DFO administration improved angiogenesis in irradiated tissue via activating HIF-1α-VEGF Pathway.

<p>A: Real-time PCR detection of VEGF expression 90 days after irradiation. B: Western-blot analysis of HIF-1α in tissues received DFO. Sham1: Pre-sterilized water group; sham2: Pre+Post sterilized water group; sham3: Post-sterilized water group. Data is presented as means ± SEM. *: P<0.05 compared with normal group; **: P<0.05 between two individual groups. C: HIF-1α in each group. Annotate: 1A represents D+IR group; 1B represents sham1; 2A represents IR+D group; 2B represents sham3; 3A represents D+IR+D group; 3B represents sham2; 4 represents IR; 5 represents normal group; β-Actin represents reference.</p

Restoring the Secretory Function of Irradiation-Damaged Salivary Gland by Administrating Deferoxamine in Mice

<div><p>Objectives</p><p>One of the major side effects of radiotherapy for treatments of the head and neck cancer is the radiation-induced dysfunction of salivary glands. The aim of the present study is to investigate the efficacy of deferoxamine (DFO) to restore the secretory function of radiation-damaged salivary glands in mice.</p><p>Methods</p><p>DFO (50 mg/kg/d) was administered intraperitoneally in C₅₇BL/6 mice for 3 days before and/or after point-fixed irradiation (18 Gy) of submandibular glands. The total 55 mice were randomly divided into: (1) Normal group: mice received no treatment (n = 5); (2) Irradiation group (IR): mice only received irradiation (n = 5); (3) Pre-DFO group (D+IR) (n = 10); (4) Pre+Post DFO group (D+IR+D) (n = 10); (5) Post-DFO group (IR+D) (n = 10); (6) For each DFO-treated group, the mice were intraperitoneally injected with 0.1 ml sterilized water alone (by which DFO was dissolved) for 3 days before and/or after irradiation, and served as control. Sham1: Pre-sterilized water group (n = 5); sham2: Pre+Post sterilized water group (n = 5); sham3: Post-sterilized water group (n = 5). The salivary flow rate (SFR) was assessed at 30^th, 60^th and 90^th day after irradiation, respectively. After 90 days, all mice were sacrificed and their submandibular glands were removed for further examinations.</p><p>Results</p><p>The salivary glands showed remarkable dysfunction and tissue damage after irradiation. DFO restored SFR in the irradiated glands to a level comparable to that in normal glands and angiogenesis in damaged tissue was greatly increased. DFO also increased the expression levels of HIF-1α and VEGF while reduced apoptotic cells. Furthermore, Sca-1⁺cells were preserved in the salivary glands treated with DFO before IR.</p><p>Conclusions</p><p>Our results indicate DFO could prevent the radiation-induced dysfunction of salivary glands in mice. The mechanism of this protective effect may involve increased angiogenesis, reduced apoptosis of acinar cells and more preserved stem cells.</p></div

Stereocontrolled Construction of Tetrahydro­pyrano­[2,3‑<i>c</i>]pyrazole Scaffold via an Organocatalyzed Formal [3 + 3] Annulation

A bifunctional squaramide catalyzed enantioselective formal [3 + 3] annulation reaction with pyrazolin-5-ones and nitroallylic acetates has been developed. Densely substituted tetrahydro­pyrano­[2,3-<i>c</i>]­pyrazoles with two adjacent stereogenic centers are obtained in a highly stereocontrolled manner. Representative transformation of the annulation product to a biologically important fused dihydroisoquinoline is achieved without any appreciable loss in the diastereo- and enantioselectivity

Salivary flow rate (SFR) was calculated at 30^th, 60^th, and 90^th day after irradiation.

<p>Sham1: Pre-sterilized water group; sham2: Pre+Post sterilized water group; sham3: Post-sterilized water group. Data is presented as means ± SEM. *: P<0.05 compared with normal group; **: P<0.05 between two individual groups; ***: P>0.05 compared with normal group.</p

Analysis of apoptotic cells by TUNEL determination at 90^th day after irradiation.

<p>TUNEL assay of apoptotic cells in different groups. A: TUNEL-positive cells of submandibular gland tissue from each group. B: Ratio of TUNEL-positive cells to total nuclei (% per gland) between different groups. Sham1: Pre-sterilized water group; sham2: Pre+Post sterilized water group; sham3: Post-sterilized water group. Data is presented as means ± SEM. *: P<0.05 compared with normal group; **: P<0.05 between two individual groups.</p

Silver-Catalyzed Decarboxylative Allylation of Aliphatic Carboxylic Acids in Aqueous Solution

Direct decarboxylative radical allylation of aliphatic carboxylic acids is described. With K₂S₂O₈ as the oxidant and AgNO₃ as the catalyst, the reactions of aliphatic carboxylic acids with allyl sulfones in aqueous CH₃CN solution gave the corresponding alkenes in satisfactory yields under mild conditions. This site-specific allylation method is applicable to all primary, secondary, and tertiary alkyl acids and exhibits wide functional group compatibility

Schematic representation of the experimental design.

<p>Local 18 Gy irradiation of salivary glands was given before or/and after 3-day DFO treatment (50 mg/kg/d). Normal: no treatment; IR: only Irradiation group; D+IR: Pre-DFO group; sham1: Pre-sterilized water group; IR+D: Post-DFO group; sham3: Post-sterilized water group; D+IR+D: Pre+Post DFO group; sham2: Pre+Post sterilized water group; DFO: deferoxamine.</p

The weight of salivary gland harvested at 90^th day post irradiation.

<p>The weight of salivary gland shows no significant difference among individual groups. Sham1: Pre-sterilized water group; sham2: Pre+Post sterilized water group; sham3: Post-sterilized water group. Data is presented as means ± SEM. *: P<0.05 compared with normal group.</p

Synthesis of Novel Cyclic Olefin Copolymer (COC) with High Performance via Effective Copolymerization of Ethylene with Bulky Cyclic Olefin

Novel cyclic olefin copolymer (COC) with high glass transition temperature, good mechanical performance, high transparency, and excellent film forming ability has been achieved in this work by effective copolymerization of ethylene and exo-1,4,4a,9,9a,10-hexahydro-9,10­(1′,2′)-benzeno-l,4-methanoanthracene (HBMN). This bulky cyclic olefin comonomer can be simply prepared in good yield via Diels–Alder reaction. By utilizing constrained geometry catalyst (CGC) activated with Al­(^<i>i</i>Bu)₃/[Ph₃C]­[B­(C₆F₅)₄], ethylene/HBMN copolymer can be obtained with excellent production, high molecular weight, and a wide range of HBMN incorporation. ¹³C NMR (DEPT) spectra reveal alternating ethylene–HBMN sequence can be detected at high HBMN incorporation. The glass transition temperature (<i>T</i>_g) of resulted copolymer enhances with increasing HBMN incorporation. A high <i>T</i>_g up to 207.0 °C is attainable at low comonomer incorporation of 30.4 mol %, which is 61 °C higher than that of commercial norbornene (NB)-derived COC (54 mol %). The tensile test indicates that the ethylene/HBMN copolymer has good mechanical performance which is more flexible than ethylene/NB copolymer and the previously reported COC even at a higher <i>T</i>_g level

Detection of proliferating cells in submandibular gland tissue at 90^th day after irradiation.

<p>A: Immunohistochemical staining of PCNA from each group. Images of lower panel represent the higher magnification of the boxed area in corresponding images of upper panel. B: Surface area occupied by PCNA-positive cells (% per gland) between different groups. Sham1: Pre-sterilized water group; sham2: Pre+Post sterilized water group; sham3: Post-sterilized water group. Data is presented as means ± SEM. *: P<0.05 compared with normal group; **: P<0.05 between two individual groups.</p