Binary Nano-inhalant Formulation of Icariin Enhances Cognitive Function in Vascular Dementia via BDNF/TrkB Signaling and Anti-inflammatory Effects.

Vascular dementia (VaD) has a serious impact on the patients' quality of life. Icariin (Ica) possesses neuroprotective potential for treating VaD, yet its oral bioavailability and blood-brain barrier (BBB) permeability remain challenges. This research introduced a PEG-PLGA-loaded chitosan hydrogel-based binary formulation tailored for intranasal delivery, enhancing the intracerebral delivery efficacy of neuroprotective agents. The formulation underwent optimization to facilitate BBB crossing, with examinations conducted on its particle size, morphology, drug-loading capacity, in vitro release, and biodistribution. Using the bilateral common carotid artery occlusion (BCCAO) rat model, the therapeutic efficacy of this binary formulation was assessed against chitosan hydrogel and PEG-PLGA nanoparticles loaded with Ica. Post-intranasal administration, enhanced cognitive function was evident in chronic cerebral hypoperfusion (CCH) rats. Further mechanistic evaluations, utilizing immunohistochemistry (IHC), RT-PCR, and ELISA, revealed augmented transcription of synaptic plasticity-associated proteins like SYP and PSD-95, and a marked reduction in hippocampal inflammatory markers such as IL-1ß and TNF-α, highlighting the formulation's promise in alleviating cognitive impairment. The brain-derived neurotrophic factor (BDNF)/tropomyosin related kinase B (TrkB) pathway was activated significantly in the binary formulation compared with the other two. Our study demonstrates that the intranasal application of chitosan hydrogel loaded with Ica-encapsulated PEG-PLGA could effectively deliver Ica into the brain and enhance its neuroprotective effect.

Effect of radioiodine therapy under thyroid hormone withdrawal on health-related quality of life in patients with differentiated thyroid cancer.

OBJECTIVE: To investigate the effect of radioactive iodine therapy under thyroid hormone withdrawal in differentiated thyroid cancer patients on health-related quality of life. METHODS: Patients who were diagnosed with differentiated thyroid cancer after thyroidectomy were involved in this study. All of them were managed with thyroid hormone withdrawal. Health-related quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and its thyroid cancer module at three different time points. Changes in health-related quality of life were evaluated by Wilcoxon and Kruskal-Wallis tests. Univariable logistic regression analysis was used to determine social-demographic and clinical factors associated with worse health-related quality of life. RESULTS: A total of 99 differentiated thyroid cancer patients were involved in this study. Changes in health-related quality of life at different time points showed that 1 month post-radioactive iodine treatment, an improvement in nausea and vomiting, insomnia and appetite loss was observed. Impairments of global health, role, cognitive and social function and problems of discomfort in the head and neck, voice concerns, dry mouth, fatigue, pain, dyspnea, thyroid fatigue, fear, tingling or numbness, joint pain and shoulder function increased after radioactive iodine treatment. Univariable logistic regression analysis demonstrated potential factors associated with worse health-related quality of life. Thyroid stimulating hormone and parathyroid hormone levels were more sensible to changes in functional domain. Patients aged ≥55-year-old, with annual income under ¥50 000, low parathyroid hormone and pT4 tumour stage experienced higher changes in symptom scales after radioactive iodine treatment. CONCLUSION: After radioactive iodine treatment, differentiated thyroid cancer patients experienced negative health-related quality of life, and most of these impairments might not recover in the short term. Thyroid stimulating hormone and parathyroid hormone levels, annual income and pT tumours stage were independent risk factors for decreased health-related quality of life.

[Clinicopathological Analysis of Autoimmune Hepatitis with Sjögren's Syndrome].

OBJECTIVE: To explore the biochemical-immune and pathological characteristics of autoimmune hepatitis (AIH) with Sjögren's syndrome (SS) . METHODS: A total of 76 cases of AIH patients were included from January 2009 to April 2017. Among them,there were 40 cases of AIH with SS and 36 cases without SS. The liver function,immunological index,histological features,length of first diagnosis and treatment costs were compared between the two groups. RESULTS: For AIH+SS group and AIH group,the proportion of women were 97.5% and 77.8%,the proportion of the first diagnosis age less than 60 years were 70% and 47.2%,the median course of disease were 30 months and 9 months,all the difference were statistically significant (P<0.05). The chief complaints in AIH+SS group and AIH group were as follows: cutaneous or scleracterus (52.5% vs. 38.9%),abnormal transaminase (17.5% vs. 44.4%),dryness of mouth and eye (15.0% vs. 2.8%),all the difference were statistically significant (P<0.05). There were no statistically significant difference in hospitalization expenses,and length of stay between the two groups (P>0.05). The median level of total bilirubin (TBIL),direct bilirubin (DBIL) and immunoglobulin (Ig) M of AIH +SS group were higher than those of AIH group,the mean level of albumin (ALB) and complement 3 (C3) of AIH +SS group were lower than those of AIH group,and the positive rate of anti-mitochondrial antibody-M2 (AMA-M2) ,anti-Ro antibody A (SSA),anti-La antibody (SSB) and anti-soluble liver antigen antibody (SLA) of AIH+SS group were higher than those of AIH group (P<0.05). There were no statistically significant difference in histological changes of hepatocytes and bile duct injury rate (P>0.05). CONCLUSION: AIH patients in young and middle-aged women need to be vigilant with SS with main manifestation of skin sclera and high specific autoantibodies positive.

Long hydrophilic-and-cationic polymers: a different pathway toward preferential activity against bacterial over mammalian membranes.

We show that simply converting the hydrophobic moiety of an antimicrobial peptide (AMP) or synthetic mimic of AMPs (SMAMP) into a hydrophilic one could be a different pathway toward membrane-active antimicrobials preferentially acting against bacteria over host cells. Our biostatistical analysis on natural AMPs indicated that shorter AMPs tend to be more hydrophobic, and the hydrophilic-and-cationic mutants of a long AMP experimentally demonstrated certain membrane activity against bacteria. To isolate the effects of antimicrobials' hydrophobicity and systematically examine whether hydrophilic-and-cationic mutants could inherit the membrane activity of their parent AMPs/SMAMPs, we constructed a minimal prototypical system based on methacrylate-based polymer SMAMPs and compared the antibacterial membrane activity and hemolytic toxicity of analogues with and without the hydrophobic moiety. Antibacterial assays showed that the hydrophobic moiety of polymer SMAMPs consistently promoted the antibacterial activity but diminished in effectiveness for long polymers, and the resultant long hydrophilic-and-cationic polymers were also membrane active against bacteria. What distinguished these long mutants from their parent SMAMPs were their drastically reduced hemolytic toxicities and, as a result, strikingly enhanced selectivity. Similar toxicity reduction was observed with the hydrophilic-and-cationic mutants of long AMPs. Taken together, our results suggest that long hydrophilic-and-cationic polymers could offer preferential membrane activity against bacteria over host cells, which may have implications in future antimicrobial development.

Interactions between intestinal microbiota and metabolites in zebrafish larvae exposed to polystyrene nanoplastics: Implications for intestinal health and glycolipid metabolism.

Previous studies have shown the harmful effects of nanoscale particles on the intestinal tracts of organisms. However, the specific mechanisms remain unclear. Our present study focused on examining the uptake and distribution of polystyrene nanoplastics (PS-NPs) in zebrafish larvae, as well as its toxic effects on the intestine. It was found that PS-NPs, marked with red fluorescence, primarily accumulated in the intestine section. Subsequently, zebrafish larvae were exposed to normal PS-NPs (0.2-25 mg/L) over a critical 10-day period for intestinal development. Histopathological analysis demonstrated that PS-NPs caused structural changes in the intestine, resulting in inflammation and oxidative stress. Additionally, PS-NPs disrupted the composition of the intestinal microbiota, leading to alterations in the abundance of bacterial genera such as Pseudomonas and Aeromonas, which are associated with intestinal inflammation. Metabolomics analysis showed alterations in metabolites that are primarily involved in glycolipid metabolism. Furthermore, MetOrigin analysis showed a significant correlation between bacterial flora (Pedobacter and Bacillus) and metabolites (D-Glycerate 2-phosphate and D-Glyceraldehyde 3-phosphate), which are related to the glycolysis/gluconeogenesis pathways. These findings were further validated through alterations in multiple biomarkers at various levels. Collectively, our data suggest that PS-NPs may impair the intestinal health, disrupt the intestinal microbiota, and subsequently cause metabolic disorders.

Behavioral impairments and disrupted mitochondrial energy metabolism induced by polypropylene microplastics in zebrafish larvae.

Polypropylene microplastics (PP-MPs) are emerging pollutant commonly detected in various environmental matrices and organisms, while their adverse effects and mechanisms are not well known. Here, zebrafish embryos were exposed to environmentally relevant concentrations of PP-MPs (0.08-50 mg/L) from 2 h post-fertilization (hpf) until 120 hpf. The results showed that the body weight was increased at 2 mg/L, heart rate was reduced at 0.08 and 10 mg/L, and behaviors were impaired at 0.4, 10 or 50 mg/L. Subsequently, transcriptomic analysis in the 0.4 and 50 mg/L PP-MPs treatment groups indicated potential inhibition on the glycolysis/gluconeogenesis and oxidative phosphorylation pathways. These findings were validated through alterations in multiple biomarkers related to glucose metabolism. Moreover, abnormal mitochondrial ultrastructures were observed in the intestine and liver in 0.4 and 50 mg/L PP-MPs treatment groups, accompanied by significant decreases in the activities of four mitochondrial electron transport chain complexes and ATP contents. Oxidative stress was also induced, as indicated by significantly increased ROS levels and significant reduced activities of CAT and SOD and GSH contents. All the results suggested that environmentally relevant concentrations of PP-MPs could induce disrupted mitochondrial energy metabolism in zebrafish, which may be associated with the observed behavioral impairments. This study will provide novel insights into PP-MPs-induced adverse effects and highlight need for further research.

Clinical summary of pediatric acute lymphoblastic leukemia patients complicated with asparaginase-associated pancreatitis in SCCLG-ALL-2016 protocol.

Asparaginase-associated pancreatitis (AAP) is a common and fatal complication after ASNase treatment in acute lymphoblastic leukemia(ALL). Here, a total of 1063 pediatric ALL patients treated with SCCLG-ALL-2016 regimen were collected since October 2016 to June 2020, including 35 patients with AAP. The clinical characteristics of AAP and non-AAP patients were compared. In AAP patients, the possible factors that affected the recurrence of AAP were analyzed, and the possible risk factors related to ALL-relapse were discussed. The results showed that age was a risk factor (P = .017) that affect the occurrence of AAP. In AAP patients, AAP tended to develop after the second use of PEG-ASNase (25.71%). In the follow-up chemotherapy, 17 patients re-exposed to ASNase and 7 cases developed AAP again with a percentage was 41.2%. There were no special factors that related with the recurrence of AAP. This study also found no association between the occurrence of AAP and prognosis of ALL, with the 4-year incidence of ALL relapse in AAP and non-AAP patients were 15.9% v.s.11.7% (HR: 1.009, 95% CI:0.370-2.752, P = .986), and there were no special factors that related with the ALL relapse among AAP patients. Based on the above results, the occurrence of AAP is related to age and should be vigilant after the second use of PEG-ASNase after use in pediatric ALL patients. Moreover, AAP is not associated with ALL relapse, but there is a high AAP recurrence rate when re-exposure to ASNase.

Preparation of baicalin-loaded ligand-modified nanoparticles for nose-to-brain delivery for neuroprotection in cerebral ischemia.

Neuroprotection in cerebral ischemia (CI) has received increasing attention. However, efficient delivery of therapeutic agents to the brain remains a major challenge due to the complex environment of the brain. Nose-to-brain-based delivery is a promising approach. Here, we optimized a nanocarrier formulation of neuroprotective agents that can be used for nose-to-brain delivery by obtaining RVG29 peptide-modified polyethylene glycol-polylactic acid-co-glycolic acid nanoparticles (PEG-PLGA RNPs) that have physicochemical properties that lead to stable and sustained drug release and thereby improve the bioavailability of neuroprotective agents. The brain-targeting ability of PEG-PLGA RNPs administered through nasal inhalation was verified in a rat model of CI. It was found that delivery to the whole brain can be achieved with little delivery to the peripheral circulation. Baicalin (BA) was selected as the neuroprotective agent for delivery. After intranasal administration of BA-PEG-PLGA RNPs, the neurological dysfunction of rats with ischemic brain injury was significantly alleviated, the cerebral infarction area was reduced, and nerve trauma and swelling were relieved. Furthermore, it was demonstrated that the neuroprotective effects of BA in a rat model of CI may be mediated by inhibition of inflammation and alleviation of oxidative stress. The immunohistochemical results obtained after treatment with nanoparticles loaded with BA showed that Nrf2/HO-1 was activated in the area in which ischemic brain damage had occurred and that its expression was significantly higher in the group treated with BA-PEG-PLGA RNPs than in the other groups. The ELISA results showed that the levels of IL-1ß, IL-6, and TNF-α were abnormally increased in the serum of rats with cerebral ischemia. After treatment with BA-loaded nanoparticles, IL-1ß, IL-6, and TNF-α levels decreased significantly. Oxidative stress was alleviated; the levels of glutathione and superoxide dismutase increased; and the levels of reactive oxygen species and malondialdehyde decreased, in animals to which BA-PEG-PLGA RNPs were delivered by intranasal inhalation. In conclusion, BA-PEG-PLGA RNPs can effectively deliver BA to rats and thereby exert neuroprotective effects against CI.

Mechanism of a prototypical synthetic membrane-active antimicrobial: Efficient hole-punching via interaction with negative intrinsic curvature lipids.

Phenylene ethynylenes comprise a prototypical class of synthetic antimicrobial compounds that mimic antimicrobial peptides produced by eukaryotes and have broad-spectrum antimicrobial activity. We show unambiguously that bacterial membrane permeation by these antimicrobials depends on the presence of negative intrinsic curvature lipids, such as phosphatidylethanolamine (PE) lipids, found in high concentrations within bacterial membranes. Plate-killing assays indicate that a PE-knockout mutant strain of Escherichia coli drastically out-survives the wild type against the membrane-active phenylene ethynylene antimicrobials, whereas the opposite is true when challenged with traditional metabolic antibiotics. That the PE deletion is a lethal mutation in normative environments suggests that resistant bacterial strains do not evolve because a lethal mutation is required to gain immunity. PE lipids allow efficient generation of negative curvature required for the circumferential barrel of an induced membrane pore; an inverted hexagonal H(II) phase, which consists of arrays of water channels, is induced by a small number of antimicrobial molecules. The estimated antimicrobial occupation in these water channels is nonlinear and jumps from approximately 1 to 3 per 4 nm of induced water channel length as the global antimicrobial concentration is increased. By comparing to exactly solvable 1D spin models for magnetic systems, we quantify the cooperativity of these antimicrobials.

[Progress in researches on synthetic antimicrobial macromolecular polymers].

Broad-spectrum antimicrobial peptides provide a new way to address the urgent growing problem of bacterial resistance. However, the limited natural resources and the high cost of extraction and purification of natural antimicrobial peptides can not meet the requirements of clinical application. In order to solve this problem, researchers have utilized two basic common structural features (amphiphilic and cationic) for designing and preparing synthetic antimicrobial macromolecular polymers. During the last decade, several kinds of amphiphilic polymers, including arylamide oligomers, phenylene ethynylenes, polymethacrylates, polynorbornenes as well as nylon-3 polymers have been synthesized. In this paper, the structures, antibacterial activities and selectivities of these polymers are reviewed, and the effects of molecular size, polarity and ratio of hydrophobic groups, positive charge density on antibacterial activity and selectivity are also summarized.

RVG29-modified microRNA-loaded nanoparticles improve ischemic brain injury by nasal delivery.

Effective nose-to-brain delivery needs to be developed to treat neurodegenerative diseases. Regulating miR-124 can effectively improve the symptoms of ischemic brain injury and provide a certain protective effect from brain damage after cerebral ischemia. We used rat models of middle cerebral artery occlusion (t-MCAO) with ischemic brain injury, and we delivered RVG29-NPs-miR124 intranasally to treat neurological damage after cerebral ischemia. Rhoa and neurological scores in rats treated by intranasal administration of RVG29-PEG-PLGA/miRNA-124 were significantly lower than those in PEG-PLGA/miRNA-124 nasal administration and RVG29-PLGA/miRNA-124 nasal administration group treated rats. These results indicate that the nose-to-brain delivery of PLGA/miRNA-124 conjugated with PEG and RVG29 alleviated the symptoms of cerebral ischemia-reperfusion injury. Thus, nasal delivery of RVG29-PEG-PLGA/miRNA-124 could be a new method for treating neurodegenerative diseases.

Divalent metal ion triggered activity of a synthetic antimicrobial in cardiolipin membranes.

One member of a prototypical class of antimicrobial oligomers was used to study pore formation in cardiolipin-rich membranes. Both vesicle dye-leakage assays and small-angle X-ray scattering were used to study bilayer remodeling. The results indicate that the presence of negative intrinsic curvature lipids is essential for pore formation by this class of molecules: In Gram-positive bacteria, cardiolipin and divalent metal cations like Ca(2+) and Mg(2+) are needed. This is consistent with the role of phosphatidylethanolamine (PE) lipid in Gram-negative bacteria, where antimicrobial activity is dependent on the negative intrinsic curvature of PE rather than a specific interaction with PE.

Overproduction of microbial extracellular polymeric substances in subtropical intertidal sediments in response to endocrine disrupting chemicals.

Microorganisms and their extracellular polymeric substances (EPS) in sediments are important in sediment stabilization and the fate of pollutants. However, how toxic organic pollutants affect bacteria and EPS in sediments, particularly in subtropical intertidal zones is poorly known. The present study aims to investigate the bacterial abundance and related EPS in simulated intertidal sandflat and mangrove sediments under the stress of endocrine disrupting chemicals (EDCs). Results showed that the temporal changes of the bacterial number in both sandflat and mangrove sediments were similar, increased from days 0 to 56 then became steady during the 84-days incubation. Bacteria exhibited an important role in the production of high molecular weight (HMW) EPS protein and the degradation of the low molecular weight (LMW) EPS protein. During incubation, the EPS polysaccharides changed from a colloidal-LMW fraction at the beginning to a more complex-HMW fraction at the end of the experiment. The increases in the concentration of HMW polysaccharides might contribute to sediment stabilization. Among different spiked EDCs, nonylphenol (NP) and 17α-ethinylestradiol (EE2) tended to accumulate in both sandflat and mangrove sediments and posed stresses to bacterial growth, especially the latter sediment. The persistent EDCs promoted a higher production of EPS polysaccharides and proteins in both sediments when compared to the respective control, but the EPS in the sandflat sediment was mainly in the colloidal fraction while the bound fraction was more abundant in the mangrove sediment. The present results enhance our understanding of the effects of EDCs on sediment biofilms in intertidal systems. This study also demonstrates the significance of EPS polysaccharides and proteins in sediment stabilization and provides a fundamental basis for future microbiology studies.

[Characterization and histocompatibility of acellular bone collagen matrices].

A processing technique has been developed to prepare acellular bone collagen matrix (ABCM) and ABCM-PDLLA composite materials. The properties of these materials were characterized through several different methods. The histocompatibility of the materials were investigated by ELISA (enzyme linked immunosorbent assay) test and healing the defection of New Zealand white rabbit bilateral radius. The spectroscopy indicated that the major inorganic and organic components of the bone blocks were carbonated hydroxyapatite and collagen respectively,and the fatty and cellular components were. completely eliminated. The test results also revealed that the materials had good mechanical property and well-internnected pore structure, and the addition of PDLLA increased the strength of the materials. The ELISA results demonstrated that the materials had low immunogenicity in short order, and the degree of immune response caused by ABCM was greater than that by ABCM-PDLLA. All of the grafts exhibited good osteoconductive ability and a new bone form after the creeping substitution. In conclusion, two kinds of materials with good histocompatibility have been prepared, and owing to its good mechanical performance and low immunogenicity, ABCM-PDLLA is a better candidate for bone substitute and bone tissue engineering scaffold when compared with single ABCM.

Skin-safe photothermal therapy enabled by responsive release of acid-activated membrane-disruptive polymer from polydopamine nanoparticle upon very low laser irradiation.

How to ablate tumor without damaging skin is a challenge for photothermal therapy. We, herein, report skin-safe photothermal cancer therapy provided by the responsive release of acid-activated hemolytic polymer (aHLP) from the photothermal polydopamine (PDA) nanoparticle upon irradiation at very low dosage. Upon skin-permissible irradiation (via an 850 nm laser irradiation at the power density of 0.4 W cm-2), the nanoparticle aHLP-PDA generates sufficient localized-heat to bring about mild hyperthermia treatment and consequently, responsively sheds off the aHLP polymer from its PDA nanocore; this leads to selective cytotoxicity to cancer cells under the acidic conditions of the extracellular microenvironment of tumor. As a result, our aHLP-PDA nanoparticle upon irradiation at a low dosage effectively inhibits tumor growth without damaging skin, as demonstrated using animal models. Effective in mitigating the otherwise inevitable skin damage in tumor photothermal therapy, the nanosystem reported herein offers an efficient pathway towards skin-safe photothermal therapy.

Calcium and Magnesium Ions Are Membrane-Active against Stationary-Phase Staphylococcus aureus with High Specificity.

Staphylococcus aureus (S. aureus) is notorious for its ability to acquire antibiotic-resistance, and antibiotic-resistant S. aureus has become a wide-spread cause of high mortality rate. Novel antimicrobials capable of eradicating S. aureus cells including antibiotic-resistant ones are thus highly desired. Membrane-active bactericides and species-specific antimicrobials are two promising sources of novel anti-infective agents for fighting against bacterial antibiotic-resistance. We herein show that Ca(2+) and Mg(2+), two alkaline-earth-metal ions physiologically essential for diverse living organisms, both disrupt model S. aureus membranes and kill stationary-phase S. aureus cells, indicative of membrane-activity. In contrast to S. aureus, Escherichia coli and Bacillus subtilis exhibit unaffected survival after similar treatment with these two cations, indicative of species-specific activity against S. aureus. Moreover, neither Ca(2+) nor Mg(2+) lyses mouse red blood cells, indicative of hemo-compatibility. This works suggests that Ca(2+) and Mg(2+) may have implications in targeted eradication of S. aureus pathogen including the antibiotic-resistant ones.

Acid-Responsive Therapeutic Polymer for Prolonging Nanoparticle Circulation Lifetime and Destroying Drug-Resistant Tumors.

How to destroy drug-resistant tumor cells remains an ongoing challenge for cancer treatment. We herein report on a therapeutic nanoparticle, aHLP-PDA, which has an acid-activated hemolytic polymer (aHLP) grafted onto photothermal polydopamine (PDA) nanosphere via boronate ester bond, in efforts to ablate drug-resistant tumors. Upon exposure to oxidative stress and/or near-infrared laser irradiation, aHLP-PDA nanoparticle responsively releases aHLP, likely via responsive cleavage of boronate ester bond, and thus responsively exhibits acid-facilitated mammalian-membrane-disruptive activity. In vitro cell studies with drug-resistant and/or thermo-tolerant cancer cells show that the aHLP-PDA nanoparticle demonstrates preferential cytotoxicity at acidic pH over physiological pH. When administered intravenously, the aHLP-PDA nanoparticle exhibits significantly prolonged blood circulation lifetime and enhanced tumor uptake compared to bare PDA nanosphere, likely owing to aHLP's stealth effects conferred by its zwitterionic nature at blood pH. As a result, the aHLP-PDA nanoparticle effectively ablates drug-resistant tumors, leading to 100% mouse survival even on the 32nd day after suspension of photothermal treatment, as demonstrated with the mouse model. This work suggests that a combination of nanotechnology with lessons learned in bacterial antibiotic resistance may offer a feasible and effective strategy for treating drug-resistant cancers often found in relapsing patients.

Cooperative Nanoparticle System for Photothermal Tumor Treatment without Skin Damage.

How to ablate tumors without using skin-harmful high laser irradiance remains an ongoing challenge for photothermal therapy. Here, we achieve this with a cooperative nanosystem consisting of gold nanocage (AuNC) "activator" and a cationic mammalian-membrane-disruptive peptide, cTL, as photothermal antenna and anticancer agent, respectively. Specifically, this nanosystem is prepared by grafting cTL onto AuNC via a Au-S bond, followed by attachment of thiolated polyethylene glycol (PEG) for stealth effects. Upon NIR irradiation at skin-permissible dosage, the resulting cTL/PEG-AuNC nanoparticle effectively ablates both irradiated and nonirradiated cancer cells, likely owing to cTL being responsively unleashed by intracellular thiols exposed to cTL/PEG-AuNC via membrane damage initiated by AuNC's photothermal effects and deteriorated by the as-released cTL. When administered systematically in a mouse model, cTL/PEG-AuNC populates tumors through their porous vessels and effectively destroys them without damaging skin.

Nanomaterial-dependent immunoregulation of dendritic cells and its effects on biological activities of contraceptive nanovaccines.

Nanovehicles are promising delivery systems for various vaccines. Nevertheless, different biophysicochemical properties of nanoparticles (NPs), dominating their in vitro and in vivo performances for vaccination, remain unclear. We attempted to elucidate the effects of NPs and their pH-sensitivity on in vitro and in vivo efficacy of resulting prophylactic nanovaccines containing a contraceptive peptide (FSHR). To this end, pH-responsive and non-responsive nanovaccines were produced using acetalated ß-cyclodextrin (Ac-bCD) and poly(lactic-co-glycolic acid) (PLGA), respectively. Meanwhile, FSHR derived from an epitope of the follicle-stimulating hormone receptor was used as the model antigen. FSHR-containing Ac-bCD and PLGA NPs were successfully prepared by a nanoemulsion technique, leading to well-shaped nanovaccines with high loading efficiency. The pH-sensitivity of Ac-bCD and PLGA nanovaccines was examined by in vitro hydrolysis and antigen release studies. Nanovaccines could be effectively engulfed by dendritic cells (DCs) via endocytosis in both dose and time dependent manners, and their intracellular trafficking was closely related to the pH-sensitivity of the carrier materials. Furthermore, nanovaccines could induce the secretion of inflammatory cytokines by DCs and T cells co-cultured with the stimulated DCs. In vivo evaluations demonstrated that nanovaccines were more potent than that based on the complete Freund's adjuvant, with respect to inducing anti-FSHR antibody, reducing the sperm count, inhibiting the sperm motility, and increasing the teratosperm rate. Immunization of male mice with nanovaccines notably decreased the parturition incidence of the mated females. Consequently, both in vitro and in vivo activities of FSHR could be considerably augmented by NPs. More importantly, our studies indicated that the pH-responsive nanovaccine was not superior over the non-responsive counterpart for the examined peptide antigen.

[Preparation and characterization of bovine bone collagen matrix].

A process of preparing bovine cortical bone in order to form materials suitable for biomedical xenograft implants was described. Fresh bone samples cut from the middiaphyseal region of bovine femora were obtained from a local slaughterhouse. The bovine bone collagen matrix (BBCM) of various shapes fabricated from bovine bone by defatting and deproteination procedure may be implanted surgically for various purposes. The bone cubes were first defatted in a mixture of defatting agent; subsequently, the samples were extracted to release noncollagenous proteins, followed by digestion using a proteolytic enzyme to remove the telopeptide portions of collagen and residual noncollagenous proteins. Finally,the samples were dried in vacuum, packed and sterilized by gamma irradiation. The bone specimens were characterized by a suite of analytical techniques involving FTIR spectroscopy, X-ray diffraction spectroscopy, differential scanning calorimetry (DSC), uniaxial tension mechanical tests and scanning electron microscopy (SEM). The result showed that BBCM occurred as a white structure with suitable porosity. It contains reasonable proprotion of mineral and organic components in the original osseous architecture of the bovine bone, which is beneficial to keeping the mechanic property and weaker immunogenicity; therefore, it can serve as a potential bone implantable material and extracellular matrix material in bone tissue engineering.