Tissue Protection Research Articles

Dopamine Receptor 1 Impedes ILC2-Mediated Antitumor Immunity.

Ever-growing evidence has revealed that group 2 innate lymphoid cells (ILC2s) exhibit pleiotropic effects in antihelminth immunity, allergy, tissue protection, and cancer. Currently, the role of ILC2s in cancer is highly controversial regarding the intricate tumor microenvironment (TME), and the tumor-promoting or antitumor immunological mechanisms of ILC2s remain largely unknown. In this study, we report that dopamine receptor 1 (DRD1) restrains ILC2 activity in the TME. DRD1 deficiency promotes ILC2 activation, which irritates eosinophil recruitment and cytotoxic CD8+ T cell expansion during ongoing malignancy. Consequently, DRD1-deficient mice exhibit delayed tumor growth and reduced tumor progression. Furthermore, fenoldopam, a selective DRD1 agonist, restrains the ILC2 response in the TME and aggravates tumor burden in mice. Taken together, our data elaborate that the DRD1 signal acts as an excitatory rheostat in regulating ILC2-dependent antitumor immunity.

The Glycosaminoglycan Side Chains and Modular Core Proteins of Heparan Sulphate Proteoglycans and the Varied Ways They Provide Tissue Protection by Regulating Physiological Processes and Cellular Behaviour.

This review examines the roles of HS-proteoglycans (HS-PGs) in general, and, in particular, perlecan and syndecan as representative examples and their interactive ligands, which regulate physiological processes and cellular behavior in health and disease. HS-PGs are essential for the functional properties of tissues both in development and in the extracellular matrix (ECM) remodeling that occurs in response to trauma or disease. HS-PGs interact with a biodiverse range of chemokines, chemokine receptors, protease inhibitors, and growth factors in immune regulation, inflammation, ECM stabilization, and tissue protection. Some cell regulatory proteoglycan receptors are dually modified hybrid HS/CS proteoglycans (betaglycan, CD47). Neurexins provide synaptic stabilization, plasticity, and specificity of interaction, promoting neurotransduction, neurogenesis, and differentiation. Ternary complexes of glypican-1 and Robbo-Slit neuroregulatory proteins direct axonogenesis and neural network formation. Specific neurexin-neuroligin complexes stabilize synaptic interactions and neural activity. Disruption in these interactions leads to neurological deficits in disorders of functional cognitive decline. Interactions with HS-PGs also promote or inhibit tumor development. Thus, HS-PGs have complex and diverse regulatory roles in the physiological processes that regulate cellular behavior and the functional properties of normal and pathological tissues. Specialized HS-PGs, such as the neurexins, pikachurin, and Eyes-shut, provide synaptic stabilization and specificity of neural transduction and also stabilize the axenome primary cilium of phototoreceptors and ribbon synapse interactions with bipolar neurons of retinal neural networks, which are essential in ocular vision. Pikachurin and Eyes-Shut interactions with an α-dystroglycan stabilize the photoreceptor synapse. Novel regulatory roles for HS-PGs controlling cell behavior and tissue function are expected to continue to be uncovered in this fascinating class of proteoglycan.

Pencil Beam Scanning Bragg Peak FLASH Technique for Ultra-High Dose Rate Intensity-Modulated Proton Therapy in Early-Stage Breast Cancer Treatment.

Bragg peak FLASH-RT can deliver highly conformal treatment and potentially offer improved normal tissue protection for radiotherapy patients. This study focused on developing ultra-high dose rate (≥40 Gy × RBE/s) intensity-modulated proton therapy (IMPT) for hypofractionated treatment of early-stage breast cancer. A novel tracking technique was developed to enable pencil beaming scanning (PBS) of single-energy protons to adapt the Bragg peak (BP) to the target distally. Standard-of-care PBS treatment plans of consecutively treated early-stage breast cancer patients using multiple energy layers were reoptimized using this technique, and dose metrics were compared between single-energy layer BP FLASH and conventional IMPT plans. FLASH dose rate coverage by volume (V40Gy/s) was also evaluated for the FLASH sparing effect. Distal tracking can precisely stop BP at the target distal edge. All plans (n = 10) achieved conformal IMPT-like dose distributions under clinical machine parameters. No statistically significant differences were observed in any dose metrics for heart, ipsilateral lung, most ipsilateral breast, and CTV metrics (p > 0.05 for all). Conventional plans yielded slightly superior target and skin dose uniformities with 4.5% and 12.9% lower dose maxes, respectively. FLASH-RT plans reached 46.7% and 61.9% average-dose rate FLASH coverage for tissues receiving more than 1 and 5 Gy plan dose total under the 250 minimum MU condition. Bragg peak FLASH-RT techniques achieved comparable plan quality to conventional IMPT while reaching adequate dose rate ratios, demonstrating the feasibility of early-stage breast cancer clinical applications.

Neuroprotective properties of xenon. Literature review

A systematic analysis of scientific research devoted to the study of neuroprotective properties of xenon was carried out to determine the possibility of its use for the protection of neuronal tissues in various pathological conditions and neurodegenerative disorders. The search was carried out in freely available scientometric databases, such as PubMed, Google Scholar, Web of Science, Scopus, etc. The criteria for inclusion in the analysis were publications that discussed the role of xenon in the protection of neuronal tissues, studies of the neuroprotective properties of xenon in animal and cellular models, clinical studies demonstrating the neuroprotective potential of xenon in available English-language sources. The literature was analyzed to identify key findings, research methodology, and outcomes related to the neuroprotective properties of xenon. This included an analysis of research methods, models used to assess the impact of xenon on neuronal structures, and the volume and quality of the data obtained. In addition, the pharmacological properties of xenon are considered, in particular, its physicochemical characteristics, mechanisms of action at the molecular level, and pharmacokinetics. The results of studies of the influence of xenon on the state of vascularization of the brain after after traumatic brain injury and the potential of xenon to prevent further injuries are presented. Studies evaluating the effects of xenon on neurological deficits after ischemic stroke and its potential efficacy as an anti-inflammatory and neuroprotective agent are discussed. The effect of xenon on the white matter of the brain in patients with aneurysmal subarachnoid hemorrhage and its potential to reduce damage are highlighted. Research data on the use of the liposomal form of xenon to improve the condition after a stroke, mental health, and the effect of xenon on the intestinal microbiota were analyzed. The results of studies on the effectiveness of repeated injections of xenon to improve sensorimotor and neuropsychic functions in patients after a stroke, as well as the use of xenon as one of the components of intensive therapy for alcohol poisoning and the potential advantages of such an approach are presented. Based on the analysis of literary sources, it was concluded that xenon is a promising tool for protecting brain structures in traumatic injuries and ischemic lesions, which improves rehabilitation. It reduces inflammation and increases the integrity of the blood-brain barrier, which helps restore brain function.

Baicalin: A potential therapeutic agent for diabetes and renal protection

Background: Diabetes is a complex metabolic disease manifested by raised glucose levels in the blood and impaired insulin function leading to various organ complications, including diabetic nephropathy. Baicalin, a flavonoid derived from Scutellaria baicalensis Georgi, has garnered substantial attention for its diverse beneficial effects, including anti-inflammatory, anti-allergic, anti- apoptotic properties, etc. Intriguingly, in vivo studies in rats have further unveiled baicalin’s potential to directly modulate pancreatic beta cells, suggesting a promising role as an anti-diabetic agent.Objective: The purpose of this study is to comprehensively explore the anti-diabetic effect of baicalin, focusing on key parameters such as plasma insulin levels, glucose levels, hemoglobin, and glycated hemoglobin levels in streptozotocin-induced diabetic rats. Additionally, we sought to explore Baicalin’s ability to provide renal protection by evaluating serum renal markers. Methodology: This study involved a total of 30 Wistar albino male rats. Diabetes was created in rats by a single intraperitoneal streptozotocin injection (40 mg/kg). After 72 hours, the rats with diabetes were segregated into four treatment groups (Group II to Group V) comprising 6 animals each. Group I consists of six normal control rats (without diabetes). The groups received different treatment protocols, including normal saline, DMSO, Baicalin (50 mg/kg/day), and glibenclamide (6 mg/kg/day) for 45 days. Throughout the study, meticulous observations were made regarding the animals’ general appearance, body weight, behavior, and their fasting glucose levels in venous blood.Results: Oral dosing with Baicalin at the rate of 50 mg/kg body weight revealed notable enhancements in insulin secretion and hemoglobin levels, alongside notable reductions in blood levels of glucose and glycated hemoglobin compared to the glibenclamide-treated type 2 diabetic rats. Additionally, Baicalin displayed a protective action on renal tissue, as shown by reduced serum creatinine, uric acid, and urea levels.Conclusion: Our investigation unveils Baicalin’s potential as a promising anti-diabetic agent with the added benefit of renal tissue protection. The observed improvements in various physiological parameters warrant further exploration of Baicalin’s therapeutic mechanisms and clinical applications, presenting it as a compelling candidate for diabetes management and diabetic nephropathy prevention. IAEC Approval No: AVMC/IAEC/2019/07/25/08 Keywords: Baicalin, Blood glucose, Diabetes, Male wistar rats, Streptozotocin

CXCR6 orchestrates brain CD8+ T cell residency and limits mouse Alzheimer's disease pathology.

Neurodegenerative diseases, including Alzheimer's disease (AD), are characterized by innate immune-mediated inflammation, but functional and mechanistic effects of the adaptive immune system remain unclear. Here we identify brain-resident CD8+ T cells that coexpress CXCR6 and PD-1 and are in proximity to plaque-associated microglia in human and mouse AD brains. We also establish that CD8+ T cells restrict AD pathologies, including β-amyloid deposition and cognitive decline. Ligand-receptor interaction analysis identifies CXCL16-CXCR6 intercellular communication between microglia and CD8+ T cells. Further, Cxcr6 deficiency impairs accumulation, tissue residency programming and clonal expansion of brain PD-1+CD8+ T cells. Ablation of Cxcr6 or CD8+ T cells ultimately increases proinflammatory cytokine production from microglia, with CXCR6 orchestrating brain CD8+ T cell-microglia colocalization. Collectively, our study reveals protective roles for brain CD8+ T cells and CXCR6 in mouse AD pathogenesis and highlights that microenvironment-specific, intercellular communication orchestrates tissue homeostasis and protection from neuroinflammation.

The influence of the tooth preparation finish line position on the expression of matrix metalloproteinase-9 and the presence of periodontopathogens in the gingival crevicular fluid.

The objective of the study was to determine the concentration of matrix metalloproteinase 9 (MMP-9) and changes in the presence of periodontopathogens in the gingival crevicular fluid before and after tooth preparation with the subgingival and equigingival finish line position. The clinical prospective study included 20 subjects with an indication for upper canine preparation, with the subgingival (group 1) and equigingival finish line (group 2). Samples were taken in four observation intervals: 5 minutes before (control samples), as well as 15 minutes, 24 and 72 hours after tooth preparation (experimental samples). Measurement of MMP-9 was done using Enzyme-linked Immunosorbent Assay (ELISA). The presence of bacteria in the gingival fluid was proven by the Polymerase chain reaction (PCR) analysis. The MMP-9 values did not differ statistically significantly between the groups (p=0.524). The MMP-9 values showed a statistically significant difference in the given observation period (p<0.001) with a significant linear increase in values (p<0.001). A significant quadratic trend recorded a decrease in the MMP-9 values 15 minutes after preparation, and an increase 24 hours after preparation, without a significant difference in the interaction between groups (p=0.392). After preparation, a significant difference in the presence of periodontopathogens was confirmed, i.e., a decrease in the presence of Prevotella intermedia (p=0.025) and Tannerella forsythia (p=0.016) in group 1, and an increase in the presence of Aggregatibacter actinomycetemcomitans in both groups (p=0.029, p=0.026). The study is a good basis for determining the influence of tooth preparation on gingival inflammation, with therapeutic (choice of preparation technique) and preventive significance regarding the protection of the periodontal tissue from possible iatrogenic damage.

Menstrual Blood-Derived Stem Cell Paracrine Factors Possess Stimulatory Effects on Chondrogenesis In Vitro and Diminish the Degradation of Articular Cartilage during Osteoarthritis.

Articular cartilage is an avascular tissue with a limited capacity for self-regeneration, leading the tissue to osteoarthritis (OA). Mesenchymal stem cells (MSCs) are promising for cartilage tissue engineering, as they are capable of differentiating into chondrocyte-like cells and secreting a number of active molecules that are important for cartilage extracellular matrix (ECM) synthesis. The aim of this study was to evaluate the potential of easily accessible menstrual blood-derived MSC (MenSC) paracrine factors in stimulating bone marrow MSC (BMMSCs) chondrogenic differentiation and to investigate their role in protecting cartilage from degradation in vitro. MenSCs and BMMSCs chondrogenic differentiation was induced using four different growth factors: TGF-β3, activin A, BMP-2, and IGF-1. The chondrogenic differentiation of BMMSCs was stimulated in co-cultures with MenSCs and cartilage explants co-cultured with MenSCs for 21 days. The chondrogenic capacity of BMMSCs was analyzed by the secretion of four growth factors and cartilage oligomeric matrix protein, as well as the release and synthesis of cartilage ECM proteins, and chondrogenic gene expression in cartilage explants. Our results suggest that MenSCs stimulate chondrogenic response in BMMSCs by secreting activin A and TGF-β3 and may have protective effects on cartilage tissue ECM by decreasing the release of GAGs, most likely through the modulation of activin A related molecular pathway. In conclusion, paracrine factors secreted by MenSCs may turn out to be a promising therapeutical approach for cartilage tissue protection and repair.

Chitosan Nanoparticles for Gastroesophageal Reflux Disease Treatment.

Gastroesophageal Reflux Disease (GERD) is a chronic ailment that results from the backward flow of stomach acid into the esophagus, causing heartburn and acid regurgitation. This review explores nanotechnology as a novel treatment approach for GERD. Chitosan nanoparticles (CSNPs) offer several advantages, including biocompatibility, biodegradability, and targeted drug delivery capabilities. CSNPs have been extensively studied due to their ability to encapsulate and release medications in a controlled manner. Different nanoparticle (NP) delivery systems, including gels, microspheres, and coatings, have been developed to enhance drug retention, drug targeting, and controlled release in the esophagus. These nanoparticles can target specific molecular pathways associated with acid regulation, esophageal tissue protection, and inflammation modulation. However, the optimization of nanoparticle formulations faces challenges, including ensuring stability, scalability, and regulatory compliance. The future may see CSNPs combined with other treatments like proton pump inhibitors (PPIs) or mucosal protectants for a synergistic therapeutic approach. Thus, CSNPs provide exciting opportunities for novel GERD treatment strategies.

Unilateral biportal endoscopic technique combined with percutaneous transpedicular screw fixation for thoracolumbar burst fractures with neurological symptoms: technical note and preliminary report

BackgroundPrevious studies on thoracolumbar fractures with neurological symptoms have focused on how to achieve satisfactory fracture reduction, adequate nerve decompression, and stable spinal alignment. With the development of the minimally invasive spine surgery technique, achieving satisfactory treatment results and reducing iatrogenic trauma at the same time has become a new goal of spinal surgery. This research used percutaneous transpedicular screw distraction to partially reduce the fractured vertebrae, followed by completing nerve decompression and reducing residual displacement bone fragments with the assistance of the unilateral biportal endoscopic (UBE) technique to achieve full protection of bone-ligament tissue and obtain good clinical efficacy.MethodsGuide wires were safely inserted into the fractured vertebra and adjacent upper and lower vertebra under the surveillance of anteroposterior and lateral X-ray fluoroscopy. Transpedicular screws were implanted via guide wires on the side with mild neurological deficits or bone fragment compression (the opposite side of the endoscopic operation). A titanium rod was installed and moderately distracted to reduce the fractured vertebra. Then, under the guidance of the endoscopic view, the laminectomy and ligamentum flavum resection were completed according to the position of the protruding bone fragment into the spinal canal, and the compressed dural sac or nerve root was fully exposed and decompressed. An L-shaped replacer was used to reduce residual bone fragments. The ipsilateral transpedicular screws and rod were installed and adjusted to match the contralateral side. The drainage tube was indwelled, and the incision was closed. The preoperative and postoperative images of the patients were evaluated, and the recovery of neurological symptoms was observed.ResultsSurgery was successfully completed on all six patients, and no intraoperative conversion to open surgery was performed. Postoperative images showed good reduction of the protruding bone fragment and good placement of all screws. At the last follow-up, the neurological symptoms of all patients returned to normal.ConclusionThe UBE technique combined with percutaneous transpedicular screw fixation in the treatment of thoracolumbar fractures with neurological symptoms can effectively achieve the reduction of displaced bone fragments, improve damaged nerve function, stabilize spinal alignment, and protect the integrity of bone-ligament tissue.

The regulatory role of differential microRNA expressions on cellular inflammatory factors IL-6 and IL-10 in Echinococcus granulosus-induced anaphylaxis.

To determine the pathogenesis and molecular targets of anaphylaxis caused by hydatid cyst fluid leakage. First, Balb/c mice were infected with Echinococcus granulosus, and then the anaphylaxis model was developed. The mice were separated into: anaphylaxis caused by the cystic echinococcosis group (ANPC), the cystic echinococcosis without anaphylaxis group (CE group), and the normal control group (CTRL). Following this, the spleen tissue was collected for microRNA (miRNA) sequencing. Using bioinformatics analysis, differentially expressed miRNAs(DEMs) were identified. Then, through the use of protein-protein interaction (PPI) networks, the key target genes for miRNA regulation associated with echinococcosis-induced anaphylaxis were identified. ANPC and CE groups have 29 and 39 DEMscompared to the CTRL group, respectively. Based on these 25 DEMs, interactions between miRNA and mRNA were screened, and 174 potential target genes were identified. We performed gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes pathwayenrichment analysis on these 174 target genes, and the results revealed that the three pathways with the highest enrichment were the PI3K-Akt signaling pathway, FoxO signaling pathway, and Focal adhesion. The interaction analysis of PPI and miRNA-hub gene networks revealed that interleukin 6 (IL-6) was regulated by miR-146a-5p and miR-149-5p, while IL-10 was regulated by miR-29b-3p and miR-29c-3. Using reverse transcription polymerase chain reaction, we found that the miRNAs regulating IL-6 and IL-10 were significantly upregulated in the ANPC group, and there are three pathways involved in that process: Pathways of PI3K-Akt signaling, FoxO signaling, and Focal adhesion. IL-6 and IL-10 play an important role in cellular pyroptosis and apoptosis. Therefore, the aforementioned results provide significant reference value for elucidating the mechanism of cellular pyroptosis and apoptosis in echinococcosis-induced anaphylaxis, and for formulating tissue and organ protection strategies for patients with cystic echinococcosis when anaphylaxis is triggered by hydatid cyst rupture.

Effect of adenosine treatment on ionizing radiation toxicity in zebrafish early life stages.

The danger of ionizing radiation exposure to human health is a concern. Since its wide use in medicine and industry, the development of radioprotectors has been very significant. Adenosine exerts anti-inflammatory actions and promotes tissue protection and repair, by activating the P1 receptors (A1, A2A, A2B, and A3). Zebrafish (Danio rerio) is an appropriate tool in the fields of toxicology and pharmacology, including the evaluation of radiobiological outcomes and in the search for radioprotector agents. This study aims to evaluate the effect of adenosine in the toxicity induced by radiation in zebrafish. Embryos were treated with 1, 10, or 100µM adenosine, 30min before the exposure to 15Gy of gamma radiation. Adenosine potentiated the effects of radiation in heart rate, body length, and pericardial edema. We evaluated oxidative stress, tissue remodeling and inflammatory. It was seen that 100µM adenosine reversed the inflammation induced by radiation, and that A2A2 and A2B receptors are involved in these anti-inflammatory effects. Our results indicate that P1R activation could be a promising pharmacological strategy for radioprotection.

Differential roles of regulatory T cells in acute respiratory infections.

Acute respiratory infections trigger an inflammatory immune response with the goal of pathogen clearance; however, overexuberant inflammation causes tissue damage and impairs pulmonary function. CD4+FOXP3+ regulatory T cells (Tregs) interact with cells of both the innate and the adaptive immune system to limit acute pulmonary inflammation and promote its resolution. Tregs also provide tissue protection and coordinate lung tissue repair, facilitating a return to homeostatic pulmonary function. Here, we review Treg-mediated modulation of the host response to respiratory pathogens, focusing on mechanisms underlying how Tregs promote resolution of inflammation and repair of acute lung injury. We also discuss potential strategies to harness and optimize Tregs as a cellular therapy for patients with severe acute respiratory infection and discuss open questions in the field.

Elevation of NAD+ by nicotinamide riboside spares spinal cord tissue from injury and promotes locomotor recovery

Spinal cord injury (SCI)-induced tissue damage spreads to neighboring spared cells in the hours, days, and weeks following injury, leading to exacerbation of tissue damage and functional deficits. Among the biochemical changes is the rapid reduction of cellular nicotinamide adenine dinucleotide (NAD+), an essential coenzyme for energy metabolism and an essential cofactor for non-redox NAD+-dependent enzymes with critical functions in sensing and repairing damaged tissue. NAD+ depletion propagates tissue damage. Augmenting NAD+ by exogenous application of NAD+, its synthesizing enzymes, or its cellular precursors mitigates tissue damage. Nicotinamide riboside (NR) is considered to be one of the most promising NAD+ precursors for clinical application due to its ability to safely and effectively boost cellular NAD+ synthesis in rats and humans. Moreover, various preclinical studies have demonstrated that NR can provide tissue protection. Despite these promising findings, little is known about the potential benefits of NR in the context of SCI. In the current study, we tested whether NR administration could effectively increase NAD+ levels in the injured spinal cord and whether this augmentation of NAD+ would promote spinal cord tissue protection and ultimately lead to improvements in locomotor function. Our findings indicate that administering NR (500 mg/kg) intraperitoneally from four days before to two weeks after a mid-thoracic contusion-SCI injury, effectively doubles NAD+ levels in the spinal cord of Long-Evans rats. Moreover, NR administration plays a protective role in preserving spinal cord tissue post-injury, particularly in neurons and axons, as evident from the observed gray and white matter sparing. Additionally, it enhances motor function, as evaluated through the BBB subscore and missteps on the horizontal ladderwalk. Collectively, these findings demonstrate that administering NR, a precursor of NAD+, increases NAD+ within the injured spinal cord and effectively mitigates the tissue damage and functional decline that occurs following SCI.

Alleviation effect of Deinococcus sp. Y35 together with autoinducer 2 on the physiological stress caused by Microcystis aeruginosa to zebrafish intestines

Microcystis aeruginosa, the dominant species causing cyanobacterial blooms, poses a serious threat to water environment security and development of aquaculture. The physiological stress in aquatic animals after exposure to M. aeruginosa has been extensively studied, however, the impacts on the physiological stress of aquatic animals in the process of controlling M. aeruginosa blooms remain unclear. In this study, we investigated the effect of quorum sensing autoinducer 2 (AI-2) on the algicidal activity of Deinococcus sp. Y35, and determined the effect of strain Y35 together with AI-2 on the physiological stress caused by M. aeruginosa to zebrafish. The results demonstrated that the synthesized AI-2 in vitro based on proteins MtnN and LuxS of strain Y35 could significantly promote the synthesis of algicidal pigment and improve the algicidal activity of strain Y35. The M. aeruginosa exposure could seriously damage the intestinal structure integrity of zebrafish, inducing oxidative stress and lipid peroxidation, as well as significant up-regulation of pro-inflammatory genes expression level. The separate application of strain Y35 could alleviate the physiological stress caused by M. aeruginosa including the protection of intestinal tissue, reducing oxidative stress and lipid peroxidation, as well as inhibition of pro-inflammatory genes expression. Meanwhile, the addition of synthesized AI-2 could significantly increase the alleviation effect of strain Y35 on the physiological stress. These results indicate that algicidal bacteria like Deinococcus sp. Y35 can play an important role in alleviating physiological stress of aquatic organisms and can be regarded as a potential resource for controlling cyanobacterial blooms and protecting aquatic organisms.

Herbal Medicines and Recent Development on Novel Herbal Drug Delivery System

The World Health Organization (WHO) defines herbal medicine as a technique that uses herbs, herbal ingredients, herbal preparations, and finished herbal products. Herbal remedies contain a variety of chemical components known as phytochemicals, which fall into a number of categories including saponins, flavonoids, glycosides, tannins, alkaloids, and terpenoids. Due to the presence of these phytochemicals, herbal medications can be used to treat a variety of ailments and diseases, including gastrointestinal problems, skin infections, arthritis, migraines, and weariness. Herbal medicines have less major adverse effects than conventional pharmaceuticals and are less expensive.&#x0D; New herbal formulations can include transfersomes, ethosomes, microspheres, phytosomes, liposomes, polymeric nanoparticles, and nanocapsules. In comparison to traditional herbal medicines, the novel herbal drug delivery systems offer many advantages, including increased solubility and bioavailability, protection from side effects, enhanced pharmacological action, increased stability, better delivery to tissue macrophages, consistent delivery, and protection against the physical and chemical breakdown of active ingredients. To incorporate standardised herbal extract or aqueously soluble active ingredients into phospholipids to build lipid companionable molecular complexes, phytosome has been described as a patented innovative herbal technology produced by a leading manufacturer of medicines and nutraceuticals. The use of herbal medicines can be expanded in order to increase their efficacy by incorporating them into more sophisticated medications.

Metabolite Changes of Perna canaliculus Following a Laboratory Marine Heatwave Exposure: Insights from Metabolomic Analyses.

Temperature is considered to be a major abiotic factor influencing aquatic life. Marine heatwaves are emerging as threats to sustainable shellfish aquaculture, affecting the farming of New Zealand's green-lipped mussel [Perna canaliculus (Gmelin, 1791)]. In this study, P. canaliculus were gradually exposed to high-temperature stress, mimicking a five-day marine heatwave event, to better understand the effects of heat stress on the metabolome of mussels. Following liquid chromatography-tandem mass spectrometry analyses of haemolymph samples, key sugar-based metabolites supported energy production via the glycolysis pathway and TCA cycle by 24 h and 48 h of heat stress. Anaerobic metabolism also fulfilled the role of energy production. Antioxidant molecules acted within thermally stressed mussels to mitigate oxidative stress. Purine metabolism supported tissue protection and energy replenishment. Pyrimidine metabolism supported the protection of nucleic acids and protein synthesis. Amino acids ensured balanced intracellular osmolality at 24 h and ammonia detoxification at 48 h. Altogether, this work provides evidence that P. canaliculus has the potential to adapt to heat stress up to 24 °C by regulating its energy metabolism, balancing nucleotide production, and implementing oxidative stress mechanisms over time. The data reported herein can also be used to evaluate the risks of heatwaves and improve mitigation strategies for aquaculture.

PARAMETERS OF OXIDATIVE BALANCE AND CHOLESTEROL METABOLISM IN MUSCLE TISSUE DURING PROLONGED RESTRICTION OF MOTOR ACTIVITY

Actuality. The leading role in the pathogenesis of metabolic disorders in hypokinesia is performed by disorders of oxidative balance and lipid metabolism. Especially important are studies of metabolic disorders at subcellular level. The aim of the study is to investigate oxidative balance and cholesterol metabolism in muscle tissue under motor activity restriction of different duration. Material and methods. Comprehensive investigation of free radical oxidation parameters (diene conjugates, ТBA contents, intensity of chemiluminescence), antioxidant protection (total antioxidant activity, antiradical activity) and cholesterol metabolism in heart muscle and thigh muscle tissues of white male rats under movement restriction during up to 28 days, which was achieved by placing animals in individual 40 cm2 cells. Results. The patterns of metabolic changes in the muscle tissue depending on the duration of motor activity restriction were established in the form of free radical oxidation intensification, reduction of antioxidant protection resources and increase of cholesterol content in the heart muscle. These metabolic changes were expressed most prominently on the 14th to 21st days of the experiment. In addition to violations of the oxidant balance, a specific feature of changes in cholesterol content in the thigh muscle was a wave-like change of this index in the form of an increase on the 7th day of the experiment, followed by a decrease with minimal values on the 21st day of the experiment. Conclusion. Decrease in antioxidant protection resources and intensification of free-radical oxidation reactions constitute one of the leading mechanisms of metabolic disturbances in restricting motor activity, which is confirmed by significant changes of the studied indicators. Comprehensive study of the indicators characterizing the processes of free-radical oxidation, antioxidant protection and cholesterol content is an informative criterion of the effects of hypokinesia on the body, and the obtained data allow the inclusion of antioxidants in the complex prevention and therapy in forced limitation of motor activity. The author declares that there is no conflict of interest in the performance of this work.

Cytotoxicity of human antibodies targeting the circumsporozoite protein is amplified by 3D substrate and correlates with protection

Human monoclonal antibodies (hmAbs) targeting the Plasmodium falciparum circumsporozoite protein (PfCSP) on the sporozoite surface are a promising tool for preventing malaria infection. However, their mechanisms of protection remain unclear. Here, using 13 distinctive PfCSP hmAbs, we provide a comprehensive view of how PfCSP hmAbs neutralize sporozoites in host tissues. Sporozoites are most vulnerable to hmAb-mediated neutralization in the skin. However, rare but potent hmAbs additionally neutralize sporozoites in the blood and liver. Efficient protection in tissues mainly associates with high-affinity and high-cytotoxicity hmAbs inducing rapid parasite loss-of-fitness in the absence of complement and host cells invitro. A3D-substrate assay greatly enhances hmAb cytotoxicity and mimics the skin-dependent protection, indicating that the physical stress imposed on motile sporozoites by the skin is crucial for unfolding the protective potential of hmAbs. This functional 3D cytotoxicity assay can thus be useful for downselecting potent anti-PfCSP hmAbs and vaccines.

Role of Klotho and N-acetylcysteine in Oxidative Stress Associated with the Vitrification of Ovarian Tissue Cytoprotective Function of Klotho in Cryopreservation.

Cryopreservation can cause mechanical and chemical stress, ultimately leading to the formation of reactive oxygen species (ROS) and oxidative stress. ROS inhibits the expression of antioxidant enzymes in cells, resulting in increased DNA fragmentation and apoptosis. In this paper, we used a vitrification method that has the advantage of producing less ice crystal formation, cost-effectiveness, and time efficiency during cryopreservation. The objective of this paper is to evaluate the degree of protection of ovarian tissue against oxidative stress when N-acetylcysteine (NAC) and Klotho proteins are treated in the vitrification process of ovarian tissue. METHODS: The control group and the cryopreservation groups were randomly assigned, and treated NAC, Klotho, or the combination (NAC + Klotho). The cell morphological change, DNA damage, senescence, and apoptosis of each group after the freeze-thaw process were compared using transmission electron microscopy, immunohistochemistry, and western blot analysis. Both NAC and Klotho were found to be more effective at protecting against DNA damage than the control; however, DNA damage was greater in the NAC + Klotho group than in the group treated with NAC and Klotho, respectively. DNA damage and cellular senescence were also reduced during the vitrification process when cells were treated with NAC, Klotho, or the combination (NAC + Klotho). NAC increased apoptosis during cryopreservation, whereas Klotho inhibited apoptosis and NAC-induced apoptosis. This study highlights Klotho's benefits in inhibiting DNA damage, cell senescence, and apoptosis, including NAC-induced apoptosis, despite its unclear role in vitrification.