56 research outputs found
CD34+/M-cadherin+ Bone Marrow Progenitor Cells Promote Arteriogenesis in Ischemic Hindlimbs of ApoEâ/â Mice
BACKGROUND: Cell-based therapy shows promise in treating peripheral arterial disease (PAD); however, the optimal cell type and long-term efficacy are unknown. In this study, we identified a novel subpopulation of adult progenitor cells positive for CD34 and M-cadherin (CD34âș/M-cadâș BMCs) in mouse and human bone marrow. We also examined the long-lasting therapeutic efficacy of mouse CD34âș/M-cadâș BMCs in restoring blood flow and promoting vascularization in an atherosclerotic mouse model of PAD. METHODS AND FINDINGS: Colony-forming cell assays and flow cytometry analysis showed that CD34âș/M-cadâș BMCs have hematopoietic progenitor properties. When delivered intra-arterially into the ischemic hindlimbs of ApoEâ»/â» mice, CD34âș/M-cadâș BMCs alleviated ischemia and significantly improved blood flow compared with CD34âș/M-cadâ» BMCs, CD34â»/M-cadâș BMCs, or unselected BMCs. Significantly more arterioles were seen in CD34âș/M-cadâș cell-treated limbs than in any other treatment group 60 days after cell therapy. Furthermore, histologic assessment and morphometric analyses of hindlimbs treated with GFPâș CD34âș/M-cadâș cells showed that injected cells incorporated into solid tissue structures at 21 days. Confocal microscopic examination of GFPâș CD34âș/M-cadâș cell-treated ischemic legs followed by immunostaining indicated the vascular differentiation of CD34âș/M-cadâș progenitor cells. A cytokine antibody array revealed that CD34âș/M-cadâș cell-conditioned medium contained higher levels of cytokines in a unique pattern, including bFGF, CRG-2, EGF, Flt-3 ligand, IGF-1, SDF-1, and VEGFR-3, than did CD34âș/M-cadâ» cell-conditioned medium. The proangiogenic cytokines secreted by CD34âș/M-cadâș cells induced oxygen- and nutrient-depleted endothelial cell sprouting significantly better than CD34âș/M-cadâ» cells during hypoxia. CONCLUSION: CD34âș/M-cadâș BMCs represent a new progenitor cell type that effectively alleviates hindlimb ischemia in ApoEâ»/â» mice by consistently improving blood flow and promoting arteriogenesis. Additionally, CD34âș/M-cadâș BMCs contribute to microvascular remodeling by differentiating into vascular cells and releasing proangiogenic cytokines and growth factors
The Quantitative Role of Child Care for Female Labor Force Participation and Fertility
Rare variants in BNC2 are implicated in autosomal-dominant congenital lower urinary-tract obstruction
Congenital lower urinary-tract obstruction (LUTO) is caused by anatomical blockage of the bladder outflow tract or by functional impairment of urinary voiding. About three out of 10,000 pregnancies are affected. Although several monogenic causes of functional obstruction have been defined, it is unknown whether congenital LUTO caused by anatomical blockage has a monogenic cause. Exome sequencing in a family with four affected individuals with anatomical blockage of the urethra identified a rare nonsense variant (c.2557C>T [p.Arg853(â)]) in BNC2, encoding basonuclin 2, tracking with LUTO over three generations. Re-sequencing BNC2 in 697 individuals with LUTO revealed three further independent missense variants in three unrelated families. In human and mouse embryogenesis, basonuclin 2 was detected in lower urinary-tract rudiments. In zebrafish embryos, bnc2 was expressed in the pronephric duct and cloaca, analogs of the mammalian lower urinary tract. Experimental knockdown of Bnc2 in zebrafish caused pronephric-outlet obstruction and cloacal dilatation, phenocopying human congenital LUTO. Collectively, these results support the conclusion that variants in BNC2 are strongly implicated in LUTO etiology as a result of anatomical blockage
Robotic surgery: disruptive innovation or unfulfilled promise? A systematic review and meta-analysis of the first 30Â years
Over-the-Counter Monocyclic Non-Steroidal Anti-Inflammatory Drugs in EnvironmentâSources, Risks, Biodegradation
Recently, the increased use of monocyclic
non-steroidal anti-inflammatory drugs has resulted in
their presence in the environment. This may have
potential negative effects on living organisms. The
biotransformation mechanisms of monocyclic nonsteroidal
anti-inflammatory drugs in the human body
and in other mammals occur by hydroxylation and
conjugation with glycine or glucuronic acid.
Biotransformation/biodegradation of monocyclic
non-steroidal anti-inflammatory drugs in the environment
may be caused by fungal or bacterial microorganisms.
Salicylic acid derivatives are degraded by
catechol or gentisate as intermediates which are
cleaved by dioxygenases. The key intermediate of
the paracetamol degradation pathways is hydroquinone.
Sometimes, after hydrolysis of this drug, 4-
aminophenol is formed, which is a dead-end metabolite.
Ibuprofen is metabolized by hydroxylation or
activation with CoA, resulting in the formation of
isobutylocatechol. The aim of this work is to attempt
to summarize the knowledge about environmental risk
connected with the presence of over-the-counter antiinflammatory
drugs, their sources and the biotransformation
and/or biodegradation pathways of these
drugs
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Degradation pathway of bisphenol A: Does ipso substitution apply to phenols containing a quaternary alpha-carbon structure in the para position?
The degradation of bisphenol A and nonylphenol involves the unusual rearrangement of stable carboncarbon bonds. Some nonylphenol isomers and bisphenol A possess a quaternary alpha-carbon atom as a common structural feature. The degradation of nonylphenol in Sphingomonas sp. strain TTNP3 occurs via a type II ipso substitution with the presence of a quaternary alpha-carbon as a prerequisite. We report here a new degradation pathway of bisphenol A. Consequent to the hydroxylation at position C-4, according to a type 11 ipso substitution mechanism, the C-C bond between the phenolic moiety and the isopropyl group of bisphenol A is broken. Besides the formation of hydroquinone and 4-(2-hydroxypropan-2-yl) phenol as the main metabolites, further compounds resulting from molecular rearrangements consistent with a carbocationic intermediate were identified. Assays with resting cells or cell extracts of Sphingomonas sp. strain TTNP3 under an 18 02 atmosphere were performed. One atom of 180, was present in hydroquinone, resulting from the monooxygenation of bisphenol A and nonylphenol. The monooxygenase activity was dependent on both NADPH and flavin adenine dinucleotide. Various cytochrome P450 inhibitors had identical inhibition effects on the conversion of both xenobiotics. Using a mutant of Sphingomonas sp. strain TTNP3, which is defective for growth on nonylphenol, we demonstrated that the reaction is catalyzed by the same enzymatic system. In conclusion, the degradation of bisphenol A and nonylphenol is initiated by the same monooxygenase, which may also lead to ipso substitution in other xenobiotics containing phenol with a quaternary a-carbon
Late Glacial and Holocene environmental history of the Ethiopian Highlands inferred from a 12 m long sediment record from Dendi crater lakes
Late Glacial and Holocene environmental history of the Ethiopian Highlands inferred from a 12Â m long sediment record from Dendi crater lakes
Abwasser und KlĂ€rschlamm in Deutschland-statistische Betrachtungen, Arbeitsbericht der DWA-Arbeitsgruppe KEK-1.2 âStatistikâ
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