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Advancements in amphiphilic polylactide/vinyl polymer bonded centered nano-assemblies for medicine delivery.
Single-use filtering face respirators (FFRs) are critical pieces of personal protective equipment for healthcare workers treating patients with suspected upper respiratory tract pathogens. Experiences during pandemics in the 2000s, as well as the ongoing COVID-19 pandemic caused by the SARS-2-CoV2, have highlighted concerns over the pressures that sustained respiratory virus pandemics may have on supplies of FFRs globally. Decontamination of FFRs has been posited as one solution to support the re-use of FFRs with a growing body of literature over the last 10+ years beginning to examine both the efficacy of disinfection of contaminated FFRs but also the impact of the decontamination process on the FFR's performance. Physical and chemical methods of decontamination have been tested for treatment of FFRs with ultraviolet germicidal irradiation, sterilization by steam, ethylene oxide and vaporous hydrogen peroxide, demonstrating the most promising results thus far. Many of these methods utilize existing equipment that may already be available in hospitals and could be re-purposed for FFR decontamination. Importantly, some methods may also be replicated on household equipment, broadening the utility of FFR decontamination across a range of healthcare settings. Utilizing techniques to experimentally contaminate FFRs with a range of microorganisms, most decontamination methods appear to reduce the risk of the mask as a source of infection to the wearer and others to negligible levels. The performance of the filter, especially the efficiency of particle penetration following treatment, varied greatly depending on the processing method as well as the model of the filter itself, however. Urgent regulatory body-supported research is required to endorse the routine decontamination of FFRs. In emergency settings, these methods should nevertheless be carefully considered as one strategy to address potential shortfalls in supplies of FFRs for healthcare workers.Bioinformatically triple negative breast cancer (TNBC) and colon adenocarcinoma (COAD), two typical "cold" cancers, were found overexpressed PD-L1 and CD47 respectively but neither of them showed satisfied response on its corresponding immune checkpoint blockade (ICB) in clinic. The initial immunotherapeutic resistance to ICB was essentially attributed to the so-called "cold" tumor immune milieu (TIM). OTS964 in vitro To overcome tumor immunological tolerance against ICBs, here we report a versatile nano-modulator for point-to-point counteracting the immune-suppressors meanwhile boosting tumor T cell infiltration. Small interfering RNA targeting indoleamine 2,3-dioxygenase-1 was first co-delivered with gemcitabine using our lab-made biocompatible nanocages for relieving the immune brakes related to regulatory T cells and myeloid-derived suppressor cells. O2-producible mineralization was then tattooed on the surface of the nanocarriers to alleviate the immune inhibition of M2 macrophages. Followed with the decoration of therapeutic ICB antibodies on the mineralized shell, a versatile nano-modulator was constructed. TNBC and COAD were employed to evaluate the tumoricidal efficacy of the nano-modulator that decorated with aPD-L1 and aCD47, respectively. Our nano-modulator demonstrated multipotencies in eliciting a "hot" TIM and greatly potentiated ICB treatment for these "cold" malignancies. The strung expansibility of the nano-modulator may be also conducive in addressing the failure of more other ICBs on the non-responsive subpopulation of patients despite the corresponding immune checkpoint highly expressed in tumors.Alzheimer's disease (AD) is a progressive, irreversible, fatal brain disease which disturbs cognitive functions. It affects 35 million people worldwide and the number of people suffering may increase to 100 million by 2050 if no effective treatments are available. The present treatment improves cognitive functions and provide temporary symptomatic relief, but do not stop or delay the disease progression. Moreover, they are mainly available as conventional oral dosage forms and these conventional oral medications lack brain specificity and also produce side effects which leads to poor patient compliance. Brain drug targeting by nanomedicines is a promising approach to improve brain targeting specificity, brain bioavailability and patient compliance. The present review discuses about the currently available pharmacotherapy for AD and the neurotherapeutic applications as well as the advancements of nanomedicine for treating AD. It also highlights the recent advancements of various nanomedicines containing phytopharmaceuticals for treating AD. It is believed that nanomedicines containing approved drugs can be transformed into the clinics hence improve the life style of AD patients.Bovine herpesvirus (BoHV) types 1 and 5 are two closely related alpha-herpesviruses of cattle with neuroinvasive potential. BoHV-5 causes non-suppurative meningoencephalitis in calve whereas encephalitis caused by BoHV-1 has been occasionally reported. As an initial step to understand the biology of both BoHV types in neural cells, undifferentiated SH-SY5Y human neuroblastoma cells were infected with BoHV-1 strains Cooper and Los Angeles (LA), BoHV-5 strain 97/613 and A663, a BoHV-5/BoHV-1 natural recombinant. Cytopathic effect (CPE) in these cells was evident earlier for BoHV-5 strain 97/613 and CPE progression was slower for BoHV-1, particularly for Cooper strain. Virus antigen was detected as early as 8 h post-infection (hpi) for all strains, with the exception of BoHV-1 Cooper for which antigen expression was detectable by 24 hpi. All strains released detectable infectious virus in the extracellular medium by 8 hpi, confirming that undifferentiated SH-SY5Y cells are fully permissive to BoHV infection. Significantly different extracellular virus titers among the different strains were detected by 24 hpi, with BoHV-5 97/613 reaching the maximal virus production. The lowest extracellular titer was recorded for BoHV-1 Cooper at all the evaluated time-points. BoHV-1 Cooper, BoHV-1 LA and BoHV-5 97/613 had a steady increase in intracellular virus production. The evaluation of lysis plaques formation revealed that BoHV-5 A663 produced the largest plaques followed by BoHV-5 97/613. Both BoHV-1 strains produced smaller plaques when compared with BoHV-5. Despite a slower replicative cycle, strain A663 is more efficient in cell to cell dissemination. Thus, it is evident that BoHV-5 strains have growth advantages in undifferentiated neural cells compared with BoHV-1. This in vitro model might be useful to analyze the neuropathogenic potential of bovine alphaherpesviruses.
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