Influences of laparoscopic-assisted gastrectomy and open gastrectomy on serum interleukin-6 levels in patients with gastric cancer among Asian populations: a systematic review.

BACKGROUND: To compare the effects of laparoscopic-assisted gastrectomy (LAG) and open gastrectomy (OG) on serum interleukin-6 (IL-6) levels in gastric cancer (GC) patients from Asia. METHODS: The following scientific literature databases were searched for relevant clinical studies: PubMed, EBSCO, Ovid, Wiley, Web of Science, Cochrane library, EMBASE, WANFANG and VIP databases. The studies retrieved from database searches were screened based on stringent inclusion and exclusion criteria to select high quality cohort studies for the present meta-analysis. The data extracted from final selected studies were analyzed using STATA 12.0 software. RESULTS: A total of 54 studies were initially retrieved from database searches, and 11 clinical cohort studies were eventually enrolled in this meta-analysis. The 11 selected studies contained a combined total of 767 GC patients (427 patients in LAG group and 340 patients in OG group). Meta-analysis results demonstrated that postoperative serum IL-6 levels in GC patients in LAG group was significantly lower than the OG group (SMD = -2.16, 95% CI = -3.19 ~ -1.14, P < 0.001). The difference in serum IL-6 levels between the preoperative and postoperative GC patients was significantly lower in the LAG group compared to the difference found in the OG group (SMD = -3.44, 95% CI = -4.87 ~ -2.01, P < 0.001). Subgroup analysis based on country showed that, in both Chinese and Japanese GC patients, the postoperative increase in serum IL-6 levels in LAG group were significantly lower than the increase observed in the OG group (all P < 0.05). In Korean GC patients, the postoperative increase in serum IL-6 levels was not significantly different between the LAG group and OG group (all P > 0.05). CONCLUSION: Our results provide strong evidence that LAG is associated with significantly lower serum IL-6 levels, compared to OG. Thus, LAG carries markedly lower risk of adverse inflammatory reactions in GC patients among Asian population.

Benzimidazole-2-one: a novel anchoring principle for antagonizing p53-Mdm2.

Herein we propose the benzimidazole-2-one substructure as a suitable tryptophan mimic and thus a reasonable starting point for the design of p53 Mdm2 antagonists. We devise a short multicomponent reaction route to hitherto unknown 2-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)acetamides by reacting mono N-carbamate protected phenylenediamine in a Ugi-3CR followed by base induced cyclisation. Our preliminary synthesis and screening results are presented here. The finding of the benzimidazolone moiety as a tryptophan replacement in mdm2 is significant as it offers access to novel scaffolds with potentially higher selectivity and potency and improved biological activities. Observing low µM affinities to mdm2 by NMR and fluorescence polarization we conclude that the 2-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)acetamide scaffold might be a good starting point to further optimize the affinities to Mdm2.

Lead discovery, chemistry optimization, and biological evaluation studies of novel biamide derivatives as CB2 receptor inverse agonists and osteoclast inhibitors.

N,N'-((4-(Dimethylamino)phenyl)methylene)bis(2-phenylacetamide) was discovered by using 3D pharmacophore database searches and was biologically confirmed as a new class of CB(2) inverse agonists. Subsequently, 52 derivatives were designed and synthesized through lead chemistry optimization by modifying the rings A-C and the core structure in further SAR studies. Five compounds were developed and also confirmed as CB(2) inverse agonists with the highest CB(2) binding affinity (CB(2)K(i) of 22-85 nM, EC(50) of 4-28 nM) and best selectivity (CB(1)/CB(2) of 235- to 909-fold). Furthermore, osteoclastogenesis bioassay indicated that PAM compounds showed great inhibition of osteoclast formation. Especially, compound 26 showed 72% inhibition activity even at the low concentration of 0.1 µM. The cytotoxicity assay suggested that the inhibition of PAM compounds on osteoclastogenesis did not result from its cytotoxicity. Therefore, these PAM derivatives could be used as potential leads for the development of a new type of antiosteoporosis agent.

A functionalizable polyester with free hydroxyl groups and tunable physiochemical and biological properties.

Polyesters with free functional groups allow facile modifications with biomolecules, which can lead to versatile biomaterials that afford controlled interactions with cells and tissues. Efficient synthesis of functionalizable polyesters (Functionalizable polymer is defined as a polymer with functional groups that readily react with biomolecules and functionalized biomaterial as one already modified with biomolecules.) is still a challenge that greatly limits the availability and widespread applications of biofunctionalized synthetic polymers. Here we report a simple route to prepare a functionalizable polyester, poly(sebacoyl diglyceride) (PSeD) bearing free hydroxyl groups. The key synthetic step is an epoxide ring-opening polymerization, instead of the traditional polycondensation that produces poly(glycerol sebacate) (PGS) (Wang YD, Ameer GA, Sheppard BJ, Langer R. A tough biodegradable elastomer. Nat Biotechnol 2002;20(6):602-6). PSeD has a more defined structure with mostly linear backbone, more free hydroxyl groups, higher molecular weight, and lower polydispersity than PGS. Crosslinking PSeD with sebacic acid yields a polymer five times tougher and more elastic than cured PGS. PSeD exhibits good cytocompatibility in vitro. Furthermore, functionalization by glycine proceeds with high efficiency. This versatile synthetic platform can offer a large family of biodegradable, functionalized polymers with tunable physiochemical and biological properties useful for a wide range of biomedical applications.

Enhanced uridine diphosphate N-acetylglucosamine production using whole-cell catalysis.

Uridine diphosphate N-acetylglucosamine (UDPAG) can be produced by chemical, enzymatic, chemoenzymatic, and fermentative methods. In this study, we used whole-cell catalysis method to produce UDPAG for the first time by Saccharomyces cerevisiae. In order to increase the ATP utilization efficiency and UDPAG conversion yield, the response surface methodology was applied to optimize the whole-cell catalytic conditions for UDPAG production. Firstly, effects of uridine 5'-monophosphate (5'-UMP), glucosamine, vitamin B1, glycerol, magnesium chloride, potassium chloride, temperature, sodium dihydrogen phosphate, sodium acetate, fructose, and pH on UDPAG production were evaluated by a fractional factorial design. Results showed that UDPAG production was mainly affected by sodium dihydrogen phosphate, temperature, and vitamin B1. Then, the concentrations of sodium dihydrogen phosphate and vitamin B1 and temperature were further investigated with a central composite design and response surface analysis. The cultivation conditions to obtain the optimal UDPAG production were determined: sodium dihydrogen phosphate, 31.2 g/L; temperature, 29 degrees C, and vitamin B1, 0.026 g/L. This optimization strategy led to an enhancement of UDPAG production from 2.51 to 4.25 g/L, yield from 44.6% to 75.6% based on the initial 5'-UMP concentration, and ATP utilization efficiency from 7.43% to 12.6%.

[Histomorphometric osseointegration evaluation of hydroxyapatite-coated and non-coated implants in dogs].

OBJECTIVE: Some reports showed the benefits of dental implants coated with hydroxyapatite, while some other studies found no significant difference between HA-coated implants and non-coated implants. The present study was to examine the osseointegration of HA-coated and non-coated implants in dogs. METHODS: Twelve implants, 6 HA-coated and 6 non-coated were placed into mandibles of six dogs after teeth extraction. Animals were sacrificed after 1, 3, 6 months, respectively. Initial healing and the bone-implant interface were histomorphometrically assessed using light microscopy. RESULTS: All implants osseointegrated; however, the ingrowth and development of new bone tissue onto HA-coated implants surface were sooner than that of non-coated ones. The index of bone osseointegration of HA-coated implants was higher than that of non-coated ones. After 1,3,6 months the osseointegration of HA-coated implants were 71.68%, 86.81%, 90.19%; While the non-coated ones'were 53.26%, 66.16%, 68.72%. The differences of them were very significant. CONCLUSION: HA-coated implants enhanced initial bone tissue ingrowth and development and thus benefited the osseointegration of implants.