Acidosis promotes the metastatic colonization of lung cancer via remodeling of the extracellular matrix and vasculogenic mimicry.

Acidosis is a hallmark of the tumor microenvironment caused by the metabolic switch from glucose oxidative phosphorylation to glycolysis. It has been associated with tumor growth and progression; however, the precise mechanism governing how acidosis promotes metastatic dissemination has yet to be elucidated. In the present study, a long­term acidosis model was established using patient­derived lung cancer cells, to identify critical components of metastatic colonization via transcriptome profiling combined with both in vitro and in vivo functional assays, and association analysis using clinical samples. Xenograft inoculates of 1 or 10 acidotic cells mimicking circulating tumor cell clusters were shown to exhibit increased tumor incidence compared with their physiological pH counterparts. Transcriptomics revealed that profound remodeling of the extracellular matrix (ECM) occurred in the acidotic cells, including upregulation of the integrin subunit α­4 (ITGA4) gene. In clinical lung cancer, ITGA4 expression was found to be upregulated in primary tumors with metastatic capability, and this trait was retained in the corresponding secondary tumors. Expression of ITGA4 was markedly upregulated around the vasculogenic mimicry structures of the acidotic tumors, while acidotic cells exhibited a higher ability of vasculogenic mimicry in vitro. Acidosis was also found to induce the enrichment of side population cells, suggesting an enhanced resistance to noxious attacks of the tumor microenvironment. Taken together, these results demonstrated that acidosis actively contributed to tumor metastatic colonization, and novel mechanistic insights into the therapeutic management and prognosis of lung cancer were discussed.

Novel silver and nanoparticle-encapsulated growth factor co-loaded chitosan composite hydrogel with sustained antimicrobility and promoted biological properties for diabetic wound healing.

Diabetic foot ulcer, one of the most common diabetic complications, is a progressive wound occurred on the skin with irregularly delayed wound healing rate due to impaired metabolism and weak immune responses. Such chronic wound remains a serious healthcare burden to the diabetics since it is often associated with high risk of limb loss due to amputation and leads to a reduced survival consequently. To improve the efficiency of diabetic wound healing, a synthetic chitosan-based composite hydrogel named SNPECHG incorporating silver ions (Ag+) and nanoparticle-encapsulated epidermal growth factor (EGF) was developed in this study. The optimal effective dosages of 24-mM Ag+ and 60-µg mL-1 EGF for the SNPECHG manufacture were first determined based on the results of antibacterial, cytotoxicity, and cell growth examinations. We then characterized the optimized SNPECHG and found that the composite hydrogel was able to provide sustained release of Ag+ and EGF, and exhibited a significantly higher hydration capacities, including the swelling degree and equilibrium water content, in PBS than those in deionized water, showing that the developed SNPECHG is highly applicable in the ion-rich environment such as chronic wound site. According to the results of in vivo study using diabetic rats, the one with SNPECHG exhibited a markedly enhanced wound healing effect compared with the other settings since day 3, and may reach a degree of wound closure of 97% at day 14 that was 7.4% (P < 0.05) and 18.9% (P < 0.05) higher than the values gained from the groups with the commercial dressing HeraDerm and gauze, respectively. Moreover, the wound treated with the SNPECHG exhibited thorough re-epithelization, sufficient collagen deposition, and accelerated collagen maturation confirmed by the histological analysis. Taken all together, we anticipate that the SNPECHG is highly advantageous for use in the clinical diabetic/chronic wound treatment.

Antimicrobial effect and mechanism of cinnamon oil and gamma radiation on Shewanella putrefaciens.

The aims of this study were to observe the antimicrobial effect and mechanism of cinnamon oil combined with gamma radiation on Shewanella putrefaciens. Gamma radiation increased the antimicrobial activity of cinnamon oil, and the relative radiation sensitivity of gamma radiation on S. putrefaciens was increased by cinnamon oil. Gamma radiation significantly increased the changes of bacterial morphology, intra-adenosine 5'-triphosphate (intra-ATP) and extra-ATP concentrations and pHin value of S. putrefaciens treated cinnamon oil. Although, gamma radiation used alone didn't damage the bacterial morphology and ATP concentrations significantly. Gamma radiation assisted cinnamon oil to damage the cell permeability and integrity of S. putrefaciens, thus the combination of cinnamon oil and gamma radiation showed a better antimicrobial activity than used alone.

N,N'-[(1S,2S)-Cyclo-hexane-1,2-di-yl]bis-(4-methyl-benzene-sulfonamide).

In the title compound, C(20)H(26)N(2)O(4)S(2), the cyclo-hexane ring has a chair conformation. The two chiral C atoms are in S configurations. In the crystal, inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into chains propagating in [001]. Weak inter-molecular C-H⋯O hydrogen bonds further stabilize the crystal packing.