Spermatozoa Transcriptional Response and Alterations in PL Proteins Properties after Exposure of Mytilus galloprovincialis to Mercury

Mercury (Hg) is an environmental pollutant that impacts human and ecosystem health. In our previous works, we reported alterations in the properties of Mytilus galloprovincialis protamine-like (PL) proteins after 24 h of exposure to subtoxic doses of toxic metals such as copper and cadmium. The present work aims to assess the effects of 24 h of exposure to 1, 10, and 100 pM HgCl₂ on spermatozoa and PL proteins of Mytilus galloprovincialis. Inductively coupled plasma–mass spectrometry indicated accumulation of this metal in the gonads of exposed mussels. Further, RT-qPCR analyses showed altered expression levels of spermatozoa mt10 and hsp70 genes. In Mytilus galloprovincialis, PL proteins represent the major basic component of sperm chromatin. These proteins, following exposure of mussels to HgCl₂, appeared, by SDS-PAGE, partly as aggregates and showed a decreased DNA-binding capacity that rendered them unable to prevent DNA damage, in the presence of CuCl₂ and H₂O₂. These results demonstrate that even these doses of HgCl₂ exposure could affect the properties of PL proteins and result in adverse effects on the reproductive system of this organism. These analyses could be useful in developing rapid and efficient chromatin-based genotoxicity assays for pollution biomonitoring programs.     

Mechanisms of Reciprocal Regulation of Gonadotropin-Releasing Hormone (GnRH)-Producing and Immune Systems: The Role of GnRH,Cytokines and Their Receptors in Early Ontogenesis in Normal and Pathological Conditions

Different aspects of the reciprocal regulatory influence on the development of gonadotropin-releasing hormone (GnRH)-producing- and immune systems in the perinatal ontogenesis and their functioning in adults in normal and pathological conditions are discussed. The influence of GnRH on the development of the immune system, on the one hand, and the influence of proinflammatory cytokines on the development of the hypothalamic-pituitary-gonadal system, on the other hand, and their functioning in adult offspring are analyzed. We have focused on the effects of GnRH on the formation and functional activity of the thymus, as the central organ of the immune system, in the perinatal period. The main mechanisms of reciprocal regulation of these systems are discussed. The reproductive health of an individual is programmed by the establishment and development of physiological systems during critical periods. Regulatory epigenetic mechanisms of development are not strictly genetically controlled. These processes are characterized by a high sensitivity to various regulatory factors, which provides possible corrections for disorders.     

The Multifaceted Mas-Related G Protein-Coupled Receptor Member X2 in Allergic Diseases and Beyond

Recent research on mast cell biology has turned its focus on MRGPRX2, a new member of the Mas-related G protein-coupled subfamily of receptors (Mrgprs), originally described in nociceptive neurons of the dorsal root ganglia. MRGPRX2, a member of this group, is present not only in neurons but also in mast cells (MCs), specifically, and potentially in other cells of the immune system, such as basophils and eosinophils. As emerging new functions for this receptor are studied, a variety of both natural and pharmacologic ligands are being uncovered, linked to the ability to induce receptor-mediated MC activation and degranulation. The diversity of these ligands, characterized in their human, mice, or rat homologues, seems to match that of the receptor’s interactions. Natural ligands include host defense peptides, basic molecules, and key neuropeptides such as substance P and vasointestinal peptide (known for their role in the transmission of pain and itch) as well as eosinophil granule-derived proteins. Exogenous ligands include MC secretagogues such as compound 48/80 and mastoparan, a component of bee wasp venom, and several peptidergic drugs, among which are members of the quinolone family, neuromuscular blocking agents, morphine, and vancomycin. These discoveries shed light on its capacity as a multifaceted participant in naturally occurring responses within immunity and neural stimulus perception, as in responses at the center of immune pathology. In host defense, the mice Mrgprb2 has been proven to aid mast cells in the detection of peptidic molecules from bacteria and in the release of peptides with antimicrobial activities and other immune mediators. There are several potential actions described for it in tissue homeostasis and repair. In the realm of pathologic response, there is evidence to suggest that this receptor is also involved in chronic inflammation. Furthermore, MRGPRX2 has been linked to the pathophysiology of non-IgE-mediated immediate hypersensitivity drug reactions. Different studies have shown its possible role in other allergic diseases as well, such as asthma, atopic dermatitis, contact dermatitis, and chronic spontaneous urticaria. In this review, we sought to cover its function in physiologic processes and responses, as well as in allergic and nonallergic immune disease.     

Discovery of New Antiproliferative Imidazopyrazole Acylhydrazones Able To Interact with Microtubule Systems

Even though immunotherapy has radically changed the search for anticancer therapies, there are still many different pathways that are open to intervention with traditional small molecules. To expand our investigation in the anticancer field, we report here a new series of compounds in which our previous pyrazole and imidazopyrazole scaffolds are linked to a differently decorated phenyl ring through an acylhydrazone linker. Preliminary tests on the library were performed at the National Cancer Institute (USA) against the full NCI 60 cell panel. The best compounds among the imidazopyrazole series were then tested by immunofluorescence staining for their inhibition of cell proliferation, apoptosis induction, and their effect on the cell cycle and on microtubules. Two compounds, in particular 4-benzyloxy-3-methoxybenzyliden imidazopyrazole-7-carbohydrazide showed good growth inhibition, with IC₅₀ values in the low-micromolar range, and induced apoptosis. Both compounds altered the cell-cycle phases with the appearance of polyploid cells. Immunofluorescence analysis evidenced microtubules alterations; tubulin polymerization assays and docking studies suggested the tubulin system to be the possible, although not exclusive, target of the new acylhydrazone series reported here.     

Use of an Online Extraction Technique Coupled to Liquid Chromatography for Determination of Caffeine in Coffee,Tea, and Cocoa

Caffeine is the most widely studied psychoactive molecule in history due to its many pharmacological activities and a high number of biological and physiological effects. In literature, there is a great number of applications that describe extraction, identification, and quantification of caffeine in foods and beverages. For this purpose, an extraction step is followed by an analytical technique for the identification and quantification of caffeine. This work proposes an innovative method in which sample preparation, separation, and detection steps are unified in a single step. To the best of our knowledge, this is the first report on the determination of caffeine in coffee, tea, and cocoa by means of an online extraction coupled to a liquid chromatographic system equipped with a photodiode array detector. The developed methodology was validated in terms of sensitivity, detection limits, accuracy, and precision. The advantages of this technique are (i) a significant reduction of analysis time (more than 70%) and of solvents used (the extraction step is integrated in the chromatographic analysis), (ii) the whole procedure is thus completely automated drastically reducing possible operator errors to occur, and (iii) easily realized by using a conventional monodimensional liquid chromatography system.     

搭载人类自体干细胞的纤维支架及其在软组织再生中的应用

文章介绍了搭载人类自体干细胞的纤维支架技术及其在软组织再生中的应用优势。选用藻酸盐材料结合人体干细胞搭载关键技术制成的纤维支架,同时具有促进血管再生和触发成脂分化的能力。     

Development of green extraction process to produce antioxidant-rich extracts from purple coneflower

The present study was conducted to develop subcritical water extraction (SWE) of Echinacea purpurea flowers. The influence of temperature and extraction time on quality of extracts considering total phenols content, total flavonoids content, antioxidant capacity and extraction yield, was determined. Optimized extraction parameters for maximised investigated responses were as follows: 147.56 °C and 8.43 min. The experimental values agreed with the values predicted, thus indicating the adequacy of central composite experimental design for modelling the SWE of bioactive compounds from E. purpurea. Results of the study also highlighted the potential application of E. purpurea subcritical water extracts as a source of valuable bioactive compounds.     

New water-soluble copolymers of 2-methacryloyloxyethyl phosphorylcholine for surface modification

New copolymers of 2-methacryloyloxyethyl phosphorylcholine with 2-Deoxy-2-methacrylamido-D-glucose, N-vinylpyrrolidone, and N-vinyl-N-methylacetamide were synthesized and characterized; the obtained copolymers contained 10–50 mol% of phosphorylcholine moieties, and their molecular masses ranged from 1.05 × 10⁵ to 4.40 × 10⁵. Reactivity ratios of the monomers were estimated. Conformational states of the copolymers in aqueous solutions were studied. The synthesized copolymer was grafted onto the surface of carbon fiber biosorbent using γ-radiation.