Traumatic brain injury (TBI) is a leading cause of mortality and disability worldwide. Although treatment guidelines have been developed, no best treatment option or medicine for this condition exists. Recently, mesenchymal stem cells (MSCs)-derived exosomes have shown lots of promise for the treatment of brain disorders, with some results highlighting the neuroprotective effects through neurogenesis and angiogenesis after TBI. However, studies focusing on the role of exosomes in the early stages of neuroinflammation post-TBI are not sufficient. In this study, we investigated the role of bone mesenchymal stem cells (BMSCs)-exosomes in attenuating neuroinflammation at an early stage post-TBI and explored the potential regulatory neuroprotective mechanism. We administered 30 μg protein of BMSCs-exosomes or an equal volume of phosphate-buffered saline (PBS) via the retro-orbital route into C57BL/6 male mice 15 min after controlled cortical impact (CCI)-induced TBI. The results showed that the administration of BMSCs-exosomes reduced the lesion size and improved the neurobehavioral performance assessed by modified Neurological Severity Score (mNSS) and rotarod test. In addition, BMSCs-exosomes inhibited the expression of proapoptosis protein Bcl-2-associated X protein (BAX) and proinflammation cytokines, tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β, while enhancing the expression of the anti-apoptosis protein B-cell lymphoma 2 (BCL-2). Furthermore, BMSCs-exosomes modulated microglia/macrophage polarization by downregulating the expression of inducible nitric oxide synthase (INOS) and upregulating the expression of clusters of differentiation 206 (CD206) and arginase-1 (Arg1). In summary, our result shows that BMSCs-exosomes serve a neuroprotective function by inhibiting early neuroinflammation in TBI mice through modulating the polarization of microglia/macrophages. Further research into this may serve as a potential therapeutic strategy for the future treatment of TBI.

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Countries in the the Asia-Pacific region and Africa tend to have the highest prevalence of hepatitis B infection worldwide. Hepatitis B infection progresses from an asymptomatic persistently infected status to chronic hepatitis B, cirrhosis, decompensated liver disease and/or hepatocellular carcinoma. The aim of this review was to summarize rates and risk factors for progression between disease states in the Asia-Pacific region and Africa. A literature search was conducted employing MEDLINE and EMBASE (1975-2003) using the following key words: hepatitis B, natural history, disease progression, cirrhosis, hepatocellular carcinoma, mortality, Africa and the Asia-Pacific region. Bibliographies of articles reviewed were also searched. Ranges for annual progression rates were: (i) asymptomatic persistent infection to chronic hepatitis B, 0.84-2.7%; (ii) chronic hepatitis B to cirrhosis, 1.0-2.4%; and (iii) cirrhosis to hepatocellular carcinoma, 3.0-6.6%. Patients with asymptomatic persistent infection and chronic hepatitis B had relatively low 5-year mortality rates (<4%); rates (>50%) were much higher in patients with decompensated liver disease and hepatocellular carcinoma. No data were found for progression rates in African populations. Hepatitis B e antigen was a risk factor for chronic hepatitis B, and bridging hepatic necrosis in chronic hepatitis B increased the risk of cirrhosis. Risk factors for hepatocellular carcinoma included cirrhosis, co-infection with hepatitis C virus, and genetic and environmental factors. In this review, wide ranges of disease progression estimates are documented, emphasizing the need for further studies, particularly in Africa, where progression rates are largely not available. Summarizing information on factors associated with disease progression should assist in focusing efforts to arrest the disease process in those at most risk.

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Efficient and cancer cell-targeted delivery of photosensitizer (PS) and therapeutic protein has great potentiality for improving the anticancer effects. Herein, zeolitic imidazolate framework-8 (ZIF-8) nanoparticles, one of the most attractive metal–organic framework materials, were used for coencapsulating the chlorin e6 (Ce6, a potent PS) and cytochrome c (Cyt c, a protein apoptosis inducer); then the nanoparticle was subsequently decorated with the hyaluronic acid (HA) shell to form cancer cell-active targeted nanoplatform (Ce6/Cyt c@ZIF-8/HA). The in vitro and in vivo experiments show the cancer cell targeting capability and pH-responsive decomposition and the release behavior of Ce6/Cyt c@ZIF-8/HA. Upon light irradiation, the released Ce6 produced cytotoxic reactive oxygen species for photodynamic therapy. Meanwhile, the released Cyt c-induced programmed cell death for protein therapy. Furthermore, the Cyt c worked normally under hypoxia conditions and could decompose H2O2 to O2 (with peroxidase-/catalase-like activity), resulting in synergistically improved therapeutic efficiency. These small molecules and protein codelivery nanoplatforms would promote the development of complementary and synergetic modes for biomedical applications.

The high printing efficiency and easy availability of desktop digital light processing (DLP) printers have made DLP 3D printing a promising technique with increasingly broad application prospects, particularly in personalized medicine. The objective of this study was to fabricate and evaluate medical samples with external and internal structures using the DLP technique. The influence of different additives and printing parameters on the printability and functionality of this technique was thoroughly evaluated. It was observed that the printability and mechanical properties of external structures were affected by the poly(ethylene glycol) diacrylate (PEGDA) concentration, plasticizers, layer height, and exposure time. The optimal printing solutions for 3D external and internal structures were 100% PEGDA and 75% PEGDA with 0.25 mg/mL tartrazine, respectively. And the optimal layer height for 3D external and internal structures were 0.02 mm and 0.05 mm, respectively. The optimal sample with external structures had an adequate drug-loading ability, acceptable sustained-release characteristics, and satisfactory biomechanical properties. In contrast, the printability of internal structures was affected by the photoabsorber, PEGDA concentration, layer height, and exposure time. The optimal samples with internal structures had good morphology, integrity and perfusion behavior. The present study showed that the DLP printing technique was capable of fabricating implants for drug delivery and physiological channels for in vivo evaluation.

Introduction: Ischemic stroke-induced inflammation and inflammasome-dependent pyroptotic neural death cause serious neurological injury. Nano-sized plasma exosomes have exhibited therapeutic potential against ischemia and reperfusion injury by ameliorating inflammation. To enhance its therapeutic potential in patients with ischemic injury, we isolated exosomes from melatonin-treated rat plasma and assessed the neurological protective effect in a rat model of focal cerebral ischemia. Methods: Basal plasma exosomes and melatonin-treated plasma exosomes were isolated and intravenously injected into a rat model of focal cerebral ischemia. Neurological recovery was evaluated by determining the modified neurological severity score (mNSS), infarct volume, and brain water content. Pyroptosis in the ischemic cortex was detected through dUTP nick-end labeling (TUNEL) assay, lactate dehydrogenase (LDH) release, and gasdermin D (GSDMD) cleavage. NLRP3 inflammasome assembly and global inflammatory cytokine secretion were detected by enzyme-linked immunosorbent assay (ELISA) and Western blot assay. In immunized Sprague-Dawley rats, microglia pyroptosis was determined through a positive percentage of IBA1 + and caspase-1 (p20) + cells. Finally, the microRNA (miRNA) profiles in melatonin-treated plasma exosomes were analyzed by exosome miRNA microarray analysis. Results: Melatonin treatment enhanced plasma exosome therapeutic effects against ischemia-induced inflammatory responses and inflammasome-mediated pyroptosis. In addition, we confirmed that ischemic stroke-induced pyroptotic cell death occurred in the microglia and neuron, while the administration of melatonin-treated exosomes further effectively decreased the infarct volume and improved recovery of function via regulation of the TLR4/NF-κB signaling pathway. Finally, the altered miRNA profiles in the melatonin-treated plasma exosomes demonstrated the regulatory mechanisms involved in neurological recovery after ischemic injury.