Neural glymphatic system: Clinical implications and potential importance of melatonin

The central nervous system was thought to lack a lymphatic drainage until the recent discovery of the neural glymphatic system. This highly specialized waste disposal network includes classical lymphatic vessels in the dura that absorb fluid and metabolic by-products and debris from the underlying cerebrospinal fluid (CSF) in the subarachnoid space. The subarachnoid space is continuous with the Virchow-Robin peri-arterial and peri-vascular spaces which surround the arteries and veins that penetrate into the neural tissue, respectively. The dural lymphatic vessels exit the cranial vault via an anterior and a posterior route and eventually drain into the deep cervical lymph nodes. Aided by the presence of aquaporin 4 on the perivascular endfeet of astrocytes, nutrients and other molecules enter the brain from peri-arterial spaces and form interstitial fluid (ISF) that baths neurons and glia before being released into peri-venous spaces. Melatonin, a pineal-derived secretory product which is in much higher concentration in the CSF than in the blood, is believed to follow this route and to clear waste products such as amyloid-β from the interstitial space. The clearance of amyloid-β reportedly occurs especially during slow wave sleep which happens concurrently with highest CSF levels of melatonin. Experimentally, exogenously-administered melatonin defers amyloid-β buildup in the brain of animals and causes its accumulation in the cervical lymph nodes. Clinically, with increased age CSF melatonin levels decrease markedly, co-incident with neurodegeneration and dementia. Collectively, these findings suggest a potential association between the loss of melatonin, decreased glymphatic drainage and neurocognitive decline in the elderly.

Avian Reproduction

There are about 10,400 living avian species belonging to the class Aves, characterized by feathers which no other animal classes possess and are warm-blooded vertebrates with four-chamber heart. They have excellent vision, and their forelimbs are modified into wings for flight or swimming, though not all can fly or swim. They lay hard-shelled eggs which are a secretory product of the reproductive system that vary greatly in colour, shape and size, and the bigger the bird, the bigger the egg. Since domestication, avian species have been basically reared for eggs, meat, pleasure and research. They reproduce sexually with the spermatozoa being homogametic and carry Z-bearing chromosomes, and the blastodisk carries either Z-bearing or W-bearing chromosomes, hence, the female is heterogametic, and thus, determines the sex of the offspring. The paired testes produce spermatozoa, sex hormones and the single ovary (with a few exceptions) produces yolk bearing the blastodisk and sex hormones. Both testis and ovary are the primary sex organs involved in sexual characteristics development in avian. In avian reproduction, there must be mating for fertile egg that must be incubated to produce the young ones. At hatch, hatchling sex is identified and reared to meet the aim of the farmer.

Benzaldehyde Attenuates the Fifth Stage Larval Excretory-Secretory Product of Angiostrongylus cantonensis-Induced Injury in Mouse Astrocytes via Regulation of Endoplasmic Reticulum Stress and Oxidative Stress

Excretory-secretory products (ESPs) are the main research targets for investigating the hosts and helminths interaction. Parasitic worms can migrate to parasitic sites and avoid the host immune response by secreting this product. Angiostrongylus cantonensisis an important food-borne zoonotic parasite that causes severe neuropathological damage and symptoms, including eosinophilic meningitis or meningoencephalitis in humans. Benzaldehydes are organic compounds composed of a benzene ring and formyl substituents. This compound has anti-inflammatory and antioxidation properties. Previous studies showed that 3-hydroxybenzaldehyde (3-HBA) and 4-hydroxybenzaldehyde (4-HBA) can reduce apoptosis in A. cantonensis ESPs treated astrocytes. These results on the protective effect underlying benzaldehyde have primarily focused on cell survival. The study was designed to investigate the molecular mechanisms of endoplasmic reticulum stress (ER stress) and oxidative stress in astrocytes in A. cantonensis ESPs treated astrocytes and to evaluate the therapeutic consequent of 3-HBA and 4-HBA. First, we initially established the RNA-seq dataset in each group, including Normal, ESPs, ESPs+3-HBA, and ESPs+4-HBA. We also found that benzaldehyde (3-HBA and 4-HBA) can stimulate astrocytes to express ER stress-related molecules after ESP treatment. The level of oxidative stress could also be decreased in astrocytes by elevating antioxidant activity and reducing ROS generation. These results suggested that benzaldehyde may be a potential therapeutic compound for human angiostrongyliasis to support brain cell survival by inducing the expression levels of ER stress- and oxidative stress-related pathway.

Haemonchus contortus Transthyretin-Like Protein TTR-31 Plays Roles in Post-Embryonic Larval Development and Potentially Apoptosis of Germ Cells

Transthyretin (TTR)-like proteins play multi-function roles in nematode and are important component of excretory/secretory product in Haemonchus contortus. In this study, we functionally characterised a secretory transthyretin-like protein in the barber’s pole worm H. contortus. A full-length of transthyretin-like protein-coding gene (Hc-ttr-31) was identified in this parasitic nematode, representing a counterpart of Ce-ttr-31 in Caenorhabditis elegans. High transcriptional levels of Hc-ttr-31 were detected in the egg and early larval stages of H. contortus, with the lowest level measured in the adult stage, indicating a decreased transcriptional pattern of this gene during nematode development. Localisation analysis indicated a secretion of TTR-31 from the intestine to the gonad, suggesting additional roles of Hc-ttr-31 in nematode reproduction. Expression of Hc-ttr-31 and Ce-ttr-31 in C. elegans did not show marked influence on the nematode development and reproduction, whereas Hc-ttr-31 RNA interference-mediated gene knockdown of Ce-ttr-31 shortened the lifespan, decreased the brood size, slowed the pumping rate and inhibited the growth of treated worms. Particularly, gene knockdown of Hc-ttr-31 in C. elegans was linked to activated apoptosis signalling pathway, increased general reactive oxygen species (ROS) level, apoptotic germ cells and facultative vivipary phenotype, as well as suppressed germ cell removal signalling pathways. Taken together, Hc-ttr-31 appears to play roles in regulating post-embryonic larval development, and potentially in protecting gonad from oxidative stress and mediating engulfment of apoptotic germ cells. A better knowledge of these aspects should contribute to a better understanding of the developmental biology of H. contortus and a discovery of potential targets against this and related parasitic worms.

Comparison of Ambrosia L. Pollen Seasons in Lublin (Poland) and Ivano-Frankivsk (Ukraine) and Presentation of the Morphotypes of Trichomes on A. artemisiifolia L. Shoots in Terms of the Allergenic Properties of the Plant

Ambrosia pollen contains strong allergens. Allergic reactions can also be caused by direct contact with the plant. The investigations of the dynamics of Ambrosia pollen seasons were conducted in Lublin (Poland) and Ivano-Frankivsk (Ukraine) in 2013–2015. The onset and end of the seasons, maximum concentrations, annual sums, and the number of days with an allergy risk were determined. Additionally, the types of trichomes present on different parts of Ambrosia artemisiifolia L. shoots were determined using light microscopy. Morphometric studies were carried out on trichomes sampled from staminate inflorescences. The maximum concentrations and annual sums of Ambrosia pollen were shown to be substantially higher in Ivano-Frankivsk than in Lublin. Similarly, the risk of allergies is higher in the study site in Ukraine. The study results indicate that the presence of Ambrosia pollen grains in Lublin may be associated with long-distance transport. The presence of non-glandular and glandular trichomes was found on the examined organs. The staminate inflorescences were covered by two types of non-glandular trichomes (short and long) and two types of glandular trichomes (linear and biseriate), whose secretory product can cause dermatitis in sensitive subjects upon contact with the plant.

Trichinella spiralis ESP inhibits tumor cell growth by regulating the immune response and inducing apoptosis

Background Although Trichinella spiralis (T. spiralis) causes zoonotic diseases, it has a strong immunomodulatory effect and has therapeutic potential for various autoimmune diseases and cancers. Our previous study results showed that T. spiralis infection can inhibit the growth of liver cancer cells, but the specific mechanism has not been elucidated. Methods BALB/c mice injected with H22 cells and then infected with T. spiralis were used to detect tumor inhibition rate. Cell proliferation and apoptosis of H22 cells treated with excretory-secretory product (ESP) were measured by Cell-Counting Kit 8 (CCK-8) and Flow Cytometry (FCM). The expression of apoptosis-related genes in H22 cells and tumor tissues was detected by western blotting and real-time quantitative PCR (qPCR). IL-2, IFN-γ and IL-4 production in the spleens were measured by qPCR and enzyme-linked immunosorbent assay(ELISA). Results The growth of tumors in tumor model mice infected with T. spiralis was significantly inhibited compared with those uninfected tumor model mice. ESP could inhibit H22 cell proliferation and induce apoptosis through the mitochondrial pathway both in vitro and in vivo. Additionally, the levels of Th1 cytokines with antitumor effects were significantly increased in the early stage of T. spiralis infection, while Th2 cytokines increased later than Th1 cytokines. Conclusions ESP can directly induce tumor cell apoptosis and indirectly inhibit tumor cell growth through the host immune system, which is the potential antitumor mechanism of T. spiralis infection.

Characteristics of species composition, biochemical and pathogenic nature of the microbiota of mammary gland and the reproductive tract in dairy cows

This research is dedicated to a relevant topic in veterinary medicine, which is connected with studying of specific features in systems that are responsible for productive and reproductive functioning in cattle. The reported study was funded by RFBR and Sverdlovsk region, project number 20-416-660004 «Molecular genetic and phenotypic characteristics of the microbiota in the reproductive system of cattle». Samples of secretory product of the mammary gland and cervical swabs of 81 cows and 5 dairy farms of Sverdlovsk region (Russia) were analyzed. A number of pathogenic and opportunistic microorganisms (S.aureus, S.lugdunensis, Streptococcus spp., Enterobacter spp., Enterococcus faecium, Enterococcus faecalis, Escherichia coli, Proteus vulgaris, Bacillus spp.)and mold fungi (Mucor spp., Penicillum spp., Aspergillus spp.) were isolated as a result of microbiological testing of the biological samples. The microbiota structure of the reproductive tract and the lacteal gland is demonstrated in physiologically normal state and during the inflammatory process. The phenotypic characteristic of isolated microorganisms, as well as evaluation of biochemical parameters and pathogenicity were indicated.

Review on Brain Decellularization Methods and their Applications for Tissue Engineering

Introduction: Tissue engineering by using decellularized tissues has been attracted attention of researchers in the regenerative medicine. Extra cellular matrix (ECM) is a secretory product of cells inside the tissues with supportive and regulatory function for homing cells. ECM contains glycosaminoglycans (GAGs) and fibrous proteins. Each particular tissue has its unique ECM, especially brain, because of its limited capacity for renovation, which is noticeable during aging and brain injuries. Recent studies reported that decellularized brain could provide necessary ECM for growth and survival of neurons. The main available decellularization techniques are based on physical, chemical and enzymatic approaches. Regarding the fragility of brain tissue, decellularization methods have been optimized to three methods: detergent, detergent enzymatic and physicochemical-enzymatic methods. Focusing on these methods, we performed this review to compare the efficacy and functionality of brain decellularization methods. Conclusion: The decellularized tissue of the brain contains a variety of glycoprotein components that can be used in the preparation of engineered scaffolds for the survival of nerve cells as well as in the preparation of brain organoids. Brain tissue decellularization has been much more successful with the methods that use the chemical solvents Triton X100, trypsin, and DNase in combination with freeze-thaw cycles and low-speed centrifuges.

Role of Adiponectin in the Pathogenesis of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic chronic inflammatory autoimmune joint disease, characterized by progressive articular damage and joint dysfunction. One of the symptoms of this disease is persistent inflammatory infiltration of the synovial membrane, the principle site of inflammation in RA. In the affected conditions, the cells of the synovial membrane, fibroblast-like synoviocytes and macrophage-like synovial cells, produce enzymes degrading cartilage and underlining bone tissue, as well as cytokines increasing the infiltration of immune cells. In patients with RA, higher levels of adiponectin are measured in the serum and synovial fluid. Adiponectin, a secretory product that is mainly white adipose tissue, is a multifunctional protein with dual anti-inflammatory and pro-inflammatory properties. Several studies underline the fact that adiponectin can play an important pro-inflammatory role in the pathophysiology of RA via stimulating the secretion of inflammatory mediators. This narrative review is devoted to the presentation of recent knowledge on the role played by one of the adipokines produced by adipose tissue—adiponectin—in the pathogenesis of rheumatoid arthritis.