Specific Signaling Research Articles

High-performance ratiometric magnetic electrochemical sensor for acetamiprid detection using Ag@PDA@Fe3O4 nanocomposites

Acetamiprid (AAP) is a renowned neonicotinoid insecticide for swift insect control that is prone to residue in agricultural products and threatens human health. Magnetic electrochemical sensor (MES) was developed for high-precision detection of AAP based on silver nanoparticle (AgNPs) and polydopamine (PDA) modified Fe3O4 nanocomposites (Ag@PDA@Fe3O4). The electrochemical signals generated by AAP hydrolysis and AgNPs oxidation are respectively used as two special signal sources. An increase in AAP concentration led to a proportional increase in the signal from AAP hydrolysis at +0.9 V (IAAP), while the signal from AgNPs oxidation at +0.27 V (IAg) correspondingly decreased. The output signal ΔIAAP/ΔIAg (R2=0.9890) demonstrates a superior linear relationship compared to ΔIAAP (R2=0.9790) or ΔIAg (R2=0.9740) alone. MES demonstrated a broad linear detection range from 0.01 to 2.00 mg L−1 and an impressive limit of detection (LOD, 3S/M) at 3.6 µg L−1. The incorporation of magnetic glassy carbon electrodes (MGCE) significantly mitigates the detachment of nanomaterials. MES has excellent stability and selectivity, and can successfully detect AAP in actual cowpea samples. This study provides pivotal insights into the design of nanomaterial-based ratiometric electrochemical sensors for the sensitive and selective detection of AAP.

Preferentially expressed endosperm genes reveal unique activities in wheat endosperm during grain filling

BackgroundBread wheat (Triticum aestivum L.) endosperm contains starch and proteins, which determine the final yield, quality, and nutritional value of wheat grain. The preferentially expressed endosperm genes can precisely provide targets in the endosperm for improving wheat grain quality and nutrition using modern bioengineering technologies. However, the genes specifically expressed in developing endosperms remain largely unknown.ResultsIn this study, 315 preferentially expressed endosperm genes (PEEGs) in the spring wheat landrace, Chinese Spring, were screened using data obtained from an open bioinformatics database, which reveals a unique grain reserve deposition process and special signal transduction in a developing wheat endosperm. Furthermore, transcription and accumulation of storage proteins in the wheat cultivar, XC26 were evaluated. The results revealed that 315 PEEG plays a critical role in storage protein fragment deposition and is a potential candidate for modifying grain quality and nutrition.ConclusionThese results provide new insights into endosperm development and candidate genes and promoters for improving wheat grain quality through genetic engineering and plant breeding techniques.

The Wavelet Transform and Its Spectral Analysis: A Modern Review and Some Results in Harmonic Discrete Analysis

The wavelet transform and its multiple versions in many aspects of the spectral analysis, the wavelet transform, likewise its relation with other transforms and special functions, needs a special treatment due to that in last years the developments in quantum electronics and recognition of signals in the frequency domain, likewise exploration profuse on new research in advanced materials like special semiconductors or fine devices in medicine, where the research is more detailed and majorly more specific in different applications. Likewise we have the wavelet transform of special function where each one can establish of very useful way the creation and design of special signal filters used in the modern industry in electronics, data processing analysis or even in the configuration of the advanced electronic equipment. Also the interphase between reception-emission devices with sensorial parts of the human body, in biomedical engineering. A version is interesting like the quantum wavelet transform which is very useful in the spectral study of traces of particles, for example studied from atomic accelerator. Finally are given general results to the discrete study of signal, which is analyzed to the wavelet transform and its spectra.

Lymphocyte homing and recirculation with tumor tertiary lymphoid structure formation: predictions for successful cancer immunotherapy.

The capacity of lymphocytes continuously home to lymphoid structures is remarkable for cancer immunosurveillance and immunotherapy. Lymphocyte homing and recirculation within the tumor microenvironment (TME) are now understood to be adaptive processes that are regulated by specialized cytokines and adhesion molecule signaling cascades. Restricted lymphocyte infiltration and recirculation have emerged as key mechanisms contributing to poor responses in cancer immunotherapies like chimeric antigen receptor (CAR)-T cell therapy and immune checkpoint blockades (ICBs). Uncovering the kinetics of lymphocytes in tumor infiltration and circulation is crucial for improving immunotherapies. In this review, we discuss the current insights into the adhesive and migrative molecules involved in lymphocyte homing and transmigration. The potential mechanisms within the TME that restrain lymphocyte infiltration are also summarized. Advanced on these, we outline the determinates for tertiary lymphoid structures (TLSs) formation within tumors, placing high expectations on the prognostic values of TLSs as therapeutic targets in malignancies.

Human Amylin as a Novel Diagnostic Marker for Hypothyroidism in Iraqi Patients

الأميلين هو هرمون ببتيد تفرزه خلية البنكرياس مع الأنسولين. بصفته هرمونًا عصبيًا صماويًا يرسل إشارة محددة إلى الدماغ ، فإن الأميلين ضروري للحفاظ على التوازن في عملية التمثيل الغذائي . كان الهدف من الدراسة الحالية هو تحديد دور الأميلين كعلامة تشخيصية لقصور الغدة الدرقية. تم تقسيم 120 عينة إلى مجموعتين المجموعة الاولى (80 مريض بقصور الغدة الدرقية) والمجموعة الثانية (40 شخصًا سليمًا) . زادت مستويات الأميلين بشكل ملحوظ في المجموعة المصابة بقصور الغدة الدرقية مقارنة بمحموعة الاصحاء ، وفقًا للبيانات (P <0.001) ، ارتفعت مستويات الأميلين في الدم في المرضى العراقيين المصابين بقصور الغدة الدرقية . يعد الأميلين علامة تشخيصية جيدة لقصور الغدة الدرقية بأكبر قدر من الدقة والحساسية مع القيمة المقطوعة 51.

Duality of Branched-Chain Amino Acids in Chronic Cardiovascular Disease: Potential Biomarkers versus Active Pathophysiological Promoters.

Branched-chain amino acids (BCAAs), comprising leucine (Leu), isoleucine (Ile), and valine (Val), are essential nutrients vital for protein synthesis and metabolic regulation via specialized signaling networks. Their association with cardiovascular diseases (CVDs) has become a focal point of scientific debate, with emerging evidence suggesting both beneficial and detrimental roles. This review aims to dissect the multifaceted relationship between BCAAs and cardiovascular health, exploring the molecular mechanisms and clinical implications. Elevated BCAA levels have also been linked to insulin resistance (IR), type 2 diabetes mellitus (T2DM), inflammation, and dyslipidemia, which are well-established risk factors for CVD. Central to these processes are key pathways such as mammalian target of rapamycin (mTOR) signaling, nuclear factor kappa-light-chain-enhancer of activate B cells (NF-κB)-mediated inflammation, and oxidative stress. Additionally, the interplay between BCAA metabolism and gut microbiota, particularly the production of metabolites like trimethylamine-N-oxide (TMAO), adds another layer of complexity. Contrarily, some studies propose that BCAAs may have cardioprotective effects under certain conditions, contributing to muscle maintenance and metabolic health. This review critically evaluates the evidence, addressing the biological basis and signal transduction mechanism, and also discusses the potential for BCAAs to act as biomarkers versus active mediators of cardiovascular pathology. By presenting a balanced analysis, this review seeks to clarify the contentious roles of BCAAs in CVD, providing a foundation for future research and therapeutic strategies required because of the rising prevalence, incidence, and total burden of CVDs.

Introduction to the Special Issue Near-Field Signal Processing: Algorithms, Implementations and Applications

Introduction to the Special Issue Near-Field Signal Processing: Algorithms, Implementations and Applications

Inhibition of the serine protease HtrA1 by SerpinE2 suggests an extracellular proteolytic pathway in the control of neural crest migration.

We previously showed that SerpinE2 and the serine protease HtrA1 modulate fibroblast growth factor (FGF) signaling in germ layer specification and head-to-tail development of Xenopus embryos. Here we present an extracellular proteolytic mechanism involving this serpin-protease system in the developing neural crest (NC). Knockdown of SerpinE2 by injected antisense morpholino oligonucleotides did not affect the specification of NC progenitors but instead inhibited the migration of NC cells, causing defects in dorsal fin, melanocyte and craniofacial cartilage formation. Similarly, overexpression of the HtrA1 protease impaired NC cell migration and the formation of NC-derived structures. The phenotype of SerpinE2 knockdown was overcome by concomitant downregulation of HtrA1, indicating that SerpinE2 stimulates NC migration by inhibiting endogenous HtrA1 activity. SerpinE2 binds to HtrA1, and the HtrA1 protease triggers degradation of the cell surface proteoglycan Syndecan-4 (Sdc4). Microinjection of Sdc4 mRNA partially rescued NC migration defects induced both by HtrA1 upregulation and SerpinE2 downregulation. These epistatic experiments suggest a proteolytic pathway by a double inhibition mechanism: SerpinE2 ┤HtrA1 protease ┤Syndecan-4 → NC cell migration

Inhibition of the serine protease HtrA1 by SerpinE2 suggests an extracellular proteolytic pathway in the control of neural crest migration

We previously showed that SerpinE2 and the serine protease HtrA1 modulate fibroblast growth factor (FGF) signaling in germ layer specification and head-to-tail development of Xenopus embryos. Here, we present an extracellular proteolytic mechanism involving this serpin-protease system in the developing neural crest (NC). Knockdown of SerpinE2 by injected antisense morpholino oligonucleotides did not affect the specification of NC progenitors but instead inhibited the migration of NC cells, causing defects in dorsal fin, melanocyte, and craniofacial cartilage formation. Similarly, overexpression of the HtrA1 protease impaired NC cell migration and the formation of NC-derived structures. The phenotype of SerpinE2 knockdown was overcome by concomitant downregulation of HtrA1, indicating that SerpinE2 stimulates NC migration by inhibiting endogenous HtrA1 activity. SerpinE2 binds to HtrA1, and the HtrA1 protease triggers degradation of the cell surface proteoglycan Syndecan-4 (Sdc4). Microinjection of Sdc4 mRNA partially rescued NC migration defects induced by both HtrA1 upregulation and SerpinE2 downregulation. These epistatic experiments suggest a proteolytic pathway by a double inhibition mechanism:SerpinE2 ┤HtrA1 protease ┤Syndecan-4 → NC cell migration.

Effects of Equatorial Plasma Bubbles on Multi-GNSS Signals: A Case Study over South China

Equatorial plasma bubbles (EPBs) occur frequently in low-latitude areas and have a non-negligible impact on navigation satellite signals. To systematically analyze the effects of a single EPB event on multi-frequency signals of GPS, Galileo, GLONASS, and BDS, all-sky airglow images over South China are jointly used to visually determine the EPB structure and depletion degree. The results reveal that scintillations, or GNSS signal fluctuations, are directly linked to EPBs and that the intensity of scintillation is positively correlated with the airglow depletion intensity. The center of the airglow depletion often corresponds to stronger GNSS scintillation, while the edge of the bubble, which is considered to have the largest density gradient, corresponds to relatively smaller scintillation instead. This work also systematically analyzes the responses of multi-constellation and multi-frequency signals to EPBs. The results show that the L2 and L5 frequencies are more susceptible than the L1 frequency is. For different constellations, Galileo’s signal has the best tracking stability during an EPB event compared with GPS, GLONASS, and BDS. The results provide a reference for dual-frequency signal selection in precise positioning or TEC calculation, that is, L1C and L2L for GPS, L1C and L5Q for Galileo, L1P and L2C for GLONASS, and L1P and L5P for BDS. Notably, BDS-2 is significantly weaker than BDS-3. And inclined geosynchronous orbit (IGSO) satellites have abnormal data error rates, which should be related to the special signal path trajectory of the IGSO satellite.

Systems level analysis of time and stimuli specific signaling through PKA.

It is well known that eukaryotic cells create gradients of cAMP across space and time to regulate the cAMP dependent protein kinase (PKA) and, in turn, growth and metabolism. However, it is unclear how PKA responds to different concentrations of cAMP. Here, to address this question, we examine PKA signaling in Saccharomyces cerevisiae in different conditions, timepoints, and concentrations of the chemical inhibitor 1-NM-PP1, using phosphoproteomics. These experiments show that there are numerous proteins that are only phosphorylated when cAMP and PKA activity are at/near their maximum level, while other proteins are phosphorylated even when cAMP levels and PKA activity are low. The data also show that PKA drives cells into distinct growth states by acting on proteins with different thresholds for phosphorylation in different conditions. Analysis of the sequences surrounding the 118 PKA-dependent phosphosites suggests that the phosphorylation thresholds are set, at least in part, by the affinity of PKA for each site.

MICRO-AND NANOCIRCUITS WITH PROGRAMMABLE STRUCTURES

In this work, structural programming does not mean the creation of algorithms for processing multi-argument functions by changing the operating pro- grams, as implemented by the microprocessor, but rather technological changes in the large-scale integrated circuits (LSIC) configurations in such a way as to synthesize logical functions at the structural-logical level. During the automated design and manufacture of programmable LSIC (FPGA or CPLD), the same technological cycle is used as for specialized circuits. Obviously, such LSICs are universal for technologists. However, programming of individual LSICs that implement given functions is performed by the user. Thus, the main advantage of universal (FPGA, CPLD) programmable LSIC over specialized ones is low cost, which is fundamentally important for small-scale production. Currently, the increase in the universality of LSIC is always accompanied by a decrease in their special application. Such inconsistency is revealed in the initial stages of automated hierarchical design. Universal micro- and nanocircuits with programmable structures are used to increase the efficiency of CAD. One of the advantages of programmable logic integrated circuits (PLCs) over LSIC is a short manufacturing time with predetermined charac- teristics. At the same time, a standard micro- or nanocircuit is taken and its parameters are directly changed by applying special signals to certain in- puts or connecting the outputs accordingly. This advantage determines the main purpose of such FPGAs - the replacement of groups of logic ICs of medium and large degrees of integration. Multiplexers can be used as simple FPGAs. The article introduces effective methods of multivariate pro- gramming of multiplexer MNPS for reproduction of Boolean and majority logic functions. The obtained results can be used for reprogramming multi- plexer functional blocks of programmable integrated circuits. Comparative modeling of logical MNPS was performed on modern CAD systems, which proved the adequacy of their functioning, advantages of frequency and disadvantages of temperature characteristics of nanomultiplexer circuits.

Roles of IL-4, IL-13, and Their Receptors in Lung Cancer.

Interleukin (IL)-4 and IL-13 are the main effectors of innate lymphoid cells (ILC2) of the type 2 innate immune response, which can carry out specific signal transmission between multiple cells in the tumor immune microenvironment. IL-4 and IL-13 mediate signal transduction and regulate cellular functions in a variety of solid tumors through their shared receptor chain, the transmembrane heterodimer interleukin-4 receptor alpha/interleukin-13 receptor alpha-1 (type II IL-4 receptor). IL-4, IL-13, and their receptors can induce the formation of a variety of malignant tumors and play an important role in their progression, growth, and tumor immunity. In order to explore possible targets for lung cancer prediction and treatment, this review summarizes the characteristics and signal transduction pathways of IL-4 and IL-13, and their respective receptors, and discusses in depth their possible role in the occurrence and development of lung cancer.

Are the P600 and P3 ERP components linked to the task-evoked pupillary response as a correlate of norepinephrine activity?

During language comprehension, anomalies and ambiguities in the input typically elicit the P600 event-related potential component. Although traditionally interpreted as a specific signal of combinatorial operations in sentence processing, the component has alternatively been proposed to be a variant of the oddball-sensitive, domain-general P3 component. In particular, both components might reflect phasic norepinephrine release from the locus coeruleus (LC/NE) to motivationally significant stimuli. In this preregistered study, we tested this hypothesis by relating both components to the task-evoked pupillary response, a putative biomarker of LC/NE activity. 36 participants completed a sentence comprehension task (containing 25% morphosyntactic violations) and a non-linguistic oddball task (containing 20% oddballs), while the EEG and pupil size were co-registered. Our results showed that the task-evoked pupillary response and the ERP amplitudes of both components were similarly affected by both experimental tasks. In the oddball task, there was also a temporally specific relationship between the P3 and the pupillary response beyond the shared oddball effect, thereby further linking the P3 to NE. Because this link was less reliable in the linguistic context, we did not find conclusive evidence for or against a relationship between the P600 and the pupillary response. Still, our findings further stimulate the debate on whether language-related ERPs are indeed specific to linguistic processes or shared across cognitive domains. However, further research is required to verify a potential link between the two ERP positivities and the LC/NE system as the common neural generator.

Integrated Omics Approach: Revealing the Mechanism of Auxenochlorella pyrenoidosa Protein Extract Replacing Fetal Bovine Serum for Fish Muscle Cell Culture.

The process of producing cell-cultured meat involves utilizing a significant amount of culture medium, including fetal bovine serum (FBS), which represents a considerable portion of production expense while also raising environmental and safety concerns. This study demonstrated that supplementation with Auxenochlorella pyrenoidosa protein extract (APE) under low-serum conditions substantially increased Carassius auratus muscle (CAM) cell proliferation and heightened the expression of Myf5 compared to the absence of APE. An integrated intracellular metabolomics and proteomics analysis revealed a total of 13 and 67 differentially expressed metabolites and proteins, respectively, after supplementation with APE in the medium containing 5%FBS, modulating specific metabolism and signaling pathways, which explained the application of APE for passage cell culture under low-serum conditions. Further analysis revealed that the bioactive factors in the APE were protein components. Moreover, CAM cells cultured in reconstructed serum-free media containing APE, l-ascorbic acid, insulin, transferrin, selenium, and ethanolamine exhibited significantly accelerated growth in a scale-up culture. These findings suggest a promising alternative to FBS for fish muscle cell culture that can help reduce production costs and environmental impact in the production of cultured meat.

Hyperbranched Chain Hybridization for Artificial Aggregates: Prolonging Intracellular Retention for Image‐Guided Cellular Fate Modulation

AbstractDesigning dynamic assemblies in living cells is crucial for creating organelle‐like structures, yet precisely controlling their morphological transitions in response to specific signals is a significant challenge. In this study, a DNA framework is combined with hybridization chain reaction (HCR) to achieve specific assembly of hyperbranched aggregates in cancer cells. HCR, distinguished for its signal amplification and linear extension capabilities, enables the morphological transition of precursors to be specifically triggered by trace amounts of endogenous microRNA‐21 (miR‐21). The spatial constraints of the framework and the diversity of hairpin orientations significantly accelerate the assembly kinetics of hyperbranched networks, and the resulting micrometer‐scale aggregates possess enhanced intracellular retention capabilities. Introducing Ce6 molecules as a proof of concept, the regulatory function of aggregates can be activated under light irradiation and remains effective over a long period. The probe we constructed demonstrates good stability and biocompatibility, offers easy functionalization, and works inside cells long‐term, making it an ideal candidate material for the construction of organelle‐like structures.

Genes involved in auxin biosynthesis, transport and signalling underlie the extreme adventitious root phenotype of the tomato aer mutant

The use of tomato rootstocks has helped to alleviate the soaring abiotic stresses provoked by the adverse effects of climate change. Lateral and adventitious roots can improve topsoil exploration and nutrient uptake, shoot biomass and resulting overall yield. It is essential to understand the genetic basis of root structure development and how lateral and adventitious roots are produced. Existing mutant lines with specific root phenotypes are an excellent resource to analyse and comprehend the molecular basis of root developmental traits. The tomato aerial roots (aer) mutant exhibits an extreme adventitious rooting phenotype on the primary stem. It is known that this phenotype is associated with restricted polar auxin transport from the juvenile to the more mature stem, but prior to this study, the genetic loci responsible for the aer phenotype were unknown. We used genomic approaches to define the polygenic nature of the aer phenotype and provide evidence that increased expression of specific auxin biosynthesis, transport and signalling genes in different loci causes the initiation of adventitious root primordia in tomato stems. Our results allow the selection of different levels of adventitious rooting using molecular markers, potentially contributing to rootstock breeding strategies in grafted vegetable crops, especially in tomato. In crops vegetatively propagated as cuttings, such as fruit trees and cane fruits, orthologous genes may be useful for the selection of cultivars more amenable to propagation.

A single-cell atlas of Drosophila trachea reveals glycosylation-mediated Notch signaling in cell fate specification

The Drosophila tracheal system is a favorable model for investigating the program of tubular morphogenesis. This system is established in the embryo by post-mitotic cells, but also undergoes remodeling by adult stem cells. Here, we provide a comprehensive cell atlas of Drosophila trachea using the single-cell RNA-sequencing (scRNA-seq) technique. The atlas documents transcriptional profiles of tracheoblasts within the Drosophila airway, delineating 9 major subtypes. Further evidence gained from in silico as well as genetic investigations highlight a set of transcription factors characterized by their capacity to switch cell fate. Notably, the transcription factors Pebbled, Blistered, Knirps, Spalt and Cut are influenced by Notch signaling and determine tracheal cell identity. Moreover, Notch signaling orchestrates transcriptional activities essential for tracheoblast differentiation and responds to protein glycosylation that is induced by high sugar diet. Therefore, our study yields a single-cell transcriptomic atlas of tracheal development and regeneration, and suggests a glycosylation-responsive Notch signaling in cell fate determination.

Abstract B089: Intratumoral expression analysis of mast cells in high grade serous ovarian cancer

Abstract Objective: The goal of this study is to examine intratumoral expression and phenotypic changes in mast cells following neoadjuvant chemotherapy (NACT) exposure in high grade serous ovarian cancer (HGSOC). Methods: 37 HGSOC matched pre-and post-NACT patient tumors were stained with a commercially available mast cell hemotoxic-based kit and both intratumoral and stromal mast cells were quantified. Immunohistochemistry was employed to stain for histamine in 19 matched HGSOC patient tumors and mean intensity and integrated optical density was quantified using Image J. Kaplan Meier curve analysis was employed to determine the relationship between mast cells levels and progression-free survival (PFS). Immortalized human mast cells, LUVA were treated with carboplatin and paclitaxel and specific genomic changes were measured by quantitative PCR (qPCR). Results. Mast cells were more prominently expressed in intraepithelial regions compared to stromal cells, however both populations were significantly (p<0.05) increased following NACT. Total mast cells stratified by upper and lower quartile demonstrated that higher levels were significantly (p<0.05) associated with improved PFS. Furthermore, histamine, a marker of mast cell degranulation was significantly (p<0.05) increased in HGSOC tumors post-NACT and significantly correlated (r=0.553, p=0.013) with the change in total mast cells. Following chemotherapy treatment LUVA cells demonstrated an over 7-fold increase in amphiregulin (AREG) expression (p<0.01), a key marker of mast cell activation. Interestingly, angiogenic and pro-tumorigenic factors IL-10, IL-8, and VEGFA exhibited no significant differences in expression following chemotherapy exposure. Conclusions: Overall, our findings suggest a correlation in NACT exposure and intratumoral mast cell recruitment, degranulation, and activation. Further studies include investigating differences in specific tumorigenic genes and cell signaling pathways in mast cells pre- and post- NACT, as well as determining if mast cells can impact HGSOC chemotherapy response. Citation Format: Julia McAdams, Jasmine Ebott, Payton De La Cruz, Nicole E. James. Intratumoral expression analysis of mast cells in high grade serous ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B089.

Modulating the Activity of the Human Organic Cation Transporter 2 Emerges as a Potential Strategy to Mitigate Unwanted Toxicities Associated with Cisplatin Chemotherapy.

Cisplatin (CDDP) stands out as an effective chemotherapeutic agent; however, its application is linked to the development of significant adverse effects, notably nephro- and ototoxicity. The human organic cation transporter 2 (hOCT2), found in abundance in the basolateral membrane domain of renal proximal tubules and the Corti organ, plays a crucial role in the initiation of nephro- and ototoxicity associated with CDDP by facilitating its uptake in kidney and ear cells. Given its limited presence in cancer cells, hOCT2 emerges as a potential druggable target for mitigating unwanted toxicities associated with CDDP. Potential strategies for mitigating CDDP toxicities include competing with the uptake of CDDP by hOCT2 or inhibiting hOCT2 activity through rapid regulation mediated by specific signaling pathways. This study investigated the interaction between the already approved cationic drugs disopyramide, imipramine, and orphenadrine with hOCT2 that is stably expressed in human embryonic kidney cells. Regarding disopyramide, its influence on CDDP cellular transport by hOCT2 was further characterized through inductively coupled plasma isotope dilution mass spectrometry. Additionally, its potential protective effects against cellular toxicity induced by CDDP were assessed using a cytotoxicity test. Given that hOCT2 is typically expressed in the basolateral membrane of polarized cells, with specific regulatory mechanisms, this work studied the regulation of hOCT2 that is stably expressed in Madin-Darby Canine Kidney (MDCK) cells. These cells were cultured in a matrix to induce the formation of cysts, exposing hOCT2 in the basolateral plasma membrane domain, which was freely accessible to experimental solutions. The study specifically tested the regulation of ASP+ uptake by hOCT2 in MDCK cysts through the inhibition of casein kinase II (CKII), calmodulin, or p56lck tyrosine kinase. Furthermore, the impact of this manipulation on the cellular toxicity induced by CDDP was examined using a cytotoxicity test. All three drugs-disopyramide, imipramine, and orphenadrine-demonstrated inhibition of ASP+ uptake, with IC50 values in the micromolar (µM) range. Notably, disopyramide produced a significant reduction in the CDDP cellular toxicity and platinum cellular accumulation when co-incubated with CDDP. The activity of hOCT2 in MDCK cysts experienced a significant down-regulation under inhibition of CKII, calmodulin, or p56lck tyrosine kinase. Interestingly, only the inhibition of p56lck tyrosine kinase demonstrated the capability to protect the cells against CDDP toxicity. In conclusion, certain interventions targeting hOCT2 have demonstrated the ability to reduce CDDP cytotoxicity, at least in vitro. Further investigations in in vivo systems are warranted to ascertain their potential applicability as co-treatments for mitigating undesired toxicities associated with CDDP in patients.