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1.
Org Lett ; 26(26): 5522-5527, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38900928

RESUMEN

Here, we use transcriptomic data from seeds of Musella lasiocarpa to identify five enzymes involved in the formation of dihydrocurcuminoids. Characterization of the substrate specificities of the enzymes reveals two distinct dihydrocurcuminoid pathways leading to phenylphenalenones and linear diarylheptanoid derivatives, the major seed metabolites. Furthermore, we demonstrate the stepwise conversion of dihydrobisdemethoxycurcumin to the phenylphenalenone 4'-hydroxylachnanthocarpone by feeding intermediates to M. lasiocarpa root protein extract.


Asunto(s)
Diarilheptanoides , Fenalenos , Diarilheptanoides/química , Fenalenos/química , Estructura Molecular , Semillas/química , Musa/química , Especificidad por Sustrato , Pueblos del Este de Asia
2.
Nat Commun ; 15(1): 4525, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38806518

RESUMEN

Medicinal compounds from plants include bicyclo[3.3.1]nonane derivatives, the majority of which are polycyclic polyprenylated acylphloroglucinols (PPAPs). Prototype molecules are hyperforin, the antidepressant constituent of St. John's wort, and garcinol, a potential anticancer compound. Their complex structures have inspired innovative chemical syntheses, however, their biosynthesis in plants is still enigmatic. PPAPs are divided into two subclasses, named type A and B. Here we identify both types in Hypericum sampsonii plants and isolate two enzymes that regiodivergently convert a common precursor to pivotal type A and B products. Molecular modelling and substrate docking studies reveal inverted substrate binding modes in the two active site cavities. We identify amino acids that stabilize these alternative binding scenarios and use reciprocal mutagenesis to interconvert the enzymatic activities. Our studies elucidate the unique biochemistry that yields type A and B bicyclo[3.3.1]nonane cores in plants, thereby providing key building blocks for biotechnological efforts to sustainably produce these complex compounds for preclinical development.


Asunto(s)
Hypericum , Hypericum/metabolismo , Hypericum/genética , Hypericum/química , Compuestos Bicíclicos con Puentes/metabolismo , Compuestos Bicíclicos con Puentes/química , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Simulación del Acoplamiento Molecular , Floroglucinol/metabolismo , Floroglucinol/análogos & derivados , Floroglucinol/química , Alcanos/metabolismo , Alcanos/química , Dominio Catalítico , Terpenos/metabolismo , Terpenos/química , Modelos Moleculares
3.
Chem Commun (Camb) ; 56(40): 5350-5353, 2020 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-32319467

RESUMEN

[(Ph3P)AuPt(nbe)3][BAr4F] (nbe = norbornene) constitutes the first olefin-containing, formal Au+IPt0 complex. The unusual coordination mode and the electronic properties have been analyzed spectroscopically and by calculations. The low binding energy of the nbe ligands make this complex a valuable precursor for formal Au+IPt0 complexes and a candidate for heterobimetallic catalysis.

4.
Pediatr Gastroenterol Hepatol Nutr ; 23(1): 72-78, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31988877

RESUMEN

Infantile hepatic hemangioma, the most common vascular tumor of the liver in infancy, can occur with acute postnatal liver and congestive heart failure. Nevertheless, its course is often benign, and many children can be diagnosed and treated without surgical intervention. The distinction from malignant diseases is not always easy and it not clear whether invasive procedures for diagnosis and therapy should be performed. Here we report our experiences in our Center for Pediatric Liver Disease and postulate that large studies are needed to avoid unnecessary invasive procedures for these patients in the future.

5.
Urology ; 106: 210-215, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28479479

RESUMEN

OBJECTIVE: To determine success rates, predictors of recurrence, and recurrence management of patients treated for short anterior urethral strictures by direct vision internal urethrotomy (DVIU). MATERIALS AND METHODS: We identified 128 patients who underwent DVIU of the anterior urethra between December 2009 and March 2016. Follow-up was conducted by telephone interviews. Success rates were assessed by Kaplan-Meier estimators. Predictors of stricture recurrence and different further therapy strategies were identified by uni- and multivariable Cox regression analyses. RESULTS: The mean age was 63.8 years (standard deviation: 16.3) and the overall success rate was 51.6% (N = 66) at a median follow-up of 16 months (interquartile range: 6-43). Median time to stricture recurrence was six months (interquartile range: 2-12). In uni- and multivariable analyses, only repeat DVIU (hazard ratio [HR] = 1.87, 95% confidence interval (CI) = 1.13-3.11, P= .015; and HR=1.78, 95% CI = 1.05-3.03, P = .032, respectively) was a risk factor for recurrence. Of 62 patients with recurrence, 35.5% underwent urethroplasty, 29% underwent further endoscopic treatment, and 33.9% did not undergo further interventional therapy. Age (HR = 1.05, 95% CI = 1.01-1.09, P = .019) and diabetes (HR = 2.90, 95% CI = 1.02-8.26, P = .047) were predictors of no further interventional therapy. CONCLUSION: DVIU seems justifiable in short urethral strictures as a primary treatment. Prior DVIU was a risk factor for recurrence. In case of recurrence, about one-third of the patients did not undergo any further therapy. Higher age and diabetes predicted the denial of any further treatment.


Asunto(s)
Manejo de la Enfermedad , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Estrechez Uretral/cirugía , Procedimientos Quirúrgicos Urológicos Masculinos/efectos adversos , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Insuficiencia del Tratamiento , Uretra/cirugía , Estrechez Uretral/diagnóstico por imagen
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