Scorpion Toxins from <em>Buthus martensii</em> Karsch (BmK) as Potential Therapeutic Agents for Neurological Disorders: State of the Art and Beyond

Scorpions are fascinating creatures which became residents of the planet well before human beings dwelled on Earth. Scorpions are always considered as a figure of fear, causing notable pain or mortality throughout the world. Their venoms are cocktails of bioactive molecules, called toxins, which are responsible for their toxicity. Fortunately, medical researchers have turned the life-threatening toxins into life-saving therapeutics. From Song Dynasty in ancient China, scorpions and their venoms have been applied in traditional medicine for treating neurological disorders, such as pain, stroke, and epilepsy. Neurotoxins purified from Chinese scorpion Buthus Martensii Karsch (BmK) are considered as the main active ingredients, which act on membrane ion channels. Long-chain toxins of BmK, composed of 58–76 amino acids, could specifically recognize voltage-gated sodium channels (VGSCs). Short-chain BmK toxins, containing 28–40 amino acids, are found to modulate the potassium or chloride channels. These components draw attention as useful scaffolds for drug-design in order to tackle the emerging global medical threats. In this chapter, we aim to summarize the most promising candidates that have been isolated from BmK venoms for drug development

Convenient synthesis of multivalent zinc(II)-dipicolylamine complexes for molecular recognition

A pair of novel dipicolylamine ligands bearing isothiocyanate groups were used as conjugation reagents to prepare multivalent molecules with anionic recognition capability. The isothiocyanates were reacted with two classes of dendritic scaffolds bearing primary amines, squaraine rotaxanes, and PAMAM dendrimers, and the products were converted into water soluble zinc(II) coordination complexes. The multivalent squaraine rotaxanes exhibit high fluorescence quantum yields in water and are very well suited for biological imaging applications

Multivalent Dendritic Molecules as Broad Spectrum Bacteria Agglutination Agents

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Etoposide-induced SENP8 confers a feed-back drug resistance on acute lymphoblastic leukemia cells

Chemotherapy is the most common treatment for acute lymphoblastic leukemia (ALL). However, many ALL patients eventually develop relapse and treating relapsed ALL has always been challenging. Therefore, exploring the resistance mechanism of chemotherapeutic drugs and proposing feasible intervention strategies are of great significance for ALL treatment. Here, we show that SENP8, whose coding protein is an important deNEDDylase targeting the substrate for deNEDDylation, is highly expressed in relapsed ALL specimens. Interestingly, overexpressing SENP8 specifically reduces the chemosensitivity of ALL cells to etoposide (VP-16) and significantly alleviates the proapoptotic effect of VP-16 on ALL cells. By contrast, NEDDylation inhibition reduces the chemosensitivity of ALL cells to VP-16. Furthermore, VP-16 induces SENP8 accumulation and the instability of MDM2 as well as the stabilization of p53 in ALL cells, and SENP8 knockdown can sensitize ALL cells to VP-16. Our study reveals a novel function of SENP8 in ALL and that VP-16-induced SENP8 confers a feed-back drug resistance on ALL cells, suggesting a possibility of overcoming the chemotherapeutic resistance to VP-16 via targeting SENP8

Enhanced Cell Death Imaging Using Multivalent Zinc(II)-bis(dipicolylamine) Fluorescent Probes

There is a clinical need for imaging technologies that can accurately detect cell death in a multitude of pathological conditions. Zinc­(II)-bis­(dipicolylamine) (Zn₂BDPA) coordination complexes are known to associate with the anionic phosphatidylserine that is exposed on the surface of dead and dying cells, and fluorescent monovalent Zn₂BDPA probes are successful cell death imaging agents. This present study compared the membrane targeting ability of two structurally related deep-red fluorescent probes, bis-Zn₂BDPA-SR and tetra-Zn₂BDPA-SR, with two and four appended Zn₂BDPA units, respectively. Vesicle and cell microscopy studies indicated that a higher number of Zn₂BDPA targeting units improved probe selectivity for phosphatidylserine-rich vesicles, and increased probe localization at the plasma membrane of dead and dying cells. The fluorescent probes were also tested in three separate animal models, (1) necrotic prostate tumor rat model, (2) thymus atrophy mouse model, and (3) traumatic brain injury mouse model. In each case, there was more tetra-Zn₂BDPA-SR accumulation at the site of cell death than bis-Zn₂BDPA-SR. The results indicate that multivalent Zn₂BDPA probes are promising molecules for effective imaging of cell death processes in cell culture and in living subjects

Absence of long-range magnetic order in Fe1−δ Te2 (δ ≈ 0.1) crystals

Transition metal dichalcogenides attract considerable attention due to a variety of interesting properties, including long-range magnetism in nanocrystals. Here we investigate the magnetic, thermal, and electrical properties of an FeTe2 single crystal with iron vacancy defects. Magnetic measurements show a paramagnetic state and the absence of magnetic order with low anisotropy in the magnetic susceptibility. Fe 3d orbitals are well hybridized, contributing to the bad metal electrical resistivity. Observed thermal conductivity values below room temperature are rather low and comparable to those of high-performance thermoelectric materials. Our results indicate that FeTe2 can form in a highly defective marcasite crystal structure which can be exploited in future materials design