Voltage-gated potassium channel 1.3: A promising molecular target in multiple disease therapy.

Voltage-gated potassium channel 1.3 (Kv1.3) has emerged as a pivotal player in numerous biological processes and pathological conditions, sparking considerable interest as a potential therapeutic target across various diseases. In this review, we present a comprehensive examination of Kv1.3 channels, highlighting their fundamental characteristics and recent advancements in utilizing Kv1.3 inhibitors for treating autoimmune disorders, neuroinflammation, and cancers. Notably, Kv1.3 is prominently expressed in immune cells and implicated in immune responses and inflammation associated with autoimmune diseases and chronic inflammatory conditions. Moreover, its aberrant expression in certain tumors underscores its role in cancer progression. While preclinical studies have demonstrated the efficacy of Kv1.3 inhibitors, their clinical translation remains pending. Molecular imaging techniques offer promising avenues for tracking Kv1.3 inhibitors and assessing their therapeutic efficacy, thereby facilitating their development and clinical application. Challenges and future directions in Kv1.3 inhibitor research are also discussed, emphasizing the significant potential of targeting Kv1.3 as a promising therapeutic strategy across a spectrum of diseases.

Dive into the details of radionuclide antibody conjugates: what role do EPR effects and LETs of different radionuclides play?

Radionuclide antibody conjugate (RAC) is a promising diagnostic and therapeutic tool. It combines radionuclides and antibodies by connecting arms and chelating agents, offering precise targeting and potent killing of tumor cells. However, further development and optimization of this radiopharmaceutical is needed to enhance the ultimate substantive efficacy for clinical translation. In this issue of AJNMMI, Strand et al. evaluated the enhanced permeability effect and different linear energy transfer (LET) of radionuclides in a prostate cancer xenograft model. The results showed that specific targeting might negatively influence normal organ uptake when targeting secreted antigens and different LETs of radionuclides might have diverse effects on receptor expression and cell proliferation in tumors. The findings provide new thinking for the development of antibody-based radiopharmaceuticals.

Improving the Photovoltaic Performance of Dithienobenzodithiophene-Based Polymers via Addition of an Additional Eluent in the Soxhlet Extraction Process.

Dithieno[2,3-d;2',3'-d']benzo[1,2-b;4,5-b']dithiophene (DTBDT) is a kind of pentacyclic aromatic electron-donating unit with unique optoelectronic properties, but it has received less attention in the design of photovoltaic polymers. In this work, we copolymerized DTBDT with the electron-deficient unit of dithieno[3',2':3,4;2″,3″:5,6]benzo[1,2-c][1,2,5]thiadiazole (DTBT) and obtained two polymers, PE55 and PE56, with a synergistic heteroatom substitution strategy. When blended with the classic nonfullerene acceptor Y6, PE55 and PE56 achieve power conversion efficiencies (PCEs) of 13.78% and 14.49%, respectively, which indicates that the introduction of sulfur atoms on the conjugated side chain of the D unit is a promising method to enhance the performance of DTBDT-based polymers. Besides, we utilize dichloromethane and chloroform to separate the low molecular weight (Mw) fractions in the solvent extraction process to obtain PE55-CF and PE56-CB, and the PCEs are further improved to 15.00% and 16.11%, respectively. The stronger π-π stacking, optimized blend film morphology, and higher charge mobilities contribute to the enhanced PCEs for polymers with higher Mw obtained via the multistep solvent extraction strategy. Our results not only provide a simple and effective way to improve the photovoltaic performance of conjugated polymers but also imply that some reported polymers purified from the traditional one-step solvent extraction method might be seriously underestimated.

Drug-induced QT Interval Prolongation in the Intensive Care Unit.

BACKGROUND: The most common acquired cause of Long QT syndrome (LQTS) is drug induced QT interval prolongation. It is an electrophysiological entity, which is characterized by an extended duration of the ventricular repolarization. Reflected as a prolonged QT interval in a surface ECG, this syndrome increases the risk for polymorphic ventricular tachycardia (Torsade de Pointes) and sudden death. METHOD: Bibliographic databases as MEDLINE and EMBASE, reports and drug alerts from several regulatory agencies (FDA, EMEA, ANMAT) and drug safety guides (ICH S7B, ICH E14) were consulted to prepare this article. The keywords used were: polymorphic ventricular tachycardia, adverse drug events, prolonged QT, arrhythmias, intensive care unit and Torsade de Pointes. Such research involved materials produced up to December 2017. RESULTS: Because of their mechanism of action, antiarrhythmic drugs such as amiodarone, sotalol, quinidine, procainamide, verapamil and diltiazem are associated to the prolongation of the QTc interval. For this reason, they require constant monitoring when administered. Other noncardiovascular drugs that are widely used in the Intensive Care Unit (ICU), such as ondansetron, macrolide and fluoroquinolone antibiotics, typical and atypical antipsychotics agents such as haloperidol, thioridazine, and sertindole are also frequently associated with the prolongation of the QTc interval. As a consequence, critical patients should be closely followed and evaluated. CONCLUSION: ICU patients are particularly prone to experience a QTc interval prolongation mainly for two reasons. In the first place, they are exposed to certain drugs that can prolong the repolarization phase, either by their mechanism of action or through the interaction with other drugs. In the second place, the risk factors for TdP are prevalent clinical conditions among critically ill patients. As a consequence, the attending physician is expected to perform preventive monitoring and ECG checks to control the QTc interval.