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Over the past decade, boldine, a naturally occurring alkaloid found in several plant species including the Chilean Boldo tree, has garnered attention for its efficacy in rodent models of human disease. Some of the properties that have been attributed to boldine include antioxidant activities, neuroprotective and analgesic actions, hepatoprotective effects, anti-inflammatory actions, cardioprotective effects and anticancer potential. Compelling data now indicates that boldine blocks connexin (Cx) hemichannels (HCs) and that many if not all of its effects in rodent models of injury and disease are due to CxHC blockade. Here we provide an overview of boldine’s pharmacological properties, including its efficacy in rodent models of common human injuries and diseases, and of its absorption, distribution, pharmacokinetics, and metabolism.

ABSTRACT The skulls of 54 specimens of the South American tapir, Tapirus terrestris collected in the department of Loreto, Peru were measured, analyzed and compared to investigate skull development of this species. Univariate, multivariate and allometric analyses were performed using 32 skull variables through traditional morphometrics. Significant skull shape variation was detected among ontogenetic classes. Young individuals (class I, n = 22) showed higher variation than subadults and adults (class II, n = 23 and class III, n = 9), without evidence of sexual dimorphism (males = 35, females = 19). Principal component analyses and discriminant function analysis showed almost complete separation of the age classes. Allometric analysis indicated a tendency of unproportioned cranial growth. All our samples come from the same population living under the same ecological condition, which eliminates the effect of confounding variables related to habitat on the pattern of ontogenetic variation of this anatomical structure.

Membrane channels such as those formed by connexins (Cx) and P2X7 receptors (P2X7R) are permeable to calcium ions and other small molecules such as adenosine triphosphate (ATP) and glutamate. Release of ATP and glutamate through these channels is a key mechanism driving tissue response to traumas such as spinal cord injury (SCI). Boldine, an alkaloid isolated from the Chilean boldo tree, blocks both Cx and Panx1 hemichannels (HCs). To test if boldine could improve function after SCI, boldine or vehicle was administered to treat mice with a moderate severity contusion-induced SCI. Boldine led to greater spared white matter and increased locomotor function as determined by the Basso Mouse Scale and horizontal ladder rung walk tests. Boldine treatment reduced immunostaining for markers of activated microglia (Iba1) and astrocytic (GFAP) markers while increasing that for axon growth and neuroplasticity (GAP-43). Cell culture studies demonstrated that boldine blocked glial HC, specifically Cx26 and Cx30, in cultured astrocytes and blocked calcium entry through activated P2X7R. RT-qPCR studies showed that boldine treatment reduced expression of the chemokine Ccl2, cytokine IL-6 and microglial gene CD68, while increasing expression of the neurotransmission genes Snap25 and Grin2b, and Gap-43. Bulk RNA sequencing revealed that boldine modulated a large number of genes involved in neurotransmission in spinal cord tissue just caudal from the lesion epicenter at 14 days after SCI. Numbers of genes regulated by boldine was much lower at 28 days after injury. These results indicate that boldine treatment ameliorates injury and spares tissue to increase locomotor function.

Este artículo presenta un análisis de la caracterización físico-mecánica de un concreto geopolimérico fibrorreforzado, cuya matriz HCV está conformada por 90% ceniza volante (CV) y 10% cemento portland ordinario (OPC), utilizando como activador alcalino una solución compuesta por silicato e hidróxido de sodio (NaOH, Na2SiO3) y agua. El refuerzo utilizado fueron fibras de acero SikaFiber Xorex incorporadas a la matriz en proporciones de 50 y 75 kg/m3. La mezcla HCV-50 reportó una resistencia a la compresión de 26,77 MPa a los 28 días de curado, clasificando como concreto estructural según la NSR-10; a la misma edad de curado se obtuvo resistencia a la tracción indirecta de 3,49 MPa, módulo de elasticidad de 29,32 GPa, resistencia a la flexión de 5,15 MPa y tenacidad hasta la deflexión de agrietamiento (δf) de 1.971,9 N.mm. Esta mezcla considerada la óptima, fue empleada en la fabricación de losas de concreto, las cuales presentaron una deflexión de ruptura δf de 4,45 mm, deflexión última de 16,15 mm, carga máxima soportada 15,6 kN, tenacidad de 49.464,8 N.mm hasta δf y 14.5847,3 N.mm hasta 3 veces δf. El material geopolimerico fibrorreforzado se propone además para ser utilizado en la producción de concreto proyectado (Shotcrete), y en la construcción de losetas aligeradas.

Para Brycon moorei, los datos sobre morfometría, en estados iniciales del desarrollo, son inexistentes. El objetivo de este estudio fue establecer las principales relaciones alométricas en los estadios tempranos de B. moorei. Se analizaron 12 variables merísticas en un tiempo experimental que transcurrió desde la eclosión hasta los 15 días post-eclosión. En el estadio larval vitelino (LV) se registró, en promedio: longitud total (LT) de 4,74 ± 0,05 mm; longitud estándar (LE) de 4,21 ± 0,07 mm; longitud del hocico (SnL) 0,3 ± 0,01; diámetro del ojo (ED) 0,37 ± 0,007 mm; longitud de la cabeza (HL) 1,02 ± 0,04 mm; altura de la cabeza (HH) 0,88 ± 0,069 mm; altura del cuerpo (BH) 1,26 ± 0,01 mm; longitud hocico-aleta pectoral (SnPF) 1,35 ± 0,034; ausencia de aletas pélvicas, anales y dorsal y el peso fue de 1,8 ± 0,2 mg. En la etapa juvenil (J), las medidas fueron: LT de 25,66 ± 0,64 mm; LE de 21,49 ± 0,63 mm; SnL de 1,69 ± 0,059 mm; ED de 1,71 ± 0,048 mm; HL de 6,33 ± 0,21 mm; HH de 4,89 ± 0,47 mm; BH de 6,13 ± 0,17 mm; SnPF de 6,48 ± 0,19 mm; SnPeF de 10,83 ± 0,28 mm; SnDF de 11,16 ± 0,33 mm; Sn-AF de 3,68 ± 0,34 mm; el peso fue de 221,6 ± 15,84 mg. Para LV, el número de miómeros pre-anales fue 28,65 ± 4,7; los post-anales fueron 23,85 ± 4,27, con un total de 52,47 ± 8,34; para J los miómeros no fueron visibles. Esta información es fundamental para fines ecológicos y productivos en B. moorei.

Individuals with diabetes mellitus present a skeletal muscle myopathy characterized by atrophy. However, the mechanism underlying this muscular alteration remains elusive, which makes it difficult to design a rational treatment that could avoid the negative consequences in muscles due to diabetes. In the present work, the atrophy of skeletal myofibers from streptozotocin-induced diabetic rats was prevented with boldine, suggesting that non-selective channels inhibited by this alkaloid are involved in this process, as has previously shown for other muscular pathologies. Accordingly, we found a relevant increase in sarcolemma permeability of skeletal myofibers of diabetic animals in vivo and in vitro due to de novo expression of functional connexin hemichannels (Cx HCs) containing connexins (Cxs) 39, 43, and 45. These cells also expressed P2X7 receptors, and their inhibition in vitro drastically reduced sarcolemma permeability, suggesting their participation in the activation of Cx HCs. Notably, sarcolemma permeability of skeletal myofibers was prevented by boldine treatment that blocks Cx43 and Cx45 HCs, and now we demonstrated that it also blocks P2X7 receptors. In addition, the skeletal muscle alterations described above were not observed in diabetic mice with myofibers deficient in Cx43/Cx45 expression. Moreover, murine myofibers cultured for 24 h in high glucose presented a drastic increase in sarcolemma permeability and levels of NLRP3, a molecular member of the inflammasome, a response that was also prevented by boldine, suggesting that, in addition to the systemic inflammatory response found in diabetes, high glucose can promote the expression of functional Cx HCs and activation of the inflammasome in skeletal myofibers. Therefore, Cx43 and Cx45 HCs play a critical role in myofiber degeneration, and boldine could be considered a potential therapeutic agent to treat muscular complications due to diabetes.

The masticatory system is a complex and highly organized group of structures, including craniofacial bones (maxillae and mandible), muscles, teeth, joints, and neurovascular elements. While the musculoskeletal structures of the head and neck are known to have a different embryonic origin, morphology, biomechanical demands, and biochemical characteristics than the trunk and limbs, their particular molecular basis and cell biology have been much less explored. In the last decade, the concept of muscle-bone crosstalk has emerged, comprising both the loads generated during muscle contraction and a biochemical component through soluble molecules. Bone cells embedded in the mineralized tissue respond to the biomechanical input by releasing molecular factors that impact the homeostasis of the attaching skeletal muscle. In the same way, muscle-derived factors act as soluble signals that modulate the remodeling process of the underlying bones. This concept of muscle-bone crosstalk at a molecular level is particularly interesting in the mandible, due to its tight anatomical relationship with one of the biggest and strongest masticatory muscles, the masseter. However, despite the close physical and physiological interaction of both tissues for proper functioning, this topic has been poorly addressed. Here we present one of the most detailed reviews of the literature to date regarding the biomechanical and biochemical interaction between muscles and bones of the masticatory system, both during development and in physiological or pathological remodeling processes. Evidence related to how masticatory function shapes the craniofacial bones is discussed, and a proposal presented that the masticatory muscles and craniofacial bones serve as secretory tissues. We furthermore discuss our current findings of myokines-release from masseter muscle in physiological conditions, during functional adaptation or pathology, and their putative role as bone-modulators in the craniofacial system. Finally, we address the physiological implications of the crosstalk between muscles and bones in the masticatory system, analyzing pathologies or clinical procedures in which the alteration of one of them affects the homeostasis of the other. Unveiling the mechanisms of muscle-bone crosstalk in the masticatory system opens broad possibilities for understanding and treating temporomandibular disorders, which severely impair the quality of life, with a high cost for diagnosis and management.

Muscular dystrophies (MDs) are a heterogeneous group of congenital neuromuscular disorders whose clinical signs include myalgia, skeletal muscle weakness, hypotonia, and atrophy that leads to progressive muscle disability and loss of ambulation. MDs can also affect cardiac and respiratory muscles, impairing life-expectancy. MDs in clude Duchenne muscular dystrophy, Emery-Dreifuss muscular dystrophy, facioscapulohumeral muscular dystrophy and limb-girdle muscular dystrophy. These and other MDs are caused by mutations in genes that encode proteins responsible for the structure and function of skeletal muscles, such as components of the dystrophin-glycoprotein-complex that connect the sarcomeric-actin with the extracellular matrix, allowing contractile force transmission and providing stability during muscle contraction. Consequently, in dystrophic conditions in which such proteins are affected, muscle integrity is disrupted, leading to local inflammatory responses, oxidative stress, Ca2+-dyshomeostasis and muscle degeneration. In this scenario, dysregulation of connexin hemichannels seem to be an early disruptor of the homeostasis that further plays a relevant role in these processes. The interaction between all these elements constitutes a positive feedback loop that contributes to the worsening of the diseases. Thus, we discuss here the interplay between inflammation, oxidative stress and connexin hemichannels in the progression of MDs and their potential as therapeutic targets.

Recientemente hemos leído con interés el trabajo de María Triolo y cols, en el cual se dice hacer una comparación de la sensibilidad de dos técnicas, ampliamente empleadas en la detección de enteroparásitos en lechugas. Conociendo la importancia de su diagnóstico en frutas y vegetales frescos, lo cual constituye un motivo de preocupación con respecto a la seguridad alimentaria, nos llaman la atención algunos aspectos conceptuales y metodológicos empleados en el estudio, que consideramos no son adecuados y por lo cual no se puede afirmar con certeza la veracidad y aplicabilidad de los resultados obtenidos, mismos que quisiéramos exponer.