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31.
Novel vascular endothelial growth factor blocker improves cellular viability and reduces hypobaric hypoxia‐induced vascular leakage and oedema in rat brain
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Deepika Saraswat Sarita Nehra Kamal Chaudhary Siva Prasad CVS 《Clinical and experimental pharmacology & physiology》2015,42(5):475-484
Vascular endothelial growth factor (VEGF) is an important cerebral angiogenic and permeability factor under hypoxia. There is a need to find effective molecules that may ameliorate hypoxia‐induced cerebral oedema. In silico identification of novel candidate molecules that block VEGF‐A site were identified and validated with a Ramachandran plot. The active site residues of VEGF‐A were detected by Pocketfinder, CASTp, and DogSiteScorer. Based on in silico data, three VEGF‐A blocker (VAB) candidate molecules (VAB1, VAB2, and VAB3) were checked for improvement in cellular viability and regulation of VEGF levels in N2a cells under hypoxia (0.5% O2). Additionally, the best candidate molecule's efficacy was assessed in male Sprague‐Dawley rats for its ameliorative effect on cerebral oedema and vascular leakage under hypobaric hypoxia 7260 m. All experimental results were compared with the commercially available VEGF blocker sunitinib. Vascular endothelial growth factor‐A blocker 1 was found most effective in increasing cellular viability and maintaining normal VEGF levels under hypoxia (0.5% oxygen) in N2a cells. Vascular endothelial growth factor‐A blocker 1 effectively restored VEGF levels, decreased cerebral oedema, and reduced vascular leakage under hypobaric hypoxia when compared to sunitinib‐treated rats. Vascular endothelial growth factor‐A blocker 1 may be a promising candidate molecule for ameliorating hypobaric hypoxia‐induced vasogenic oedema by regulating VEGF levels. 相似文献
32.
Sandeep Chaudhary Bharti Rajesh K. Shyamlal Lalit Yadav Mohit K. Tiwari Krishan Kumar 《RSC advances》2018,8(41):23152
Herein, we disclose the first example of an efficient, silver oxide nanoparticle-catalyzed, direct regioselective synthesis of 3-ylidenephthalides 11–16 and isocoumarins 17–20via sonogashira type coupling followed by substrate-controlled 5-exo-dig or 6-endo-dig cyclization reaction, respectively. This one pot coupling involves reaction of substituted 2-halobenzoic acid with meta/para-substituted and ortho-substituted terminal alkynes, which proceeded in a regioselective manner resulting in the formation of 3-ylidenephthalides or isocoumarins, respectively, in excellent yields (up to 95%) with complete Z-selectivity. This protocol features relatively broad substrate scope, mild conditions, operational simplicity, and is favourable with aromatic/alicyclic terminal alkynes. The competition experiments and gram-scale synthesis further highlight the importance and versatility of the methodology. The proposed mechanistic pathways illustrate that the regioselectivity is substantially being controlled by the substituent(s) present on the acetylenic phenyl ring.We report the first example of an efficient, Ag2O nanoparticle-catalyzed, direct regioselective synthesis of 3-ylidenephthalides and isocoumarins via Sonogashira type coupling followed by substrate-controlled 5-exo-dig or 6-endo-dig cyclization reaction, respectively. 相似文献
33.
34.
Brown KE Khan CM Zimmerman MB Brunt EM 《The American journal of gastroenterology》2003,98(7):1594-1598
OBJECTIVE: Genetic susceptibility to iron loading is an important factor in the development of iron overload in Africans. This suggests that persons of African descent may be at risk to develop iron overload with its attendant complications, but relatively little is known about hepatic iron overload among blacks. The aim of this study was to compare the prevalence, histological features, and clinical correlates of hepatic iron overload in a group of autopsied black and white veterans. METHODS: Hepatic iron concentrations (HIC) were determined on liver tissue from autopsies performed at the John Cochran Veterans Affairs Medical Center during the period 1993 to 1996. Clinical information was obtained from autopsy protocols. Sections from livers in which the HIC exceeded the upper limit of normal were examined histologically. RESULTS: Of 256 specimens, 99 were from blacks (39%), whereas 157 were from whites (61%). Thirty-one blacks (31%) had an elevated HIC versus 44 whites (28%) (ns). In the majority of these cases (18 blacks, 30 whites), the HIC was less than twice the upper limit of normal. Nine of 15 subjects with an HIC greater than twice the upper limit of normal and no evident cause of secondary iron overload were black. CONCLUSIONS: The prevalence of mild-to-moderate hepatic iron overload was similar in this group of black and white veterans. Because of the inherent limitations of autopsy studies, prospective assessment of iron stores in healthy blacks is needed to determine more accurately the prevalence and clinical significance of iron overload in this population. 相似文献
35.
Hepatitis B virus reactivation with clinical flare in allogeneic stem cell transplants with chronic graft-versus-host disease 总被引:4,自引:0,他引:4
Seth P Alrajhi AA Kagevi I Chaudhary MA Colcol E Sahovic E Aljurf M Gyger M 《Bone marrow transplantation》2002,30(3):189-194
We conducted a retrospective study with the aim of identifying risk factors and clinical characteristics associated with HBV reactivation and clinical flare after allogeneic stem cell transplantation (aSCT). We reviewed the King Faisal Specialist Hospital and Research Center International Bone Marrow Transplant Registry database from January 1998 to June 2000. Complete serological screening for HBV was available in 128 of 131 patients transplanted during that period. Fifty-four (42%) had evidence of prior infection and recovery from HBV before transplant (hepatitis B core antibody positive, B surface antigen negative). Forty-two were evaluable for HBV reactivation and clinical flare. Six (14%) reactivated with clinical flare as documented by seroconversion and/or positive HBV DNA in the serum with biochemical hepatitis at 5.5, 18, 18, 19, 21 and 23 months post-transplant. Five of fifteen patients with chronic graft-versus-host disease (cGVHD) reactivated with clinical flare in contrast to 1/27 without cGVHD (RR: 9.0, 95% CI: 1.2-70.1 P < 0.02). HBV reactivation with clinical flare occurred during immunosuppressive therapy tapering or withdrawal in all patients. In conclusion, hepatitis B core antibody positive allogeneic stem cell recipients with cGVHD are at significant risk of HBV reactivation with clinical flare. 相似文献
36.
Role of endotoxin of Aspergillus fumigatus in its pathogenicity 总被引:1,自引:0,他引:1
37.
Isabela J. Wastowski Renata T. Simões Layale Yaghi Eduardo A. Donadi João T. Pancoto Isabelle Poras Emmanuèle Lechapt-Zalcman Myriam Bernaudin Samuel Valable Carlos G. Carlotti Sébastien Flajollet Stine S. Jensen Soldano Ferrone Edgardo D. Carosella Bjarne W. Kristensen Philippe Moreau 《The American journal of pathology》2013,182(2):540-552
38.
Kimberly M. Kelly Mayank Ajmera Sandipan Bhattacharjee Rini Vohra Gerry Hobbs Lubna Chaudhary Jame Abraham Doreen Agnese 《Patient education and counseling》2013
Objective
Breast cancer is the most common cancer among women worldwide. Given the advances in extending survival, the number of recently diagnosed breast cancer patients and longer-term breast cancer survivors is growing. The goals of this study were to better understand (1) perceptions of provider cancer recurrence risk communication, (2) perceived risk of breast cancer recurrence in cancer patients and survivors, and (3) accuracy of perceived risk.Methods
A survey was conducted on women with a prior breast cancer (n = 141).Results
Approximately 40% of women perceived that providers had not talked about their breast cancer recurrence risk; although only 1 person reported not wanting a physician to talk to her about her risk. Women were largely inaccurate in their assessments of risk. Greater worry, living in a rural area, and longer time since diagnosis were associated with greater inaccuracy. Women tended to think about distal recurrence of cancer as often of local recurrence.Conclusions
Perceived risk of breast cancer recurrence was inaccurate, and patients desired more communication about recurrence risk.Practice implications
Consistent with findings from other studies, greater efforts are needed to improve the communication of cancer recurrence risk to patients. Attention should be paid to those from rural areas and to distal cancer recurrence in women with a previous history of breast cancer. 相似文献39.
40.
Trimurti L. Lambat Ratiram G. Chaudhary Ahmed A. Abdala Raghvendra Kumar Mishra Sami H. Mahmood Subhash Banerjee 《RSC advances》2019,9(54):31683
A protocol for the efficient synthesis of arylbenzodioxy xanthenedione scaffolds was developed via a one-pot multi-component reaction of aromatic aldehydes, 2-hydroxy-1,4-naphthoquinone, and 3,4-methylenedioxy phenol using mesoporous PbO nanoparticles (NPs) as a catalyst under ball milling conditions. The synthesis protocol offers outstanding advantages, including short reaction time (60 min), excellent yields of the products (92–97%), solvent-free conditions, use of mild and reusable PbO NPs as a catalyst, simple purification of the products by recrystallization, and finally, the use of a green process of dry ball milling.An efficient one-pot multicomponent protocol was developed for the synthesis of arylbenzodioxy xanthenedione scaffolds using mesoporous PbO nanoparticles as reusable catalyst under solvent-free ball milling conditions.Recently, the ball milling technique has received great attention as an environmentally benign strategy in the context of green organic synthesis.1a The process of “ball milling” has been developed by adding mechanical grinding to the mixer or shaker mills. The ball milling generates a mechanochemical energy, which promotes the rupture and formation of the chemical bonds in organic transformations.1b Subsequently, detailed literature1c and books on this novel matter have been published.2a,b Several typical examples include carbon–carbon and carbon–heteroatom bond formation,2c organocatalytic reactions,2d oxidation by using solid oxidants,2e dehydrogenative coupling, asymmetric, and peptide or polymeric material synthesis, which have been reported under ball milling conditions.2e Hence, the organic reactions using ball milling activation carried out under neat reaction environments, exhibit major advantages,2f including short reaction time, lower energy consumption, quantitatively high yields and superior safety with the prospective for more improvement than the additional solvent-free conditions and clear-cut work-up.3–5On the other hand, the organic transformations using metal and metal oxide nanoparticles6 are attracting enormous interest due to the unique and interesting properties of the NPs.7,8,9a Particularly, PbO NPs9b provide higher selectivity in some organic reactions9c and find applications in various organic reactions, like Paal–Knorr reaction,10 synthesis of diethyl carbonate,11 phthalazinediones,12 disproportionation of methyl phenyl carbonate to synthesize diphenyl carbonate,13 the capping agent in organic synthesis, and selective conversion of methanol to propylene.14 In addition, the PbO NPs are also used in many industrial materials.15,16However, till date, PbO NPs have not been explored in MCRs leading to biologically important scaffolds. Among others, the xanthene scaffolds17 are one of the important heterocyclic compounds18 and are extensively used as dyes, fluorescent ingredients for visual imaging of the bio-molecules, and in optical device technology because of their valuable chemical properties.19 The xanthene molecules have conjointly been expressed for their antibacterial activity,20 photodynamic medical care, anti-inflammatory drug impact, and antiviral activity. Because of their various applications, the synthesis of these compounds has received a great deal of attention.21 Similarly, vitamin K nucleus22,23 shows a broad spectrum of biological properties, like anti-inflammatory, antiviral, antiproliferative, antifungal, antibiotic, and antipyretic.24a As a consequence, a variety of strategies24b have been demonstrated in the literature for the synthesis of xanthenes and their keto derivatives, like rhodomyrtosone-B,25a rhodomyrtosone-I,25b and BF-6 25c as well as their connected bioactive moieties. Few biologically active xanthene scaffolds are shown in (Fig. 1).Open in a separate windowFig. 1Some biologically important xanthenes and their keto derivatives.Due to the significance of these compounds, the synthesis of xanthenes and their keto derivatives using green protocols is highly desirable. Reported studies reveal that these scaffolds are synthesized by three-component condensations using p-TSA26 and scolecite27 as catalysts. However, these methods suffer from the use of toxic acidic catalysts like p-TSA, long reaction times (3 h), harsh refluxing26 or microwave reaction conditions,27 and tedious work-up procedures. The previously reported methods for the synthesis of xanthenediones are shown in Scheme 1.Open in a separate windowScheme 1Previous protocol for the synthesis of xanthenedione derivatives.Herein, we report an economical and facile multicomponent protocol, using ball milling, for the synthesis of 7-aryl-6H-benzo[H][1,3]dioxolo[4,5-b]xanthene-5,6(7H)-dione using PbO NPs as a heterogeneous catalyst (Scheme 2). The PbO NPs are non-corrosive, inexpensive, and easily accessible.Open in a separate windowScheme 2General reaction scheme of PbO NP-catalyzed synthesis of the xanthenedione scaffolds under ball milling conditions.In our protocol,28 the PbO NPs were initially prepared by mixing sodium dodecyl sulphate (2.5 mmol) and sodium hydroxide (10 mL, 0.1 N) with an aqueous methanolic solution of lead nitrate (2 mmol) under magnetic stirring at 30 °C by continuing the reaction for 2 h. Then, the obtained white polycrystalline product was filtered, washed with H2O, and dried at 120 °C, followed by calcination at 650 °C for 2 h. During this step, the white PbO NPs turned pale yellow in colour. Eventually, the synthesized PbO was then characterized by spectroscopic and analytical techniques.The powder X-ray diffraction (XRD) pattern revealed the crystalline nature of the PbO NPs as the diffraction peaks corresponding to (131), (311), (222), (022), (210), (200), (002), and (111) crystal planes were identified (Fig. 2). The XRD outline of the synthesized PbO NPs was further established for the formation of space group Pca21 29 with a single orthorhombic structure (JCPDS card number 76-1796). The sharp diffraction peaks indicated good crystallinity, and the average particle size of the PbO NPs was estimated to be 69 nm, as calculated using the Debye–Scherer equation.Open in a separate windowFig. 2The powder XRD pattern of PbO NPs.The surface morphology of the PbO NPs was analyzed by scanning electron microscopy (SEM), and the SEM image revealed the discrete and spongy appearance of the PbO NPs (Fig. 3).Open in a separate windowFig. 3The SEM image of PbO NPs.Moreover, the elemental composition obtained from energy dispersive X-ray (EDX) analysis confirmed that the material contains Pb and O elements, and no other impurity was present (Fig. 4).Open in a separate windowFig. 4The EDAX spectrum of crystalline PbO NPs.The transmission electron microscopy (TEM) image shown in Fig. 5 indicated the formation of orthorhombic crystallites of PbO with several hexagon-shaped particles. The dark spot in the TEM micrograph further confirmed the synthesis of PbO NPs, as the selected area diffraction pattern associated with such spots reveals the occurrence of the PbO NPs in total agreement with the X-ray diffraction data (Fig. 6). The average size of the PbO nanocrystals by TEM was approximated to be around 20 nm.Open in a separate windowFig. 5The TEM image of nanocrystalline PbO NPs.Open in a separate windowFig. 6The SAED image of nanocrystalline PbO NPs.The Fourier transform infrared (FT-IR) spectrum (ESI, S6†) of the PbO NPs displayed peaks at 575, 641, and 848 cm−1, which corresponds to the Pb–O vibrations. Furthermore, the absorption band at ∼3315 cm−1 was due to the presence of the hydroxyl group (–OH) in the NPs.The N2 adsorption–desorption isotherms of the PbO nanoparticles shown in Fig. 7 was consistent with type IV adsorption–desorption isotherms with H1 hysteresis corresponding to the cylindrical mesoporous structure. Moreover, the surface area, pore-volume, and BJH pore diameter were found to be 32.0 m2 g−1, 0.023 cm3 g−1, and 30.9 Å, respectively.Open in a separate windowFig. 7BET surface area and pore size of nanocrystalline PbO catalyst.The catalytic activity of the synthesized PbO NPs was tested in a one-pot multicomponent synthesis of arylbenzodioxoloyl xanthenedione derivative under ball milling condition according to the reaction scheme 2a, with 3,4-dimethoxybenzaldehyde (166.2 mg, 1.0 mmol), 3,4-methylenedioxyphenol (138.0 mg, 1.0 mmol), and 2-hydroxy-1,4-naphthoquinone (174.0 mg, 1.0 mmol) as reactants. The reaction conditions, the ball milling parameters (speed, time, and ball to solids ratio), and the PbO nanocatalyst amount were first optimized to produce the highest yield using experimental design as shown in Entry Conditions Rotation (rpm) Catalyst (mol%) Time (min) Yield (%)a 1 Ball milling 400 00 50 21 2 Ball milling 400 10 50 48 3 Ball milling 400 15 60 54 4 Ball milling 400 20 70 59 5 Ball milling 500 10 50 62 6 Ball milling 500 15 50 65 7 Ball milling 500 20 60 67 8 Ball milling 600 10 70 71 9 Ball milling 600 15 50 77 10 Ball milling 600 20 60 82 11 Ball milling 600 05 70 90 12 Ball milling 600 10 50 91 13 Ball milling b 600 15 60 97 14 Ball milling 600 20 70 97 15 No ball millingc — 15 60 —