Pollen-Mimetic Metal-Organic Frameworks with Tunable Spike-Like Nanostructures That Promote Cell Interactions to Improve Antigen-Specific Humoral Immunity.

The exine capsules of pollen particles exhibit a variety of characteristic surface morphologies that promote their cell interactions; their use as antigen carriers for vaccination has been proposed. However, the allergy-causing substances in pollen particles may not all be removed, even by vigorous chemical treatments. To resolve this issue, this work develops systemic approaches for synthesizing pollen-mimetic metal-organic frameworks (MOFs), which comprise aluminum (Al) ions and an organic linker (2-aminoterephthalic acid), with tunable spike-like nanostructures on their surfaces. The as-synthesized MOFs act not only as a delivery vehicle that carries a model antigen (ovalbumin, OVA) but also as an adjuvant (Al). Scanning and transmission electron microscopies images reveal that the aspect ratio of the nanospikes that are grown on the MOFs can be controlled. A higher aspect ratio of the nanospikes on the MOFs is associated with greater cell attachment and faster and more efficient phagocytosis in cells, which results in greater expressions of pro-inflammatory cytokines. Consequently, a more robust immune response against the antigen of interest is elicited. These findings have broad implications for the rational design of the future antigen/adjuvant-presenting particles for vaccination.

Modulation of tumor microenvironment using a TLR-7/8 agonist-loaded nanoparticle system that exerts low-temperature hyperthermia and immunotherapy for in situ cancer vaccination.

Most cancer vaccines under development are associated with defined tumor antigens rather than with all antigens of whole tumor cells, limiting the anti-tumor immune responses that they elicit. This work proposes an immunomodulator (R848)-loaded nanoparticle system (R848@NPs) that can absorb near-infrared light (+NIR) to cause low-temperature hyperthermia that interacts synergistically with its loaded R848 to relieve the tumor-mediated immunosuppressive microenvironment, generating robust anti-tumor memory immunity. In vitro results reveal that the R848@NPs could be effectively internalized by dendritic cells, causing their maturation and the subsequent regulation of their anti-tumor immune responses. Post-treatment observations in mice in which tumors were heat-treated at high temperatures reveal that tumor growth was significantly inhibited initially but not in the longer term, while low-temperature hyperthermia or immunotherapy alone simply delayed tumor growth. In contrast, a combined therapy that involved low-temperature hyperthermia and immunotherapy using R848@NPs/+NIR induced a long-lasting immunologic memory and consequently inhibited tumor growth and prevented cancer recurrence and metastasis. These results suggest that the method that is proposed herein is promising for generating cancer vaccines in situ, by using the tumor itself as the antigen source and the introduced R848@NPs/+NIR to generate a long-term anti-tumor immunity, for personalized immunotherapy.

Acidity-triggered charge-convertible nanoparticles that can cause bacterium-specific aggregation in situ to enhance photothermal ablation of focal infection.

Focal infections that are caused by antibiotic-resistant bacteria are becoming an ever-growing challenge to human health. To address this challenge, a pH-responsive amphiphilic polymer of polyaniline-conjugated glycol chitosan (PANI-GCS) that can self-assemble into nanoparticles (NPs) in situ is developed. The PANI-GCS NPs undergo a unique surface charge conversion that is induced by their local pH, favoring bacterium-specific aggregation without direct contact with host cells. Following conjugation onto GCS, the optical-absorbance peak of PANI is red-shifted toward the near-infrared (NIR) region, enabling PANI-GCS NPs to generate a substantial amount of heat, which is emitted to their neighborhood. The local temperature of the NIR-irradiated PANI-GCS NPs is estimated to be approximately 5 °C higher than their ambient tissue temperature, ensuring specific and direct heating of their aggregated bacteria; hence, damage to tissue is reduced and wound healing is accelerated. The above results demonstrate that PANI-GCS NPs are practical for use in the photothermal ablation of focal infections.

Synergistic antibacterial effects of localized heat and oxidative stress caused by hydroxyl radicals mediated by graphene/iron oxide-based nanocomposites.

This work develops a composite system of reduced graphene oxide (rGO)-iron oxide nanoparticles (rGO-IONP) that can synergistically induce physical and chemical damage to methicillin-resistant Staphylococcus aureus (MRSA) that are present in subcutaneous abscesses. rGO-IONP was synthesized by the chemical deposition of Fe(2+)/Fe(3+) ions on nanosheets of rGO in aqueous ammonia. The antibacterial efficacy of the as-prepared rGO-IONP was evaluated in a mouse model with MRSA-infected subcutaneous abscesses. Upon exposure to a near-infrared laser in vitro, rGO-IONP synergistically generated localized heat and large amounts of hydroxyl radicals, which inactivated MRSA. The in vivo results reveal that combined treatment with localized heat and oxidative stress that is caused by hydroxyl radicals accelerated the healing of wounds associated with MRSA-infected abscesses. The above results demonstrate that an rGO-IONP nanocomposite system that can effectively inactivate multiple-drug-resistant bacteria in subcutaneous infections was successfully developed. FROM THE CLINICAL EDITOR: The emergence of methicillin-resistant S. aureus (MRSA) has posed a significant problem in the clinical setting. Thus, it is imperative to develop new treatment strategies against this. In this study, the authors described the use of reduced graphene oxide (rGO)-iron oxide nanoparticles (rGO-IONP) to induce heat and chemical damage to MRSA. This approach may provide a platform the design of other treatment modalities against multiple-drug-resistant bacteria.

[Comparation of effect and cost-benefit analysis between acupoint catgut-embedding and electroacupuncture on simple obesity].

OBJECTIVE: To compare the clinical effect of acupoint catgut-embedding and electroacupuncture on simple obesity and evaluate the economics benefit by cost-benefit analysis. METHODS: Sixty cases were randomly devided into an acupoint catgut-embedding group and an electroacupuncture group, 30 cases in each group. Zhongwan (CV 12), Tianshu (ST 25), Daheng (SP 15), Shuifen (CV 9), Qihai (CV 6), Guanyuan (CV 4), Zusanli (ST 36) and Ashi acupoints were selected as the main acupoints in both groups. The acupoint catgut-embedding group was treated with acupoint catgut-embedding, once each week, four weeks as a course for two courses. The electroacupuncture group was treated with electroacupuncture, three times each week for eight weeks. RESULTS: 1) The total effective rate in the acupoint catgut-embedding group was 90.0% (27/30) and in the electroacupuncture group was 86.7% (26/30), with the similar therapeutic effect between the two groups (P > 0.05). 2) The body mass, body mass index (BMI), waistline, hip circumference and waist-to-hip ratio in the two groups were all decreased significantly (all P < 0.05). 3) The total medical treatment cost in the acupoint catgut-embedding group was 61 500 yuan and the cost per patient was 2050 yuan, and in the electroacupuncture group, the total cost was 117 210 yuan and the cost per patient was 3907 yuan. The cost effect analysis showed that there were 1857 yuan of the cost per patient in the acupoint catgut-embedding group less than that in the electroacupuncture group. CONCLUSION: Acupoint catgut-embedding has significant effect in treating simple obesity with low cost and fine economics benefit.

[Observation on treatment of chronic pelvic inflammatory with point injection combined with ultra-laser radiation].

OBJECTIVE: To probe into clinical therapeutic effect of point injection combined with ultra-laser radiation on chronic pelvic inflammatory. METHODS: Sixty cases of chronic pelvic inflammatory were divided into a treatment group and a control group, 30 cases in each group. The treatment group were treated with point injection of Yuxingcao Injectio combined with ultra-laser point radiation, and the control group with simple point injection of Yuxingcao Injectio, once each day, for 4 weeks. RESULTS: Twenty-eight cases were effective with a total effective rate of 93.3% in the treatment group, and 23 cases were effective with a total effective rate of 76.7%; the weighty pain of lower abdomen, abnormal leucorrhea and signs of gynecological examination, etc. in the treatment group significantly improved as compared with the control group (P<0.05). CONCLUSION: Point injection combined with ultra-laser radiation has definite therapeutic effect on chronic pelvic inflammatory.

Four new 6-nor5(6-->7)abeo-abietane type diterpenes and antitumoral cytotoxic diterpene constituents from the bark of Taiwania cryptomerioides.

Four new 6-nor-5(6-->7) abeo-abietane type diterpenes designated as taiwaniaquinone G, taiwaniaquinone H, taiwaniaquinol E and taiwaniaquinol F and eight known diterpenes, taiwaniaquinones A (5), D (6), E, F (8), and taiwaniaquinols A (9), B, C (11), D (12) were isolated from the bark of Taiwania cryptomerioides. Their structures were elucidated on the basis of spectroscopic studies. These twelve diterpenes were evaluated for in vitro antitumoral cytotoxic activity. The result demonstrated that compounds 5, 6, 8, 9, 11, and 12 bearing an aldehyde group possessed potent cytotoxic activity against KB epidermoid carcinoma cancer cell lines with IC50 values of 6.9, 7.2, 4.4, 8.3, 8.1, and 3.5 microM, respectively.