A hydrogel microcapsule with an intermediate thin oil layer is presented to achieve smart release of a broad range of cargoes triggered via diverse stimuli. A microfluidic technique is used to ...produce triple emulsion droplets with a thin oil layer that separates the innermost aqueous phase from the hydrogel prepolymer phase, which transforms into a hydrogel shell via photopolymerization. The intermediate oil layer within the hydrogel microcapsule acts as an effective diffusion barrier, allowing encapsulation of various small cargoes within a porous hydrogel shell until a stimulus is applied to destabilize the oil layer. It is demonstrated that diverse stimuli including chemical dissolution, mechanical stress, and osmotic pressure can be utilized to release the encapsulated cargo on‐demand. In addition, osmotic pressure and the hydrogel shell thickness can be independently tuned to control the onset time of release as well as the release behavior of multi‐cargo encapsulated hydrogel microcapsule. The release can be either simultaneous or selective.
A hydrogel microcapsule with an intermediate thin oil layer enables smart release of a broad range of cargoes via diverse stimuli. The oil layer in the microcapsules acts as an effective diffusion barrier until only when the oil layer is destabilized. The osmotic pressure and the overall stiffness of the microcapsule can be fine‐tuned to control the release behavior of the multi‐cargo encapsulated microcapsule.
Obesity‐induced hypothalamic inflammation is closely associated with various metabolic complications and neurodegenerative disorders. Astrocytes, the most abundant glial cells in the central nervous ...system, play a crucial role in pathological hypothalamic inflammatory processes. Here, we demonstrate that hypothalamic astrocytes accumulate lipid droplets under saturated fatty acid‐rich conditions, such as obese environment, and that the lipid‐laden astrocytes increase astrogliosis markers and inflammatory cytokines (TNFα, IL‐1β, IL‐6, MCP‐1) at the transcript and/or protein level. Medium conditioned by the lipid‐laden astrocytes stimulate microglial chemotactic activity and upregulate transcripts of the microglia activation marker Iba‐1 and inflammatory cytokines. These findings indicate that the lipid‐laden astrocytes formed in free fatty acid‐rich obese condition may participate in obesity‐induced hypothalamic inflammation through promoting microglia migration and activation.
Tumor-infiltrating lymphocytes (TILs) have been known for their strong prognostic and predictive significance in triple-negative breast cancer (TNBC). Several mechanisms for TIL influx in TNBC have ...been elucidated. Major histocompatibility complex class II (MHC-II) is an essential component of the adaptive immune system and is generally restricted to the surface of antigen-presenting cells. However, it has been reported that interferon-gamma signaling may induce MHC-II in almost all cell types, including those derived from cancer. We aimed to examine the relationship between MHC-II expression in tumor cells and the amount of TILs in 681 patients with TNBC. Further, the prognostic significance of MHC-II and the association of MHC-II with a couple of molecules involved in the interferon signaling pathway were investigated using immunohistochemical staining. Higher MHC-II expression in tumor cells was associated with the absence of lymphovascular invasion (p = 0.042); larger amounts of TILs (p < 0.001); frequent formations of tertiary lymphoid structures (p < 0.001); higher expression of myxovirus resistance gene A, one of the main mediators of the interferon signaling pathway (p < 0.001); and higher expression of double-stranded RNA-activated protein kinase, which can be induced by interferons (p = 0.008). Moreover, tumors that showed high MHC class I expression and any positivity for MHC-II had larger amounts of CD4- and CD8-positive T lymphocytes (p < 0.001). Positive MHC-II expression in tumor cells was associated with better disease-free survival in patients who had lymph node metastasis (p = 0.009). In conclusion, MHC-II expression in tumor cells was closely associated with an increase in TIL number and interferon signaling in TNBC. Further studies are warranted to improve our understanding regarding TIL influx, as well as patients' responses to immunotherapy.
Background
This study aimed to determine the correlation between occlusal contact area and masticatory performance using BiteEye®, a photo occlusal analysis device and the multiple sieve method.
...Objectives
To calculate the occlusal contact area at various levels of interocclusal thicknesses and to measure masticatory performance with peanuts as the test material.
Methods
Fifty‐two adults (30 men and 22 women) were enrolled according to specific exclusion/inclusion criteria. The occlusal contact area was measured by obtaining the interocclusal record of the maximum intercuspal position (MIP) using silicone impression material. Occlusal contact area measurements were performed in the ranges of 0–149, 0–89, 0–59, 0–29 and 0–9 μm. Masticatory performance was measured by obtaining the median particle size (X 50) after converting the weight of comminuted peanuts into size using the multiple sieve method. Statistical analysis was performed at 95% significance level.
Results
Interocclusal thickness comparison revealed the highest correlation with X 50 in the 0–149 μm range. Stronger correlations between the occlusal contact area and X 50 were observed in cases of 20 strokes of mastication (r = −.451) than in cases of 10 strokes (r = −.383), in the posterior occlusal contact area (r = −.456) than in the full arch occlusal contact area (r = −.451) and the molar area (r = −.478) than in the premolar area (r = −.296).
Conclusions
The larger the occlusal contact area, the higher the masticatory performance; this correlation was statistically significant. Regarding interocclusal thickness, the highest correlation between the occlusal contact area and masticatory performance was observed in the 0–149 μm range.
Clinical Trial Registration Number: GWNUDH IRB 2020‐A001.
The highest correlation between masticatory performance and occlusal contact area was exhibited in an interocclusal thickness range of 0‐149 μm.
Most previous studies have been focused on the variation of tea chemical composition by fermentative processes as well as different cultivars and regions. The detailed changes of flavonoid profiles ...were described for the first time by each processing step of green and black tea leaves in this study. A total of 24 flavonoid derivatives including catechins, theaflavins, and flavonols were separated and identified from the tea samples based on UPLC-DAD-QToF/MS data and constructed library. Among these, the fragmentation pathway of theaflavins was proposed specifically in positive ionization mode for structural interpretation. During leaf processing, the individual flavonols were changed as diverse patterns according to their aglycone types and glycosylated forms, but their total content showed a slight difference. EGCG and ECG were increased after roasting approximately twofold higher than that of fresh leaves (EGCG, 2709.5 →6085.6; ECG, 1548.0 →2318.2 mg/100 g dry weight, respectively) in green tea while considerably decreased their contents due to oxidation and conversion to theaflavins after fermentation during black tea processing. Especially, the drying steps also found to be factor to influence positively to increase the flavonoid contents in both tea processing. Therefore, this result indicated that detailed conditions of each processing step played important roles in changing the flavonoid profiles from tea leaves.
Graphical abstract
Clinical translation of nanoparticles is limited because of their short circulation time, which hampers targeting to prolong therapeutic effects. Angiogenesis is required to regenerate damaged sites ...under inflammation, and CD11b+ cells turn vasculogenic under hypoxia. As a turning‐point strategy to increase the circulation time, this study explores liposomal targeting of splenic CD11b+ cells, which are gathered in the spleen and move to inflamed sites inherently. Moreover, nano‐hypoxia is strategized as a therapeutic method by loading liposomes with a hypoxic‐mimetic agent (CoCl2) to induce in situ reprogramming of splenic CD11b+ cells upon venous injection. Consequently, the vasculogenic potential of reprogrammed cells accelerates regeneration through inflammation‐responsive homing. Hydrophilic coating of liposomes improves the selectivity of splenic targeting in contrast to fast targeting without coating. Hypoxia chambers and surgical induction of splenic hypoxia are compared to validate the reprogramming effect. The strategy is validated in mouse models of inflamed skin, ischemic hindlimbs, and 70% hepatectomy compared with a conventional approach using bone marrow cells. Intravital multiphoton microscopy, 19F 2D/3D MRI, and microchannel hydrogel chips for 3D tissue culture are used as advanced tools. Overall, nanocarrier change to CD11b+ cells prolong targeting by inducing in situ reprogramming for inflammation‐responsive vasculogenic therapy.
Because the spleen serves as a reservoir of CD11b+ cells, a liposomal delivery through blood circulation undergoes splenic filtering for carrier changing from the liposomes to CD11b+ cells. Loading a hypoxic‐mimetic agent to these liposomes induced vasculogenic reprograming of CD11b+ cells with inherent homing into inflamed sites, rescues tissue damages upon hindlimb ischemia and hepatectomy in rodent models.
Trichothecenes are a family of terpenoid toxins produced by multiple genera of fungi, including plant and insect pathogens. Some trichothecenes produced by the fungus Fusarium are among the ...mycotoxins of greatest concern to food and feed safety because of their toxicity and frequent occurrence in cereal crops, and trichothecene production contributes to pathogenesis of some Fusarium species on plants. Collectively, fungi produce over 150 trichothecene analogs: i.e., molecules that share the same core structure but differ in patterns of substituents attached to the core structure. Here, we carried out genomic, phylogenetic, gene-function, and analytical chemistry studies of strains from nine fungal genera to identify genetic variation responsible for trichothecene structural diversity and to gain insight into evolutionary processes that have contributed to the variation. The results indicate that structural diversity has resulted from gain, loss, and functional changes of trichothecene biosynthetic (TRI) genes. The results also indicate that the presence of some substituents has arisen independently in different fungi by gain of different genes with the same function. Variation in TRI gene duplication and number of TRI loci was also observed among the fungi examined, but there was no evidence that such genetic differences have contributed to trichothecene structural variation. We also inferred ancestral states of the TRI cluster and trichothecene biosynthetic pathway, and proposed scenarios for changes in trichothecene structures during divergence of TRI cluster homologs. Together, our findings provide insight into evolutionary processes responsible for structural diversification of toxins produced by pathogenic fungi.
Cell–cell interactions regulate intracellular signaling via reciprocal contacts of cell membranes in tissue regeneration and cancer growth, indicating a critical need of membrane‐derived tools in ...studying these processes. Hence, cell‐membrane‐derived nanoparticles (CMNPs) are produced using tonsil‐derived mesenchymal stem cells (TMSCs) from children owing to their short doubling time. As target cell types, laryngeal cancer cells are compared to bone‐marrow‐derived MSCs (BMSCs) because of their cartilage damaging and chondrogenic characteristics, respectively. Treating spheroids of these cell types with CMNPs exacerbates interspheroid hypoxia with robust maintenance of the cell–cell interaction signature for 7 days. Both cell types prefer a hypoxic environment, as opposed to blood vessel formation that is absent in cartilage but is required for cancer growth. Hence, angiogenesis is inhibited by displaying the Notch‐1 aptamer on CMNPs. Consequently, laryngeal cancer growth is suppressed efficiently in contrast to improved chondroprotection observed in a series of cell and animal experiments using a xenograft mouse model of laryngeal cancer. Altogether, CMNPs execute a two‐edged sword function of inducing hypoxic cell–cell packing, followed by suppressing angiogenesis to promote laryngeal cancer death and chondrogenesis simultaneously. This study presents a previously unexplored therapeutic strategy for anti‐cancer and chondroprotective treatment using CMNPs.
Cell‐derived nanoparticles (CMNPs) promote physical tightening of cell–cell interactions and cell packing, thereby inducing hypoxia as a favorable setting for cancer progression and cartilage development. The conjugation of aptamers to CMNPs suppresses Notch‐1 signaling‐mediated angiogenesis with consequent activation of anti‐cancer and chondroprotective effects (“two‐edged sword”) in a xenograft model of human laryngeal cancer.
The link between chronic lymphocytic thyroiditis (CLT) and papillary thyroid carcinoma (PTC) is widely recognized. Considering the strong association between raised antithyroidperoxidase antibody ...(TPOAb) and CLT, we postulated that the preoperative TPOAb can predict the prognosis of PTC, particularly for recurrence. A total of 2,070 patients who underwent total thyroidectomy for classical type PTC with tumor size ≥1 cm and with available data on preoperative TPOAb and TgAb were enrolled to compare disease‐free survival (DFS) according to the presence of preoperative TPOAb, TgAb, and coexistent CLT. Patients with positive preoperative TPOAb had a significantly better DFS compared to patients without positive preoperative TPOAb (hazard ratio (HR) 0.53; 95% confidence interval (CI) 0.30–0.94, p = 0.028) while no difference in DFS was found according to preoperative TgAb status. Positive preoperative TPOAb was an independent prognostic factor for structural persistent/recurrent disease after adjustment for major preoperative risk factors such as age, sex, and tumor size (HR 0.52, 95% CI 0.28–0.99, p = 0.048). Although the coexistence of CLT lowered the risk for structural persistence/recurrence in univariate analysis (HR 0.52, 95% CI 0.31–0.86, p = 0.012), it was not an independent favorable prognostic factor by multivariate analysis (HR 0.65, 95% CI 0.38–1.10, p = 0.106). However, when coexistent CLT was combined with positive preoperative TPOAb, it indicated an independent protective role in structural persistent/recurrent disease (HR 0.39, 95% CI 0.16–0.98, p = 0.045). Our study clearly showed that presence of preoperative TPOAb can be a novel prognostic factor in predicting structural persistence/recurrence of PTC.
What's new?
While chronic lymphocytic thyroiditis (CLT) is generally accepted as a risk factor for papillary thyroid carcinoma (PTC), it is also suspected to protect against PTC recurrence when it coexists with PTC. Our study indicates that coexistent CLT predicts PTC recurrence risk, wherein copositivity for both CLT and preoperative antithyroid peroxidase antibody (TPOAb) is associated with reduced risk of recurrent PTC. In addition, among PTC patients who underwent thyroidectomy, those with preoperative TPOAb positivity had significantly better disease‐free survival than those lacking TPOAb positivity. The findings suggest that preoperative TPOAb and CLT evaluation could help improve accuracy in PTC prognosis.
Mesenchymal stem cells (MSCs) are an attractive candidate for the treatment of inflammatory bowel disease (IBD), but their poor delivery rate to an inflamed colon is a major factor hampering the ...clinical potential of stem cell therapies. Moreover, there remains a formidable hurdle to overcome with regard to survival and homing in to injured sites. Here, we develop a strategy utilizing monodisperse hydrogel microcapsules with a thin intermediate oil layer prepared by a triple-emulsion drop-based microfluidic approach as an in-situ oral delivering carrier. The oral delivery of stem-cell-loaded hydrogel microcapsules (SC-HM) enhances MSC survival and retention in the hostile stomach environment due to the intermediate oil layer and low value of the overall stiffness, facilitating programmable cell release during gastrointestinal peristalsis. SC-HM is shown to induce tissue repair, reduce the colonic macrophage infiltration responsible for the secretion of the pro-inflammatory factors, and significantly mitigate the severity of IBD in a mouse model, where MSCs released by SC-HM successfully accumulate at the colonic crypt. Moreover, a metagenomics analysis reveals that SC-HM ameliorates the dysbiosis of specific bacterial genera, including Bacteroides acidifaciens, Lactobacillus (L.) gasseri, Lactobacillus reuteri, and L. intestinalis, implying optimization of the microorganism's composition and abundance. These findings demonstrate that SC-HM is a potential IBD treatment candidate.
Stem-cell-loaded hydrogel microcapsules (SC-HM) with a thin oil layer has the potential to rupture and release the encapsulated stem cells by the segmenting during the moment and peristalsis in the gut. Stem cells released from SC-HM induce the tissue repair, reduce the colonic macrophage infiltration responsible for the secretion of the pro-inflammatory factors, and significantly mitigate the severity of IBD in a mouse model. Moreover, SC-HM can restore gut microbiome dysbiosis and reestablish the composition of the gut microbiota in acute colitis. Display omitted
•We develop the SC-HM prepared by a triple-emulsion drop-based microfluidic approach.•The delivery of SC-HM augments the local retention of the cell at colonic sites.•Stem cells released from the SC-HM ameliorate gut inflammation in a mouse IBD model.•SC-HM restores gut microbiome dysbiosis in active colitis.
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