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BMC Ophthalmology Mar 2024To investigate the effect of topical nonsteroidal anti-inflammatory drugs (NSAIDs,) bromfenac on the intraretinal cystic lesions (IRC) when performing simultaneous...
PURPOSE
To investigate the effect of topical nonsteroidal anti-inflammatory drugs (NSAIDs,) bromfenac on the intraretinal cystic lesions (IRC) when performing simultaneous cataract and idiopathic epiretinal membrane (iERM) surgery.
METHODS
This study included patients with iERM who had been followed up for 6 months after vitrectomy, membrane removal, and concurrent cataract surgery. Eyes were treated with topical bromfenac or not. The baseline fluorescein angiography (FA) was obtained to assess the microvascular leakage (ML). Structural changes of macula, including IRC and central macular thickness (CMT) were assessed using optical coherence tomography (OCT). The main outcome measures were changes in IRCs and best-corrected visual acuity (BCVA) regarding FA findings.
RESULTS
One hundred eighteen eyes were included. IRC and ML were observed in 51 eyes (43.2%) and 63 eyes (53.4%), respectively. The IRC did not show any association with the ML. Of total, 29 eyes (24.6%) were treated with topical bromfenac (Group A). Compared to Group B, topical bromfenac did not show beneficial effects in aspect of preventions for the newly developed IRC and treatment for pre-existed IRC. Whether the ML existed or not, topical bromfenac did not show any different effect on the changes in BCVA and IRC.
CONCLUSION
When performing simultaneous cataract and ERM surgery, topical NSAIDs, bromfenac did not show beneficial effects on the preventions and treatment of IRC in both eyes with and without the ML.
Topics: Humans; Epiretinal Membrane; Macular Edema; Cataract; Tomography, Optical Coherence; Anti-Inflammatory Agents, Non-Steroidal; Retrospective Studies; Vitrectomy; Benzophenones; Bromobenzenes
PubMed: 38491368
DOI: 10.1186/s12886-024-03380-2 -
Chemical Science Feb 2024Pd clusters offer unique selectivity and exploitable reactivity in catalysis. Understanding the behavior of Pd clusters is thus critical for catalysis, applied synthetic...
Pd clusters offer unique selectivity and exploitable reactivity in catalysis. Understanding the behavior of Pd clusters is thus critical for catalysis, applied synthetic organic chemistry and greener outcomes for precious Pd. The Pd cluster, [Pd(μ-Cl)(μ-PPh)(PPh)][Cl] (denoted as PdCl), which exhibits distinctive reactivity, was synthesized and immobilized on a phosphine-functionalized polystyrene resin (denoted as immob-PdCl). The resultant material served as a tool to study closely the role of Pd clusters in a prototypical Suzuki-Miyaura cross-coupling of 4-fluoro-1-bromobenzene and 4-methoxyphenyl boronic acid at varying low Pd ppm concentrations (24, 45, and 68 ppm). Advanced heterogeneity tests such as Hg poisoning and the three-phase test showed that leached mononuclear or nanoparticulate Pd are unlikely to be the major active catalyst species under the reaction conditions tested. EXAFS/XANES analysis from (pre)catalyst and filtered catalysts during and after catalysis has shown the intactness of the triangular structure of the PdX cluster, with exchange of chloride (X) by bromide during catalytic turnover of bromoarene substrate. This finding is further corroborated by treatment of immob-PdCl after catalyzing the Suzuki-Miyaura reaction with excess PPh, which releases the cluster from the polymer support and so permits direct observation of [Pd(μ-Br)(μ-PPh)(PPh)] ions by ESI-MS. No evidence is seen for a proposed intermediate in which the bridging halogen on the Pd motif is replaced by an aryl group from the organoboronic acid, formed by a transmetallation-first process. Our findings taken together indicate that the 'PdX' motif is an active catalyst species, which is stabilized by being immobilized, providing a more robust Pd cluster catalyst system. Non-immobilized PdCl is less stable, as is followed by stepwise XAFS of the non-immobilized PdCl, which gradually changes to a species consistent with 'Pd(PPh)' type material. Our findings have far-reaching future implications for Pd cluster involvement in catalysis, showing that immobilization of Pd cluster species offers advantages for rigorous mechanistic examination and applied chemistries.
PubMed: 38404373
DOI: 10.1039/d3sc06447f -
Molecules (Basel, Switzerland) Dec 2023A synthetic pathway to a novel 4-aryl-3,4-dihydro-2-1,4-benzoxazine scaffold was developed and a series of compounds based on the scaffold were synthesised as potential...
A synthetic pathway to a novel 4-aryl-3,4-dihydro-2-1,4-benzoxazine scaffold was developed and a series of compounds based on the scaffold were synthesised as potential anticancer agents. The 4-aryl-substituted compounds were prepared via Buchwald-Hartwig cross-coupling between substituted bromobenzenes and various 1,4-benzoxazines, which in turn were generated from a cascade hydrogenation and reductive amination one-pot reaction. These analogues exhibited moderate to good potency against various cancer cell lines. Structure-activity relationship analysis indicated that the inclusion of hydroxyl groups on ring A and ring B was beneficial to biological activity, while having a -amino group on ring C significantly enhanced potency. Molecule displayed the most potent anticancer activity (IC = 7.84-16.2 µM against PC-3, NHDF, MDA-MB-231, MIA PaCa-2, and U-87 MG cancer cell lines), indicating its potential as a lead compound for further structural optimisation. All the synthesised compounds were fully characterised with NMR, HMRS, and IR. The novel benzoxazine scaffold described in this study holds promise and deserves further in-depth studies.
Topics: Benzoxazines; Hydrogenation; Amination; Bromobenzenes; Cell Line
PubMed: 38202749
DOI: 10.3390/molecules29010166 -
Scientific Reports Jan 2024Metal or metal cluster-doped zeolites catalyse a wide variety of reactions. In this work, a coupling reaction between bromobenzene and phenylboronic acid to yield...
Metal or metal cluster-doped zeolites catalyse a wide variety of reactions. In this work, a coupling reaction between bromobenzene and phenylboronic acid to yield biphenyl with the Pd-H-Beta zeolite catalyst was investigated with density functional theory (DFT) calculations. Utilizing a model system with tetrahedral Pd clusters within the H-Beta zeolite, it was demonstrated that the catalyst exhibited notable reactivity by effectively reducing the activation energy barrier for the reaction. Our investigation revealed that the zeolite framework facilitated electron transfer to the Pd cluster, thereby increasing the reaction activity. The coupling reaction was shown to be exothermic and comprise three main steps: oxidative addition of bromobenzene (CHBr), transmetallation with phenylboronic acid (CHB(OH)), and reductive elimination of biphenyl (CH). Specifically, in the transmetallation step, which was the rate-determining step, the C-B bond breaking in phenylboronic acid (CHB(OH)) and the phenylboronate anion (CHB(OH)) were compared under neutral and basic conditions, respectively. This comprehensive study clarifies the mechanism for the reaction with the modified Pd zeolite catalyst and highlights the essential role of the zeolite framework.
PubMed: 38182728
DOI: 10.1038/s41598-023-51116-x -
Environmental Science and Pollution... Dec 2023Hexabromobenzene (HBB), pentabromotoluene (PBT), and pentabromoethylbenzene (PBEB) are current-use brominated flame retardants (cuBFRs) which have been repeatedly...
Hydroxylated transformation products obtained after UV irradiation of the current-use brominated flame retardants hexabromobenzene, pentabromotoluene, and pentabromoethylbenzene.
Hexabromobenzene (HBB), pentabromotoluene (PBT), and pentabromoethylbenzene (PBEB) are current-use brominated flame retardants (cuBFRs) which have been repeatedly detected in environmental samples. Since information on hydroxylated transformation products (OH-TPs) was scarcely available, the three polybrominated compounds were UV irradiated for 10 min in benzotrifluoride. Fractionation on silica gel enabled the separate collection and identification of OH-TPs. For more insights, aliquots of the separated OH-TPs were UV irradiated for another 50 min (60 min total UV irradiation time). The present investigation of polar UV irradiation products of HBB, PBT, and PBEB was successful in each case. Altogether, eight bromophenols were detected in the case of HBB (three Br-, four Br-, and one Br-isomer), and nine OH-TPs were observed in the case of PBT/PBEB (six Br- and three Br-congeners). In either case, Br➔OH exchange was more relevant than H➔OH exchange. Also, such exchange was most relevant in meta- and ortho-positions. As a further point, and in agreement with other studies, the transformation rate decreased with decreasing degree of bromination. UV irradiation of HBB additionally resulted in the formation of tri- and tetrabrominated dihydroxylated compounds (brominated diphenols) that were subsequently identified. These dihydroxylated transformation products were found to be more stable than OH-TPs.
Topics: Bromobenzenes; Environmental Monitoring; Flame Retardants; Halogenated Diphenyl Ethers; Hydrocarbons, Brominated; Toluene; Ultraviolet Rays
PubMed: 37917263
DOI: 10.1007/s11356-023-30566-w -
Drug Metabolism and Disposition: the... Oct 2023In the early '70s, Dr B. B. Brodie, Head of the LCP, NHI, NIH, initiated a program to elucidate the mechanism of hepatic necrosis induced in rats by bromobenzene. These...
In the early '70s, Dr B. B. Brodie, Head of the LCP, NHI, NIH, initiated a program to elucidate the mechanism of hepatic necrosis induced in rats by bromobenzene. These studies showed a crucial role for its 3,4-epoxide intermediate, known in part, to collapse to 4-bromophenol. To examine a possible contribution of this phenol to tissue toxicity, some rats were co-administered a high dose of acetaminophen to suppress phenolic clearance by glucuronidation and sulfation. Subsequent examination of liver slices showed that the acetaminophen-only control rats had extensive centrilobular liver necrosis. This article is a personal reminiscence of the events that led up to this accidental observation, how it happened, and the subsequent resolution of the underlying mechanism, including the covalent binding of NAPQI to liver protein as the initial "hit", the glutathione protective threshold, the antidotal activity of cysteine, and the existence of the "therapeutic window" for antidotal therapy. Collectively, these studies formed the basis for antidotal therapy of acetaminophen overdose patients, Not applicable.
PubMed: 37793785
DOI: 10.1124/dmd.123.001278 -
Environment International Aug 2023Municipal solid waste incinerator (MSWI) not only is deemed one of the uppermost sources of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), but also produces...
Municipal solid waste incinerator (MSWI) not only is deemed one of the uppermost sources of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), but also produces substantial amount of polybrominated dibenzo-p-dioxins/furans (PBDD/Fs) owing to the existence of brominated flame retardants (BFRs) in the waste. So far, however, PBDD/Fs in the vicinal environments of MSWI and their associated risks remain rarely studied. Based on a one-year passive air sampling (PAS) scheme, we investigated airborne PBDD/Fs and PCDD/Fs around a large-scale MSWI that has been operated for multi-years. Both the concentrations of PBDD/Fs and PCDD/Fs showed spatially decreasing trends with the distance away from the MSWI, confirming the influence of the MSWI on the dioxin levels in its ambient air. But its influence on PBDD/Fs was less because PBDD/Fs exhibit lower volatility and therefore lower gaseous concentrations than PCDD/Fs. Compared to the existing global data of airborne PCDD/Fs and PBDD/Fs, our data of the MSWI vicinity were at medium levels, despite PAS samples only represent the concentrations of gaseous dioxins in theory. The seasonal data suggest that meteorological conditions exerted apparent influences over the concentrations and sources of airborne dioxins around the MSWI. As for PCDD/Fs, the MSWI was diagnosed as their uppermost source, followed by local traffic and volatilization/deposition. Whereas the top three PBDD/F sources were related to PBDEs, bromophenol/bromobenzene, and traffic vehicles, respectively. The bioassay-derived TEQs based on the aryl hydrocarbon receptor activation of airborne dioxins around the MSWI were one or two orders of magnitudes higher than their concentration-based TEQs, and the corresponding carcinogenic risks at some MSWI-vicinal sites exceeded the acceptable threshold proposed by the U. S. EPA (10 ∼ 10) and deserve continuous attention.
Topics: Dioxins; Polychlorinated Dibenzodioxins; Solid Waste; Dibenzofurans; Carcinogens; Environmental Monitoring; Sampling Studies; Air Pollutants; Incineration; Gases; Dibenzofurans, Polychlorinated
PubMed: 37490788
DOI: 10.1016/j.envint.2023.108104 -
Biological & Pharmaceutical Bulletin 2023Circadian rhythms are endogenous oscillators that regulate 24 h behavioral and physiological processes. Our previous investigation demonstrated that bromobenzene...
Circadian rhythms are endogenous oscillators that regulate 24 h behavioral and physiological processes. Our previous investigation demonstrated that bromobenzene metabolite (4-bromocatechol: 4-BrCA) exhibited chronotoxicity (i.e., the nephrotoxicity induced by 4-BrCA was observed during the dark phase, while not observed at light phase in mice). However, the molecular mechanism is still unknown. The aim of the present study is to investigate the cellular molecule(s) involved in the 4-BrCA-induced nephrotoxicity using mouse renal cortex tubular cell lines (MuRTE61 cells). We found that 4-BrCA showed dose dependent (0.01-1 mM) cell proliferation defect in MuRTE61 cells. By treating with 0.03 mM 4-BrCA, we demonstrated that major clock genes (Bmal1, Clock, Cry1, Cry2, Per1, and Per2) were significantly downregulated. Interestingly, the expression levels of two genes, Bmal1 and Clock, continued to decrease after 3 h of treatment with 4-BrCA, while Cry1, Per1, and Per2 were unchanged until 24 h of treatment. Moreover, BMAL1 and CLOCK levels are higher at light phase. We speculated that BMAL1 and CLOCK might function defensively against 4-BrCA-induced nephrotoxicity since the expression levels of Bmal1 and Clock were rapidly decreased. Finally, overexpression of Bmal1 and Clock restored 4-BrCA-induced cell proliferation defect in MuRTE61 cells. Taken together, our results suggest that Bmal1 and Clock have protective roles against 4-BrCA-induced nephrotoxicity.
Topics: Mice; Animals; ARNTL Transcription Factors; Bromobenzenes; Circadian Rhythm; Gene Expression Regulation
PubMed: 37258148
DOI: 10.1248/bpb.b23-00072 -
Chemical Science Apr 2023The growth of porous aromatic frameworks (PAFs) on the surface of polymer brushes is reported for the first time. In contrast to PAFs formed in solution, polymer brushes...
The growth of porous aromatic frameworks (PAFs) on the surface of polymer brushes is reported for the first time. In contrast to PAFs formed in solution, polymer brushes provide a confined environment for PAF growth, resulting in nanosized and homogeneous spherical PAFs formed amongst the polymer brushes. 4-Bromobenzene functionalities from the polymer brushes are utilized to induce PAF growth by a Yamamoto-type Ullman coupling reaction. The size of PAFs can be tailored from 30 nm to 500 nm by subtly changing the structural parameters: reaction time, grafting density, and concentration of 4-bromobenzene on the surface. The established strategy is not only applicable to the preparation of PAF-1, but can also be extended to the controlled preparation of PAF-5. In addition, free-standing and flexible PS/PAF-1 hybrid membranes are obtained dissolving the oxidized layer between the polymer layer and the silicon substrate, which can be transferred to any flat substrate. The obtained PS/PAF-1 membrane is proven to show high efficiency in removing dye from water and is promising for eliminating other foulants, such as microorganisms and trace organics.
PubMed: 37035702
DOI: 10.1039/d2sc06930j -
IUCrJ Mar 2023The transformation processes of non-solvated ibrutinib into a series of halogenated benzene solvates are explored in detail here. The transformation was studied in real...
The transformation processes of non-solvated ibrutinib into a series of halogenated benzene solvates are explored in detail here. The transformation was studied in real time by X-ray powder diffraction in a glass capillary. Crystal structures of chlorobenzene, bromobenzene and iodobenzene solvates are isostructural, whereas the structure of fluorobenzene solvate is different. Four different mechanisms for transformation were discovered despite the similarity in the chemical nature of the solvents and crystal structures of the solvates formed. These mechanisms include direct transformations and transformations with either a crystalline or an amorphous intermediate phase. The binding preference of each solvate in the crystal structure of the solvates was examined in competitive slurry experiments and further confirmed by interaction strength calculations. Overall, the presented system and online X-ray powder diffraction measurement provide unique insights into the formation of solvates.
PubMed: 36815712
DOI: 10.1107/S2052252523001197