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Fructose impacting morphology and inducing β-fructofuranosidases throughout Penicillium janczewskii.
Coronavirus disease has overwhelmed the healthcare systems around the globe at an unprecedented level. The same was observed in the Romanian medical system. Interventional cardiology units have experienced a dramatic reduction in elective and urgent interventional procedures. The present report highlights the total number of coronary interventions, peripheral interventions, and interventions for structural heart diseases that were performed in 2020 in Romania in comparison to 2019.BackgroundUnruptured intracranial aneurysms (UIAs) can be presented with various symptoms, including atypical headaches and cranial nerve deficits. Vertigo is often referred in the literature as a coexisting symptom. Our aim was to investigate the importance of vertigo in the UIA symptomatology and present a possible explanation for its existence. MethodsWe conducted a retrospective observational multicenter study concerning patients with surgically treated intracranial aneurysms. During a period of 10 years, 1 085 patients with cerebral aneurysms underwent surgery. There were 812 patients with ruptured intracranial aneurysms (RIA) and 273 with UIA. The medical records for each of the 273 patients were analyzed. Results After the implementation of exclusion criteria, 89 (32.6%) of UIA patients were selected in the study, from which 71 (79.8%) were females and 18 (20.2%) males. The mean age was 56.9 (± 12.876) years old. Vertigo existed in 72 (80.9%), headache in 41 (46.1%) and visual symptoms in 21 (23.6%) patients. learn more No significant correlation (p >0.05) was demonstrated between gender, age or aneurysm location in correlation with vertigo, headache or visual symptoms, apart from a negative significant correlation between age and vertigo (p=0.031). ConclusionVertigo is an alarming symptom that could indicate the existence of an UIA. The pathophysiological mechanism could be explained by the formation of an aneurysmal vortex that projects into the parent artery, leading to disturbances in the laminar flow and formation of an irregular/turbulent flow, which potentially affects the cerebral autoregulation and by consequence, the central processing of movement.To explore the structure-activity connections of amphiphilic permeation enhancers containing the length of the hydrophobic chains as well as the properties of the polar head, O-acylgeraniol and O-acylnerol derivatives were synthesized from geraniol/nerol (cis-isomer of geraniol) and pharmaceutical excipient acids in this research. Their promotion of the percutaneous absorption of three drugs as the model, flurbiprofen (FP), isosorbide dinitrate (ISDN) and donepezil (DNP), which were selected based on their physicochemical properties, was tested by in vitro skin penetration and in vivo. Molecular simulation, ATR-FTIR, CLSM and histological observation were implement to evaluate the mode of action of the enhancers. The results indicated that (E)-3,7-dimethyl-2,6-octadien-1-yl tetradecanoate (GER-C14, trans-) achieved the highest enhancement ability for the three drugs; additionally, the in vivo results obtained were in good correlation with the in vitro data. Molecular docking results suggested that enhancers loosen the hydrogen bonds between ceramides, and the results of molecular simulation indicated that GER-C14, NER-C14 could insert into the middle of the lipid bilayer to form an independent phase. According to ATR-FTIR and histological evaluation, the enhancers extracted lipids and influenced the protein region, thereby disturbing the skin array. In addition, CLSM described the dynamic effects of enhancers on lipids between stratum corneum (SC) cells. In conclusion, GER-C14 had a better penetration promotion effect, which broadened our understanding of stereoisomeric penetration enhancers.Nanomedicine has made great progress in the targeted therapy of cancer. Here, we established a novel drug-mate strategy by studying the formulation of nanodrugs at the molecular level. In the drug-mate combination, the drug is a hydrophobic drug that is poorly soluble in water, and the mate is an amphiphilic small molecule (SMA) that has both hydrophilic and lipophilic properties. We proposed that the hydrophobic drug could co-assemble with a suitable SMA on a nanoscale without additive agents. The proof-of-concept methodology and results were presented to support our hypothesis. We selected five hydrophobic drugs and more than ten amphiphilic small molecules to construct a library. Through molecular dynamic simulation and quantum chemistry computation, we speculated that the formation of nanoassemblies was related to the binding energy of the drug-mate, and the drug-mate interaction must overcome drug-drug interaction. Furthermore, the obtained SF/VECOONa nanoassemblieswas selected as a model, which had an ultra-high drug loading content (46%), improved pharmacokinetics, increased bioavailability, and enhanced therapeutic efficacy. In summary, the drug-mate strategy is an essential resource to design exact SMA for many hydrophobic drugs and provides a reference for the design of a carrier-free drug delivery system.Photothermal (PTT) and photodynamic (PDT) combined therapy has been hindered to clinical translation, due to the lack of available biomaterials, difficult designs of functions, and complex chemical synthetic or preparation procedures. To actualize a high-efficiency combination therapy for cancer via a feasible approach, three readily available materials are simply associated together in one-pot, namely the single-walled carbon nanohorns (SWCNH), zinc phthalocyanine (ZnPc), and surfactant TPGS. The established nanodispersion is recorded as PCT. The association of SWCNH/ZnPc/TPGS was confirmed by energy dispersive spectrum, Raman spectrum and thermogravimetric analysis. Under lighting, PCT induced a temperature rising up to about 60 °C due to the presence of SWCNH, production a 7-folds of singlet oxygen level elevation because of ZnPc, which destroyed almost all 4T1 tumor cells in vitro. The photothermal effect of PCT depended on both laser intensity and nanodispersion concentration in a linear and nonlinear manner, respectively. After a single peritumoral injection in mice and laser treatment, PCT exhibited the highest tumor temperature rise (to 65 °C) among all test groups, completely destroyed primary tumor without obvious toxicity, and inhibited distant site tumor. Generally, this study demonstrated the high potential of PCT nanodispersion in tumor combined therapy.This study focused on the encapsulation of vancomycin (VAN) into liposomes coated with a red blood cell membrane with a targeting ligand, daptomycin-polyethylene glycol-1,2-distearoyl-sn-glycero-3-phosphoethanolamine, formed by conjugation of DAPT and N-hydroxysuccinimidyl-polyethylene glycol-1,2-distearoyl-sn-glycero-3-phosphoethanolamine. This formulation is capable of providing controlled and targeted drug delivery to the bacterial cytoplasm. We performed MALDI-TOF, NMR and FTIR analyses to confirm the conjugation of the targeting ligand via the formation of amide bonds. Approximately 45% of VAN could be loaded into the aqueous cores, whereas 90% DAPT was detected using UV-vis spectrophotometry. In comparison to free drugs, the formulations controlled the release of drugs for > 72 h. Additionally, as demonstrated using CLSM and flow cytometry, the resulting formulation was capable of evading detection by macrophage cells. In comparison to free drugs, red blood cell membrane-DAPT-VAN liposomes, DAPT liposomes, and VAN liposomes reduced the MIC and significantly increased bacterial permeability, resulting in > 80% bacterial death within 4 h. Cytotoxicity tests were performed in vitro and in vivo on mammalian cells, in addition to hemolytic activity tests in human erythrocytes, wherein drugs loaded into the liposomes and RBCDVL exhibited low toxicity. Thus, the findings of this study provide insight about a dual antibiotic targeting strategy that utilizes liposomes and red blood cell membranes to deliver targeted drugs against MRSA.Spinal cord injury (SCI) causes Ca2+ overload, which can lead to inflammation and neuronal apoptosis. In this study, we prepared a nanovesicle derived from macrophage membrane (MVs), which encapsulated sodium alginate (SA) and naloxone (NAL) to inhibit inflammation and protect neurons by reducing the free Ca2+concentration at the SCI site. Based on the transmission electron microscopy (TEM) image, the encapsulated sample (NAL-SA-MVs) had a particle size of approximately 134 ± 11 nm and exhibited a sustained release effect. The encapsulation rate of NAL and SA was 82.07% ± 3.27% and 72.13% ± 2.61% in NAL-SA-MVs, respectively. Targeting tests showed that the NAL-SA-MVs could accumulate in large quantities and enhance the concentration of SA and NAL at the lesion sites. In vivo and in vitro studies indicated that the NAL-SA-MVs could decrease the concentration of free Ca2+, which should further alleviate the inflammatory response and neuronal apoptosis. Anti-inflammation results demonstrated that the NAL-SA-MVs could reduce the pro-inflammation factors (iNOS, TNF-α, IL-1β, IL-6) and increase the expression of anti-inflammation factors (IL-10) at the cell and animal level. Concurrently, fluorescence, flow cytometry and western blot characterization showed that the apoptotic condition of the neurons was significantly inhibited. In addition, the motor function of C57 mice were significantly improved after NAL-SA-MVs treatment. In conclusion, it is suggested that the NAL-SA-MVs has tremendous potential in the treatment of SCI.Parenteral sustained release drug formulations, acting as preferable platforms for long-term exposure therapy, have been wildly used in clinical practice. However, most of these delivery systems must be given by hypodermic injection. Therefore, issues including needle-phobic, needle-stick injuries and inappropriate reuse of needles would hamper the further applications of these delivery platforms. Microneedles (MNs) as a potential alternative system for hypodermic needles can benefit from minimally invasive and self-administration. Recently, polymeric microneedle-mediated sustained release systems (MN@SRS) have opened up a new way for treatment of many diseases. Here, we reviewed the recent researches in MN@SRS for transdermal delivery, and summed up its typical design strategies and applications in various diseases therapy, particularly focusing on the applications in contraception, infection, cancer, diabetes, and subcutaneous disease. An overview of the present clinical translation difficulties and future outlook of MN@SRS was also provided.Nanotechnologies have been successfully applied to the treatment of various diseases. Plant-derived exosome-like nanoparticles (PENs) are expected to become effective therapeutic modalities for treating disease or in drug-delivery. PENs are minimally cytotoxic to healthy tissues, with which they show excellent biocompatibility, and are biased towards tumors by targeting specific tissues through special endocytosis mechanisms. Thus, the use of these PENs may expand the scope of drug therapies while reducing the off-target effects. In this review, we summarize the fundamental features and bioactivities of PENs extracted from the grape, grapefruit, ginger, lemon, and broccoli and discuss the applications of these particles as therapeutics and nanocarriers.
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