneration is poorly understood. Circular RNAs (circRNAs) play important roles in multiple biological processes and disease progression. Here, we investigated the role of circRNA in pericyte biology and diabetes-induced retinal vascular dysfunction. cZNF532 expression was upregulated in pericytes under diabetic stress, in the retinal vessels of a diabetic murine model, and in the vitreous humor of diabetic patients. cZNF532 silencing reduced the viability, proliferation, and differentiation of pericytes and suppressed the recruitment of pericytes toward endothelial cells in vitro. cZNF532 regulated pericyte biology by acting as a miR-29a-3p sponge and inducing increased expression of NG2, LOXL2, and CDK2. Knockdown of cZNF532 or overexpression of miR-29a-3p aggravated streptozotocin-induced retinal pericyte degeneration and vascular dysfunction. By contrast, overexpression of cZNF532 or inhibition of miR-29a-3p ameliorated human diabetic vitreous-induced retinal pericyte degeneration and vascular dysfunction. Collectively, these data identify a circRNA-mediated mechanism that coordinates pericyte biology and vascular homeostasis in DR. Induction of cZNF532 or antagonism of miR-29a-3p is an exploitable therapeutic approach for the treatment of DR.
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