Notes

The outcome in the COVID-19 lockdown about medication support provision within Eu jails.
Ranitidine drug products were recently recalled because they contained carcinogenic nitrosamines (NAs), such as N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA). This episode emphasises the importance of developing analytical methods to determine NAs in this type of product. This study describes the development and validation of an analytical method for the determination of nine NAs (NDMA, N-nitrosomethylethylamine (NEMA), NDEA, N-nitrosopyrrolidine (NPYR), N-nitrosomorpholine (NMOR) N-nitrosodi-n-propylamine (NDPA) N-nitrosopiperidine (NPIP), N-nitrosodi-n-butylamine (NDBA) and N-nitrosodiphenylamine (NDPhA)) in ranitidine drug samples using a combination of microextraction and gas chromatography-mass spectrometry. The procedure involved the dissolution of 1 g of sample in 10 mL of water. For the dispersive liquid-liquid microextraction, 0.5 g of NaCl was added to this aqueous solution, followed by a mixture containing 0.5 mL methanol as dispersant and 150 μL chloroform as extractant solvent. The recovered organic phase was injected into the GC-MS system and a 20 min oven programme was applied. Quantification limits were in the 0.21-21 ng g-1 range, corresponding the lower limit to NDPhA and the higher to NDMA. Relative standard deviations lower than 12% were achieved in all cases, which indicates the adequate precision of the method. Seven pharmaceutical products containing two different amounts of ranitidine (150 and 300 mg) were analysed. None of the samples contained NEMA, NDEA, NPYR, NMOR, NDPA or NPIP, while NDMA, NDBA and NDPhA were found in three products.The photoacoustic detection of ozone using the Chappuis band is demonstrated. A visible red laser diode emitting at 638 nm was employed as a light source. The photoacoustic cell consisted of a conventional resonance tube with a MEMS (microelectromechanical systems) microphone placed outside an opening along the tube. A calibration curve for the range from 33 ppmV to 215 ppmV was found to be highly linear with a coefficient of determination (r2) of 0.9999, when allowing for different measurement frequencies to account for shifts in the speed of sound due to changes in the gas matrix. The limit of detection was found to be 1.6 ppmV for an optical power of the laser diode of about 130 mW.The preparation of gold nanoparticles via green routes applying plant extracts as the reducing agents and stabilizers has received broad interest in the last decades. Plant-gold nanoparticles have been well-developed and applied in biochemical and medical research, but there are still challenges that must be overcome. The main challenges include the construction of chemically-robust plant-gold nanoparticles, the precise design of biomimetic surfaces to fabricate nanozymes with high catalytic activities, and the development of approaches to construct biosensors with high selectivities and sensitivities. The cores and surfaces of plant-gold nanoparticles must be considered, as well as their catalytic activities and biosensing mechanisms. This review highlights the latest achievements in plant-gold nanoparticle preparation, heterogeneous nucleation, and surface functionalization, while also focusing on their optical properties and various biological and catalytic activities. Moreover, their antioxidant and cell apoptosis mechanisms, and biological activities are described. Plant-gold nanoparticles have shown great potential in high-performance analytical assays, high-activity catalysts, effective intracellular imaging, and clinical treatment.The ability to read, write, and edit genomic information in living organisms can have a profound impact on research, health, economic, and environmental issues. The CRISPR/Cas system, recently discovered as an adaptive immune system in prokaryotes, has revolutionized the ease and throughput of genome editing in mammalian cells and has proved itself indispensable to the engineering of immune cells and identification of novel immune mechanisms. In this review, we summarize the CRISPR/ Cas9 system and the history of its discovery and optimization. We then focus on engineering T cells and other types of immune cells, with emphasis on therapeutic applications. Last, we describe the different modifications of Cas9 and their recent applications in the genome-wide screening of immune cells. [BMB Reports 2021; 54(1) 59-69].In the last decade, we have witnessed an unprecedented clinical success in cancer immunotherapies targeting the programmed cell-death ligand 1 (PD-L1) and programmed cell-death 1 (PD-1) pathway. Besides the fact that PD-L1 plays a key role in immune regulation in tumor microenvironment, recently a plethora of reports has suggested a new perspective of non-immunological functions of PD-L1 in the regulation of cancer intrinsic activities including mesenchymal transition, glucose and lipid metabolism, stemness, and autophagy. Here we review the current understanding on the regulation of expression and intrinsic protumoral activity of cancer-intrinsic PD-L1. [BMB Reports 2021; 54(1) 12-20].Breast cancer is one of the most frequently diagnosed cancers. Although biomarkers are continuously being discovered, few specific markers, rather than classification markers, representing the aggressiveness and invasiveness of breast cancer are known. In this study, we used samples from canine mammary tumors in a comparative approach. We subjected 36 fractions of both canine normal and mammary tumor plasmas to highperformance quantitative proteomics analysis. Among the identified proteins, LCAT was selectively expressed in mixed tumor samples. With further MRM and Western blot validation, we discovered that the LCAT protein is an indicator of aggressive mammary tumors, an advanced stage of cancer, possibly highly metastatic. Interestingly, we also found that LCAT is overexpressed in high-grade and lymph-node-positive breast cancer in silico data. We also demonstrated that LCAT is highly expressed in the sera of advanced-stage human breast cancers within the same classification. In conclusion, we identified a possible common plasma protein biomarker, LCAT, that is highly expressed in aggressive human breast cancer and canine mammary tumor. [BMB Reports 2020; 53(12) 664-669].The well-known second messenger cyclic adenosine monophosphate (cAMP) regulates the morphology and physiology of neurons and thus higher cognitive brain functions. The discovery of exchange protein activated by cAMP (Epac) as a guanine nucleotide exchange factor for Rap GTPases has shed light on protein kinase A (PKA)-independent functions of cAMP signaling in neural tissues. Studies of cAMP-Epac-mediated signaling in neurons under normal and disease conditions also revealed its diverse contributions to neurodevelopment, synaptic remodeling, and neurotransmitter release, as well as learning, memory, and emotion. In this mini-review, the various roles of Epac isoforms, including Epac1 and Epac2, highly expressed in neural tissues are summarized, and controversies or issues are highlighted that need to be resolved to uncover the critical functions of Epac in neural tissues and the potential for a new therapeutic target of mental disorders. [BMB Reports 2021; 54(3) 149-156].Antibody-based therapeutics targeting the inhibitory receptors PD-1, PD-L1, or CTLA-4 have shown remarkable clinical progress on several cancers. However, most patients do not benefit from these therapies. Thus, many efforts are being made to identify new immune checkpoint receptor-ligand pathways that are alternative targets for cancer immunotherapies. Nectin and nectin-like molecules are widely expressed on several types of tumor cells and play regulatory roles in T- and NK-cell functions. TIGIT, CD226, CD96 and CD112R on lymphoid cells are a group of immunoglobulin superfamily receptors that interact with Nectin and nectin-like molecules with different affinities. These receptors transmit activating or inhibitory signals upon binding their cognate ligands to the immune cells. The integrated signals formed by their complex interactions contribute to regulating immune-cell functions. Several clinical trials are currently evaluating the efficacy of anti-TIGIT and anti-CD112R blockades for treating patients with solid tumors. However, many questions still need to be answered in order to fully understand the dynamics and functions of these receptor networks. This review addresses the rationale behind targeting TIGIT, CD226, CD96, and CD112R to regulate T- and NK-cell functions and discusses their potential application in cancer immunotherapy. [BMB Reports 2021; 54(1) 2-11].Dendritic cells (DC), which consist of several different subsets, specialize in antigen presentation and are critical for mediating the innate and adaptive immune responses. DC subsets can be classified into conventional, plasmacytoid, and monocyte-derived DC in the tumor microenvironment, and each subset plays a different role. Because of the role of intratumoral DCs in initiating antitumor immune responses with tumor-derived antigen presentation to T cells, DCs have been targeted in the treatment of cancer. By regulating the functionality of DCs, several DCbased immunotherapies have been developed, including administration of tumor-derived antigens and DC vaccines. In addition, DCs participate in the mechanisms of classical cancer therapies, such as radiation therapy and chemotherapy. Thus, regulating DCs is also important in improving current cancer therapies. Here, we will discuss the role of each DC subset in antitumor immune responses, and the current status of DC-related cancer therapies. [BMB Reports 2021; 54(1) 31-43].The clustered regularly interspaced short palindromic repeats (CRISPR) system is a family of DNA sequences originally discovered as a type of acquired immunity in prokaryotes such as bacteria and archaea. In many CRISPR systems, the functional ribonucleoproteins (RNPs) are composed of CRISPR protein and guide RNAs. They selectively bind and cleave specific target DNAs or RNAs, based on sequences complementary to the guide RNA. The specific targeted cleavage of the nucleic acids by CRISPR has been broadly utilized in genome editing methods. In the process of genome editing of eukaryotic cells, CRISPRmediated DNA double-strand breaks (DSB) at specific genomic loci activate the endogenous DNA repair systems and induce mutations at the target sites with high efficiencies. Two of the major endogenous DNA repair machineries are non-homologous end joining (NHEJ) and homology-directed repair (HDR). In case of DSB, the two repair pathways operate in competition, resulting in several possible outcomes including deletions, insertions, and substitutions. O6-Benzylguanine cost Due to the inherent stochasticity of DSB-based genome editing methods, it was difficult to achieve defined single-base changes without unanticipated random mutation patterns. In order to overcome the heterogeneity in DSB-mediated genome editing, novel methods have been developed to incorporate precise single-base level changes without inducing DSB. The approaches utilized catalytically compromised CRISPR in conjunction with base-modifying enzymes and DNA polymerases, to accomplish highly efficient and precise genome editing of single and multiple bases. In this review, we introduce some of the advances in single-base level CRISPR genome editing methods and their applications. [BMB Reports 2021; 54(2) 98-105].
Read More: https://www.selleckchem.com/products/o6-benzylguanine.html