Parabacteroides goldsteinii mitigates parkinsonism in LRRK2 mutant mice by reducing neuroinflammation through Gut-Brain axis.

Relevance. Due to global climate changes, it is of particular interest to study the issue of increasing crop rotation productivity in conditions with uneven precipitation during the growing season. It is possible to identify the most effective crop rotation schemes, regardless of pricing policy, using bioenergy assessment. The inclusion of drought-resistant late crops capable of making up for crop losses of other crops in unfavorable years ensures the stabilization of output and increases the efficiency of agrocenoses.Methods. The study of the effectiveness of the inclusion of grain sorghum and corn in the fourfield crop rotation was carried out on the basis of bioenergetic analysis. The following indicators were calculated based on the amount of accumulated energy from the harvest and the cost of total energy for crop cultivation: energy gain, bioenergy coefficient, energy profitability and energy cost of harvest. The mathematical processing of the results was carried out by the method of variance analysis using the AGROS 2.09 program.Results. As a result of the energy analysis, it was revealed that the inclusion of row crops in agrocenoses significantly increases the efficiency of using arable land in conditions of insufficient moisture. In the variants with saturation of crop rotations with row crops, the maximum energy output is set with a harvest of steam — winter wheat — soybeans — grain sorghum (32.67 GJ/ha) and steam — winter wheat — soybeans — corn (35.12 GJ/ha) at a total energy consumption of 11.16–11.35 GJ/ha. In these variants, the energy gain was 21.68–23.94 GJ/ha, the energy profitability was 194.33–211.12%, the cost of crop energy was 0.39–0.41 GJ/ha, and the energy efficiency coefficients were 2.94–3.12. Correlation analysis revealed a strong positive dependence of the coefficients of bioenergetic efficiency of crop rotations on the hydrothermal conditions of crop cultivation, the correlation coefficient between the indicators was 0.71–0.74. In acute arid years, differences in the efficiency of crop rotations with different crop alternations are more pronounced than in average and moistened ones.

Although often perceived as resilient, college student-athletes (SAs) face mental health challenges yet underuse university counselling services (UCS), underscoring the need for accessible interventions. This exploratory study aimed to examine how Dohsa Therapy (DT), a body psychotherapy, affects SAs physiologically. Progressive Muscle Relaxation (PMR), a standardised relaxation method, was included as a contrasting comparison. Five Japanese SAs receiving UCS support participated. Heart rate variability (HRV) was assessed using time- and frequency-domain indices via a wearable ECG device. DT generally increased RMSSD and SDNN, suggesting enhanced parasympathetic activity and autonomic flexibility. PMR consistently lowered heart rate, while effects on HRV indices varied across individuals. Findings demonstrate the feasibility of HRV measurement in DT and PMR and suggest both as practical body-oriented tools for student-athletes experiencing stress and performance-related concerns. Future work may integrate relational perspectives to bridge quantitative and qualitative approaches in the study of somatic and dance/movement therapy.

We use stories to navigate the complexity of life and to try to make sense of our lives. When someone has a medically unexplained voice problem, there are various ways in which we can help them navigate this reality. One such suggestion of a story helping us navigate this is The Myth of Io. This case study of Jo seeks to compare the themes of voicelessness and voice disorders to themes present in The Myth of Io, to seek an understanding of the flare-ups associated with a psychogenic voice problem or functional neurological voice disorder.

Cartilage extracellular matrix (ECM) destruction is a hallmark of femoral head necrosis (FHN) in broilers. Chondrocytes undergo metabolic reprogramming under stress to maintain function. However, the metabolic alterations in FHN chondrocytes remain unclear. This study aims to investigate the overall changes of metabolic state in FHN chondrocytes and its functions. Femoral head cartilage of healthy and FHN broilers was collected for non-targeted metabolome and transcriptome analyses. Additionally, primary chondrocytes were isolated from femoral head cartilage of control (CON) and FHN broilers for bioenergetic analysis and mechanistic investigation. Multi-omics profiling revealed significant enrichment of the glycolysis pathway, decreased levels of tricarboxylic acid cycle metabolites (citrate and malate), upregulation of the lactate dehydrogenase A (Ldha) gene, and downregulation of genes encoding mitochondrial complexes in cartilage from FHN broilers. Compared with primary chondrocytes isolated from CON broilers, FHN primary chondrocytes exhibited elevated basal extracellular acidification rate (ECAR) and increased lactate production. Concurrently, the basal respiration of FHN chondrocytes was decreased, accompanied by unbalanced mitochondrial dynamics and decreased ATP production. Furthermore, fructose-1,6-bisphosphate (FBP) or rotenone treatment was used to mimic the metabolic shift from oxidative phosphorylation to glycolysis, resulting in downregulation of matrix synthesis genes and upregulation of matrix degradation genes in CON primary chondrocytes. Glycolysis inhibition suppressed matrix degradation gene expression in FHN chondrocytes. These findings suggest that glycolytic reprogramming occurs in FHN chondrocytes, and targeting glycolysis may alleviate ECM destruction in FHN broilers, providing a novel insight into the pathological mechanisms of FHN.

Background:As of 2023, approximately 100.1 million adults and 14.7 million children in the USA are obese. Many comorbidities develop with obesity, which impairs quality of life and burdens the health care system. Consequently, there is an urgent need for interventions and treatments to reverse obesity and its comorbidities and restore health. Sphingosine Kinase 1 (SphK1), a key enzyme in sphingolipid metabolism, produces sphingosine-1-phosphate (S1P), a bioactive lipid implicated in obesity and metabolic dysfunction. While global deletion of Sphk1 protects against diet-induced obesity, adipocyte-specific SPHK1 deficiency paradoxically promotes weight gain, glucose intolerance, and adipose inflammation. Given the known role of sphingolipids in adipose thermogenesis, we investigated whether Sphk1 regulates adipocyte beiging and mitochondrial function.Methods:We assessed thermogenic responses in SphK1-deficient adipocytes and adipocyte-specific Sphk1 knockout (Ad-SphK1Δ) mice under basal and β3-adrenergic stimulation using CL 316,243. Thermoneutral housing (30°C) and room temperature (23°C) conditions were used to minimize and assess ambient temperature effects on thermogenesis. Molecular, histological, and bioenergetic analyses were conducted across multiple adipose depots.Results:β3-adrenergic stimulation upregulated Sphk1 expression in mature white adipocytes, while SphK1-deficient adipocytes exhibited enhanced Ucp1 expression, indicating a suppressive role for SphK1 in beiging. In vivo, adipocyte-specific Sphk1 knockout (Ad-SphK1Δ) mice showed elevated Ucp1 expression in inguinal and gonadal white adipose tissue (iWAT, gWAT), both basally and after CL 316,243 treatment. These changes were accompanied by depot-specific alterations in adipocyte size and increased adiposity, independent of ambient temperature. Despite similar elevation of thermogenic markers, Sphk1 deletion had differential effect on mitochondrial function: iWAT showed increased mitochondrial content but reduced complex IV activity and ATP production, whereas gWAT showed reduced mitochondrial abundance without changes in respiration.Conclusion:Our work suggests that Sphk1 may act as a negative regulator of thermogenic expression and affect mitochondrial function in a depot-specific manner. Loss of Sphk1 enhances beiging but compromises mitochondrial efficiency, revealing a complex role for the SphK1/S1P axis in adipose plasticity and metabolic regulation. These insights may inform future therapeutic strategies targeting sphingolipid pathways for obesity and metabolic disease.

The article discusses the methodological foundations of holistic pulsation massage (palsing) as one of the systems of body-oriented psychotherapy, as well as the results of psychological research on the therapeutic mechanisms of its effects on the human body. Using his practical experience, the author examines and substantiates a number of methodological and methodical provisions that make it possible to consider holistic pulsation massage as a separate system of psychological correction and rehabilitation of law enforcement officers.

A comprehensive spatial analysis of kidney metabolism is essential for advancing knowledge of both normal kidney physiology and pathophysiology. The kidney exhibits marked regional differences in bioenergetic demands and substrate utilization, reflecting the distinct functional profiles of each nephron segment. To complement existing approaches with freshly isolated tubules or primary cell cultures, we established and validated an ex vivo respirometry method using structurally preserved kidney slices on a Seahorse XFe24 platform. This protocol avoids tissue disruption or enzymatic digestion and enables simultaneous, region-specific measurements of metabolic fluxes in the cortex, outer medulla, and inner medulla. It provides an integrated readout of the metabolic properties of the cell types present within each anatomical region. We demonstrate the utility of this approach through proof-of-principle studies that profile region-specific metabolic fluxes under hyperglycemic conditions in a mouse model of obesity and type 2 diabetes, as well as the metabolic alterations that accompany the transition from acute ischemic injury to chronic kidney disease. Furthermore, to highlight its relevance for therapeutic discovery, we applied this method to assess the impact of pharmacological hypoxia-inducible factor activation on regional kidney bioenergetics. In summary, this protocol advances the study of kidney metabolism by providing a robust platform for region-specific analysis of kidney respiration and bioenergetics and holds promise for accelerating the development of novel therapies targeting metabolic pathways in kidney disease.NEW & NOTEWORTHY Assessment of regional metabolism in kidney tissue is crucial for understanding normal physiology and disease. We have developed a robust ex vivo method to measure respiration in structurally preserved kidney slices using a metabolic flux analyzer. This approach enables analysis of metabolic fluxes and substrate utilization in the kidney cortex, outer medulla, and inner medulla while maintaining tissue architecture, providing region-specific insights into kidney metabolism with broad applications in disease modeling and therapeutic discovery.

Hypoxia-ischemia (HI), which disrupts the oxygen supply-demand balance in the brain by impairing blood oxygen supply and the cerebral metabolic rate of oxygen (CMRO2), is a leading cause of neonatal brain injury. However, it is unclear how post-HI hypothermia helps to restore the balance, as cooling reduces CMRO2. Also, how transient HI leads to secondary energy failure (SEF) in neonatal brains remains elusive. Using photoacoustic microscopy, we examined the effects of HI on CMRO2 in awake 10-day-old mice, supplemented by bioenergetic analysis of purified cortical mitochondria. Our results show that while HI suppresses ipsilateral CMRO2, it sparks a prolonged CMRO2-surge post-HI, associated with increased mitochondrial oxygen consumption, superoxide emission, and reduced mitochondrial membrane potential necessary for ATP synthesis—indicating oxidative phosphorylation (OXPHOS) uncoupling. Post-HI hypothermia prevents the CMRO2-surge by constraining oxygen extraction fraction, reduces mitochondrial oxidative stress, and maintains ATP and N-acetylaspartate levels, resulting in attenuated infarction at 24 hours post-HI. Our findings suggest that OXPHOS-uncoupling induced by the post-HI CMRO2-surge underlies SEF and blocking the surge is a key mechanism of hypothermia protection. Also, our study highlights the potential of optical CMRO2-measurements for detecting neonatal HI brain injury and guiding the titration of therapeutic hypothermia at the bedside.

Lepidium meyenii Walpers (LMW), a high-altitude plant, is known to stimulate hormone release, counteract neurodegeneration, and protect against oxidative stress. Saliva is vital for oral health, and reduced production leads to xerostomia, often caused by aging, radiation, or Sjögren's syndrome. Key pathological features include mesenchymal fibrosis and acinar atrophy, largely regulated by the TGF-β1 pathway. Current treatments are limited, with many patients relying on artificial saliva. Developing therapies to restore salivary function could offer significant benefits. In this study, we assessed the protective effects of LMW extract (LMWE) in irradiated C57BL/6J mice and TGF-β1-treated rat parotid acinar cells (Par-C10) using histological, molecular, bioenergetic, and 3D organoid analyses to evaluate salivary gland regeneration and lineage-specific differentiation. LMWE significantly restored gland weight, shortened secretion lag time, and increased amylase activity in irradiated mice. Histological and molecular analyses showed reduced acinar atrophy and fibrosis, preservation of epithelial polarity, and upregulation of Mist1, AQP5, and amylase. In vitro, LMWE protected Par-C10 cells from TGF-β1-induced senescence, preserved mitochondrial membrane potential, and improved epithelial barrier function. In 3D organoid cultures of Par-C10 cells embedded in matrix, (1E,4Z)-1-(2,4-dihydroxyphenyl)-5-(3,4-dihydroxyphenyl) penta-1,4-dien-3-one (DHPPD) and (Z)-N-phenyldodec-2-enamide (E4Z-PD)-selectively enhanced acinar and ductal lineage differentiation, respectively. These results suggest that LMWE promotes salivary gland regeneration through antioxidative and lineage-specific mechanisms and may represent a safe and effective therapeutic strategy for xerostomia.

Investigating prolactin-induced protein and its role in modulating the metabolic state of the keratoconus microenvironment.

Background: Neurofibromin 2 (NF2) is a tumor suppressor that can engage signaling pathways to modulate cell proliferation and survival. We previously demonstrated that NF2 mediates cardiomyocyte apoptosis and cardiac injury caused by acute myocardial infarction. Research Aim: The role of NF2 in heart failure remains uncharacterized. This study sought to determine whether NF2 modulates heart failure due to chronic stress. Approach: We generated cardiomyocyte-specific NF2 knockout (cKO) mice and used transverse aortic constriction (TAC) to generate chronic pressure overload (PO) stress, which elicits cardiac remodeling and failure. Complementary cell-based experiments were performed in neonatal rat ventricular myocytes (NRVMs). We analyzed cardiac function by echocardiographic and hemodynamic analysis. We used RNAseq and validated the novel findings using promoter pulldown, Seahorse metabolic profiling, and biochemical analyses to investigate underlying mechanisms. Results: We found that NF2 is transiently upregulated in wild-type mouse myocardium in response to early phase of PO, but is downregulated during heart failure. Following TAC, NF2 cKO hearts unexpectedly showed significantly worsened cardiac function, compared to controls. RNAseq analysis followed by qPCR indicated downregulation of several metabolic pathways and impaired Estrogen Related Receptor (ERR) signaling in NF2 cKO hearts. Luciferase experiments employing NRVMs confirmed that NF2 promoted expression of ERR isoforms (a, g), and DNA pulldown assays demonstrated NF2 association with ERR proximal promoters. Analysis of NRVM bioenergetics demonstrated that NF2 depletion impaired mitochondrial respiration, which was reversed by concomitant expression of ERRg. Moreover, AAV9-mediated restoration of ERRg in NF2 cKO mice normalized cardiac function in response to PO. As NF2 does not directly bind DNA, leveraging a proteomics-based approach we identified the transcription factor linking NF2 to ERR isoform expression and further validated its regulation using NRVMs based experiments. Conclusion: Based on these findings, we conclude that NF2 is essential and therefore transiently upregulated during PO stress to compensate and regulate metabolic demand.

Assessing Hemopure Based Oxygenated Flushing in Liver Transplantation: A Bioenergetic Molecular Analysis Approach

На данный момент существует огромное количество методов телесно-ориентированной психотерапии, однако в отечественной и мировой практике до сих пор отсутствует единая теоретико-методологическая основа для их систематизации, объединения полученных результатов и проведения исследований на научной основе. Цель работы – определить возможность применения в рамках телесно-ориентированной психотерапии существующих отечественных научных подходов к исследованию поведения и деятельности человека. Методология: поиск и анализ литературы, содержащей психологический, физиологический и системно-функциональный подход к исследованию деятельности человека. Результаты и их анализ: приведено описание физиологического и психологического подходов к изучению деятельности человека. Показана возможность объединения полученных результатов в рамках теории функциональных систем. Введены понятия функционального континуума «деятельность – действие – движение» и четырехуровневой модели психофизиологической структуры деятельности человека. Заключение: функционально-структурный подход позволяет на системном уровне объединить результаты психологических, физиологических и психофизиологических научных исследований и использовать их для синтеза нового знания в психологии телесности и прикладной практической деятельности в рамках телесно-ориентированной психотерапии. Currently, there are a huge number of methods of body-oriented psychotherapy, but in domestic and world practice there is still no single theoretical and methodological basis for their systematization, unification of the obtained results and conducting research on a scientific basis. The purpose of this work is to determine the possibility of applying existing domestic scientific approaches to the study of human behavior and activity within the framework of body-oriented psychotherapy. Methodology: search and analysis of literature containing a psychological, physiological and system-functional approach to the study of human activity. The results and their analysis: a description of the physiological and psychological approaches to the study of human activity is provided. The possibility of combining the obtained results within the framework of the theory of functional systems is shown. The concepts of the functional continuum «activity - action – movement» and a four-level model of the psychophysiological structure of human activity are introduced. Conclusion: the functional-structural approach allows us to combine the results of psychological, physiological and psychophysiological scientific research at the systemic level and use them to synthesize new knowledge in the psychology of corporeality and applied practical activity within the framework of body-oriented psychotherapy.

This study uncovers the pivotal role of acetyl-CoA carboxylase 1 (ACC1) in regulating platelet lipid composition, bioenergetics, activation, and thrombus formation, as demonstrated using a targeted glycoprotein Ibα (GPIbα)-Cre+/- mouse model. By comparing platelet-specific ACC1 knockout mice (GPIbα-Cre+/- × ACC1flx/flx) with both GPIbα-Cre+/- and ACC1flx/flx control groups, we showed that ACC1 deficiency profoundly reshaped the platelet phospholipidome. Specifically, ACC1 deletion led to decreased levels of arachidonic acid-containing phosphatidylethanolamine plasmalogens, thereby limiting thromboxane A2 synthesis, dense granule secretion, and platelet activation upon agonist stimulation. Bioenergetic analysis of ACC1-deficient platelets revealed reduced glycolytic activity, potentially worsening their activation defects. Notably, ACC1 deficiency also enhanced the mitochondrial reserve respiratory capacity, without altering basal respiration or adenosine triphosphate turnover. This increased reserve respiratory capacity correlated with reduced phosphatidylserine exposure, suggesting lower procoagulant activity. Importantly, we showed that ACC1 deficiency impaired thrombus formation without compromising hemostasis. Together, these findings identified ACC1 as a critical regulator of platelet function and highlighted its potential as a target for innovative antithrombotic therapies.

The article considers a relevant but at the same time little-studied issue of developing and strengthening resilience using body-oriented psychotherapy. An analysis of the concept of resilience and various categories that make up this concept (S. R Maddi, D. A. Leontiev, G. Allport, E. A. Rylskaya, M. A. Odintsova) are presented in the article. The main related concepts in the body-oriented approach are considered (W. Reich, A. Lowen, D. Boadella). An attempt is made to look at the key ideas of the body-oriented approach in terms and categories of resilience. It is shown that many aspects of resilience appear in works on body therapy, although they are described in other terms. The practical part of the article highlights the key characteristics of resilience that are developed and strengthened by means of body-oriented therapy and describes specific practices and techniques that can be successfully used in working with clients in order to increase the level of resilience.

Mitochondrial bioenergetics analysis on SLC-selected boar spermatozoa during liquid storage.

Mesenchymal stem cell secretome restores monocrotophos induced toxicity in human neural progenitor cells.

Introduction:Epidemiological and experimental studies support an association between exposure to particulate matter during pregnancy and the development of fetal growth restriction (FGR). The etiology of FGR is often attributed to poor nutrient delivery. Glucose is the primary energy substrate for fetal growth and an important energy source for placental tissue function; therefore, the health of the feto-placental unit depends on sufficient delivery of this nutrient to the tissue. Preeclampsia and FGR are associated with altered placental metabolism; moreover, the underlying causes and progression of these pathologies are influenced by fetal sex. The goal of this study was to investigate sex-related metabolic changes in the placenta after gestational exposure to particulate matter.Methods:Sprague Dawley rats were exposed to nano-titanium dioxide (nano-TiO2) aerosols throughout pregnancy [gestational day (GD) 6-GD20]. For these studies, we developed a novel precision-cut placenta slice model for analysis of tissue bioenergetics using an Agilent Seahorse Analyzer.Results:Exposure of pregnant rats to nano-TiO2 aerosols (9.74 ± 0.11 mg/m3) resulted in an overall decrease in placental metabolic function with an increased reliance on glycolytic ATP production. Reductions in maximum metabolic function were sex-related, revealing that female placentas are more sensitive to environmentally induced metabolic changes.Discussion:These data show that there are sex-related mechanisms within the glycolytic pathway for increased glucose utilization. As increased metabolism of glucose by the placenta can reduce fetal glucose delivery, it may contribute to adverse effects on fetal growth induced by nano-TiO2.

Alteration in metabolic activities is a critical step in cancer progression. Myriad metabolic-based therapy options are increasingly being proposed for human tumours. However, emerging evidence highlights interpatient metabolic heterogeneity and underscores the importance of metabolic phenotyping in cancer treatment. To investigate metabolic heterogeneity in cutaneous squamous cell carcinoma (cSCC) and its impact on cSCC characteristics and treatment responses. We applied combined proteomic and bioenergetic analyses to patient samples representing various stages of cSCC, ranging from precancerous actinic keratosis to metastatic cSCC. To investigate the functional impacts of the identified metabolic heterogeneities on tumour characteristics and treatment responses, we used patient-derived tumour cell (PDC) and patient-derived xenograft (PDX) models by transplanting tumour cells and freshly resected patient tumours into immunocompromised mice. Three subgroups with low, medium and high metabolic scores, respectively, were identified across all stages of carcinogenesis. Functional analyses indicated that, in both models (PDC and PDX), the sensitivities of tumours to leflunomide, an inhibitor of dihydroorotate dehydrogenase (DHODH), were inversely correlated with their metabolic scores and directly correlated with DHODH protein expression level. Moreover, DHODH overexpression in nonresponding groups rendered them sensitive to leflunomide. The findings demonstrate the relevance of metabolic profiling and scoring in the design of therapeutic approaches targeting the bioenergetic vulnerabilities of tumours and suggest DHODH as a promising therapeutic target in the low metabolic score subgroup of cSCC.