Breathable, antifreezing, mechanically skin-like hydrogel textile wound dressings with dual antibacterial mechanisms.

Hydrogels are emerging as the most promising dressings due to their excellent biocompatibility, extracellular matrix mimicking structure, and drug loading ability. However, existing hydrogel dressings exhibit limited breathability, poor environmental adaptability, potential drug resistance, and limited drug options, which extremely restrict their therapeutic effect and working scenarios. Here, the current research introduces the first paradigm of hydrogel textile dressings based on novel gelatin glycerin hydrogel (glyhydrogel) fibers fabricated by the Hofmeister effect based wet spinning. Benefiting from the unique knitted structure, the textile dressing features excellent breathability (1800 times that of the commercially available 3 M dressing) and stretchability (535.51 ± 38.66%). Furthermore, the glyhydrogel textile dressing can also withstand the extreme temperature of -80 °C, showing the potential for application in subzero environments. Moreover, the introduction of glycerin endows the textile dressing with remarkable antibacterial property and expands the selection of loaded drugs (e.g., clindamycin). The prepared glyhydrogel textile dressing shows an excellent infected wound healing effect with a complete rat skin closure within 14 days. All these functions have not been achievable by traditional hydrogel dressings and provide a new approach for the development of hydrogel dressings.

Multi-omics insights reveal the remodeling of gut mycobiome with P. gingivalis.

As a keystone periodontal pathogen, Porphyromonas gingivalis (P. gingivalis) was suggested to be involved in the progression of systemic diseases by altering the intestinal microecology. However, studies concerning gut microbiome have focused entirely on the bacterial component, while the fungal community (gut mycobiome) has been overlooked. In this study, we aimed to characterize the alteration of gut mycobiome profile with P. gingivalis administration using mice fecal samples. Metagenomic analysis showed a distinct composition pattern of mycobiome and significant difference of beta diversity between control and the P. gingivalis group. Some fungal species were differentially characterized with P. gingivalis administration, among which Pyricularia pennisetigena and Alternaria alternata showed positive correlation with P. gingivalis. KEGG functional analyses revealed that three pathways, namely, "pentose and glucuronate interconversions", "metabolic pathways", and "two-component system", were statistically enriched with P. gingivalis administration. Moreover, the alteration of gut mycobiome was also closely related with serum metabolites, especially lipid and tryptophan metabolic pathways. Taken together, this study demonstrated the alteration of fungal composition and function with P. gingivalis administration for the first time, and investigated the fungi-bacterial interaction and fungi-metabolite interaction preliminarily, providing a whole insight into gut mycobiome remodeling with oral pathobiont through multi-omics analyses.

Correlation Analysis of Gut Microbiota and Serum Metabolome With Porphyromonas gingivalis-Induced Metabolic Disorders.

Periodontitis has been demonstrated to increase the risk of metabolic syndrome (MetS), but the underlying mechanism remains unclear. Recent studies have indicated periodontopathic bacteria such as Porphyromonas gingivalis could induce gut microbiota (GM) dysbiosis and aggravate metabolic disorders. However, the effects of microbial metabolites have barely been evaluated. Here, we investigated the alteration of serum metabolome with P. gingivalis-induced metabolic disorders, and explored the correlations of GM and serum metabolites. In this study, we orally administered P. gingivalis ATCC33277 to C57BL/6 mice and performed metagenomic sequencing and untargeted metabolomics with fecal samples and serum collection. In vivo experiments showed a higher proportion of fat mass and worse glucose tolerance in P. gingivalis-administered mice, accompanied with an increase of adipose inflammation and gut permeability, which was similar to HFD-induced obese mice. Metagenomic sequencing indicated a compositional and functional alteration of GM. Untargeted metabolomics revealed an alteration of metabolites in P. gingivalis-administered mice, and most of them were engaged in metabolic pathways, such as tryptophan metabolism and choline metabolism. Correlation analysis between GM and serum metabolome indicated strong relativity with P. gingivalis administration. These results demonstrated some specific microbiota-derived metabolites in the pathogenesis of P. gingivalis-induced metabolic disorders, providing promising targets for the development of novel treatment strategies for MetS.

Corrigendum to "A Chemically Defined Serum-Free Culture System for Spontaneous Human Mesenchymal Stem Cell Spheroid Formation".

[This corrects the article DOI: 10.1155/2020/1031985.].

Depletion of the diabetic gut microbiota resistance enhances stem cells therapy in type 1 diabetes mellitus.

Microbiome, considered as the "second genome" of the host, is altered in type 1 diabetes mellitus (T1DM) patients to a state of dysbiosis. Mesenchymal stem cell (MSC) transplantation is a promising treatment for T1DM but is limited by several factors in the diabetic host. In this study, we tested the hypothesis that dysbiotic gut microbiota may limit MSC therapy, and modulating gut microbiota may help to improve the effects of MSC transplantation. Methods: NOD/Ltj mice, treated with adipose-derived stem cells (ADSCs), were fed with an antibiotics cocktails (Abx) for 1 week. The blood glucose levels, insulitis, intestinal permeability and gut bacteria translocation to the pancreas were evaluated. 16s rRNA and colon tissue transcription sequencing were performed to analyze beneficial bacteria and reactive host biomolecules in the ADSCs+Abx group. Based on the sequencing results, specific bacteria were gavaged orally to diabetic mice to confirm their effect on ADSCs transplantation in T1DM was determined. Results: We found that the recolonized the diabetic gut microbiota abolished the therapeutic effect of ADSCs. On the contrary, depletion of the diabetic gut microbiota by antibiotics treatment in diabetic mice significantly enhanced the therapeutic effects of ADSCs as measured by reversal of hyperglycemia, insulitis, and increased insulin output. Mechanistically, treatment with antibiotics increased the abundance of Bifidobacterium in the gut and reduced bacterial translocation to the pancreas by promoting Mucin2 expression and thickening the mucus layer through TRPM7. The mechanism was confirmed the re-colonization of the gut by B.breve through oral gavage that produced similar results. Conclusions: These results provide the rationale for a new approach to improve MSC therapy for T1DM by altering the gut microbiota.

A Chemically Defined Serum-Free Culture System for Spontaneous Human Mesenchymal Stem Cell Spheroid Formation.

Mesenchymal stem cells (MSCs) possess promising potential in tissue engineering and regenerative medicine. Previous studies demonstrated that spheroid formation of MSCs exhibited improved stemness maintenance and therapeutic potential compared with monolayer culture. To date, various spheroid culture systems have been developed but most of them required low adhesion conditions or special equipment. In this study, we demonstrated that inoculation of dissociated MSCs in TeSR-E8 medium could induce self-assemble spheroid formation in conventional tissue culture polystyrene dishes. Compared with monolayer culture, adipose-derived stem cell (ADSC) spheroids enhanced the proliferation and osteogenic capability of ADSCs compared with monolayer culture. When reseeded in normal serum-containing medium, the expression level of stemness biomarkers was even higher in spheroid-derived ADSCs than monolayer culture. Importantly, spheroid ADSCs could effectively promote the M2 polarization of macrophages both in vitro and in vivo. After transplantation into mouse, spheroid ADSCs improved the survival rate and significantly decreased serum levels of proinflammatory factors IL-1ß and TNF-α following LPS challenge. In summary, we developed a 3D spheroid culture system through TeSR-E8 medium without the involvement of low adhesion conditions and special equipment, which provided a practical and convenient method for spheroid formation of MSCs with great potential for stem cell clinical therapy.

Gene editing of the extra domain A positive fibronectin in various tumors, amplified the effects of CRISPR/Cas system on the inhibition of tumor progression.

BACKGROUND: The low efficiency of clustered, regularly interspaced, palindromic repeats-associated Cas (CRISPR/Cas) system editing genes in vivo limits the application. A components of the extracellular matrix (ECM), the extra domain A positive fibronectin (EDA+FN), may be a target for CRISPR/Cas system for the pro-oncogenic effects. The exclusion of EDA exon would alter the microenvironment and inhibit tumor progression, even the frequency of gene editing is still limited. RESULTS: The pro-oncogenic effects were confirmed by the exclusion of EDA exon from the fibronectin gene, as illustrated by the down-regulated proliferation, migration and invasion of CNE-2Z or SW480 cells (P<0.05). Furthermore, although the efficacy of EDA exon knockout through CRISPR/Cas system was shown to be low in vivo, the EDA+FN protein levels decrease obviously, inhibiting the tumor growth rate significantly (P<0.05), which was accompanied by a decrease in Ki-67 expression and microvessel numbers, and increased E-cadherin or decreased Vimentin expression (P<0.05). METHODS AND MATERIALS: Human nasopharyngeal carcinoma cell line CNE-2Z, and the colorectal carcinoma cell line SW480 were transfected with CRISPR/Cas9 plasmids targeting EDA exon. The effects of the exclusion of EDA on the cell proliferation, motility and epithelial-mesenchymal transition (EMT) were investigated, and the western blot and real-time PCR were performed to analyze the underlying mechanisms. Furthermore, CRISPR/Cas9 plasmids were injected into xenograft tumors to knockout EDA exon in vivo, and tumor growth, cell proliferation, EMT rate, or vascularization were investigated using western blot, PCR and immunohistochemistry. CONCLUSION: CRISPR/Cas system targeting ECM components was shown to be an effective method for the inhibition of tumor progression, as these paracrine or autocrine molecules are necessary for various tumor cells. This may represent a novel strategy for overcoming the drug evasion or resistance, in addition, circumventing the low efficiency of CRISPR/Cas system in vivo.

Involvement of non-B cell-derived immunoglobulin G in the metastasis and prognosis of salivary adenoid cystic carcinoma.

Cancer cell-derived immunoglobulin G (cancer-IgG) has been implicated in the pathogenesis and progression of various types of cancer. However, its role in salivary adenoid cystic carcinoma (SACC) remains unclear. The present study aimed to investigate the effects of cancer-IgG on metastasis and prognosis in 96 patients with SACC. Immunohistochemical staining showed that cancer-IgG expression was present in all 96 individual SACC tissues. Additionally, high cancer-IgG expression was significantly correlated with metastasis, nerve invasion and recurrence in SACC (P<0.05). Moreover, cancer-IgG expression was significantly correlated with the survival duration of patients with SACC (P<0.05). Proliferation, cell motility and invasion all decreased significantly following knockdown of cancer-IgG in SACC cells (P<0.05) through population-doubling time, wound healing and transwell invasion assays. Additionally, cancer-IgG-knockdown in SACC cells induced the increased expression of E-cadherin and matrix metalloproteinase 9, and promoted the epithelial-mesenchymal transition, but decreased the expression of F-actin filaments. Taken together, these results showed that the high expression of cancer-IgG was strongly associated with metastasis, recurrence and invasion in SACC, suggesting that cancer-IgG expression could serve as a useful biomarker to predict the prognosis of the disease.

Expression of cancer cell-derived IgG and extra domain A-containing fibronectin in salivary adenoid cystic carcinoma.

OBJECTIVE: Cancer-IgG is a newly-discovered molecule, mainly derived from epithelial carcinoma cells and is significantly correlated with differentiation, metastasis, local invasion, and poor prognosis of many cancers. In our previous study we detected IgG expression in oral epithelial carcinoma, including salivary adenoid cystic carcinoma (SACC), using an IgG-specific commercial antibody. Here, we explored the correlation between cancer-IgG and clinicopathological features of SACC. DESIGN: A total of 68 human SACC tissue specimens and 2 siRNAs were used to analyze the correlation between cancer-IgG and extra domain A (EDA+)-containing fibronectin using the cancer-IgG-specific monoclonal antibody, RP215. RESULTS: We found an unexpected correlation between cancer-IgG and EDA+ fibronectin, both of which showed aberrant expression in SACC tissue samples. Both were highly expressed in SACC with nerve invasion. In our previous study, EDA+ fibronectin overexpression in SACC cells decreased N-cadherin expression. In the present study, we used SACC-83 cells, wherein EDA+ fibronectin is overexpressed and cancer-IgG is knocked down. EDA+ fibronectin expression was reduced with cancer-IgG knockdown, while cancer-IgG expression did not affect EDA+ fibronectin overexpression. Furthermore, knockdown of non-B cell-derived IgG in SACC cells decreased cellular motility (P<0.05) as well as increased E-cadherin and alpha-smooth muscle actin levels. CONCLUSION: The results suggest that cancer IgG potentially regulates EDA+ fibronectin expression, thereby suggesting possible new therapeutic approaches for SACC.