Preparation of ultra-porous UPM/PHBV nanofibres using solvent-etching technology and drug-loading efficiency

In this study, ultra-porous fibres have been produced by partly washing out poly(3-hydroxybutyrateco-3-hydroxyvalerate) (PHBV) from the heat-crosslinked electrospun unsaturated polyester macromonomers/poly(3-hydroxybutyrateco-3-hydroxyvalerate) (UPM/PHBV) fibrous composite using chloroform. Tetracycline hydrochloride has been used as the module drug to test the drug-loading efficiency of porous fibres. Field emission scanning electron microscope images show that the etched UPM/PHBV fibres have lost the original smooth surface. The result demonstrates that the PHBV is successfully washed by chloroform, but most of UPM is remained because of the heat-crosslinking. Furthermore, with the increase of PHBV ratio in composite fibres, the etched fibres show much rougher surface. The drug absorption behavior also varies with the different PHBV ratios

Overexpression of TRPM7 suppresses AngII-induced phenotypic changes in hypertensive human vascular smooth muscle cells

Purpose: To study the role of TRPM7 in suppressing AngII-induced phenotype changes in human vascular smooth muscle cells (HAVSMCs).Methods: Relative levels of TRPM7, α-SMA and OPN in AngII-induced HAVSMCs were determined, and the regulatory effects of TRPM7 on levels of α-SMA and OPN, wound healing effect, 5-ethynyl-2’- deoxyuridine (EdU)-positive ratio, and viability in AngII-induced HAVSMCs were assessed. A total of 159 patients with essential hypertension attending The Second Xiangya Hospital, Central South University, Changsha, China, and 70 healthy controls were enrolled; after treatment with angiotensin receptor blocker (ARB), changes in SBP, DBP and plasma level of TRPM7 in hypertension patients were examined. Potential correlation between TRPM7 level with SBP and DBP was assessed.Results: TRPM7 and α-SMA were downregulated, while OPN was upregulated in AngII-induced HAVSMCs, but this trend was partially reversed by losartan treatment (p < 0.05). Overexpression of TRPM7 reversed the expression changes of α-SMA and OPN in AngII-induced HAVSMCs. In addition, the overexpression of TRPM7 significantly inhibited the enhanced migratory and proliferative capacities in AngII-induced HAVSMCs (p < 0.05). After ARB treatment, SBP, DBP and plasma TRPM7 were significantly reduced in hypertension patients, while TRPM7 level positively correlated with SBP and DBP in hypertensive patients.Conclusion: Overexpression of TRPM7 blocked AngII-induced phenotype changes in HAVSMCs under the pathological circumstance of hypertension.&nbsp

RSL3 Drives Ferroptosis Through GPX4 Inactivation and ROS Production in Colorectal Cancer

Ferroptosis is an iron-dependent, oxidative cell death, and is characterized by iron-dependent accumulation of reactive oxygen species (ROS) within the cell. It has been implicated in various human diseases, including cancer. Recently, ferroptosis, as a non-apoptotic form of cell death, is emerging in specific cancer types; however, its relevance in colorectal cancer (CRC) is unexplored and remains unclear. Here, we showed that ferroptosis inducer RSL3 initiated cell death and ROS accumulation in HCT116, LoVo, and HT29 CRC cells over a 24 h time course. Furthermore, we found that ROS levels and transferrin expression were elevated in CRC cells treated with RSL3 accompanied by a decrease in the expression of glutathione peroxidase 4 (GPX4), indicating an iron-dependent cell death, ferroptosis. Overexpression GPX4 resulted in decreased cell death after RSL3 treatment. Therefore, RSL3 was able to induce ferroptosis on three different CRC cell lines in vitro in a dose- and time-dependent manner, which was due to increased ROS and an increase in the cellular labile iron pool. Moreover, this effect was able to be reversed by overexpression of GPX4. Taken together, our results suggest that the induction of ferroptosis contributed to RSL3-induced cell death in CRC cells and ferroptosis may be a pervasive and dynamic form of cell death for cancer treatment

The Roles of Serum Selenium and Selenoproteins on Mercury Toxicity in Environmental and Occupational Exposure

Many studies have found that mercury (Hg) exposure is associated with selenium (Se) accumulation in vivo. However, human studies are limited. To study the interaction between Se and Hg, we investigated the total Se and Hg concentrations in body fluids and serum Se-containing proteins in individuals exposed to high concentrations of Hg. Our objective was to elucidate the possible roles of serum Se and selenoproteins in transporting and binding Hg in human populations. We collected data from 72 subjects: 35 had very low Hg exposure as evidenced by mean Hg concentrations of 0.91 and 1.25 ng/mL measured in serum and urine, respectively; 37 had high exposure (mean Hg concentrations of 38.5 and 86.8 ng/mL measured in serum and urine, respectively). An association between Se and Hg was found in urine (r = 0.625; p < 0.001) but not in serum. Hg exposure may affect Se concentrations and selenoprotein distribution in human serum. Expression of both selenoprotein P and glutathione peroxidase (GSH-Px) was greatly increased in Hg miners. These increases were accompanied by elevated Se concentrations in serum. In addition, selenoprotein P bound more Hg at higher Hg exposure concentrations. Biochemical observations revealed that both GSH-Px activity and malondialdehyde concentrations increased in serum of the Hg-exposed group. This study aids in the understanding of the interaction between Se and Hg. Selenoproteins play two important roles in protecting against Hg toxicity. First, they may bind more Hg through their highly reactive selenol group, and second, their antioxidative properties help eliminate the reactive oxygen species induced by Hg in vivo

Effects of organic and inorganic selenium on selenium bioavailability, growth performance, antioxidant status and meat quality of a local beef cattle in China

Selenium (Se) is an essential nutrient with multiple health benefits to humans and animals. Cattle generally require dietary Se supplementation to meet their daily requirements. The two main forms of dietary Se in cattle are organic Se and inorganic Se. Data comparing the health and productivity effects of organic Se and inorganic Se on cattle are still insufficient, and it is necessary to conduct more research to evaluate the bioavailability, nutritional value, deposition, and body functions of Se sources in different breeds and physiological stages of cattle raised in areas with different Se levels. The objectives of this study were to determine the effects of organic and inorganic sources of Se on plasma biochemical indices, Se bioavailability, deposition in body tissues and organs, growth performance, antioxidant capacity and meat quality of beef cattle raised in Se-deficient areas. Fifteen Chinese Xiangzhong Black beef cattle with an average weight of 254.5 ± 8.85 kg were assigned to three dietary groups. The three groups were fed the same basal ration and supplemented with either an inorganic [sodium selenite (SS)] or organic [selenomethionine (SM) or Se-enriched yeast (SY)] source of Se (0.1 mg/kg dry matter) for 60 days. At the end of the experiment, three cattle from each group were randomly selected and slaughtered, and samples were collected from tissues and organs for analysis. The results revealed that growth performance, slaughter performance, Se content of tissues and organs, meat quality characteristics including chemical composition, pH45min, pH24h, drip loss, and cooking losses did not differ (p &gt; 0.05) due to supplementation of the different organic and inorganic sources of Se. SM and SY were more effective in increasing (p &lt; 0.05) immunoglobulin M (IgM) concentrations in the blood and reducing (p &lt; 0.05) malondialdehyde (MDA) content in the longissimus dorsi than SS. In conclusion, organic Se is more effective than inorganic Se in improving the immune and antioxidant capacity of Chinese Xiangzhong Black beef cattle

Prime-boost vaccination of mice and rhesus macaques with two novel adenovirus vectored COVID-19 vaccine candidates.

ABSTRACTCOVID-19 vaccines are being developed urgently worldwide. Here, we constructed two adenovirus vectored COVID-19 vaccine candidates of Sad23L-nCoV-S and Ad49L-nCoV-S carrying the full-length gene of SARS-CoV-2 spike protein. The immunogenicity of two vaccines was individually evaluated in mice. Specific immune responses were observed by priming in a dose-dependent manner, and stronger responses were obtained by boosting. Furthermore, five rhesus macaques were primed with 5 × 109 PFU Sad23L-nCoV-S, followed by boosting with 5 × 109 PFU Ad49L-nCoV-S at 4-week interval. Both mice and macaques well tolerated the vaccine inoculations without detectable clinical or pathologic changes. In macaques, prime-boost regimen induced high titers of 103.16 anti-S, 102.75 anti-RBD binding antibody and 102.38 pseudovirus neutralizing antibody (pNAb) at 2 months, while pNAb decreased gradually to 101.45 at 7 months post-priming. Robust T-cell response of IFN-γ (712.6 SFCs/106 cells), IL-2 (334 SFCs/106 cells) and intracellular IFN-γ in CD4+/CD8+ T cell (0.39%/0.55%) to S peptides were detected in vaccinated macaques. It was concluded that prime-boost immunization with Sad23L-nCoV-S and Ad49L-nCoV-S can safely elicit strong immunity in animals in preparation of clinical phase 1/2 trials

Chromosome-level genome and multi-omics analyses provide insights into the geo-herbalism properties of Alpinia oxyphylla

IntroductionAlpinia oxyphylla Miquel (A. oxyphylla), one of the “Four Famous South Medicines” in China, is an essential understory cash crop that is planted widely in the Hainan, Guangdong, Guangxi, and Fujian provinces. Particularly, A. oxyphylla from Hainan province is highly valued as the best national product for geo-herbalism and is an important indicator of traditional Chinese medicine efficacy. However, the molecular mechanism underlying the formation of its quality remains unspecified.MethodsTo this end, we employed a multi-omics approach to investigate the authentic quality formation of A. oxyphylla.ResultsIn this study, we present a high-quality chromosome-level genome assembly of A. oxyphylla, with contig N50 of 76.96 Mb and a size of approximately 2.08Gb. A total of 38,178 genes were annotated, and the long terminal repeats were found to have a high frequency of 61.70%. Phylogenetic analysis demonstrated a recent whole-genome duplication event (WGD), which occurred before A. oxyphylla’s divergence from W. villosa (~14 Mya) and is shared by other species from the Zingiberaceae family (Ks, ~0.3; 4DTv, ~0.125). Further, 17 regions from four provinces were comprehensively assessed for their metabolite content, and the quality of these four regions varied significantly. Finally, genomic, metabolic, and transcriptomic analyses undertaken on these regions revealed that the content of nootkatone in Hainan was significantly different from that in other provinces.DiscussionOverall, our findings provide novel insights into germplasm conservation, geo-herbalism evaluation, and functional genomic research for the medicinal plant A. oxyphylla