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Intracellular methicillin-resistant Staphylococcus aureus (MRSA) is extremely difficult to remove by common antibiotics, leading to infection recurrence and resistance. Herein we report a novel exosome-based antibiotic delivery platform for eradicating intracellular MRSA, where mannosylated exosome (MExos) is employed as the drug carrier and preferentially taken up by macrophages, delivering lysostaphin (MExoL) and vancomycin (MExoV) to intracellular pathogens. Combination of MExoL and MExoV eradicated intracellular quiescent MRSA. Moreover, MExos rapidly accumulated in mouse liver and spleen, the target organs of intracellular MRSA, after intravenous (IV) administration. Thus, the MExos antibiotic delivery platform is a promising strategy for combating intracellular infection.

Perineuronal nets (PNNs) are insoluble aggregates of extracellular matrix molecules in the brain that consist of hyaluronan (HA) and chondroitin sulfate proteoglycans (CSPGs). PNNs promote the acquisition and storage of memories by stabilizing the formation of synapses in the adult brain. Although the deterioration of PNNs has been suggested to contribute to the age-dependent decline in brain function, the molecular mechanisms underlying age-related changes in PNNs remain unclear.

The amount and solubility of PNN components were investigated by sequential extraction followed by a disaccharide analysis and immunoblotting. We examined the interaction between HA and aggrecan, a major HA-binding CSPG, by combining mass spectrometry and pull-down assays.

The solubility and amount of HA increased in the brain with age. Among several CSPGs, the solubility of aggrecan was selectively elevated during aging. In contrast to alternations in biochemical properties, the expression of PNN components at the transcript level was not markedly changed by aging. The increased solubility of aggrecan was not due to the loss of HA-binding properties. Our results indicated that the degradation of high-molecular-mass HA induced the release of the HA-aggrecan complex from PNNs in the aged brain.

The present study revealed a novel mechanism underlying the age-related deterioration of PNNs in the brain.

The present study revealed a novel mechanism underlying the age-related deterioration of PNNs in the brain.

Host-directed therapy is considered a novel anti-tuberculosis strategy in tackling the tuberculosis burden through autophagy induction by various inducers to curtail the growth of intracellular Mycobacterium tuberculosis.

In this study, we investigated the anti-tubercular role of soybean lectin, a lectin isolated from Glycine max (Soybean). Effect of SBL on intracellular mycobacterial viability through autophagy and the mechanism involved in differentiated THP-1 cells was studied using different experimental approaches.

We initially performed a time kinetic experiment with the non-cytotoxic dose of SBL (20 μg/ml) and observed autophagy induction after 24 h of treatment. Abrogation of autophagy in the presence of 3-MA and an increase in LC3 puncta formation upon Baf-A1 addition elucidated the specific effect on autophagy and autophagic flux. SBL treatment also led to autophagy induction in mycobacteria infected macrophages that restricted the intracellular mycobacterial growth, thus emphasizing the host defensive role of SBL induced autophagy. Mechanistic studies revealed an increase in P2RX7 expression, NF-κB activation and reactive oxygen species generation upon SBL treatment. Inhibition of P2RX7 expression suppressed NF-κB dependent ROS level in SBL treated cells. Moreover, SBL induced autophagy was abrogated in the presence of either different inhibitors or P2RX7 siRNA, leading to the reduced killing of intracellular mycobacteria.

Taken together, these results conclude that SBL induced autophagy exerts an anti-mycobacterial effect in P2RX7-NF-κB dependent manner through the generation of ROS.

This study has provided a novel anti-mycobacterial role of SBL, which may play an important role in devising new therapeutic interventions.

This study has provided a novel anti-mycobacterial role of SBL, which may play an important role in devising new therapeutic interventions.The purpose of this study was to enhance the anti-leishmanial efficacy of miltefosine (MTF) and reduce its toxic effects by loading it into nanostructured lipid carriers (NLCs). Micro-emulsion technique was used to prepare MTF-loaded NLCs. The optimized NLCs were characterized in terms of various physicochemical parameters including particle size, poly dispersity index (PDI), zeta potential, transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) technique. In vitro and in vivo assays were performed to evaluate the potential of NLCs as an effective nanocarrier system for oral delivery of MTF in Cutaneous Leishmaniasis. The optimized MTF-loaded NLCs exhibited mean particle size of 160.8 ± 5.3 nm with narrow PDI and high incorporation efficiency (IE%) of 96.17 ± 1.3%. MTF-loaded NLCs demonstrated slow release of the incorporated drug as compared to the drug solution. The optimized formulation showed significant decrease in hemolytic potential, 2.5~folds increase in anti-leishmanial efficacy and 6~fold decrease in macrophage cytotoxicity as compared to MTF solution, in vitro. Macrophage uptake study confirmed passive targeting ability of MTF-loaded NLCs. In-vivo analysis demonstrated enhanced anti-leishmanial effect of the MTF-loaded NLCs and better pharmacokinetic profiles with no gastrointestinal (GI) toxicity. NLCs are potential nanocarriers for the oral delivery of MTF with enhanced anti-leishmanial activity, better safety profile and reduced hemolytic potential.Selective laser sintering (SLS) sinters a powder layer by layer with a laser beam to prepare 3D printlets, which are widely used in the field of tissue engineering and personalized implants. To promote the SLS printing of oral solid preparations, the printability of commonly used drugs and excipients was evaluated using a 450 nm low energy laser. It was found that yellow drugs could absorb laser energy and sinter, while white drugs and pharmaceutical excipients had SLS printability when tartrazine lake was added as a photoabsorber. The printing mechanism of non-crystalline and crystalline polymers was powder sintering and powder melting, respectively. Increasing the laser energy density was beneficial to the printing efficiency but reduced printing accuracy. To ensure the integrity of multilayer printlets, the sintered thickness of each layer should be greater than the layer thickness. learn more Furthermore, ibuprofen immediate-release tablets and metoprolol tartrate sustained-release tablets were prepared. Using 10% carboxy methyl starch sodium as an additive, the shell tablets with a side thickness of 1.