Co-delivery of siAEG-1 and doxorubicin to treat osteosarcoma via nanomicelles for azide-alkyne "click" conjugation of poly(l-lysine) dendrons onto Zein.

Astrocyte elevated gene-1 (AEG-1) oncogene is a notorious and evolving target in a variety of human malignancies including osteosarcoma. The RNA interference (RNAi) has been clinically proven to effectively knock down specific genes. To successfully implement RNAi in vivo, protective vectors are required not only to protect unstable siRNAs from degradation, but also to deliver siRNAs to target cells with controlled release. Here, we synthesized a Zein-poly(l-lysine) dendrons non-viral modular system that enables efficient siRNA-targeted AEG-1 gene silencing in osteosarcoma and encapsulation of antitumor drugs for controlled release. The rational design of the ZDP integrates the non-ionic and low immunogenicity of Zein and the positive charge of the poly(l-lysine) dendrons (DPLL) to encapsulate siRNA and doxorubicin (DOX) payloads via electrostatic complexes and achieve pH-controlled release in a lysosomal acidic microenvironment. Nanocomplexes-directed delivery greatly improves siRNA stability, uptake, and AEG-1 sequence-specific knockdown in 143B cells, with transfection efficiencies comparable to those of commercial lipofectamine but with lower cytotoxicity. This AEG-1-focused RNAi therapy supplemented with chemotherapy inhibited, and was effective in inhibiting the growth in of osteosarcoma xenografts mouse models. The combination therapy is an alternative or combinatorial strategy that can produce durable inhibitory responses in osteosarcoma patients.

Fabrication and release property of self-assembled garlic essential oil-amylose inclusion complex by pre-gelatinization coupling with high-speed shear.

Our aim was to investigate the preparation of self-assembled garlic essential oil-amylose inclusion complexes (SGAs) using garlic essential oil (GEO) and corn starch (CS), and evaluated their release properties. SGAs were fabricated by pre-gelatinization coupling with high-speed shear at different GEO-CS mass ratios. When the mass ratio of GEO to pre-gelatinized corn starch was set at 15 % (SGA-15 %), with a fixed shear rate of 9000 rpm and a shear time of 30 min, the allicin content was 0.573 ± 0.023 mg/g. X-ray diffraction (XRD) results revealed a starch V-type crystalline structure in SGAs with peaks at 13.0°, 18.0°, and 20.0° (2θ). Fourier Transform Infrared (FTIR) spectra of SGAs displayed a shift in the characteristic peak of diallyl trisulfide from 987.51 cm-1 to 991.45 cm-1. Scanning electron microscope (SEM) images revealed that SGAs exhibited lamellar structures covered with small granules. SGAs exhibited higher residual mass (approximately 12 %) than other samples. The resistant starch content of SGAs increased from 10.1 % to 18.4 % as GEO contents varied from 5 % to 15 %. In vitro digestion tests showed that about 53.21 % of allicin remained in SGA-15 % after 8 h. Therefore, this dual treatment can be a new method for fabricating controlled-release inclusion complexes of guest molecules.

Qingchang Wenzhong Decoction ameliorates intestinal inflammation and intestinal barrier dysfunction in ulcerative colitis via the GC-C signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colonic mucosa, accompanied with abdominal pain, and bloody diarrhea. Currently, clinical treatment options for UC are limited. Qingchang Wenzhong Decoction (QCWZD) is an effective prescription of traditional Chinese medicine for the treatment of UC. However, the mechanism of QCWZD in alleviating intestinal barrier dysfunction in UC has not been clearly explained. AIM OF THE STUDY: To determine the mechanism whereby QCWZD promotes the recovery of intestinal barrier dysfunction in UC. MATERIALS AND METHODS: A secondary analysis of colonic mucosa from UC patients acquired from a prior RCT clinical trial was performed. The effects of QCWZD on intestinal mucus and mechanical barriers in UC patients were evaluated using colon tissue paraffin-embedded sections from UC patients. The mechanism was further investigated by in vivo and in vitro experiments. UC mice were established in sterile water with 3.0% dextran sodium sulfate (DSS). Meanwhile, mice in the treatment group were dosed with QCWZD or mesalazine. In vitro, an intestinal barrier model was constructed using Caco-2 and HT29 cells in co-culture. GC-C plasmid was used to overexpress/knock down GC-C to clarify the target of QCWZD. HE, AB-PAS, ELISA, immunohistochemistry and immunofluorescence assays were used to assess the level of colonic inflammation and intestinal barrier integrity. Rt-qPCR, Western Blot were used to detect the expression of genes and proteins related to GC-C signaling pathway. Molecular docking was used to simulate the binding sites of major components of QCWZD to GC-C. RESULTS: In UC patients, QCWZD increased mucus secretion, goblet cell number, and promoted MUC2 and ZO-1 expression. QCWZD accelerated the recovery of UC mice from DSS-induced inflammation, including weight gain, reduced disease activity index (DAI) scores, colon length recovery, and histological healing. QCWZD promoted mucus secretion and increased ZO-1 expression in in vivo and in vitro experiments, thereby repairing mucus mechanical barrier damage. The effects of QCWZD are mediated through regulation of the GC-C signaling pathway, which in turn affects CFTR phosphorylation and MUC2 expression to promote mucus secretion, while inhibiting the over-activation of MLCK and repairing tight junctions to maintain the integrity of the mechanical barrier. Molecular docking results demonstrate the binding of the main components of QCWZD to GC-C. CONCLUSION: Our study demonstrated that QCWZD modulates the GC-C signaling pathway to promote remission of mucus-mechanical barrier damage in the UC. The clarification of the mechanism of QCWZD holds promise for the development of new therapies for UC.

Protective Effects of a Jellyfish-Derived Thioredoxin Fused with Cell-Penetrating Peptide TAT-PTD on H2O2-Induced Oxidative Damage.

Thioredoxin (Trx) plays a critical role in maintaining redox balance in various cells and exhibits anti-oxidative, anti-apoptotic, and anti-inflammatory effects. However, whether exogenous Trx can inhibit intracellular oxidative damage has not been investigated. In previous study, we have identified a novel Trx from the jellyfish Cyanea capillata, named CcTrx1, and confirmed its antioxidant activities in vitro. Here, we obtained a recombinant protein, PTD-CcTrx1, which is a fusion of CcTrx1 and protein transduction domain (PTD) of HIV TAT protein. The transmembrane ability and antioxidant activities of PTD-CcTrx1, and its protective effects against H2O2-induced oxidative damage in HaCaT cells were also detected. Our results revealed that PTD-CcTrx1 exhibited specific transmembrane ability and antioxidant activities, and it could significantly attenuate the intracellular oxidative stress, inhibit H2O2-induced apoptosis, and protect HaCaT cells from oxidative damage. The present study provides critical evidence for application of PTD-CcTrx1 as a novel antioxidant to treat skin oxidative damage in the future.

Protective Effects of Epigallocatechin-3-gallate (EGCG) against the Jellyfish Nemopilema nomurai Envenoming.

Jellyfish stings are the most common marine animal injuries worldwide, with approximately 150 million envenomation cases annually, and the victims may suffer from severe pain, itching, swelling, inflammation, arrhythmias, cardiac failure, or even death. Consequently, identification of effective first aid reagents for jellyfish envenoming is urgently needed. Here, we found that the polyphenol epigallocatechin-3-gallate (EGCG) markedly antagonized the hemolytic toxicity, proteolytic activity, and cardiomyocyte toxicity of the jellyfish Nemopilema nomurai venom in vitro and could prevent and treat systemic envenoming caused by N. nomurai venom in vivo. Moreover, EGCG is a natural plant active ingredient and widely used as a food additive without toxic side effects. Hence, we suppose that EGCG might be an effective antagonist against systemic envenoming induced by jellyfish venom.

Genome-wide identification and expression analysis of SUT gene family members in sugar beet (Beta vulgaris L.).

Sucrose transporters (SUTs) play an important role in the transmembrane transport and distribution of sucrose, and their activity has an important impact on plant growth and crop yield. In this study, the SUT gene family was identified in the whole beet genome using bioinformatics methods, and gene characteristics, subcellular localization prediction, phylogenetic evolution, promoter cis-elements and expression patterns were systematically analyzed. A total of 9 SUT gene family members were identified from in beet genome and divided into 3 different groups (group 1, group 2, and Group 3), which were unevenly distributed on 4 chromosomes. Most SUT family members contained photoresponsive and hormone-regulated response elements. Subcellular localization prediction showed that the BvSUT genes are all located in the inner membrane, and most of the terms identified through GO enrichment analysis are classified as "membrane" related. The results of qRT-PCR showed that the expression level of the BvSUT gene was significantly higher in the tuber enlargement stage (100-140 d) than in other stages. This study is the first to analyze the BvSUT gene family in sugar beet, and it provides a theoretical basis for the functional exploration and application of SUT genes in crop improvement, especially in sugar crops.

Curative Effect and Mechanisms of Radix Arnebiae Oil on Burn Wound Healing in Rats.

Radix arnebiae oil (RAO) is a clinically useful traditional Chinese medical formula with outstanding curative effects on burns. However, the mechanism of the effect of RAO on wound healing remains unclear. The present study investigates the molecular mechanisms of the potential curative effect of RAO on wound healing. The concentrations of the main constituents, shikonin, imperatorin, and ferulic acid in RAO detected by HPLC were 24.57, 3.15, and 0.13 mg/mL, respectively. A rat burn model was established, and macroscopic and histopathological studies were performed. RAO significantly accelerated wound closure and repair scarring, increased superoxide dismutase activities, and reduced malondialdehyde. RAO also downregulated interleukin (IL)-6, IL-1ß and tumor necrosis factor-α in wound tissues and increased secretion of vascular endothelial growth factor, epidermal growth factor, and transforming growth factor (TGF)-ß1. RAO increased the gene expression of TGF-ß1, type I and III collagen, and increased the protein expression of TGF-ß1 and phosphorylation of PI3K and Akt. In conclusion, RAO likely promotes wound healing via antioxidant and anti-inflammatory activities and increases re-epithelization. Activation of the TGF-ß1/PI3K/Akt pathway may play an important role in the healing efficacy of RAO. These findings suggest that RAO could be a promising alternative local treatment for burn wound healing.

Ethyl Acetate Extract from Artemisia argyi Prevents Liver Damage in ConA-Induced Immunological Liver Injury Mice via Bax/Bcl-2 and TLR4/MyD88/NF-κB Signaling Pathways.

BACKGROUND: Immunological liver injury (ILI) is a common liver disease and lacks potent drugs for treatment. Artemisia argyi Lévl. et Vant. (A. argyi), a medicinal and edible homologous plant usually used in diet therapy to cure various liver diseases, provides a great option for the prevention of ILI. PURPOSE: To investigate the effect that ethyl acetate extract of A. argyi (AaEA) on Concanavalin A (ConA)-induced ILI and the mechanism of regulating Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways. METHODS: The chemical components of AaEA were studied by LC-MS. In animal experiments, the positive control group was administrated diammonium glycyrrhizinate (DIG, 100 mg/kg), while different doses of AaEA groups (AaEA-H, AaEA-M, AaEA-L) were pretreated with AaEA 2.00, 1.00, and 0.50 g/kg, respectively, by intragastric for seven days, once every day. Then, ConA (12.00 mg/kg) was used through tail intravenous injection to establish the ILI model. The blood samples and livers were collected to test the degree of liver dysfunction, inflammation, oxidative stress, histopathological changes, and cell apoptosis. Real-time PCR and Western blotting analysis were used to explain the mechanism of regulating Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways. RESULTS: The way in which AaEA prevents liver damage in immunological liver injury (ILI) mice caused by ConA was investigated for the first time. Pretreatment with AaEA reduced the expression of ALT, AST, and inflammatory factors (TNF-α and IFN-γ). Meanwhile, AaEA also reduced MDA levels but upregulated the contents of IL-4, SOD, and GSH-px, alleviating oxidative stress induced by ILI. Western blotting and real-time PCR analysis demonstrated that AaEA could regulate the expression level and relative mRNA expression of key proteins on Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways. Finally, 504 components from AaEA were identified by LC-MS analysis, mainly including flavones, phenolic acids, and terpenoids with anti-inflammatory and liver protective activities, which highlights the potential of AaEA for diet treatment of ILI. CONCLUSION: AaEA can work against ConA-induced ILI in mice by regulating Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways, which has the potential to be a great strategy for the prevention of ILI.

[Enrichment and Ecological Risk Assessment of Available Phosphorus in Paddy Soil of Fujian Province Over Past 40 years].

The ecological risks such as water eutrophication caused by soil phosphorus loss have attracted extensive attention, and its dynamic changes and enrichment effects are the basis for formulating reasonable control measures. In this study, based on the paddy soils of 1.8×106 hm2 in Fujian province, the dynamic changes and ecological risks of available phosphorus in paddy soils over the past 40 years were analyzedusing a soil database of 1:50000. The soil database contained 1471, 215534, and 2895 paddy soil samples in different periods, respectively. The paddy soil samples were derived from the 1982 Second National Soil Census, the 2008 Ministry of Agriculture and Rural Areas Soil Testing and Formulated Fertilization Project and the 2018 Ministry of Agriculture, and the Rural Areas Arable Land Quality Monitoring Project, respectively. The results showed that from 1982 to 2018, the content of available phosphorus in paddy soils increased by 47 mg·kg-1, and the enriched area reached 1.65×106 hm2, accounting for 91% of the total paddy soils in Fujian province. From 1982 to 2008, the available phosphorus content of paddy soils in Fujian province increased by 28 mg·kg-1, with the enriched area reaching 1.47×106 hm2, accounting for 82% of the total paddy soils in Fujian province. From 2008 to 2018, the available phosphorus content of paddy soils in Fujian province increased by 19 mg·kg-1, with the enriched area reaching 1.22×106 hm2, accounting for 69% of the total paddy soils in Fujian province. Further ecological risk assessment showed that from 2008 to 2018, the area of paddy soil with ecological phosphorus enrichment risk in the province gradually increased, mainly distributed in percogenic paddy soils and hydromorphic paddy soils with a slope of less than 2°. In the future, effective phosphorus fertilizer management measures should be formulated for different types of paddy soil to prevent the occurrence of environmental problems such as water eutrophication.

Role of jellyfish in mesozooplankton community stability in a subtropical bay under the long-term impacts of temperature changes.

To understand zooplankton community changes in the context of climate change and anthropogenic disturbances, we analyzed mesozooplankton samples from four seasons in the subtropical Daya Bay, which is susceptible to perceived disturbances in the South China Sea. The zooplankton community was found to be divided into two clusters, namely the Outer-bay Cluster (OC) comprising Noctiluca scintillans, Temora turbinata, and Paracalanus spp., and the Inner-bay Cluster (IC) which was dominated by Pseudevadne tergestina, Oikopleura rufescens, and Paracalanus spp. The OC was recorded in waters with low Chl a concentrations and high salinity, coinciding with open seawater intrusion. The IC occurred in waters with high Chl a concentrations, low salinity, with terrestrial inputs from the Dan'ao River. The dominant cladoceran species has changed in spring from Penilia avirostris to Pseudevadne tergestina owing to suitable temperature conditions and the low wind speed in this region. Most of the keystone species recorded during all seasons were found to be copepods based on co-occurrence network analysis. Numbers of keystone jellyfish (cnidaria) species, such as Geryonia proboscidalis, Chelophyes contorta, and Aeginura grimaldi were significantly higher in summer than in other seasons due to a low-temperature seawater intrusion, which can result in the highest stability of community structures and affect coastal food webs and fishery resources. Our results highlight that zooplankton community succession may occur with long-term temperature changes in the subtropical Daya Bay under global climate change conditions.

Coal gangue modified bioretention system for runoff pollutants removal and the biological characteristics.

In this study, coal gangue (CG) was applied as media in bioretention system to remove runoff pollutant. CG modified bioretention systems show good removal efficiency towards runoff pollutant due to the high adsorption capacity of CG. The removal of total phosphorus (TP), total nitrogen (TN), ammonia (NH4+-N) and chemical oxygen demand (COD) by CG modified bioretention systems was influenced by diverse rainfall conditions including rainfall concentration, recurrence period and drying period, and their removal rate ranged 94-99%, 30-70%, 83-97% and 33-86%, respectively. The effluent concentration of Zn, Pb and Cu was as low as 3.14-10.99 µg/L, 0.66-2.56 µg/L and 0.60-3.15 µg/L, respectively. In addition, CG could promote the plant heavy metal uptake and thus decrease their accumulation in soil to a certain extent. Meanwhile, Malondialdehyde (MDA) content and peroxidases (POD) activities of plants in CG modified bioretention were lower than that in tradition bioretention, indicating that CG could help plants recovery and lessened the oxidative stress for the negative impact of high heavy metals accumulation. CG-based media alleviated the inhibitory effect of rainwater runoff pollutant accumulation (especially heavy metals) on microbial diversity and the enhancement of the dominant bacteria (such as Proteobacteria and Bacteroidota) could conduce the nutrients removal in the bioretention systems. In overall, this study demonstrated that the CG modified bioretention systems show an excellent removal performance combine with biological effects.

Effect of Different Oxygen Delivery Methods on Transcutaneous Oxygen Pressure and Fraction of Inspired Oxygen During Noninvasive Positive Pressure Ventilation.

Objective: The aim of this study was to investigate the effects of different oxygen delivery methods during noninvasive positive-pressure ventilation (NPPV) on transcutaneous oxygen pressure (PtcO2), transcutaneous carbon dioxide pressure (PtcCO2) and fraction of inspired oxygen (FiO2) in order to find more effective oxygen delivery methods. Methods: A total of 20 healthy volunteers participated in this study, all of whom received NPPV. All volunteers received oxygen through a nasal cannula (NC) located in a mask or through a mask alone (OSTM) (oxygen flow rate was 3L/min and 5L/min), PtcO2 and PtcCO2 were measured, and the effects of the 2 methods of oxygen concentration on PtcO2 and PtcCO2 levels were evaluated during noninvasive ventilation. Then, the additional oxygen concentration was stopped, oxygen was delivered through the ventilator, and the oxygen concentration was adjusted so that the PtcO2 reached the same oxygen concentration level as noted through the NC or OSTM. This concentration of oxygen indirectly reflects FiO2 in different oxygen delivery methods. Results: When NPPV was used under the same pressure, FiO2 increased from 44.4% to 65.3% when oxygen was delivered through an NC compared with oxygen supplied by OSTM alone. PtcO2 was also significantly increased from 18.9% to 24.9%; the difference was significant (P < .05), while there was no significant change in PtcCO2 (P > .05). Conclusion: When NPPV is used, an NC can obviously improve FiO2 and PtcO2 without increasing PtcCO2. It can save oxygen and is more suitable for NPPV during an emergency and for home use.

The association between urinary phytoestrogens and depressive symptoms.

Present evidence outlining the association between different types of phytoestrogens and depressive symptoms in the general population is limited and contradictory. Data from the 2007-2010 National Health and Nutrition Examination Survey (NHANES) were used to examine their association. Phytoestrogens were measured in urine samples and depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). Logistic regression and restricted cubic spline models were used to evaluate associations. In one model, lignans and enterolactone were inversely associated with the prevalence of depressive symptoms. Compared with the lowest quartile (Q1), the odds ratios (ORs; 95% confidence intervals [CIs]) for participants in the highest quartile of lignans and enterolactone were 0.44 (0.27-0.72) and 0.42 (0.26-0.67) for depressive symptoms, respectively. Additionally, the dose-response relationships between urinary lignans or enterolactone and depressive symptoms showed a linear trend. Our results suggest that urinary lignans and enterolactone are inversely associated with the prevalence of depressive symptoms.

Diaphragma juglandis extracts modifies the gut microbiota during prevention of type 2 diabetes in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The diaphragma juglandis (DJ) comes from the wooden septum in the core of Juglans regia L, also known as the walnut septum. In Iranian traditional medicine, walnut distraction wood was widely used in the treatment of diabetes. However, there is a lack of research data on the mechanism of DJ against diabetes. AIM OF THE STUDY: To explore the protective effect of diaphragma juglandis extract (DJE) on type 2 diabetic rats and the hypoglycemic mechanism of DJE. MATERIAL AND METHODS: Supplemented DJE and fed a high-fat diet for five weeks, and then injected low-dose STZ, successfully induced type 2 diabetic rats. Collected rat serum, liver, pancreas and feces to determine the biochemical parameters of serum and liver, analyze the pathological damages of pancreas and liver, and measure the changes of gut microbes in feces. RESULTS: DJE could inhibit the metabolic abnormalities of T2DM by improving insulin resistance, abnormal lipid metabolism, liver damage, oxidative stress, and reducing inflammation. DJE significantly held fasting blood glucose, glycosylated serum protein, serum low density lipoprotein, high density lipoprotein, oral glucose tolerance test, nitric oxide, superoxide dismutase and catalase, serum and liver triglycerides, total cholesterol, aspartate aminotransferase, alanine aminotransferase, malondialdehyde, lipopolysaccharide, fasting insulin and tumor necrosis factor-α and prevented the pathological damage of pancreas and liver. The 16SrRNA gene sequencing results showed that DJE intercepted the disorders of the fecal gut microbes, mainly including Lactobacillaceae, Rikenella, Pygmaiobacter, Oscillospiraceae and Klebsiella. Spearman correlation analysis showed that the changes of gut microbes were closely relative with biochemical parameters. CONCLUSION: DJE might prevent type 2 diabetes and its complications and hold up the disorders of gut microbes.

A Network Pharmacology Approach to Investigate the Mechanism of Erjing Prescription in Type 2 Diabetes.

Erjing prescription (EJP) was an ancient formula that was recorded in the General Medical Collection of Royal Benevolence of the Song Dynasty. It has been frequently used to treat type 2 diabetes mellitus (T2DM) in the long history of China. The formula consists of Lycium barbarum L. and Polygonatum sibiricum F. Delaroche with a ratio of 1 : 1. This study aimed to identify the potential effects and mechanisms of EJP treatment T2DM. The target proteins and possible pathways of EJP in T2DM treatment were investigated by the approach of network pharmacology and real-time PCR (RT-PCR). 99 diabetes-related proteins were regulated by 56 bioactive constituents in EJP in 26 signal pathways by Cytoscape determination. According to GO analysis, 606 genes entries have been enriched. The PPI network suggested that AKT1, EGF, EGFR, MAPK1, and GSK3ß proteins were core genes. Among the 26 signal pathways, the PI3K-AKT signal pathway was tested by the RT-PCR. The expression level of PI3K p85, AKT1, GSK3ß, and Myc mRNA of this pathway was regulated by EJP. The study based on network pharmacology and RT-PCR analysis revealed that the blood sugar level was regulated by EJP via regulating the PI3K-AKT signal pathway. Plenty of new treatment methods for T2DM using EJP were provided by network pharmacology analysis.

Nanoparticles composed of the tea polysaccharide-complexed cationic vitamin B12-conjugated glycogen derivative.

Tea polysaccharides exhibit multiple important bioactivities, but very few of them can be absorbed through the small intestine. To enhance the absorption efficacy of tea polysaccharides, a cationic vitamin B12-conjugated glycogen derivative bearing the diethylenetriamine residues (VB12-DETA-Gly) was synthesized and characterized using FTIR, 1H NMR, and UV-vis spectroscopy. An acidic tea polysaccharide (TPSA) was isolated from green tea. The TPSA/VB12-DETA-Gly complexed nanoparticles were prepared, which showed positive zeta potentials and were irregular spherical nanoparticles in the sizes of 50-100 nm. To enable the fluorescence and UV-vis absorption properties of TPSA, a Congo red residue-conjugated TPSA derivative (CR-TPSA) was synthesized. The interactions and complexation mechanism between the CR-TPSA and the VB12-DETA-Gly derivatives were investigated using fluorescence spectroscopy, resonance light scattering spectroscopy, and UV-vis spectroscopy. The results indicated that the electrostatic interaction could play a major role during the CR-TPSA and VB12-DETA-Gly-II complexation processes. The TPSA/VB12-DETA-Gly nanoparticles were nontoxic and exhibited targeted endocytosis for the Caco-2 cells, and showed high permeation through intestinal enterocytes using the Caco-2 cell model. Therefore, they exhibit potential for enhancing the absorption efficacy of tea polysaccharides through the small intestinal mucosa.

Heat/pH-boosted release of 5-fluorouracil and albumin-bound paclitaxel from Cu-doped layered double hydroxide nanomedicine for synergistical chemo-photo-therapy of breast cancer.

Considerable attention has been devoted to nanomedicine development for breast cancer therapy, while the therapeutic efficiency is far from satisfactory owing to non-specific biodistribution-caused side effects and limitation of single modal treatment. In this study, we have developed a novel nanomedicine for efficient combination breast cancer therapy. This nanomedicine was based on copper-doped layered double hydroxide (Cu-LDH) nanoparticles loaded with two FDA-approved anticancer drugs, i.e. 5-fluorouracil (5-FU) and albumin-bound paclitaxel (nAb-PTX) with complementary chemotherapeutic actions. The 5-FU/Cu-LDH@nAb-PTX nanomedicine showed pH-sensitive heat-facilitated therapeutic on-demand release and demonstrated the moderate-to-strong synergy of photothermal therapy and chemotherapy in inducing apoptosis of breast cancer cells (4 T1). This nanomedicine had a high colloidal stability in saline and serum, and efficiently accumulated in the tumor tissue. Remarkably, this nanomedicine nearly eliminated 4 T1 tumors in vivo after a two-course treatment under mild 808 nm laser irradiation (0.75 W/cm2, 3 min) at very low doses of 5-FU and nAb-PTX (0.25 and 0.50 mg/kg, 8-50 times less than that used in other nanoformulations), without observable side effects. Therefore, this research provides a novel approach to designing multifunctional nanomedicines for on-demand release of chemotherapeutics to cost-effectively treat breast cancer with minimal side effects in future clinic applications.

Protective Effect of n-Butanol Extract from Viola yedoensis on Immunological Liver Injury.

Viola yedoensis Makino was used to treat inflammation, viral hepatitis, acute pyogenic infection, and ulcerative carbuncles. However, the protective effect on immunological liver injury (ILI) of V. yedoensis had been rarely reported. This study aimed to explore the protective effect of n-butanol extract (BE) from V. yedoensis on ILI in vitro and in vivo. In vitro, the BE significantly inhibited the secretions of Hepatitis B surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg) in the HepG2.2.15 cells and the replication of HBV DNA. The research data in vivo revealed that the BE reduced the levels of alanine transaminase (ALT), aspartate transaminase (AST), and methane dicarboxylic aldehyde (MDA) in liver tissues of the ConA-induced mice, while increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and the effective contents of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and the BE could ameliorate liver histological lesions. These results motivated a further investigation into the chemical constituents of BE. Four coumarins (esculetin, prionanthoside, cichoriin, and esculin) and one flavonoid (quercetin-3-O-galactoside) were isolated from the BE by silica gel column chromatography and recrystallization, of which structures were eventually confirmed by 1 H-NMR, 13 C-NMR, and MS.

Efficacy of autologous platelet-rich plasma in treating patients with burn wounds: A protocol for systematic review and meta-analysis.

BACKGROUND: Burns are still regarded among severe health problems related to high morbidity and mortality rates globally. In essence, health problems associated with burns can cause significant economic burden to society. Regardless of treatment available options, no best treatment was considered adequate for treating severe burns. In particular, only a few studies have focused on the effect of autologous platelet-rich plasma to treat burn wounds. The present study aim to systematically review existing literature to examine the effectiveness and safety of autologous platelet-rich plasma (PRP) to treat burn wounds. METHODS: For this study, we will conduct a systematic search using MEDLINE, EMBASE, the Cochrane Library, Web of Science, CINAHL, as well as Scopus to discover randomised controlled trials (RCTs) for the examination of effectiveness and safety of autologous PRP to treat burn wounds from their inception to March 2021 with no language restrictions. Additionally, we will search Google Scholar, ClinicalTrials.gov, as well as the reference lists of studies considered in the research to ascertain possibly eligible studies. We used two independent authors to evaluate studies for inclusion and conduct data extraction. We intend to assess study bias and quality utilizing the Cochrane Collaboration's Risk of Bias Tool 2.0. Also, we will pool study results using the fixed-effects model or random-effects model. Finally, any disagreements emanating from the process will be addressed through discussion or using a third author to mediate situations leading to disagreement. RESULTS: The study aims at assessing the effectiveness and safety of autologous PRP for treating burn wounds. CONCLUSION: The study will provide specific substantiation to assess autologous PRP's effectiveness and safety in treating patients with burn wounds. ETHICS AND DISSEMINATION: The study does not require ethical approval since no published studies are used in it. OSF REGISTRATION NUMBER: March 29, 2021.osf.io/74z5u. (https://osf.io/74z5u/).

Cationic nanoparticles self-assembled from amphiphilic chitosan derivatives containing poly(amidoamine) dendrons and deoxycholic acid as a vector for co-delivery of doxorubicin and gene.

Combination treatment through the co-delivery of drugs and genes by nanoformulations may achieve a synergistic effect. In our previous study, poly(amidoamine) dendronized chitosan derivative (PAMAM-Cs) showed good gene transfection efficiency and low cytotoxicity. Here, we incorporated hydrophobic deoxycholic acid (DCA) onto the chitosan backbone of PAMAM-Cs to obtain an amphiphilic derivative-PAMAM-Cs-DCA, which could self-assemble into cationic nanoparticles (NPs). The resulting NPs with diameters of 140-220 nm can encapsulate the hydrophobic anticancer drug doxorubicin (DOX) in the core while bind pDNA via the positively charged PAMAM shell. PAMAM-Cs-DCA NPs could completely complex with pDNA at a ratio of nitrogen to phosphorous (N/P) low as 1 and the complexes achieved a transfection efficiency up to 74 % at N/P 20. Moreover, low-dose co-delivered DOX could enhance the transgene expression, showing a synergistic effect. These results suggest that PAMAM-Cs-DCA NPs hold great promise to co-deliver chemotherapeutics and nucleic acid drugs.