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Introduction The contribution of neuroinflammation in cognitive impairment is increasingly recognized. Non-steroidal anti-inflammatory drugs had been proven that it could improve cognitive impairment in large dose but with more side effect, which limited the application. The main objective of this study was to investigate whether the combined use of nicotine and celecoxib could obtain synergistic neuroprotective effect in ischemic rats. Methods Twenty adult Sprague-Dawley (SD) rats underwent ischemic model surgery by injecting endothelin-1 into the left thalamus, which were classified into four groups with different interventions: nicotine (1.5 mg/kg/d), celecoxib (15 mg/kg/d), nicotine (1.5 mg/kg/d) +celecoxib (15 mg/kg/d), or saline after surgery. The other five SD rats also underwent same surgery by injecting saline instead of endothelin-1, as the control group. Morris water maze (MWM) test was adopted to assess the cognition. Micro PET/CT with 2-[18F]-A-85380 were performed for α4β2-nAChRs detection in vivo. Western blot, real-time PCR and immunohistochemical staining were adopted to detect the expression of α4β2-nAChRs and inflammatory factors which included TNF-α, IL-1β, IL-6 in brain tissue. Microglial activation in the brain was monitored by immunofluorescence with IBA1 staining. Results The MWM test showed rats given with nicotine or celecoxib alone showed much better memory than rats with saline, no difference was observed between nicotine and celecoxib. The rat memory was recovered most significant when the nicotine and celecoxib were combined (p Conclusions The study revealed the combined use of nicotine and celecoxib may improve the cognitive function in ischemic rats, with a better effect than either alone. Both nicotine and celecoxib can inhibit inflammation, but through different mechanisms: nicotine can activate α4β2-nAChRs while celecoxib is cyclooxygenase-2 inhibitor. Our findings suggest the combined application of two drugs with different anti-inflammation mechanism could attenuate cognitive impairment more effectively in ischemic rats, which may hold therapeutic potential in the clinical practice.

Nanomedicine has shown remarkable progress in preclinical studies of tumor treatment. Over the past decade, scientists have developed various nanocarriers (NCs) for delivering drugs into the tumor area. However, the average amount of accumulated drugs in tumor sites is far from satisfactory. This limitation is strongly related to the corona formation during blood circulation. To overcome this issue, NCs should be designed to become highly stealthy by modifying their surface charge. However, at the same time, stealthy effects not only prevent protein formation but also alleviate the cellular uptake of NCs. Therefore, it is necessary to develop NCs with switchable properties, which are stealthy in the circulation system and sticky when arriving at tumor sites. In this review, we discuss the recent strategies to develop passive and active charge-switchable NCs, known as chameleon-like drug delivery systems, which can reversibly transform their surface from stealthy to sticky and have various designs.

Bacterial biofilms caused by antibiotic resistance are a severe cause of infection threatening human health nowadays. The primary causes of this emerging threat are poor penetration of conventional antibiotics and the growing number of varied strains of resistant bacteria. Recently, bulk phytochemical oils have been widely explored for their potential as antibacterial agents. However, due to their poor solubility, low stability, and highly volatile properties, essential oils are not effective for in vitro and in vivo antibacterial applications and require further preparation. In this review, we discuss the recent progress and strategies to overcome the drawbacks of bulk phytochemical oils using nano-delivery, as well as the current challenges and future outlook of these nano-delivery systems against bacterial resistance.

Immunotherapy has remarkable success outcomes against hematological malignancies with high rates of complete remission. To date, many studies have been conducted to increase its effectiveness in other types of cancer. However, it still yields unsatisfying results in solid tumor therapy. This limitation is partly attributed to the lack of understanding of how immunotherapy works in cancer from other perspectives. The traditional studies focus on the biological and chemical perspectives to determine which molecular substrates are involved in the immune system that can eradicate cancer cells. In the last decades, accumulating evidence has shown that physical properties also play important roles in the immune system to combat cancer, which is studied in mechanoimmunology. Mechanoimmunology analysis requires special tools; and herein, atomic force microscopy (AFM) appears as a versatile tool to determine and quantify the mechanical properties of a sample in nanometer precisions. Owing to its multifunctional capabilities, AFM can be used to explore immune system function from the physical perspective. This review paper explains the mechanoimmunology of how immune systems work through AFM, which includes mechanosignaling, mechanosensing, and mechanotransduction, with the aim to deepen the understanding of the mechanistic role of immunotherapy for further development in cancer treatment.

Local abnormal angiogenesis and cardiovascular system reorganization have been observed in embryos exposed to a simulated microgravity (SM) environment. In this study, changes in key molecular signals and pathways in cardiovascular development have been investigated under microgravity conditions. In particular, the caudal vein plexus (CVP) network, formed by sprouting angiogenesis has been chosen. Zebrafish embryos were exposed to SM using a ground-based microgravity bioreactor for 24 and 36 h. The SM was observed to have no effect on the zebrafish length, tail width and incubation time whereas it was observed to significantly reduce the heart rate frequency and to promote abnormal development of the CVP network in the embryos. Nitric oxide (NO) content demonstrated that the total proteins in zebrafish embryos were significantly higher in SM than in the control group grown under normal conditions. It was then preliminarily determined how NO signals were involved in SM regulated zebrafish CVP network formation. nos2b MO was injected and CVP network evolution was observed in 36 h post fertilization (hpf) under SM condition. The results showed that the CVP network formation was considerably decreased in the nos2b MO treated group. However, this inhibition of the CVP network development was not observed in control MO group, indicating that nos2b is involved in the SM-regulated vascular development process in zebrafish. Moreover, specific phosphoinositide 3-kinase (PI3K) inhibitors such as LY294002 were also tested on zebrafish embryos under SM condition. This treatment significantly inhibited the formation of zebrafish CVP network. Furthermore, overexpression of nos2b partly rescued the LY294002-caused CVP network failure. Therefore, it can be concluded that SM affects zebrafish CVP network remodeling by enhancing angiogenesis. Additionally, the PI3K-nos2b signaling pathway is involved in this process.

Background The compromise of blood brain barrier (BBB) integrity is often associated with human hemorrhage stroke and neurodegeneration diseases, including retina diseases, such as age-related macular degeneration and diabetic retinopathy. Brain pericytes play pivotal roles in regulation and maintenance of BBB integrity. However, the mechanisms underlying brain pericyte development to establish BBB integrity remain unclear. Methods Zebrafish transgenic lines Tg(flk1:GFP; gata1:dsRed), Tg(flk1:GFP), Tg(fli1:GFP) and Tg(BRE:GFP) were used in this work. The functional studies of bmp3 were performed by mopholino oligonucleotide (MO) injection, dye-based permeability assay, RT-PCR, in vivo imaging, immunofluorescence staining and statics analysis. Results Here we report that bmp3 regulates BBB integrity in zebrafish brain by promoting pericyte development. Knockdown of bmp3 with injection of bmp3-MO causes intracerebral hemorrhage in zebrafish embryos. Meanwhile, disruption of bmp3 function by bmp3-MO injection impairs cerebral pericyte coverage in zebrafish embryos. Mechanistically, knockdown of bmp3 disrupts the pattern and activities of BMP signaling in zebrafish brain, thus probably disrupting the balance of TGFβ/BMP signaling in zebrafish embryos. Conclusion In summary, our data shows that bmp3 regulates BBB integrity potentially by promoting pericyte development.

Chitosan is a natural biopolymer and is made up of D-glucosamine subunits linked by beta-(1,4) glycosidic bond. In recent years, the application of chitosan has attracted more and more attention because of its good biological function in cell biology. The properties of chitosan-based biomaterial are attributed to the physical properties and chemical composition of chitosan. The author of this paper summarized recent related studies and progresses of the influence of physical properties of chitosan on cell activity and cell mechanics property at home and abroad. The findings show that most studies mainly focused on the influence of chitosan and cell activity, while few were on cell mechanics property. The related studies of the influence of chitosan on cell will contribute to the explanation for the mechanism of the interaction between chitosan and cell, and provide the theoretical support for the further study.