Extracellular vesicle-encapsulated microRNA-296-3p from cancer-associated fibroblasts promotes ovarian cancer development through regulation of the PTEN/AKT and SOCS6/STAT3 pathways.

Cancer-associated fibroblasts (CAFs), as important components of the tumor microenvironment, can regulate intercellular communication and tumor development by secreting extracellular vesicles (EVs). However, the role of CAF-derived EVs in ovarian cancer has not been fully elucidated. Here, using an EV-microRNA sequencing analysis, we reveal specific overexpression of microRNA (miR)-296-3p in activated CAF-derived EVs, which can be transferred to tumor cells to regulate the malignant phenotypes of ovarian cancer cells. Moreover, overexpression of miR-296-3p significantly promotes the proliferation, migration, invasion, and drug resistance of ovarian cancer cells in vitro, as well as tumor growth in vivo, while its inhibition has the opposite effects. Further mechanistic studies reveal that miR-296-3p promotes ovarian cancer progression by directly targeting PTEN and SOCS6 and activating AKT and STAT3 signaling pathways. Importantly, increased expression of miR-296-3p encapsulated in plasma EVs is closely correlated with tumorigenesis and chemoresistance in patients with ovarian cancer. Our results highlight the cancer-promoting role of CAF-derived EVs carrying miR-296-3p in ovarian cancer progression for the first time, and suggest that miR-296-3p encapsulated in CAF-derived EVs could be a diagnostic biomarker and therapeutic target for ovarian cancer.

Effect of plasma exosome lncRNA on isoproterenol hydrochloride-induced cardiotoxicity in rats.

Isoprenaline hydrochloride (IH) is a ß-adrenergic receptor agonist commonly used in the treatment of hypotension, shock, asthma, and other diseases. However, IH-induced cardiotoxicity limits its application. A large number of studies have shown that long noncoding RNA (lncRNA) regulates the occurrence and development of cardiovascular diseases. This study aimed to investigate whether abnormal lncRNA expression is involved in IH-mediated cardiotoxicity. First, the Sprague-Dawley (SD) rat myocardial injury model was established. Circulating exosomes were extracted from the plasma of rats and identified. In total, 108 differentially expressed (DE) lncRNAs and 150 DE mRNAs were identified by sequencing. These results indicate that these lncRNAs and mRNAs are substantially involved in chemical cardiotoxicity. Further signaling pathway and functional studies indicated that lncRNAs and mRNAs regulate several biological processes, such as selective mRNA splicing through spliceosomes, participate in sphingolipid metabolic pathways, and play a certain role in the circulatory system. Finally, we obtained 3 upregulated lncRNAs through reverse transcription-quantitative PCR (RT-qPCR) verification and selected target lncRNA-mRNA pairs according to the regulatory relationship of lncRNA/mRNA, some of which were associated with myocardial injury. This study provides valuable insights into the role of lncRNAs as novel biomarkers of chemical-induced cardiotoxicity.

A New Sono-Chemo Sensitizer Overcoming Tumor Hypoxia for Augmented Sono/Chemo-Dynamic Therapy and Robust Immune-Activating Response.

Novel sonosensitizers with intrinsic characteristics for tumor diagnosis, efficient therapy, and tumor microenvironment regulation are appealing in current sonodynamic therapy. Herein, a manganese (Mn)-layered double hydroxide-based defect-rich nanoplatform is presented as a new type of sono-chemo sensitizer, which allows ultrasound to efficiently trigger reactive oxygen species generation for enhanced sono/chemo-dynamic therapy. Moreover, such a nanoplatform is able to relieve tumor hypoxia and achieve augmented singlet oxygen production via catalyzing endogenous H2 O2 into O2 . On top of these actions, the released Mn2+ ions and immune-modulating agent significantly intensify immune activation and reverse the immunosuppressive tumor microenvironment to the immunocompetent one. Consequently, this nanoplatform exhibits excellent anti-tumor efficacy and effectively suppresses both primary and distant tumor growth, demonstrating a new strategy to functionalize nanoparticles as sono-chemo sensitizers for synergistic combination cancer therapy.

Galangin: A food-derived flavonoid with therapeutic potential against a wide spectrum of diseases.

Galangin is an important flavonoid with natural activity, that is abundant in galangal and propolis. Currently, various biological activities of galangin have been disclosed, including anti-inflammation, antibacterial effect, anti-oxidative stress and aging, anti-fibrosis, and antihypertensive effect. Based on the above bioactivities, more and more attention has been paid to the role of galangin in neurodegenerative diseases, rheumatoid arthritis, osteoarthritis, osteoporosis, skin diseases, and cancer. In this paper, the natural sources, pharmacokinetics, bioactivities, and therapeutic potential of galangin against various diseases were systematically reviewed by collecting and summarizing relevant literature. In addition, the molecular mechanism and new preparation of galangin in the treatment of related diseases are also discussed, to broaden the application prospect and provide reference for its clinical application. Furthermore, it should be noted that current toxicity and clinical studies of galangin are insufficient, and more evidence is needed to support its possibility as a functional food.

FAPhigh α-SMAlow cancer-associated fibroblast-derived SLPI protein encapsulated in extracellular vesicles promotes ovarian cancer development via activation of PI3K/AKT and downstream signaling pathways.

Ovarian cancer is the most lethal gynecological malignancy worldwide with high metastasis and poor prognosis rates. Cancer-associated fibroblasts (CAFs), a heterogeneous population of cells that constitutes a major component of the tumor microenvironment, secrete extracellular vesicles (EVs) loading with proteins, lipids, and RNAs to promote tumorigenesis. However, the specific roles of CAF-derived proteins contained in EVs in ovarian cancer remain poorly understood at present. Using the gene expression microarray analysis, we identified a list of dysregulated genes between the α-SMA+ CAF and FAP+ CAF subpopulations, from which secretory leukocyte protease inhibitor (SLPI) was chosen for further validation. Quantitative PCR, western blot, immunohistochemistry, and enzyme-linked immunosorbent assays were used to assess SLPI expression in ovarian cancer cells, tissues, CAFs, and EVs. Additionally, we evaluated the effects of exogenous SLPI on proliferation, migration, invasion, and adhesion of ovarian cancer cells in vitro. Our results showed SLPI protein was upregulated in CAFs, particularly in the FAPhigh α-SMAlow CAF subpopulation, and associated with increased tumor grade and decreased overall survival (OS). Importantly, CAF-derived SLPI protein could be encapsulated in EVs for delivery to ovarian cancer cells, thus facilitating cell proliferation, migration, invasion, and adhesion via activating the PI3K/AKT and downstream signaling pathways. Moreover, high plasma expression of SLPI encapsulated in EVs was closely correlated with tumor stage in ovarian cancer patients. Our collective results highlight an oncogenic role of plasma EV-encapsulated SLPI secreted by CAFs in tumor progression for the first time, supporting its potential utility as a prognostic biomarker of ovarian cancer.

Sheet-like clay nanoparticles deliver RNA into developing pollen to efficiently silence a target gene.

Topical application of double-stranded RNA (dsRNA) can induce RNA interference (RNAi) and modify traits in plants without genetic modification. However, delivering dsRNA into plant cells remains challenging. Using developing tomato (Solanum lycopersicum) pollen as a model plant cell system, we demonstrate that layered double hydroxide (LDH) nanoparticles up to 50 nm in diameter are readily internalized, particularly by early bicellular pollen, in both energy-dependent and energy-independent manners and without physical or chemical aids. More importantly, these LDH nanoparticles efficiently deliver dsRNA into tomato pollen within 2-4 h of incubation, resulting in an 89% decrease in transgene reporter mRNA levels in early bicellular pollen 3-d post-treatment, compared with a 37% decrease induced by the same dose of naked dsRNA. The target gene silencing is dependent on the LDH particle size, the dsRNA dose, the LDH-dsRNA complexing ratio, and the treatment time. Our findings indicate that LDH nanoparticles are an effective nonviral vector for the effective delivery of dsRNA and other biomolecules into plant cells.

Shikonin as a WT1 Inhibitor Promotes Promyeloid Leukemia Cell Differentiation.

This study aims to observe the differentiating effect of shikonin on Wilms' tumor 1 (WT1)-positive HL-60 cells and investigate the fate of the differentiated leukemia cells. WT1 overexpression unaffected cell viability but promoted resistance to H2O2-induced DNA injury and cell apoptosis. The binding of shikonin to the WT1 protein was confirmed by molecular docking and drug affinity reaction target stability (DARTS). Shikonin at the non-cytotoxic concentration could decrease the WT1 protein and simultaneously reduced the CD34 protein and increased the CD11b protein in a dose-dependent manner in normal HL-60 cells but not in WT1-overexpressed HL-60 cells. Shikonin unaffected HL-60 cell viability in 48 h. However, it lasted for 10 days; could attenuate cell proliferation, mitochondrial membrane potential (MMP), and self-renewal; prevent the cell cycle; promote cell apoptosis. In a mouse leukemia model, shikonin could decrease the WT1 protein to prevent leukemia development in a dose-dependent manner. In this study, we also confirmed preliminarily the protein-protein interactions between WT1 and CD34 in molecular docking and CO-IP assay. Our results suggest that: 1. shikonin can down-regulate the WT1 protein level for leukemia differentiation therapy, and 2. the interaction between WT1 and CD34 proteins may be responsible for granulocyte/monocyte immaturity in HL-60 cells.

Biomimetic 2D layered double hydroxide nanocomposites for hyperthermia-facilitated homologous targeting cancer photo-chemotherapy.

BACKGROUND: Multi-modal therapy has attracted increasing attention as it provides enhanced effectiveness and potential stimulation of the immune community. However, low accumulation at the tumor sites and quick immune clearance of the anti-tumor agents are still insurmountable challenges. Hypothetically, cancer cell membrane (CCM) can homologously target the tumor whereas multi-modal therapy can complement the disadvantages of singular therapies. Meanwhile, moderate hyperthermia induced by photothermal therapy can boost the cellular uptake of therapeutic agents by cancer cells. RESULTS: CCM-cloaked indocyanine green (ICG)-incorporated and abraxane (PTX-BSA)-loaded layered double hydroxide (LDH) nanosheets (LIPC NSs) were fabricated for target efficient photo-chemotherapy of colorectal carcinoma (CRC). The CCM-cloaked LDH delivery system showed efficient homologous targeting and cytotoxicity, which was further enhanced under laser irradiation to synergize CRC apoptosis. On the other hand, CCM-cloaking remarkably reduced the uptake of LDH NSs by HEK 293T cells and macrophages, implying mitigation of the side effects and the immune clearance, respectively. In vivo data further exhibited that LIPC NSs enhanced the drug accumulation in tumor tissues and significantly retarded tumor progression under laser irradiation at very low therapeutic doses (1.2 and 0.6 mg/kg of ICG and PTX-BSA), without observed side effects on other organs. CONCLUSIONS: This research has demonstrated that targeting delivery efficiency and immune-escaping ability of LIPC NSs are tremendously enhanced by CCM cloaking for efficient tumor accumulation and in situ generated hyperthermia boosts the uptake of LIPC NSs by cancer cells, a potential effective way to improve the multi-modal cancer therapy.

Albumin-stabilized layered double hydroxide nanoparticles synergized combination chemotherapy for colorectal cancer treatment.

Combination chemotherapy with two or more complimentary drugs has been widely used for clinical cancer treatment. However, the efficacy and side effects of combination chemotherapy still remain a challenge. Here, we constructed an albumin-stabilized layered double hydroxide nanoparticle (BLDH) system to simultaneously load and deliver two widely used anti-tumor drugs, i.e. 5-fluorouracil (5FU) and albumin-bound PTX (Abraxane, ABX) for colorectal cancer treatment. The cellular uptake test has revealed that 5FU-ABX encapsulated BLDH (BLDH/5FU-ABX) nanoparticles were efficiently internalized by the colorectal cancer cell (HCT-116), synergistically inducing apoptosis of colon cancer cells. The in vivo test has demonstrated that BLDH/5FU-ABX nanomedicine significantly inhibited the tumor growth after three intravenous injections, without any detectable side effects. The enhanced therapeutic effectiveness is attributed to efficient accumulation of BLDH/5FU-ABX at tumor sites and acid-sensitive release of co-loaded drugs. Thus, combination chemotherapy based on BLDH/5FU-ABX nanomedicine would be a new strategy for colorectal cancer treatment.

Clinical characteristics of 41 patients with pneumonia due to 2019 novel coronavirus disease (COVID-19) in Jilin, China.

BACKGROUND: The clinical characteristics of patients with confirmed 2019 novel coronavirus disease (COVID-19) in Jilin Province, China were investigated. METHODS: Clinical, laboratory, radiology, and treatment data of 41 hospitalized patients with confirmed COVID-19 were retrospectively collected. The population was stratified by disease severity as mild, moderate, or severe, based on guidelines of the National Health and Medical Commission of China. RESULTS: The 41 hospitalized patients with COVID-19 were studied, and the median age was 45 years (interquartile range [IQR], 31-53; range, 10-87 years) and 18 patients (43.9%) were female. All of the patients had recently visited Wuhan or other places (ie, Beijing, Thailand) or had Wuhan-related exposure. Common symptoms included fever (32[78%]) and cough (29[70.7%]). All patients were without hepatitis B/C virus hepatitis. CRP (C-reactive protein, 11.3 mg/L [interquartile range {IQR}, 2.45-35.2]) was elevated in 22 patients (53.7%), and cardiac troponin I (1.5 ng/mL [IQR, 0.8-5.0]) was elevated in 41 patients (100%). Chest computed tomographic scans showed bilateral ground glass opacity (GGO) or GGO with consolidation in the lungs of 27(65.9%) patients. 31(75.6%) patients had an abnormal electrocardiograph (ECG). Comparing the three groups, the levels of CRP and cardiac troponin I, GGO distribution in bilateral lungs, and electrocardiogram changes were statistically significant (p < 0.05). Cardiac troponin I had a strong positive correlation with CRP (r = 0.704, p = 0.042) and LDH (r = 0.738, p = 0.037). CONCLUSION: Significant differences among the groups suggest that several clinical parameters may serve as biomarkers of COVID-19 severity at hospital admission. Elevated cTnI could be considered as a predictor of severe COVID-19, reflecting the prognosis of patients with severe COVID-19. The results warrant further inspection and confirmation.

The effect of Notch signal pathway on PM2.5-induced Muc5ac in Beas-2B cells.

BACKGROUND: Atmospheric pollutants could induced over-expression of Muc5ac, which is a major pathological feature in acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD) and fatal asthma. Notch signaling pathway could promote mucus cell proliferation and mucus secretion. However, the effects of Notch signaling pathway on the airway mucus secretion induced by PM2.5 remain unknown. In this study, we investigated the role of the Notch signaling pathway on Muc5ac by atmospheric PM2.5 in Beas-2B cell. METHODS: The mRNA and protein levels of the Notch1-4, downstream target gene Hes1 and Muc5ac in the Notch signaling pathway were detected by qPCR and western after Beas-2B cells were exposed to PM2.5 of different concentrations for 12h, 24h, and 48h. RESULTS: The longer the exposure time and the higher the concentration of PM2.5, the lower the survival rate of Beas-2B cells. The expressions of Hes1 and Muc5ac in mRNA and protein were significantly increased after PM2.5 exposure. Correlation analysis indicated that there was a positive correlation between the expression of Muc5ac and Hes1 in mRNA and protein. CONCLUSION: Atmospheric PM2.5 can induce the express of Muc5ac, the Notch signaling pathway may be involved in the regulation of Muc5ac by Hes1.

Understanding the epidemiological characteristics of EV71 and CVA16 infection to aid the diagnosis and treatment of hand, foot, and mouth disease.

Hand, foot, and mouth disease (HFMD) have been recognized over the past several years as a highly infectious disease in children. Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the two major causative agents. The objective of this study was to determine the optimal time and method of HFMD detection, explore the seroconversion of IgM and IgG antibodies, and examine the response of neutralizing antibody (NtAb) to EV71 or CVA16. Between January 2016 and December 2017, a total of 460 patients, diagnosed with HFMD based on clinical symptoms and hospitalized in the First Hospital of Jilin University, were recruited for the study. At approximately 72 hours post illness onset, we observed that the positive rate of both IgM and real-time polymerase chain reaction detection of EV71 or CVA16 was the highest, this could be considered as the optimal detection time for clinical diagnosis. During the initial 0 -96 hours, the relative highest IgM and the relative lowest IgG antibody levels were observed. The NtAb titers to EV71 and CVA16 also gradually increased with time, showing a positive correlation with age, and being the predominant factor during the hospitalized days. Thus, our study provides important information for the clinical diagnosis and treatment of HFMD.

TRIM65 negatively regulates p53 through ubiquitination.

Tripartite-motif protein family member 65 (TRIM65) is an important protein involved in white matter lesion. However, the role of TRIM65 in human cancer remains less understood. Through the Cancer Genome Atlas (TCGA) gene alteration database, we found that TRIM65 is upregulated in a significant portion of non-small cell lung carcinoma (NSCLC) patients. Our cell growth assay revealed that TRIM65 overexpression promotes cell proliferation, while knockdown of TRIM65 displays opposite effect. Mechanistically, TRIM65 binds to p53, one of the most critical tumor suppressors, and serves as an E3 ligase toward p53. Consequently, TRIM65 inactivates p53 through facilitating p53 poly-ubiquitination and proteasome-mediated degradation. Notably, chemotherapeutic reagent cisplatin induction of p53 is markedly attenuated in response to ectopic expression of TRIM65. Cell growth inhibition by TRIM65 knockdown is more significant in p53 positive H460 than p53 negative H1299 cells, and knockdown of p53 in H460 cells also shows compromised cell growth inhibition by TRIM65 knockdown, indicating that p53 is required, at least in part, for TRIM65 function. Our findings demonstrate TRIM65 as a potential oncogenic protein, highly likely through p53 inactivation, and provide insight into development of novel approaches targeting TRIM65 for NSCLC treatment, and also overcoming chemotherapy resistance.

miR-124/ATF-6, a novel lifespan extension pathway of Astragalus polysaccharide in Caenorhabditis elegans.

MicroRNAs (miRNAs), especially evolutionarily conserved miRNAs play critical roles in regulating various biological process. However, the functions of conserved miRNAs in longevity are still largely unknown. Astragalus polysaccharide (APS) was recently shown to extend lifespan of Caenorhabditis elegans, but its molecular mechanisms have not been fully understood. In the present study, we characterize that microRNA mediated a novel longevity pathway of APS in C. elegans. We found that APS markedly extended the lifespan of C. elegans at the second and the fourth stages. A highly conserved miRNA miR-124 was significantly upregulated in APS-treated C. elegans. Overexpression miR-124 caused the lifespan extension of C. elegans and vice versa, indicating miR-124 regulates the longevity of C. elegans. Using luciferase assay, atf-6 was established as a target gene of miR-124 which acting on three binding sites at atf-6 3'UTR. Consistently, agomir-cel-miR-124 was also shown to inhibit ATF-6 expression in C. elegans. APS-treated C. elegans showed the down-regulation of atf-6 at protein level. Furthermore, the knockdown of atf-6 by RNAi extended the lifespan of C. elegans, indicating atf-6 regulated by miR-124 contributes to lifespan extension. Taken together, miR-124 regulating ATF-6 is a new potential longevity signal pathway, which underlies the lifespan-extending effects of APS in C. elegans.

MicroRNA-23a mediates mitochondrial compromise in estrogen deficiency-induced concentric remodeling via targeting PGC-1α.

It is well known that menopause could worsen age-related ventricular concentric remodeling following estrogen (E2) deficiency. However the underlying mechanisms of such phenomena are not fully understood. Mitochondria, as the 'cellular power station' of hearts, play an important role in maintaining normal cardiac function and structure. Therefore, the present study aims to investigate whether mitochondrial compromise is responsible for E2 deficiency associated concentric remodeling and, if so, what is its underlying molecular mechanism. We found evident concentric remodeling pattern in both postmenopausal and ovariectomized (OVX) mice, which could be attenuated by E2 replacement. Further study showed mitochondrial structural damages and respiratory function impairment in myocardium of both postmenopausal and OVX mice and E2 supplement reversed mitochondrial dysfunction in OVX mice, suggesting that E2 deficiency could induce mitochondrial compromise in the heart. Then, peroxisome proliferator-activated receptor-γ co-activator 1-α (PGC-1α), a key mitochondrial function and biology regulator, was found significantly reduced in both postmenopausal and OVX mice. The reduction of PGC-1α protein level in OVX mice could be rescued by E2 delivery, indicating that E2 could positively regulate PGC-1α expression. Next, we found that microRNA-23a (miR-23a) could be negatively regulated by E2 in both myocardium and cultured cardiomyocytes. Moreover, miR-23a could directly downregulate PGC-1α expression in cardiomyocytes via binding to its 3'UTR which implied that miR-23a could be critical for the downregulation of PGC-1α under E2 deficiency. Overexpression of miR-23a was also found to damage mitochondria in cultured cardiomyocytes, ascribed to PGC-1α downregulation. Taken together, E2 deficiency may cause mitochondrial compromise through miR-23a-mediated PGC-1α downregulation, which may subsequently lead to the menopause-associated concentric remodeling.

Family Resilience and Its Influencing Factors in Patients with Stress Urinary Incontinence after Cervical Cancer Surgery: A Retrospective Study.

OBJECTIVE: This study aimed to analyse the family resilience of patients with stress urinary incontinence (SUI) after cervical cancer surgery and its influencing factors. METHODS: Patients with cervical cancer postoperative SUI admitted to our hospital from May 2020, to May 2023, were retrospectively selected. They were divided into low-resilience group and high-resilience group in accordance with the Family Resilience Questionnaire (FaREQ). The general demographic data of the two groups were statistically analysed, and correlation and logistic regression analyses were performed. RESULTS: The FaREQ score of 222 patients was (93.61 ± 8.45). Amongst these patients, 21.62% scored less than 84 points, and 78.38% scored more than 84 points. Significant differences were found in the educational level, indwelling catheter time, family monthly income, religious belief, hope index, psychological resilience, family function and social support between the two groups (p < 0.05). A significant positive correlation was observed between family resilience and the above indicators (p < 0.05). The variance inflation coefficient values of educational level and indwelling catheter time were 15.764 and 43.766, and the tolerance values were 0.063 and 0.023, respectively. After removing them, family monthly income, religious belief, hope index, psychological resilience, family function and social support were the factors affecting the family resilience level of patients with SUI after cervical cancer surgery. CONCLUSIONS: The level of family resilience of patients with SUI after cervical cancer surgery is low. Many factors, such as family monthly income and religious belief, affect the level of resilience. Therefore, corresponding measures could be formulated in advance to improve the level of family resilience of such patients.

Investigation into the fabrication of plant-based simulant connective tissue utilizing algae polysaccharide-derived hydrogel.

Connective tissue is an important component of meat products that provides support to animal muscles. Hydrogels are considered a promising alternative to connective tissues and simulate actual products by adjusting the gel texture and mouthfeel. This study used soybean protein isolate (SPI), corn starch (CS), konjac glucomannan (KGM), and seaweed powder (SP) as raw materials to examine the effect of different added SP and KGM concentrations on the gel texture. The G' of the gel increased five-fold when the SP and KGM concentration was increased from 1 % to 3 %. The results of mechanical property tests showed that with the addition of SP, the gel hardness increased from 316.00 g to 1827.23 g and the tensile strength increased from 0.027 MPa to 0.089 MPa. Sensory evaluation showed that the samples with 2 % SP and KGM presented the highest overall acceptability score and the most significant similarity to real connective tissue. The connective tissue simulants exhibited excellent water-holding capacity (>90 %), significantly increasing their juiciness. SEM indicated that 2 % KGM addition improved gel network structure stability. The results demonstrate the potential of seaweed polysaccharide-derived hydrogels as connective tissue mimics. This provides a new strategy for the preparation of high mechanical strength hydrogels and lays the foundation for structural diversification of plant-based meat.

Salt ions improve soybean protein isolate/curdlan complex fat substitutes: Effect of molecular interactions on freeze-thaw stability.

Although emulsion gels show significant potential as fat substitutes, they are vulnerable to degreasing, delamination, and other undesirable processes during freezing, storage, and thawing, leading to commercial value loss in terms of juiciness, flavor, and texture. This study investigated the gel strength and freeze-thaw stability of soybean protein isolate (SPI)/curdlan (CL) composite emulsion gels after adding sodium chloride (NaCl). Analysis revealed that adding low salt ion concentrations promoted the hardness and water-holding capacity (WHC) of fat substitutes, while high levels displayed an inhibitory effect. With 40 mM NaCl as the optimum concentration, the hardness increased from 259.33 g (0 mM) to 418.67 g, the WHC increased from 90.59 % to 93.18 %, exhibiting good freeze-thaw stability. Confocal laser scanning microscopy (CLSM) and particle size distribution were used to examine the impact of salt ion concentrations on protein particle aggregation and the damaging effect of freezing and thawing on the proteoglycan complex network structure. Fourier-transform infrared spectroscopy (FTIR) and protein solubility evaluation indicated that the composite gel network structure consisted of covalent contacts between the proteoglycan molecules and hydrogen bonds, playing a predominant role in non-covalent interaction. This study showed that the salt ion concentration in the emulsion gel affected its molecular interactions.

Investigation of polysaccharide from Radix Aconiti Lateralis Preparata (Fuzi) cardio protective effect on doxorubicin-induced chronic cardiotoxicity.

OBJECTIVES: Doxorubicin (DOX) is a chemotherapy drug for treating malignant tumours. However, its cardiotoxicity has limited its clinical application. The Radix Aconiti Lateralis Preparata, also known as Fuzi, has been used for treating heart failure. Nevertheless, there is still a deficiency of claeity as to whether the Fuzi polysaccharide (FPS) may prevent the side effects of DOX. METHODS: Mice were intraperitoneally administered DOX (15 mg/kg) to establish a mouse model of DOX-induced chronic cardiotoxicity (DICC). The mice were then administered different doses of FPS or enalapril intragastrically. KEY FINDINGS: In the DOX group, the activity of CK-MB and LDH and the content of NT-proBNP in serum of mice were increased. Myocardial infiltration of inflammatory cells and cytoplasmic vacuolation occurred. Levels of NLRP3, ASC, Caspase-1, IL-1ß, IL-18, IL-6, and Bax increased, whereas levels of Bcl-2, STAT3, and p-STAT3 decreased. After administering FPS (100 mg/kg and 200 mg/kg), there were reductions in CK-MB activity and NT-proBNP levels. Cytoplasmic vacuolation, interstitial infiltration of blood, and infiltration of inflammatory cells were alleviated. The changes in protein expression mentioned above were reversed. CONCLUSIONS: FPS can protect heart function and structure in DICC mice by inhibiting NLRP3 inflammasome-mediated pyroptosis and IL-6/STAT3 pathway-induced apoptosis.

Proteomic characterization of hUC-MSC extracellular vesicles and evaluation of its therapeutic potential to treat Alzheimer's disease.

In recent years, human umbilical cord mesenchymal stem cell (hUC-MSC) extracellular vesicles (EVs) have been used as a cell replacement therapy and have been shown to effectively overcome some of the disadvantages of cell therapy. However, the specific mechanism of action of EVs is still unclear, and there is no appropriate system for characterizing the differences in the molecular active substances of EVs produced by cells in different physiological states. We used a data-independent acquisition (DIA) quantitative proteomics method to identify and quantify the protein composition of two generations EVs from three different donors and analysed the function and possible mechanism of action of the proteins in EVs of hUC-MSCs via bioinformatics. By comparative proteomic analysis, we characterized the different passages EVs. Furthermore, we found that adaptor-related protein complex 2 subunit alpha 1 (AP2A1) and adaptor-related protein complex 2 subunit beta 1 (AP2B1) in hUC-MSC-derived EVs may play a significant role in the treatment of Alzheimer's disease (AD) by regulating the synaptic vesicle cycle signalling pathway. Our work provides a direction for batch-to-batch quality control of hUC-MSC-derived EVs and their application in AD treatment.