Physiological Activity Research Articles

Intracranial substrates of meditation-induced neuromodulation in the amygdala and hippocampus

Meditation is an accessible mental practice associated with emotional regulation and well-being. Loving-kindness meditation (LKM), a specific subtype of meditative practice, involves focusing one's attention on thoughts of well-being for oneself and others. Meditation has been proven to be beneficial in a variety of settings, including therapeutic applications, but the neural activity underlying meditative practices and their positive effects are not well understood. It has been difficult to understand the contribution of deep limbic structures given the difficulty of studying neural activity directly in the human brain. Here, we leverage a unique patient population, epilepsy patients chronically implanted with responsive neurostimulation devices that allow chronic, invasive electrophysiology recording to investigate the physiological correlates of LKM in the amygdala and hippocampus of novice meditators. We find that LKM-associated changes in physiological activity were specific to periodic, but not aperiodic, features of neural activity. LKM was associated with an increase in γ (30 to 55 Hz) power and an alternation in the duration of β (13 to 30 Hz) and γ oscillatory bursts in both the amygdala and hippocampus, two regions associated with mood disorders. These findings reveal the nature of LKM-induced modulation of limbic activity in first-time meditators.

Atrioventricular Block Treatment: Pacing Site, AV Synchrony, or Both?

Background/Objectives: Right ventricular pacing (RVP), leadless pacing (LL), and conduction system pacing (CSP) are treatment options for atrioventricular block (AVB), each with distinct characteristics. However, the long-term outcomes of these pacing strategies remain insufficiently compared. This study evaluates clinical and echocardiographic outcomes of patients with AVB treated with dual chamber RVP, His bundle pacing (HBP), or LL. Methods: This single-center observational registry study included 22 consecutive patients receiving LL with atrioventricular resynchronization functionality (October 2020 to October 2022), matched with 66 control patients receiving either RVP (33 patients) or HBP (33 patients) using propensity score matching (2:3:3 ratio). Primary and secondary endpoints included all-cause mortality, cardiovascular mortality, heart failure, and echocardiographic outcomes. Atrioventricular synchrony in the LL group was assessed. Results: At two years, all-cause mortality was significantly higher in the LL group compared to RVP (36.4% vs. 6.1%, p = 0.002) and HBP (36.4% vs. 12.1%, p = 0.03), but LL had a more severe clinical profile. Cardiovascular mortality and heart failure incidence showed no significant differences. Patients receiving RVP showed a significant decrease in left ventricular ejection fraction and an increase in ventricular volumes. In contrast, HBP patients exhibited favorable cardiac remodeling. Stratification based on atrial sensing showed that LL patients with >66% AV synchrony had a lower mortality (p = 0.02). Conclusions: CSP offers superior results compared to other pacing methods in terms of ventricular function owing to a physiological ventricular activation and maintenance of AV synchrony. However, LL may be a viable alternative for frail and high-risk patients, as the suboptimal AV synchrony is traded off with lesser ventricular dyssynchrony.

Pericytes Are Odontoblast Progenitor Cells Depending on ER Stress.

Odontoblasts are terminally differentiated cells that exhibit mechanosensitivity and mineralization capacity. Mechanosensitive ion channels such as Piezo1 are present in odontoblasts and are associated with their physiological functions via Ca2+ signaling. Both Ca2+ signals via Ca2+ influx from mechanosensitive ion channels and Ca2+ release from Ca2+ stores function as secondary messenger systems for various biological phenomena. The endoplasmic reticulum (ER) serves as an intracellular Ca2+ store that mobilizes intracellular Ca2+. Changes in Ca2+ concentration inside the ER are among the factors that cause ER stress. Perivascular cells are located around odontoblasts in the dental pulp. Although such formation indicates that perivascular cells interact with odontoblasts, their detailed profiles under developmental and pathological conditions remain unclear. In this study, we revealed that pericyte marker, neural/glial antigen 2 (NG2)-positive cells, in cell-rich zones (CZs) can differentiate into Piezo1-positive odontoblasts following genetic odontoblast depletion in mice, and modeled as odontoblast death after severe dentin injury and as reparative dentin formation. NG2-positive pericytes differentiated into odontoblasts faster than glial cells. To determine how NG2-positive cells differentiate into Piezo1-positive odontoblasts, we focused on the ER-stress sensor protein, activating transcription factor 6a (ATF6a). After genetic odontoblast depletion, NG2-positive cells regenerated in the odontoblast layer and were capable of acting as functional odontoblasts. In the presence of extracellular Ca2+, the application of a sarco/ER Ca2+-ATPase (SERCA) inhibitor, thapsigargin, known as an ER-stress inducer, increased the intracellular Ca2+ concentration in the odontoblast lineage cells (OLCs). The increase was significantly inhibited by the application of a pharmacologic Piezo1 inhibitor, indicating that ER stress by SERCA inhibition augmented Piezo1-induced responses in odontoblast progenitor cells. However, the physiological activation of Gq-coupled receptors by adenosine diphosphate did not induce Piezo1 activation. Gene silencing of ATF6a and/or NG2 impaired the mineralization of OLCs. Overall, ATF6a orchestrates the differentiation of NG2-positive pericytes into functional odontoblasts that act as sensory receptor cells and dentin-forming cells.

Modulation of virulence and metabolic profiles in Klebsiella pneumoniae under indole-mediated stress response

Indole, a crucial bacterial signaling molecule, plays a fundamental role in regulating various physiological processes within bacteria, including growth, acid tolerance, biofilm development, motility, and other cellular functions. Its regulatory influence extends beyond indole-producing bacteria, significantly impacting the physiological activities in non-indole-producing species. In this study, we demonstrate that indole enhances the pathogenicity and viability of Klebsiella pneumoniae using the Galleria mellonella infection model and serum killing assay. Concurrently, indole has varying effects on biofilm formation in K. pneumoniae, with some strains showing enhanced biofilm formation ability. To elucidate the underlying molecular mechanisms, transcriptome analysis revealed that indole exposure in K. pneumoniae led to the upregulation of genes associated with pili formation and iron acquisition systems, while simultaneously inducing oxidative stress responses. Additionally, our analysis uncovered extensive metabolic remodeling. Specifically, we observed significant upregulation of genes involved in simple carbohydrate utilization pathways, including those responsible for galactose, mannose, and maltose metabolism, as well as enhanced expression of genes associated with pyrimidine biosynthesis. These findings collectively indicate that indole enhances the intestinal colonization and pathogenicity of K. pneumoniae primarily by modulation of fimbriae expression and metabolic pathway regulation.

Multifunctional Strain/Pressure Sensor Based on Ag@Polydopamine Nanohybrid Methacrylamide Chitosan/Polyacrylamide Hydrogel for Healthcare Monitoring.

Hydrogels have emerged as promising candidates for flexible sensors due to their softness, biocompatibility, and tunable physicochemical properties. However, achieving synchronous satisfaction of conformality, conductivity, and diverse biological functions in hydrogel sensors remains a challenge. Here, we proposed a multifunctional hydrogel sensor by incorporating silver-loaded polydopamine nanoparticles (Ag@PDA) into a thermally cross-linked methacrylamide chitosan (CSMA) and acrylamide network, namely, Ag@PDA/(CSMA-PAM). The Ag@PDA/(CSMA-PAM) hydrogel showed the capability to respond effectively to both strain and pressure, enabling its independent application as either a strain sensor or a pressure sensor. The sensitivity of the hydrogel can reach 2.13 within the strain range of 65 to 150%, exhibiting a response and recovery time of 550 ms when utilized as a strain sensor. In contrast, its sensitivity was 0.07 kPa-1 during pressures ranging from 0 to 2.15 kPa, with a response and recovery time of 136 ms when employed as a pressure sensor. Additionally, the hydrogel sensor demonstrated high linearity (0.998 for strain and 0.98 for pressure), stable cycling ability (500 cycles), and low detection limit (0.5% for strain and 150 Pa for pressure). Moreover, the Ag@PDA/(CSMA-PAM) hydrogel exhibited good stability and reliability for a variety of practical applications, including the detection of subtle and large deformations, as well as real-time physiological activity monitoring. Further, owing to the bioactive components of chitosan and Ag@PDA present in the hydrogel, the Ag@PDA/(CSMA-PAM) sensor exhibited satisfactory biocompatibility along with excellent antioxidant and antibacterial activities, making it highly promising for applications as wearable sensors in personalized healthcare.

The effects of waterlogging duration on responses of above- and belowground organs of Pinus thunbergii seedlings after the release from waterlogging

ABSTRACT The tsunami in March 2011 heavily damaged the Pinus thunbergii Parlatore erosion-control coastal forests of northeastern Japan. The restoration is in process but has been challenged by waterlogging resulting from soil compaction of artificial growth bases. In this study, a pot experiment was conducted to elucidate the waterlogging responses of two-year-old P. thunbergii seedlings in terms of waterlogging duration. Three waterlogging durations were set (7 days, 17 days, and 32 days, water table at soil surface) during August, followed by a waterlogging-free recovery period (28 days) in September. In this experiment, the responses of both above- and belowground organs during waterlogging and after the release from waterlogging were elucidated, focusing on parameters, such as transpiration and photosynthesis rates, as well as fine root growth and morphology. As a result, we found that under the conditions of our experiment, if the waterlogging duration is within 17 days, P. thunbergii seedlings can recover physiological activity in about a week; however, if the waterlogging duration is over 32 days, recovery after the release from waterlogging largely varied among seedlings. For the seedlings that could recover, recovery took at least 2 weeks, which required new fine root growth. In cases where the damage was irreversible, seedlings showed an overall decline. These results suggest that it is important to manage the waterlogging conditions so that P. thunbergii seedlings can recover without prolonged negative effects.

The chemical and biological characteristics of fatty acid esters of hydroxyl fatty acids.

With the continuous advancements in detection methods and the exploration of unknown substances, an increasing number of bioactive compounds are being discovered. Fatty acid esters of hydroxyl fatty acids (FAHFAs), a class of endogenous lipids found in 2014, exhibit various physiological activities, such as improving glucose tolerance and insulin sensitivity, stimulating insulin secretion, and demonstrating broad anti-inflammatory effects. Moreover, some FAHFAs are closely linked to intestinal health and can serve as potential biomarkers for gut health. Various FAHFAs have been observed in food, including palmitic acid esters of hydroxy stearic acids (PAHSA), oleic acid esters of hydroxy stearic acids (OAHSA), linoleic acid esters of hydroxy linoleic acid (LAHLA). As a type of lipid regularly consumed in the daily diet, it is highly important to ascertain the types and quantities of FAHFAs present in the diet. This article, based on existing research, provides a review of the analysis methods for FAHFAs, particularly focusing on the separation of chiral isomers. It also summarizes the sources and contents of dietary FAHFAs, emphasizing their bioavailability and impact on the gut. Understanding the beneficial effects of these lipids in the diet can serve as a valuable reference for the development of specific functional foods.

Research progress on the performance of expandable systems for long-term gastric retention.

Gastroretentive systems have gained attention due to their prolonged retention time in the human body, and they have the potential to improve treatment effects, simplify treatment regimens, and improve patient compliance. Among these systems, expandable gastroretentive systems (EGRSs) have emerged as an important type of carrier that can reside in the stomach for a desired period through on-demand expansion for drug delivery, obesity intervention, and medical diagnosis. As the physiological environment significantly influences the performance of EGRSs, here, the physiological factors such as the stomach's physiological structure and activity pattern, and the character of gastric juice are summarized. Following this, the research progress of EGRSs from ingestion to removal for long-term gastric retention is discussed with respect to the influencing factors and reinforcement strategies in mechanics. Additionally, as the duration of gastric retention increases, safety concerns arise. As such, safety issues in terms of removal after retention or in an emergency are also analyzed. Finally, the biomedical application of EGRSs as diagnostic and therapeutic tools and the potential direction for further research are discussed. STATEMENT OF SIGNIFICANCE: Expandable gastroretentive systems (EGRSs) resist gastric emptying due to their size exceeding the pylorus diameter, offering promising advantages for obesity intervention, drug delivery, and carrying sensors. However, a long gastroretentive time only by such a size mismatch is hard to be achieved due to the uninterrupted stomach contraction and gastric juice erosion. Recent studies indicate that the retention time and stability of EGRSs can be regulated by adjusting their mechanical properties. Hence, this review summarizes the state-of-art progress of EGRSs for long-term gastric retention from a mechanical perspective for the first time, focuses on material components and synthesis methods, and the reinforcement strategies, and suggests the required mechanical property parameters of EGRSs.

The differential physiological responses to heat stress in the scleractinian coral Pocillopora damicornis are affected by its energy reserve.

The scleractinian corals conduct various responses upon heat stress such as bleaching and tissue loss, and colonies from the same coral species can conduct differential physiological activities with the biochemical basis unknown. In the present study, factors that influence the heat stress responses in coral Pocillopora damicornis were investigated. It was observed that P. damicornis conducted three differential physiological responses under heat treatment including tissue loss, bleaching, and polyp bailout. During heat response process, coral colonies conducting tissue loss had significantly higher total antioxidant capacity (T-AOC) level, while the bleached coral colonies exhibited higher caspase-3 activation level. Moreover, the stress response varied based on the energy reserve status. Colonies with higher lipid and sugar reserves were more likely to bleach, while those with lower reserves tended to undergo polyp bailout. We demonstrate that energy reserves influence the heat response patterns of P. damicornis. Colonies with higher lipid and sugar reserves may survive longer under heat stress, suggesting that these energy reserves contribute to their heat resistance. This study suggests that colonies with higher energy reserves prior to thermal stress may have greater thermal resistance, indicating that long-term environmental stressors that deplete energy reserves could increase susceptibility to thermal stress.

Allatotropin, DH31, and Proctolin reduce chill tolerance in the two-spotted cricket, Gryllus bimaculatus

The ability of insects to tolerate low temperatures, known as chill tolerance, contributes to their global distribution. However, the mechanisms underlying insect chill tolerance remain poorly understood. At low temperatures, insects enter chill coma, a reversible state of paralysis, owing to disrupted ion and water homeostasis. Upon returning to normal temperatures, insects reestablish ion and water homeostasis and recover the ability to move. In this study, we used the two-spotted cricket, Gryllus bimaculatus, as an experimental model and unveiled the roles of neuropeptides in regulating chill tolerance, typically evaluated by the time taken to recover from chill coma. Screening of 37 neuropeptides revealed that Allatotropin, DH31, and Proctolin inhibited chill coma recovery and decreased the survival rate under cold stress. RT-qPCR analyses revealed that the receptors for Allatotropin and DH31 were predominantly expressed in the hindgut. Injection of the three neuropeptides decreased both hemolymph mass and gut water content at low temperatures, most likely by increasing water excretion from the hindgut due to their effects on the rectum contraction. Additionally, Allatotropin and DH31 were produced by the terminal abdominal ganglion (TAG) innervating the hindgut since they were partly co-localized in the TAG, and their mature peptides were detected in the TAG-hindgut nerves. Moreover, the transcriptional levels of the neuropeptides in the TAG and receptors in the hindgut changed with cold exposure and rewarming. Based on these findings, we propose that Allatotropin, DH31, and Proctolin affect the physiological activities of the gut, probably the hindgut, to disrupt water homeostasis at low temperatures, thereby reducing chill tolerance in crickets.

Discovery of specific activity of 2-hydroxypentanoic acid acting on the mPR alpha (Paqr7) from the marine algae Padina.

Membrane progesterone receptors (mPRs) are members of the progestin and adipoQ (PAQR) receptor family that are stimulated by endogenous steroids to initiate rapid intracellular signaling through a nongenomic pathway. Previously, water-soluble compounds with mPRα binding activity from the marine algae Padina arborescens were fractionated by HPLC. Nuclear magnetic resonance spectroscopy revealed that the major component of the HPLC fraction was 2-hydroxypentanoic acid (2-HPA). In this study, the physiological activity of 2-HPA and its analogues was investigated using in vitro goldfish and in vivo zebrafish oocyte maturation and ovulation assays. Only 2-HPA showed inhibitory activity on oocyte maturation and ovulation of fish oocytes. The inhibitory activity of 2-HPA was compared between S- and R-type 2-HPA. The results showed that both types had the same level of activity. Furthermore, the interaction of 2-HPA with mPRα was analyzed by binding assay. 2-HPAs showed a substantial competitive binding affinity for the human membrane progesterone receptor α (hmPRα) in the graphene quantum dots (GQDs)-hmPRα binding assay. In contrast, synthetic structural analogues of 2-HPA showed no competitive binding activity. These results indicate that 2-HPA is a novel mPRα antagonist, and its chemical structure is highly restricted to show its activity.

Intermodal Consistency of Whole-Brain Connectivity and Signal Propagation Delays.

Measuring propagation of perturbations across the human brain and their transmission delays is critical for network neuroscience, but it is a challenging problem that still requires advancement. Here, we compare results from a recently introduced, noninvasive technique of functional delays estimation from source-reconstructed electro/magnetoencephalography, to the corresponding findings from a large dataset of cortico-cortical evoked potentials estimated from intracerebral stimulations of patients suffering from pharmaco-resistant epilepsies. The two methods yield significantly similar probabilistic connectivity maps and signal propagation delays, in both cases characterized with Pearson correlations greater than 0.5 (when grouping by stimulated parcel is applied for delays). This similarity suggests a correspondence between the mechanisms underpinning the propagation of spontaneously generated scale-free perturbations (i.e., neuronal avalanches observed in resting state activity studied using magnetoencephalography) and the spreading of cortico-cortical evoked potentials. This manuscript provides evidence for the accuracy of the estimate of functional delays obtained noninvasively from reconstructed sources. Conversely, our findings show that estimates obtained from externally induced perturbations in patients capture physiological activities in healthy subjects. In conclusion, this manuscript constitutes a mutual validation between two modalities, broadening their scope of applicability and interpretation. Importantly, the capability to measure delays noninvasively (as per MEG) paves the way for the inclusion of functional delays in personalized large-scale brain models as well as in diagnostic and prognostic algorithms.

Uncovering the intricacies of IGF-1 in Alzheimer's disease: new insights from regulation to therapeutic targeting.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β plaques and tau tangles, leading to cognitive decline and dementia. Insulin-like Growth Factor-1 (IGF-1) is similar in structure to insulin and is crucial for cell growth, differentiation, and regulating oxidative stress, synaptic plasticity, and mitochondrial function. IGF-1 exerts its physiological effects by binding to the IGF-1 receptor (IGF-1R) and activating PI3K/Akt pathway. In addition to the physiological activities in the brain, numerous studies point to a potential protective role of the IGF-1 pathway in the pathogenesis of neurodegenerative diseases, such as AD. Interestingly, patients with AD often exhibit altered insulin and IGF-1 levels, along with an inadequate insulin response. Dysregulation of IGF-1 signaling contributes to hyperphosphorylation of tau, NFT accumulation, increased β- and γ-secretase activity, elevated Aβ production, and impaired Aβ clearance, highlighting the need to explore the role of this signaling for potential therapeutic targets of AD. This review explores the role of IGF signaling in AD pathology, highlighting IGF-1 as a promising therapeutic target due to its significant involvement in disease mechanisms. Modulating IGF-1 activity could help mitigate neurodegeneration and preserve cognitive function in AD. A comprehensive understanding of the mechanisms underlying IGF-1 dysregulation is crucial for developing targeted therapeutic strategies to address the complex and multifaceted nature of AD.

Application of mean maximum Young’s modulus value as a new parameter for differential diagnosis of prostate diseases

Transrectal shear wave elastography (T-SWE) can be used non-invasively to diagnose prostate cancer (PCa) and benign prostatic hyperplasia (BPH). The prostate tissue can be viewed as an ellipsoidal sphere with viscoelastic characterization. Linear elastic model has been used to characterize soft tissues, and the simplification of partial characterization provides incomplete information. This retrospective study included 144 suspected prostate disease patients who had completed T-SWE from our hospital. The mean maximum Young’s modulus value (m-Emax) of the maximum transverse section of prostate was obtained by calculating the mean of 12 measured maximum Young’s modulus value (Emax) in the four quadrants. M-Emax was statistically correlated with and good discriminability for PCa and BPH. There was a nonlinear dose-response relationship between m-Emax and PCa risk, as well as between m-Emax and BPH risk. The relationship between m-Emax and prostate disease was consistent with the nonlinear effect showed by tissues as an elastic model in normal physiological activity areas. When stiffness increasing, the stress-strain relationship was approximates linear. M-Emax can be used as an innovative parameter of Young’s modulus value, which represents the stiffness of prostate tissue in T-SWE, and has a good effect in the differential diagnosis of prostate diseases.

Stereoselective Reaction Enabling Simultaneous Analysis of Carbon-Carbon Double-Bond Configuration and the Position of Monounsaturated Fatty Acids through UHPLC-ESI-MRM-MS.

Monounsaturated fatty acids (MUFA) are an important class of nutrients and are involved in lipid metabolism. The positions of the C=C bond and cis-trans isomerism have a significant influence on their physiological activity. However, simultaneously detecting these two structural properties has been challenging due to multiple isomers of MUFA. In this study, we developed a method that involved an N-aminophthalimide (PhthNH2) derivatization of the C=C bond in MUFA, followed by analysis using ultrahigh-performance liquid chromatography-electrospray ionization-multiple reaction monitoring mass spectrometry (UHPLC-ESI-MRM-MS) technology to achieve analysis of cis-trans isomers and positional isomers of the C=C bond. The derivatives of cis-trans isomers of the C=C bond were well separated in UHPLC, and their corresponding C=C bond positions were deduced from characteristic fragment ions in tandem mass spectrometry. With our method, we found MUFA with different double-bond positions and cis-trans isomers in several samples, including mouse kidney, butter, etc., achieving qualitative analysis and relative quantitation. This method is expected to be applied by more researchers in lipidomics studies in the future.

Schwann cells in regeneration and cancer

Schwann cells are specific peripheral glial cells with remarkable plasticity following peripheral nerve injury. Injury responses stimulate c-Jun activation in Schwann cells, drive epithelial-mesenchymal transition and cellular phenotypic changes, and induce the generation of reprogrammed repair Schwann cells to orchestrate peripheral nerve regeneration process. Schwann cells and/or Schwann cell-derived molecules are commonly used as supporting cells and/or neurotrophic factors to construct Schwann cell-based tissue-engineered nerve grafts for repairing severe peripheral nerve injury with long defects. Transplantation of Schwann cells and/or Schwann cell-derived molecules also serves as a helpful approach for the treatment of other injured tissues, such as the spinal cord, skin, digit tip, and bone. Schwann cells are not only associated with tissue regeneration but also involved in tumorigenesis and tumor progression. Schwann cells are the major cellular component of neurofibromatosis type 1 and the sole cell type in neurofibromatosis type 2 and schwannomatosis. In addition, Schwann cells also function as an important player in the tumor microenvironment and aid in the growth and invasiveness of many other solid cancers. In the present review, we outline the physiological and pathological activities of Schwann cells and discuss the functional roles of Schwann cells in homeostasis, regeneration, and cancer.

Does Normothermic Machine Perfusion Still Provide an Advantage for Deceased Donor Kidney Transplantation? A Systematic Review and Preliminary Meta-Analysis.

Patients with end-stage renal disease often face prolonged waiting times for kidney transplants. Historically, the use of marginal kidneys was limited due to suboptimal preservation methods. Normothermic machine perfusion (NMP) preserves physiological activity during the preservation process, potentially improving graft function and viability, expanding the use of marginal kidneys. While preliminary results are promising, NMP has not yet undergone sufficient clinical trials to determine whether it offers advantages over more widely used techniques. The aim of this systematic review is to assess several outcomes between kidneys that underwent NMP compared to traditional preservation methods after kidney transplant. A systematic review was conducted following PRISMA guidelines. Randomized controlled trials, case series, and studies comparing NMP with hypothermic machine perfusion (HMP) or static cold storage (SCS) were included. The primary outcome assessed was delayed graft function (DGF). Secondary outcomes included primary non-function (PNF), acute rejection, and 1-year graft survival. Eight NMP studies met the inclusion criteria. Meta-analysis showed significant differences in DGF between NMP and control (HMP or SCS) groups (OR: 0.47 [0.22, 0.99], p < 0.05). There were no significant differences between NMP and controls for PNF, acute rejection, or 1-year graft survival. These findings suggest that NMP yields similar adverse outcome rates compared to traditional methods. Notably, NMP could be associated with reduced rates of DGF. While NMP is a promising technique for renal allograft preservation, further randomized controlled trials are necessary to definitively establish its benefits over conventional preservation methods.

Lysosomal cationic proteins as the basis of cellular and humoral immunity of animals: the role of neutrophil extracellular traps (NETs) in immune homeostasis (review)

Relevance. Lysosomal cationic proteins (LCP) of granulocytic leukocytes: elastase, cathepsin G, proteinase-3, calgranulin, cathelicidins, defensins, lactoferrin, protegrins are active against viruses, bacteria, fungi, protozoa. The issues of physiological regulatory, immune and pathological effects of LCP and their derivatives – neutrophil (heterophil) extracellular traps (NETs) on pathogens, healthy cellular and tissue structures of the body are noted.Results. The increment of LCP granulocytes is realized by: 1. merocrine type — by degranulation; 2. exocytosis and false degranulation, that is, the process of decationization of lysosomes containing granules of cationic proteins with apocrine or holocrine type of secretion. Decationization implements exocytosis of LCP, extrusion of intact lysosomes from the cell with LCP, and diffusion of LCP through the lysosome membrane. Lysosome degranulation reactions with LCP form phagolysosomes and initiate phagocytosis, lysosome decationization reactions with LCP ensure the formation and functions of NETs. NETs is formed by non-lytic (non-lytic) and lytic (lyzed) pathways in septic and aseptic inflammation, with the ontogenetic development of immune links. NETs is stereotypically formed intravascular during aseptic inflammation, oxidative stress and in a physiological regime, when granulocytes are stimulated by products of oxidative metabolism. Using a cytochemical test with a highly sensitive acid-base bromophenol blue indicator, subcellular and cellular manifestations of the physiological age-related immune activity of cationic proteins accumulated in granulocyte lysosomes were studied on the avian model organism (Aves), and nonspecific adaptive reactions (NAR) of vertebrates in early postnatal ontogenesis were studied. The basis for the formation of NAR is the relationship of groups of leukocytes (lymphocytes, monocytes and granulocytes) with the dynamics of their lysosomal cationic proteins. The method for calculating the level of activity and potential capabilities of granulocytes in phagocytic reactions and in the formation of .NETs includes indices characterizing the directions and intensity of immune reactions of granulocytes, taking into account the processes: 1. degranulation of lysosomes with LCP — in the initiation of the cellular phagocytic link; 2. decationization of lysosomes with LCP — in the initiation of extracellular traps involved in the implementation of the humoral link of immunity.

Inhibiting NLRP3 enhances cellular autophagy induced by outer membrane vesicles from Pseudomonas aeruginosa.

The bacterium Pseudomonas aeruginosa is able to invade lung epithelial cells and survive intracellularly. During this process, it secretes outer membrane vesicles (OMVs), however, it is currently unclear how OMVs from P. aeruginosa (PA-OMVs) affect lung epithelial cells and their impact on oxidative stress, autophagy, and other physiological activities of lung epithelial cells. In this study, we found that PA-OMVs activated oxidative stress and autophagy in cells. We demonstrated that the NLRP3 (NLR family, pyrin domain containing 3) inhibitor MCC950 can enhance autophagy induced by PA-OMVs. The main function of NLRP3 is related to the body's immune response and inflammation regulation. MCC950 is the most common inhibitor of NLRP3. Additionally, we showed that PA-OMVs not only enhanced the expression of AMP-activated protein kinase, a key regulator of cellular energy homeostasis, and reactive oxygen species, which play a crucial role in cellular signaling and oxidative stress, but also significantly enhanced the expression of NLRP3. Inhibiting the expression of NLRP3 further enhanced the process of PA-OMVs induced autophagy. These results demonstrate that PA-OMVs activate both autophagy and the NLRP3 inflammasome, with NLRP3 suppressing autophagy to a certain extent, hoping to provide broad ideas for the future applications of PA-OMVs.IMPORTANCEThe discovery that lung epithelial cells exposed to outer membrane vesicles from Pseudomonas aeruginosa (PA-OMVs) activate cellular autophagy and induce protective immunity is significant. Specifically, the addition of an NLRP3 inhibitor, MCC950, has been found to decrease NLRP3 targets while simultaneously enhancing the autophagy activity induced by PA-OMVs. This finding unveils a novel theoretical framework for the development of PA-OMVs vaccines, highlighting new targets for enhancing the body's anti-infective responses. By elucidating the mechanisms through which PA-OMVs trigger autophagy and bolster immune defenses, this research opens avenues for innovative vaccine design strategies aimed at combatting infections effectively.

Neuroregulation during Bone Formation and Regeneration: Mechanisms and Strategies.

The skeleton is highly innervated by numerous nerve fibers. These nerve fibers, in addition to transmitting information within the bone and mediating bone sensations, play a crucial role in regulating bone tissue formation and regeneration. Traditional bone tissue engineering (BTE) often fails to achieve satisfactory outcomes when dealing with large-scale bone defects, which is frequently related to the lack of effective reconstruction of the neurovascular network. In recent years, increasing research has revealed the critical role of nerves in bone metabolism. Nerve fibers regulate bone cells through neurotransmitters, neuropeptides, and peripheral glial cells. Furthermore, nerves also coordinate with the vascular and immune systems to jointly construct a microenvironment favorable for bone regeneration. As a signaling driver of bone formation, neuroregulation spans the entire process of bone physiological activities from the embryonic formation to postmaturity remodeling and repair. However, there is currently a lack of comprehensive summaries of these regulatory mechanisms. Therefore, this review sketches out the function of nerves during bone formation and regeneration. Then, we elaborate on the mechanisms of neurovascular coupling and neuromodulation of bone immunity. Finally, we discuss several novel strategies for neuro-bone tissue engineering (NBTE) based on neuroregulation of bone, focusing on the coordinated regeneration of nerve and bone tissue.