Establishment of Translational Luciferase-Based Cancer Models to Evaluate Antitumoral Therapies.

Luciferase (luc) bioluminescence (BL) is the most used light-emitting protein that has been engineered to be expressed in multiple cancer cell lines, allowing for the detection of tumor nodules in vivo as it can penetrate most tissues. The goal of this study was to develop an oncolytic adenovirus (OAd)-resistant human triple-negative breast cancer (TNBC) that could express luciferase. Thus, when combining an OAd with chemotherapies or targeted therapies, we would be able to monitor the ability of these compounds to enhance OAd antitumor efficacy using BL in real time. The TNBC cell line HCC1937 was stably transfected with the plasmid pGL4.50[luc2/CMV/Hygro] (HCC1937/luc2). Once established, HCC1937/luc2 was orthotopically implanted in the 4th mammary gland fat pad of NSG (non-obese diabetic severe combined immunodeficiency disease gamma) female mice. Bioluminescence imaging (BLI) revealed that the HCC1937/luc2 cell line developed orthotopic breast tumor and lung metastasis over time. However, the integration of luc plasmid modified the HCC1937 phenotype, making HCC1937/luc2 more sensitive to OAdmCherry compared to the parental cell line and blunting the interferon (IFN) antiviral response. Testing two additional luc cell lines revealed that this was not a universal response; however, proper controls would need to be evaluated, as the integration of luciferase could affect the cells' response to different treatments.

Seasonal and between-population variation in heat tolerance and cooling efficiency in a Mediterranean songbird.

Discrete populations of widely distributed species may inhabit areas with marked differences in climatic conditions across geographic and seasonal scales, which could result in intraspecific variation in thermal physiology reflecting genetic adaptation, phenotypic plasticity, or both. However, few studies have evaluated inter-population variation in physiological responses to heat. We evaluated within- and inter-population seasonal variation in heat tolerance, cooling efficiency and other key thermoregulatory traits in two Mediterranean populations of Great tit Parus major experiencing contrasting thermal environments: a lowland population subject to hotter summers and a higher annual thermal amplitude than a montane population. Specifically, we measured heat tolerance limits (HTL), body temperature, resting metabolic rate, evaporative water loss, and evaporative cooling efficiency (the ratio between evaporative heat loss to metabolic heat production) within and above the thermoneutral zone during winter and summer. Heat tolerance during summer was greater in lowland than in montane birds; indeed, lowland birds seasonally increased this trait to a significant level, while montane ones did to a lesser extent. Besides, lowland birds showed greater evaporative cooling efficiency during summer (possibly due in part to reductions in total endogenous heat load), while surprisingly montane ones showed the opposite trend. Thus, lowland birds displayed greater seasonal flexibility in HTL, body temperature and resting metabolic rate above thermoneutrality, thus giving some support to the climatic variability hypothesis - that flexibility in thermoregulatory traits should increase with climatic variability. Our results partially support the idea that songbirds' adaptive thermoregulation in the heat is flexible, highlighting the importance of considering intraspecific variation in thermoregulatory traits when modelling the future distribution and persistence of species under different climate change scenarios.

Sum of Skinfold-Corrected Girths Correlates with Resting Energy Expenditure: Development of the NRGCO Equation.

Our study aimed to validate existing equations and develop the new NRGCO equation to estimate resting energy expenditure (REE) in the Colombian population with moderate-to-high physical activity levels. Upon satisfying the inclusion criteria, a total of 86 (43F, 43M) healthy adults (mean [SD]: 27.5 [7.7] years; 67.0 [13.8] kg) were evaluated for anthropometric variables and REE by indirect calorimetry using wearable gas analyzers (COSMED K4 and K5). Significant positive correlations with REE were found for body mass (r = 0.65), body mass-to-waist (r = 0.58), arm flexed and tensed girth (r = 0.66), corrected thigh girth (r = 0.56), corrected calf girth (r = 0.61), and sum of breadths (∑3D, r = 0.59). As a novelty, this is the first time a significant correlation between REE and the sum of corrected girths (∑3CG, r = 0.63) is reported. Although existing equations such as Harris-Benedict (r = 0.63), Mifflin-St. Jeor (r = 0.67), and WHO (r = 0.64) showed moderate-to-high correlations with REE, the Bland-Altman analysis revealed significant bias (p < 0.05), indicating that these equations may not be valid for the Colombian population. Thus, participants were randomly distributed into either the equation development group (EDG, n = 71) or the validation group (VG, n = 15). A new model was created using body mass, sum of skinfolds (∑8S), corrected thigh, corrected calf, and age as predictors (r = 0.755, R2 = 0.570, RMSE = 268.41 kcal). The new NRGCO equation to estimate REE (kcal) is: 386.256 + (24.309 × BM) - (2.402 × ∑8S) - (21.346 × Corrected Thigh) + (38.629 × Corrected Calf) - (7.417 × Age). Additionally, a simpler model was identified through Bayesian analysis, including only body mass and ∑8S (r = 0.724, R2 = 0.525, RMSE = 282.16 kcal). Although external validation is needed, our validation resulted in a moderate correlation and concordance (bias = 91.5 kcal) between measured and estimated REE values using the new NRGCO equation.

Leveraging social media and other online data to study animal behavior.

The widespread sharing of information on the Internet has given rise to ecological studies that use data from digital sources including digitized museum records and social media posts. Most of these studies have focused on understanding species occurrences and distributions. In this essay, we argue that data from digital sources also offer many opportunities to study animal behavior including long-term and large-scale comparisons within and between species. Following Nikko Tinbergen's classical roadmap for behavioral investigation, we show how using videos, photos, text, and audio posted on social media and other digital platforms can shed new light on known behaviors, particularly in a changing world, and lead to the discovery of new ones.

Role of MicroRNA-204 in Regulating the Hallmarks of Breast Cancer: An Update.

microRNA-204-5p (miR-204) is a small noncoding RNA with diverse regulatory roles in breast cancer (BC) development and progression. miR-204 is implicated in the instauration of fundamental traits acquired during the multistep development of BC, known as the hallmarks of cancer. It may act as a potent tumor suppressor by inhibiting key cellular processes like angiogenesis, vasculogenic mimicry, invasion, migration, and metastasis. It achieves this by targeting multiple master genes involved in these processes, including HIF-1α, ß-catenin, VEGFA, TGFBR2, FAK, FOXA1, among others. Additionally, miR-204 modulates signaling pathways like PI3K/AKT and interacts with HOTAIR and DSCAM-AS1 lncRNAs, further influencing tumor progression. Beyond its direct effects on tumor cells, miR-204 shapes the tumor microenvironment by regulating immune cell infiltration, suppressing pro-tumorigenic cytokine production, and potentially influencing immunotherapy response. Moreover, miR-204 plays a crucial role in metabolic reprogramming by directly suppressing metabolic genes within tumor cells, indirectly affecting metabolism through exosome signaling, and remodeling metabolic flux within the tumor microenvironment. This review aims to present an update on the current knowledge regarding the role of miR-204 in the hallmarks of BC. In conclusion, miR-204 is a potential therapeutic target and prognostic marker in BC, emphasizing the need for further research to fully elucidate its complex roles in orchestrating aggressive BC behavior.

Theranostic nanoparticles for detection and treatment of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most recalcitrant cancers due to its late diagnosis, poor therapeutic response, and highly heterogeneous microenvironment. Nanotechnology has the potential to overcome some of the challenges to improve diagnostics and tumor-specific drug delivery but they have not been plausibly viable in clinical settings. The review focuses on active targeting strategies to enhance pancreatic tumor-specific uptake for nanoparticles. Additionally, this review highlights using actively targeted liposomes, micelles, gold nanoparticles, silica nanoparticles, and iron oxide nanoparticles to improve pancreatic tumor targeting. Active targeting of nanoparticles toward either differentially expressed receptors or PDAC tumor microenvironment (TME) using peptides, antibodies, small molecules, polysaccharides, and hormones has been presented. We focus on microenvironment-based hallmarks of PDAC and the potential for actively targeted nanoparticles to overcome the challenges presented in PDAC. It describes the use of nanoparticles as contrast agents for improved diagnosis and the delivery of chemotherapeutic agents that target various aspects within the TME of PDAC. Additionally, we review emerging nano-contrast agents detected using imaging-based technologies and the role of nanoparticles in energy-based treatments of PDAC. This article is categorized under: Implantable Materials and Surgical Technologies > Nanoscale Tools and Techniques in Surgery Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Anthropogenic debris as nest material in three swift species: New insights into the interactions of atmospheric pollution with wildlife.

Plastic pollution has become a global concern, affecting many species around the world. While well-documented for marine ecosystems, the impact of plastic pollution on terrestrial ecosystems is comparatively limited. In fact, only recently have some studies begun to explore the occurrence, pathways, and impacts of plastic in the atmosphere and on terrestrial species. Here, we assess the presence of synthetic material in nests of three swift species breeding in the Western Palearctic: the common swift (Apus apus), the pallid swift (Apus pallidus), and the alpine swift (Tachymarptis melba). Using data from 487 nests spanning 25 colonies and seven European countries, we show that 36.5 % of the examined nests contained anthropogenic materials, mainly plastic debris. Notably, Pallid swifts' nests, with 85 % of the total nests examined with plastic, rank among birds with the highest plastic content in nests. We also demonstrate that the probability of finding plastic in the nest increased substantially with the human footprint of the landscape. Last, we recorded four cases of swifts entangled in their own nest, a low proportion compared to other species studied previously. Our study provides compelling evidence that plastic pollution may also be considered a concern for other terrestrial species, particularly for birds with highly aerial lifestyles, such as other swifts. The correlation with the human footprint suggests that areas with higher human activity contribute more significantly. Moreover, the entanglement cases, although low, indicate a threat to bird health and welfare. To our knowledge, our study is the first to report a direct interaction between floating plastic debris in the atmosphere and any species. Understanding this interaction is key, not only due to the lack of research on the topic, but also because it highlights that plastic pollution is a multifaceted environmental issue affecting various ecosystem categories, and the broader implications of atmospheric plastic circulation on wildlife and ecosystems health.

Development of Airway Hemorrhage Simulation Scenarios With Pilot of an Airway Team Leader Assessment Tool.

INTRODUCTION: Airway hemorrhage requires rapid treatment to prevent adverse patient outcomes. Simulation education programs are challenged to recreate learning environments with adequate fidelity for team management of airway hemorrhage. METHODS: We developed Airway Hemorrhage Simulation Scenarios consisting of low-cost partial-task simulators to mimic airway hemorrhage (nasopharyngeal, oropharyngeal, expanding neck hematoma) and multiple methods to assess team leader performance in emergent airway management [Airway Team Leader Assessment Tool (ATLAT), Airway Checklist Performance, and Global Performance Rating]. We assigned trainees in Emergency Medicine (EM) and Critical Care (CC) sequentially to 1 of the 3 possible hemorrhage scenarios, and each trainee participated in a single 1-hour session composed of 3 repeated opportunities of deliberate practice of the assigned scenario. We assessed the trainees after session 1 and session 3 with independent expert evaluators of trainee performance using the ATLAT, Airway Checklist Performance, and Global Performance Rating. RESULTS: We collected data on 26 trainees: 19 EM residents [postgraduate year (PGY) 1-3] and 7 CC fellows (PGY 4-7). Trainees had significant improvement for all ATLAT domain measures, Airway Checklist Total Score, and Global Performance Rating between session 1 and session 3. CONCLUSIONS: Our pilot evaluation suggests that deliberate practice of Airway Hemorrhage Simulation Scenarios improves airway team leader performance from multiple disciplines in managing high-acuity, low-occurrence airway hemorrhage.

Advances in Melanoma: From Genetic Insights to Therapeutic Innovations.

Advances in melanoma research have unveiled critical insights into its genetic and molecular landscape, leading to significant therapeutic innovations. This review explores the intricate interplay between genetic alterations, such as mutations in BRAF, NRAS, and KIT, and melanoma pathogenesis. The MAPK and PI3K/Akt/mTOR signaling pathways are highlighted for their roles in tumor growth and resistance mechanisms. Additionally, this review delves into the impact of epigenetic modifications, including DNA methylation and histone changes, on melanoma progression. The tumor microenvironment, characterized by immune cells, stromal cells, and soluble factors, plays a pivotal role in modulating tumor behavior and treatment responses. Emerging technologies like single-cell sequencing, CRISPR-Cas9, and AI-driven diagnostics are transforming melanoma research, offering precise and personalized approaches to treatment. Immunotherapy, particularly immune checkpoint inhibitors and personalized mRNA vaccines, has revolutionized melanoma therapy by enhancing the body's immune response. Despite these advances, resistance mechanisms remain a challenge, underscoring the need for combined therapies and ongoing research to achieve durable therapeutic responses. This comprehensive overview aims to highlight the current state of melanoma research and the transformative impacts of these advancements on clinical practice.

Association of CTLA-4 (AT)n Variants in Basal Cell Carcinoma and Squamous Cell Carcinoma Patients from Western Mexico.

The incidence of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) is constantly increasing, becoming a significant health problem. CTLA-4 is a critical immune checkpoint, and it has been suggested that a variant of variable-number tandem repeat in the 3'-UTR of its gene, known as (AT)n, may be associated with a higher susceptibility to some cancers; however, little is known about genetic variants of the CTLA-4 gene in NMSC. To establish the association of this genetic variant in the CTLA-4 gene with the susceptibility of NMSC carcinogenesis in the Western Mexican population, samples from 150 BCC patients, 150 SCC patients, and 150 healthy individuals as the reference group (RG) were analyzed by endpoint PCR, followed by electrophoresis to genotype the samples. We found that the short-repeat 104/104 bp genotype may be a risk factor for BBC carcinogens (OR = 2.92, p = 0.03), whereas the long-repeat 106/106 bp genotype may be a protective factor for both BCC (OR = 0.13, p = 0.01) and SCC (OR = 0.32, p = 0.01) susceptibility. Our results show that in the Western Mexican population, long-repeat (AT)n variants in the CTLA-4 gene are associated with a protective factor in BCC and SCC. In contrast, short repeats are associated with a risk factor.

Sensing and Control Strategies Used in FES Systems Aimed at Assistance and Rehabilitation of Foot Drop: A Systematic Literature Review.

Functional electrical stimulation (FES) is a rehabilitation and assistive technique used for stroke survivors. FES systems mainly consist of sensors, a control algorithm, and a stimulation unit. However, there is a critical need to reassess sensing and control techniques in FES systems to enhance their efficiency. This SLR was carried out following the PRISMA 2020 statement. Four databases (PubMed, Scopus, Web of Science, Wiley Online Library) from 2010 to 2024 were searched using terms related to sensing and control strategies in FES systems. A total of 322 articles were chosen in the first stage, while only 60 of them remained after the final filtering stage. This systematic review mainly focused on sensor techniques and control strategies to deliver FES. The most commonly used sensors reported were inertial measurement units (IMUs), 45% (27); biopotential electrodes, 36.7% (22); vision-based systems, 18.3% (11); and switches, 18.3% (11). The control strategy most reported is closed-loop; however, most of the current commercial FES systems employ open-loop strategies due to their simplicity. Three main factors were identified that should be considered when choosing a sensor for gait-oriented FES systems: wearability, accuracy, and affordability. We believe that the combination of computer vision systems with artificial intelligence-based control algorithms can contribute to the development of minimally invasive and personalized FES systems for the gait rehabilitation of patients with FDS.

Shar-Pei autoinflammatory disease with skin necrosis due to neutrophilic vasculitis: a case report.

A 4-month-old female Shar-pei dog was admitted with apathy, anorexia, and vomiting. The patient had an appropriate vaccination protocol, with the last vaccine administered 2.5 weeks prior to the onset of clinical signs. Physical examination revealed tachycardia, fever and swelling of the tibiotarsal joints. Several diagnostic tests including complete blood cell count, biochemistry profile, urinalysis, thoracic radiographs, hind limbs radiographs, abdominal ultrasound, and infectious diseases tests, were conducted to determine the underlying cause. Shar-Pei Auto-inflammatory Disease (SPAID) was diagnosed. Additionally, the patient developed skin necrosis in the inner aspect of the tibiotarsal joints as a complication. A skin biopsy revealed cutaneous vasculopathy causing degeneration, abrupt ulceration, and ischemic necrosis with intense neutrophilic inflammation of the dermis and subcutis. Moreover, a hospital-acquired infection was identified by skin culture. Debridement of the necrotic skin was performed, and due to its' severity and extent, the wound was closed by secondary intention. A diagnostic protocol and the therapeutic dose of acetylsalicylic acid, which led to clinical improvement, are recommended here. The patient has continued to present episodic manifestations of SPAID mainly fever and swelling of the tibiotarsal joints, but there has been no recurrence of necrosis or other cutaneous lesion in the last two years.

IL10 promoter variants are associated with gene expression but they are not markers of susceptibility to acute coronary syndrome.

Interleukin-10 (IL-10) is an immunomodulatory cytokine that plays a pivotal role in the pathogenesis of acute coronary syndromes (ACS). Here, we evaluated the role of IL10 promoter variants as markers for ACS susceptibility in Western Mexican patients as well as its association with IL10 mRNA and IL-10 plasma levels. Three promoter variants (- 1082 A > G, - 819 T > C and - 592 A > C) were analyzed in 300 ACS patients and 300 control group (CG) individuals. IL10 relative gene expression was evaluated in peripheral blood mononuclear cells (PBMC) and IL-10 levels were quantified in plasma. The allelic, genotypic and haplotypic frequencies did not show significant differences between groups. ACS patients had sevenfold higher mRNA IL10 level compared to CG (p = 0.0013). Homozygous C/C carriers in both - 819 T > C and - 592 A > C variants had 0.4-fold higher IL10 mRNA expression than heterozygous and polymorphic allele homozygous genotypes (p = 0.0357) in ACS group. There were significant differences in plasma IL-10 levels in CG and ACS group (1.001 vs 1.777 pg/mL, p = 0.0051). The variants were not markers of susceptibility to ACS in Western Mexican individuals. ACS patients showed higher IL10 expression than CG individuals which could be mediated by - 819 T > C and - 592 A > C variants and pharmacotherapy.

Association of Postoperative Serum Lactate Levels with Acute Kidney Injury in Mexican Patients Undergoing Cardiac Surgery.

Acute kidney injury (AKI) is a highly prevalent and a critical complication of cardiac surgery (CS). Serum lactate (sLac) levels have consistently shown an association with morbimortality after CS. We performed a cross-sectional study including 264 adult patients that had a cardiac surgery between January and December 2020. Logistic regression analysis was performed to determine factors associated with AKI development. We measured the postoperative levels of sLac for all participants immediately after CS (T0) and at 4 h (T4) after the surgical intervention. A linear regression model was used to identify the factors influencing both sLac metrics. We identified four risk predictors of AKI; one was preoperative (atrial fibrillation), one intraoperative (cardiopulmonary bypass time), and two were postoperative (length of hospital stay and postoperative sLac). T0 and T4 sLac levels were higher among CS-AKI patients than in Non-CS-AKI patients. Postoperative sLac levels were significant independent predictors of CSA-AKI, and sLac levels are influenced by length of hospital stay, the number of transfused packed red blood cells, and the use of furosemide in CS-AKI patients. These findings may facilitate the earlier identification of patients susceptible to AKI after CS.

Antivirulence and antipathogenic activity of Mayan herbal remedies against Pseudomonas aeruginosa.

ETHNOPHARMACOLOGICAL RELEVANCE: The Yucatan Peninsula has a privileged wealth of vascular plants with which various Mayan herbal formulations have been developed. However, studies on their antipathogenic and antivirulence properties are scarce. AIM OF THE STUDY: Identify antivirulence properties in Mayan herbal remedies and determine their antipathogenic capacity in burn wounds infected with Pseudomonas aeruginosa. MATERIALS AND METHODS: An ethnobotanical study was conducted in Mayan communities in central and southern Quintana Roo, Mexico. Furthermore, the antipathogenic capacity of three Mayan herbal remedies was analyzed using an animal model of thermal damage and P. aeruginosa infection. Antivirulence properties were determined by inhibiting phenotypes regulated by quorum sensing (pyocyanin, biofilm, and swarming) and by the secretion of the ExoU toxin. The chemical composition of the most active herbal remedy was analyzed using molecular network analysis. RESULTS: It was found that topical administration of the remedy called "herbal soap" (HS) for eleven days maintained 100% survival of the animals, reduced establishment of the bacteria in the burn and prevented its systemic dispersion. Although no curative effect was recorded on tissue damaged by HS treatment, its herbal composition strongly reduced swarming and ExoU secretion. Through analysis of Molecular Networks, it was possible to carry out a global study of its chemical components, and identify the family of oxindole monoterpenoid alkaloids and carboline and tetrahydropyrididole alkaloids. In addition, flavonols, flavan-3-ols, and quinic acid derivatives were detected. CONCLUSIONS: The antipathogenic and antivirulence capacity of ancient Mayan remedies makes them a potential resource for developing new antibacterial therapies to treat burns infected by P. aeruginosa.

Utilization of RNA sequencing to investigate olfactory dysfunction in chronic rhinosinusitis without nasal polyps: A pilot study.

Objectives: Prior research on olfactory dysfunction in chronic rhinosinusitis (CRS) has focused on patients with polyps and suggests that direct inflammation of the olfactory cleft mucosa plays a contributory role. The purpose of this study was to evaluate gene expression in superior turbinate mucosal specimens, comparing normosmic and dysosmic CRS patients without polyps (CRSsNP). Methods: Tissue samples were obtained from the superior turbinates of patients with CRSsNP at the time of endoscopic sinus surgery. Samples subsequently underwent RNA sequencing and functional analysis to investigate biological pathways associated with differentially expressed genes between dysosmic (n = 7) and normosmic (n = 4) patients. Results: Differential gene expression analysis comparing dysosmic and normosmic CRSsNP patients showed upregulation of 563 genes and downregulation of 327 genes. Using stringent criteria for multiple comparisons, one upregulated gene (Immediate Early Response 3 [IER3]) had an false discovery rate (FDR) correction adjusted P value considered statistically significant (P < 0.001, fold change 2.69). Reactome functional analysis revealed eight biological pathways significantly different between dysosmic and normosmic patients (P < 0.05, FDR correction) including IL-4 and IL-13 signaling, IL-10 signaling, and rhodopsin-like receptors. Conclusions: RNA sequencing of the superior turbinates in patients with CRSsNP can provide valuable information regarding biological pathways and genes involved in olfactory dysfunction. This study supports literature suggesting that Type 2 inflammation may play a role in olfactory dysfunction in at least some patients with CRSsNP. This study also prompts questions regarding the role of IL-10, rhodopsin-like receptors, and IER3 in the pathogenesis of olfactory dysfunction.

Correction: Garza-Morales et al. Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In Vitro. Cancers 2018, 10, 144.

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