Notes

Clostridium acetobutylicum atpG-Knockdown Mutants Enhance Extracellular ph inside Set Cultures.
Eight new jatrophane diterpenoids, Euphosorophane F-M (1-8), as well as fourteen known jatrophane diterpenoids (9-22) were separated and purified from the fructus of Euphorbia sororia, and the chemical structures were determined based on extensive spectroscopic analysis, 1D, 2D NMR and HRESIMS data included. Their absolute configurations of compounds 1, 2, 9, and 22 were elucidated by X-ray crystallographic analysis. These jatrophane diterpenoids showed lower cytotoxicity and compounds 3, 4, 11, 12, 13, 14, and 20 revealed promising multidrug resistance (MDR) reversal ability as modulators compared to verapamil (VRP) by MTT assay. The structure-activity relationship (SAR) exhibited that the absence of keto-carbonyl at C-9 and C-14 was essential to MDR reversal activity and the acyloxies substitution at C-5, C-7, C-8, and C-14 also made the activity difference. Euphosorophane I (4) particularly unfold greater potency (EC50 = 1.82 μM) in reversing P-gp-mediated resistance to doxorubicin (DOX). As shown by fluorescence microscopy, 4 promoted intracellular accumulation of rhodamine 123 (Rh123) and DOX in a dose-dependentmanner than VRP. Flow cytometry indicated that 4 inhibitedP-glycoprotein (P-gp) -dependentRh123 efflux in drug-resistant MCF-7/ADR cells. 4 stimulated P-gp-ATPase activity in a concentration-dependent way and inhibited DOX transport activity. Western blot and real-time qPCR results further illustrated that 4 exhibited superior MDR reversal effect in MCF-7/ADR cells attributed to the activation of ATPase rather than the upregulation of P-gp expression and mRNA levels. In addition, 4 bond to the drug-binding site of P-gp predicted by the molecular docking analysis. Collectively, these results indicated that 4 efficiently reversed P-gp-mediated MDR via inhibiting the ABCB1 drug efflux function. 4 with the advantage of low toxicity and efficient could be used as an adjuvanttherapy drug for breast cancer.Antibiotic resistance and emerging viral pandemics have posed an urgent need for new anti-infective drugs. By screening our microbial extract library against the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the notorious ESKAPE pathogens, an active fraction was identified and purified, leading to an initial isolation of adipostatins A (1) and B (2). In order to diversify the chemical structures of adipostatins toward enhanced biological activities, a type III polyketide synthase was identified from the native producer, Streptomyces davawensis DSM101723, and was subsequently expressed in an E. coli host, resulting in the isolation of nine additional adipostatins 3-11, including two new analogs (9 and 11). The structures of 1-11 were established by HRMS, NMR, and chemical derivatization, including using a microgram-scale meta-chloroperoxybenzoic acid epoxidation-MS/MS analysis to unambiguously determine the double bond position in the alkyl chain. The present study discovered SARS-CoV-2 main protease inhibitory activity for the class of adipostatins for the first time. Several of the adipostatins isolated also exhibited antimicrobial activity against selected ESKAPE pathogens.Current understanding on the interactions between micro/nano-structured Ti surfaces and macrophages is still limited. In this work, TiO2 nano-structures were introduced onto acid-etched Ti surfaces by alkali-heat treatment, ion exchange and subsequent heat treatment. By adjusting the concentration of NaOH during alkali-heat treatment, nano-flakes, nano-flakes mixed with nano-wires or nano-wires could formed on acid-etched Ti surfaces. The micro- and micro/nano-structured Ti surfaces possessed similar surface chemical and phase compositions. In vitro results indicate that the morphology of macrophages was highly dependent on the morphological features of nano-structures. Nano-flakes and nano-wires were favorable to induce the formation of lamellipodia and filopodia, respectively. Compared to micro-structured Ti surface, micro/nano-structured Ti surfaces polarized macrophages to their M2 phenotype and enhanced the gene expressions of osteogenic growth factors in macrophages. The M2 polarized macrophages promoted the maturation of osteoblasts. Compared to that with nano-flakes or nano-wires, the surface with mixed features of nano-flakes and nano-wires exhibited stronger anti-inflammatory and osteo-immunomodulatory effects. The findings presented in the current work suggest that introducing micro/nano-topographies onto Ti-based implant surfaces is a promising strategy to modulate the inflammatory response and mediate osteogenesis.Nanoparticles (NPs) were hypothesized to enhance fermentation processes and assist microorganisms in producing valuable biopolymers. Donors of trace iron, i.e., FeSO4·7H2O, zero-valence iron nanoparticles (Fe NPs), and ferric oxide nanoparticles (α-Fe2O3 NPs), were tested to study the impact on hyaluronic acid (HA) production. The bioprocess with the addition of 30 mg/L Fe NPs produced higher HA than the other groups. However, Fe NPs were limited by the synergistic effect of geomagnetism and high surface energy, resulting in obvious agglomeration behavior. To address this, we developed novel sucrose-modified iron nanoparticles (SM-Fe NPs), which showed effective improvement of dispersion and agglomeration. Concerning the SM-Fe NP additives, an adequate supply of nutrients and trace elements provided sufficient substrates and energy for the reproduction of Streptococcus zooepidemicus. Furthermore, the highest HA production with the addition of 30 mg/L SM-Fe NPs was 0.226 g/L, and the dry weight of the produced HA increased 3.28 times compared with the control group (0.069 g/L). This work significantly improved HA production and presented promising opportunities for industrial production.In this work, a simple and rapid screening strategy was developed combining capillary electrophoresis analysis with enzymatic assay based on immobilized α-glucosidase. For α-glucosidase immobilization, magnetic core-shell metal-organic frameworks composite (Fe3O4@CS@ZIF-8) was fabricated by a step-by-step assembly method, and α-glucosidase was in situ encapsulated in crystal lattice of ZIF-8. The composite was characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction and vibrating sample magnetometer. After immobilization, α-glucosidase exhibited enhanced tolerance to temperature and pH, and its reusability was greatly improved with 74 % of initial enzyme activity after being recycled 10 times. The Michaelis-Menten constant of immobilized enzyme was calculated to be 0.47 mM and its inhibition constant and IC50 for acarbose were 0.57 μM and 0.18 μM, respectively. The immobilized enzyme was subsequently applied to inhibitor screening from 14 TCMs, and Rhei Radix et Rhizoma was screened out. Among the commercially available 10 components presented in Rhei Radix et Rhizoma, gallic acid, (+)-catechin and epicatechin exhibited the strongest inhibitory effect on α-glucosidase. Their binding sites and modes with α-glucosidase were simulated via molecular docking to further verify the inhibition screening assay results. The positive results indicated that the Fe3O4@CS@ZIF-8-based screening strategy may provide a new avenue for discovering enzyme inhibitors from TCMs.Ferulic acid (FA) is a ubiquitous natural plant bioactive with distinctive promise in neurodegenerative disorders. learn more However, its therapeutic efficacy gets compromised owing to its poor aqueous solubility, inadequate permeability across lipophilic barriers, and extensive first-pass metabolism. The current studies, therefore, were undertaken to systematically develop chitosan-coated solid lipid nanoparticles (SLNs) using QbD paradigms for improved efficacy of FA in the management of Alzheimer's disease (AD). SLNs of FA were formulated employing Compritol as lipid and polysorbate 80 as surfactant and optimised using a 32 Central Composite Design (CCD). The optimized formulation, surface-coated with chitosan using ionic gelation, exhibited particle size of 185 nm, entrapment efficiency of 51.2 % and zeta potential of 12.4 mV. FTIR and DSC studies verified the compatibility of FA with formulation excipients, PXRD construed significant loss of drug crystallinity, while FESEM depicted existence of uniform spherical nanoparticles with little aggregation. Notable improvement in ex vivo mucoadhesion and permeation studies using goat nasal mucosa, coupled with extension in in vitro drug release, was obtained with SLNs. Substantial improvement with SLNs in cognitive ability through the reduction in escape latency time during behavioural studies, together with significant improvement in various biochemical parameters and body weight gain was observed in AD-induced rats. Histopathological images of different rat organs showed no perceptible change(s) in tissue morphology. Overall, these preclinical findings successfully demonstrate improved anti-AD efficacy, superior nasal mucoadhesion and permeation, extended drug release, improved patient compliance potential, safety and robustness of the developed lipidic nanoconstructs of FA through intranasal route.18β-Glycyrrhetinic acid (GA) is often topically applied in clinical treatment of inflammatory skin diseases. However, GA has poor solubility in water, which results in poor skin permeability and low bioavailability. Nanocrystallization of drugs can enhance their permeability and improve bioavailability. We prepared GA nanocrystals (Nano GA) by high-pressure homogenization. These nanocrystals were characterized by photon correlation spectroscopy, scanning electron microscopy, thermogravimetric analysis, and X-ray diffractometry. The ability of Nano GA to improve dermal permeability was investigated ex vivo using Franz diffusion vertical cells and mouse skin. The topical anti-inflammatory activity of Nano GA was assessed in vivo by a 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced model in mouse ears. The average particle size of a GA nanocrystalline suspension was 288.6 ± 7.3 nm, with a narrow particle-size distribution (polydispersity index ∼0.13 ± 0.10), and the particle size of the lyophilized powder increased (552.0 ± 9.8 nm). After nanocrystallization, the thermal stability and crystallinity decreased but solubility increased significantly. Nano GA showed higher dermal permeability than Coarse GA. Macroscopic and staining-based observations of mouse ears and the levels of proinflammatory factors and myeloperoxidase revealed that the Nano GA hydrogel exhibited better anti-edema ability and more strongly inhibited inflammation development than the Coarse GA hydrogel and indomethacin hydrogel (positive drug). These results suggest that Nano GA could be an efficacious topical therapeutic agent for skin inflammation.The formulation of nanoparticles with intrinsically therapeutic properties in a tailorable and appropriate manner is critical in nanomedicine for effective treatments of infectious diseases. Here, we present a biomedical strategy to formulate silver nanoparticles (AgNPs) as intrinsically therapeutic agents for the treatment of Staphylococcus aureus (S. aureus) keratitis. Specifically, AgNPs are controllably obtained as spheres, wrapped with a biopolymer, and varied in sizes. in vitro and in vivo studies indicate that biological interactions between the AgNPs and corneal keratocytes, S. aureus bacteria, and blood vessels are strongly determined by the particle sizes. As the size increased from 3.3 ± 0.7 to 37.2 ± 5.3 nm, the AgNPs exhibit better ocular biocompatibility and stronger antiangiogenic activity, but poorer bactericidal performance. In a rabbit model of S. Aureus-induced keratitis, intrastromal injection of AgNP formulations (single dose) show substantial influences of particle size on the treatment efficacy.
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