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1.
Eur J Nutr ; 2024 Apr 13.
Article in English | MEDLINE | ID: mdl-38613694

ABSTRACT

PURPOSE: Accurate height and weight measurement can be challenging in older adults and complicates nutritional status assessment. Other parameters like the neutrophil-to-lymphocyte ratio (NLR) and the lymphocyte count (LC) could be an option to these measurements. We aimed to test these variables as subrogates of body mass index (BMI) or calf-circumference (CC) for malnutrition screening in community-dwelling older adults. METHODS: This is a secondary analysis from the Salud, Bienestar y Envejecimiento (SABE) survey from Ecuador (2009). Includes data on demographics, health-related factors, physical assessments, and complete blood count, allowing to calculate NLR and LC to be used as part of the Mini Nutritional Assessment (MNA), instead of the BMI. Consequently, 4 models were included: standard MNA, MNA-CC, MNA-NLR and MNA-LC. Finally, age, sex, and comorbidities were considered as confounding variables. RESULTS: In our analysis of 1,663 subjects, 50.81% were women. Positive correlations with standard MNA were found for MNA-NLR (Estimate = 0.654, p < 0.001) MNA-CC (Estimate = 0.875, p value < 0.001) and MNA-LC (Estimate = 0.679, p < 0.001). Bland-Altman plots showed the smallest bias in MNA-CC. Linear association models revealed varying associations between MNA variants and different parameters, being MNA-NLR strongly associated with all of them (e.g. Estimate = 0.014, p = 0.001 for albumin), except BMI. CONCLUSION: The newly proposed model classified a greater number of subjects at risk of malnutrition and fewer with normal nutrition compared to the standard MNA. Additionally, it demonstrated a strong correlation and concordance with the standard MNA. This suggests that hematological parameters may offer an accurate alternative and important insights into malnutrition.

2.
Opt Express ; 32(2): 2460-2472, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38297775

ABSTRACT

We explore the synchronization of chaotic microresonator frequency combs, emphasizing the modulation instability state, which is known for its inherent chaotic behaviors. Our study confirms that the synchronization of two such combs is feasible by injecting the output from the lead microresonator into the next microresonator's input. We also identify the optimal parameters for this synchronization. Remarkably, even partial injection from the leader is sufficient for synchronization, paving the way for versatile future system configurations. Such systems could simultaneously utilize distinct spectral components for synchronization and transmission. This work advances our understanding of chaotic microresonator combs, showing them to be pivotal elements in next-generation optical communication systems.

3.
Viruses ; 14(10)2022 09 30.
Article in English | MEDLINE | ID: mdl-36298734

ABSTRACT

Interferon gamma (IFN-γ) may be potential adjuvant immunotherapy for COVID-19 patients. In this work, we assessed gene expression profiles associated with the IFN-γ pathway in response to SARS-CoV-2 infection. Employing a case-control study from SARS-CoV-2-positive and -negative patients, we identified IFN-γ-associated pathways to be enriched in positive patients. Bioinformatics analyses showed upregulation of MAP2K6, CBL, RUNX3, STAT1, and JAK2 in COVID-19-positive vs. -negative patients. A positive correlation was observed between STAT1/JAK2, which varied alongside the patient's viral load. Expression of MX1, MX2, ISG15, and OAS1 (four well-known IFN-stimulated genes (ISGs)) displayed upregulation in COVID-19-positive vs. -negative patients. Integrative analyses showcased higher levels of ISGs, which were associated with increased viral load and STAT1/JAK2 expression. Confirmation of ISGs up-regulation was performed in vitro using the A549 lung cell line treated with Poly (I:C), a synthetic analog of viral double-stranded RNA; and in different pulmonary human cell lines and ferret tracheal biopsies infected with SARS-CoV-2. A pre-clinical murine model of Coronavirus infection confirmed findings displaying increased ISGs in the liver and lungs from infected mice. Altogether, these results demonstrate the role of IFN-γ and ISGs in response to SARS-CoV-2 infection, highlighting alternative druggable targets that can boost the host response.


Subject(s)
COVID-19 , Humans , Animals , Mice , Interferon-gamma/genetics , SARS-CoV-2 , Case-Control Studies , RNA, Double-Stranded , Ferrets , MAP Kinase Kinase 6/genetics
4.
Sensors (Basel) ; 22(17)2022 Aug 24.
Article in English | MEDLINE | ID: mdl-36080844

ABSTRACT

In the last few years, the growing demand for electric vehicles (EVs) in the transportation sector has contributed to the increased use of electric rechargeable batteries. At present, lithium-ion (Li-ion) batteries are the most commonly used in electric vehicles. Although once their storage capacity has dropped to below 80-70% it is no longer possible to use these batteries in EVs, it is feasible to use them in second-life applications as stationary energy storage systems. The purpose of this study is to present an embedded system that allows a Nissan® LEAF Li-ion battery to communicate with an Ingecon® Sun Storage 1Play inverter, for control and monitoring purposes. The prototype was developed using an Arduino® microcontroller and a graphical user interface (GUI) on LabVIEW®. The experimental tests have allowed us to determine the feasibility of using Li-ion battery packs (BPs) coming from the automotive sector with an inverter with no need for a prior disassembly and rebuilding process. Furthermore, this research presents a programming and hardware methodology for the development of the embedded systems focused on second-life electric vehicle Li-ion batteries. One second-life battery pack coming from a Nissan® Leaf and aged under real driving conditions was integrated into a residential microgrid serving as an energy storage system (ESS).

5.
Rev Esp Geriatr Gerontol ; 57(5): 269-272, 2022.
Article in Spanish | MEDLINE | ID: mdl-36123267

ABSTRACT

INTRODUCTION: Hip fracture is one of the most frequent disabling injuries, presenting serious complications during the acute and subacute phase. Rehabilitation at home, after hospital discharge, allows rapid functional recovery. The objective of this study is to evaluate the possible usefulness of a home rehabilitation program in patients with hip fracture integrated in a Hospital at Home Unit. METHODS: Retrospective study that consecutively included patients accepted for home rehabilitation treatment between September 9, 2019 and December 31, 2021 in the Hospital at Home Unit of the Hospital Universitario de la Ribera, Alzira, Valencia. Demographic, clinical, functional and quality of care variables were collected. RESULTS: Two hundred twenty-four subjects were included. The mean age was 84.6 (SD 7.7) years, with 66% women and 34% men, with 32% of patients diagnosed with dementia in one of its degrees of severity. The mean hospital stay was 8.4 (SD 4.1) days and 6.5 (5.3) days in the Hospital at Home Unit rehabilitation program. 90% of the patients included in the program reached the therapeutic goal outlined during hospital admission. CONCLUSIONS: The home rehabilitation of patients with hip fracture contributes to a functional recovery of the patient in a shorter time. Further studies are necessary to confirm the results obtained.


Subject(s)
Hip Fractures , Male , Humans , Female , Aged, 80 and over , Retrospective Studies , Hip Fractures/complications , Hospitalization , Length of Stay , Patient Discharge
6.
Rev. esp. geriatr. gerontol. (Ed. impr.) ; 57(5): 269-272, Sept.-oct. 2022. tab, graf
Article in Spanish | IBECS | ID: ibc-210505

ABSTRACT

Introducción: La fractura de cadera es una de las lesiones incapacitantes más frecuentes, presentando complicaciones graves durante la fase aguda y subaguda. La rehabilitación en el domicilio, tras el alta hospitalaria, permite una rápida recuperación funcional. El objetivo de este estudio es evaluar la posible utilidad de un programa domiciliario de rehabilitación en pacientes con fractura de cadera integrado en la una unidad de hospitalización a domicilio. Métodos: Estudio retrospectivo que incluyó consecutivamente a los pacientes aceptados para tratamiento rehabilitador domiciliario entre el 9 de septiembre del 2019 y el 31 de diciembre del 2021en la Unidad de hospitalización a domicilio del Hospital Universitario de la Ribera, Alzira, Valencia. Se recogieron variables demográficas, clínicas, funcionales y de calidad asistencial. Resultados: Se incluyeron 224 sujetos. La edad media fue de 84,6 (DT 7,7) años, con un 66% de mujeres, estando un 32% de pacientes diagnosticados de demencia en alguno de sus grados de severidad. La estancia media en el hospital fue de 8,4 (DT 4,1) días y de 6,5 (5,3) días en el programa rehabilitador de la unidad de hospitalización a domicilio. El 90% de los pacientes incluidos en el programa alcanzaron el objetivo terapéutico trazado durante el ingreso hospitalario. Conclusiones: La rehabilitación domiciliaria de pacientes con fractura de cadera contribuye a una recuperación funcional del paciente en un menor tiempo. Son necesarios más estudios para confirmar los resultados obtenidos. (AU)


Introduction: Hip fracture is one of the most frequent disabling injuries, presenting serious complications during the acute and subacute phase. Rehabilitation at home, after hospital discharge, allows rapid functional recovery. The objective of this study is to evaluate the possible usefulness of a home rehabilitation program in patients with hip fracture integrated in a Hospital at Home Unit. Methods: Retrospective study that consecutively included patients accepted for home rehabilitation treatment between September 9, 2019 and December 31, 2021 in the Hospital at Home Unit of the Hospital Universitario de la Ribera, Alzira, Valencia. Demographic, clinical, functional and quality of care variables were collected. Results: Two hundred twenty-four subjects were included. The mean age was 84.6 (SD 7.7) years, with 66% women and 34% men, with 32% of patients diagnosed with dementia in one of its degrees of severity. The mean hospital stay was 8.4 (SD 4.1) days and 6.5 (5.3) days in the Hospital at Home Unit rehabilitation program. 90% of the patients included in the program reached the therapeutic goal outlined during hospital admission. Conclusions: The home rehabilitation of patients with hip fracture contributes to a functional recovery of the patient in a shorter time. Further studies are necessary to confirm the results obtained. (AU)


Subject(s)
Humans , Male , Female , Aged , Aged, 80 and over , Hip Fractures/rehabilitation , House Calls , Retrospective Studies , Patient Discharge
7.
Sci Rep ; 12(1): 9774, 2022 Jun 13.
Article in English | MEDLINE | ID: mdl-35697925

ABSTRACT

Phase-change integrated photonics has emerged as a new platform for developing photonic integrated circuits by integrating phase-change materials like GeSbTe (GST) onto the silicon photonics platform. The thickness of the GST patch that is usually placed on top of the waveguide is crucial for ensuring high optical performance. In this work, we investigate the impact of the GST thickness in terms of optical performance through numerical simulation and experiment. We show that higher-order modes can be excited in a GST-loaded silicon waveguide with relatively thin GST thicknesses (<100 nm), resulting in a dramatic reduction in the extinction ratio. Our results would be useful for designing high-performance GST/Si-based photonic devices such as non-volatile memories that could find utility in many emerging applications.

8.
Cancers (Basel) ; 14(9)2022 Apr 21.
Article in English | MEDLINE | ID: mdl-35565211

ABSTRACT

Metastatic prostate cancer (PCa) cells soiling in the bone require a metabolic adaptation. Here, we identified the metabolic genes fueling the seeding of PCa in the bone niche. Using a transwell co-culture system of PCa (PC3) and bone progenitor cells (MC3T3 or Raw264.7), we assessed the transcriptome of PC3 cells modulated by soluble factors released from bone precursors. In a Principal Component Analysis using transcriptomic data from human PCa samples (GSE74685), the altered metabolic genes found in vitro were able to stratify PCa patients in two defined groups: primary PCa and bone metastasis, confirmed by an unsupervised clustering analysis. Thus, the early transcriptional metabolic profile triggered in the in vitro model has a clinical correlate in human bone metastatic samples. Further, the expression levels of five metabolic genes (VDR, PPARA, SLC16A1, GPX1 and PAPSS2) were independent risk-predictors of death in the SU2C-PCF dataset and a risk score model built using this lipid-associated signature was able to discriminate a subgroup of bone metastatic PCa patients with a 23-fold higher risk of death. This signature was validated in a PDX pre-clinical model when comparing MDA-PCa-183 growing intrafemorally vs. subcutaneously, and appears to be under the regulatory control of the Protein Kinase A (PKA) signaling pathway. Secretome analyses of conditioned media showcased fibronectin and type-1 collagen as critical bone-secreted factors that could regulate tumoral PKA. Overall, we identified a novel lipid gene signature, driving PCa aggressive metastatic disease pointing to PKA as a potential hub to halt progression.

9.
Opt Express ; 30(9): 14518-14529, 2022 Apr 25.
Article in English | MEDLINE | ID: mdl-35473192

ABSTRACT

Transparent conducting oxides (TCOs) have emerged as both particularly appealing epsilon-near-zero (ENZ) materials and remarkable candidates for the design and fabrication of active silicon nanophotonic devices. However, the leverage of TCO's ultrafast nonlinearities requires precise control of the intricate physical mechanisms that take place upon excitation. Here we investigate such behavior for ultrafast all-optical phase switching in hybrid TCO-silicon waveguides through numerical simulation. The model is driven from the framework of intraband-transition-induced optical nonlinearity. Transient evolution is studied with a phenomenological two-temperature model. Our results reveal the best compromise between energy consumption, insertion losses and phase change per unit length for enabling ultrafast switching times below 100 fs and compact active lengths in the order of several micrometers.

10.
Antioxidants (Basel) ; 11(2)2022 Jan 29.
Article in English | MEDLINE | ID: mdl-35204159

ABSTRACT

Heme oxygenase 1 (HO-1), the rate-limiting enzyme in heme degradation, is involved in the maintenance of cellular homeostasis, exerting a cytoprotective role by its antioxidative and anti-inflammatory functions. HO-1 and its end products, biliverdin, carbon monoxide and free iron (Fe2+), confer cytoprotection against inflammatory and oxidative injury. Additionally, HO-1 exerts antiviral properties against a diverse range of viral infections by interfering with replication or activating the interferon (IFN) pathway. Severe cases of coronavirus disease 2019 (COVID-19), an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are characterized by systemic hyperinflammation, which, in some cases, leads to severe or fatal symptoms as a consequence of respiratory failure, lung and heart damage, kidney failure, and nervous system complications. This review summarizes the current research on the protective role of HO-1 in inflammatory diseases and against a wide range of viral infections, positioning HO-1 as an attractive target to ameliorate clinical manifestations during COVID-19.

11.
Antioxidants (Basel) ; 11(2)2022 Jan 31.
Article in English | MEDLINE | ID: mdl-35204174

ABSTRACT

Prostate cancer (PCa) cells display abnormal expression of proteins resulting in an augmented capacity to resist chemotherapy and colonize distant organs. We have previously shown the anti-tumoral role of heme oxygenase 1 (HO-1) in this disease. In this work, we undertook a mass spectrometry-based proteomics study to identify HO-1 molecular interactors that might collaborate with its modulatory function in PCa. Among the HO-1 interactors, we identified proteins with nuclear localization. Correlation analyses, using the PCa GSE70770 dataset, showed a significant and positive correlation between HMOX1 and 6 of those genes. Alternatively, HMOX1 and YWHAZ showed a negative correlation. Univariable analyses evidenced that high expression of HNRNPA2B1, HSPB1, NPM1, DDB1, HMGA1, ZC3HAV1, and HMOX1 was associated with increased relapse-free survival (RFS) in PCa patients. Further, PCa patients with high HSPB1/HMOX1, DDB1/HMOX1, and YWHAZ/HMOX1 showed a worse RFS compared with patients with lower ratios. Moreover, a decrease in RFS for patients with higher scores of this signature was observed using a prognostic risk score model. However, the only factor significantly associated with a higher risk of relapse was high YWHAZ. Multivariable analyses confirmed HSPB1, DDB1, and YWHAZ independence from PCa clinic-pathological parameters. In parallel, co-immunoprecipitation analysis in PCa cells ascertained HO-1/14-3-3ζ/δ (protein encoded by YWHAZ) interaction. Herein, we describe a novel protein interaction between HO-1 and 14-3-3ζ/δ in PCa and highlight these factors as potential therapeutic targets.

12.
Viruses ; 13(10)2021 10 15.
Article in English | MEDLINE | ID: mdl-34696514

ABSTRACT

Nuclear transport and vesicle trafficking are key cellular functions involved in the pathogenesis of RNA viruses. Among other pleiotropic effects on virus-infected host cells, ivermectin (IVM) inhibits nuclear transport mechanisms mediated by importins and atorvastatin (ATV) affects actin cytoskeleton-dependent trafficking controlled by Rho GTPases signaling. In this work, we first analyzed the response to infection in nasopharyngeal swabs from SARS-CoV-2-positive and -negative patients by assessing the gene expression of the respective host cell drug targets importins and Rho GTPases. COVID-19 patients showed alterations in KPNA3, KPNA5, KPNA7, KPNB1, RHOA, and CDC42 expression compared with non-COVID-19 patients. An in vitro model of infection with Poly(I:C), a synthetic analog of viral double-stranded RNA, triggered NF-κB activation, an effect that was halted by IVM and ATV treatment. Importin and Rho GTPases gene expression was also impaired by these drugs. Furthermore, through confocal microscopy, we analyzed the effects of IVM and ATV on nuclear to cytoplasmic importin α distribution, alone or in combination. Results showed a significant inhibition of importin α nuclear accumulation under IVM and ATV treatments. These findings confirm transcriptional alterations in importins and Rho GTPases upon SARS-CoV-2 infection and point to IVM and ATV as valid drugs to impair nuclear localization of importin α when used at clinically-relevant concentrations.


Subject(s)
Active Transport, Cell Nucleus/drug effects , Atorvastatin/pharmacology , COVID-19 Drug Treatment , Ivermectin/pharmacology , SARS-CoV-2/drug effects , alpha Karyopherins/metabolism , A549 Cells , Actin Cytoskeleton/drug effects , Animals , Antiviral Agents/pharmacology , Cell Line, Tumor , Chlorocebus aethiops , Drug Repositioning , HeLa Cells , Humans , NF-kappa B/metabolism , Vero Cells , rho GTP-Binding Proteins/metabolism
13.
Oncogene ; 40(44): 6284-6298, 2021 11.
Article in English | MEDLINE | ID: mdl-34584218

ABSTRACT

Prostate cancer (PCa) that progresses after androgen deprivation therapy (ADT) remains incurable. The underlying mechanisms that account for the ultimate emergence of resistance to ADT, progressing to castrate-resistant prostate cancer (CRPC), include those that reactivate androgen receptor (AR), or those that are entirely independent or cooperate with androgen signaling to underlie PCa progression. The intricacy of metabolic pathways associated with PCa progression spurred us to develop a metabolism-centric analysis to assess the metabolic shift occurring in PCa that progresses with low AR expression. We used PCa patient-derived xenografts (PDXs) to assess the metabolic changes after castration of tumor-bearing mice and subsequently confirmed main findings in human donor tumor that progressed after ADT. We found that relapsed tumors had a significant increase in fatty acids and ketone body (KB) content compared with baseline. We confirmed that critical ketolytic enzymes (ACAT1, OXCT1, BDH1) were dysregulated after castrate-resistant progression. Further, these enzymes are increased in the human donor tissue after progressing to ADT. In an in silico approach, increased ACAT1, OXCT1, BDH1 expression was also observed for a subset of PCa patients that relapsed with low AR and ERG (ETS-related gene) expression. Further, expression of these factors was also associated with decreased time to biochemical relapse and decreased progression-free survival. Our studies reveal the key metabolites fueling castration resistant progression in the context of a partial or complete loss of AR dependence.


Subject(s)
Androgen Antagonists/pharmacology , Ketone Bodies/metabolism , Prostatic Neoplasms, Castration-Resistant/pathology , Receptors, Androgen/metabolism , Animals , Cell Line, Tumor , Disease Progression , Fatty Acids/metabolism , Gene Expression Regulation, Neoplastic/drug effects , Humans , Male , Mice , Neoplasm Transplantation , Prostatic Neoplasms, Castration-Resistant/metabolism , Signal Transduction/drug effects
14.
Antioxidants (Basel) ; 10(6)2021 Jun 16.
Article in English | MEDLINE | ID: mdl-34208670

ABSTRACT

Prostate cancer (PCa) is the second most diagnosed malignancy and the fifth leading cause of cancer associated death in men worldwide. Dysregulation of cellular energetics has become a hallmark of cancer, evidenced by numerous connections between signaling pathways that include oncoproteins and key metabolic enzymes. We previously showed that heme oxygenase 1 (HO-1), a cellular homeostatic regulator counteracting oxidative and inflammatory damage, exhibits anti-tumoral activity in PCa cells, inhibiting cell proliferation, migration, tumor growth and angiogenesis. The aim of this study was to assess the role of HO-1 on the metabolic signature of PCa. After HO-1 pharmacological induction with hemin, PC3 and C4-2B cells exhibited a significantly impaired cellular metabolic rate, reflected by glucose uptake, ATP production, lactate dehydrogenase (LDH) activity and extracellular lactate levels. Further, we undertook a bioinformatics approach to assess the clinical significance of LDHA, LDHB and HMOX1 in PCa, identifying that high LDHA or low LDHB expression was associated with reduced relapse free survival (RFS). Interestingly, the shortest RFS was observed for PCa patients with low HMOX1 and high LDHA, while an improved prognosis was observed for those with high HMOX1 and LDHB. Thus, HO-1 induction causes a shift in the cellular metabolic profile of PCa, leading to a less aggressive phenotype of the disease.

15.
Sci Rep ; 11(1): 9474, 2021 May 04.
Article in English | MEDLINE | ID: mdl-33947896

ABSTRACT

A wide variety of nanophotonic applications require controlling the optical phase without changing optical absorption, which in silicon (Si) photonics has been mostly pursued electrically. Here, we investigate the unique light-matter interaction exhibited by epsilon-near-zero (ENZ) materials for all-optical phase control in nanophotonic silicon waveguides. Thermo-optic all-optical phase tuning is achieved using an ENZ material as a compact, low-loss, and efficient optical heat source. For a 10-[Formula: see text]m-long ENZ/Si waveguide, insertion loss below 0.5 dB for the transverse electric (TE) polarization is predicted together with a high control efficiency of [Formula: see text] [Formula: see text]. Our proposal provides a new approach to achieve all-optical, on-chip, and low-loss phase tuning in silicon photonic circuits.

16.
STAR Protoc ; 2(2): 100478, 2021 06 18.
Article in English | MEDLINE | ID: mdl-33907739

ABSTRACT

Differential gene expression analysis is widely used to study changes in gene expression profiles between two or more groups of samples (e.g., physiological versus pathological conditions, pre-treatment versus post-treatment, and infected versus non-infected tissues). This protocol aims to identify gene expression changes in a pre-selected set of genes associated with severe acute respiratory syndrome coronavirus 2 viral infection and host cell antiviral response, as well as subsequent gene expression association with phenotypic features using samples deposited in public repositories. For complete details on the use and outcome of this informatics analysis, please refer to Bizzotto et al. (2020).


Subject(s)
COVID-19/genetics , RNA, Viral/genetics , SARS-CoV-2/isolation & purification , Sequence Analysis, RNA/methods , Transcriptome , Workflow , COVID-19/virology , Humans , RNA, Viral/analysis , SARS-CoV-2/genetics , Exome Sequencing
17.
Commun Biol ; 4(1): 103, 2021 01 22.
Article in English | MEDLINE | ID: mdl-33483585

ABSTRACT

Some prostate cancers (PCas) are histo-pathologically grouped within the same Gleason Grade (GG), but can differ significantly in outcome. Herein, we aimed at identifying molecular biomarkers that could improve risk prediction in PCa. LC ESI-MS/MS was performed on human PCa and benign prostatic hyperplasia (BPH) tissues and peptide data was integrated with omic analyses. We identified high YWHAZ and NDRG1 expression to be associated with poor PCa prognosis considering all Gleason scores (GS). YWHAZ and NDRG1 defined two subpopulations of PCa patients with high and intermediate risk of death. Multivariable analyses confirmed their independence from GS. ROC analysis unveiled that YWHAZ outperformed GS beyond 60 months post-diagnosis. The genomic analysis of PCa patients with YWHAZ amplification, or increased mRNA or protein levels, revealed significant alterations in key DNA repair genes. We hereby state the relevance of YWHAZ in PCa, showcasing its role as an independent strong predictor of aggressiveness.


Subject(s)
14-3-3 Proteins/metabolism , Adenocarcinoma/metabolism , Cell Cycle Proteins/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Prostatic Hyperplasia/metabolism , Prostatic Neoplasms/metabolism , Adenocarcinoma/mortality , Adult , Aged , Biomarkers, Tumor/metabolism , Humans , Male , Mass Spectrometry , Middle Aged , Prostatic Neoplasms/mortality , Proteome , Risk Assessment
18.
iScience ; 23(10): 101585, 2020 Oct 23.
Article in English | MEDLINE | ID: mdl-32989429

ABSTRACT

In a published case-control study (GSE152075) from SARS-CoV-2-positive (n = 403) and -negative patients (n = 50), we analyzed the response to infection assessing gene expression of host cell receptors and antiviral proteins. The expression analysis associated with reported risk factors for COVID-19 was also assessed. SARS-CoV-2 cases had higher ACE2, but lower TMPRSS2, BSG/CD147, and CTSB expression compared with negative cases. COVID-19 patients' age negatively affected ACE2 expression. MX1 and MX2 were higher in COVID-19 patients. A negative trend for MX1 and MX2 was observed as patients' age increased. Principal-component analysis determined that ACE2, MX1, MX2, and BSG/CD147 expression was able to cluster non-COVID-19 and COVID-19 individuals. Multivariable regression showed that MX1 expression significantly increased for each unit of viral load increment. Altogether, these findings support differences in ACE2, MX1, MX2, and BSG/CD147 expression between COVID-19 and non-COVID-19 patients and point out to MX1 as a critical responder in SARS-CoV-2 infection.

19.
Biomolecules ; 10(7)2020 07 06.
Article in English | MEDLINE | ID: mdl-32640729

ABSTRACT

The inflammatory tumor microenvironment is a fertile niche accelerating prostate cancer (PCa). We have reported that heme-oxygenase (HO-1) had a strong anti-tumoral effect in PCa. We previously undertook an in-depth proteomics study to build the HO-1 interactome in PCa. In this work, we used a bioinformatics approach to address the biological significance of HO-1 interactors. Open-access PCa datasets were mined to address the clinical significance of the HO-1 interactome in human samples. HO-1 interactors were clustered into groups according to their expression profile in PCa patients. We focused on the myxovirus resistance gene (MX1) as: (1) it was significantly upregulated under HO-1 induction; (2) it was the most consistently downregulated gene in PCa vs. normal prostate; (3) its loss was associated with decreased relapse-free survival in PCa; and (4) there was a significant positive correlation between MX1 and HMOX1 in PCa patients. Further, MX1 was upregulated in response to endoplasmic reticulum stress (ERS), and this stress triggered apoptosis and autophagy in PCa cells. Strikingly, MX1 silencing reversed ERS. Altogether, we showcase MX1 as a novel HO-1 interactor and downstream target, associated with ERS in PCa and having a high impact in the clinical setting.


Subject(s)
Computational Biology/methods , Heme Oxygenase-1/metabolism , Myxovirus Resistance Proteins/metabolism , Prostatic Neoplasms/metabolism , Case-Control Studies , Cell Proliferation , Data Mining , Databases, Genetic , Endoplasmic Reticulum Stress , Gene Expression Regulation, Neoplastic , Heme Oxygenase-1/genetics , Humans , Male , Myxovirus Resistance Proteins/genetics , PC-3 Cells , Prostatic Neoplasms/genetics , Survival Analysis , Tumor Microenvironment
20.
Opt Express ; 28(7): 9393-9404, 2020 Mar 30.
Article in English | MEDLINE | ID: mdl-32225547

ABSTRACT

Typically, materials with large optical losses such as metals are used as microheaters for silicon based thermo-optic phase shifters. Consequently, the heater must be placed far from the waveguide, which could come at the expense of the phase shifter performance. Reducing the gap between the waveguide and the heater allows reducing the power consumption or increasing the switching speed. In this work, we propose an ultra-low loss microheater for thermo-optic tuning by using a CMOS-compatible transparent conducting oxide such as indium tin oxide (ITO) with the aim of drastically reducing the gap. Using finite element method simulations, ITO and Ti based heaters are compared for different cladding configurations and TE and TM polarizations. Furthermore, the proposed ITO based microheaters have also been fabricated using the optimum gap and cladding configuration. Experimental results show power consumption to achieve a π phase shift of 10 mW and switching time of a few microseconds for a 50 µm long ITO heater. The obtained results demonstrate the potential of using ITO as an ultra-low loss microheater for high performance silicon thermo-optic tuning and open an alternative way for enabling the large-scale integration of phase shifters required in emerging integrated photonic applications.

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