Biology subjects

Sanchez, P. L.

Publications and source records attributed to Sanchez, P. L..

4 recordsLinked to original sources

bioRxiv2026

Hierarchically engineered multi-enzyme nanoreactors for in vitro drug biosynthesis and pathway transplantation into cells

Even though most proteins evolved to function within multi-protein systems such as metabolic networks or signaling pathways, most technical protein applications are based on isolated proteins, for example therapeutic antibodies or industrial enzymes. Reliable methods for the stabilization, in vitro operation and intracellular delivery of multi-protein systems could unlock new applications in green biotechnology, diagnostics, and medical therapy. We demonstrate that the entire violacein biosynthesis pathway, consisting of up to six separately purified enzymes, can be infiltrated into a hierarchically etched MIL-101 (eMIL) metal organic framework. eMIL nanoreactors reshaped pathway dynamics and reaction flows, multiplied violacein yield in vitro and enabled pathway reuse, lyophilization and storage. Moreover, eMIL nanoreactors delivered the six-protein system into mammalian cells, where it produced violacein from cell-provided substrates and cofactors. These findings pave the way for the design of "smart" stimuli-responsive multi-enzyme nanoreactors for biotechnological and medical applications. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=87 SRC="FIGDIR/small/704820v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@2ce26forg.highwire.dtl.DTLVardef@c5fe1eorg.highwire.dtl.DTLVardef@ae8e06org.highwire.dtl.DTLVardef@1ee4f24_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2020

Remote Ischemic Preconditioning Ameliorates Anthracycline-induced Cardiotoxicity and Preserves Mitochondrial Integrity

AimsAnthracycline-induced cardiotoxicity (AIC) is a serious adverse effect in a significant proportion of cancer patients. A central mechanism of AIC is irreversible mitochondrial damage. Despite major efforts, there are currently no effective therapies able to prevent AIC. Methods and ResultsForty Large-White pigs were included. In Study 1, 20 pigs were randomized 1:1 to remote ischemic pre-conditioning (RIPC, 3 cycles of 5 min leg ischemia followed by 5 min reperfusion) or no pretreatment. RIPC was performed immediately before each of five intracoronary doxorubicin injections (0.45 mg/kg) given at weeks 0, 2, 4, 6, and 8. A group of 10 pigs with no exposure to doxorubicin served as healthy controls. Pigs underwent serial cardiac magnetic resonance (CMR) exams at baseline and at weeks 6, 8, 12, and 16. After 16-week CMR, pigs were sacrificed and tissue samples collected. In study 2, 10 new pigs received 3 doxorubicin injections (with/out preceding RIPC) and were sacrificed 2 weeks after the third dose. In Study 1, LVEF remained unchanged in doxorubicin-treated pigs until week 6 (time of the fourth doxorubicin injection). From there on, LVEF progressively declined, but LVEF depression was blunted animals receiving RIPC before doxorubicin (RIPC-Doxo), which had a significantly higher LVEF at week 16 than doxorubicin treated pigs that received no pretreatment (Untreated-Doxo) (41.5{+/-}9.1% vs 32.5{+/-}8.7%, p=0.04). Preserved LVEF was mainly due to conserved contractile function, as evidenced by smaller LVESV, and better regional contractile function. In Study 2, transmission electron microscopy (TEM) after 3 doxorubicin doses showed fragmented mitochondria with severe morphological abnormalities in RIPC+Doxo pigs, together with upregulation of fission proteins and autophagy markers on western blot. At the end of the 16-week Study 1 protocol, TEM revealed overt mitochondrial fragmentation with structural fragmentation in Untreated-Doxo pigs, whereas interstitial fibrosis was significantly less severe in the RIPC+Doxo pigs. ConclusionIn a translatable large animal model of AIC, RIPC applied immediately before each doxorubicin injection resulted in preserved cardiac contractility with significantly higher long-term LVEF and less cardiac fibrosis. RIPC prevented mitochondrial fragmentation and dysregulated autophagy from the early stages of AIC. RIPC is a promising intervention for testing in clinical trials in AIC.

molecular biology↗

bioRxiv2018

Exploratory and prospective model of stent restenosis after Percutaneous Coronary Intervention using MultivariateGaussian Subspatial Regression

A new statistical analysis methodology, "Multivariate Gaussian Subspatial Regression" (MGSR), has been applied to randomized clinical trial data collected from percutaneous coronary intervention (PCI) patients, which combines the descriptive quality of Factorial Techniques and the predictive power of Gaussian Processes. This model has been built from 3 different quantitative coronary angiographic core-lab measures of the same lesion from 2 separate angiograms (at baseline before PCI, at baseline immediately after PCI and at 12 months follow-up). Measurements of the pre-PCI variables of a patient are mapped to the factorial plane and predictions are visualized as regions of interest in this plane. MGSR makes it possible to detect patients at risk of coronary stent restenosis or patients in whom ruling out the disease, in a graphical way; avoiding unnecessary, costly and possibly risky treatments for patients with no complications predicted; and advising to closely follow patients at risk. In addition, the model recovers missing values regardless of the variables, and once fitted, it corrects itself when more dependent variables are included. MGSR software is freely available online at https://github.com/victorvicpal/MGSR.

bioinformatics↗

bioRxiv2017

A Century of Guayule: Comprehensive Genetic Characterization of the Guayule (Parthenium argentatum A. Gray) USDA Germplasm Collection

The fragility of a single-source, geographically concentrated supply of natural rubber, a critical material of the modern economy, has brought guayule (Parthenium argentatum A. Gray) to the forefront as an alternative source of natural rubber. The improvement of guayule for commercial-scale production has been limited by the lack of genomic tools and well-characterized genetic resources required for genomics-assisted breeding. To address this issue, we developed nearly 50,000 single nucleotide polymorphism (SNP) genetic markers and genotyped 69 accessions of guayule and its sister taxa mariola (Parthenium incanum Kunth), representing the entire available NALPGRU germplasm collection. We identified multiple interspecific hybrid accessions previously considered guayule, including six guayule-mariola hybrids and non-mariola interspecific hybrid accessions AZ-2 and AZ-3, two commonly used high-yielding cultivars. We dissected genetic diversity within the collection to identify a highly diverse subset of guayule accessions, and showed that wild guayule stands in Big Bend National Park, Texas, USA have the potential to provide hitherto untapped guayule genetic diversity. Together, these results provide the most thorough genetic characterization of guayule germplasm to date and lay the foundation for rapid genetic improvement of commercial guayule germplasm.\n\nKey Results O_LISix guayule accessions are guayule-mariola hybrids\nC_LIO_LIGuayule collections from Big Bend National Park contain novel guayule genotypes not present in collections from Mexico\nC_LIO_LICommonly cultivated accessions AZ2 and AZ3 contain introgressions from other Parthenium species\nC_LIO_LIThe triploid accessions 11591, 11646, N576, N565, N565II, and RICHARDSON are generally indistinguishable from each other with respect to genetic background and likely represent the 4265-I source genotype (Johnson, 1950)\nC_LIO_LIOpen pollinated and purposefully outcrossed tetraploid selections derived from 4265-I incorporate further genetic diversity and form distinct genotypes\nC_LI

plant biology↗