IntroductionAs a deadly disease induced by Mycobacterium tuberculosis (Mtb), tuberculosis remains one of the top killers among infectious diseases. The low intracellular Mtb killing efficiency of current antibiotics introduced the long duration anti-TB therapy in clinic with strong side effects and increased drug-resistant mutants. Therefore, the exploration of novel anti-TB agents with potent anti-TB efficiency becomes one of the most urgent issues for TB therapies. MethodsHere, we firstly introduced a novel method for the preparation of zinc oxide-selenium nanoparticles (ZnO-Se NPs) by the hybridization of zinc oxide and selenium to combine the anti-TB activities of zinc oxide nanoparticles and selenium nanoparticles. We characterized the ZnO-Se NPs by dynamic laser light scattering and transmission electron microscopy, and then tested the inhibition effects of ZnO-Se NPs on extracellular Mtb by colony-forming units (CFU) counting, bacterial ATP analysis, bacterial membrane potential analysis and scanning electron microscopy imaging. We also analyzed the effects of ZnO-Se NPs on the ROS production, mitochondrial membrane potential, apoptosis, autophagy, polarization and PI3K/Akt/mTOR signaling pathway of Mtb infected THP-1 macrophages. At last, we also tested the effects of ZnO-Se NPs on intracellular Mtb in THP-1 cells by colony-forming units (CFU) counting. ResultsThe obtained spherical core-shell ZnO-Se NPs with average diameters of 90 nm showed strong killing effects against extracellular Mtb, including BCG and the virulent H37Rv, by disrupting the ATP production, increasing the intracellular ROS level and destroying the membrane structures. More importantly, ZnO-Se NPs could also inhibit intracellular Mtb growth by promoting M1 polarization to increase the production of antiseptic nitric oxide and also promote apoptosis and autophagy of Mtb infected macrophages by increasing the intracellular ROS, disrupting mitochondria membrane potential and inhibiting PI3K/Akt/mTOR signaling pathway. DiscussionThese ZnO-Se NPs with synergetic anti-TB efficiency by combining the Mtb killing effects and host cell immunological inhibition effects were expected to serve as novel anti-TB agents for the development of more effective anti-TB strategy.

Our study focuses on the morphological parameters of bone growth and bone formation in Sprague-Dawley (SD) rats of different ages, using fluorochrome labeling in vivo. We concluded that bone longitudinal growth rate (LGR) and bone mineral apposition rate (MAR) were significantly increased in both the 1-and 3-month-old rats compared with the 6-and 14-monthold rats, and that of the parameters were significantly decreased in both the 6-and 14-month-old rats. Meanwhile, bone formation rate (BFR) and percent labeled perimeter (%L.Pm) peaked in 3-month-old rats, and were followed by remarkable decrease with aging. In the present study, static parameters including percent trabecular area (%Tb.Ar), trabecular thickness (Tb.Th) and trabecular number (Tb.N), contrary to previous reports, progressively increased, whereas trabecular separation (Tb.Sp) reduced with increasing age. Furthermore, bone mass increased for 14-month-old rats due to the significantly decreased bone turnover rate.

Morinda officinalis F.C. How. (Rubiaceae) is a herbal medicine. It has been recorded that its oligosaccharides have neuroprotective properties. In order to understand the oligosaccharides extracted from Morinda officinalis (OMO), a systematic study was conducted to provide evidence that supports its use in neuroprotective therapies for Alzheimer’s disease (AD). AD rat models were prepared with D-galactose and Aβ25–35. The following groups were used in the present experiment: normal control group, sham-operated group, model group, Aricept group, OMO low-dose group, OMO medium-dose group, and OMO high-dose group. The effects on behavioral tests, antioxidant levels, energy metabolism, neurotransmitter levels, and AD-related proteins were detected with corresponding methodologies. AD rats administered with different doses of OMO all exhibited a significant (P<0.05) decrease in latency and an increase (P<0.05) in the ratio of swimming distance to total distance in a dose-dependent manner in the Morris water maze. There was a significant (P<0.05) increase in antioxidant enzyme activities (SOD, GSH-Px, and CAT), neurotransmitter levels (acetylcholine, γ-GABA, and NE and DA), energy metabolism (Na+/K+-ATPase), and relative synaptophysin (SYP) expression levels in AD rats administered with OMO. Furthermore, there was a significant (P<0.05) decrease in MDA levels and relative expression levels of APP, tau, and caspase-3 in AD rats with OMO. The present research suggests that OMO protects against D-galactose and Aβ25–35-induced neurodegeneration, which may provide a novel strategy for improving AD in clinic.

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The lysozyme-modified nanoparticles (LY@ZnO NPs) were synthesized by the reduction–oxidation method, and the morphology and structure of LY@ZnO were analyzed by Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (XRD), scanning electron microsclope (SEM), and particle size analysis. The antibacterial effects of LY@ZnO against Escherichia coli (E. coli, Gram-negative bacteria) and Staphylococcus aureus (S. aureus, Gram-positive bacteria) were discussed by measuring the zone of inhibition (ZOI) and growth inhibition. The antimicrobial experiments showed that the LY@ZnO NPs possessed better antibacterial activity than ZnO. Besides, the antibacterial mechanism of LY@ZnO was also investigated, which was attributed to the generation of reactive oxygen species (ROS). Furthermore, the toxicities of LY@ZnO in vivo and in vitro were discussed by the cell counting kit-8 method and animal experiments, showing that LY@ZnO possessed excellent biocompatibility. Finally, the therapeutic effect of LY@ZnO on a rat skin infection model caused by methicillin-resistant Staphylococcus aureus (MRSA) was also studied, which exhibited good anti-infective activity. Our findings showed that LY@ZnO possessed remarkable antibacterial ability due to its excellent membrane permeability and small particle size. Besides, LY@ZnO also exhibited certain stability and great safety, which showed tremendous prospects for microbial infection in patients. It would also be helpful for a better understanding of the enzyme-modified nanomaterials against bacteria.