Quantification of early biofilm growth in microtiter plates through a novel image analysis software.

Given the significant impact of biofilms on human health and material corrosion, research in this field urgently needs more accessible techniques to facilitate the testing of new control agents and general understanding of biofilm biology. Microtiter plates offer a convenient format for standardized evaluations, including high-throughput assays of alternative treatments and molecular modulators. This study introduces a novel Biofilm Analysis Software (BAS) for quantifying biofilms from microtiter plate images. We focused on early biofilm growth stages and compared BAS quantification to common techniques: direct turbidity measurement, intrinsic fluorescence detection linked to pyoverdine production, and standard crystal violet staining which enables image analysis and optical density measurement. We also assessed their sensitivity for detecting subtle growth effects caused by cyclic AMP and gentamicin. Our results show that BAS image analysis is at least as sensitive as the standard method of spectrophotometrically quantifying the crystal violet retained by biofilms. Furthermore, we demonstrated that bacteria adhered after short incubations (from 10 min to 4 h), isolated from planktonic populations by a simple rinse, can be monitored until their growth is detectable by intrinsic fluorescence, BAS analysis, or resolubilized crystal violet. These procedures are widely accessible for many laboratories, including those with limited resources, as they do not require a spectrophotometer or other specialized equipment.

Highly Sensitive Whole-Cell Mercury Biosensors for Environmental Monitoring.

Whole-cell biosensors could serve as eco-friendly and cost-effective alternatives for detecting potentially toxic bioavailable heavy metals in aquatic environments. However, they often fail to meet practical requirements due to an insufficient limit of detection (LOD) and high background noise. In this study, we designed a synthetic genetic circuit specifically tailored for detecting ionic mercury, which we applied to environmental samples collected from artisanal gold mining sites in Peru. We developed two distinct versions of the biosensor, each utilizing a different reporter protein: a fluorescent biosensor (Mer-RFP) and a colorimetric biosensor (Mer-Blue). Mer-RFP enabled real-time monitoring of the culture's response to mercury samples using a plate reader, whereas Mer-Blue was analysed for colour accumulation at the endpoint using a specially designed, low-cost camera setup for harvested cell pellets. Both biosensors exhibited negligible baseline expression of their respective reporter proteins and responded specifically to HgBr2 in pure water. Mer-RFP demonstrated a linear detection range from 1 nM to 1 µM, whereas Mer-Blue showed a linear range from 2 nM to 125 nM. Our biosensors successfully detected a high concentration of ionic mercury in the reaction bucket where artisanal miners produce a mercury-gold amalgam. However, they did not detect ionic mercury in the water from active mining ponds, indicating a concentration lower than 3.2 nM Hg2+-a result consistent with chemical analysis quantitation. Furthermore, we discuss the potential of Mer-Blue as a practical and affordable monitoring tool, highlighting its stability, reliance on simple visual colorimetry, and the possibility of sensitivity expansion to organic mercury.

Estilos de vida y factores asociados a la automedicación en estudiantes de medicina humana / Lifestyles and factors associated with self-medication in human medicine students / Estilos de vida e fatores associados à automedicação em estudantes de medicina humana

Los estilos de vida adoptados por las personas pueden influir en la automedicación, al afectar sus decisiones sobre el uso de fármacos sin supervisión médica. Objetivo: Indagar en los factores asociados y estilos de vida que influyen en la automedicación en estudiantes de Medicina Humana de la Universidad Nacional de Cajamarca. Materiales y Métodos: Estudio de tipo cuantitativo, analítico correlacional y transversal. Se aplicó el cuestionario "Automedicación", desarrollado por Espilco y Félix en 2020, a 100 estudiantes, el cual consta de 16 ítems distribuidos en las categorías "Factores" (9 ítems) y "Automedicación" (7 ítems), y ha sido validado con un Alfa de Cbronbach de 0.750. Además, se utilizó un Alfa de Bronbach de 0.943 para evaluar los "Estilos de Vida", que abarcan las siguientes dimensiones: actividad física, salud con responsabilidad, nutrición saludable, gestión de tensiones y relaciones interpersonales. Resultados: Se identificó como factores asociados a la automedicación a: demográficos-culturales, donde el estado civil es el más significativo con una (p=0.0205); sociales, siendo significativo el lugar de accesibilidad del medicamento con una (p=0.0001) y la información del medicamento con una (p=0.0014) y finalmente económicos donde tiene más significancia el ingreso mensual del estudiante con una (p=0.0001). Además, se halló una prevalencia de automedicación del 82%, asimismo el tipo de estilo de vida no saludable (86%) y no hubo relación significativa con la automedicación (p=0.8119). Conclusión: Los factores asociados a la automedicación abarcan aspectos demográficos-culturales, sociales y económicos. Se ha observado una alta prevalencia de automedicación, alcanzando un 82%. No se halló una relación significativa entre el nivel de estilo de vida y la práctica de automedicación en este contexto particular.

The lifestyles adopted by people can influence self-medication, by affecting their decisions about the use of drugs without medical upervisión. Objective: To investigate the associated factors and lifestyles that influence self-medication in Human Medicine students of the National University of Cajamarca. Materials and Methods: Quantitative, correlational and cross-sectional analytical study. The questionnaire "Self-medication", developed by Espilco and Félix in 2020, was applied to 100 students, which consists of 16 items distributed in the categories "Factors" (9 items) and "Self-medication" (7 items), and has been validated with a Cbronbach's Alpha of 0.750. In addition, a Bronbach's Alpha of 0.943 was used to evaluate "Lifestyles", which cover the following dimensions: physical activity, health with responsibility, healthy nutrition, stress management and interpersonal relationships. Results: The following were identified as factors associated with self-medication: demographic-cultural, where marital status is the most significant with one (p=0.0205); social, being significant the place of accessibility of the medication with one (p=0.0001) and medication information with one (p=0.0014) and finally economic where the student's monthly income with one has more significance (p=0.0001). In addition, a prevalence of self-medication of 82% was found, as well as the type of unhealthy lifestyle (86%) and there was no significant relationship with self-medication (p=0.8119). Conclusion: The factors associated with self-medication cover demographic-cultural, social and economic aspects. A high prevalence of self-medication has been observed, reaching 82%. No significant relationship was found between lifestyle level and self-medication practice in this particular context.

Os estilos de vida adotados pelas pessoas podem influenciar a automedicação, afetando suas decisões sobre o uso de medicamentos sem supervisão médica. Objetivo: investigar os fatores associados e estilos de vida que influenciam a automedicação em estudantes de Medicina Humana da Universidade Nacional de Cajamarca. Materiais e Métodos: estudo de tipo quantitativo, analítico correlacional e transversal. O questionário "automedicação", desenvolvido por Espilco e Felix em 2020, foi aplicado a 100 estudantes, composto por 16 itens distribuídos nas categorias "fatores" (9 itens) e "automedicação" (7 itens), e foi validado com um Alfa de Cbronbach de 0,750. Além disso, um Alfa de Bronbach de 0, 943 foi usado para avaliar "Estilos de vida", abrangendo as seguintes dimensões: atividade física, saúde com responsabilidade, nutrição saudável, gerenciamento de tensões e relações interpessoais. Resultados: identificou-se como fatores associados à automedicação a: demográficos-culturais, onde o estado civil é o mais significativo com uma (p=0,0205); sociais, sendo significativo o local de acessibilidade do medicamento com uma (p=0,0001) e a informação do medicamento com uma (p=0,0014) e finalmente econômicos onde tem mais significância a renda mensal do estudante com uma (p=0,0001). Além disso, foi encontrada uma prevalência de automedicação de 82%, assim como o tipo de estilo de vida não saudável (86%) e não houve relação significativa com a automedicação (p=0,8119). Conclusão: os fatores associados à automedicação abrangem aspectos demográficos-culturais, sociais e econômicos. Foi observada uma alta prevalência de automedicação, atingindo 82%. Não foi encontrada relação significativa entre o nível de estilo de vida e a prática de automedicação neste contexto particular.

Physioprophylaxis post-stress test in soccer players: effects blood lactate concentrations

Abstract Objective: To determine the effects of physioprophylaxis (PP) on blood lactate (BL) concentrations after maximal incremental stress test, considering that this is the application of techniques in sports physiotherapy to reduce signs of muscle fatigue that can trigger injuries due to overload. Materials and Methods: Quantitative study, experimental type, longitudinal section in 12 university players. The group is divided into one control group (CG) with recovery at rest without PP and another experimental group (EG) to which PP is applied at the end of the test. Blood lactate is recorded with Accutrend Plus at the beginning of the test, (1) five minutes after finishing the test (2) and after the PP (3) at two different moments for intra-subject analysis. Results: The following data were obtained regarding blood lactate clearance, Moment 1: Without Plan (WoP) 4.86±1.4 and With Plan (WP) 8.85±1.25 (p<0.05), moment 2: (WoP) 5.6±1.76 and (WP) 7.8±1.3 (p<0.05) in mmol/L, and intra-subject: (WoP): 5.25±1.58; (WP): 8.35±1.33 (p<0.05). Conclusions: The clearance of lactate in the blood at 30 minutes post stress test in the EG is bigger than the CG, because they recovered with the physioprophylactic plan.

Resumen Objetivo: Determinar los efectos de la fisioprofilaxis (PP) sobre las concentraciones de lactato en sangre (BL) tras la prueba de esfuerzo incremental máximo, considerando que se trata de la aplicación de técnicas en fisioterapia deportiva para reducir los signos de fatiga muscular que pueden desencadenar lesiones por sobrecarga. Materiales y métodos: Estudio cuantitativo, tipo experimental, sección longitudinal en 12 jugadores universitarios. El grupo se divide en un grupo control (GC) con recuperación en reposo sin PP y otro grupo experimental (GE) al que se aplica PP al final de la prueba. El lactato sanguíneo se registra con Accutrend Plus al inicio de la prueba, (1) cinco minutos después de finalizar la prueba (2) y después de la PP (3) en dos momentos diferentes para el análisis intra-sujeto. Resultados: Se obtuvieron los siguientes datos con respecto al aclaramiento de lactato en sangre, Momento 1: Sin Plan (WoP) 4.86 ± 1.4 y Con Plan (WP) 8.85 ± 1.25 (p <0.05), Momento 2: (WoP) 5.6 ± 1.76 y (WP) ) 7,8 ± 1,3 (p <0,05) en mmol / L, e intra-sujeto: (WoP): 5,25 ± 1,58; (WP): 8,35 ± 1,33 (p <0,05). Conclusiones: El aclaramiento de lactato en sangre a los 30 minutos post prueba de esfuerzo en el GE es mayor que en el GC, debido a que se recuperaron con el plan fisioprofiláctico.

SMARCE1 deficiency generates a targetable mSWI/SNF dependency in clear cell meningioma.

Mammalian SWI/SNF (mSWI/SNF) ATP-dependent chromatin remodeling complexes establish and maintain chromatin accessibility and gene expression, and are frequently perturbed in cancer. Clear cell meningioma (CCM), an aggressive tumor of the central nervous system, is uniformly driven by loss of SMARCE1, an integral subunit of the mSWI/SNF core. Here, we identify a structural role for SMARCE1 in selectively stabilizing the canonical BAF (cBAF) complex core-ATPase module interaction. In CCM, cBAF complexes fail to stabilize on chromatin, reducing enhancer accessibility, and residual core module components increase the formation of BRD9-containing non-canonical BAF (ncBAF) complexes. Combined attenuation of cBAF function and increased ncBAF complex activity generates the CCM-specific gene expression signature, which is distinct from that of NF2-mutated meningiomas. Importantly, SMARCE1-deficient cells exhibit heightened sensitivity to small-molecule inhibition of ncBAF complexes. These data inform the function of a previously elusive SWI/SNF subunit and suggest potential therapeutic approaches for intractable SMARCE1-deficient CCM tumors.

The FUS::DDIT3 fusion oncoprotein inhibits BAF complex targeting and activity in myxoid liposarcoma.

Mammalian SWI/SNF (mSWI/SNF or BAF) ATP-dependent chromatin remodeling complexes play critical roles in governing genomic architecture and gene expression and are frequently perturbed in human cancers. Transcription factors (TFs), including fusion oncoproteins, can bind to BAF complex surfaces to direct chromatin targeting and accessibility, often activating oncogenic gene loci. Here, we demonstrate that the FUS::DDIT3 fusion oncoprotein hallmark to myxoid liposarcoma (MLPS) inhibits BAF complex-mediated remodeling of adipogenic enhancer sites via sequestration of the adipogenic TF, CEBPB, from the genome. In mesenchymal stem cells, small-molecule inhibition of BAF complex ATPase activity attenuates adipogenesis via failure of BAF-mediated DNA accessibility and gene activation at CEBPB target sites. BAF chromatin occupancy and gene expression profiles of FUS::DDIT3-expressing cell lines and primary tumors exhibit similarity to SMARCB1-deficient tumor types. These data present a mechanism by which a fusion oncoprotein generates a BAF complex loss-of-function phenotype, independent of deleterious subunit mutations.

Biosupramolecular complexes of amphiphilic photosensitizers with human serum albumin and cucurbit[7]uril as carriers for photodynamic therapy.

In the present work, we evaluated the supramolecular interactions between three photosensitizers, namely toluidine blue O (TBO, positively charged) and two fatty acid conjugates of 6 and 14 carbon atoms chain lengths (TBOC6 and TBOC14), with human serum albumin (HSA) and the macrocycle cucurbit[7]uril (CB[7]), alone or in combination within a biosupramolecular system as potential carriers of photosensitizers for Photodynamic therapy (PDT). Binding studies were carried out using photophysical and calorimetric techniques and accompanied with molecular docking simulations. Amphiphilic photosensitizers, particularly TBOC14, showed stronger binding to HSA and (CB[7]). Comparing the different delivery systems, (CB[7]) had a marginal effect on cell uptake and phototoxicity in HeLa cells, while HSA showed enhanced cell uptake with phototoxicities that depended on the photosensitizer. Despite low cell uptake, the combination of both (CB[7]) and HSA was the most phototoxic, which illustrates the potential of combining these systems for PDT applications.

A review of shared decision-making: A call to arms for health care professionals.

OBJECTIVE: To illustrate the use of shared decision-making (SDM) and SDM tools and aids as the essential components in the care of asthma. DATA SOURCES: We reviewed individual randomized controlled studies conducted between 1998 and 2020 to compare SDM interventions and the use of SDM tools and aids for the care of asthma. All studies were published or translated in English. STUDY SELECTIONS: We excluded studies of interventions that involved multiple components other than the SDM intervention unless the control group also received these interventions. We evaluated the existing literature on both SDM tools and aids and the process of SDM to summarize in this review. RESULTS: Shared decision-making tools and aids most commonly clarify the diagnostics and options for a treatment. The 6 elements of SDM were clearly supported. We found no considerable association between the presence of these elements of SDM and asthma outcomes. CONCLUSION: We found that SDM for asthma and SDM tools and aids were often made to transfer information about asthma treatment options and their harms and benefits. The correlation between their support of SDM key elements and their impact on asthma outcomes is often difficult to ascertain but when present, there was positive correlation to improving risk communication, adherence, patient satisfaction, and possibly decreasing liability.

YejM Modulates Activity of the YciM/FtsH Protease Complex To Prevent Lethal Accumulation of Lipopolysaccharide.

Lipopolysaccharide (LPS) is an essential glycolipid present in the outer membrane (OM) of many Gram-negative bacteria. Balanced biosynthesis of LPS is critical for cell viability; too little LPS weakens the OM, while too much LPS is lethal. In Escherichia coli, this balance is maintained by the YciM/FtsH protease complex, which adjusts LPS levels by degrading the LPS biosynthesis enzyme LpxC. Here, we provide evidence that activity of the YciM/FtsH protease complex is inhibited by the essential protein YejM. Using strains in which LpxC activity is reduced, we show that yciM is epistatic to yejM, demonstrating that YejM acts upstream of YciM to prevent toxic overproduction of LPS. Previous studies have shown that this toxicity can be suppressed by deleting lpp, which codes for a highly abundant OM lipoprotein. It was assumed that deletion of lpp restores lipid balance by increasing the number of acyl chains available for glycerophospholipid biosynthesis. We show that this is not the case. Rather, our data suggest that preventing attachment of lpp to the peptidoglycan sacculus allows excess LPS to be shed in vesicles. We propose that this loss of OM material allows continued transport of LPS to the OM, thus preventing lethal accumulation of LPS within the inner membrane. Overall, our data justify the commitment of three essential inner membrane proteins to avoid toxic over- or underproduction of LPS.IMPORTANCE Gram-negative bacteria are encapsulated by an outer membrane (OM) that is impermeable to large and hydrophobic molecules. As such, these bacteria are intrinsically resistant to several clinically relevant antibiotics. To better understand how the OM is established or maintained, we sought to clarify the function of the essential protein YejM in Escherichia coli Here, we show that YejM inhibits activity of the YciM/FtsH protease complex, which regulates synthesis of the essential OM glycolipid lipopolysaccharide (LPS). Our data suggest that disrupting proper communication between LPS synthesis and transport to the OM leads to accumulation of LPS within the inner membrane (IM). The lethality associated with this event can be suppressed by increasing OM vesiculation. Our research has identified a completely novel signaling pathway that we propose coordinates LPS synthesis and transport.

Intestinal microbiota regulates tryptophan metabolism following oral infection with Toxoplasma gondii.

INTRODUCTION: The intestinal microbiota plays an important role in modulating host immune responses. Oral Toxoplasma gondii infection can promote intestinal inflammation in certain mice strains. The IDO-AhR axis may control tryptophan (Trp) metabolism constituting an important immune regulatory mechanism in inflammatory settings. AIMS: In the present study, we investigated the role of the intestinal microbiota on Trp metabolism during oral infection with T gondii. METHODS AND RESULTS: Mice were treated with antibiotics for four weeks and then infected with T gondii by gavage. Histopathology and immune responses were evaluated 8 days after infection. We found that depletion of intestinal microbiota by antibiotics contributed to resistance against T gondii infection and led to reduced expression of AhR on dendritic and Treg cells. Mice depleted of Gram-negative bacteria presented higher levels of systemic Trp, downregulation of AhR expression and increased resistance to infection whereas depletion of Gram-positive bacteria did not affect susceptibility or expression of AhR on immune cells. CONCLUSION: Our findings indicate that the intestinal microbiota can control Trp availability and provide a link between the AhR pathway and host-microbiota interaction in acute infection with T gondii.

Synthetic Approaches to Phosphasugars (2-oxo-1,2-oxaphosphacyclanes) Using the Anomeric Alkoxyl Radical ß-Fragmentation Reaction as the Key Step.

The anomeric alkoxyl radical ß-fragmentation (ARF) of carbohydrates possessing an electron-withdrawing group (EWG) at C2, promoted by PhI(OAc)2/I2, gives rise to an acyclic iodide through which a pentavalent atom of phosphorus can be introduced via the Arbuzov reaction. After selective hydrolysis and subsequent cyclization, the phosphonate or phosphinate intermediates can be converted into 2-deoxy-1-phosphahexopyranose and 2-deoxy-1-phosphapentopyranose sugars. The ARF of carbohydrates with an electron-donor group (EDG) at C2 proceeds by a radical-polar crossover mechanism, and the cyclization occurs by nucleophilic attack of a conveniently positioned phosphonate or phosphinate group to the transient oxocarbenium ion. This alternative methodology leads to 5-phosphasugars with a 4-deoxy-5-phosphapentopyranose framework. The structure and conformation of the 2-oxo-1,2-oxaphosphinane and 2-oxo-1,2-oxaphospholane ring systems in different carbohydrate models have been studied by NMR and X-ray crystallography.

Photochemical C-H Amination of Ethers and Geminal Difunctionalization Reactions in One Pot.

A mild, atom-economic, and metal-free α-C-H amination of ethers using relatively stable nonafluorobutanesulfonyl (nonaflyl, Nf) azide as the aminating reagent to give N-sulfonyl hemiaminals is reported. This enables unprecedented C(sp3 ) difunctionalization reactions, leading to diverse functionalized amino group containing compounds starting from simple ethers in one pot.

Pericytes Act as Key Players in Spinal Cord Injury.

Spinal cord injury results in locomotor impairment attributable to the formation of an inhibitory fibrous scar, which prevents axonal regeneration after trauma. The scarcity of knowledge about the molecular and cellular mechanisms involved in scar formation after spinal cord lesion impede the design of effective therapies. Recent studies, by using state-of-the-art technologies, including genetic tracking and blockage of pericytes in combination with optogenetics, reveal that pericyte blockage facilitates axonal regeneration and neuronal integration into the local neural circuitry. Strikingly, a pericyte subset is essential during scarring after spinal cord injury, and its arrest results in motor performance improvement. The arising knowledge from current research will contribute to novel approaches to develop therapies for spinal cord injury. We review novel advances in our understanding of pericyte biology in the spinal cord.

Individualised or Standardised Outcome Measures: A Co-habitation?

Mental health outcome measurement is conflicted between two different schools of thought which underlie the division between standardised (nomothetic) and individualised or patient-generated (idiographic) measures. The underpinning philosophies of both approaches have very different starting points in terms of how we understand the world. And yet the strengths of both may contribute something useful for patients and mental health services. We suggest a convergence of approaches with new thinking on options for co-habitation.

[Quality of life in chronic urticaria and its relationship with economic impact and disease control in patients attended to at the University Hospital of Monterrey, Mexico]. / Calidad de vida en urticaria crónica y su relación con el impacto económico y control de la enfermedad en pacientes atendidos en el Hospital Universitario de Monterrey, México.

BACKGROUND: Chronic urticaria (CU) manifests itself with hives and sometimes angioedema. Physical and social discomfort worsens patient quality of life. CU has an important impact on patients' economy. OBJECTIVE: To evaluate the relationship of quality of life (QoL) with economic burden and chronic urticaria control of in patients treated at our center. METHODS: Cross-sectional, descriptive, observational study. We included CU-diagnosed adult patients. The CU-Q2oL and UCT questionnaires in Spanish and the economic burden and comorbidities questionnaire developed by our center were applied. A sample size of 36 patients was calculated. RESULTS: 36 patients were included, out of which 58.3% were females. Mean age was 39.9 ± 15.6 years. Regarding QoL, 66.7% of patients reported being "A little" affected, 25% "Somewhat" and 8.3% "A lot", and its relationship with monthly income yielded a p-value of 0.017. 38.9% of patients reported having a monthly income of less than $ 5000 pesos. When disease control was compared with the CU-Q2oL, a significant difference was obtained for questions concerning itching. CONCLUSION: There was association between the quality of life of patients with chronic urticaria and monthly income, the lower the income, the more will the quality of life be affected. Furthermore, greater CU control was observed to reduce the negative effects on quality of life caused by itching.

Antecedentes: La urticaria crónica se manifiesta con erupciones y ocasionalmente con angioedema. La molestia física y social empeora la calidad de vida de los pacientes, quienes, además, enfrentan importantes gastos. Objetivo: Evaluar la relación de la calidad de vida con la carga económica y el control de la urticaria crónica. Métodos: Estudio transversal, descriptivo y observacional. Se incluyeron adultos con diagnóstico de urticaria crónica. Se aplicaron los cuestionarios CU-Q2oL y UCT en español y un cuestionario sobre carga económica y enfermedades coexistentes. Se calculó un tamaño de muestra de 36 pacientes. Resultados: Se incluyeron 36 pacientes, 58.3 % fue del sexo femenino. La edad fue de 39.9 años ± 15.6. Respecto a la calidad de vida, 66.7 % reportó poca afectación, 25 % bastante y 8.3 % mucha; la relación con el ingreso económico mensual obtuvo p = 0.017; 38.9 % refirió ingresos mensuales menores a $5000. Al comparar el control de la enfermedad con el CU-Q2oL se obtuvo diferencia significativa para las preguntas referentes a prurito. Conclusiones: Existió asociación entre calidad de vida de los pacientes con urticaria crónica e ingreso familiar mensual: a menor ingreso, más afectación de la calidad de vida. A mayor control de la enfermedad, menor afectación.

Role of Schwann cells in cutaneous wound healing.

Dermal wound healing is the process of repairing and remodeling skin following injury. Delayed or aberrant cutaneous healing poses a challenge for the health care system. The lack of detailed understanding of cellular and molecular mechanisms involved in this process hampers the development of effective targeted treatments. In a recent study, Parfejevs et al.-using state-of-the-art technologies, including in vivo sophisticated Cre/loxP techniques in combination with a mouse model of excisional cutaneous wounding-reveal that Schwann cells induce adult dermal wound healing. Strikingly, genetic ablation of Schwann cells delays wound contraction and closure, decreases myofibroblast formation, and impairs skin re-epithelization after injury. From a drug development perspective, Schwann cells are a new cellular candidate to be activated to accelerate skin healing. Here, we summarize and evaluate recent advances in the understanding of Schwann cells roles in the skin microenvironment.

Targeting glioblastoma-derived pericytes improves chemotherapeutic outcome.

Glioblastoma is the most common malignant brain cancer in adults, with poor prognosis. The blood-brain barrier limits the arrival of several promising anti-glioblastoma drugs, and restricts the design of efficient therapies. Recently, by using state-of-the-art technologies, including thymidine kinase targeting system in combination with glioblastoma xenograft mouse models, it was revealed that targeting glioblastoma-derived pericytes improves chemotherapy efficiency. Strikingly, ibrutinib treatment enhances chemotherapeutic effectiveness, by targeting pericytes, improving blood-brain barrier permeability, and prolonging survival. This study identifies glioblastoma-derived pericyte as a novel target in the brain tumor microenvironment during carcinogenesis. Here, we summarize and evaluate recent advances in the understanding of pericyte's role in the glioblastoma microenvironment.

Pericytes in the Premetastatic Niche.

The premetastatic niche formed by primary tumor-derived molecules contributes to fixation of cancer metastasis. The design of efficient therapies is limited by the current lack of knowledge about the details of cellular and molecular mechanisms involved in the premetastatic niche formation. Recently, the role of pericytes in the premetastatic niche formation and lung metastatic tropism was explored by using state-of-the-art techniques, including in vivo lineage-tracing and mice with pericyte-specific KLF4 deletion. Strikingly, genetic inactivation of KLF4 in pericytes inhibits pulmonary pericyte expansion and decreases metastasis in the lung. Here, we summarize and evaluate recent advances in the understanding of pericyte contribution to premetastatic niche formation. Cancer Res; 78(11); 2779-86. ©2018 AACR.