Pharmacological interaction and immune response of purinergic receptors in therapeutic modulation.

Nucleosides and purine nucleotides serve as transmitter and modulator agents that extend their functions beyond the cell. In this context, purinergic signaling plays a crucial role in regulating energy homeostasis and modulating metabolic alterations in tumor cells. Therefore, it is essential to consider the pharmacological targeting of purinergic receptors (PUR), which encompass the expression and inhibition of P1 receptors (metabotropic adenosine receptors) as well as P2 receptors (extracellular ATP/ADP) comprising P2X and P2Y receptors. Thus, the pharmacological interaction between inhibitors (such as RNA, monoclonal antibodies, and small molecules) and PUR represents a key aspect in facilitating the development of therapeutic interventions. Moreover, this review explores recent advancements in pharmacological inhibitors and the regulation of innate and adaptive immunity of PUR, specifically in relation to immunological and inflammatory responses. These responses encompass the release of pro-inflammatory cytokines (PIC), the production of reactive oxygen and nitrogen species (ROS and RNS), the regulation of T cells, and the activation of inflammasomes in all human leukocytes.

Natural killer cell-derived exosomes for cancer immunotherapy: innovative therapeutics art.

Chimeric antigen receptor natural killer cells (CAR-NK) promote off-the-shelf cellular therapy for solid tumors and malignancy.However,, the development of CAR-NK is due to their immune surveillance uncertainty and cytotoxicity challenge was restricted. Natural killer cell-derived exosome (NK-Exo) combine crucial targeted cellular therapies of NK cell therapies with unique non-toxic Exo as a self-origin shuttle against cancer immunotherapy. This review study covers cytokines, adoptive (autologous and allogenic) NK immunotherapy, stimulatory and regulatory functions, and cell-free derivatives from NK cells. The future path of NK-Exo cytotoxicity and anti-tumor activity with considering non-caspase-independent/dependent apoptosis and Fas/FasL pathway in cancer immunotherapy. Finally, the significance and implication of NK-Exo therapeutics through combination therapy and the development of emerging approaches for the purification and delivery NK-Exo to severe immune and tumor cells and tissues were discussed in detail.

Molecular investigation of Toxocara infection from the serum of people living with HIV in Alborz, Iran.

BACKGROUND: Toxocara infection is one of the most common neglected infections of poverty and a helminthiasis of global importance. Traditional diagnostic methods such as antibodies detection in serum samples are limited due to cross-reactivity and poor sensitivity. The use of molecular base methods for diagnosis of Toxocara infection in Iran has not been fully explored. The purpose of the current study was to estimate the prevalence of Toxocara infection from serum samples of people living with HIV in Alborz province, Iran using serological and molecular methods. METHODS: Blood samples were collected from 105 people living with HIV. Epidemiological data of participant were obtained through a structured questionnaire to investigate the risk factors. Patients CD4+ T cell count were recorded. Anti-Toxocara IgG antibodies were detected by ELISA, with a cut-off point of 11. PCR was performed to detect genetic material of Toxocara species in the serum samples. RESULTS: The mean CD4+ count in HIV-infected individuals with positive toxocariasis serology was 255.1 ± 21.6 cells/µL. Seropositivity for Toxocara species was observed in 12/105 (11.4%) people living with HIV. Three samples gave positive results on PCR analysis. Based on the data, a statistically significant relationship was found between anti-Toxocara IgG antibodies seropositivity and underlying conditions (p = 0.017). No significant statistical association was observed between seropositivity for Toxocara and gender, age, exposure to domestic animals or pet keeping, education levels, and occupation (p > 0.05). The findings of PCR confirmed Toxocara DNA in 3/12 (25.0%) serum samples. CONCLUSION: These findings demonstrated for the first time that people living with HIV from Alborz province, are being exposed to this zoonosis and a relatively high seroprevalence of Toxocara in HIV/AIDS people needs comprehensive health education regarding personal hygiene and how to avoid exposure to this parasite infection, especially in people with an impaired immune system.

Well-being and relative deprivation in a digital era.

Social unrest is a feature of the early 21st century, yet relatively little research binds theoretical aspects with empirical validation of the drivers of protests and revolutions. This study aims to empirically validate the Davies J-Curve considering the digital era, with economic, social, and political factors. Using big data techniques, network analysis, and theoretical analysis, we analyzed countries' similarities by analyzing Human Development Index (HDI) and Worldwide Governance Indicator (WGI) as proxies of social well-being. Results established the existence of a J-Curve during social crises in countries prior to an occurrence of large-scale social unrest. In addition, our results suggest that HDI was not a sufficient indicator regarding countries' experienced well-being, likely because it is missing the highly granular aspects of daily life. We further recommended that other indicators from political and psychological areas should be considered and treated in the data preparation phase for future society-wide well-being research for a more realistic baseline.

Larva migrans in BALB/c mice experimentally infected with Toxocara cati ensured by PCR assay.

BACKGROUND: Toxocara cati, the cat roundworm, is a parasitic nematode that known to cause toxocariasis in intermediate hosts and humans. In this study, we characterized the dynamics of T. cati larvae migration in BALB/c mice after inoculation with eggs and ensured the migration detecting the larval DNA by a PCR. To evaluate the dynamics of larval migration and distribution, twenty-four BALB/c mice were orally inoculated with 2500 T. cati infective eggs and the visceral organs of the infected animals were examined by pepsin digestion and microscopic parasite counts, followed by PCR at day 1 to 28 post-inoculation. RESULTS: The PCR assays were successfully used for detection of T. cati larvae in tissue samples and T. cati larvae and the DNAs were found in the liver, lungs, heart, kidneys and the brain. We detected T. cati in 92.2% of tissue samples by PCR, 30% higher than the conventional pepsin digestion technique. CONCLUSION: Our findings demonstrated that the PCR assay is a sensitive and specific for the detection of T. cati larvae. Therefore, it could become a useful tool for the investigation of the dynamics of larval migration and Toxocara infection in murine model.

A proposed framework for holding intensive 3Rs workshops in laboratory animal science.

Principles of 3Rs are the backbone of today's animal research. Applying 3Rs in practice requires proper education and training. Although this could be achieved via long-term courses ranging from several weeks to years, in some circumstances a short-term course may be the only viable option. In this paper we define scientific and ethical objectives for running short-term 3Rs workshops. To meet these objectives, we propose a 2-day workshop curriculum and an ethical framework. The curriculum comprises theoretical and practical sessions and covers Replacement, Reduction, and Refinement strategies. The ethical framework defines the responsibilities of lecturers and attendees, and proposes the animals and facilities requirements to run the proposed workshop curriculum. The attendees will be assessed at the end of the workshop and they receive certificates for working under supervision until they are deemed competent at their intended functions. The proposed curriculum and framework are not subscriptive, instead they share the experience gained through running more than 60 laboratory animal 3Rs workshops.

Nanoparticle-mediated synergistic chemoimmunotherapy for tailoring cancer therapy: recent advances and perspectives.

Nowadays, a potent challenge in cancer treatment is considered the lack of efficacious strategy, which has not been able to significantly reduce mortality. Chemoimmunotherapy (CIT) as a promising approach in both for the first-line and relapsed therapy demonstrated particular benefit from two key gating strategies, including chemotherapy and immunotherapy to cancer therapy; therefore, the discernment of their participation and role of potential synergies in CIT approach is determinant. In this study, in addition to balancing the pros and cons of CIT with the challenges of each of two main strategies, the recent advances in the cancer CIT have been discussed. Additionally, immunotherapeutic strategies and the immunomodulation effect induced by chemotherapy, which boosts CIT have been brought up. Finally, harnessing and development of the nanoparticles, which mediated CIT have expatiated in detail.

Zinc oxide-gold nanocomposite as a proper platform for label-free DNA biosensor.

In this study, a simple and cost-effective electrochemical DNA biosensor was developed for sensitive detection of mycobacterium tuberculosis (TB). Nanocomposite of zinc oxide (ZnO) and gold nanoparticles (AuNPs) was used as a platform for immobilizing thiolated TB DNA (probe DNA). ZnO was electrodeposited on a glassy carbon electrode by potentiostat electrolysis of Zn (NO3)2 solution at -1.0 V (vs. Ag/AgCl), then AuNPs were loaded as the second layer at -0.4 V from HAuCl4 solution. Thiolated probe DNA was then covalently attached to AuNPs. Anodic peak current of Fe (CN)63-/4- was followed in hybridization experiments and a linear calibration curve was obtained in concentration range of 2.5-250 pM and limit of detection (LOD) of 1.8 pM for target DNA. The label-free TB biosensor exhibited high selectivity, suitable stability, and reproducibility.

Application of metal-organic framework as redox probe in an electrochemical aptasensor for sensitive detection of MUC1.

In this work, an electrochemical aptasensor was developed for sensitive detection of MUC1 based on metal-organic framework-reduced graphene oxide nanocomposite (Cu-MOF-RGO). Cu- MOF-RGO appeared to be suitable as a platform for immobilization of MUC1 aptamer, and also as an electrochemical probe, which exhibited well-defined peaks with good stability and reproducibility. Cu-MOF-graphene oxide (Cu-MOF-GO) nanocomposite was prepared and cast on the electrode surface, then in order to increase the conductivity of the electrode, GO was electrochemically reduced to RGO. In the presence of MUC1, the peak current of Cu in the nanocomposite decreased, which could be explained based on the formation of MUC1-aptamer complexes on the electrode, and consequence blocking the electron transfer of Cu at the electrode surface. Under optimum experimental conditions, a linear calibration curve was obtained by differential pulse voltammetry in the concentration range of 0.1 pM-10 nM (25 pg mL-1 - 2500 ng mL-1) with a limit of detection (LOD) of 0.033 pM (7.5 pg mL-1) of MUC1. The proposed aptasensor offers acceptable selectivity, stability, and reproducibility in the determination of MUC1 spiked to human blood serum samples.

A review on nanomaterial-based electrochemical, optical, photoacoustic and magnetoelastic methods for determination of uranyl cation.

This review (with 177 refs) gives an overview on nanomaterial-based methods for the determination of uranyl ion (UO22+) by different types of transducers. Following an introduction into the field, a first large section covers the fundamentals of selective recognition of uranyl ion by receptors such as antibodies, aptamers, DNAzymes, peptides, microorganisms, organic ionophores (such as salophens, catechols, phenanthrolines, annulenes, benzo-substituted macrocyclic diamides, organophosphorus receptors, calixarenes, crown ethers, cryptands and ß-diketones), by ion imprinted polymers, and by functionalized nanomaterials. A second large section covers the various kinds of nanomaterials (NMs) used, specifically on NMs for electrochemical signal amplification, on NMs acting as signal tags or carriers for signal tags, on fluorescent NMs, on NMs for colorimetric assays, on light scattering NMs, on NMs for surface enhanced Raman scattering (SERS)-based assays and wireless magnetoelastic detection systems. We then discuss detection strategies, with subsections on electrochemical methods (including ion-selective and potentiometric systems, voltammetric systems and impedimetric systems). Further sections treat colorimetric, fluorometric, resonance light scattering-based, SERS-based and photoacoustic methods, and wireless magnetoelastic detection. The current state of the art is summarized, and current challenges are discussed at the end. Graphical abstract An overview is given on nanomaterial-based methods for the detection of uranyl ion by different types of transducers (such as electrochemical, optical, photoacoustic, magnetoelastic, etc) along with a critical discussion of their limitations, benefits and application to real samples.

Multiple Mechanisms Increase Levels of Resistance in Rapistrum rugosum to ALS Herbicides.

Rapistrum rugosum (turnip weed) is a common weed of wheat fields in Iran, which is most often controlled by tribenuron-methyl (TM), a sulfonylurea (SU) belonging to the acetolactate synthase (ALS) inhibiting herbicides group. Several cases of unexplained control failure of R. rugosum by TM have been seen, especially in Golestan province-Iran. Hence, there is lack of research in evaluation of the level of resistance of the R. rugosum populations to TM, using whole plant dose-response and enzyme assays, then investigating some potential resistance mechanisms Results revealed that the resistance factor (RF) for resistant (R) populations was 2.5-6.6 fold higher than susceptible (S) plant. Neither foliar retention, nor (14)C-TM absorption and translocation were the mechanisms responsible for resistance in turnip weed. Metabolism of TM was the second resistant mechanism in two populations (Ag-R5 and G-1), in which three metabolites were found. The concentration of TM for 50% inhibition of ALS enzyme activity in vitro showed a high level of resistance to the herbicide (RFs were from 28 to 38) and cross-resistance to sulfonyl-aminocarbonyl-triazolinone (SCT), pyrimidinyl-thiobenzoate (PTB) and triazolopyrimidine (TP), with no cross-resistance to imidazolinone (IMI). Substitution Pro 197 to Ser 197 provided resistance to four of five ALS-inhibiting herbicides including SU, TP, PTB, and SCT with no resistance to IMI. These results documented the first case of R. rugosum resistant population worldwide and demonstrated that both RST and NRST mechanisms are involved to the resistance level to TM.

Fast Electrocatalytic Determination of Methimazole at an Activated Glassy Carbon Electrode.

A fast and simple voltammetric method for the determination of methimazole in pharmaceutical products was reported. A glassy carbon electrode was pretreated by anodization at +1.75 V (vs. SCE) for 5 min, followed by potential cycling in the range of 0.3-1.3 V (20 cycles). The pretreated electrode showed an excellent electrocatalytic effect on the oxidation of methimazole. Compared with untreated electrode, a large decrease (~300 mV) in the oxidation peak of methimazole was observed. The oxidation peak current at the new potential (0.4 V vs. SCE) was linearly dependent on the concentration of methimazole in the range of 7.0 - 130 µM with a detection limit of 3.7 µM (S/N = 3). The method was successfully used in the determination of methimazole in thyramozol tablets. Due to the simple and fast electrode preparation, there is no need for electrode cleaning or storage.