Facile photopatterning of perfusable microchannels in hydrogels for microphysiological systems.

Perfusable hydrogels have garnered substantial attention in recent years for the fabrication of microphysiological systems. However, current methodologies to fabricate microchannels in hydrogel platforms involve sophisticated equipment and techniques, which hinder progress of the field. In this protocol, we present a cost-effective, simple, versatile and ultrafast method to create perfusable microchannels of complex shapes in photopolymerizable hydrogels. Our method uses one-step UV photocross-linking and a photomask printed on inexpensive transparent films, to photopattern both synthetic (PEG-norbornene) and natural (hyaluronic acid-norbornene) hydrogels in just 0.8 s. Moreover, these perfusable hydrogels are fully integrated into a custom-made microfluidic device that allows continuous fluid perfusion when connected to an external pump system. This methodology can be easily reproduced by professionals with basic laboratory skills and a fundamental knowledge of polymers and materials science. In this protocol, we demonstrate the functionality of our photopatterned hydrogels by seeding human endothelial cells into the microchannels, culturing them under dynamic conditions for 7 d, and exposing them to inflammatory stimuli to elicit cellular responses. This highlights the versatility of our platform in fabricating microphysiological systems and different microenvironments. The fabrication of perfusable channels within the hydrogels, including the fabrication of the microfluidic devices, requires ~3 d. The development of the cell-seeded microphysiological system, including the stimulation of cells, takes ~7 d. In conclusion, our approach provides a straightforward and widely applicable solution to simplify and reduce the cost of biofabrication techniques for developing functional in vitro models using perfusable three-dimensional hydrogels.

Improving Functional Muscle Regeneration in Volumetric Muscle Loss Injuries by Shifting the Balance of Inflammatory and Pro-Resolving Lipid Mediators.

Severe tissue loss resulting from extremity trauma, such as volumetric muscle loss (VML), poses significant clinical challenges for both general and military populations. VML disrupts the endogenous tissue repair mechanisms, resulting in acute and unresolved chronic inflammation and immune cell presence, impaired muscle healing, scar tissue formation, persistent pain, and permanent functional deficits. The aberrant healing response is preceded by acute inflammation and immune cell infiltration which does not resolve. We analyzed the biosynthesis of inflammatory and specialized pro-resolving lipid mediators (SPMs) after VML injury in two different models; muscle with critical-sized defects had a decreased capacity to biosynthesize SPMs, leading to dysregulated and persistent inflammation. We developed a modular poly(ethylene glycol)-maleimide hydrogel platform to locally release a stable isomer of Resolvin D1 (AT-RvD1) and promote endogenous pathways of inflammation resolution in the two muscle models. The local delivery of AT-RvD1 enhanced muscle regeneration, improved muscle function, and reduced pain sensitivity after VML by promoting molecular and cellular resolution of inflammation. These findings provide new insights into the pathogenesis of VML and establish a pro-resolving hydrogel therapeutic as a promising strategy for promoting functional muscle regeneration after traumatic injury.

Validation of Saliva as the Clinical Specimen Type for a University-Wide COVID-19 Surveillance Program.

At the beginning of the COVID-19 pandemic, the Georgia Institute of Technology made the decision to keep the university doors open for on-campus attendance. To manage COVID-19 infection rates, internal resources were applied to develop and implement a mass asymptomatic surveillance program. The objective was to identify infections early for proper follow-on verification testing, contact tracing, and quarantine/isolation as needed. Program success depended on frequent and voluntary sample collection from over 40,000 students, faculty, and staff personnel. At that time, the nasopharyngeal (NP) swab, not saliva, was the main accepted sample type for COVID-19 testing. However, due to collection discomfort and the inability to be self-collected, the NP swab was not feasible for voluntary and frequent self-collection. Therefore, saliva was selected as the clinical sample type and validated. A saliva collection kit and a sample processing and analysis workflow were developed. The results of a clinical sample-type comparison study between co-collected and matched NP swabs and saliva samples showed 96.7% positive agreement and 100% negative agreement. During the Fall 2020 and Spring 2021 semesters, 319,988 samples were collected and tested. The program resulted in maintaining a low overall mean positivity rate of 0.78% and 0.54% for the Fall 2020 and Spring 2021 semesters, respectively. For this high-throughput asymptomatic COVID-19 screening application, saliva was an exceptionally good sample type.

Altitude is correlated with body size differences among Cotesia flavipes (Hymenoptera: Braconidae) wasps collected in two mountain ranges.

Living at high altitudes impose physiological and ecological challenges to which species may respond altering their body size, body proportions, and the shape of their body parts. Despite the importance of this topic for understanding the origin of species diversity, little attention has been invested in this phenomenon at the populational level. This paper study the relationship between altitude and body size, body proportions, and forewing shape venation of two populations of the parasitoid wasp Cotesia flavipes. Wasps were collected from Diatraea spp. larvae from sugarcane crops in two Colombian mountain ranges that cover between 600 m and 2143 m of altitude. Linear measurements of different body regions and geometric morphometrics of the forewing were subject to multivariate comparisons and allometric analyses to assess variation and to compare trends between ranges. Central (600 m to 1704 m) and Eastern Cordillera (877 m to 2143 m) populations showed different trends between body size and altitude. Allometric trends were not uniform within or between populations nor between structures. The allometric slopes of five body measurements from a single altitude differed from these from its own mountain range suggesting that body size trends along the cordilleras are a consequence of altitude and not of intrinsic body resource allocation processes. Wing shape between populations differed; however, these changes were poorly related to altitude. In agreement with recent studies in other groups, the observed allometric and wing shape differences between the two C. flavipes populations could be a plasticity response to altitude with interesting implications for posterior genetic differentiation.

Harnessing cellular therapeutics for type 1 diabetes mellitus: progress, challenges, and the road ahead.

Type 1 diabetes mellitus (T1DM) is a growing global health concern that affects approximately 8.5 million individuals worldwide. T1DM is characterized by an autoimmune destruction of pancreatic ß cells, leading to a disruption in glucose homeostasis. Therapeutic intervention for T1DM requires a complex regimen of glycaemic monitoring and the administration of exogenous insulin to regulate blood glucose levels. Advances in continuous glucose monitoring and algorithm-driven insulin delivery devices have improved the quality of life of patients. Despite this, mimicking islet function and complex physiological feedback remains challenging. Pancreatic islet transplantation represents a potential functional cure for T1DM but is hindered by donor scarcity, variability in harvested cells, aggressive immunosuppressive regimens and suboptimal clinical outcomes. Current research is directed towards generating alternative cell sources, improving transplantation methods, and enhancing cell survival without chronic immunosuppression. This Review maps the progress in cell replacement therapies for T1DM and outlines the remaining challenges and future directions. We explore the state-of-the-art strategies for generating replenishable ß cells, cell delivery technologies and local targeted immune modulation. Finally, we highlight relevant animal models and the regulatory aspects for advancing these technologies towards clinical deployment.

Squeezing Out Nanoparticles from Perovskites: Controlling Exsolution with Pressure.

Nanoparticle exsolution has emerged as a versatile method to functionalize oxides with robust metallic nanoparticles for catalytic and energy applications. By modifying certain external parameters during thermal reduction (temperature, time, reducing gas), some morphological and/or compositional properties of the exsolved nanoparticles can be tuned. Here, it is shown how the application of high pressure (<100 bar H2) enables the control of the exsolution of ternary FeCoNi alloyed nanoparticles from a double perovskite. H2 pressure affects the lattice expansion and the nanoparticle characteristics (size, population, and composition). The composition of the alloyed nanoparticles could be controlled, showing a reversal of the expected thermodynamic trend at 10 and 50 bar, where Fe becomes the main component instead of Ni. In addition, pressure drastically lowers the exsolution temperature to 300 °C, resulting in unprecedented highly-dispersed and small-sized nanoparticles with a similar composition to those obtained at 600 °C and 10 bar. The mechanisms behind the effects of pressure on exsolution are discussed, involving kinetic, surface thermodynamics, and lattice-strain factors. A volcano-like trend of the exsolution extent suggests that competing pressure-dependent mechanisms govern the process. Pressure emerges as a new design tool for metallic nanoparticle exsolution enabling novel nanocatalysts and surface-functionalized materials.

Mini-colons predict drug toxicity in vitro.

Mitrofanova et al.1 engineer a human colonic in vitro model capable of producing an intestinal mucus barrier, with potential applications for predicting drug-induced gastrointestinal toxicity. This improved system paves the way for more accurate and efficient drug development processes.

Exploring New Frontiers: Innovations and Therapeutic Targets in Dermatology.

The focus of dermatology has increasingly shifted towards exploring new and innovative approaches [...].

ß3-Adrenergic receptor overexpression in cardiomyocytes preconditions mitochondria to withstand ischemia-reperfusion injury.

ß3-Adrenergic receptor (ß3AR) agonists have been shown to protect against ischemia-reperfusion injury (IRI). Since ß3ARs are present both in cardiomyocytes and in endothelial cells, the cellular compartment responsible for this protection has remained unknown. Using transgenic mice constitutively expressing the human ß3AR (hß3AR) in cardiomyocytes or in the endothelium on a genetic background of null endogenous ß3AR expression, we show that only cardiomyocyte expression protects against IRI (45 min ischemia followed by reperfusion over 24 h). Infarct size was also limited after ischemia-reperfusion in mice with cardiomyocyte hß3AR overexpression on top of endogenous ß3AR expression. hß3AR overexpression in these mice reduced IRI-induced cardiac fibrosis and improved long-term left ventricular systolic function. Cardiomyocyte-specific ß3AR overexpression resulted in a baseline remodeling of the mitochondrial network, characterized by upregulated mitochondrial biogenesis and a downregulation of mitochondrial quality control (mitophagy), resulting in elevated numbers of small mitochondria with a depressed capacity for the generation of reactive oxygen species but improved capacity for ATP generation. These processes precondition cardiomyocyte mitochondria to be more resistant to IRI. Upon reperfusion, hearts with hß3AR overexpression display a restoration in the mitochondrial quality control and a rapid activation of antioxidant responses. Strong protection against IRI was also observed in mice infected with an adeno-associated virus (AAV) encoding hß3AR under a cardiomyocyte-specific promoter. These results confirm the translational potential of increased cardiomyocyte ß3AR expression, achieved either naturally through exercise or artificially through gene therapy approaches, to precondition the cardiomyocyte mitochondrial network to withstand future insults.

Monoallelic de novo AJAP1 loss-of-function variants disrupt trans-synaptic control of neurotransmitter release.

Adherens junction-associated protein 1 (AJAP1) has been implicated in brain diseases; however, a pathogenic mechanism has not been identified. AJAP1 is widely expressed in neurons and binds to γ-aminobutyric acid type B receptors (GBRs), which inhibit neurotransmitter release at most synapses in the brain. Here, we show that AJAP1 is selectively expressed in dendrites and trans-synaptically recruits GBRs to presynaptic sites of neurons expressing AJAP1. We have identified several monoallelic AJAP1 variants in individuals with epilepsy and/or neurodevelopmental disorders. Specifically, we show that the variant p.(W183C) lacks binding to GBRs, resulting in the inability to recruit them. Ultrastructural analysis revealed significantly decreased presynaptic GBR levels in Ajap1-/- and Ajap1W183C/+ mice. Consequently, these mice exhibited reduced GBR-mediated presynaptic inhibition at excitatory and inhibitory synapses, along with impaired synaptic plasticity. Our study reveals that AJAP1 enables the postsynaptic neuron to regulate the level of presynaptic GBR-mediated inhibition, supporting the clinical relevance of loss-of-function AJAP1 variants.

Temporal relationship between sarcoidosis and malignancies in a nationwide cohort of 1942 patients.

PURPOSE: To investigate the phenotype of sarcoidosis according to the time when a malignancy is diagnosed (preexisting to the diagnosis of sarcoidosis, concomitant, or sequential) and to identify prognostic factors associated with malignancies in a large cohort of patients with sarcoidosis. METHODS: We searched for malignancies in the SARCOGEAS cohort, a multicenter nationwide database of consecutive patients diagnosed with sarcoidosis according to the ATS/ESC/WASOG criteria. Solid malignancies were classified using the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) nomenclature, and hematological malignancies using the 2016 WHO classification. We excluded patients with a biopsy-proven diagnosis of sarcoidosis based exclusively on demonstrating granulomas in tissues also involved by malignant cells. RESULTS: Out of 1942 patients with sarcoidosis, 233 (12%) developed 250 malignancies, including solid (n = 173), hematological (n = 57), and both types of malignancies (n = 3). Concerning the time interval between the diagnoses of both conditions, 83 (36%) patients were diagnosed with malignancy at least 1 year before sarcoidosis diagnosis, 22 (9%) had s synchronous diagnosis of both diseases, and 118 (51%) developed malignancies at least 1 year after the diagnosis of sarcoidosis (the remaining cases developed malignancies in different time intervals). The multivariate-adjusted model showed that individuals with sarcoidosis who developed a malignancy had an hazard ratio (HR) of 2.27 [95% confidence interval (CI), 1.62-3.17] for having an asymptomatic clinical phenotype at diagnosis of sarcoidosis and that spleen (presence vs. absence: HR = 2.06; 95% CI, 1.21-3.51) and bone marrow (presence vs. absence: HR = 3.04; 95% CI, 1.77-5.24) involvements were independent predictors for the development of all-type malignancies. No predictive factors were identified when the analysis was restricted to the development of solid malignancies. The analysis limited to the development of hematological malignancies confirmed the presence of involvement in the spleen (HR = 3.73; 95% CI, 1.38-10.06) and bone marrow (presence vs. absence: HR = 8.00; 95% CI, 3.15-20.35) at the time of sarcoidosis diagnosis as predictive factors. CONCLUSION: It is essential to consider the synchronous or metachronous timing of the diagnosis of malignancies in people with sarcoidosis. We found that half of the malignancies were diagnosed after a diagnosis of sarcoidosis, with spleen and bone marrow involvement associated with a four to eight times higher risk of developing hematological malignancies. Key messages What is already known on this topic Malignancies are one of the comorbidities more frequently encountered in people with sarcoidosis What this study adds Malignancies occur in 12% of patients with sarcoidosis Malignancy may precede, coincide with, or follow the diagnosis of sarcoidosis One-third were identified before sarcoidosis, and half were diagnosed after Spleen and bone marrow involvement are risk factors for developing hematological malignancies How this study might affect research, practice or policy Patients with sarcoidosis should be regularly monitored for neoplasms, informed of the increased risk, and educated on early detection. Those with spleen or bone marrow involvement must be closely followed.

Do patients with inflammatory bowel disease really know what other immune-mediated inflammatory diseases they are diagnosed with?

BACKGROUND AND AIMS: The association of inflammatory bowel disease (IBD) with other immune-mediated inflammatory diseases (IMIDs) in the same patient is well known. We aimed to evaluate the degree of knowledge that patients with IBD have regarding the coexistence of other IMIDs and to analyze the factors associated with the concordance between self-reported and confirmed medical information. METHODS: Patients with IBD at a tertiary hospital answered a questionnaire on the presence of 54 IMIDs (self-reported diagnosis), and their IMID diagnosis was confirmed in their medical records (reference diagnosis). Agreement between the self-reported IMID and the IMID according to medical records was evaluated. The association between concordance and different predictors was evaluated using logistic regression models. RESULTS: A total of 1,620 patients were included. Six hundred and twenty-six (39%) patients were diagnosed with at least one IMID, and 177 (11%) with two or more. Overall agreement between patients´ self-report and medical records was k:0.61. When we grouped IMIDs according to affected organs or systems, agreement on rheumatic IMIDs was moderate (k:0.58), whereas agreement on cutaneous (k:0.66), endocrine (k: 0.74) and ocular (k:0.73) IMIDs was substantial. Among patients who had IMIDs, the factor associated with greater concordance was female gender, while lower concordance was associated with a lower educational level and the fact that the IMID had been diagnosed at the same time or later than IBD. CONCLUSION: The knowledge that patients with IBD have regarding the coexistence of other IMIDs is poor, especially in rheumatic IMIDs.

Evaluating the Safety of the Intragastric Balloon: Spanish Multicenter Experience in 20,680 Cases and with 12 Different Balloon Models.

INTRODUCTION: Intragastric balloon (IGB) is a minimally invasive and reversible option for obesity treatment. There is a worldwide growing number of different IGB models. The efficacy and safety profile for each model must be demonstrated. We aim to evaluate IGB safety profile according to the experience of the Spanish Bariatric Endoscopy Group (GETTEMO). METHODS: A survey of 37 IGBs safety-related questions was sent to all GETTEMO members, to retrospectively collect a multicenter Spanish registry. Incidence, causes, and resolution of both major and minor complications and adverse events (AEs), including legal consequences, differentiated for each balloon model were evaluated. Secondary outcome was weight loss data to confirm efficacy. RESULTS: Twenty-one Spanish hospitals experienced in IGBs responded. The overall data encompassed 20,680 IGBs, including 12 different models. Mean %TBWL of 17.66 ± 2.5% was observed. Early removal rate due to intolerance was 3.62%. Mean major complications rate was 0.70% (> 1% in Spatz2, HB, and Spatz3 models), mainly complicated gastric ulcer. Minor AEs rate was 6.37%, mainly esophagitis. Nine cases (0.04%) required surgery. A single case of mortality (0.0048%) occurred. Seven lawsuits (0.0034%) were received, all with favorable resolution. CONCLUSIONS: In the Spanish experience accumulating 20,680 IGBs and including 12 different balloon models, a low incidence rate of major complications and minor AEs are observed (0.70% and 6.37%, respectively), mostly resolved with medical/endoscopic management. IGB shows good tolerance and efficacy profile. These safety data are within the accepted quality standards.

Tear Cytokines as Predictive Biomarkers of Success in Contact Lens Discomfort Management.

PURPOSE: To analyze changes in tear levels of inflammatory mediators in symptomatic contact lens (CL) wearers after refitting with daily disposable CLs and to identify potential biomarkers of success in CL discomfort (CLD) management. METHODS: Symptomatic CL wearers (CLDEQ-8 ≥ 12) were refitted (V1) with daily disposable CLs (Delefilcon A). After one month (V2), participants were classified into the post-fitting non-symptomatic (CLDEQ <12) and symptomatic (CLDEQ ≥12) groups. At each visit, the participants were clinically evaluated, tears were collected, and 20 inflammatory mediators and substance P (SP) were measured using multiplex immunobead analysis and ELISA, respectively. The detection rates and concentrations were compared between visits and groups, and logistic regression models were performed. RESULTS: Forty-three subjects (32 women/11 men; mean age: 23.2 ± 4.9 years) were enrolled. The IL-1ß and IL-9 detection rates were higher at V2 (p ≤ 0.044). The detection rates of IL-1ß, IL-9, MIP-1α/CCL3, and MMP-9 at V1 (p ≤ 0.045) and IL-17A at V2 (p ≤ 0.014) were higher in the post-fitting symptomatic group. The tear IL-9 concentration was increased at V2 (p = 0.018). The tear concentrations of fractalkine/CX3CL1, IL-2, IL-6, IL-10, MCP-3/CCL7, MIP-1ß, NGF, RANTES/CCL5, and TNF-α were higher in the post-fitting symptomatic group (p ≤ 0.044). Additionally, levels of fractalkine/CX3CL1, IL-2, IL-6, IL-10, RANTES/CCL5, and TNF-α at V1 were significantly associated with the post-fitting grouping (p ≤ 0.044). CONCLUSIONS: Low tear concentrations of specific inflammatory mediators may be used as a predictive biomarker of success for refitting symptomatic CL wearers with daily disposable CLs. However, complementary treatments might be required for symptomatic CL wearers with higher levels of these inflammatory molecules.

SIRT7 promotes lung cancer progression by destabilizing the tumor suppressor ARF.

Sirtuin 7 (SIRT7) is a member of the mammalian family of nicotinamide adenine dinucleotide (NAD+)-dependent histone/protein deacetylases, known as sirtuins. It acts as a potent oncogene in numerous malignancies, but the molecular mechanisms employed by SIRT7 to sustain lung cancer progression remain largely uncharacterized. We demonstrate that SIRT7 exerts oncogenic functions in lung cancer cells by destabilizing the tumor suppressor alternative reading frame (ARF). SIRT7 directly interacts with ARF and prevents binding of ARF to nucleophosmin, thereby promoting proteasomal-dependent degradation of ARF. We show that SIRT7-mediated degradation of ARF increases expression of protumorigenic genes and stimulates proliferation of non-small-cell lung cancer (NSCLC) cells both in vitro and in vivo in a mouse xenograft model. Bioinformatics analysis of transcriptome data from human lung adenocarcinomas revealed a correlation between SIRT7 expression and increased activity of genes normally repressed by ARF. We propose that disruption of SIRT7-ARF signaling stabilizes ARF and thus attenuates cancer cell proliferation, offering a strategy to mitigate NSCLC progression.

Gelatin maleimide microgels for hematopoietic progenitor cell encapsulation.

Hematopoietic stem cells (HSCs) are the apical cells of the hematopoietic system, giving rise to cells of the blood and lymph lineages. HSCs reside primarily within bone marrow niches that contain matrix and cell-derived signals that help inform stem cell fate. Aspects of the bone marrow microenvironment have been captured in vitro by encapsulating cells within hydrogel matrices that mimic native mechanical and biochemical properties. Hydrogel microparticles, or microgels, are increasingly being used to assemble granular biomaterials for cell culture and noninvasive delivery applications. Here, we report the optimization of a gelatin maleimide hydrogel system to create monodisperse gelatin microgels via a flow-focusing microfluidic process. We report characteristic hydrogel stiffness, stability, and swelling characteristics as well as encapsulation of murine hematopoietic stem and progenitor cells, and mesenchymal stem cells within microgels. Microgels support cell viability, confirming compatibility of the microfluidic encapsulation process with these sensitive bone marrow cell populations. Overall, this work presents a microgel-based gelatin maleimide hydrogel as a foundation for future development of a multicellular artificial bone marrow culture system.

The utility of 18F-FDG-PET/CT in detecting extracranial large vessel vasculitis in rheumatic polymyalgia or giant cell arteritis. A systematic review and meta-analysis.

OBJECTIVE: Systematic review of current evidence to analyze the prevalence of extracranial large vessel vasculitis (LVV) using 18F-FDG PET/CT in patients with polymyalgia rheumatica (PMR) or giant cell arteritis (GCA). MATERIALS AND METHODS: PubMed and EMBASE were searched and the results were screened by two reviewers. Study quality was assessed using a modified version of the Newcastle-Ottawa scale. Heterogeneity between studies was assessed using the I2 statistic and the Q test. Further subgroup analyses were performed by disease type, study quality, and 18F-FDG PET/CT uptake criteria. Publication bias was assessed by funnel plot and Egger's test. RESULTS: 268 publications were identified, of which 17 met the selection criteria and were included in the meta-analysis. The overall pooled prevalence of extracranial LVV by 18F-FDG PET/CT was 54.5% [95% CI: 42.6%-66.1%]. In patients with GCA the prevalence was significantly higher than in patients with PMR (60.1% vs. 41.8%, P = 0.006). Likewise, studies with a lower risk of bias reported a higher prevalence of extracranial LVV (61.1% vs. 46.9%; P = 0.010). No publication bias was observed. CONCLUSIONS: The 18F-FDG PET/CT test may be useful in the detection of extracranial LVV, both in patients with PMR or GCA. Such involvement is more frequent in patients with GCA, and may vary depending on the quality of the studies.

New trends in nanoparticle exsolution.

Many relevant high-temperature chemical processes require the use of oxide-supported metallic nanocatalysts. The harsh conditions under which these processes operate can trigger catalyst degradation via nanoparticle sintering, carbon depositions or poisoning, among others. This primarily affects metallic nanoparticles created via deposition methods with low metal-support interaction. In this respect, nanoparticle exsolution has emerged as a promising method for fabricating oxide-supported nanocatalysts with high interaction between the metal and the oxide support. This is due to the mechanism involved in nanoparticle exsolution, which is based on the migration of metal cations in the oxide support to its surface, where they nucleate and grow as metallic nanoparticles partially embedded in the oxide. This anchorage confers high robustness against sintering or coking-related problems. For these reasons, exsolution has attracted great interest in the last few years. Multiple works have been devoted to proving the high catalytic stability of exsolved metallic nanoparticles in several applications for high-temperature energy storage and conversion. Additionally, considerable attention has been directed towards understanding the underlying mechanism of metallic nanoparticle exsolution. However, this growing field has not been limited to these types of studies and recent discoveries at the forefront of materials design have opened new research avenues. In this work, we define six new trends in nanoparticle exsolution, taking a tour through the most important advances that have been recently reported.

Correction: Beyond words: From jaguar population trends to conservation and public policy in Mexico.

[This corrects the article DOI: 10.1371/journal.pone.0255555.].

General Direct Anticancer Effects of Deer Growing Antler Extract in Several Tumour Cell Lines, and Immune System-Mediated Effects in Xenograft Glioblastoma.

Deer antlers are the fastest growing tissue. Because they are based on proto-oncogenes, to avoid the risk of cancer, antlers evolved strong anticancer mechanisms, and thus their extract (DVA) is effective also against the few human tumours studied so far. We assessed whether DVA is a general anticancer compound by testing the direct effects in cells of different tumours: glioblastoma (GBM; lines U87MG and U251), colorectal (CRC; lines DLD-1, HT-29, SW480, and SW620), breast cancer (BRCA; lines MCF7, SKBR3, and PA00), and leukaemia (THP-1). DVA reduced the viability of tumours but not healthy cells (NHC; lines 293T and HaCaT). Mobility decreased at least for the longest test (72 h). Intraperitoneal/oral 200 mg DVA/kg administration in GBM xenograft mice for 28 d reduced tumour weight by 66.3% and 61.4% respectively, and it also reduced spleen weight (43.8%). In addition, tumours treated with DVA showed symptoms of liquefactive necrosis. Serum cytokines showed DVA up-regulated factors related to tumour fighting and down-regulated those related to inducing immune tolerance to the tumour. DVA shows general anticancer effects in the lines tested and, in GBM mice, also strong indirect effects apparently mediated by the immune system. DVA may contain a future anticancer medicine without secondary effects.