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1.
BVES-AS1 suppresses the colorectal cancer progression via the miR-1269a/b-SVEP1-PI3K/AKT axis.
Yang, J, Deng, Q, Chen, Z, Chen, Y, Fu, Z
Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 2024
Abstract
BACKGROUND Numerous studies have indicated the engagement of long non-coding RNA (lncRNA) in various cancer types, including colorectal cancer (CRC). However, the functional and mechanistic roles of lncRNAs in CRC remain largely elusive. OBJECTIVES The aim of this study was to explore the function and mechanism of lncRNA BVES-AS1 in CRC. MATERIAL AND METHODS The expression levels of BVES-AS1 were validated in CRC tissues and paired normal samples using quantitative real-time polymerase chain reaction (qPCR) Subsequently, the biological functions of BVES-AS1 in CRC cells were investigated both in vitro and in vivo. Various experimental techniques such as western blot, fluorescence in situ hybridization, RNA-sequencing (RNA-seq), biotin-labeled miRNA pulldown assay, dual-luciferase reporter gene assay, and RNA-protein immunoprecipitation (RIP) assay were employed to elucidate the potential mechanism of BVES-AS1. RESULTS The findings of this study demonstrated that BVES-AS1 expression was downregulated in CRC tissues compared to normal tissues, and its expression level was associated with tumor infiltration and tumor-nodule-metastasis (TNM) stage. Furthermore, BVES-AS1 was found to suppress CRC cell proliferation, migration and metastasis both in vitro and in vivo. Mechanistically, BVES-AS1 acted as a sponge for miR-1269a and miR-1269b, thereby regulating SVEP1. Additionally, the silencing of SVEP1 activated the PI3K/AKT pathway. CONCLUSIONS These results suggest that BVES-AS1 plays a crucial role in the progression of CRC through the miR-1269a/b-SVEP1-PI3K/AKT axis, providing new insights into the therapeutic strategies for CRC.
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2.
Printing GelMA bioinks: a strategy for buildingin vitromodel to study nanoparticle-based minocycline release and cellular protection under oxidative stress.
Fu, Z, Hai, N, Zhong, Y, Sun, W
Biofabrication. 2024;(2)
Abstract
Owing to its thermoresponsive and photocrosslinking characteristics, gelatin methacryloyl (GelMA)-based biomaterials have gained widespread usage as a novel and promising bioink for three-dimensional bioprinting and diverse biomedical applications. However, the flow behaviors of GelMA during the sol-gel transition, which are dependent on time and temperature, present significant challenges in printing thick scaffolds while maintaining high printability and cell viability. Moreover, the tunable properties and photocrosslinking capabilities of GelMA underscore its potential for localized drug delivery applications. Previous research has demonstrated the successful incorporation of minocycline (MH) into GelMA scaffolds for therapeutic applications. However, achieving a prolonged and sustained release of concentrated MH remains a challenge, primarily due to its small molecular size. The primary aim of this study is to investigate an optimal extrusion printing method for GelMA bioink in extrusion bioprinting, emphasizing its flow behaviors that are influenced by time and temperature. Additionally, this research seeks to explore the potential of GelMA bioink as a carrier for the sustained release of MH, specifically targeting cellular protection against oxidative stress. The material properties of GelMA were assessed and further optimization of the printing process was conducted considering both printability and cell survival. To achieve sustained drug release within GelMA, the study employed a mechanism using metal ion mediation to facilitate the interaction between MH, dextran sulfate (DS), and magnesium, leading to the formation of nanoparticle complexes (MH-DS). Furthermore, a GelMA-basedin vitromodel was developed in order to investigate the cellular protective properties of MH against oxidative stress. The experimental results revealed that the printability and cell viability of GelMA are significantly influenced by the printing duration, nozzle temperature, and GelMA concentrations. Optimal printing conditions were identified based on a thorough assessment of both printability and cell viability. Scaffolds printed under these optimal conditions exhibited exceptional printability and sustained high cell viability. Notably, it was found that lower GelMA concentrations reduced the initial burst release of MH from the MH-dextran sulfate (MH-DS) complexes, thus favoring more controlled, sustained release profiles. Additionally, MH released under these conditions significantly enhanced fibroblast viability in anin vitromodel simulating oxidative stress.
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3.
Recent development of carrier materials in anthocyanins encapsulation applications: A comprehensive literature review.
Fu, Z, Ju, H, Xu, GS, Wu, YC, Chen, X, Li, HJ
Food chemistry. 2024;:138104
Abstract
Anthocyanins are natural polyphenols belonging to the flavonoid family that possess a variety of putative health benefits when consumed in a balanced diet. However, applications of anthocyanins in, for example, functional foods are limited due to poor stability, degradation, and low transmembrane efficiency. To maintain bioactivities of anthocyanins and optimize their use, various carrier materials have been developed. Here, we reviewed the uses of the different carrier materials (organic/inorganic, micro/nano) for anthocyanin encapsulation and delivery over the past five years. The performance of different materials and interactions between anthocyanins and these materials are described. Lastly, we give our perspective on the future development trend of anthocyanin encapsulation strategies.
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4.
U-Shaped Relationship of Sodium-to-chloride Ratio on admission and Mortality in Elderly Patients with Heart Failure: A Retrospective Cohort Study.
Fu, Z, Zhang, X, Zhao, X, Wang, Q
Current problems in cardiology. 2023;(1):101419
Abstract
Serum sodium and chloride have clinical significance in the prognosis of heart failure. Little is known regarding the prognostic value of sodium-to-chloride (Na/Cl) ratio in patients with heart failure. This study sought to investigate the association between Na/Cl ratio on admission and mortality risk of elderly patients with acute heart failure in a retrospective cohort. We included 1819 patients (aged over 60) from the Zigong Heart Failure Study. Patients were grouped according to Na/Cl ratio and followed up for all-cause mortality at 3 months. Restricted cubic spline, cox proportional hazard regression and Kaplan-Meier curve were used to examine the correlation between serum Na/Cl ratio on admission and mortality risk. Restricted cubic spline analysis suggested a U-shaped association between Na/Cl ratio on admission and 3 months mortality risk (P nonlinearity <0.001), with the nadir of risk at 1.34. After adjustment for multivariate, patients with Na/Cl ratio <1.3 or ≥ 1.4 had hazard ratios for mortality of 3.58 (95% CI, 1.63-7.84) and 2.66 (95% CI, 1.23-5.72) compared with those with Na/Cl ratio of 1.3-1.4. The cumulative hazard of mortality estimates significantly differed across Na/Cl ratio groups (log-rank P<0.001). Subgroup analysis showed there were no interactions with absent or present of hyponatremia and hypochloremia (P for interaction all >0.05). Both low and high Na/Cl ratios were associated with an increased mortality risk in elderly patients with acute heart failure. Further studies need to verify these 2 biochemical phenotypes and develop corresponding treatment strategies.
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5.
Amelioration of intestinal barrier function and reduction of blood lead level in adult women with recurrent spontaneous abortion by a novel product of dietary fiber mixture, Holofood.
Tian, Y, Pan, Z, Lan, L, Chang, Y, Zhao, T, Fu, Z, Wu, S, Deng, T, Cao, M, Wang, W, et al
Journal of health, population, and nutrition. 2023;(1):63
Abstract
BACKGROUND The elevated circulating toxins secondary to the impairment of intestinal barrier integrity commonly elicit a chronic inflammatory response and finally contribute to multiple diseases. These toxins, including bacterial by-products and heavy metals, are the potent risk factors for the development of recurrent spontaneous abortion (RSA). Preclinical evidence suggests that several dietary fibers can restore intestinal barrier function and decrease the accumulation of heavy metals. However, it is uncertain whether treatment with a newly developed blend of dietary fibers product (Holofood) benefits patients with RSA. METHODS In this trial, we enrolled 70 adult women with RSA, who were randomly assigned into the experiment group and the control group in a 2:1 ratio. Upon the basis of conventional therapy, subjects in the experiment group (n = 48) received 8 weeks oral administration with Holofood three times daily at a dose of 10 g each time. Subjects without Holofood consumption were set as the control (n = 22). Blood samples were collected for the determinations of metabolic parameters, heavy mental lead, and the indices related to intestinal barrier integrity (D-lactate, bacterial endotoxin, and diamine oxidase activity). RESULTS The reduction amplitude in blood lead from baseline to week 8 was 40.50 ± 54.28 (μg/L) in the experiment group as compared with 13.35 ± 36.81 (μg/L) in the control group (P = 0.037). The decreased level of serum D-lactate from baseline to week 8 was 5.58 ± 6.09 (mg/L) in the experiment group as compared with - 2.38 ± 8.90 (mg/L, P < 0.0001) in the control group. The change in serum DAO activity from baseline to week 8 was 3.26 ± 2.23 (U/L) in the experiment group as compared with - 1.24 ± 2.22 (U/L, P < 0.0001) in the control group. Participants who received Holofood had a greater decline in blood endotoxin from baseline to week 8 than those in the control group. Moreover, by comparing with the self-baseline, Holofood consumption significantly decreased the blood levels of lead, D-lactate, bacterial endotoxin, and DAO activity. CONCLUSION Our results suggest that Holofood affords a clinically relevant improvements in blood lead level and intestinal barrier dysfunction in patients with RSA.
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6.
Calcium hypochlorite-coupled aged refuse promotes hydrogen production from sludge anaerobic fermentation.
Zhao, J, Wang, Y, Guan, D, Fu, Z, Zhang, Q, Guo, L, Sun, Y, Zhang, Q, Wang, D
Bioresource technology. 2023;:128534
Abstract
This work investigated the effect of calcium hypochlorite (CH) coupled aged refuse (AR) treatment on the enhanced hydrogen generation from sludge anaerobic dark fermentation (SADF). The enhanced mechanism was systematically revealed through sludge disintegration, organic matter biotransformation, and microbial community characteristics, etc. The experimental data showed that CH coupled AR increased the hydrogen yield to 18.1 mL/g, significantly higher than that in the AR or CH group alone. Mechanistic analysis showed that CH-coupled AR significantly promoted sludge disintegration and hydrolysis processes, providing sufficient material for hydrogen-producing bacteria. Microbiological analysis showed that CH-coupled AR increased the relative abundance of responsible hydrogen-producing microorganisms. In addition, CH-coupled AR was very effective in reducing phosphate content in the fermentation liquid and fecal coliforms in the digestate, thus facilitating the subsequent treatment of fermentation broth and digestate. CH coupled AR is an alternative strategy to increase hydrogen production from sludge.
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7.
Application of Novel Transcription Factor Machine Learning Model and Targeted Drug Combination Therapy Strategy in Triple Negative Breast Cancer.
Pang, J, Li, H, Zhang, X, Luo, Z, Chen, Y, Zhao, H, Lv, H, Zheng, H, Fu, Z, Tang, W, et al
International journal of molecular sciences. 2023;(17)
Abstract
Transcription factors (TFs) have been shown to play a key role in the occurrence and development of tumors, including triple-negative breast cancer (TNBC), with a worse prognosis. Machine learning is widely used for establishing prediction models and screening key tumor drivers. Current studies lack TF integration in TNBC, so targeted research on TF prognostic models and targeted drugs is beneficial to improve clinical translational application. The purpose of this study was to use the Least Absolute Shrinkage and Selection Operator to build a prognostic TFs model after cohort normalization based on housekeeping gene expression levels. Potential targeted drugs were then screened on the basis of molecular docking, and a multi-drug combination strategy was used for both in vivo and in vitro experimental studies. The machine learning model of TFs built by E2F8, FOXM1, and MYBL2 has broad applicability, with an AUC value of up to 0.877 at one year. As a high-risk clinical factor, its abnormal disorder may lead to upregulation of the activity of pathways related to cell proliferation. This model can also be used to predict the adverse effects of immunotherapy in patients with TNBC. Molecular docking was used to screen three drugs that target TFs: Trichostatin A (TSA), Doxorubicin (DOX), and Calcitriol. In vitro and in vivo experiments showed that TSA + DOX was able to effectively reduce DOX dosage, and TSA + DOX + Calcitriol may be able to effectively reduce the toxic side effects of DOX on the heart. In conclusion, the machine learning model based on three TFs provides new biomarkers for clinical and prognostic diagnosis of TNBC, and the combination targeted drug strategy offers a novel research perspective for TNBC treatment.
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8.
[Dachengqi decoction reduces inflammatory response and promotes recovery of gastrointestinal function in patients with mild acute pancreatitis by regulating the intestinal microbiota].
Li, J, Dai, Y, Cao, H, Xiao, T, Ge, B, Xing, L, Yu, X, Fu, Z
Zhonghua wei zhong bing ji jiu yi xue. 2023;(2):170-176
Abstract
OBJECTIVE To explore the therapeutic effect and mechanism of Dachengqi decoction on patients with mild acute pancreatitis (MAP). METHODS A parallel randomized controlled trial was conducted. Sixty-eight patients with acute pancreatitis (AP) admitted to Shanghai Traditional Chinese Medicine (TCM)-Integrated Hospital from March 2018 to February 2021 were enrolled. Referring to the condition on admission of the patients and whether they agreed to receive the Dachengqi decoction or not, they were divided into conventional treatment group and Dachengqi decoction group according to the principle of 1:1 equal randomness. Meanwhile, 20 healthy volunteers were recruited as controls. Both groups of patients were treated with octreotide, fasting, gastrointestinal decompression, antipyretic and analgesic, anti-inflammatory, inhibition of gastric acid and pancreatic juice secretion, maintenance of electrolyte balance and other western conventional medicine. The patients in the Dachengqi decoction group received Dachengqi decoction orally on the basis of routine treatment, 100 mL each time, twice a day, for seven consecutive days. The inflammation parameters [white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6)] before and after treatment and the recovery time of gastrointestinal function (first exhaust time, time to recover bowel sounds, first defecation time) of patients were recorded. 16S rRNA gene sequencing of stool samples was recorded, and normalized data were obtained after quality control and other related processing. The data were subjected to diversity analysis (Alpha diversity and Beta diversity) and linear discriminant analysis effect size analysis (LEfSe analysis) to observe changes in the gut microbiota of MAP patients. Spearman rank correlation coefficient was used to analyze the correlation between inflammatory indexes and microorganisms at the intestinal genus level. Blood, urine, stool samples, renal function, and electrocardiogram (ECG) during treatment of MAP patients were detected to assess the safety of the treatment. RESULTS Of the 68 patients with AP, 16 were excluded from moderate-severe AP, 4 were not collected or voluntarily abandoned treatment. Finally, 48 patients with MAP were enrolled, 24 in the conventional treatment group and 24 in the Dachengqi decoction group. The inflammation parameters levels at 7 days of treatment in both groups were significantly lower than those before treatment. CRP, PCT and IL-6 levels in the Dachengqi decoction group were significantly lower than those in the conventional treatment group [CRP (mg/L): 8.50 (3.50, 13.00) vs. 16.00 (9.25, 29.75), PCT (μg/L): 0.06 (0.03, 0.08) vs. 0.09 (0.05, 0.11), IL-6 (ng/L): 6.36 (3.96, 10.79) vs. 13.24 (6.69, 18.87), all P < 0.05]. The first exhaust time, time to recover bowel sounds and first defecation time in the Dachengqi decoction group were significantly shorter than those in the conventional treatment group [first exhaust time (days): 1.62±0.65 vs. 2.80±0.65, time to recover bowel sounds (days): 1.13±0.58 vs. 2.31±0.76, first defecation time (days): 3.12±0.75 vs. 4.39±0.76, all P < 0.05]. The analysis of intestinal microflora diversity showed that both the diversity and abundance of microbial communities were the highest in the healthy control group and the lowest in the conventional treatment group. In addition, the coincidence degree of microbial communities in healthy controls and MAP patients was small, while the coincidence degree of MAP patients among different treatment methods was relatively large. LEfSe analysis showed that Dachengqi decoction reduced the relative abundance of Escherichia coli-Shigella and Clostridium erysipelae, and increased the relative abundance of three beneficial bacteria, namely Lactobacillus, Rombutzia and Brutella. In the intestines of MAP patients, Lactobacillus mucilaginus and Lactobacillus conjunctus were significantly enriched. Correlation analysis showed that positive correlations between Escherichia coli-Shigella and the four inflammatory indicators including WBC, CRP, PCT, IL-6 were statistically significant (r value was 0.31, 0.41, 0.57, 0.43, respectively, all P < 0.05). There was no significant correlation between other bacteria and inflammatory indicators. During the treatment, there was no obvious abnormality in blood, urine and feces, renal function and ECG of MAP patients. CONCLUSIONS Dachengqi decoction could reduce inflammatory responses and promote recovery of intestinal microecological balance and gastrointestinal function in patients with MAP by regulating the composition of intestinal flora. No significant adverse effects were observed during the treatment period.
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9.
The role of tumor neogenesis pipelines in tumor progression and their therapeutic potential.
Fu, Z, Yuan, Y
Cancer medicine. 2023;(2):1558-1571
Abstract
Pipeline formation between tumor cells and the tumor microenvironment (TME) is a key event leading to tumor progression. These pipelines include blood vessels, lymphatics, and membranous vessels (the former two can be collectively referred to as vasculature). Pipeline regeneration is a feature of all solid tumors; it delivers nutrients to tumors and promotes tumor invasion and metastasis such that cancer cells grow rapidly, escape unfavorable TME, spread to secondary sites, generate tumor drug resistance, and promote postoperative tumor recurrence. Novel tumor therapy strategies must exploit the molecular mechanisms underpinning these pipelines to facilitate more targeted drug therapies. In this review, pipeline generation, influencing factors, pipeline functions during tumor progression, and pipeline potential as drug targets are systematically summarized.
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10.
Comparison of Bisphosphonates Versus Teriparatide in Therapy of the Glucocorticoid-Induced Osteoporosis (GIOP): A Meta-Analysis of Randomized Controlled Trials.
Dong, B, Zhou, Y, Wang, J, Li, C, Fu, Z, Huang, Y, Wang, Y, Xu, L
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2023;(4):236-244
Abstract
Osteoporosis (OP) is characterized as decreased bone mineral density (BMD) and increased risk of bone fracture. Secondary OP resulting from excess endogenous or exogenous glucocorticoid is defined as glucocorticoid-induced osteoporosis (GIOP). Current therapeutic strategies for GIOP are similar to menopausal osteoporosis, including calcium and vitamin D supplementation, bisphosphonates, and parathyroid hormone (PTH) analogues (teriparatide). Previously, several published meta-analyses compared anti-osteoporotic agents for the menopausal or aging-dependent OP. However, the physiopathologic bone metabolism of GIOP is different. In this study, we investigated the efficacy of BMD enhancement, bone fracture rate and safety of bisphosphonates versus teriparatide in the therapy of GIOP. We searched databases including PubMed, Embase, and the Cochrane Library until Jan 2023, and selected ten random clinical trials (RCT)s that compared the efficacy and/or safety of bisphosphonate versus teriparatide for GIOP patients. Teriparatide therapy increased lumber spinal BMD by 3.96% (95% CI 3.01-4.9%, p<0.00001), 1.23% (95% CI 0.36-2.1%, p=0.006) at total hip, and 1.45% (95% CI 0.31-2.58%, p=0.01) at femoral neck, respectively, compared to bisphosphonates at 18-month therapy for GIOP. Teriparatide also reduced bone fracture especially in vertebral bone (p=0.0001, RR 6.27, 95% CI 2.44-16.07), and increased bone formation and resorption marker levels. There was no difference in the incidence of adverse effects in bisphosphonate and teriparatide groups. Teriparatide showed better performance over bisphosphonate in BMD enhancement, bone fracture reduction, and bone remodeling improvement, without increasing the incidence of adverse effects.