Macrophage-Derived Cathepsin S Remodels the Extracellular Matrix to Promote Liver Fibrogenesis.

BACKGROUND & AIMS: Liver fibrosis is an intrinsic wound-healing response to chronic injury and the major cause of liver-related morbidity and mortality worldwide. However, no effective diagnostic or therapeutic strategies are available, owing to its poorly characterized molecular etiology. We aimed to elucidate the mechanisms underlying liver fibrogenesis. METHODS: We performed a quantitative proteomic analysis of clinical fibrotic liver samples to identify dysregulated proteins. Further analyses were performed on the sera of 164 patients with liver fibrosis. Two fibrosis mouse models and several biochemical experiments were used to elucidate liver fibrogenesis. RESULTS: We identified cathepsin S (CTSS) up-regulation as a central node for extracellular matrix remodeling in the human fibrotic liver by proteomic screening. Increased serum CTSS levels efficiently predicted liver fibrosis, even at an early stage. Secreted CTSS cleaved collagen 18A1 at its C-terminus, releasing endostatin peptide, which directly bound to and activated hepatic stellate cells via integrin α5ß1 signaling, whereas genetic ablation of Ctss remarkably suppressed liver fibrogenesis via endostatin reduction in vivo. Further studies identified macrophages as the main source of hepatic CTSS, and splenectomy effectively attenuated macrophage infiltration and CTSS expression in the fibrotic liver. Pharmacologic inhibition of CTSS ameliorated liver fibrosis progression in the mouse models. CONCLUSIONS: CTSS functions as a novel profibrotic factor by remodeling extracellular matrix proteins and may represent a promising target for the diagnosis and treatment of liver fibrosis.

TFCP2, a binding protein of ATF3, promotes the progression of glioma by activating the synthesis of serine.

Glioma is one of the most common malignancies. De novo serine synthesis promotes glioma progression and therapeutic resistance. Therefore, clarifying the regulatory mechanism of serine synthesis is of great significance for glioma therapy. In this study, we found that the expression of TFCP2 was upregulated in glioma and that TFCP2 promoted glioma cell growth and sphere formation. Knockdown of TFCP2 expression inhibited glioma cell growth, sphere formation and tumorigenicity in nude mice. In terms of its molecular mechanism, TFCP2 was found to interact with ATF3 to cooperatively regulate the de novo synthesis of serine. Knockdown of TFCP2 expression significantly inhibited the binding of ATF3 to the promoter of PHGDH (a rate-limiting enzyme in the serine synthesis process). In conclusion, our studies proved that TFCP2 jointly regulates the de novo synthesis of serine through interaction with ATF3, thus promoting glioma progression. This study suggests that TFCP2 is a potential target for glioma therapy.

A predictive model for postoperative progressive haemorrhagic injury in traumatic brain injuries.

BACKGROUND: Progressive haemorrhagic injury after surgery in patients with traumatic brain injury often results in poor patient outcomes. This study aimed to develop and validate a practical predictive tool that can reliably estimate the risk of postoperative progressive haemorrhagic injury (PHI) in patients with traumatic brain injury (TBI). METHODS: Data from 645 patients who underwent surgery for TBI between March 2018 and December 2020 were collected. The outcome was postoperative intracranial PHI, which was assessed on postoperative computed tomography. The least absolute shrinkage and selection operator (LASSO) regression model, univariate analysis, and Delphi method were applied to select the most relevant prognostic predictors. We combined conventional coagulation test (CCT) data, thromboelastography (TEG) variables, and several predictors to develop a predictive model using binary logistic regression and then presented the results as a nomogram. The predictive performance of the model was assessed with calibration and discrimination. Internal validation was assessed. RESULTS: The signature, which consisted of 11 selected features, was significantly associated with intracranial PHI (p < 0.05, for both primary and validation cohorts). Predictors in the prediction nomogram included age, S-pressure, D-pressure, pulse, temperature, reaction time, PLT, prothrombin time, activated partial thromboplastin time, FIB, and kinetics values. The model showed good discrimination, with an area under the curve of 0.8694 (95% CI, 0.8083-0.9304), and good calibration. CONCLUSION: This model is based on a nomogram incorporating CCT and TEG variables, which can be conveniently derived at hospital admission. It allows determination of this individual risk for postoperative intracranial PHI and will facilitate a timely intervention to improve outcomes.

Clinical significance of mismatch negativity in predicting the awakening of comatose patients after severe brain injury.

We assessed the clinical significance of mismatch negativity (MMN) in predicting the awakening of comatose patients with severe brain injury. The clinical data of patients with severe brain injury, admitted to the neurosurgical intensive care unit of Xiangya Hospital of Central South University from July 2018 to March 2020, who underwent auditory MMN examinations within 28 days after coma onset, were reviewed. Correlations between clinical factors and prognosis [Glasgow Outcome Scale (GCS) for 3 mo] were analyzed. Fifty-three patients were included; 37 (69.8%) had favorable outcomes. A univariate analysis revealed the Glasgow Coma Scale (GCS) and absolute MMN amplitudes at electrodes Fz and Cz were significantly correlated with prognosis. Only GCS scores and MMN amplitude at Fz were independent predictors in multivariate logistic regression analysis (area under the curve 0.744 vs. 0.753, respectively); both combined, improved accuracy to 84.6%. MMN amplitudes at Fz were dichotomized at a value of 1.08 µV with a sensitivity and specificity of 81.1% and 68.7%, respectively, for predicting comatose patients' awakening. In conclusion, MMN amplitude at Fz is a reliable prognostic indicator for comatose patients with severe brain injury; the prediction value improved when combined with GCS. Thus, an event-related potential component with a clear site and cutoff value may support prognostication in severe brain injury.NEW & NOTEWORTHY Mismatch negativity (MMN) can assess the prognosis of comatose patients after severe brain injury, especially for MMN amplitude. In addition, MMN analysis at electrode Fz best predicts recovery of consciousness in patients with severe brain injury. Importantly, a quantitative approach (cutoff value of 1.08 µV) may improve the use of MMN for prognostication.

Effects of RNA methylation N6-methyladenosine regulators on malignant progression and prognosis of melanoma.

BACKGROUND: Melanoma is an extremely aggressive type of skin cancer and experiencing a expeditiously rising mortality in a current year. Exploring new potential prognostic biomarkers and therapeutic targets of melanoma are urgently needed. The ambition of this research was to identify genetic markers and assess prognostic performance of N6-methyladenosine (m6A) regulators in melanoma. METHODS: Gene expression data and corresponding clinical informations of melanoma patients as well as sequence data of normal controls are collected from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Quantitative real-time PCR (qRT-PCR) analysis was carried out to detect the RNA expression of IGF2BP3 in A375 cell line, melanoma tissues, and normal tissues. Western blot, cell proliferation, and migration assays were performed to assess the ability of IGF2BP3 in A375 cell line. RESULTS: Differently expressed m6A regulators between tumor samples and normal samples were analyzed. A three-gene prognostic signature including IGF2BP3, RBM15B, and METTL16 was constructed, and the risk score of this signature was identified to be an independent prognostic indicator for melanoma. In addition, IGF2BP3 was verified to promote melanoma cell proliferation and migration in vitro and associate with lymph node metastasis in clinical samples. Moreover, risk score and the expression of IGF2BP3 were positively associated with the infiltrating immune cells and these hub genes made excellent potential drug targets in melanoma. CONCLUSION: We identified the genetic changes in m6A regulatory genes and constructed a three-gene risk signature with distinct prognostic value in melanoma. This research provided new insights into the epigenetic understanding of m6A regulators and novel therapeutic strategies in melanoma.

EDAG mediates Hsp70 nuclear localization in erythroblasts and rescues dyserythropoiesis in myelodysplastic syndrome.

During human erythroid maturation, Hsp70 translocates into the nucleus and protects GATA-1 from caspase-3 cleavage. Failure of Hsp70 to localize to the nucleus was found in Myelodysplastic syndrome (MDS) erythroblasts and can induce dyserythropoiesis, with arrest of maturation and death of erythroblasts. However, the mechanism of the nuclear trafficking of Hsp70 in erythroblasts remains unknown. Here, we found the hematopoietic transcriptional regulator, EDAG, to be a novel binding partner of Hsp70 that forms a protein complex with Hsp70 and GATA-1 during human normal erythroid differentiation. EDAG overexpression blocked the cytoplasmic translocation of Hsp70 induced by EPO deprivation, inhibited GATA-1 degradation, thereby promoting erythroid maturation in an Hsp70-dependent manner. Furthermore, in myelodysplastic syndrome (MDS) patients with dyserythropoiesis, EDAG is dramatically down-regulated, and forced expression of EDAG has been found to restore the localization of Hsp70 in the nucleus and elevate the protein level of GATA-1 to a significant extent. In addition, EDAG rescued the dyserythropoiesis of MDS patients by increasing erythroid differentiation and decreasing cell apoptosis. This study demonstrates the molecular mechanism of Hsp70 nuclear sustaining during erythroid maturation and establishes that EDAG might be a suitable therapeutic target for dyserythropoiesis in MDS patients.

Trans-base and trans-vault low-velocity penetrating brain injury: A retrospective comparative study of characteristics, treatment, and outcomes.

PURPOSE: Low-velocity penetrating brain injury (LVPBI) caused by foreign bodies can pose life-threatening emergencies. Their complexity and lack of validated classification data have prevented standardization of clinical management. We aimed to compare the trans-base and trans-vault phenotypes of LVPBI to help provide guidance for clinical decision-making of such injury type. METHODS: A retrospective study on LVPBI patients managed at our institution from November 2013 to March 2020 was conducted. We included LVPBI patients admitted for the first time for surgery, and excluded those with multiple injuries, gunshot wounds, pregnancy, severe blunt head trauma, etc. Patients were categorized into trans-base and trans-vault LVPBI groups based on the penetration pathway. Discharged patients were followed up by outpatient visit or telephone. The data were entered into the Electronic Medical Record system by clinicians, and subsequently derived by researchers. The demography and injury characteristics, treatment protocols, complications, and outcomes were analyzed and compared between the two groups. A t-test was used for analysis of normally distributed data, and a Mann-Whitney U test for non-parametric data. A generalized linear model was further established to determine whether the factors length of stay and performance scale score were influenced by each factor. RESULTS: A total of 27 LVPBI patients were included in this analysis, comprised of 13 (48.1%) trans-base cases and 14 (51.9%) trans-vault cases. Statistical analyses suggested that trans-base LVPBI was correlated with deeper wounds; while the trans-vault phenotype was correlated with injury by metal foreign bodies. There was no difference in Glasgow Coma Scale score and the risk of intracranial hemorrhage between the two groups. Surgical approaches in the trans-base LVPBI group included subfrontal (n = 5, 38.5%), subtemporal (n = 5, 38.5%), lateral fissure (n = 2, 15.4%), and distal lateral (n = 1, 7.7%). All patients in the trans-vault group underwent a brain convex approach using the foreign body as reference (n = 14, 100%). Moreover, the two groups differed in application prerequisites for intracranial pressure monitoring and vessel-related treatment. Trans-base LVPBI was associated with higher rates of cranial nerve and major vessel injuries; in contrast, trans-vault LVPBI was associated with lower functional outcome scores. CONCLUSION: Our findings suggest that trans-base and trans-vault LVPBIs differ in terms of characteristics, treatment, and outcomes. Further understanding of these differences may help guide clinical decisions and contribute to a better management of LVPBIs.

Effect of exosome-derived non-coding RNA on traumatic brain injury. / èƒžå¤–ä½“æ¥æºçš„éžç¼–ç RNAåœ¨é¢ è„‘åˆ›ä¼¤ä¸­çš„ä½œç”¨.

Traumatic brain injury (TBI) is a main cause of death and disability worldwide, posing a serious threat to public health. But currently, the diagnosis and treatments for TBI are still very limited. Exosomes are a group of extracellular vesicles and participate in multiple physiological processes including intercellular communication and substance transport. Non-coding RNAs (ncRNA) are of great abundancy as cargo of exosomes. Previous studies have shown that ncRNAs are involved in several pathophysiological processes of TBI. However, the concrete mechanisms involved in the effects induced by exosome-derived ncRNA remain largely unknown. As an important component of exosomes, ncRNA is of great significance for diagnosis, precise treatment, response evaluation, prognosis prediction, and complication management after TBI.

Bleomycin Suppresses the Proliferation and the Mobility of Human Gastric Cancer Cells Through the Smad Signaling Pathway.

BACKGROUND/AIMS: Extensive studies have demonstrated that Bleomycin (BLM) is a glycopeptide antibiotic that has been used as an anticancer chemotherapeutic reagent. It can induce both single- and double-strand DNA damage, inhibit synthesis of DNA, suppress proliferation, and induce apoptosis in cancer cells. Smad signaling transducers are considered as important molecules in tumor development and progression, and may closely be related to the biological behaviors of some malignant carcinomas, including gastric cancer. METHODS: The effects of different concentrations of BLM on the proliferation, cell cycle, apoptosis, migration, and invasion on gastric cancer cell lines MKN45 and AGS were assayed by using CCK-8 assay, Annexin V/PI double staining, PI staining, and transwell assay. Western blot and Immunohistochemistry were applied to analyze the potential mechanism(s). RESULTS: BLM treatment resulted in a low proliferation, high apoptosis, low migration and invasion in MKN45 and AGS cells. Furthermore, the possible mechanisms underlying that Smad3 activity could be changed after binding with BLM, and subsequently the Smad signaling pathway had a cascade response. CONCLUSION: These results highlight BLM as an exciting theme for gastric cancer treatment, which may represent an effective clinical therapeutic reagent for gastric cancer patients.

Determination of hydroxysafflor yellow A in biological fluids of patients with traumatic brain injury by UPLC-ESI-MS/MS after injection of Xuebijing.

A simple, novel, specific, rapid and reproducible ultra-performance liquid chromatography electrospray ionization tandem mass spectrometry method has been developed and validated for the determination of hydroxysafflor yellow A (HSYA) in biological fluids (plasma, urine and cerebrospinal fluid) of patients with traumatic brain injury after intravenous injection of Xuebijing (XBJ). Liquid-liquid extraction was performed, and separation was carried out on an Acquity UPLC™ BEH C18 column, with gradient elution using a mobile phase composed of methanol and 0.1% formic acid at a flow rate of 0.3 mL/min. A triple quadrupole tandem mass spectrometer with electrospray ionization was used for the detection of HSYA. The mass transition followed was m/z 611.0 → 491. The retention time was less than 3.0 min. The calibration curve was linear in the concentration range from 2 to 6125 ng/mL for cerebrospinal fluid, plasma and urine. The intra- and inter-day precisions were <10%, and the relative standard deviation of recovery was <15% for HSYA in biological matrices. The method was successfully applied for the first time to quantify HSYA in the biological fluids (especially in cerebrospinal fluid) of patients with traumatic brain injury following intravenous administration of XBJ.

Effects of chitosan molecular weight and mass ratio with natural blue phycocyanin on physiochemical and structural stability of protein.

Phycocyanin (PC), an algae-extracted colorant, has extensive applications for its water-solubility and fresh blue shade. When PC is added to acidified media, dispersions are prone to aggregate and decolorize into cloudy systems. For palliating this matter, chitosan with high, medium, and low molecular weights (HMC, MMC, and LMC) were adopted in PC dispersions, and their protective effects were compared based on physiochemical stabilities. The optimal mass ratio between chitosan and PC was identified as 1:5 based on preliminary evaluations and was supported by the higher ζ-potential (31.0-32.1 mV), lower turbidity (39.6-43.6 NTU), and polyacrylamide gel electrophoresis results. Through interfacial and antioxidant capacity analyses, LMC was found to display a higher affinity to PC, which was also confirmed by SEM images and the maximum increase in transition temperature of their complex (155.70 °C) in DSC measurements. The mechanism of electrostatic interaction reinforced by hydrophobic effects and hydrogen bonding was elucidated by FT-IR and Raman spectroscopy. Further comprehensive stability evaluations revealed that, without light exposure, LMC kept PC from internal secondary structure to external blueness luster to the maximum extent. While with light exposure, LMC was not so flexible as HMC, to protect chromophores from attack of free radicals.

Anoikis patterns via machine learning strategy and experimental verification exhibit distinct prognostic and immune landscapes in melanoma.

BACKGROUND: Anoikis is a cell death programmed to eliminate dysfunctional or damaged cells induced by detachment from the extracellular matrix. Utilizing an anoikis-based risk stratification is anticipated to understand melanoma's prognostic and immune landscapes comprehensively. METHODS: Differential expression genes (DEGs) were analyzed between melanoma and normal skin tissues in The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression data sets. Next, least absolute shrinkage and selection operator, support vector machine-recursive feature elimination algorithm, and univariate and multivariate Cox analyses on the 308 DEGs were performed to build the prognostic signature in the TCGA-melanoma data set. Finally, the signature was validated in GSE65904 and GSE22155 data sets. NOTCH3, PIK3R2, and SOD2 were validated in our clinical samples by immunohistochemistry. RESULTS: The prognostic model for melanoma patients was developed utilizing ten hub anoikis-related genes. The overall survival (OS) of patients in the high-risk subgroup, which was classified by the optimal cutoff value, was remarkably shorter in the TCGA-melanoma, GSE65904, and GSE22155 data sets. Low-risk patients exhibited low immune cell infiltration and high expression of immunophenoscores and immune checkpoints. They also demonstrated increased sensitivity to various drugs, including dasatinib and dabrafenib. NOTCH3, PIK3R2, and SOD2 were notably associated with OS by univariate Cox analysis in the GSE65904 data set. The clinical melanoma samples showed remarkably higher protein expressions of NOTCH3 (P = 0.003) and PIK3R2 (P = 0.009) than the para-melanoma samples, while the SOD2 protein expression remained unchanged. CONCLUSIONS: In this study, we successfully established a prognostic anoikis-connected signature using machine learning. This model may aid in evaluating patient prognosis, clinical characteristics, and immune treatment modalities for melanoma.

Undenatured type II collagen nanofibrils with sodium alginate coating: Structural characterization, physicochemical properties and capability to load curcumin.

In this study, the structural design and physicochemical property enhancement of undenatured type II collagen (UC-II) nanofibrils with sodium alginate (SA) coating induced by calcium ions (Ca2+) were investigated. The research aimed to elucidate the impact of Ca2+ concentration on the morphology, thermal stability, and digestive resistance, as well as to assess the potential of UC-II/SA nanofibrils as a delivery system for curcumin (Cur). A series of Ca2+ concentrations (1-9 mM) were methodically applied to optimize the condition that maintains the triple-helical structure of UC-II, thereby enhancing its functional properties. It was found that the Ca2+ level up to 5 mM effectively preserved the structural integrity and improved thermal stability of UC-II, with the added benefit of ensuring the substantial delivery of active fragment to small intestine (70.7 %), which was 3.43 times greater than that of uncoated UC-II. Moreover, incorporating Cur into the UC-II/SA nanofibrils resulted in a 300 times increase in Cur solubility and showcased the superior dispersion stability, antioxidant activity, and sustained release profile during simulated digestion. These findings underscored the dual functionality of the UC-II/SA system as both a stabilizing agent for UC-II nanofibrils and an efficient carrier for Cur delivery.

Bioactive triterpenoid compounds of Poria cocos (Schw.) Wolf in the treatment of diabetic ulcers via regulating the PI3K-AKT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic ulcers represent a chronic condition characterized by prolonged hyperglycemia and delayed wound healing, accompanied by endocrine disorders, inflammatory responses, and microvascular damage in the epidermal tissue, demanding effective clinical treatment approaches. For thousands of years, ancient Chinese ethnopharmacological studies have documented the use of Poria cocos (Schw.) Wolf in treating diabetic ulcers. Recent research has substantiated the diverse pharmacological effects of Poria cocos (Schw.) Wolf, including its potential to alleviate hyperglycemia and exhibit anti-inflammatory, antioxidant, and immune regulatory properties, which could effectively mitigate diabetic ulcer symptoms. Furthermore, being a natural medicine, Poria cocos (Schw.) Wolf has demonstrated promising therapeutic effects and safety in the management of diabetic ulcers, holding significant clinical value. Despite its potential clinical efficacy and applications in diabetic ulcer treatment, the primary active components and underlying pharmacological mechanisms of Poria cocos (Schw.) Wolf remains unclear. Further investigations are imperative to establish a solid foundation for drug development in this domain. AIM OF THE STUDY AND MATERIALS AND METHODS: In this study, we aimed to identify the active compounds and potential targets of Poria cocos (Schw.) Wolf using UHPLC-Q-TOF-MS and TCMSP databases. Additionally, we attempt to identify targets related to diabetic ulcers. Following enrichment analysis, a network of protein-protein interactions was constructed to identify hub genes based on the common elements between the two datasets. To gain insights into the binding activities of the hub genes and active ingredients, molecular docking analysis was employed. Furthermore, to further validate the therapeutic effect of Poria cocos (Schw.) Wolf, we exerted in vitro experiments using human umbilical vein vascular endothelial cells and human myeloid leukemia monocytes (THP-1). The active ingredient of Poria cocos (Schw.) Wolf was applied in these experiments. Our investigations included various assays, such as CCK-8, scratch test, immunofluorescence, western blotting, RT-PCR, and flow cytometry, to explore the potential of Poria cocos (Schw.) Wolf triterpenoid extract (PTE) in treating diabetic ulcers. RESULTS: The findings here highlighted PTE as the primary active ingredient in Poria cocos (Schw.) Wolf. Utilizing network pharmacology, we identified 74 potential targets associated with diabetic ulcer treatment for Poria cocos (Schw.) Wolf, with five hub genes (JUN, MAPK1, STAT3, AKT1, and CTNNB1). Enrichment analysis revealed the involvement of multiple pathways in the therapeutic process, with the PI3K-AKT signaling pathway showing significant enrichment. Through molecular docking, we discovered that relevant targets within this pathway exhibited strong binding with the active components of Poria cocos (Schw.) Wolf. In vitro experiments unveiled that PTE (10 mg/L) facilitated the migration of human umbilical vein vascular endothelial cells (P < 0.05). PTE also increased the expression of CD31 and VEGF mRNA (P < 0.05) while activating the expressions of p-PI3K and p-AKT (P < 0.05). Moreover, PTE demonstrated its potential by reducing the expression of IL-1ß, IL-6, TNF-α, and NF-κB mRNA in THP-1 (P < 0.05) and fostering M2 macrophage polarization. These results signify the potential therapeutic effects of PTE in treating diabetic ulcers, with its beneficial actions mediated through the PI3K-AKT signaling pathway. CONCLUSIONS: PTE is the main active ingredient in Poria cocos (Schw.) Wolf that exerts therapeutic effects. Through PI3K-AKT signaling pathway activation and inflammatory response reduction, PTE promotes angiogenesis, thereby healing diabetic ulcers.

4-Di-phenyl-phosphanyl-8-methyl-1,5-naphthyridine.

In the title compound, C21H17N2P, the dihedral angles between the 1,5-naphthyridine ring system (r.m.s. deviation = 0.005 Å) and the phenyl rings are 89.18 (8) and 77.39 (8)°. The phenyl rings are almost perpendicular, making a dihedral angle of 88.12 (8)°. The only possible inter-molecular inter-action is a very weak aromatic π-π stacking inter-action [centroid-centroid separation = 3.898 (2) Å].

Rapid Preparation of Flame-Retardant Coatings Using Polyurethane Emulsion Mixed with Inorganic Fillers.

The traditional aqueous flame-retardant coating faces the problem of slow solvent evaporation rate in the preparation process. It is an urgent problem to ensure that the function of the membrane is not destroyed while accelerating the solvent volatilization. Herein, we fabricated films on the metal substrate surface by a totally novel method: demulsification-induced fast solidification to rapidly obtain the flame-retardant coating. The environmentally friendly flame retardants aluminum hydroxide and red phosphorus were mixed with the commercial water-based polyurethane 906 emulsion to explore the optimal mixing ratio, where the adhesion of the flame-retardant reached the Grade 3 standard, the sample remained intact after the 100 cm drop hammer test and the limiting oxygen index value reached 30.4%. In addition, compared with the traditional process, this method, with the advantages of rapidly drying, environmentally friendly, uniformly prepared coatings on the surface of any shape substrates, as well as accurate and controllable coating thickness, can be widely applied in the flame-retardant field.

Insight into the composite assembly process, nanofibril structure and stability of undenatured type II collagen in the presence of different types of nanocelluloses.

Four types of nanocelluloses (CNs), including cellulose nanocrystals (CNC), cellulose nanofibrils (CNF), cationic etherified nanocellulose (CCNF) and TEMPO-oxidized nanocellulose (TOCNF), were incorporated into the assembly process of undenatured type II collagen (UC-II). In the presence of CNs, the kinetics of UC-II composite assembly slightly fluctuated and the magnitude of UC-II assembly increased (from 59.93 to 66.83-85.06 %). CNC and CNF disrupted the triple helix structure of UC-II while CCNF and TOCNF had weak impact on it. Hydrogen bonding and hydrophobic interactions were dominant driving forces of UC-II/CNs, and electrostatic interactions were also involved in the fabrication of UC-II/CCNF and UC-II/TOCNF. UC-II/CNs exhibited distinct nanostructures due to the differences in shape, level, and surface group of CNs. CCNF and TOCNF contributed to the enhanced physical stability due to the increased surface charge. In addition, the thermal stability and rheological properties of UC-II/CNs were also improved. The composite assembly process, nanofibril structure and stability of UC-II in the presence of different types and levels of CNs, which was useful to develop the novel composite nanofibrils for the application in functional foods.

Effects of different mechanical processes on the structural and powdery properties of insoluble undenatured type II collagen.

This study aimed to investigate the effects of dynamic high-pressure homogenization (DHPH), dynamic high-pressure microfluidization (DHPM), and wet media milling (WMM) processes on the particle size, microstructure, triple helix structure, wettability and suspension stability of insoluble undenatured type II collagen (IUC-II). The structural and powdery properties were regulated by different processes and parameters. By contrast, WMM-treated IUC-II showed smallest particle size (15.70 µm), highest wetting rate (216.94 mm/h) and best suspension stability. However, individual mechanical processes caused partial disruption of IUC-II triple helix structure. Low-acyl gellan gum (LAGG) could bind to IUC-II through hydrogen bonds and hydrophobic interactions, which protected the triple helix structure and further enhanced powdery properties of IUC-II treated by WMM process, but restrained the soluble transition during digestion. These results demonstrated that WMM process was more suitable for enhancing powdery properties of IUC-II, while the triple helix structure of IUC-II could be effectively protected by LAGG.

Nanostructured lipid carriers (NLCs) stabilized by natural or synthetic emulsifiers for lutein delivery: Improved physicochemical stability, antioxidant activity, and bioaccessibility.

This study investigated the impacts of individual emulsifiers on the physicochemical stability, antioxidant ability, and in vitro digestion behavior of lutein-loaded nanostructured lipid carriers (NLCs). NLCs particles stabilized by ethyl lauroyl arginate, rhamnolipid, or tea saponin were fabricated by high-pressure microfluidization method. Differential scanning calorimetry and X-ray diffraction results confirmed the regulatory effect of emulsifiers on the crystallization behavior of NLCs. NLCs stabilized by rhamnolipid presented higher encapsulation efficiency (94.73%) for lutein than those stabilized by tea saponin (90.39%) or ethyl lauroyl arginate (88.86%). Meanwhile, the stability of embedded lutein during storage or photothermal treatments was greatly enhanced. Individual emulsifiers, together with lutein, endowed NLCs with excellent antioxidant capacity. During in vitro digestion, rhamnolipid-stabilized NLCs showed the slowest release of free fatty acids (50.87%) and provided an optimal sustained release for lutein with relatively high bioaccessibility (23.01%).

Loading neural stem cells on hydrogel scaffold improves cell retention rate and promotes functional recovery in traumatic brain injury.

Neural stem cell (NSC) has gained considerable attention in traumatic brain injury (TBI) treatment because of their ability to replenish dysfunctional neurons and stimulate endogenous neurorestorative processes. However, their therapeutic effects are hindered by the low cell retention rate after transplantation into the dynamic brain. In this study, we found cerebrospinal fluid (CSF) flow after TBI is an important factor associated with cell loss following NSC transplantation. Recently, several studies have shown that hydrogels could serve as a beneficial carrier for stem cell transplantation, which provides a solution to prevent CSF flow-induced cell loss after TBI. For this purpose, we evaluated three different hydrogel scaffolds and found the gelatin methacrylate (GelMA)/sodium alginate (Alg) (GelMA/Alg) hydrogel scaffold showed the best capabilities for NSC adherence, growth, and differentiation. Additionally, we detected that pre-differentiated NSCs, which were loaded on the GelMA/Alg hydrogel and cultured for 7 days in neuronal differentiation medium (NSC [7d]), had the highest cell retention rate after CSF impact. Next, the neuroprotective effects of the NSC-loaded GelMA/Alg hydrogel scaffold were evaluated in a rat model of TBI. NSC [7d]-loaded GelMA/Alg markedly decreased microglial activation and neuronal death in the acute phase, reduced tissue loss, alleviated astrogliosis, promoted neurogenesis, and improved neurological recovery in the chronic phase. In summary, we demonstrated that the integration with the GelMA/Alg and modification of NSC differentiation could inhibit the influence of CSF flow on transplanted NSCs, leading to increased number of retained NSCs and improved neuroprotective effects, providing a promising alternative for TBI treatment.