Transcriptomic profile induced in bone marrow mesenchymal stromal cells after interaction with multiple myeloma cells: implications in myeloma progression and myeloma bone disease

This is an open-access article distributed under the terms of the Creative Commons Attribution License.Despite evidence about the implication of the bone marrow (BM) stromal microenvironment in multiple myeloma (MM) cell growth and survival, little is known about the effects of myelomatous cells on BM stromal cells. Mesenchymal stromal cells (MSCs) from healthy donors (dMSCs) or myeloma patients (pMSCs) were co-cultured with the myeloma cell line MM.1S, and the transcriptomic profile of MSCs induced by this interaction was analyzed. Deregulated genes after co-culture common to both d/pMSCs revealed functional involvement in tumor microenvironment cross-talk, myeloma growth induction and drug resistance, angiogenesis and signals for osteoclast activation and osteoblast inhibition. Additional genes induced by co-culture were exclusively deregulated in pMSCs and predominantly associated to RNA processing, the ubiquitine-proteasome pathway, cell cycle regulation, cellular stress and non-canonical Wnt signaling. The upregulated expression of five genes after co-culture (CXCL1, CXCL5 and CXCL6 in d/pMSCs, and Neuregulin 3 and Norrie disease protein exclusively in pMSCs) was confirmed, and functional in vitro assays revealed putative roles in MM pathophysiology. The transcriptomic profile of pMSCs co-cultured with myeloma cells may better reflect that of MSCs in the BM of myeloma patients, and provides new molecular insights to the contribution of these cells to MM pathophysiology and to myeloma bone disease.This work was supported by grants from the Spanish MINECO-ISCIII (PI12/02591, PI12/00624) and FEDER (European Funds for Regional Development); the Centro en Red for Regenerative Medicine and Cellular Therapy from Castilla y León; the Spanish Health Thematic Network of Cooperative Research in Cancer (RTICC RD12/0056/0058 and RD12/0036/0003), and Spanish FIS (PS09/01897 and PS09/00843). AG-G received support from the Centro en Red for Regenerative Medicine and Cellular Therapy from Castilla y León and from the Spanish Society of Hematology and Hemotherapy (SEHH), and EDR from the Spanish Association for Cancer Research (AECC).Peer Reviewe

Transcriptomic profile induced in bone marrow mesenchymal stromal cells after interaction with multiple myeloma cells: implications in myeloma progression and myeloma bone disease

Despite evidence about the implication of the bone marrow (BM) stromal microenvironment in multiple myeloma (MM) cell growth and survival, little is known about the effects of myelomatous cells on BM stromal cells. Mesenchymal stromal cells (MSCs) from healthy donors (dMSCs) or myeloma patients (pMSCs) were co-cultured with the myeloma cell line MM.1S, and the transcriptomic profile of MSCs induced by this interaction was analyzed. Deregulated genes after co-culture common to both d/pMSCs revealed functional involvement in tumor microenvironment cross-talk, myeloma growth induction and drug resistance, angiogenesis and signals for osteoclast activation and osteoblast inhibition. Additional genes induced by co-culture were exclusively deregulated in pMSCs and predominantly associated to RNA processing, the ubiquitine-proteasome pathway, cell cycle regulation, cellular stress and non-canonical Wnt signaling. The upregulated expression of five genes after co-culture (CXCL1, CXCL5 and CXCL6 in d/pMSCs, and Neuregulin 3 and Norrie disease protein exclusively in pMSCs) was confirmed, and functional in vitro assays revealed putative roles in MM pathophysiology. The transcriptomic profile of pMSCs co-cultured with myeloma cells may better reflect that of MSCs in the BM of myeloma patients, and provides new molecular insights to the contribution of these cells to MM pathophysiology and to myeloma bone disease.This work was supported by grants from the Spanish MINECO-ISCIII (PI12/02591, PI12/00624) and FEDER (European Funds for Regional Development); the Centro en Red for Regenerative Medicine and Cellular Therapy from Castilla y León; the Spanish Health Thematic Network of Cooperative Research in Cancer (RTICC RD12/0056/0058 and RD12/0036/0003), and Spanish FIS (PS09/01897 and PS09/00843). AG-G received support from the Centro en Red for Regenerative Medicine and Cellular Therapy from Castilla y León and from the Spanish Society of Hematology and Hemotherapy (SEHH), and EDR from the Spanish Association for Cancer Research (AECC

Hábitos, actitudes y conocimientos sobre la exposición solar de corredores de fondo en la Costa del Sol

A nivel dermatológico, la elevada exposición solar a radiación ultravioleta asociada a la práctica de actividades deportivas al aire libre, máxime en actividades recreativas de larga duración como son los corredores de fondo, aumenta el fotoenvejecimiento de la piel y la incidencia de cáncer de piel. El propósito del estudio fue evaluar los hábitos, actitudes y conocimientos sobre la exposición solar de corredores de fondo de nuestra comunidad. Se realizó un estudio transversal descriptivo mediante encuesta con un muestreo de conveniencia entre aquellos participantes de las medias maratones populares de Fuengirola y Marbella celebradas en el mes de septiembre del año 2016. En la muestra evaluada se ha hallado una intensa exposición solar realizando actividades al aire libre, asociado ello a una prevalencia de quemaduras solares elevada (uno de cada 2 corredores). Exposure to UV radiation during the practice of sports in the open air is especially high in sustained recreational activities such as long-distance running. UV exposure increases skin photoaging and the incidence of skin cancer. This study aimed to describe habits and attitudes related to sun exposure among long-distance runners in our area of southern Spain as well as to evaluate the runners’ knowledge of exposure. A cross-sectional descriptive study was designed to survey a convenience sample of participants in half marathons in Fuengirola and Marbella in September 2016. We found a high level of sun exposure among participants in this outdoor activity. The prevalence of sunburn was also high, experienced by half of the runners surveyed

Antebrachial microvascular flap for reconstruction of the pelvic limb: case report

Complex defects in the soft tissues of the foot and ankle caused by high-energy trauma, infection, cancer or diabetes require rapid and effective treatment which decreases the risk of infection, bone healing time, hospital stay and number total of surgical approaches. Authors report a clinical case of a 23-year-old female patient who suffers high-energy trauma due to a motorcycle accident which causes exposure of the distal third of the tibia, loss of the tibial joint face, and loss of tissue throughout the region of the malleolus medial of the right pelvic extremity. Tissue transfer to the pelvic limb is performed using left contralateral radial antebrachial free flap as donor area. This case report aims to emphasize the key aspects of the high energy trauma approach by using microvascular flaps, as well as the satisfactory evolution of the patient that directly affects the prognosis for life and function

The Use of Corticosteroids or Tocilizumab in COVID-19 Based on Inflammatory Markers

SEMI-COVID-19 Network.[Background] The inflammatory cascade is the main cause of death in COVID-19 patients. Corticosteroids (CS) and tocilizumab (TCZ) are available to treat this escalation but which patients to administer it remains undefined.[Objective] We aimed to evaluate the efficacy of immunosuppressive/anti-inflammatory therapy in COVID-19, based on the degree of inflammation. .[Design] A retrospective cohort study with data on patients collected and followed up from March 1st, 2020, to May 1st, 2021, from the nationwide Spanish SEMI-COVID-19 Registry. Patients under treatment with CS vs. those under CS plus TCZ were compared. Effectiveness was explored in 3 risk categories (low, intermediate, high) based on lymphocyte count, C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, and d-dimer values.[Patients] A total of 21,962 patients were included in the Registry by May 2021. Of these, 5940 met the inclusion criteria for the present study (5332 were treated with CS and 608 with CS plus TCZ).[Main Measures] The primary outcome of the study was in-hospital mortality. Secondary outcomes were the composite variable of in-hospital mortality, requirement for high-flow nasal cannula (HFNC), non-invasive mechanical ventilation (NIMV), invasive mechanical ventilation (IMV), or intensive care unit (ICU) admission.[Key Results] A total of 5940 met the inclusion criteria for the present study (5332 were treated with CS and 608 with CS plus TCZ). No significant differences were observed in either the low/intermediate-risk category (1.5% vs. 7.4%, p=0.175) or the high-risk category (23.1% vs. 20%, p=0.223) after propensity score matching. A statistically significant lower mortality was observed in the very high–risk category (31.9% vs. 23.9%, p=0.049).[Conclusions] The prescription of CS alone or in combination with TCZ should be based on the degrees of inflammation and reserve the CS plus TCZ combination for patients at high and especially very high risk.Peer reviewe

A magnetically-driven piston pump for ultra-clean applications

A magnetically driven piston pump for xenon gas recirculation is presented. The pump is designed to satisfy extreme purity and containment requirements, as is appropriate for the recirculation of isotopically enriched xenon through the purification system and large liquid xenon TPC of EXO-200. The pump, using sprung polymer gaskets, is capable of pumping more than 16 standard liters per minute (SLPM) of xenon gas with 750 torr differential pressure.Comment: 6 pages, 5 figure

The Variant rs1867277 in FOXE1 Gene Confers Thyroid Cancer Susceptibility through the Recruitment of USF1/USF2 Transcription Factors

In order to identify genetic factors related to thyroid cancer susceptibility, we adopted a candidate gene approach. We studied tag- and putative functional SNPs in genes involved in thyroid cell differentiation and proliferation, and in genes found to be differentially expressed in thyroid carcinoma. A total of 768 SNPs in 97 genes were genotyped in a Spanish series of 615 cases and 525 controls, the former comprising the largest collection of patients with this pathology from a single population studied to date. SNPs in an LD block spanning the entire FOXE1 gene showed the strongest evidence of association with papillary thyroid carcinoma susceptibility. This association was validated in a second stage of the study that included an independent Italian series of 482 patients and 532 controls. The strongest association results were observed for rs1867277 (OR[per-allele] = 1.49; 95%CI = 1.30–1.70; P = 5.9×10−9). Functional assays of rs1867277 (NM_004473.3:c.−283G>A) within the FOXE1 5′ UTR suggested that this variant affects FOXE1 transcription. DNA-binding assays demonstrated that, exclusively, the sequence containing the A allele recruited the USF1/USF2 transcription factors, while both alleles formed a complex in which DREAM/CREB/αCREM participated. Transfection studies showed an allele-dependent transcriptional regulation of FOXE1. We propose a FOXE1 regulation model dependent on the rs1867277 genotype, indicating that this SNP is a causal variant in thyroid cancer susceptibility. Our results constitute the first functional explanation for an association identified by a GWAS and thereby elucidate a mechanism of thyroid cancer susceptibility. They also attest to the efficacy of candidate gene approaches in the GWAS era

Adaptation of sea turtles to climate warming: Will phenological responses be sufficient to counteract changes in reproductive output?

Sea turtles are vulnerable to climate change since their reproductive output is influenced by incubating temperatures, with warmer temperatures causing lower hatching success and increased feminization of embryos. Their ability to cope with projected increases in ambient temperatures will depend on their capacity to adapt to shifts in climatic regimes. Here, we assessed the extent to which phenological shifts could mitigate impacts from increases in ambient temperatures (from 1.5 to 3°C in air temperatures and from 1.4 to 2.3°C in sea surface temperatures by 2100 at our sites) on four species of sea turtles, under a “middle of the road” scenario (SSP2-4.5). Sand temperatures at sea turtle nesting sites are projected to increase from 0.58 to 4.17°C by 2100 and expected shifts in nesting of 26–43 days earlier will not be sufficient to maintain current incubation temperatures at 7 (29%) of our sites, hatching success rates at 10 (42%) of our sites, with current trends in hatchling sex ratio being able to be maintained at half of the sites. We also calculated the phenological shifts that would be required (both backward for an earlier shift in nesting and forward for a later shift) to keep up with present-day incubation temperatures, hatching success rates, and sex ratios. The required shifts backward in nesting for incubation temperatures ranged from −20 to −191 days, whereas the required shifts forward ranged from +54 to +180 days. However, for half of the sites, no matter the shift the median incubation temperature will always be warmer than the 75th percentile of current ranges. Given that phenological shifts will not be able to ameliorate predicted changes in temperature, hatching success and sex ratio at most sites, turtles may need to use other adaptive responses and/or there is the need to enhance sea turtle resilience to climate warming.18 página

Persistent effects of pre-Columbian plant domestication on Amazonian forest composition

The extent to which pre-Columbian societies altered Amazonian landscapes is hotly debated. We performed a basin-wide analysis of pre-Columbian impacts on Amazonian forests by overlaying known archaeological sites in Amazonia with the distributions and abundances of 85 woody species domesticated by pre-Columbian peoples. Domesticated species are five times more likely to be hyperdominant than non-domesticated species. Across the basin the relative abundance and richness of domesticated species increases in forests on and around archaeological sites. In southwestern and eastern Amazonia distance to archaeological sites strongly influences the relative abundance and richness of domesticated species. Our analyses indicate that modern tree communities in Amazonia are structured to an important extent by a long history of plant domestication by Amazonian peoples