A multifunctional platform with single-NIR-laser-triggered photothermal and NO release for synergistic therapy against multidrug-resistant Gram-negative bacteria and their biofilms.

BACKGROUND: Infectious diseases caused by multidrug-resistant (MDR) bacteria, especially MDR Gram-negative strains, have become a global public health challenge. Multifunctional nanomaterials for controlling MDR bacterial infections via eradication of planktonic bacteria and their biofilms are of great interest. RESULTS: In this study, we developed a multifunctional platform (TG-NO-B) with single NIR laser-triggered PTT and NO release for synergistic therapy against MDR Gram-negative bacteria and their biofilms. When located at the infected sites, TG-NO-B was able to selectively bind to the surfaces of Gram-negative bacterial cells and their biofilm matrix through covalent coupling between the BA groups of TG-NO-B and the bacterial LPS units, which could greatly improve the antibacterial efficiency, and reduce side damages to ambient normal tissues. Upon single NIR laser irradiation, TG-NO-B could generate hyperthermia and simultaneously release NO, which would synergistically disrupt bacterial cell membrane, further cause leakage and damage of intracellular components, and finally induce bacteria death. On one hand, the combination of NO and PTT could largely improve the antibacterial efficiency. On the other hand, the bacterial cell membrane damage could improve the permeability and sensitivity to heat, decrease the photothermal temperature and avoid damages caused by high temperature. Moreover, TG-NO-B could be effectively utilized for synergistic therapy against the in vivo infections of MDR Gram-negative bacteria and their biofilms and accelerate wound healing as well as exhibit excellent biocompatibility both in vitro and in vivo. CONCLUSIONS: Our study demonstrates that TG-NO-B can be considered as a promising alternative for treating infections caused by MDR Gram-negative bacteria and their biofilms.

Traditional Chinese medicine Bushen-Jianpi-Huoxue decoction prevents diabetic osteoporosis in rats via Wnt and nuclear factor-kappa B signaling pathways.

AIM: The aim of this study was to evaluate the therapeutic effect of a traditional Chinese medicine (TCM), Bushen-Jianpi-Huoxue decoction (BJHD), on diabetic osteoporosis (DOP) and the action mechanisms likely mediated by nuclear factor-kappa B (NF-κB) and Wnt signaling pathways. METHODS: Fifty-five male Wistar rats were used in this study; they were divided into normal control (n = 10) and established DOP model (n = 45) groups. The DOP model was induced using a combination high carbohydrate - high fat diet and intraperitoneal injections of streptozotocin (STZ). The successfully induced animals were randomized to the model, Western medicine, TCM and control groups. Levels of fasting blood glucose; insulin; serum Ca, P and alkaline phosphatase, and the femoral bone mineral density (BMD) were measured. Furthermore, messenger RNA (mRNA) levels of cytokines in the Wnt and NF-κB signaling pathways were measured using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Thirty rats were successfully established as the DOP model (10/group). After treatment, the levels of fasting blood glucose, insulin resistance and alkaline phosphatase in the TCM group rats were lower, while P and BMD were higher than those in the model groups. The mRNA levels of cytokines in the Wnt signaling pathway were higher in the TCM group than those in the model group. Moreover, the expressions of factors in the NF-κB pathway were markedly lower in the TCM group than they were in the model group. CONCLUSION: Bushen-Jianpi-Huoxue decoction relieved DOP by activating the Wnt signaling pathway while inhibiting NF-κB signaling.

A traditional Chinese medicine formula extracts stimulate proliferation and inhibit mineralization of human mesenchymal stem cells in vitro.

AIM OF THE STUDY: To investigate the effects of a traditional Chinese medicine (TCM) formula extract, named as ZD-I, on the proliferation and osteogenic differentiation of human mesenchymal stem cells (hMSCs) in vitro. MATERIALS AND METHODS: When hMSCs cultivated in the basal medium with ZD-I, cell viability was assessed by MTT assay and cellular proliferation was assessed by SYBR green I assay. The effects of ZD-I on osteogenic differentiation of hMSCs were assessed by alkaline phosphatase (ALP) activity, mineralization assay and real-time RT-PCR. RESULTS: ZD-I (0.78-100 microg/ml) was non-cytotoxic. The 50% inhibitory concentration (IC50) of hMSCs was 200 microg/ml. ZD-I (0.78-50 microg/ml) stimulated the proliferation of hMSCs. ZD-I did not change ALP activity of hMSCs cultivated in osteogenic medium in the early stage (4 and 7 days), but ZD-I inhibited the mineralization of hMSCs through down-regulation of several osteogenic markers (e.g. osteocalcin, bone morphogenetic protein 2 and osteopontin) in the late stage. CONCLUSIONS: ZD-I stimulate cellular proliferation and decrease the bone mineral deposition of hMSCs. These results suggest ZD-I may play an important therapeutic role in osteoarthritic patients by improving proliferative capacity of hMSCs and inhibiting the mineralization of hMSCs.

Effect of hyaluronan on osteogenic differentiation of porcine bone marrow stromal cells in vitro.

Hyaluronan (HA) plays a predominant role in tissue morphogenesis, cell migration, proliferation, and cell differentiation. The aims of the present study were to investigate whether (i) prolonged presence of high concentration (4.0 mg/mL) 800 KDa HA and (ii) pretreatment with HA can modify osteogenic differentiation of pig bone marrow stromal cells (pBMSC). Cell proliferation and mineralization were measured. Expression of differentiation-related genes was evaluated by means of real-time reverse transcription polymerase chain reaction (RT-PCR). HA increased cell proliferation on day 7. HA decreased the basal level of bone-related gene expression and increased the basal level of sox9 marginally during 7-day pretreatment with HA. HA increased calcium deposit on day 21. cbfa1, ALP, and type 1 alpha collagen (Col1) expression was increased when pBMSC were cultivated in osteogenic medium, whereas their expression was decreased in the presence of HA on day 7. On day 14, the addition of HA upregulated cbfa1 and ALP expression compared to osteogenic medium group; there was no significant difference in Col1 expression. At day 21, osteocalcin (OC) expression showed 2.5-fold upregulation over osteogenic medium. These results suggest that exogenous HA stimulates endogenous HA, which together may play a synergetic role in osteogenic differentiation under osteoinducing conditions although gene expression was inhibited at the early stage.