Wheat Protein Hydrolysates Improving the Stability of Purple Sweet Potato Anthocyanins under Neutral pH after Commercial Sterilization at 121 °C.

Anthocyanins are prone to degradation and color fading after sterilization. This work examined the potential of wheat protein hydrolysates (WPHs, 40 g/L) in improving the stability of purple sweet potato anthocyanins (PSPAs) under a pH of 6.8 after sterilization at 121 °C followed by storage. Results showed that WPHs increased the thermal degradation half-life of PSPAs 1.65 times after sterilization. Compared to PSPAs alone, after being stored at 37 °C and 45 °C for 7 days, the retention concentration of PSPAs with WPHs was 5.4 and 32.2 times higher, and the color change of PSPAs with WPHs decreased from 6.19 and 10.46 to 0.29 and 0.77, respectively. AFM data, fluorescence and UV spectrograms indicated the formation of complexes between PSPAs and WPHs by hydrophobic attraction confirmed by zeta-potential data. PSPAs with WPHs had stable particle size and zeta potential, which may also significantly increase the concentrations after digestion and antioxidant power of PSPAs. This work indicated that the assembled PSPAs composite structure by WPHs significantly reduced the degradation of PSPAs at a pH of 6.8 after sterilization at 121 °C followed by long-term storage.

In Vitro Assessment of Ozone-Treated Deoxynivalenol by Measuring Cytotoxicity and Wheat Quality.

Deoxynivalenol (DON), a trichothecene mycotoxin, could lead to cytotoxicity in both animal bodies and plant seed cells. Ozone degradation technology has been applied to DON control. However, the safety and quality of the contaminated grain after DON degradation are largely obscured. In this work, we evaluated the cytotoxicity of ozone-treated DON through seed germination experiments and cytotoxicity tests. Cell experiments showed that the inhibition rate of HepG2 viability gradually increased within the concentrations of 1-10 mg/L of DON, alongside which an IC50 (half maximal inhibitory concentration) of 9.1 mg/L was determined. In contrast, degrading DON had no significant inhibitory effect on cell growth. Moreover, a 1-10 mg/L concentration of DON increased production of a large amount of reactive oxygen radicals in HepG2, with obvious fluorescence color development. However, fluorescence intensity decreased after DON degradation. Further, DON at a concentration of >1 mg/L significantly inhibited the germination of mung bean seeds, whereas no significant inhibition of their germination or growth were observed if DON degraded. Changes in total protein content, fatty acid value, and starch content were insignificant in wheat samples suffering ozone degradation, compared to the untreated group. Lastly, the ozone-treated wheat samples exhibited higher tenacity and whiteness. Together, our study indicated that the toxicity of DON-contaminated wheat was significantly reduced after ozone degradation.

Regulated intestinal microbiota and gut immunity to ameliorate type 1 diabetes mellitus: A novel mechanism for stem cell-based therapy.

Although stem cell transplantation is an effective strategy in the treatment of type 1 diabetes mellitus (T1DM), the mechanisms underlying its therapeutic effects remain unclear. We hypothesized that stem cells target gut microbiota and intestinal mucosal immunity to promote therapeutic effects against T1DM. We investigated the effects of human amniotic mesenchymal stem cells (hAMSCs) on intestinal microbiota and mucosal immunity in streptozotocin-induced T1DM mice. hAMSCs promoted significant reductions in blood glucose levels and increased the number of insulin-secreting cells in the T1DM model. Compared with T1DM model mice, 16S rRNA sequencing revealed significant differences in the composition, diversity, and abundance of microbiota in the ileum of hAMSC-treated mice. Bifidobacterium, Prevotella, and Alcaligenes species were among the 15 most abundant differential bacterial species. LC-MS revealed significant changes in ileal metabolites, and among the top 100 differential metabolites identified, we found that a significant increase in taurine was closely associated with hAMSC therapy. Additionally, we detected significant differences between the two groups with respect to the frequency and phenotype of CD4+ T cell subsets in mesenteric lymph nodes, and hAMSCs promoted significant increases in Th2 and Treg cell frequencies and reduced the frequencies of Th1 and Th17 cells. Moreover, correlation analysis revealed pairwise correlations between differential microflora and differential metabolites and immune signatures. hAMSCs thus have positive effects on the microbiota and their metabolites in the ileum and intestinal mucosal immunity in T1DM. Our findings indicate that gut microbiota and intestinal mucosal immunity may play vital roles in the hAMSC-based treatment of T1DM.

Hyaluronan delays human amniotic epithelial stem cell senescence by regulating CD44 isoform switch to activate AKT/mTOR signals.

The replicative senescence of human amniotic epithelial stem cells (hAECs) is a major concern towards its clinical application. This study found that a 300-kDa hyaluronic acid (HA) could effectively delay the replicative senescence of hAECs, as indicated by the downregulation of cellular senescence markers and alteration of the cell cycle, and substantially improve the differentiation capacities of hAECs. HA was confirmed to regulate the CD44 isoform switch by upregulating the CD44s and downregulating the CD44v, thus exerting an anti-aging effect. We further found that HA induced the upregulation of hyaluronan synthase (HAS) 2, resulting in the activation of epithelial splicing regulatory protein 1 (ESRP1) and alternative splicing of CD44 mRNA, thereby promoting CD44s expression and inhibiting CD44v expression. Knockdown of HAS2 blocked ESRP1 expression and attenuated the anti-aging effects of HA. Hermes-1, a specific blocker of CD44, caused partial loss of the anti-aging effect of HA, upregulated senescence markers, and downregulated stemness markers. Furthermore, CD44s receptor activation was shown to initiate the AKT/mTOR downstream signaling. Conclusively, the study suggested that HA delayed hAEC senescence by regulating CD44 isoform switch to activate the AKT/mTOR signaling pathway, and there is potential for the clinical application of hAECs in combination with HA.

Simulating ozone degradation of deoxynivalenol and its bio-safety assessment by mouse model.

Deoxynivalenol (DON), a trichothecene mycotoxin, is one of the most prevalent mycotoxins globally, primarily produced by Fusarium species. DON exposure could cause a range of symptoms, including nausea, vomiting, gastroenteritis, growth retardation, immunosuppression, and intestinal flora disorders in both humans and animals. Recently, ozone degradation technology has been applied for DON control. However, the safety of the contaminated grain after degradation was often ignored. Therefore, the implementation technology for assessing the safety of DON-contaminated grain degradation is of great significance for food safety. In this study, based on previous degradation result of DON, we further studied and assessed the toxicity of corn contaminated with ozone-degrading DON by animal experiments in mice. We simulated feed made from corn contaminated with DON produced by inoculated Fusarium graminearum, which was treated with an ozone aqueous solution. DON treated by ozone could effectively increase the expression of total protein in mice and improve the immune system efficacy. Meanwhile, compared with DON directly-exposed mice, the corn with degrading DON could effectively maintain the level of liver and kidney immune function, and improved growth performance, enterohepatic circulation, and energy metabolism. Our study indicated that the toxicity of fed corn contaminated with degrading-DON decreased significantly after ozone degradation, resulting in a much lower toxicity compared to the DON group, or nontoxicity to some extent. Therefore, we hope that this mouse model could be used as a promising approach for assessing the risk of fungal toxins on metabolism, immunity, and intestinal health.

Polyphenol-fortified extruded sweet potato starch vermicelli: Slow-releasing polyphenols is the main factor that reduces the starch digestibility.

To investigate the digestive behavior of extruded starch-polyphenols system, extruded sweet potato starch vermicelli (ESPSV) was used as a model. The multi-scale structure, starch digestibility, polyphenol release, digestive enzyme activity during digestion and their correlation of ESPSV supplemented with matcha (MT), green tea extract (GTE), tea polyphenols (TP) and epigallocatechin gallate (EGCG) (at 1% polyphenol level) were discussed. Results showed that tea products in whatever form could retard starch digestion, with EGCG working best. The predicted glycemic index (pGI) of ESPSV was decreased from 82.50 to 65.46 after adding EGCG. Starch formed larger molecular aggregates with tea products under extrusion, showing a "B + V" type pattern. The order of V-type crystals content was EGCG + ESPSV (1.41) > TP + ESPSV (1.50) > GTE + ESPSV (1.88) > MT + ESPSV (2.62) > ESPSV (3.20). Under external pressure, EGCG, as tea monomer, was more likely to enter the spiral cavity of amylose and form V-type inclusion complex. Notably, polyphenols released during digestion could still reduce digestive enzyme activity, with a 15.53% decrease in EGCG + ESPSV compared to ESPSV. This was verified by correlation analysis, where RDS content (0.961, p < 0.01) and pGI (0.966, p < 0.01) were highly significantly correlated with the enzyme activity. Furthermore, tea products did not break or even enhance the quality of ESPSV as the final product.

Role of exosome-derived miRNAs in diabetic wound angiogenesis.

Chronic wounds with high disability are among the most common and serious complications of diabetes. Angiogenesis dysfunction impair wound healing in patients with diabetes. Compared with traditional therapies that can only provide symptomatic treatment, stem cells-owing to their powerful paracrine properties, can alleviate the pathogenesis of chronic diabetic wounds and even cure them. Exosome-derived microRNAs (miRNAs), important components of stem cell paracrine signaling, have been reported for therapeutic use in various disease models, including diabetic wounds. Exosome-derived miRNAs have been widely reported to be involved in regulating vascular function and have promising applications in the repair and regeneration of skin wounds. Therefore, this article aims to review the current status of the pathophysiology of exosome-derived miRNAs in the diabetes-induced impairment of wound healing, along with current knowledge of the underlying mechanisms, emphasizing the regulatory mechanism of angiogenesis, we hope to document the emerging theoretical basis for improving wound repair by restoring angiogenesis in diabetes.

Increased production and anti-senescence activity of exopolysaccharides in Ganoderma lingzhi by co-overexpression of ß-1,3-glucan synthase and UDP-glucose pyrophosphorylase.

A ß-1,3-glucan synthase gene (gls) was cloned and overexpressed in Ganoderma lingzhi. The content of intracellular polysaccharides (IPS) in G. lingzhi overexpressing gls was 22.36 mg/100 mg dry weight (DW), 19 % higher than those in the wild-type (WT) strain. Overexpression of gls did not affect the expression of the phosphoglucomutase gene and the UDP-glucose pyrophosphorylase gene (ugp) in the polysaccharide biosynthesis. The gls and ugp were then simultaneously overexpressed in G. lingzhi for the first time. The combined overexpression of these two genes increased the IPS content and exopolysaccharides (EPS) production to a greater extent than the overexpression of gls independently. The maximum IPS content of the overexpressed strain was 24.61 mg/100 mg, and the maximum EPS production was 1.55 g/L, 1.31- and 1.50-fold higher than that in the WT strain, respectively. Moreover, the major EPS fractions from the overexpression strain contained more glucose (86.7 % and 72.5 %) than those from the WT strain (78.2 % and 62.9 %). Furthermore, the major fraction G+U-0.1 from the overexpression strain exhibited stronger antioxidant and anti-senescence activities than the WT-0.1 fraction from the WT strain. These findings will aid in the hyperproduction and application of Ganoderma polysaccharides and facilitate our understanding of mushroom polysaccharide biosynthesis.

Self-programmed dynamics of T cell receptor condensation.

A common event upon receptor-ligand engagement is the formation of receptor clusters on the cell surface, in which signaling molecules are specifically recruited or excluded to form signaling hubs to regulate cellular events. These clusters are often transient and can be disassembled to terminate signaling. Despite the general relevance of dynamic receptor clustering in cell signaling, the regulatory mechanism underlying the dynamics is still poorly understood. As a major antigen receptor in the immune system, T cell receptors (TCR) form spatiotemporally dynamic clusters to mediate robust yet temporal signaling to induce adaptive immune responses. Here we identify a phase separation mechanism controlling dynamic TCR clustering and signaling. The TCR signaling component CD3ε chain can condensate with Lck kinase through phase separation to form TCR signalosomes for active antigen signaling. Lck-mediated CD3ε phosphorylation, however, switched its binding preference to Csk, a functional suppressor of Lck, to cause the dissolvement of TCR signalosomes. Modulating TCR/Lck condensation by targeting CD3ε interactions with Lck or Csk directly affects T cell activation and function, highlighting the importance of the phase separation mechanism. The self-programmed condensation and dissolvement is thus a built-in mechanism of TCR signaling and might be relevant to other receptors.

Comparison of in vitro starch digestibility and structure of matcha-fortified starch vermicelli from different botanical sources.

BACKGROUND: In a study to explore the utilization of polyphenols in complex digestive systems, starch-based vermicelli was employed as the carrier and matcha (MT) was used as the source of polyphenols. Four percent MT was extruded with A-, B-, and C-type starch of rice, sweet potato, and mung bean to prepared starch vermicelli rice starch vermicelli (RSV), sweet potato starch vermicelli (SPSV), and mung bean starch vermicelli (MBSV), respectively. The multi-scale structure of starch, the digestive kinetics of starch, and the bioaccessibility of polyphenols during in vitro digestion were monitored. RESULTS: Matcha did not change the crystal configuration of vermicelli, but increased the relative crystallinity of RSV. Vermicelli with MT possessed a more uniform structure, and the polydispersity index decreased from 3.85-4.89 to 2.56-3.69. However, these structural changes made only a limited contribution to delaying digestion. The detection of polyphenols during digestion revealed that the release of most polyphenols was accomplished in the first 20 min of digestion. The release amount was in the order RSV + MT > MBSV + MT > SPSV + MT, and reached 4.81-5.45 mg GAE g-1 . Correspondingly, the activity of digestive enzyme decreased in the order RSV + MT < MBSV + MT < SPSV + MT. Consequently, MT significantly (P < 0.05) reduced the digestive rate of vermicelli, and the rapidly digested starch and predicted glycemic index of RSV + MT decreased from 71.28% to 56.31% and from 74.68 to 62.86, respectively. The released polyphenols were also the main source of the strong antioxidant capacity of vermicelli with MT. CONCLUSIONS: These results provided a theoretical basis for using polyphenols to pursue healthy starch-based food. © 2023 Society of Chemical Industry.

Ocular manifestations and quality of life in patients after hematopoietic stem cell transplantation.

AIM: To explore the relationship between ocular and systemic conditions and the impact of ocular complications on the quality of life (QOL) in patients after allogeneic hematopoietic stem cell transplantation (ALLO-HSCT). METHODS: Forty-four patients with severe hematopoietic disease were enrolled after ALLO-HSCT at our center from July 2018 to October 2020. They completed two questionnaires: the Ocular Surface Disease Index (OSDI) and the quality-of-life scale for Chinese patients with visual impairment (SQOL-DV1). Ocular conditions and systemic conditions were also assessed. RESULTS: Eye damage was correlated with total bilirubin (P=0.005), and gamma-glutamyl transferase (GGT) (P=0.021). There was no significant correlation between the overall QOL score and OSDI (P=0.8226) or SQOL-DV1 (P=0.9526) scores. The OSDI and the overall QOL score were not correlated with ocular conditions, including best-corrected visual acuity (BCVA), intraocular pressure, Schirmer tear test II, sodium fluorescein staining, tear film breakup time, and tear meniscus height. SQOL-DV1 was correlated with BCVA (P=0.0007), sodium fluorescein staining (P=0.007), and tear film breakup time (P=0.0146). CONCLUSION: In some patients, early ocular symptoms are not evident after ALLO-HSCT, while ocular surface complications can be observed after a comprehensive ophthalmological examination. Especially for those with elevated total bilirubin or GGT, regular ophthalmic follow-up visits are essential to diagnose and treat ocular graft versus host disease (oGVHD), especially for patients with elevated total bilirubin or GGT.

Inflammatory auxo-action in the stem cell division theory of cancer.

Acute inflammation is a beneficial response to the changes caused by pathogens or injuries that can eliminate the source of damage and restore homeostasis in damaged tissues. However, chronic inflammation causes malignant transformation and carcinogenic effects of cells through continuous exposure to pro-inflammatory cytokines and activation of inflammatory signaling pathways. According to the theory of stem cell division, the essential properties of stem cells, including long life span and self-renewal, make them vulnerable to accumulating genetic changes that can lead to cancer. Inflammation drives quiescent stem cells to enter the cell cycle and perform tissue repair functions. However, as cancer likely originates from DNA mutations that accumulate over time via normal stem cell division, inflammation may promote cancer development, even before the stem cells become cancerous. Numerous studies have reported that the mechanisms of inflammation in cancer formation and metastasis are diverse and complex; however, few studies have reviewed how inflammation affects cancer formation from the stem cell source. Based on the stem cell division theory of cancer, this review summarizes how inflammation affects normal stem cells, cancer stem cells, and cancer cells. We conclude that chronic inflammation leads to persistent stem cells activation, which can accumulate DNA damage and ultimately promote cancer. Additionally, inflammation not only facilitates the progression of stem cells into cancer cells, but also plays a positive role in cancer metastasis.

Aberrant gut microbiota and fecal metabolites in patients with coal-burning endemic fluorosis in Guizhou, China.

Chronic exposure to excessive environmental fluoride has caused fluorosis to become a major public health problem worldwide. Although studies on stress pathways, signaling pathways, and apoptosis induced by fluoride have provided an in-depth understanding of the mechanism of this disease, its exact pathogenesis remains unclear. We hypothesized that the human gut microbiota and metabolome are associated with the pathogenesis of this disease. To get further insight into the profiles of intestinal microbiota and metabolome in coal-burning-induced endemic fluorosis patients, we conducted 16S rRNA sequencing of the intestinal microbial DNA and carried out non-targeted metabolomics of fecal samples from 32 patients with skeletal fluorosis and 33 matched healthy controls in Guizhou, China. We found that the gut microbiota of coal-burning endemic fluorosis patients displayed significant differences in composition, diversity, and abundance compared with healthy controls. This was characterized by an increase in the relative abundance of Verrucomicrobiota, Desulfobacterota, Nitrospirota, Crenarchaeota, Chloroflexi, Myxococcota, Acidobacteriota, Proteobacteria, and unidentified_Bacteria, and a significant decrease in the relative abundance of Firmicutes and Bacteroidetes at the phylum level. Additionally, at the genus level, the relative abundance of some beneficial bacteria, such as Bacteroides, Megamonas, Bifidobacterium, and Faecalibacterium, was significantly reduced. We also demonstrated that, at the genus level, some gut microbial markers, including Anaeromyxobacter, MND1, oc32, Haliangium, and Adurb.Bin063_1, showed potential for identifying coal-burning endemic fluorosis. Moreover, non-targeted metabolomics and correlation analysis revealed the changes in the metabolome, particularly the gut microbiota-derived tryptophan metabolites such as tryptamine, 5-hydroxyindoleacetic acid, and indoleacetaldehyde. Our results indicated that excessive fluoride might cause xenobiotic-mediated dysbiosis of human gut microbiota and metabolic disorders. These findings suggest that the alterations in gut microbiota and metabolome play vital roles in regulating disease susceptibility and multi-organ damage after excessive fluoride exposure.

Microvascular and neural alterations in carotid cavernous fistulas: An optical coherence tomography angiography study.

BACKGROUND: Current modalities for diagnosing carotid cavernous fistula (CCF) are inaccurate in analysing retinal microcirculations and nerve fibre changes. Retinal microvascular and neural alterations occur in CCF patients and can be quantitatively measured using optical coherence tomography angiography (OCTA). We measured the neurovascular changes in the eyes of CCF patients and used OCTA as a supplementary method. METHODS: This cross-sectional study studied 54 eyes of 27 unilateral CCF subjects and 54 eyes of 27 healthy age- and sex-matched controls. OCTA parameters in the macula and optic nerve head (ONH) were analysed using a one-way analysis of variance with further Bonferroni corrections. Parameters with statistical significance were included in a multivariable binary logistic regression analysis and receiver operating characteristic (ROC) curves were generated. RESULTS: There was significantly less deep-vessel density (DVD) and ONH-associated capillary density in both eyes of CCF patients than in controls, while the differences between the affected and contralateral eyes were insignificant. The retinal nerve fibre layer and ganglion cell complex thickness were lower in the affected eyes than in the contralateral or controlled eyes. ROC curves identified DVD and ONH-associated capillary density as significant parameters in both eyes of CCF patients. CONCLUSION: The retinal microvascular circulation was affected in both eyes of unilateral CCF patients. Microvascular alterations occurred before retinal neural damage. This quantitative study suggests a supplementary measurement for diagnosing CCF and detecting early neurovascular impairments.

Increased peripapillary capillaries in patients with acute leukemia by using optical coherence tomography angiography.

PURPOSE: To evaluate the radial peripapillary capillary vessel density (RPC-VD) and thickness of the retinal nerve fiber layer (RNFL) in acute leukemia (AL) and the associations of these characteristics with blood laboratory parameters. METHODS: A cross-sectional study was performed at the Ophthalmology Department of the Sun Yat-sen Memorial Hospital from February 2019 to April 2022. Sixty eyes of 30 patients diagnosed with AL and sixty eyes of 30 matched healthy controls were included. Optical coherence tomography angiography (OCTA) in the 4.5-mm Angio Disc scan mode and the Ganglion cell complex scan mode were performed for all participants. Correlation analyses were used to examine the associations of RPC-VD and RNFL with blood laboratory parameters. RESULTS: Patients in the AL group had significantly increased RPC-VD in the whole-image (51.42±0.35 vs. 49.52±0.36) and peripapillary fields (53.90±0.43 vs. 51.17±0.50) compared with people in the control group (all P<0.001), while no difference was found for RPC-VD in the inside optic disk fields in the two groups. The RNFL in the AL group was significantly thicker than that in the control group (131.10±3.89 µm vs. 115.03±2.22 µm, P<0.05). Complete blood count (CBC) parameters, including red blood cells, hemoglobin and hematocrit, had a significant negative correlation with RPC-VD and RNFL (all P <0.05). CONCLUSION: An increased RPC-VD and a thicker RNFL are evidence of fundus changes in patients with early-stage AL, and these metrics may be related to decreases in red blood cells, hemoglobin and hematocrit.

The alleviative effect of curdlan on the quality deterioration of konjac glucomannan thermo-irreversible gels after commercial sterilization at 121 °C.

This work employed different curdlan concentrations (0.00 %, 1.00 %, 1.50 %, 2.00 %, and 2.50 %) to alleviate the quality degradation of konjac glucomannan (KGM) gels after commercial sterilization at 121 °C for 15 min. The results showed that all levels of curdlan could retard the deterioration of KGM gels, with the best effect at 2.00 %. After commercial sterilization, incorporating curdlan into KGM gels greatly reduced the Tan σ (G"/ G'), total relaxation time and half-free water from 0.52, 89.85 ms and 98.26 % to 0.27, 38.48 ms and 21.42 %, respectively. Moreover, the addition of curdlan imparted a better texture to KGM gels, as reflected in the increase of hardness, springiness, water-holding capacity and whiteness value from 1400.85 g, 0.42, 87.92 % and 33.33 to 3461.68 g, 0.80, 96.50 % and 49.27, respectively. Furthermore, SEM images revealed that curdlan endowed KGM gels with a tighter structure and smaller pores, and the pore size distribution was reduced from 113.46 µm to17.91 µm, indicating a stronger interaction among molecules, as evidenced by XRD and FTIR results. KGM gels with curdlan possessed less proportion of complete crystallites and crystalline region. These findings suggested that curdlan can be the potently protectant for improving the quality of commercially sterilized KGM gel-based products.

A nomogram model for predicting ocular GVHD following allo-HSCT based on risk factors.

OBJECTIVE: To develop and validate a nomogram model for predicting chronic ocular graft-versus-host disease (coGVHD) in patients after allogenic haematopoietic stem cell transplantation (allo-HSCT). METHODS: This study included 61 patients who survived at least 100 days after allo-HSCT. Risk factors for coGVHD were screened using LASSO regression, then the variables selected were subjected to logistic regression. Nomogram was established to further confirm the risk factors for coGVHD. Receiver operating characteristic (ROC) curves were constructed to assess the performance of the predictive model with the training and test sets. Odds ratios and 95% confidence intervals (95% CIs) were calculated by using logistic regression analysis. RESULTS: Among the 61 patients, 38 were diagnosed with coGVHD. We selected five texture features: lymphocytes (LYM) (OR = 2.26), plasma thromboplastin antecedent (PTA) (OR = 1.19), CD3 + CD25 + cells (OR = 1.38), CD3 + HLA-DR + cells (OR = 0.95), and the ocular surface disease index (OSDI) (OR = 1.44). The areas under the ROC curve (AUCs) of the nomogram with the training and test sets were 0.979 (95% CI, 0.895-1.000) and 0.969 (95% CI, 0.846-1.000), respectively.And the Hosmer-Lemeshow test was nonsignificant with the training (p = 0.9949) and test sets (p = 0.9691). CONCLUSION: We constructed a nomogram that can assess the risk of coGVHD in patients after allo-HSCT and help minimize the irreversible loss of vision caused by the disease in high-risk populations.

Collagen hydrolysates improve the efficiency of sodium alginate-encapsulated tea polyphenols in beads and the storage stability after commercial sterilization.

This study showed that sodium alginates (SA)-based beads reinforced with collagen hydrolysates (CHs) significantly increased an encapsulation rate of tea polyphenols (TP) from 34.54 % to 85.06 % when the mass ratio of SA: CHs increased from1.5:0 to 1.5:0.5. And after the 30-day storage at 37 °C, the retention rate of TP in beads with CHs at the solutions with pH = 4.0 or pH = 7.0 increased from 61.10 % to 80.21 %, or from 67.72 % to 80.47 % after sterilization at 98 °C or 121 °C for 30 min, respectively. Also, the addition of CHs at 0.5 % resulted in a greater retention of the polyphenolic compositions values of TP determined by UPLC-Orbitrap-MS system. Additionally, the DPPH and ABTS+ free-radical scavenging capacities and ferric-reducing antioxidant power of beads with CHs after sterilization at 98 °C or 121 °C for 30 min were significantly higher than which without CHs. Physical phenomena based on ζ-potential, particle size, fluorescence, UV spectroscopy and confocal laser scanning microscope showed that tightly non-covalent complexes of CHs in combination to TP could be uniformly and stably distributed in the network of SA solution for encapsulating TP in SA-based beads. These findings provided suggestions for the co-encapsulation design and development of hydrophilic nutritive compounds based on CHs in SA-based beads.

CD44 mediates hyaluronan to promote the differentiation of human amniotic mesenchymal stem cells into chondrocytes.

OBJECTIVES: CD44 is the major receptor for hyaluronan (HA), but its effect on HA-induced differentiation of human amnion mesenchymal stem cells into chondrocytes is unclear. This study aimed to investigate the effects and mechanisms of CD44 in HA-induced chondrogenesis. METHODS: Immunocytochemistry and toluidine blue staining were used to assess the secretion of type II collagen and aggrecan, respectively. qRT-PCR and western blotting were performed to evaluate the expression of key genes and proteins. RESULTS: The expression of aggrecan and type II collagen was downregulated after using the anti-CD44 antibody (A3D8). The transcriptional levels of chondrocytes­associated genes SRY­box transcription factor 9, aggrecan, and collagen type II alpha 1 chain were also decreased. Thus, CD44 may mediate HA-induced differentiation of hAMSCs into chondrocytes. Further investigation indicated that expression of phosphorylated (p)­Erk1/2 and p­Smad2 decreased following CD44 inhibition. The changes in the expression of p-Erk1/2 and p-Smad2 were consistent after using the ERK1/2 inhibitor (U0126) and agonist (EGF), respectively. After administering the p-Smad2 inhibitor, the expression levels of p-ERK1/2 and p-Smad2 appeared downregulated. The results showed crosstalk between Erk1/2 and Smad2. Moreover, inhibition of p-Erk1/2 and p-Smad2 significantly reduced the accumulation of aggrecan and type II collagen. CONCLUSION: These data indicate that CD44 mediates HA-induced differentiation of hAMSCs into chondrocytes by regulating Erk1/2 and Smad2 signaling.

Combination therapy with human amniotic epithelial cells and hyaluronic acid promotes immune balance recovery in type 1 diabetic rats through local engraftment.

Stem cell engraftment is currently a promising approach for type 1 diabetes mellitus (T1DM) treatment. In our previous study, engraftment of a combination of human amniotic epithelial cells (hAECs) and hyaluronic acid (HA) showed potent anti-diabetic effect in streptozotocin (STZ)-induced T1DM mice via tail vein injection. Here, we adopted a different route of stem cell delivery, that is via pancreatic subcapsular transplantation. This combined local engraftment of hAECs and HA in STZ-induced T1DM rats showed potent anti-diabetic activity, leading to stronger hypoglycaemia, more intact islet structure and increased number of insulin-positive cells compared with those with hAECs or insulin treatments. Engraftment of hAECs alone increased the proportion of Th1 and T-reg cells and decreased the proportion of Th2 and Th17 cells to protect islet ß cells in STZ-induced T1DM rats, whereas the combined engraftment of hAECs and HA showed more potent regulatory capacity, considerably decreased the level of TNF-α and IL-17 and increased the level of TGF-ß1 compared with those by other treatments. The potent synergistic effect of HA contributed to the recovery of immune balance in the diabetic rat model, thereby suggesting a new strategy for effective treatment of T1DM.