Abstract Background: The tarantula Chilobrachys jingzhao is one of the largest venomous spiders in China. In previous studies, we purified and characterized at least eight peptides from C. jingzhao venom. In this report, we describe the purification and characterization of Jingzhaotoxin-X (JZTX-X), which selectively blocks Kv4.2 and Kv4.3 potassium channels. Methods: JZTX-X was purified using a combination of cation-exchange HPLC and reverse-phase HPLC. The amino-acid sequence was determined by automated Edman degradation and confirmed by mass spectrometry (MS). Voltage-gated ion channel currents were recorded in HEK293t cells transiently transfected with a variety of ion channel constructs. In addition, the hyperalgesic activity of JZTX-X and the toxin´s effect on motor function were assessed in mice. Results: JZTX-X contained 31 amino acids, with six cysteine residues that formed three disulfide bonds within an inhibitory cysteine knot (ICK) topology. In whole-cell voltage-clamp experiments, JZTX-X inhibited Kv4.2 and Kv4.3 potassium channels in a concentration- and voltage-dependent manner, without affecting other ion channels (Kv1.1, 1.2, 1.3, 2.1, delayed rectifier potassium channels, high- and low-voltage-activated Ca2+ channels, and voltage-gated sodium channels Nav1.5 and 1.7). JZTX-X also shifted the voltage-dependent channel activation to more depolarized potentials, whereas extreme depolarization caused reversible toxin binding to Kv4.2 channels. JZTX-X shifted the Kv4.2 and Kv4.3 activities towards a resting state, since at the resting potential the toxin completely inhibited the channels, even in the absence of an applied physical stimulus. Intrathecal or intraplantar injection of JZTX-X caused a long-lasting decrease in the mechanical nociceptive threshold (hyperalgesia) but had no effect on motor function as assessed in the rotarod test. Conclusions: JZTX-X selectively suppresses Kv4.2 and Kv4.3 potassium channel activity in a concentration- and voltage-dependent manner and causes long-lasting mechanical hyperalgesia.

Abstract Spider venoms are known to contain proteins and polypeptides that perform various functions including antimicrobial, neurotoxic, analgesic, cytotoxic, necrotic, and hemagglutinic activities. Currently, several classes of natural molecules from spider venoms are potential sources of chemotherapeutics against tumor cells. Some of the spider peptide toxins produce lethal effects on tumor cells by regulating the cell cycle, activating caspase pathway or inactivating mitochondria. Some of them also target the various types of ion channels (including voltage-gated calcium channels, voltage-gated sodium channels, and acid-sensing ion channels) among other pain-related targets. Herein we review the structure and pharmacology of spider-venom peptides that are being used as leads for the development of therapeutics against the pathophysiological conditions including cancer and pain.

Aims: To evaluate the nutritional status of patients undergoing chemoradiotherapy for esophageal cancer using subjective global assessment (SGA) and association of prealbumin levels to nutritional status. Methods: A prospective study was performed on 154 patients with esophageal cancer who were treated with concurrent chemoradiotherapy at center of radiation oncology in Huai�fan First People�fs Hospital from January 2012 to May 2013. The patients�f nutritional status after receiving concurrent chemoradiotherapy were evaluated using SGA tool. Serum total protein, prealbumin, albumin and other biochemical nutrition parameters including triglyceride, total cholesterol, cholesterol and glucose were determined before beginning and after the end of radiotherapy. Results: Malnutrition developed in 129 (83.8%) patients. According to SGA results, 16.2%, 66.2%, and 17.6% of patients were classified as A, B, or C, respectively. Loss of subcutaneous fat or muscle wasting (odds ratio [OR] 11.522); increased metabolic demand/ stress (OR 8.637); ankle, sacral edema, or ascites (OR 3.229) and weight loss ≥5% (OR 2.294) were significantly associated with malnutrition (SGA B or C; p < 0.001). Prealbumin level after the end of radiotherapy was significantly lower in patients with malnutrition (17 ±5 g/ dl vs. 21 �±5 g/dl, p = 0.005), but it showed no difference before beginning radiotherapy (24 �±4 g/dl vs. 22 �±5 g/ dl, p > 0.05). On the other hand, there was no significant difference in term of other nutrition parameters whether before beginning or after the end of radiotherapy (p > 0.05). Conclusions: The prevalence of malnutrition was high in esophageal cancer patients undergoing concurrent chemoradiotherapy. The results serve as a basis for implementation of nutrition intervention to patients being treated at radiotherapy departments. Prealbumin showed relation with SGA rating and should be considered as a sensitive nutritional biomarker for evaluating nutritional status of esophageal cancer patients undergoing concurrent chemoradiotherapy.

Objetivos: Evaluar el estado nutricional de los pacientes sometidos a quimioterapia para cancer esofagico usando subjetiva evaluacion mundial(SGA) y Asociacion de prealbumina a niveles de estado nutricional. Metodos: Se realiza un estudio prospectivo en 154 pacientes con cancer esofagico que fueron tratados con quimiorradioterapia concurrente en centro de Oncologia de radiacion en Huai �ean First People�f s Hospital desde enero de 2012 a mayo de 2013. El estado nutricional de los pacientes despues de recibir quimiorradioterapia concurrente fueron evaluados utilizando la herramienta de SGA. Albumina, prealbumina, proteina serica total, nutricion y otros parametros bioquimicos, incluyendo trigliceridos, colesterol total, colesterol y glucosa fueron determinados antes de empezar y despues del final de la radioterapia. Resultados: La desnutricion desarrollada en 129 (83,8%) pacientes. Segun SGA resultados, 16,2%, 66,2%, y 17,6% de los pacientes fueron clasificados como a, B, o C, respectivamente. La perdida de grasa subcutanea o atrofia muscular (odds ratio [OR] 11.522); demanda metabolica creciente / estres (o 8.637); tobillo edema sacro, o ascitis (o -) y la perdida de peso ≥ 5% (o 3) estuvieron significativamente asociados con la malnutricion (SGA B o C; p < 0,001). El nivel de prealbumina despues del final de la radioterapia fue significativamente menor en los pacientes con desnutricion (17 ± 5 g / dl vs. 21 ± 5 g / dl, p = 0,005), pero no mostro diferencia antes de comenzar la radioterapia (24 �± 4 g / dl vs. 22 �± 5 g / dl, p > 0,05). Por otro lado, no hubo diferencia significativa en el plazo de otros parametros si la nutricion fue antes de comenzar o despues del final de la radioterapia (p > 0,05). Conclusiones: La prevalencia de la malnutricion era alta en cancer de esofago en pacientes sometidos a quimiorradioterapia concurrente. Los resultados sirven de base para la aplicacion de la intervencion en materia de nutricion para pacientes en tratamiento en los servicios de radioterapia. La prealbumina mostro relacion con SGA a valorar y debe ser considerado como un biomarcador sensible nutricional para evaluar el estado nutricional de cáncer esofágico en pacientes sometidos a quimiorradioterapia concurrente.