Physiological Functions Research Articles

Taurocholic acid represents an earlier and more sensitive biomarker and promotes cholestatic hepatotoxicity in ANIT-treated rats.

Bile acid homeostasis is crucial for the normal physiological functioning of the liver. Disruptions in bile acid profiles are closely linked to the occurrence of cholestatic liver injury. As part of our diagnostic and therapeutic approach, we aimed to investigate the disturbance in bile acid profiles during cholestasis and its correlation with cholestatic liver injury. Before the occurrence of liver injury, alterations in bile acid profiles were detected in both plasma and liver between 8 and 16 h, persisting up to 96 h. TCA, TCDCA, and TUDCA in the plasma, as well as TCA, TUDCA, TCDCA, TDCA, TLCA, and THDCA in the liver, emerged as early sensitive and potential markers for diagnosing ANIT-induced cholestasis at 8-16 h. The distinguishing features of ANIT-induced liver injury were as follows: T-BAs exceeding G-BAs and serum biochemical indicators surpassing free bile acids. Notably, plasma T-BAs, particularly TCA, exhibited higher sensitivity to cholestatic hepatotoxicity compared with serum enzyme activity and liver histopathology. Further investigation revealed that TCA exacerbated ANIT-induced liver injury by elevating liver function enzyme activity, inflammation, and bile duct proliferation and promoting the migration of bile duct epithelial cell. Nevertheless, no morphological changes or alterations in transaminase activity indicative of liver damage were observed in the rats treated with TCA alone. Additionally, there were no changes in bile acid profiles or inflammatory responses under physiological conditions with maintained bile acid homeostasis. In summary, our findings suggest that taurine-conjugated bile acids in both plasma and liver, particularly TCA, can serve as early and sensitive markers for predicting intrahepatic cholestatic drugs and can act as potent exacerbators of cholestatic liver injury progression. However, exogenous TCA does not induce liver injury under physiological conditions where bile acid homeostasis is maintained.

Frailty and Malnutrition as Predictors of Major Complications Following Posterior Thoracolumbar Fusion in Elderly Patients: A Retrospective Cohort Study

Background ContextThe number of elderly patients with degenerative spinal deformity (DSD) is increasing, and posterior thoracolumbar fusion surgery is an effective treatment option, but there are often postoperative major complications, which may hinder the benefit for elderly patients. Currently, there is no consensus on the best risk assessment technique for predicting major complications in elderly patients undergoing long-segment fusion surgery. PurposeThis study constructs a risk assessment model using the Modified 5-Item Frailty Index (mFI-5) and serum albumin and evaluates its predictive value. Study DesignThis is a retrospective analysis of a prospectively established database of DSD. Patient SampleConsecutive patients (aged 65 and older) who underwent open posterior thoracolumbar fusion surgery for DSD between April 2018 and December 2023 were included. Outcome MeasuresOutcome measures included postoperative major complications, length of hospital stay [LOS], readmission and reoperation within 30 days, discharge disposition, physiological function recovery. MethodsThe study reviewed consecutive patients who underwent open posterior thoracolumbar fusion surgery for DSD. Patients were divided into three groups based on the presence or absence of frailty or frailty combined with malnutrition. Spearman ρ analysis was used to assess the correlation between mFI-5 and serum albumin levels. Univariate analyses and multivariate logistic regression were conducted to explore the relationship between frailty and malnutrition defined by mFI-5 and serum albumin and major postoperative complications. Finally, the Receiver Operating Characteristic (ROC) curve was used to evaluate the predictive value of this model for major complications. ResultsCompared to the Normal group (n = 59), both the Frailty group (n = 121) and the Frailty and Malnutrition group (n = 50) had higher rates of major complications (21.5% vs. 8.5%, p = .035; 28% vs. 8.5%, p = .002). Multivariate logistic regression showed that frailty and malnutrition status, higher ASA score, and more bleeding were independent predictors of major postoperative complications. The ROC curve demonstrated that frailty combined with malnutrition defined by mFI-5 and serum albumin had a larger area under the curve compared to mFI-5 or serum albumin alone (AUC: 0.676; 95% CI: 1.101-14.129; p < .001). ConclusionsCompared to considering frailty or malnutrition alone, the combined assessment of frailty and malnutrition using mFI-5 and serum albumin is valuable in predicting major complications in elderly patients undergoing posterior thoracolumbar fusion surgery. Level of evidenceIII

Barriers and Facilitators in Lactation Support for the Preterm Mother-Infant Dyad: An Integrated Approach.

Breastfeeding offers significant health benefits for both mothers and infants, particularly preterm infants, where it serves as a therapeutic strategy to reduce mortality and morbidities. However, breastfeeding practices are threatened globally by societal norms and systemic barriers at both micro and macro levels. This paper explores the complex interplay of these barriers and facilitators, focusing on the Neonatal Intensive Care Unit (NICU) setting. Preterm infants face specific feeding challenges due to immature physiological functions, yet evidence supports that strategies like cue-based feeding and individualized care can enhance feeding success and health outcomes. For mothers, initiating and maintaining lactation after preterm birth is critical but challenging, with early lactation support and achieving sufficient milk volume being key predictors of success. Partner support significantly influences lactation outcomes, although more inclusive research is needed for diverse family structures. In the NICU, a multidisciplinary approach to lactation care is vital, emphasizing the need for experienced staff and family-centered practices. NICU design, policies promoting parental presence, and adherence to Baby-friendly Hospital Initiative guidelines further support breastfeeding. This paper aims to provide directives for local breastfeeding policies through an integrated approach, considering societal attitudes and healthcare practices. The findings advocate for improved lactation support in NICUs, inclusive language and policies, and further research into diverse familial and gender roles in breastfeeding.

Does succulence in woody plants delay desiccation, and is stored water used to maintain physiological function during drought conditions?

Succulence is a trait that describes water storage in plant organs and tissues regardless of life form. Plants use the stored water to maintain physiological function and delay desiccation. However, it is unclear whether succulence in leaves, stems and roots of woody plants delays desiccation, whether it provides 'utilizable water' to maintain physiological function, or buffers changes in water status in drying soils through capacitance. We conducted a pot dry-down experiment with nine shrub species to determine whether woody plants with greater leaf, stem, or root succulence have greater shoot utilizable water or capacitance. We also investigated whether greater succulence delays desiccation, represented by cumulative VPD, until evapotranspiration ceased or until utilizable water was exhausted. Greater leaf and stem succulence were strongly related to greater shoot utilizable water and capacitance. However, desiccation time was not delayed in plants with greater total shoot succulence, utilizable water, or capacitance. Instead, woody plants with greater root succulence had longer desiccation times. This suggests that woody plants use aboveground succulence to maintain physiological function and water status during drought, whereas root succulence extends desiccation time. Our study improves the mechanistic understanding of how woody plants use stored water to survive in dryland ecosystems.

The effects of D-allulose on the gelatinization and gelling properties of wheat starch

D-Allulose, with its low calorie content and sweetness comparable to sucrose, has gained significant attention from researchers as an ideal substitute for sucrose. Here, we investigated the effects of D-allulose on the physicochemical properties and texture of wheat starch. The gelatinization results showed that D-allulose (D-allulose: wheat starch = 1:1 w/w) increased the pasting temperature (56.4 to 65.2 °C) and transition enthalpy (7.9 to 9.0 J/g) of wheat starch systems, and the impact was significantly lower than that of other commonly used small-molecule sugars (sucrose, fructose, glucose). In addition, rheological, texture, and X-ray diffraction analyses confirmed that the addition of D-allulose improved the hardness, gumminess, and recrystallization of retrograded wheat starch gels. Microstructure analysis indicated that the addition of D-allulose enhanced the structural density of wheat starch system, thereby significantly slowing down the retrogradation of wheat starch. D-allulose exhibited unique properties, promoting the gelatinization of wheat starch and delaying its retrogradation. These results will help to promote the wide application of D-allulose in starchy foods with special physiological functions.

In-vitro evidence indicating that IL-10 causes aging-related hypoalbuminemia via JAK1/STAT3 and CEBP-β

Albumin (ALB) has numerous vital physiological outcomes for healthy aging. A decrease in serum albumin, i.e., hypoalbuminemia, is one of the risk factors associated with aging, which affects physiological functioning. Hypoalbuminemia is the outcome of either decreased ALB synthesis or increased degradation. However, the potential mechanism controlling ALB's mRNA level expression in aged individuals is yet to be explored. We noted decreased serum ALB concentrations in aged individuals participating in our study, as compared to the young ones. We found that IL-10, a paradoxical inflammaging marker, reduced ALB concentration in HepG2 cells. Inhibiting the JAK/STAT3 signalling increased albumin mRNA suggesting its IL-10-driven regulation via JAK/STAT3 pathway. Albumin promotor analysis revealed the presence of a CEBP-β binding site. We showed that CEBP-β binds to the albumin promoter in an IL-10-dependent manner. Further, IL-10 increased the expressions of all CEBP-β isoforms, including the inhibitory isoform (LIP). The CEBP-β inhibition either by a functional inhibitor (i.e., quercetin) or shRNA silencing increased albumin mRNA in HepG2 cells. Our finding showed that IL-10 likely regulates albumin expression in a JAK/STAT3 and CEBP-β dependent manner in aging. A better understanding of the underlying condition can improve albumin protein levels and the well-being of the aged population.

Unveiling the biological activities of the microbial long chain hydroxy fatty acids as dual agonists of GPR40 and GPR120

The physiological functions of various fatty acid-originating metabolites from foods and fermented products remained mostly untouched. Thereby, this study examined the biological activities of hydroxy fatty acids as agonists of G protein-coupled receptors (i.e., GPR40 and GPR120), which are derived from long-chain fatty acids (e.g., oleic acid and linoleic acid) by microbiota. Cell-based Ca2+ mobilization assays and in silico docking simulations revealed that not only the degree of unsaturation but also the number and position of hydroxyl groups played a key role in their agonist activities. For instance, 8,11-dihydroxyoctadec-9Z-enoic acid exhibited significantly greater Ca2+ response in the GPR40/GPR120-expressing cells as compared to the endogenous agonists (e.g., linoleic acid and docosahexaenoic acid), forming hydrogen bond interactions with residues in the ligand-binding pockets of receptors. This study will contribute to understanding the relationships between fatty acid structures and agonist activities.

Systematic Review on The Role of Gender and Language Learning Strategies (LLS)

le to master the language. These struggles generally encompass internal as well as external challenges. Some examples of internal factors comprise low motivation, interest, and focus besides a poor attitude towards the target language in question. Meanwhile, some external factors normally include ineffective and inappropriate teaching and learning (T &amp; L) methods, an unsupportive classroom environment, and a lack of support and encouragement from family and friends. This study aims to determine the role of gender in English as a second language (ESL) learners’ use of language learning strategies (LLS). Online databases such as Google Scholar, Education Resources Information Centre (ERIC), Scopus, and ProQuest were used to identify the relevant literature. Online searches conducted from 2010 and 2022 revealed 197 studies on the topic. The systematic literature review method was employed for this study. However, only 23 kinds of literature out of 197 were selected for inclusion according to specific criteria outlined by the research purpose mentioned above. Based on the results it was found that gender does play a significant role in the ESL learners' use of LLS due to several factors such as aptitude, emotional and communicative motivation, and positive attitude. Moreover, individual personality, social differences, physiological functioning, and home environment can influence the LLS used by ESL learners. It was found that the preferred LLS includes cognitive, compensation, and affective strategies.

Identifying Calmodulin and Calmodulin-like Protein Members in Canavalia rosea and Exploring Their Potential Roles in Abiotic Stress Tolerance.

Calmodulins (CaMs) and calmodulin-like proteins (CMLs) belong to families of calcium-sensors that act as calcium ion (Ca2+) signal-decoding proteins and regulate downstream target proteins. As a tropical halophyte, Canavalia rosea shows great resistance to multiple abiotic stresses, including high salinity/alkalinity, extreme drought, heat, and intense sunlight. However, investigations of calcium ion signal transduction involved in the stress responses of C. rosea are limited. The CaM and CML gene families have been identified and characterized in many other plant species. Nevertheless, there is limited available information about these genes in C. rosea. In this study, a bioinformatic analysis, including the gene structures, conserved protein domains, phylogenetic relationships, chromosome distribution, and gene synteny, was comprehensively performed to identify and characterize CrCaMs and CrCMLs. A spatio-temporal expression assay in different organs and environmental conditions was then conducted using the RNA sequencing technique. Additionally, several CrCaM and CrCML members were then cloned and functionally characterized using the yeast heterogeneous expression system, and some of them were found to change the tolerance of yeast to heat, salt, alkalinity, and high osmotic stresses. The results of this study provide a foundation for understanding the possible roles of the CrCaM and CrCML genes, especially for halophyte C. rosea's natural ecological adaptability for its native habitats. This study also provides a theoretical basis for further study of the physiological and biochemical functions of plant CaMs and CMLs that are involved in tolerance to multiple abiotic stresses.

Roles of PDGF/PDGFR signaling in various organs.

Platelet-derived growth factors (PDGFs) ligands and their corresponding receptors, PDGF receptor (PDGFR)α and PDGFRβ, play a crucial role in controlling diverse biological functions, including cell growth, viability and migration. These growth factors bind to PDGFRs, which are receptor tyrosine kinases present on the surface of target cells. The interaction between PDGFs and PDGFRs induces receptor dimerization and subsequent activation through auto-phosphorylation, which in turn triggers a cascade of intracellular signaling pathways. PDGF/PDGFR signaling is essential for maintaining normal physiological functions, including tissue regeneration and growth. However, dysregulation of this signaling pathway leads to pathological conditions, including fibrosis, atherosclerosis, and cancer development in various organs. The pathological impact of PDGF/PDGFR signaling primarily stems from its capacity to promote excessive cell proliferation, enhanced migration, and increased extracellular matrix deposition, resulting in tissue overgrowth, scarring, and abnormal vessel formation. These processes are integral to the pathogenesis of fibrotic, neoplastic, and vascular disorders. Therefore, understanding these pathways is crucial for developing targeted treatments designed to inhibit PDGF/PDGFR signaling in these diseases. This review delves into the dual role of PDGF/PDGFR signaling in both physiological and pathophysiological contexts across different organs and provides insights into current pharmacological therapies designed to target the PDGF signaling pathway. INTRODUCTION Platelet-derived growth factors (PDGFs) are key signaling molecules that interact with specific cell to modulate various cellular responses. Upon binding to their receptors (PDGFRs), PDGFs initiate dimerization and tyrosine phosphorylation, which activates downstream signaling pathways. The PDGF signaling network comprises four ligands-PDGF-A, PDGF-B, PDGFC, and PDGF-D, that interact with two receptors, PDGFRα and PDGFRβ [1-6]. PDGFRα exhibits broader ligand specificity, binding to PDGF-A, PDGF-B, PDGF-C homodimers, and PDGFAB heterodimers, whereas PDGFRβ specifically binds to PDGFB and PDGF-D homodimers. Under both physiological and pathol.

Comprehensive circular RNA profiling in various sheep tissues

Despite the scientific relevance of circular RNAs (circRNAs), the study of these RNAs in non-model organisms, especially in sheep, is still in its infancy. On the other hand, while some studies have focused on sheep circRNA identification in a limited number of tissues, there is a lack of comprehensive analysis that profile circRNA expression patterns across the tissues not yet investigated. In this study, 61 public RNA sequencing datasets from 12 different tissues were uniformly analyzed to identify circRNAs, profile their expression and investigate their various characteristics. We reported for the first time a circRNA expression landscape with functional annotation in sheep tissues not yet investigated including hippocampus, BonMarrowMacrophage, left-ventricle, thymus, ileum, reticulum and 23-day-embryo. A stringent computational pipeline was employed and 8919 exon-derived circRNAs with high confidence were identified, including 88 novel circRNAs. Tissue-specificity analysis revealed that 3059 circRNAs were tissue-specific, which were also more specific to the tissues than linear RNAs. The highest number of tissue-specific circRNAs was found in kidney, hippocampus and thymus, respectively. Co-expression analysis revealed that expression of circRNAs may not be affected by their host genes. While most of the host genes produced more than one isoform, only one isoform had dominant expression across the tissues. The host genes of the tissue-specific circRNAs were significantly enriched in biological/pathways terms linked to the important functions of their corresponding tissues, suggesting potential roles of circRNAs in modulating physiological activity of those tissues. Interestingly, functional terms related to the regulation and various signaling pathways were significantly enriched in all tissues, suggesting some common regulatory mechanisms of circRNAs to modulate the physiological functions of tissues. Finding of the present study provide a valuable resource for depicting the complexity of circRNAs expression across tissues of sheep, which can be useful for the field of sheep genomic and veterinary research.

Skin Structure, Physiology, and Pathology in Topical and Transdermal Drug Delivery

Several industries are increasingly focused on enhancing the delivery of active ingredients through the skin to optimize therapeutic outcomes. By facilitating the penetration of active ingredients through the skin barrier, these enhancers can significantly improve the efficacy of various formulations, ranging from skincare products to therapeutic agents targeting systemic circulation. As the understanding of skin physiology and the mechanisms of drug absorption deepen, these industries are adopting permeation enhancers more widely, ultimately leading to better patient outcomes and expanded treatment options. However, the structure and physiological function of the skin can vary according to different factors, such as the area of the body and between individuals. These variations, along with external environmental exposures, aging and pathological conditions, introduce complexities that must be carefully considered when designing effective delivery systems. Considering the intricacies of skin structure and physiology, tailoring systems to account for regional differences, individual variability, and changes induced by environmental factors or disease is critical to optimizing therapeutic outcomes. This review discusses the features of skin structure, physiology, and pathologies, as well as the application of permeation enhancers in these contexts. Furthermore, it addresses the use of animal skin models in transdermal delivery and dermatological studies, along with the latest developments in this field.

Pathogen spectrum and microbiome in lower respiratory tract of patients with different pulmonary diseases based on metagenomic next-generation sequencing.

The homeostasis of the microbiome in lower respiratory tract is crucial in sustaining normal physiological functions of the lung. Different pulmonary diseases display varying degrees of microbiome imbalance; however, the specific variability and clinical significance of their microbiomes remain largely unexplored. In this study, we delineated the pathogen spectrum and commensal microorganisms in the lower respiratory tract of various pulmonary diseases using metagenomic sequencing. We analyzed the disparities and commonalities of the microbial features and examined their correlation with disease characteristics. We observed distinct pathogen profiles and a diversity in lower airway microbiome in patients diagnosed with cancer, interstitial lung disease, bronchiectasis, common pneumonia, Nontuberculous mycobacteria (NTM) pneumonia, and severe pneumonia. This study illustrates the utility of Metagenomic Next-generation Sequencing (mNGS) in identifying pathogens and analyzing the lower respiratory microbiome, which is important for understanding the microbiological aspect of pulmonary diseases and essential for their early and precise diagnosis.

GutMGene v2.0: an updated comprehensive database for target genes of gut microbes and microbial metabolites.

The gut microbiota is essential for various physiological functions in the host, primarily through the metabolites it produces. To support researchers in uncovering how gut microbiota contributes to host homeostasis, we launched the gutMGene database in 2022. In this updated version, we conducted an extensive review of previous papers and incorporated new papers to extract associations among gut microbes, their metabolites, and host genes, carefully classifying these as causal or correlational. Additionally, we performed metabolic reconstructions for representative gut microbial genomes from both human and mouse. gutMGene v2.0 features an upgraded web interface, providing users with improved accessibility and functionality. This upgraded version is freely available at http://bio-computing.hrbmu.edu.cn/gutmgene. We believe that this new version will greatly advance research in the gut microbiota field by offering a comprehensive resource.

Effects of physicochemical stressors on marine copepod populations: A review

Copepods are the key organisms in aquatic ecosystems; they are exposed to a variety of stressors that can significantly influence their behavior, distribution, and life cycle. Understanding how stressors influence such communities becomes a priority in marine ecology. This paper reviews the most important effects of stressors such as temperature, salinity, light, oxygen, and nutrients, and their effects on marine copepods that have been analyzed in laboratory experiments highlighting the impact of stressors on organisms. Most stressors influence the distribution and behavior of the organisms. Temperature also influences the metabolic activity, development, and reproduction of copepods; variations in salinity can affect osmotic regulation and physiological functioning, while oxygen influences the processes of respiration and metabolism. Light and nutrients also significantly impact the growth and reproduction of copepods and are essential for sustaining their populations in aquatic ecosystems. Complex interactions between multiple stressors and their effects on marine copepods are less studied. By studying the bibliography related to the experiments carried out on marine copepods and how they are influenced by the environmental factors mentioned above, I can provide a better understanding of the fact that copepods are vulnerable to environmental changes, and this information can contribute to the development of strategies effective for the conservation and management of marine ecosystems.

Exogenous Hormone Treatments in Maize.

Plant hormones have key functions in plant morphology, physiology, and stress responses. Studies on the biology of hormones and their effect on plant physiology and metabolism are greatly facilitated by the exogenous application of these compounds. In general, methods for exogenous hormone application are easy and fast, and provide useful information about their effects in planta. Although hormone effects have been studied in several plant species, the used methods need to be tailored specifically to each species to get robust data. Maize is an established model for basic and applied research, and an excellent system for studying the effects of hormones on developmental and stress responses in a cereal crop. Different methods have been reported for the exogenous application of plant growth regulators in maize, including watering, spraying, immersion, and application to the apical whorl. These various methods are useful to analyze hormone responses at different developmental stages, in specific organs, and within tissues. As with all exogenous application assays, suitable experimental design and the inclusion of proper controls are critical factors in these methods, to obtain reliable and reproducible results. Here, we provide an overview of various methods for hormone exogenous application in maize, and technical considerations to get successful results.

Beyond the Harvard Definition: A Critique of Josef Seifert’s Realistic Phenomenological Approach to Brain Death

This article explores the significance of context in defining death, particularly through the lens of the Harvard definition and the critiques offered by Josef Seifert. The Harvard definition, established in 1968, is examined within its medical context, highlighting how it reflects pragmatic interests and raises critical questions about the boundaries between life and death. Seifert’s critiques focus on the reductionist nature of equating personhood with consciousness, emphasizing the need for a broader understanding of life indicators beyond mere physiological functions. The article also discusses the social implications of medicalization in the dying process. Furthermore, it addresses the challenges posed by the cessation of brain function as a criterion for death, contrasting it with more observable signs of life such as breathing and heartbeat. Ultimately, the article argues for a more nuanced understanding of death that incorporates social, cultural, and ethical dimensions, advocating for ongoing dialogue and potential revisions of death definitions to reflect the complexities of human experience. This comprehensive approach aims to bridge the gap between medical definitions and the lived realities of individuals facing death.

Ethylamine, beyond the synthetic precursor of theanine: CsCBF4-CsAlaDC module promoted ethylamine synthesis to enhance osmotic tolerance in tea plants.

The tea plant (Camellia sinensis) is a perennial green plant, and its tender leaves are rich in secondary metabolites, such as theanine. Ethylamine (EA), a small amine, is an important prerequisite for theanine synthesis. However, beyond its involvement in theanine synthesis, the other physiological functions of EA in tea plants remain unknown. In vitro experiments indicate that EA may function as scavengers of reactive oxygen species (ROS) to protect the plant against damage caused by osmotic stress. Additionally, a significant correlation between EA levels and osmotic tolerance has been observed in different tea varieties. From the results, alanine decarboxylase (CsAlaDC)-silenced tea leaves and overexpressed CsAlaDC Arabidopsis thaliana lines decreased and increased EA levels, respectively, and mediated ROS homeostasis, thus exhibiting a sensitive and tolerant phenotype. In addition, the transcription factor (TF) CsCBF4 was functionally identified, which can directly bind to the CsAlaDC promoter. CsCBF4-silenced tea leaves significantly reduced the expression levels of CsAlaDC and in turn EA content, resulting in excess ROS accumulation and an osmotic-sensitive phenotype. Taken together, these results established a new regulatory module consisting of CBF4-CsAlaDC responsible for EA accumulation and ROS homeostasis in response to osmotic stress.

Delayed effects of antibiotic therapy in endotoxinemia

BACKGROUND: Nowadays, due to the increasing number of infectious and inflammatory diseases, the problem of the use of antibacterial drugs becomes especially important. As a result of the action of toxins, inflammatory processes can affect the central nervous system with the subsequent development of neuroinflammation. Activation of neuroinflammation leads to dysregulation of many physiological functions. These negative appearances can be observed even after a long period. It is known that doxycycline is a tetracycline-type antibiotic, which is able to penetrate the blood-brain barrier and has anti-inflammatory activity. AIM: The aim of this study was to investigate the nature of delayed physiological changes in rats against the background of administration of the antibacterial drug doxycycline in the LPS-induced model of neuroinflammation. MATERIALS AND METHODS: Four groups of Wistar rats, 10 males in each group, were used in the experiment. The first group was injected once intraperitoneally with physiological solution, the second group — with lipopolysaccharide (1 mg/kg). Animals of the third and fourth groups received intragastrically doxycycline solution (25 mg/kg) daily for two weeks. On the 15th day of the experiment, rats from the fourth group were injected with lipopolysaccharide (1 mg/kg). Body weight of animals, mass coefficients of immunocompetent organs, as well as behaviour and motor activity of rats in the “Open Field” test were evaluated at several time points. RESULTS: It was shown that systemic injection of lipopolysaccharide led to an increase in the mass coefficients of spleen, kidneys and adrenal glands compared to the group of animals receiving doxycycline beforehand. These changes were noted 48 h and 2 months after the injection of endotoxin. In the “Open Field” test, animals that were injected with doxycycline and lipopolysaccharide showed no violations of motor activity and research behavior, unlike the group that received only lipopolysaccharide. CONCLUSIONS: It can be assumed that the physiological effects of doxycycline in the lipopolysaccharide-induced model of neuroinflammation revealed at early and late terms are not limited to the antibacterial effect of the drug and are mediated by anti-inflammatory and potential neuroprotective effects on the central nervous system.

TRPV4-A Multifunctional Cellular Sensor Protein with Therapeutic Potential.

Transient receptor potential vanilloid (TRPV) channel proteins belong to the superfamily of TRP proteins that form cationic channels in the animal cell membranes. These proteins have various subtype-specific functions, serving, for example, as sensors for pain, pressure, pH, and mechanical extracellular stimuli. The sensing of extracellular cues by TRPV4 triggers Ca2+-influx through the channel, subsequently coordinating numerous intracellular signaling cascades in a spatio-temporal manner. As TRPV channels play such a wide role in various cellular and physiological functions, loss or impaired TRPV protein activity naturally contributes to many pathophysiological processes. This review concentrates on the known functions of TRPV4 sensor proteins and their potential as a therapeutic target.