Protective Mechanism Research Articles

Curcumin triggers the Wnt/β-catenin pathway and shields neurons from injury caused by intermittent hypoxia

The objective of this study was to explore the molecular basis through which Curcumin (Cur) mitigates neuronal damage caused by obstructive sleep apnea (OSA). HT22 was used to simulate intermittent hypoxia (IH) injury and explore the effect of Cur on these cells. We evaluated the cell viability, cytotoxicity, apoptosis, proliferation, and Wnt/β-catenin (WβC) pathway. IWR-1 was used to block the pathway and investigate the protective mechanism of Cur. We constructed an in vivo model of IH to validate the results of the cellular experiments. IH accelerated apoptosis and cytotoxicity, suppressed proliferation, and decreased the activity of the WβC pathway. Cur can significantly improve cell viability, reduce apoptosis rate and cell toxicity, promote cell proliferation, and up-regulate the WβC. After blocking the WβC pathway, the proliferative effect of Cur was observably weakened. In vivo, IH caused hippocampal damage and inhibited WβC pathway activity in mice, which was ameliorated by Cur treatment. This implies that Cur could be a novel treatment option for neurological impairment brought on by OSA.

An Andrias davidianus derived composite hydrogel with enhanced antibacterial and bone repair properties for osteomyelitis treatment.

Effective antibacterial therapy while accelerating the repair of bone defects is crucial for the treatment of osteomyelitis. Inspired by the protective mechanism of Andrias davidianus, we constructed an antibacterial hydrogel scaffold with excellent rigidity and long-term slow-release activity. While retaining the toughness of the skin secretion of Andrias davidianus (SSAD), the rigidity of the hydrogel material is increased by incorporating hydroxyapatite to meet the demands of bone-defect-filling materials. It also exerted antibacterial effects via the slow-release of vancomycin from local osteomyelitis lesions. Notably, the hydrogel can also carry a high stable recombinant miR-214-3p inhibitor (MSA-anti214). By the delivery of nano vector polyvinylamine, the long-term slow-release of MSA-anti214 is achieved to promote bone repair, making this composite hydrogel a potential SSAD-based osteomyelitis alleviator (SOA). In vitro and vivo results verified that the SOA effectively eliminated Staphylococcus aureus and repaired bone defects, ultimately mitigating the progression of osteomyelitis. This composite hydrogel extends the economic application prospects of A. davidianus and has provided new insights for the treatment of osteomyelitis. The study also explored new insights for the bone filling materials of bone defection and other skeletal system diseases.

Impact of Neuron-Derived HGF on c-Met and KAI-1 in CNS Glial Cells: Implications for Multiple Sclerosis Pathology.

Demyelination and axonal degeneration are fundamental pathological characteristics of multiple sclerosis (MS), an inflammatory disease of the central nervous system (CNS). Although the molecular mechanisms driving these processes are not fully understood, hepatocyte growth factor (HGF) has emerged as a potential regulator of neuroinflammation and tissue protection in MS. Elevated HGF levels have been reported in MS patients receiving immunomodulatory therapy, indicating its relevance in disease modulation. This study investigated HGF's neuroprotective effects using transgenic mice that overexpressed HGF. The experimental autoimmune encephalomyelitis (EAE) model, which mimics MS pathology, was employed to assess demyelination and axonal damage in the CNS. HGF transgenic mice showed delayed EAE progression, with reduced CNS inflammation, decreased demyelination, and limited axonal degeneration. Scanning electron microscopy confirmed the preservation of myelin and axonal integrity in these mice. In addition, we explored HGF's effects using a cuprizone-induced demyelination model, which operates independently of the immune system. HGF transgenic mice exhibited significant protection against demyelination in this model as well. We also investigated the expression of key HGF receptors, particularly c-Met and KAI-1. While c-Met, which is associated with increased inflammation, was upregulated in EAE, its expression was significantly reduced in HGF transgenic mice, correlating with decreased neuroinflammation. Conversely, KAI-1, which has been linked to axonal protection and stability, showed enhanced expression in HGF transgenic mice, suggesting a protective mechanism against axonal degeneration. These findings underscore HGF's potential in preserving CNS structure and function, suggesting it may be a promising therapeutic target for MS, offering new hope for mitigating disease progression and enhancing neuroprotection.

Kolaviron: a Bioflavonoid from Seed Extract of Garcinia kola Attenuates Chromium (VI)-Induced Gut Dysfunction and Oxidative Damage in Drosophila melanogaster.

Hexavalent chromium [Cr(VI)] is of public health significance due to its toxicity and carcinogenic effects. Kolaviron, a bio-flavonoid fraction from Garcinia kola seed, has been reported to possess gastroprotective and antioxidative properties. We hypothesize that Kolaviron-fortified diet will attenuate chromium (VI)-induced gut dysfunction and oxidative damage in Drosophila melanogaster. We exposed D. melanogaster (Oregon strain of 1-3days old of both male and female) to a 1.0mg/kg diet of chromium (VI), with or without Kolaviron (100mg/kg diet) orally for 5days. We evaluated markers of oxidative stress (total peroxide and protein carbonyl), antioxidative status (total thiols (T-SH), non-protein thiols (NP-SH), and catalase), and inflammatory (nitric oxide (nitrite and nitrate) and gut's morphology. The data indicated that Kolaviron ameliorated chromium (VI)-induced reduction in the levels of T-SH, NP-SH, and catalase activity (p < 0.05). In addition, Kolaviron attenuated chromium (VI)-induced elevation of total peroxide, protein carbonyl, and nitric oxide (p < 0.05). Kolaviron offered a protective role in chromium VI-induced toxicity in the gut of D. melanogaster. This study provided further insights into the protective mechanisms of Kolaviron against chromium (VI)-induced toxicity in D. melanogaster by maintaining epithelial integrity of the gut and oxidative stress-antioxidant balance.

Tong-Qiao-Huo-Xue Decoction promotes synaptic remodeling via cAMP/PKA/CREB pathway in vascular dementia rats

BackgroundTong-Qiao-Huo-Xue Decoction (TQHXD) is a traditional Chinese medicinal formula widely used in the treatment of vascular dementia (VD). Although it has demonstrated good clinical efficacy, the specific molecular mechanisms underlying its therapeutic effects on VD remain unclear. ObjectiveThis study aimed to elucidate the neuroprotective mechanisms of TQHXD to provide a scientific basis for the clinical treatment of VD. MethodsThe chemical components of TQHXD were qualitatively analyzed using ultra-performance liquid chromatography (UPLC) and gas chromatography (GC). Network pharmacology predicted the potential protective mechanisms of TQHXD against VD. A rat model of VD was established through bilateral vessel occlusion (2-VO), and an oxygen-glucose deprivation/reperfusion (OGD/R) model was used to induce damage to neuronal cells of the hippocampus. In vivo experiments assessed changes in cerebral blood flow, learning and memory capabilities, hippocampal neuronal morphology, dendritic length, dendritic spine density, and synapse number in rats. We examined the expression of synaptic remodeling-related proteins and pathway proteins in the hippocampal region. In vitro assays evaluated cell viability, apoptosis, reactive oxygen species (ROS) levels, and expression of synaptic remodeling-related proteins and signaling pathway. ResultsMultiple active components were identified in TQHXD. KEGG enrichment analysis suggested that the therapeutic effects of TQHXD on VD may be related to the cAMP signaling pathway. Treatment with TQHXD significantly improved learning and memory performance in VD rats, improved hippocampus morphology, and increased dendritic length, dendritic spine density, and number of synapses. Furthermore, TQHXD improved cell viability, reduced apoptosis, and decreased intracellular ROS levels in vitro. Western blotting, immunofluorescence, and enzyme-linked immunosorbent assay results collectively demonstrated that TQHXD upregulated the expression of synaptic remodeling-related proteins and pathway-related proteins both in vivo and in vitro. ConclusionsTQHXD treated VD by promoting synaptic remodeling in hippocampal neurons, likely through activation of the cAMP/PKA/CREB pathway.

Neuroprotective effect of empagliflozin against doxorubicin-induced chemobrain in rats: Interplay between SIRT-1/MuRF-1/PARP-1/NLRP3 signaling pathways and enhanced expression of miRNA-34a and LncRNA HOTAIR

Chemobrain, a challenging side effect of doxorubicin (DOX)-based chemotherapy, impairs cognitive abilities in cancer survivors. DOX triggers chemobrain via oxidative stress, leading to inflammation and apoptosis. Empagliflozin (EMPA), a sodium glucose co-transporter-2 inhibitor, demonstrated neuroprotective effects by reducing reactive oxygen species (ROS) and inflammation, but its protective mechanisms against DOX-induced chemobrain is not fully known. Thus, this study aimed to investigate EMPA’s neuroprotective effects on DOX-induced chemobrain in rats and to uncover the underlying protective mechanisms. Fifty male Wistar rats were divided into control, EMPA, DOX (2 mg/kg, IP, once/week for 4 weeks), and two treated groups (DOX+ EMPA 5 and 10 mg/kg/day, PO, for 4 weeks). Behavioral tests showed improved memory, motor performance, and reduced anxiety in EMPA-treated groups compared to DOX, with superior results at the higher dose. Histopathological analysis revealed increased intact neurons in the cortex and hippocampus in EMPA-treated groups, with 346.4 % increase in CA3 (p < 0.0001), 19.1 % in dentate gyrus (p = 0.0006), and 362.6 % in cortex (p < 0.0001) in the high-dose EMPA group. Biochemical investigations of the high-dose EMPA group revealed significant decreases in inflammatory and apoptotic markers (JNK/PARP-1/NLRP3/MuRF-1/FOXO-1), increased SIRT-1 protein expression by 389.9 % (p < 0.0001), and reduced miRNA-34a and LncRNA HOTAIR gene expression (50.4 % and 53.4 % respectively, p < 0.0001) relative to DOX group. Conclusively, EMPA demonstrated superior behavioral and histopathological outcomes particularly at higher dose, positioning it as a promising neuroprotective candidate against DOX-induced chemobrain, possibly through modulating SIRT-1, NF-κb, NLRP3, and oxidative stress pathways.

Activity of photosynthetic pigments and the antioxidant system in sunflower under drought stress

Background. The study is of particular importance in view of the increasing pace of global climate aridization. The article highlights the results of an experiment on the effect of drought on the physiological status of seedlings of cv. ‘Poseidon 625’ representing an important food crop – sunflower (Helianthus annuus L.). Materials and methods. The experiment included a group of control samples grown with sufficient moisture and four impact groups subjected to osmotic stress. The intensity of accumulation of lipid peroxidation products (LPP) was measured by the reaction of malondialdehyde (MDA) with thiobarbeturic acid; catalase activity was assessed by a photocolorimetric method based on the interaction between hydrogen peroxide and potassium iodide; the content of pigments (Chl a, Chl b, Сar) was calculated spectrophotometrically in acetone extract. Results. The degree of POL accumulation in the impact groups of the experiment was found to be many times higher than the values in the control samples, which was confirmed by a rapid increase in the MDA concentration in response to a growing water shortage. The accumulation of oxygen free radicals triggered the mechanisms of antioxidant protection of seedlings by synthesizing catalase, the concentration of which increased proportionally to the accumulation of POL. At the same time, the rapid accumulation of POL in the absence of irrigation and under osmotic stress of 3 and 5 atm led to a suppression of low-molecular-weight components of protection (carotenoids) and activation of their synthesis only when critical values of osmotic stress were reached. Conclusion. As a result of the experiment, catalase was identified as the main component of antioxidant protection in sunflower seedlings. Due to the activation of its synthesis, the concentrations of Chl a and Chl b decreased, attesting to the activation of the mechanisms protecting the photosynthetic activity in seedlings, and their antioxidant status.

Rosmarinic Acid Attenuates Salmonella enteritidis-Induced Inflammation via Regulating TLR9/NF-κB Signaling Pathway and Intestinal Microbiota.

Salmonella enteritidis (SE) infection disrupts the homeostasis of the intestinal microbiota, causing an intestinal inflammatory response and posing a great threat to human and animal health. The unreasonable use of antibiotics has led to an increase in the prevalence of drug-resistant SE, increasing the difficulty of controlling SE. Therefore, new drug strategies and research are urgently needed to control SE. Rosmarinic acid (RA) is a natural phenolic acid with various pharmacological activities, including antioxidant, anti-inflammatory and antibacterial properties. However, the protective effects and mechanism of RA on intestinal inflammation and the gut microbial disorders caused by SE have not been fully elucidated. In this study, RAW264.7 cells, MCECs and BALB/c mice were challenged with SE to assess the protective effects and mechanisms of RA. The results showed that RA enhanced the phagocytic ability of RAW264.7 cells, reduced the invasion and adhesion ability of SE in MCECs, and inhibited SE-induced inflammation in cells. Moreover, RA inhibited the activation of the NF-κB signaling pathway by upregulating TLR9 expression. Importantly, we found that RA provided protection against SE and increased the diversity and abundance of the intestinal microbiota in mice. Compared with infection control, RA significantly increased the abundance of Firmicutes and Acidibacteria and decreased the abundance of Proteobacteria, Epsilonbacteraeota and Bacteroidota. However, RA failed to alleviate SE-induced inflammation and lost its regulatory effects on the TLR9/NF-κB signaling pathway after destroying the gut microbiota with broad-spectrum antibiotics. These results indicated that RA attenuated SE-induced inflammation by regulating the TLR9/NF-κB signaling pathway and maintaining the homeostasis of the gut microbiota. Our study provides a new strategy for preventing SE-induced intestinal inflammation.

The Effect of Psychological Crime of Virtual Bullying on Social Media on Victims Under the ITE Law

Cyberbullying takes many forms and adapts rapidly to technological developments. This study explores the psychological effects of virtual bullying on social media on victims, with the legal basis set out in Indonesia's Electronic Information and Transaction Law (UU ITE). Online bullying has become a major problem in the digital age, significantly impacting the psychological well-being of victims, and often having a more severe impact than conventional bullying. This study aims to identify the forms of virtual bullying regulated by the ITE Law, analyze the psychological impact on victims, and evaluate the effectiveness of legal protection provided by the ITE Law. Using a normative juridical approach, this research evaluates the articles in the ITE Law that are relevant to cyberbullying and relates them to the cases that occur. The results show that cyberbullying can cause various psychological disorders, including anxiety, depression, and decreased self-esteem. The ITE Law provides a strong legal framework to address these acts, with strict criminal sanctions and protection mechanisms for victims. However, the effectiveness of the ITE Law is highly dependent on consistent implementation by law enforcement as well as increased public awareness and education regarding digital ethics. This study concludes that collaborative efforts between the government, educational institutions, and communities are needed to reduce the incidence of virtual bullying and ensure that victims receive the support they need.

TMT-based quantitative proteomics unveils the protective mechanism of Polygonatum sibiricum polysaccharides on septic acute liver injury

Polygonatum sibiricum polysaccharides (PSP) has been shown to possess multiple pharmacological functions. Our previous study found that PSP could protect against acute liver injury during sepsis via inhibiting inflammatory response. However, the underlying molecular mechanism by which PSP alleviates septic acute liver injury (SALI) remains unknown. Herein, TMT-based quantitative proteomics was utilized to explore the essential pathways and proteins involved in the protective effects of PSP on SALI. The results revealed that 632 and 176 differentially expressed proteins (DEPs) were identified in Model_vs_Control and PSP_vs_Model, respectively. GO annotation showed similar trends, suggesting that these DEPs were primarily involved in the cellular anatomical entity in Cellular Component, the cellular processe and the biological regulation in Biological Process, the binding and the catalytic activity in Molecular Function. Meanwhile, KEGG enrichment analysis implied that four common pathways, including the NF-κB signaling pathway, the IL-17 signaling pathway, the TNF signaling pathway and the Toll-like receptor signaling pathway, were closely associated with the pathogenesis of sepsis among the top 20 remarkably enriched pathways in Model_vs_Control_up and PSP_vs_Model_down. Moreover, the levels of several common DEPs, including TLR2, IKKi, JunB and CXCL9, were validated by WB, which was in line with the results of proteomics. Therefore, the protective effects of PSP on SALI might exert via blocking the above-mentioned inflammation pathways.Significance: PSP, recognized as a key component of Polygonatum sibiricum, exhibits a range of pharmacological functions. Our previous study found that PSP could protect against SALI, yet failing to clarify the mechanism of action. To reveal the underlying molecular mechanism involved in the protective effects of PSP on SALI, a TMT-based quantitative proteomic analysis was performed to detect and analyse the DEPs in liver tissue among the control group, the model group and the PSP group in this study. The results provide theoretical references for exploring the action mechanism of drugs and facilitate the comprehensive utilization of PSP. SignificancePSP have been identified as the most crucial components of Polygonatum sibiricum with various pharmacological functions. Our previous study found that PSP could protect against SALI, but the mechanism of action remains unknown. To reveal the underlying molecular mechanism involved in the protective effects of PSP on SALI, a TMT-based quantitative proteomic analysis was performed to detect and analyse the DEPs in liver tissue among the control group, the model group and the PSP group in this study. The results provide theoretical references for exploring the action mechanism of drugs and facilitate the comprehensive utilization of PSP.

Long-term corrosion protection of reinforcing bars via a self-responsive coating incorporating ZrP functional fillers

The conventional coating of reinforcing bars exhibits inadequate anti-corrosion efficacy stemming from a non-specific, blind protection mechanism, poses a threat to the durability of concrete. We devised a novel self-responsive functional filler, L-arginine (LA) intercalated zirconium phosphate (LCZrP), synthesized via an intercalation reaction. This innovative filler was seamlessly integrated into an epoxy (EP) resin matrix, yielding a smart anticorrosive coating that harmoniously combines active and passive corrosion protection strategies. The integration of LCZrP within the coating matrix serves a trifecta of purposes: it extends the corrosion propagation path, effectively disperses nanofiller agglomeration, and enhances interfacial adhesion with the epoxy coating. Critically, the controlled release of corrosion inhibitors from the interlayer further fortifies the coating's resistance to corrosion, imparting a multi-layered protective shield. After enduring a 60-day immersion in a simulated concrete pore solution, the LCZrP/EP coating demonstrated exceptional durability, maintaining a low-frequency impedance modulus value consistently within the range of 4.27×1010 to 5.12×1010 Ω·cm2, marking a remarkable 34-fold enhancement over the performance of the epoxy coating alone. This breakthrough underscores the LCZrP/EP coating's potential as a groundbreaking solution for reinforcing bar protection in concrete, harnessing the complementary strengths of epoxy resin's physical barrier, the impermeability of two-dimensional lamellar structures, and the proactive release of corrosion inhibitors to forge a robust, multi-faceted passivation layer.

Ensuring compliance with Antarctic environmental protection through inspections: Problems and prospects

Environmental protection occupies an increasingly important place in Antarctic governance, but compliance mechanisms for Antarctic environmental protection have received little attention compared to multilateral environmental agreements. Antarctic inspection is an important tool for ensuring compliance by States Parties. However, it has been shown that inspection is mostly used as a means of information exchange and capacity building, while its monitoring role tends to be undermined. Based on empirical analysis, this paper identifies the outstanding issues in existing inspection practices, and proposes specific measures for improvement. It also explores the possibility of establishing an independent inspection body to complement existing inspections undertaken by Consultative Parties, with a view to fully utilizing its monitoring role as part of compliance mechanisms for the Antarctic environment.

Combining Physiology and Transcriptome Data Screening for Key Genes in Actinidia arguta Response to Waterlogging Stress

Actinidia arguta is a cold-resistant fruit tree but intolerant to waterlogging. Waterlogging stress is the major abiotic stress in A. arguta growth, and several pathways are involved in the response mechanisms. Fifteen physiological indices and transcriptome data of two A. arguta cultivars, which showed two forms under waterlogging, were used to identify the major factor following the leaf senescence in waterlogging. Through principal component analysis (PCA) of 15 physiological indices in ‘Kuilv’ and ‘Lvwang’, the hormone contents were selected as the most important principal component (PCA 2) out of four components in response to waterlogging stress. According to the analysis of transcriptome data, 21,750 differentially expressed genes were identified and 10 genes through WGCNA, including hormone metabolism and sucrose metabolism, were screened out on the 6th day of waterlogging. In particular, the ABA signal transduction pathway was found to be closely related to the response to waterlogging based on the correlation analysis between gene expression level and plant hormone content, which may have regulated physiological indicators and morphological changes together with other hormones. Overall, the phenomenon of leaves falling induced by ABA might be a protective mechanism. The results provided more insights into the response mechanism of coping with waterlogging stress in A. arguta.

Ground Truths: Engaging Kansas Public Libraries in Resilience Research

In Kansas, the NSF-funded statewide initiative Adaptive and Resilient Infrastructure for Social Equity (ARISE) was formed with the goal to create tools and programs that ensure support for communities in rural and urban areas who are most vulnerable to disaster, both natural and human-made. Data literacy has been identified as a foundational infrastructure need. This poster describes emerging findings from Data Literacy for All: A Kansas Public Library Initiative, a project within the ARISE initiative. This year-long study seeks to engage Kansas public library leaders in community-based research to identify the needs of their libraries for supporting everyday life data literacy in the communities they serve. Everyday life data literacy, defined as “the sociocultural data practices that occur within and across different domains of existing literacy practices,” is fundamental for social and economic resilience and can serve as a protective mechanism against misinformation. Using surveys and interviews with public library leaders, this study set out to uncover the ground truths of public library needs across the state of Kansas. An early and emerging picture suggests that public libraries may be best positioned to support data literacy and other resilience initiatives when they are recognized within their communities as critical infrastructure. This poster will report on continued findings in the Data Literacy for All project; the benefits and challenges of using community-engaged methods to involve library professionals in resilience research endeavors; and implications for preparing pre-service librarians for the profession.

Heme Oxygenase-1 Protected Against Severe Acute Pancreatitis by Inhibiting Inflammatory Response

Abstract Background Activation of NLPR3 inflammasome promotes the maturation and secretion of IL-1β and IL-18, leading to a series of inflammatory reactions, while inhibition of NLRP3 inflammasome alleviates the severity of Severe Acute Pancreatitis (SAP). An inducible enzyme responsible for heme decomposition, heme oxygenase-1 (HO-1), has anti-inflammatory, antioxidant, and anti-proliferative effects. HO-1 activity profoundly affects the host ability to forbear infection by reducing tissue damage or affecting resistance and increasing the capacity to pathogen load. We postulated that hemin, a strong HO-1 inducer, could decrease NLRP3 inflammasome activation, which would alleviate the severity of SAP and acute lung injury caused by pancreatitis. Methods By administering intraperitoneal injections of caerulein (Cae) and lipopolysaccharide (LPS), the SAP rat model was created. Then, the SAP rats were pretreated with Hemin or zinc protoporphyrin IX (Znpp, a HO-1 inhibitor) to stimulate or inhibit the HO-1 enzyme respectively, and the effects and mechanisms were investigated. Results The pancreas and lung tissue of the SAP rats suffered considerable pathological damage after Cae and LPS injection, with significant increases of amylase, lipase, IL-1β and IL-18 levels in the serum. Hemin pretreatment decreased IL-1β and IL-18 release in the serum and prevented pancreatic and pulmonary damage. Hemin dramatically reduced oxidative stress, downregulated the expression of NLRP3, ASC, and Caspase-1, and elevated HO-1 expression. On the contrary, there were no discernible changes between the SAP control and Znpp treated groups. Conclusion These results showed that hemin prevented Cae and LPS-induced lung and pancreatic injury through suppression of the inflammatory response. The impact of hemin on the activity of the NLRP3 inflammasome was depending critically on HO-1 activity. The protective role and mechanism HO-1 against the acute and severe inflammatory responses may provide a novel and effective therapeutic approach for SAP treatment.

Modern views on the etiology and role of microbial persistence in the development of inflammatory processes in the periodontal complex (review)

Alveolar tissue diseases cause the appearance of dentition defects, thereby reducing the patients' work capacity and quality of life. The purpose of this research was to investigate, modern views on the etiology of periodontitis and the role of microbial persistence in the development of inflammatory processes of periodontal complex basing on a review of literary sources. Literature review was conducted using PubMed, Web of Science, Scopus, Google Scholar from 2018 to March 2024. There were no restrictions on the date of publication or the language of scientific sources. Searches were conducted according to MeSH (Medical Subject Headings) with using the following search terms: "periodontitis", "oral mucosa", "gums", "dental plaque", "periodontium", "traumatic occlusion", "microorganisms". In total, during the initial analysis 82 literary sources were selected and processed, after further systematization of the selected information using general scientific methods, 70 of them remained. Used methods: bibliographic and analytical. Generalized perio­dontitis is a chronic inflammatory-dystrophic process that occurs as a result of various factors. In the pathogenesis of this disease, the key role is played by the inflammatory process, which is a complex interaction of microcirculatory, he­matological and connective tissue reactions to the lesion. Local (exogenic) and general (endogenic) causative factors are distinguished. The main factors that cause pathological changes in periodontium are bacterial biofilm, traumatic occlusion and various anatomical anomalies. Dental plaque occupies a special and main place among the causes of periodontitis. At present, leading pathogenetic links in the development of the inflammation in the periodontium, in par­ticular, the disruption of free radical oxidation, the processes of peroxide oxidation of lipids and proteins, the disorder of the functional state of the antioxidant system, the formation of oxidative stress, as well as the humoral link of adaptive immune protection and cytokinesis, have not been sufficiently studied. There is no doubt about the role of the microbial factor in the etiology of periodontal diseases, but the penetration of microbes into the periodontium does not always lead to the development of the disease, because the organism has a number of protective mechanisms that counteract the development of inflammation.

Striatal cholinergic transmission in an inducible transgenic mouse model of paroxysmal non-kinesiogenic dyskinesia

Altered interaction between striatonigral dopaminergic (DA) inputs and local acetylcholine (ACh) in striatum has long been hypothesized to play a central role in the pathophysiology of dystonia and dyskinesia. Indeed, previous research using several genetic mouse models of human isolated dystonia identified a shared endophenotype with paradoxical excitation of striatal cholinergic interneuron (ChIs) activity in response to activation of dopamine D2 receptors (D2R). These mouse models lack a dystonic motor phenotype, which leaves a critical gap in comprehending the role of DA and ACh transmission in the manifestations of dystonia. To tackle this question, we used a combination of ex vivo slice physiology and in vivo monitoring of striatal ACh dynamics in the inducible, phenotypically penetrant, transgenic mouse model of paroxysmal non-kinesiogenic dyskinesia (PNKD), an animal with both dystonic and dyskinetic features. We found that, similarly to genetic models of isolated dystonia, the PNKD mouse displays D2R-induced paradoxical excitation of ChI firing in ex vivo striatal brain slices. In vivo, caffeine triggers dystonic symptoms while reversing the D2R-mediated excitation of ChIs and desynchronizing ACh release in PNKD mice. In WT littermate controls, caffeine stimulates spontaneous locomotion through a similar but reversed mechanism involving an excitatory switch of the D2R control of ChI activity, associated with enhanced synchronization of ACh release. These observations suggest that the “paradoxical excitation” of cholinergic interneurons described in isolated dystonia models could represent a compensatory or protective mechanism that prevents manifestation of movement abnormalities and that phenotypic dystonia is possible only when this is absent. These findings also suggest that D2Rs may play an important role in synchronizing the ChI network leading to rhythmic ACh release during heightened movement states. Dysfunction of this interaction and corresponding desynchrony of ACh release may contribute to aberrant movements.

The role of nicotinamide riboside in the preservation of retinal ganglion cells using an in vitro glutamate-induced excitotoxicity model

Delaying or preventing the loss of retinal ganglion cells (RGCs) in glaucoma is needed for vision preservation. Glutamate-mediated neurotoxicity arises from the excessive stimulation of N-methyl-D-aspartate membrane receptors by glutamate. This overstimulation, occurring specifically in RGCs, triggers a progressive deterioration of the optic nerve that ultimately leads to the vision loss in glaucoma. Our previous investigation demonstrated that nicotinamide riboside (NR) effectively preserved RGCs in multiple mouse models of glaucoma. To investigate the precise role of NR concerning RGCs which remains uncertain, a glutamate-induced excitotoxicity RGCs damage model was established using R28 cells in this study. Results showed that NR treatment could not only prevent the decrease in cell viability but also effectively inhibit the apoptosis of R28 cells induced by glutamate, as proven by flow cytometry and expression of key pro-apoptotic proteins. Additionally, it significantly attenuated oxidative stress induced by glutamate, as evaluated by the production of inflammatory factors, reactive oxygen species (ROS) and mitochondrial ROS (mtROS). Furthermore, NR elevated the intracellular nicotinamide adenine dinucleotide (NAD+) levels in R28 cells. Lastly, we used RNA-seq to reveal the underlying mechanism of NR protection. Combining the results of RNA-seq and Western blot, we found that NR also restored the decreased protein expression of sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-gamma coactivator (PGC1α) induced by glutamate. These findings strongly indicated that NR exhibits a protective effect against R28 cell apoptosis in a glutamate-induced excitotoxicity RGCs damage model. This protective effect is likely mediated through the activation of the SIRT1/PGC1α pathway, achieved by increasing intracellular NAD + levels.

Kui-Jie-Ling capsule inhibits ulcerative colitis by modulating inflammation and gut microbiota.

Kui-Jie-Ling capsule (Kui-Jie-Ling) is a hospital preparation for ulcerative colitis (UC) in China. This study aimed at evaluating the protective effects and mechanisms of Kui-Jie-Ling and Kui-Jie-Ling combined with adalimumab on UC induced by dextran sulfate sodium (DSS). Network pharmacology was combined with an animal experiment to reveal the targets of Kui-Jie-Ling alleviating UC. The UC model was established by drinking 2.5% DSS solution for 7days. On the second day, the mice in the Kui-Jie-Ling group were orally administered with Kui-Jie-Ling (1.5 and 3.0g/kg) daily for seven consecutive days, and the mice in the combination group were orally administered with Kui-Jie-Ling (3.0g/kg) once a day for seven consecutive days and received one subcutaneous injection of adalimumab. The disease activity index, the colon length, the spleen index, the cytokines, the colon, the short-chain fatty acid content, and the gut microbiota in the colon were analyzed. The role of gut microbiota against UC was verified by fecal microbiota transplantation experiments. The animal study's results were consistent with the network pharmacology analysis, which reflected that Kui-Jie-Ling alleviated UC via multi-pathway. Kui-Jie-Ling ameliorated UC by inhibiting the formation of neutrophil extracellular traps (NETs), regulating inflammatory factors through the lipopolysaccharide-toll-like receptor 4/nuclear factor kappa B and interleukin-23-Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway, and restoring intestinal homeostasis. These studies provided the experimental basis for the clinical administration of Kui-Jie-Ling and Kui-Jie-Ling combined with adalimumab against UC.

PROTECTING OF CHILDREN’S RIGHTS BY THE PROSECUTOR THROUGH REPRESENTATIVE MEANS: SEARCH FOR THE INTERESTS OF THE STATE

The article highlights some peculiarities of the legislative regulation of the prosecutor’s protection of children’s rights by means of representative means through the prism of court practice on determining the State’s interest in this area. The purpose of the article is to highlight the peculiarities of legislative regulation of the prosecutor’s function of representing the State’s interests in court in the area of child protection and also to make proposals for improving the efficiency of the mechanism of protection of children’s rights by means of prosecutorial representation. The author notes the imperfection of the legislative regulation of the representative function of the prosecutor’s office, which narrows its human rights protection potential. It is proved that imperfect legislation and the lack of consistent and unambiguous judicial practice create difficulties in the prosecutor’s office’s function of representing the interests of the State in the field of child protection. The author formulates the author’s own concept of prosecutorial representation in the field of child protection, which is proposed to be understood as the activities carried out by specially authorized subjects - juvenile prosecutors - with a valueoriented social focus on the realisation of a child’s rights to life, healthcare, treatment, recreation, education, social security, comprehensive development and upbringing in a family environment, as well as on the protection of the State’s interests in this area as a strategic national priority. In order to increase the effectiveness of representative activities and the efficiency of protection and enforcement of children’s rights in this area, it is proposed to introduce appropriate legislative changes to the mechanism for calculating and making appropriate payments to orphans and children deprived of parental care.