Bypassing cisplatin resistance in Nrf2 hyperactivated head and neck cancer through effective PI3Kinase targeting.

Background: For patients with head and neck squamous cell carcinoma (HNSCC), failure of definitive radiation combined with cisplatin nearly universally results in death. Although hyperactivation of the Nrf2 pathway can drive radiation and cisplatin resistance along with suppressed anti-tumor immunity, treatment-refractory HNSCC tumors may retain sensitivity to targeted agents secondary to synergistic lethality with other oncogenic drivers (e.g.

Comparative Analysis of the Enzymatic, Coagulant, and Neuromuscular Activities of Two Variants of Venom and Antivenom Efficacy.

We compared the enzymatic, coagulant, and neuromuscular activities of two variants (yellow-CDRy and white-CDRw) of venom with a sample of (CDT) venom and examined their neutralization by antivenom against CDT venom. The venoms were screened for enzymatic and coagulant activities using standard assays, and electrophoretic profiles were compared by SDS-PAGE. Neutralization was assessed by preincubating venoms with crotalic antivenom and assaying the residual activity.

Venom proteomics and Duvernoy's venom gland histology of Pseudoboa neuwiedii (Neuwied's false boa; Dipsadidae, Pseudoboini).

The venom of Colombian specimens of the rear-fanged snake Pseudoboa neuwiedii contains proteolytic and phospholipase A (PLA) activities, but is devoid of esterases. Mass spectrometric analysis of electrophoretic bands indicated that this venom contains C-type lectins (CTL), cysteine-rich secretory proteins (CRiSP), PLA, snake venom metalloproteinases (SVMP), and snake venom matrix metalloproteinases (svMMP). In this investigation, we extended our characterization of P.

Disruption of exploratory behavior and olfactory memory in cockroaches exposed to sublethal doses of the neonicotinoid Thiamethoxam.

Neonicotinoid insecticides (NNI) are agonists of insect nicotinic acetylcholine receptors (nAChR) that induce non-elucidate mechanisms of abnormal behavior in insects. In this work, we investigated the effects of sublethal doses of the neonicotinoid thiamethoxam (TMX) on neurochemical and physiological parameters in cockroaches. Sublethal doses of TMX (0.

Snakebites by venomous snakes in Brazilian serpentaria and zoos over a 10-year period (2012-2021).

Despite the wide range of institutions that maintain venomous snakes in captivity in Brazil there are no comprehensive data on the occurrence of snakebites and envenomations in these places. We examined the range of native and exotic species of venomous snakes kept by Brazilian zoos and serpentaria (scientific and commercial) and assessed the frequency of snakebites in workers handling these snakes during a 10-year period (2012-2021). Twenty-two (73.

Recent advances on the influence of fipronil on insect behavior.

Fipronil, a pesticide widely used to control agricultural and household insect pests, blocks insect GABA and glutamate (GluCl) ionotropic receptors, resulting in uncontrolled hyperexcitation and paralysis that eventually leads to death. The use of fipronil is controversial because unintentional exposure to this compound may contribute to the ongoing global decline of insect pollinator populations. Although the sublethal effects of fipronil have been linked to aberrant behavior and impaired olfactory learning in insects, the precise mechanisms involved in these responses remain unclear.

Multifactoral immune modulation potentiates durable remission in multiple models of aggressive malignancy.

Tumors typically lack canonical danger signals required to activate adaptive immunity and also frequently employ substantial immunomodulatory mechanisms that downregulate adaptive responses and contribute to escape from immune surveillance. Given the variety of mechanisms involved in shielding tumors from immune recognition, it is not surprising that single-agent immunomodulatory approaches have been largely unsuccessful in generating durable antitumor responses. Here we report a unique combination of immunomodulatory and cytostatic agents that recondition the tumor microenvironment and eliminate complex and/or poor-prognosis tumor types including the non-immunogenic 4T-1 model of TNBC, the aggressive MOC-2 model of HNSCC, and the high-risk MYCN-amplified model of neuroblastoma.

The Cloning and Characterization of a Three-Finger Toxin Homolog (NXH8) from the Coralsnake That Interacts with Skeletal Muscle Nicotinic Acetylcholine Receptors.

Coralsnakes ( spp.) are the only elapids found throughout the Americas. They are recognized for their highly neurotoxic venom, which is comprised of a wide variety of toxins, including the stable, low-mass toxins known as three-finger toxins (3FTx).

Biochemical and toxicological profiles of venoms from an adult female South American bushmaster (Lachesis muta rhombeata) and her offspring.

In this work, we compared the biochemical and toxicological profiles of venoms from an adult female specimen of Lachesis muta rhombeata (South American bushmaster) and her seven offspring born in captivity, based on SDS-PAGE, RP-HPLC, enzymatic, coagulant, and hemorrhagic assays. Although adult and juvenile venoms showed comparable SDS-PAGE profiles, juveniles lacked some chromatographic peaks compared with adult venom. Adult venom had higher proteolytic (caseinolytic) activity than juvenile venoms (p < 0.

Involvement of phospholipase A in the neuromuscular blockade caused by coralsnake (Micrurus spp.) venoms in mouse phrenic nerve-diaphragm preparations in vitro.

In this work, we examined the neuromuscular blockade caused by venoms from four South-American coralsnakes (Micrurus altirostris - MA, M. corallinus - MC, M. spixii - MS, and M.

Fipronil affects cockroach behavior and olfactory memory.

Fipronil (Fpl), an insecticide belonging to the class of phenylpyrazoles, is associated with the widespread mortality of pollinator insects worldwide. Based on studies carried out on residual concentrations of Fpl commonly found in the environment, in this study, we evaluated the sublethal effects of Fpl on behavior and other neurophysiological parameters using the cockroach Nauphoeta cinerea as a biological model. Sublethal doses of Fpl (0.

Assessment of local pain and analgesia in envenoming by wandering spiders (Phoneutria spp.).

Phoneutrism (bites by wandering spiders of the genus Phoneutria) frequently results in local pain. We describe a retrospective cohort study of a case series of phoneutrism admitted to our Emergency Department (ED), in which we used the Numeric Pain Rating Scale (NPRS 0-10) to assess the intensity of local pain upon admission, and recorded the analgesic measures used to control this pain. Other criteria for inclusion were: (1) An age ≥8 years, (2) Treatment exclusively at our ED, and (3) Visualization or photographing the spider at the time of the bite and/or bringing the spider for identification.

Cardiac Effects of Micrurus corallinus and Micrurus dumerilii carinicauda (Elapidae) Venoms and Neutralization by Brazilian Coralsnake Antivenom and Varespladib.

In this work, we examined the action of two South American coralsnake (Micrurus corallinus and Micrurus dumerilii carinicauda) venoms on rat heart function in the absence and presence of treatment with Brazilian coralsnake antivenom (CAV) and varespladib (VPL), a potent phospholipase A inhibitor. Anesthetized male Wistar rats were injected with saline (control) or a single dose of venom (1.5 mg/kg, i.

Proinflammatory microenvironment promotes lymphoma progression in mice with high megakaryocyte and TPO levels.

Platelets have been shown to enhance the survival of lymphoma cell lines. However, it remains unclear whether they play a role in lymphoma. Here, we investigated the potential role of platelets and/or megakaryocytes in the progression of Eμ-myc lymphoma.

Plasmodium vivax malaria serological exposure markers: Assessing the degree and implications of cross-reactivity with P. knowlesi.

Serological markers are a promising tool for surveillance and targeted interventions for Plasmodium vivax malaria. P. vivax is closely related to the zoonotic parasite P.

Effect of the phospholipase A inhibitor Varespladib, and its synergism with crotalic antivenom, on the neuromuscular blockade induced by Crotalus durissus terrificus venom (with and without crotamine) in mouse neuromuscular preparations.

The venom of the South American rattlesnake Crotalus durissus terrificus causes an irreversible neuromuscular blockade in isolated preparations due to action of the presynaptically-acting heterodimeric phospholipase A (PLA) crotoxin. Some populations of this subspecies contain, in addition to crotoxin, the toxin crotamine, which acts directly on muscle fibers. In this study we used C.

Temporal evolution of dermonecrosis in loxoscelism assessed by photodocumentation.

Background: Although loxoscelism (bites by brown spiders of the genus Loxosceles) frequently results in dermonecrosis, no previous clinical reports have provided detailed temporal photodocumentation of the evolution of dermonecrotic lesions in a case series.

Methods: This was a retrospective cohort study involving a case series of loxoscelism. Only cases of dermonecrosis with photodocumentation of lesion evolution (from admission until complete or almost complete healing) were included.

Action of Varespladib (LY-315920), a Phospholipase A Inhibitor, on the Enzymatic, Coagulant and Haemorrhagic Activities of (South-American Bushmaster) Venom.

Varespladib (VPL) was primarily developed to treat inflammatory disturbances associated with high levels of serum phospholipase A (PLA). VPL has also demonstrated to be a potential antivenom support agent to prevent PLA-dependent effects produced by snake venoms. In this study, we examined the action of VPL on the coagulant, haemorrhagic and enzymatic activities of (South-American bushmaster) venom.

Adenoviral delivery of an immunomodulatory protein to the tumor microenvironment controls tumor growth.

Targeted modulation of the immune system against tumors can achieve responses in otherwise refractory cancers, which has spurred efforts aimed at optimizing such strategies. To this end, we have previously investigated cancer immunotherapy approaches using recombinant adenovirus vectors, as well as via modulation of the self-ligand receptor SLAMF7. Here, we present a gene transfer-based immunotherapy approach using targeted expression of a SLAMF7-Fc fusion construct directly into tumors at high concentrations via a recombinant adenoviral vector (Ad-SF7-Fc).

Evaluation of Protection by Caffeic Acid, Chlorogenic Acid, Quercetin and Tannic Acid against the In Vitro Neurotoxicity and In Vivo Lethality of (South American Rattlesnake) Venom.

Systemic envenomation by (South American rattlesnake) can cause coagulopathy, rabdomyolysis, acute kidney injury, and peripheral neuromuscular blockade, the latter resulting in flaccid paralysis. Previous studies have shown that plant products such as tannic acid and theaflavin can protect against the neuromuscular blockade caused by venom in vitro. In this work, we used mouse-isolated phrenic nerve-diaphragm preparations to examine the ability of caffeic acid, chlorogenic acid, and quercetin to protect against venom-induced neuromuscular blockade in vitro.

SARS-CoV-2 Multi-Antigen Serology Assay.

Serology tests are extremely useful for assessing whether a person has been infected with a pathogen. Since the onset of the COVID-19 pandemic, measurement of anti-SARS-CoV-2-specific antibodies has been considered an essential tool in identifying seropositive individuals and thereby understanding the extent of transmission in communities. The Luminex system is a bead-based technology that has the capacity to assess multiple antigens simultaneously using very low sample volumes and is ideal for high-throughput studies.

Beyond "Watching the Sweets": An interpretive description of adolescent's understandings and insights into preventing prediabetes and type 2 diabetes.

Purpose: The purpose of this study was to explore adolescents' experiences and knowledge of type 2 diabetes (T2D) and identify appropriate T2D education and prevention interventions for this population.

Design And Methods: This interpretive description study was conducted at two urban high schools in midwestern Canada. Participants had been previously screened and considered at high risk for T2D, prediabetes, or as having T2D.