Vitamin C enhances the sensitivity of osteosarcoma to arsenic trioxide via inhibiting aerobic glycolysis.

Osteosarcoma (OS) is a common malignant tumor disease in the department of orthopedics, which is prone to the age of adolescents and children under 20 years old. Arsenic trioxide (ATO), an ancient poison, has been reported to play a critical role in a variety of tumor treatments, including OS. However, due to certain poisonous side effects such as cardiotoxicity and hepatotoxicity, clinical application of ATO has been greatly limited. Here we report that low doses of ATO (1 µM) observably reduced the half-effective inhibitory concentration (IC50) of vitamin C on OS cells. Compared with the treatment alone, the synthetic application of vitamin C (VitC, 800 µM) and ATO (1 µM) significantly further inhibited the proliferation, migration, and invasion of OS cells and promoted cell apoptosis in vitro. Meanwhile, we observed that the combined application of VitC and ATO directly suppresses the aerobic glycolysis of OS cells with the decreased production of pyruvate, lactate, and ATP via inhibiting the expression of the critical glycolytic genes (PGK1, PGM1, and LDHA). Moreover, the combination of VitC (200 mg/kg) and ATO (1 mg/kg) with tail vein injection significantly delayed OS growth and migration of nude mice by inhibiting aerobic glycolysis of OS. Thus, our results demonstrate that VitC effectively increases the sensitivity of OS to low concentrations of ATO via inhibiting aerobic glycolysis to alleviate the toxic side effects of high doses of arsenic trioxide, suggesting that synthetic application of VitC and ATO is a promising approach for the clinical treatment of human OS.

Amino Acid-Based Protein-Mimic Hydrogel Incorporating Pro-Regenerative Lipid Mediator and Microvascular Fragments Promotes the Healing of Deep Burn Wounds.

Pro-regenerative lipid mediator 1 (PreM1) is a specialized pro-resolving lipid mediator that promotes wound healing and regenerative functions of mesenchymal stem cells (MSCs), endothelial cells, and macrophages. The healing of third-degree (3°) burns and regenerative functions of MSCs are enhanced by ACgel1, an arginine-and-chitosan-based protein-mimic hybrid hydrogel. Adipose-tissue derived microvascular fragments (MVFs) are native vascularization units and a rich source of MSCs, endothelial cells, and perivascular cells for tissue regeneration. Here we describe an innovative PreM1-MVFs-ACgel1 construct that incorporated PreM1 and MVFs into ACgel1 via optimal design and fabrication. This construct delivered PreM1 to 3°-burn wounds at least up to 7 days-post-burn (dpb), and scaffolded and delivered MVFs. PreM1-MVFs-ACgel1 promoted the healing of 3°-burns in mice, including vascularization and collagen formation. The re-epithelization and closure of 3° burn wounds were promoted by ACgel1, MVFs, PreM1, MVFs-ACgel1, PreM1-ACgel1, or PreM1-MVFs-ACgel1 at certain time-point(s), while PreM1-MVFs-ACgel1 was most effective with 97% closure and 4.69% relative epithelial gap at 13 dpb compared to saline control. The PreM1-ACgel1 and MVFs-ACgel1 also promoted blood vessel regeneration of 3°-burns although PreM1-MVFs-ACgel1 is significantly more effective. These PreM1- and/or MVF-functionalized ACgel1 have nonexistent or minimal graft-donor requirements and are promising adjuvant therapeutic candidates for treating deep burns.

Occurrence of polycyclic aromatic hydrocarbons in the Yellow River delta: Sources, ecological risks, and microbial response.

This research investigated the distribution, sources, and ecological risks of polycyclic aromatic hydrocarbons (PAHs) in the Yellow River Delta (YRD), China, emphasizing the response of soil microorganisms. The study involved quantitative analyses of 16 PAHs specified by the U.S. Environmental Protection Agency (USEPA) in both water and soil, utilizing metagenomic technique to determine the response of microbial communities and metabolism within the soil. Results noted that PAHs in the water mainly originate from pyrogenic source and in the soil originate from mixture source, with higher concentrations found in wetland areas compared to river regions. The ecological risk assessment revealed low-to-moderate risk. Microbial analysis demonstrated increased diversity and abundance of bacteria associated with PAHs in areas with higher PAHs pollution. Metagenomic insights revealed significant effects of organic carbon on PAHs degradation genes (ko00624 and ko00626), as well as significant differences in specific metabolic pathways including phenanthrene degradation, with key enzymes showing significant differences between the two environments. The study underscores the importance of understanding PAHs distribution and microbial responses to effectively manage and mitigate pollution in estuarine environments.

Effects of electron beam irradiation treatment on the structural and functional properties of okara insoluble dietary fiber.

BACKGROUND: Insoluble dietary fiber (IDF) has beneficial physiological effects, such as the promoting of intestinal peristalsis, the improving of intestinal flora, and the absorbing of some harmful substances. Okara, a byproduct of soybean processing, is a potential source of IDF. But the larger particle size and poor water solubility of okara IDF have adverse effects on sensory properties and functional characteristics. Therefore, we used an emerging type of physical method is electron beam irradiation (EBI) to modify okara, and investigated that the effects of EBI doses on the structure and functional properties of okara IDF. RESULTS: It was found that the electron beam treatment damaged the crystalline structure of IDF. Observation of the surface of EBI-treated IDF revealed a loose and porous morphology rather than the typical smooth structure. At a dose of 6 kGy, a smallest particle size and largest specific surface area of IDF was obtained, and these factors increased the apparent viscosity of an IDF dispersion. The water holding capacity, swelling capacity and the oil holding capacity upon irradiation at 6 kGy increased 74.13%, 84.76% and 41.62%, respectively. In addition, the capacity for adsorption of cholesterol, sodium cholate, glucose and nitrite ion were improved after electron beam treatment. CONCLUSION: The modified okara IDF showed improved particle sizes and hydration properties, and these changes correlated with an improvement to the rough taste of IDF and improvements to the texture and storage period upon supplementation into food. © 2022 Society of Chemical Industry.

Determination of EGFR-overexpressing tumor cells by magnetic gold-decorated graphene oxide nanocomposites based impedance sensor.

This work developed an electrochemical impedance spectroscopy (EIS) sensor for detection of EGFR (epidermal growth factor receptor)-overexpressing tumor cell and preliminary estimation of EGFR expression. Here, EGFR antibodies as the specific antibodies for cancer cells were conjugated on magnetic gold-decorated graphene oxide nanocomposites, which were used to capture the EGFR-overexpressing tumor cells. The magnetically responsive tumor cells were enriched and immobilized on a magnetic glassy carbon electrode (mGCE) surface, leading to increased electron-transfer resistance (Ret) utilized for determination of cells and preliminary evaluation of EGFR expression level. This strategy enables the enrichment, fixation and detection of tumor cells to be accomplished in a facile way. An excellent linearity in the range of 2.0 × 102 - 3.0 × 105 cell mL-1 with the detection limit of 152 cell mL-1 for MDA-MB-231 cells was obtained. Investigation on the expression levels of EGFR on various types of cells was conducted. MDA-MB-231 cells showed a distinctly higher EGFR expression, compared with MHCC97-L and L02 cells, providing the possibility for the EGFR-targeted therapy of the tumors. It is expected that the proposed sensor has the potential to be applied for cancer monitoring.

The measurement of molecular interactions, structure and physical properties of okara cellulose composite hydrogels using different analytical methods.

BACKGROUND: Aiming to address the practical problems of a low utilization rate and the serious waste of soybean residue, novel composite hydrogels based on okara cellulose before and after 2,2,6,6-tetramethylpiperidine oxide (TEMPO) oxidation and high polymers of chitosan (CH), carrageenan (CA) or Arabic gum (AG) were prepared by a homogeneous mixture in ionic liquid. RESULTS: In the present study, composite hydrogels fabricated from okara cellulose and CH, CA or AG were prepared by dissolving them in an ionic liquid, followed by heating (100 °C, 3 h) and then soaking them in a 1:1 water-isopropanol solution. The composite hydrogels prepared from TEMPO oxidation-treated cellulose were physically cross-linked to CH, CA or AG. The results showed that the intramolecular hydrogen bonds in the amorphous regions of the cellulose were disrupted, whereas the intermolecular hydrogen bonds between the biopolymers were increased, which promoted the formation of composite gels with crystalline structures. The TEMPO treatment increased the gel strength. For example, for the cellulose/CA gels, the hardness, fracturability, springiness and cohesiveness values were 5.9-, 4.3-, 2.4- and 3.6-fold higher compared to the non-treated ones, respectively. The composite hydrogels exhibited good thermal stability, swelling properties and mechanical properties. These novel composite polysaccharide-based hydrogels may therefore have great potential in various food and non-food fields. CONCLUSION: In summary, the addition of polymers (CH, CA or AG) and TEMPO oxidized cellulose was suitable for increasing the swelling, textural properties, thermal stability and rheological properties of hydrogels, which provides new ideas and new methods for the preparation of bio-based composite hydrogels. © 2022 Society of Chemical Industry.

Characteristics and structure of a soy protein isolate-lutein nanocomplex produced via high-pressure homogenization.

BACKGROUND: In recent years, nanocarriers for transporting active substances have attracted attention. This study was to explore the soy protein isolate (SPI) after high-pressure homogenization (HPH) (0, 30, 60, 90 and 120 MPa) as potential lutein carriers. RESULTS: The load amount (LA) and encapsulation efficiency (EE) of the SPI-lutein nanocomplexes at a homogenization pressure of 60 MPa were the highest (2.32 mg mL-1 and 92.85%, respectively), and the average particle size and ζ-potential of the SPI-lutein nanocomplexes were 192.1 nm and -30.06 mV, respectively. The DPPH (2,2-diphenyl-1-picrylhydrazyl) and hydroxyl-antioxidant activities of the complex increased from 12.4% and 23.3% to 52.7% and 61.07%, respectively, after the protein was treated with HPH. The surface hydrophobicity of the SPI and the SPI-lutein nanocomplexes increased with increasing homogenization pressure treatment. Fourier transform-infrared spectrophotometry analyses suggested that the homogenization treatments resulted in partial unfolding of the protein molecules, and the addition of lutein can also lead to the change of protein secondary structure. The fluorescence emission of SPI was quenched by lutein through the static quenching mechanism. Fluorescence experiments revealed that SPI and lutein had the strongest binding ability through hydrophobic interaction at a homogenization pressure of 60 MPa. CONCLUSION: After HPH, the combination of SPI and lutein was beneficial, and the stability of lutein also improved after the combination. This study is conducive to expanding the application of soybean protein in the food industry. © 2022 Society of Chemical Industry.

Blue LED causes autophagic cell death in human osteosarcoma by increasing ROS generation and dephosphorylating EGFR.

Osteosarcoma (OS) is the most common primary malignant bone tumour in adolescence. Lately, light-emitting diodes (LED)-based therapy has emerged as a new promising approach for several diseases. However, it remains unknown in human OS. Here, we found that the blue LED irradiation significantly suppressed the proliferation, migration and invasion of human OS cells, while we observed blue LED irradiation increased ROS production through increased NADPH oxidase enzymes NOX2 and NOX4, as well as decreased Catalase (CAT) expression levels. Furthermore, we revealed blue LED irradiation-induced autophagy characterized by alterations in autophagy protein markers including Beclin-1, LC3-II/LC3-I and P62. Moreover, we demonstrated an enhanced autophagic flux. The blockage of autophagy displayed a remarkable attenuation of anti-tumour activities of blue LED irradiation. Next, ROS scavenger N-acetyl-L-cysteine (NAC) and NOX inhibitor diphenyleneiodonium (DPI) blocked suppression of OS cell growth, indicating that ROS accumulation might play an essential role in blue LED-induced autophagic OS cell death. Additionally, we observed blue LED irradiation decreased EGFR activation (phosphorylation), which in turn led to Beclin-1 release and subsequent autophagy activation in OS cells. Analysis of EGFR colocalization with Beclin-1 and EGFR-immunoprecipitation (IP) assay further revealed the decreased interaction of EGFR and Beclin-1 upon blue LED irradiation in OS cells. In addition, Beclin-1 down-regulation abolished the effects of blue LED irradiation on OS cells. Collectively, we concluded that blue LED irradiation exhibited anti-tumour effects on OS by triggering ROS and EGFR/Beclin-1-mediated autophagy signalling pathway, representing a potential approach for human OS treatment.

Barriers and facilitators to online medical and nursing education during the COVID-19 pandemic: perspectives from international students from low- and middle-income countries and their teaching staff.

BACKGROUND: The COVID-19 pandemic posed a huge challenge to the education systems worldwide, forcing many countries to provisionally close educational institutions and deliver courses fully online. The aim of this study was to explore the quality of the online education in China for international medical and nursing students from low- and middle-income countries (LMICs) as well as the factors that influenced their satisfaction with online education during the COVID-19 pandemic. METHODS: Questionnaires were developed and administered to 316 international medical and nursing students and 120 teachers at a university in China. The Chi-square test was used to detect the influence of participants' personal characteristics on their satisfaction with online education. The Kruskal-Wallis rank-sum test was employed to identify the negative and positive factors influencing the online education satisfaction. A binary logistic regression model was performed for multiple-factor analysis to determine the association of the different categories of influential factors-crisis-, learner-, instructor-, and course-related categories, with the online education satisfaction. RESULTS: Overall, 230 students (response rate 72.8%) and 95 teachers (response rate 79.2%) completed the survey. It was found that 36.5% of students and 61.1% of teachers were satisfied with the online education. Teachers' professional title, students' year of study, continent of origin and location of current residence significantly influenced the online education satisfaction. The most influential barrier for students was the severity of the COVID-19 situation and for teachers it was the sense of distance. The most influential facilitating factor for students was a well-accomplished course assignment and for teachers it was the successful administration of the online courses. CONCLUSIONS: Several key factors have been identified that affected the attitudes of international health science students from LMICs and their teachers towards online education in China during the COVID-19 pandemic. To improve the online education outcome, medical schools are advised to promote the facilitating factors and cope with the barriers, by providing support for students and teaching faculties to deal with the anxiety caused by the pandemic, caring for the state of mind of in-China students away from home, maintaining the engagement of out-China students studying from afar and enhancing collaborations with overseas institutions to create practice opportunities at students' local places.

Impact of COVID-19 pandemic on the professional intention of medical and related students.

BACKGROUND: The outbreak of COVID-19 has led to increased workload and infection risks among medical staff. This situation may influence current medical and health-related students' decision on the choices of their future careers. Hence, this study investigated the impact of COVID-19 on their future career intentions. METHODS: This is a cross-sectional observational study that included medical and health-related students from three universities between October 2020 and January 2021. The study questionnaire was divided into two main sections: Section 1, which comprised students' basic information. And section 2 focused mainly on the impact of COVID-19 pandemic on students' professional intentions. The chi-squared χ2 test was used to compare the responses before and after the pandemic outbreak among Chinese and non-Chinese students. RESULTS: In overall, 1253 students completed the questionnaires. The responses showed that the number of students who preferred clinical medicine, public health, pharmacy and oral medicine increased significantly after the pandemic outbreak. In contrast, the number of students who chose nursing and medical technology decreased significantly. The change mainly occurred in Chinese students, predominantly females. Half of students (50.35%) were more willing to engage in medical and health work after completing their current program. Also, 36.39% of students felt that knowledge was too limited in the pandemic's face and would like to continue studying after graduation to gain more knowledge. Due to the pandemic, 34.18% of students would like a future workplace near their hometown, and 19.63% preferred to work in urban areas. CONCLUSION: The COVID-19 outbreak impacted current medical and health-related students' career planning on their future workplaces and employment time choices. Additionally, the pandemic influenced the intention of Chinese students in choosing their future careers. This study provided the basis for the policymaking, specialty setting of colleges and supplied the medical health department's talent reserve information.

The Long Non-coding RNA-ORLNC1 Regulates Bone Mass by Directing Mesenchymal Stem Cell Fate.

Bone marrow-derived mesenchymal stem cells (BMSCs) have the potential to differentiate into osteoblasts or adipocytes, and the shift between osteogenic and adipogenic differentiation determines bone mass. The aim of this study was to identify whether lncRNAs are involved in the differentiation commitment of BMSCs during osteoporosis. Here, we found ORLNC1, a functionally undefined lncRNA that is highly conserved, which exhibited markedly higher expression levels in BMSCs, bone tissue, and the serum of OVX-induced osteoporotic mice than sham-operated counterparts. Notably, a similar higher abundance of lncRNA-ORLNC1 expression was also observed in the bone tissue of osteoporotic patients. The transgenic mice overexpressing lncRNA-ORLNC1 showed a substantial increase in the osteoporosis-associated bone loss and decline in the osteogenesis of BMSCs. The BMSCs pretreated with lncRNA-ORLNC1-overexpressing lentivirus vector exhibited the suppressed capacity of osteogenic differentiation and oppositely enhanced adipogenic differentiation. We then established that lncRNA-ORLNC1 acted as a competitive endogenous RNA (ceRNA) for miR-296. Moreover, miR-296 was found markedly upregulated during osteoblast differentiation, and it accelerated osteogenic differentiation by targeting Pten. Taken together, our results indicated that the lncRNA-ORLNC1-miR-296-Pten axis may be a critical regulator of the osteoporosis-related switch between osteogenesis and adipogenesis of BMSCs and might represent a plausible therapeutic target for improving osteoporotic bone loss.

MicroRNA-92b-5p modulates melatonin-mediated osteogenic differentiation of bone marrow mesenchymal stem cells by targeting ICAM-1.

Osteoporosis is closely associated with the dysfunction of bone metabolism, which is caused by the imbalance between new bone formation and bone resorption. Osteogenic differentiation plays a vital role in maintaining the balance of bone microenvironment. The present study investigated whether melatonin participated in the osteogenic commitment of bone marrow mesenchymal stem cells (BMSCs) and further explored its underlying mechanisms. Our data showed that melatonin exhibited the capacity of regulating osteogenic differentiation of BMSCs, which was blocked by its membrane receptor inhibitor luzindole. Further study demonstrated that the expression of miR-92b-5p was up-regulated in BMSCs after administration of melatonin, and transfection of miR-92b-5p accelerated osteogenesis of BMSCs. In contrast, silence of miR-92b-5p inhibited the osteogenesis of BMSCs. The increase in osteoblast differentiation of BMSCs caused by melatonin was attenuated by miR-92b-5p AMO as well. Luciferase reporter assay, real-time qPCR analysis and western blot analysis confirmed that miR-92b-5p was involved in osteogenesis by directly targeting intracellular adhesion molecule-1 (ICAM-1). Melatonin improved the expression of miR-92b-5p, which could regulate the differentiation of BMSCs into osteoblasts by targeting ICAM-1. This study provided novel methods for treating osteoporosis.

A Novel Pseudo-Protein-Based Biodegradable Nanomicellar Platform for the Delivery of Anticancer Drugs.

Amino acid-based poly(ester amide)s are a new family of biodegradable polymers that exhibit "pseudo-protein" characteristics and the structural varieties of poly(ester amide)s make them hold great potential in multiple biomedical applications. In this study, a lysine-phenylalanine-based pseudo-protein is developed as the self-assembled nanomicellar carrier for efficient delivery of doxorubicin. The lysine moieties from the pseudo-protein provide available sites for further functionalization, and methylcoumarin is introduced for easy and photocontrollable crosslinking, to effectively improve the micellar stability in serum containing environment and against dilution. However, photocrosslinks do not bring in any barrier for the intracellular release of doxoubicin. Doxorubicin release is significantly accelerated by proteolytic enzyme, due to the biodegradability of pseudo-protein micelles. In addition, pseudo-protein delivery system exhibits unique interactions with HCT116 human colon cancer cells. Doxorubicin loaded in pseudo-protein micelles colocalizes with mitochondria and endolysosomes, while free doxorubicin is distributed only in the nuclei. Doxorubicin-loaded pseudo-protein micelles stimulate increased level of intracellular reactive oxygen species and mitochondrial damage. Free doxorubicin induces conditional apoptosis in HCT116 cells between 0.5× 10-6 and 2 × 10-6 m, while DOX loaded in pseudo-protein micelles induces apoptosis over a higher/broader concentration range (2 × 10-6 -10 × 10-6 m).

Application of a liquid chromatography-tandem mass spectrometry method to the pharmacokinetics, tissue distribution and excretion in the study of anemoside B4, a novel antiviral agent candidate, in rats.

A simple, sensitive and reliable LC-MS/MS method was developed and validated for the quantification of anemoside B4, a potential antiviral constituent isolated from Pulsatilla chinensis in rat plasma, tissue, bile, urine and feces. All biological samples were prepared by protein precipitation method, and ginsenoside-Rg1 was chosen as the internal standard (IS). The analyte and IS were separated using a C18 column (2.1 × 50 mm, 1.8 µm) and a mobile phase consisting of 0.1% formic acid in water (v/v) and acetonitrile running at a flow rate of 0.2 mL/min for 5 min. The multiple reaction monitoring transitions were monitored at m/z 1219.5-749.5 for anemoside B4 and 845.4-637.4 for ginsenoside-Rg1 in electrospray ionization negative mode. The calibration curve was linear in the range of 10-2000 ng/mL for all biological matrices with a lower limit of quantification of 10 ng/mL. The validated method was successfully applied to a pharmacokinetics, tissue distribution and excretion study. These preclinical data will be beneficial for further development of anemoside B4 in future studies.

[Association between depression during pregnancy and low birth weight in neonates: a Meta analysis].

OBJECTIVE: To study the association between depression during pregnancy and low birth weight in neonates, and to provide a scientific basis for the prevention of low birth weight. METHODS: Cohort studies on the association between depression during pregnancy and low birth weight were collected and a Meta analysis was performed. Data were extracted independently by two investigators, and quality assessment was performed according to Newcastle-Ottawa Scale. The Egger's test was used to evaluate publication bias. RESULTS: A total of 12 cohort studies with 37 192 samples were included. The results of the Meta analysis showed that depression during pregnancy was associated with low birth weight (Z=2.08, P=0.038), and the neonates whose mothers had depression during pregnancy tended to have a high risk of low birth weight (RR=1.303, 95%CI: 1.015-1.672). The sensitivity analysis showed that the results of this Meta analysis were stable and reliable, and the Egger's test showed no publication bias. CONCLUSIONS: Depression during pregnancy may be a risk factor for low birth weight in neonates.

[Risk factors for congenital heart disease in Chinese neonates: a Meta analysis].

OBJECTIVE: To investigate the major risk factors for congenital heart disease (CHD) in Chinese neonates and to provide a reference for the prevention of CHD. METHODS: A literature search was performed to collect the case-control studies on the risk factors for CHD in Chinese neonates published in 2001-2016. The relevant data were extracted accordingly. The quality of included studies was assessed by Newcastle-Ottawa Scale. Sensitivity analysis was conducted using different models to analyze the same data. The publication bias was assessed by Egger's test. RESULTS: A total of 17 case-control studies involving 2 930 cases and 4 952 controls were included. The Meta analysis showed that the major risk factors for CHD in Chinese neonates were as follows: mother with advanced age (OR=2.649, 95%CI: 1.675-4.189), cold or fever (OR=4.558, 95%CI: 2.901-7.162), medication use in early pregnancy (OR=3.961, 95%CI: 2.816-5.573), passive smoking (OR=2.766, 95%CI: 1.982-3.859), abnormal childbearing history (OR=2.992, 95%CI: 1.529-5.856), noise exposure (OR=3.030, 95%CI: 1.476-6.217), radiation exposure (OR=2.363, 95%CI: 1.212-4.607), decoration (OR=4.979, 95%CI: 3.240-7.653), gestational diabetes (OR=5.090, 95%CI: 3.132-8.274), and pet raising (OR=2.048, 95%CI: 1.385-3.029). CONCLUSIONS: Mothers with advanced age, cold or fever, medication use in early pregnancy, passive smoking, abnormal childbearing history, noise exposure, radiation exposure, decoration, gestational diabetes, and pet raising may increase the risk of CHD in Chinese neonates.

Self-Assembled Cationic Biodegradable Nanoparticles from pH-Responsive Amino-Acid-Based Poly(Ester Urea Urethane)s and Their Application As a Drug Delivery Vehicle.

The objective of this study is to develop a new family of biodegradable and biologically active copolymers and their subsequent self-assembled cationic nanoparticles as better delivery vehicles for anticancer drugs to achieve the synergism between the cytotoxicity effects of the loaded drugs and the macrophage inflammatory response of the delivery vehicle. This family of cationic nanoparticles was formulated from a new family of amphiphilic cationic Arginine-Leucine (Arg-Leu)-based poly(ester urea urethane) (Arg-Leu PEUU) synthesized from four building blocks (amino acids, diols, glycerol α-monoallyl ether, and 1,6 hexamethylene diisocyanate). The chemical, physical, and biological properties of Arg-Leu PEUU biomaterials can be tuned by controlling the feed ratio of the four building blocks. The Arg-Leu PEUU copolymers have weight-average molecular weights from 13.4 to 16.8 kDa and glass-transition temperatures from -3.4 to -4.6 °C. The self-assembled cationic nanoparticles (Arg-Leu PEUU NPs) were prepared using a facile dialysis method. Arg-Leu PEUU NPs have average diameters ranging from 187 to 272 nm, show good biocompatibility with 3T3 fibroblasts, and they support bovine aortic endothelial cell (BAEC) proliferation and adhesion. Arg-Leu PEUU NPs also enhanced the macrophages' production of tumor necrosis factor-α (TNF-α) and nitric oxide (NO), but produced relatively low levels of interleukin-10 (IL-10), and therefore, the antitumor activity of macrophages might be enhanced. Arg-Leu PEUU NPs were taken up by HeLa cells after 4 h of incubation. The in vitro hemolysis assay showed the cationic Arg-Leu PEUU NPs increased their chance of endosomal escape at a more acidic pH. Doxorubicin (DOX) was successfully incorporated into the Arg-Leu PEUU NPs, and the DOX-loaded Arg-Leu PEUU NPs exhibited a pH-dependent drug release profile with accelerated release kinetics in a mild acidic condition. The DOX-loaded 6-Arg-4-Leu-4 A/L-2/1 NPs showed higher HeLa cell toxicity than the free DOX at the same concentration after 24 h of treatment. The results suggest the cationic Arg-Leu PEUU NPs could potentially be a useful carrier family for hydrophobic anticancer drugs and produce a synergistic effect between DOX cytotoxicity and the production of TNF-α and NO by macrophages.

Magnetic nanoparticles-immobilized phospholipase LM and phospholipase 3G: Preparation, characterization, and application on soybean crude oil degumming.

Immobilization of enzymes improves their stability and recoverability and is therefore crucial for scientific research and industrial applications. In this study, phospholipase LM (PLLM) and phospholipase 3G (PL3G) were immobilized using Fe3O4@SiO2@CS-COOH polycarboxylated magnetic nanoparticles (MNPs-COOH) as carriers and then used for degumming soybean crude oil. The immobilization rates and relative enzyme activities of these immobilized phospholipases were evaluated to determine the optimal immobilization parameters. The enzyme activities of PLLM-MNPs-COOH and PL3G-MNPs-COOH were 2830.87 and 1162.25 U/g, respectively. Enzymatic properties of the free and immobilized enzymes were compared. Both immobilized phospholipases exhibited higher condition tolerance and stability after immobilization. After 30-day storage at 4 °C, both immobilized phospholipases retained approximately 1.3 times the residual activity of the corresponding free phospholipases. When the degumming conditions were optimized, the residual phosphorus contents of the PLLM-MNPs-COOH- and PL3G-MNPs-COOH-degummed oils were 4.91 and 7.41 mg/kg, respectively, which were consistent with the safety standards for oil products. After 6 cycles, PLLM-MNPs-COOH and PL3G-MNPs-COOH continued to preserve 71.88 % and 70.00 % of their initial activities, respectively. The immobilized phospholipases are thus suitable for degumming soybean crude oil, and the mixed enzymes exhibited better degumming potential.

FSGT capsule inhibits IL-1ß-induced inflammation in chondrocytes and ameliorates osteoarthritis by upregulating LncRNA PACER and downregulating COX2/PGE2.

OBJECTIVE: To explore the efficacy and potential mechanism of Fengshi Gutong capsule (FSGTC) in osteoarthritis (OA) inflammation. METHODS: The impact of FSGTC on laboratory indicators of OA patients was explored using data mining technology and association rule analysis. Then, the OA cell model was constructed by inducing chondrocytes (CHs) with interleukin-1ß (IL-1ß). In the presence of FSGTC intervention, the regulatory mechanism of PACER/COX2/PGE2 in OA-CH viability and inflammatory responses was evaluated. RESULTS: Retrospective data mining showed that FSGTC effectively reduced inflammation indexes (ESR, HCRP) of OA patients. Cell experiments showed that LncRNA PACER (PACER) silencing inhibited the proliferation activity of OA-CHs, increased the level of COX2 protein, elevated the levels of PGE2, TNF-α, and IL-1ß, and decreased the levels of IL-4 and IL-10 (p < .01). On the contrary, FSGTC-containing serum reversed the effect of PACER silencing on OA-CHs (p < .01). After the addition of COX2 pathway inhibitor, the proliferation activity of OA-CHs was enhanced; the levels of PGE2, TNF-α, and IL-1ß were decreased while the levels of IL-4 and IL-10 were increased (p < .01). CONCLUSION: FSGTC inhibits IL-1ß-induced inflammation in CHs and ameliorates OA by upregulating PACER and downregulating COX2/PGE2.

Effect of ultrasonic pretreatment on physicochemical, thermal, and rheological properties of chemically modified corn starch.

This study investigated the effects of ultrasonic and three chemical individual and dual modification treatments on corn starch's physicochemical, thermal, and rheological properties. Ultrasonication and the three chemical treatments disrupted the starch granules with a decrease in particle size and a significant increase in the ζ-potential. The hydrophilicity of ultrasonic-oxidized dual-modified starch (U-O-CS) was the highest, at 0.854 g/g. The lipophilicity of ultrasonic-esterified dual-modified starch (U-E-CS) was the highest, at 1.485 g/g. The gelatinization temperature of ultrasonic, oxidation, and cross-linking modified starches increased significantly, with cross-linking starches being the largest. Oxidative treatment significantly decreased the starch's G' and G" and weakened the textural properties. The rheological properties of U-O-CS were further weakened. The G' of the starch decreased after the esterification treatment, while the G" increased, and the textural properties were cut. The maximum rheological and textural properties were obtained for crosslinked modification, with a hardness value of 284.70 g.