Multilayered hydrogel scaffold construct with native tissue matched elastic modulus: A regenerative microenvironment for urethral scar-free healing.

The unsuitable deformation stimulus, harsh urine environment, and lack of a regenerative microenvironment (RME) prevent scaffold-based urethral repair and ultimately lead to irreversible urethral scarring. The researchers clarify the optimal elastic modulus of the urethral scaffolds for urethral repair and design a multilayered PVA hydrogel scaffold for urethral scar-free healing. The inner layer of the scaffold has self-healing properties, which ensures that the wound effectively resists harsh urine erosion, even when subjected to sutures. In addition, the scaffold's outer layer has an extracellular matrix-like structure that synergizes with adipose-derived stem cells to create a favorable RME. In vivo experiments confirm successful urethral scar-free healing using the PVA multilayered hydrogel scaffold. Further mechanistic study shows that the PVA multilayer hydrogel effectively resists the urine-induced inflammatory response and accelerates the transition of urethral wound healing to the proliferative phase by regulating macrophage polarization, thus providing favorable conditions for urethral scar-free healing. This study provides mechanical criteria for the fabrication of urethral tissue-engineered scaffolds, as well as important insights into their design.

Fat body glycolysis defects inhibit mTOR and promote distant muscle disorganization through TNF-α/egr and ImpL2 signaling in Drosophila larvae.

The fat body in Drosophila larvae functions as a reserve tissue and participates in the regulation of organismal growth and homeostasis through its endocrine activity. To better understand its role in growth coordination, we induced fat body atrophy by knocking down several key enzymes of the glycolytic pathway in adipose cells. Our results show that impairing the last steps of glycolysis leads to a drastic drop in adipose cell size and lipid droplet content, and downregulation of the mTOR pathway and REPTOR transcriptional activity. Strikingly, fat body atrophy results in the distant disorganization of body wall muscles and the release of muscle-specific proteins in the hemolymph. Furthermore, we showed that REPTOR activity is required for fat body atrophy downstream of glycolysis inhibition, and that the effect of fat body atrophy on muscles depends on the production of TNF-α/egr and of the insulin pathway inhibitor ImpL2.

Fechamento de comunicação bucossinusal com retalho de corpo adiposo de bochecha: relato de caso clínico / Closure of bucosinusal communication with cheek adipose body flap: Clinical case report

A comunicação bucossinusal (CBS) é uma complicação relativamente frequente na prática odontológica que ocorre em procedimentos cirúrgicos, principalmente, exodontias dos molares superiores. O diagnóstico dessa comunicação é feito através de exames clínicos intraorais, empregando a manobra de Valsava, e para a confirmação do diagnóstico, utiliza-se exame radiográfico. A literatura cita inúmeros métodos de tratamento, entretanto não evidenciam a técnica específica para cada caso, entre esses métodos existe o retalho com o corpo adiposo da bochecha, que apresenta alto índice de sucesso no fechamento das CBS. Quando a CBS é fechada incorretamente ou de forma tardia o paciente fica propício a desenvolver quadros de sinusite crônica ou aguda, além de fístulas bucossinusais. Portanto, deve-se identificar e tratar essa comunicação de imediato para evitar o desenvolvimento de outras complicações. O objetivo do presente trabalho é apresentar um caso clínico de um paciente com comunicação bucossinusal atendido na clínica odontológica da Unidade de Ensino Superior de Feira de Santana (UNEF), com a finalidade de demostrar a técnica cirúrgica utilizando a rotação do corpo adiposo da bochecha (Bola de Bichat).

The bucosinusal communication (BCS) is a relatively frequent complication in dental practice that occurs in surgical procedures, especially extractions of the upper molars. The diagnosis of this communication is made through intraoral clinical examinations, using the Valsava maneuver, and for the confirmation of the diagnosis, radiographic examination is used. The literature cites numerous methods of treatment, however they do not evidence the specific technique for each case, among these methods there is the graft with the adipose body of the cheek, which has a high success rate in the closure of the CBS. When the CBS is closed incorrectly or late, the patient is prone to develop chronic or acute sinusitis, in addition to bucosinusal fistulas. Therefore, this communication should be identified and treated immediately to prevent the development of other complications. The objective of the present study is to present a clinical case of a patient with bucosinusal communication attended at the dental clinic of Unidade de Ensino Superior de Feira de Santana (UNEF), with the purpose of demonstrating the surgical technique using the rotation of the adipose body of the cheek (Bichat ball).

Age and duration of obesity modulate the inflammatory response and expression of neuroprotective factors in mammalian female brain.

Obesity has become a global epidemic and is associated with comorbidities, including diabetes, cardiovascular, and neurodegenerative diseases, among others. While appreciable insight has been gained into the mechanisms of obesity-associated comorbidities, effects of age, and duration of obesity on the female brain remain obscure. To address this gap, adolescent and mature adult female mice were subjected to a high-fat diet (HFD) for 13 or 26 weeks, whereas age-matched controls were fed a standard diet. Subsequently, the expression of inflammatory cytokines, neurotrophic/neuroprotective factors, and markers of microgliosis and astrogliosis were analyzed in the hypothalamus, hippocampus, and cerebral cortex, along with inflammation in visceral adipose tissue. HFD led to a typical obese phenotype in all groups independent of age and duration of HFD. However, the intermediate duration of obesity induced a limited inflammatory response in adolescent females' hypothalamus while the hippocampus, cerebral cortex, and visceral adipose tissue remained unaffected. In contrast, the prolonged duration of obesity resulted in inflammation in all three brain regions and visceral adipose tissue along with upregulation of microgliosis/astrogliosis and suppression of neurotrophic/neuroprotective factors in all brain regions, denoting the duration of obesity as a critical risk factor for neurodegenerative diseases. Importantly, when female mice were older (i.e., mature adult), even the intermediate duration of obesity induced similar adverse effects in all brain regions. Taken together, our findings suggest that (1) both age and duration of obesity have a significant impact on obesity-associated comorbidities and (2) early interventions to end obesity are critical to preserving brain health.

Brown Adipose Tissue Activity and Childhood Exposure to Cold Are Associated With Hot Flashes at Menopause.

OBJECTIVE: Hot flashes (HFs) are experienced as sudden sensations of heat. We hypothesized that brown adipose tissue (BAT) activation could increase the likelihood of HFs in winter. The aim of this study was to test whether women with more BAT activity were more likely to experience self-reported or biometrically measured HFs. METHODS: Women aged 45-55 years (n = 270) participated in face-to-face interviews and anthropometric and ambulatory measures. Level of BAT activity was estimated from the difference in supraclavicular skin temperature measured by infrared thermography before and after cooling. Logistic regressions were applied to examine whether bothersome HFs (yes/no) during the past 2 weeks were associated with BAT activity, adjusting for menopausal status, childhood exposure to cold, waist/hip ratio, and self-reported health. Linear regressions were used to examine the frequency of self-reported and biometrically measured HFs during the study period and BAT activity, adjusting for potential confounders. RESULTS: Menopausal status, childhood exposure to cold, waist-to-hip ratio (WHR), and self-reported health were associated with both BAT activity and HFs. After adjusting for potential confounders, an increase in BAT activity almost tripled the likelihood of bothersome HFs (OR 2.84, 95% CI 1.26-6.43). In linear regressions, BAT activity was not associated with frequency of subjective or objective HFs during the study period, but childhood exposure to cold was associated with subjective HF report (ß = 0.163, p = 0.010). CONCLUSION: To our knowledge, this is the first study of BAT activation and HFs. Our results support a role for BAT activity in HF experience. Therefore, we encourage further examination of the role of BAT, as well as childhood exposure to cold, in HFs.

Characterization of Ucp1-iCre Knockin Mice Reveals the Recombination Activity in Male Germ Cells.

Ucp1 promoter-driven Cre transgenic mice are useful in the manipulation of gene expression specifically in thermogenic adipose tissues. However, the wildly used Ucp1-Cre line was generated by random insertion into the genome and showed ectopic activity in some tissues beyond adipose tissues. Here we characterized a knockin mouse line Ucp1-iCre generated by targeting IRES-Cre cassette immediately downstream the stop codon of the Ucp1 gene. The Cre insertion had little to no effect on UCP1 protein levels in brown adipose tissue. Ucp1-iCre mice of both genders exhibited normal thermogenesis and cold tolerance. When crossed with Rosa-tdTomato reporter mice, Ucp1-iCre mice showed robust Cre activity in thermogenic adipose tissues. Additionally, limited Cre activity was sparsely present in the hypothalamus (VMH), choroid plexus, kidney, adrenal glands, ovary, and testis in Ucp1-iCre mice, albeit to a much lesser extent and with reduced intensity compared to the conventional Ucp1-Cre line. Single-cell transcriptome analysis revealed UCP1 mRNA expression in male spermatocytes. Moreover, male Ucp1-iCre mice displayed a high frequency of Cre-mediated recombination in the germline, whereas no such effect was observed in female Ucp1-iCre mice. These findings suggest that Ucp1-iCre mice offer promising utility in the context of conditional gene manipulation in thermogenic adipose tissues, while also highlighting the need for caution in mouse mating and genotyping procedures.

Lycium barbarum polysaccharide increases thermogenesis and energy metabolism through modulation of the gut microbiota to confer resistance to cold temperatures.

Traditional Chinese medical literature contains numerous records of many traditional Chinese herbal medicines that exhibit efficacy in enhancing resistance to cold, yet there is a lack of scientific explanation. Lycium barbarum is among the herbal medicines that are explicitly documented to enhance resistance to cold in the "Ben Cao Gang Mu (Compendium of Materia Medica)". Herein, we investigated L. barbarum polysaccharide (LBP)-induced browning of inguinal white adipose tissue (iWAT), energy expenditure and thermogenic function in a long-term (4 months) treatment mouse model. LBP supplementation resulted in a significant reduction in weight and adipocyte size in iWAT, along with increased gut microbiota diversity. Specifically, the levels of Lachnospiraceae, Ruminococcaceae and Bacteroidaceae (short-chain fatty acid-producing bacteria) were elevated, leading to a higher level of short-chain fatty acids (SCFAs) in the caecal content. These effects subsequently triggered the release of glucagon-like peptide-1 (GLP-1) and activated the CREB/PGC1α signaling pathway in iWAT, thereby increasing energy expenditure and enhancing thermogenic function. The antibiotic treatment experiments confirmed that the LBP-mediated gut microbiota participated in the process of iWAT browning. In summary, our findings provide the first scientific explanation and mechanistic insights into the cold resistance of L. barbarum and identify potentially safe natural product supplements for individuals in alpine areas.

Understanding and controlling the variables for stromal vascular fraction therapy.

In regenerative medicine, the isolation of mesenchymal stromal cells (MSCs) from the adipose tissue's stromal vascular fraction (SVF) is a critical area of study. Our review meticulously examines the isolation process of MSCs, starting with the extraction of adipose tissue. The choice of liposuction technique, anatomical site, and immediate processing are essential to maintain cell functionality. We delve into the intricacies of enzymatic digestion, emphasizing the fine-tuning of enzyme concentrations to maximize cell yield while preventing harm. The review then outlines the filtration and centrifugation techniques necessary for isolating a purified SVF, alongside cell viability assessments like flow cytometry, which are vital for confirming the efficacy of the isolated MSCs. We discuss the advantages and drawbacks of using autologous vs allogeneic SVF sources, touching upon immunocompatibility and logistical considerations, as well as the variability inherent in donor-derived cells. Anesthesia choices, the selection between hypodermic needles vs liposuction cannulas, and the role of adipose tissue lysers in achieving cellular dissociation are evaluated for their impact on SVF isolation. Centrifugation protocols are also analyzed for their part in ensuring the integrity of the SVF. The necessity for standardized MSC isolation protocols is highlighted, promoting reproducibility and successful clinical application. We encourage ongoing research to deepen the understanding of MSC biology and therapeutic action, aiming to further the field of regenerative medicine. The review concludes with a call for rigorous research, interdisciplinary collaboration, and strict adherence to ethical and regulatory standards to safeguard patient safety and optimize treatment outcomes with MSCs.

DNA Methyltransferase Inhibition by RG108 Improves Stemness and Multipotential Differentiation of Human Adipose Tissue-derived Stem Cells.

Background: DNA methylation plays important roles in regulating various biological processes, including self-renewal, differentiation and regenerative capacity of stem cells. Previous studies have demonstrated that lineage-specific differentiation of mesenchymal stem cells can be promoted using nontoxic chromatin-modifying drugs. Objectives: Here we evaluated the impact of RG108, a known DNA methyltransferase inhibitor, on the expression of pluripotency genes in human adipose tissue-derived stem cells (hADSCs) and their proliferation and differentiation. Materials and Methods: Human ADSCs were isolated by collagenase treatment and characterized. Then, ADSCs were treated with 5 µM RG108 for four days. The control and RG108-treated cells were analyzed for the cell cycle progression, apoptosis and the expression of pluripotency genes. Also, ADSCs were cultured in adipogenic and osteogenic differentiation media for three weeks and were assessed by Oil Red O and Alizarin Red S staining and qPCR analysis. Results: We showed that RG108 treatment increased proliferation of hADSCs and upregulated the expression of pluripotency-related genes. Additionally, RG108 had a positive impact on the differentiation capability of ADSCs. This was evident through elevated levels of Oil Red O staining in the RG108 treatment group. Also, qPCR analysis showed the upregulation of some adipogenic and osteogenic markers by RG108. Conclusion: These findings indicate that pretreatment with RG108 improves the differentiation potential of ADSCs, probably making these cells more beneficial for cell therapy applications.

Contents of exosomes derived from adipose tissue and their regulation on inflammation, tumors, and diabetes.

Adipose tissue (AT) serves as an energy-capacitive organ and performs functions involving paracrine- and endocrine-mediated regulation via extracellular vesicles (EVs) secretion. Exosomes, a subtype of EVs, contain various bioactive molecules with regulatory effects, such as nucleic acids, proteins, and lipids. AT-derived exosomes (AT-exos) include exosomes derived from various cells in AT, including adipocytes, adipose-derived stem cells (ADSCs), macrophages, and endothelial cells. This review aimed to comprehensively evaluate the impacts of different AT-exos on the regulation of physiological and pathological processes. The contents and functions of adipocyte-derived exosomes and ADSC-derived exosomes are compared simultaneously, highlighting their similarities and differences. The contents of AT-exos have been shown to exert complex regulatory effects on local inflammation, tumor dynamics, and insulin resistance. Significantly, differences in the cargoes of AT-exos have been observed among diabetes patients, obese individuals, and healthy individuals. These differences could be used to predict the development of diabetes mellitus and as therapeutic targets for improving insulin sensitivity and glucose tolerance. However, further research is needed to elucidate the underlying mechanisms and potential applications of AT-exos.

The association between visceral adipose accumulation and hyperuricemia risk among Chinese elder individuals: A nationwide prospective cohort study.

Background: Lipid accumulation product (LAP), visceral adiposity index (VAI) and Chinese visceral adiposity index (CVAI) are proposed indices of visceral adipose accumulation. This study aimed to explore their relationship and temporal changes with hyperuricemia (HUA) development in a Chinese population. Methods: A total of 4268 participants aged ≥45 years from the baseline survey of the China Health and Retirement Longitudinal Study were followed up for 4 years (from 2011 to 2015). The relationships among VAI, LAP, CVAI and HUA were analyzed using logistic regression. The predictive abilities of the VAI, LAP and CVAI for HUA were compared using receiver operating characteristic curves. Nonlinear relationships between the indices and HUA were analyzed using restricted cubic spline regression. Results: During the four-year follow-up, 415 (9.72 %) patients experienced incident HUA . Elevated baseline VAI (odds ratio (OR): 1.19 (95 % confidence interval (95 %CI: 1.10, 1.29)), LAP (OR: 1.21 (95 % CI: 1.09, 1.34)) and CVAI (OR: 1.19 (95 % CI: 1.02, 1.40)) were significantly correlated with increased HUA risk (all P < 0.05). Compared to individuals with consistently low VAI,CVAIor LAP levels, those with elevated or consistently high levels of these indicators are more likely to have HUA. The area under curve (AUC) was slightly greater and more significant for the CVAI (AUC=0.641) than for the VAI (AUC=0.604) and LAP (AUC=0.628) (P < 0.05). Conclusion: VAI, LAP and CVAI can predict HUA, with CVAI more efficient than VAI and LAP. Early management can lessen the burden of HUA in Chinese people aged 45 years or older with elevated CVAI levels.

Exercise-Induced cytokines, diet, and inflammation and their role in adipose tissue metabolism.

Background: Obesity poses a significant global health challenge, necessitating effective prevention and treatment strategies. Exercise and diet are recognized as pivotal interventions in combating obesity. This study reviews the literature concerning the impact of exercise-induced cytokines, dietary factors, and inflammation on adipose tissue metabolism, shedding light on potential pathways for therapeutic intervention. Methodology: A comprehensive review of relevant literature was conducted to elucidate the role of exercise-induced cytokines, including interleukin-6 (IL-6), interleukin-15 (IL-15), brain-derived neurotrophic factor (BDNF), irisin, myostatin, fibroblast growth factor 21 (FGF21), follistatin (FST), and angiopoietin-like 4 (ANGPTL4), in adipose tissue metabolism. Various databases were systematically searched using predefined search terms to identify relevant studies. Articles selected for inclusion underwent thorough analysis to extract pertinent data on the mechanisms underlying the influence of these cytokines on adipose tissue metabolism. Results and Discussion: Exercise-induced cytokines exert profound effects on adipose tissue metabolism, influencing energy expenditure (EE), thermogenesis, fat loss, and adipogenesis. For instance, IL-6 activates AMP-activated protein kinase (AMPK), promoting fatty acid oxidation and reducing lipogenesis. IL-15 upregulates peroxisome proliferator-activated receptor delta (PPARδ), stimulating fatty acid catabolism and suppressing lipogenesis. BDNF enhances AMPK-dependent fat oxidation, while irisin induces the browning of white adipose tissue (WAT), augmenting thermogenesis. Moreover, myostatin, FGF21, FST, and ANGPTL4 each play distinct roles in modulating adipose tissue metabolism, impacting factors such as fatty acid oxidation, adipogenesis, and lipid uptake. The elucidation of these pathways offers valuable insights into the complex interplay between exercise, cytokines, and adipose tissue metabolism, thereby informing the development of targeted obesity management strategies. Conclusion: Understanding the mechanisms by which exercise-induced cytokines regulate adipose tissue metabolism is critical for devising effective obesity prevention and treatment modalities. Harnessing the therapeutic potential of exercise-induced cytokines, in conjunction with dietary interventions, holds promise for mitigating the global burden of obesity. Further research is warranted to delineate the precise mechanisms underlying the interactions between exercise, cytokines, and adipose tissue metabolism.

Human adipose mesenchymal stem cell-derived exosomes alleviate fibrosis by restraining ferroptosis in keloids.

Background: Keloid is a fibroproliferative disease with unsatisfactory therapeutic effects and a high recurrence rate. exosomes produced by adipose-derived mesenchymal stem cells (ADSC-Exos) have attracted significant interest due to their ability to treat fibrosis. However, the molecular mechanisms of ADSC-Exos in keloids remain inconclusive. Objective: Our study revealed the relationship between ferroptosis and fibrosis in keloids. Subsequently, this study aimed to explore further the anti-fibrotic effect of ADSC-Exos on keloids through ferroptosis and the potential underlying mechanisms. Methods: To investigate the impact of ferroptosis on keloid fibrosis, Erastin and ferrostatin-1 (fer-1) were utilized to treat keloid fibroblast. Keloid keloids treated with Erastin and fer-1 were cocultured with ADSC-Exos to validate the impact of ferroptosis on the effect of ADSC-Exos on keloid anti-ferrotic protein, peroxidase 4 (GPX4) and anti-fibrotic effects in vivo and in vitro by Western blot, as well as variations in iron metabolite expression, malondialdehyde (MDA), liposomal peroxidation (LPO) and glutathione (GSH) were analyzed. The effect of solute carrier family 7-member 11 (SLC7A11) silencing on ADSC-Exo-treated keloid fibroblast was investigated. Results: Iron metabolite dysregulation was validated in keloids. Fibrosis progression is enhanced by Erastin-induced ferroptosis. The anti-fibrotic effects of ADSC-Exos and fer-1 are related to their ability to prevent iron metabolism. ADSC-Exos effectively suppressed keloid fibrosis progression and increased GSH and GPX4 gene expression. Additionally, the use of Erastin limits the effect of ADSC-Exos in keloids. Furthermore, the effect of ADSC-Exos on keloids was associated with SLC7A11-GPX4 signaling pathway. Conclusion: We demonstrated a new potential mechanism by which anti-ferroptosis inhibits the progression of keloid fibrosis and identified an ADSC-Exo-based keloid therapeutic strategy. Resisting the occurrence of ferroptosis and the existence of the SLC7A11-GPX4 signaling pathway might serve as a target for ADSC-Exos.

Actein ameliorates diet-induced obesity through the activation of AMPK-mediated white fat browning.

BACKGROUND: Targeting white adipose tissue (WAT) browning to increase systemic energy expenditure is a promising therapeutic strategy to combat obesity. Actein from Actaea cimicifuga L. has recently been reported to ameliorate high fat-induced hepatic steatosis. However, the effect of actein on diet-induced obesity merits more and further investigation. PURPOSE: We aimed to examine the anti-obesity potential of actein and unravel its actions on WAT browning. METHODS: The effect of actein on diet-induced obesity was evaluated using a high-fat diet model in C57BL/6 mice. Systemic energy expenditure of mice was measured with a combined indirect calorimetry system. Quantitative real-time PCR analyses were performed to investigate the mRNA levels of genes involved in thermogenesis, browning, and lipolysis. The protein levels were assessed by Western blot. Moreover, WAT explants and a transwell co-culture system consisting of SVFs and adipocytes were constructed to study the mechanisms of actein on promoting WAT browning and lipolysis. RESULTS: At a dosage of 5 mg/kg/d, actein not only protected mice against diet-induced obesity and insulin resistance, but also reversed pre-established obesity and glucose intolerance in mice. Meanwhile, actein facilitated systemic energy expenditure by activating WAT lipolysis and browning. Further, mechanistic studies revealed that actein indirectly induced epididymal adipocyte lipolysis and directly promoted a white-to-beige conversion of subcutaneous adipocytes by activating the AMPK signaling. CONCLUSION: Actein ameliorated diet-induced obesity and was discovered as a natural lead compound directly targeting white-to-beige conversion of subcutaneous adipocytes, suggesting the potential of developing new therapies for obesity and associated metabolic disorders.

Murine Nuclear Tyrosyl-tRNA Synthetase Deficiency Leads to Fat Storage Deficiency and Hearing Loss.

Aminoacyl-tRNA synthetases (aaRS) are fundamental to the translation machinery with emerging roles in transcriptional regulation. Previous cellular studies have demonstrated tyrosyl-tRNA synthetase (YARS1 or TyrRS) as a stress response protein through its cytosol-nucleus translocation to maintain cellular homeostasis. Here, we established a mouse model with a disrupted TyrRS nuclear localization signal, revealing its systemic impact on metabolism. Nuclear TyrRS deficiency (YarsΔNLS) led to reduced lean mass, reflecting a mild developmental defect, and reduced fat mass, possibly due to increased energy expenditure. Consistently, YarsΔNLS mice exhibit improved insulin sensitivity and reduced insulin levels, yet maintain normoglycemia, indicative of enhanced insulin action. Notably, YarsΔNLS mice also develop progressive hearing loss. These findings underscore the crucial function of nuclear TyrRS in the maintenance of fat storage and hearing and suggest that aaRSs' regulatory roles can affect metabolic pathways and tissue-specific health. This work broadens our understanding of how protein synthesis interconnects metabolic regulation to ensure energy efficiency.

Exploring the impact of acetylsalicylic acid and conditioned medium obtained from mesenchymal cells, individually and in combination, on cognitive function, histological changes, and oxidant-antioxidant balance in male rats with hippocampal injury.

BACKGROUND: The hippocampus is susceptible to damage, leading to negative impacts on cognition. Conditioned medium (CM) obtained from adipose tissue-derived mesenchymal stem cells (MSCs) and acetylsalicylic acid (ASA) have shown neuroprotective effects independently. This study explored the synergistic potential of ASA and CM from adipose-derived MSCs against hippocampal injury. METHODS: Adult male Wistar rats received bilateral hippocampal ethidium bromide (EB) injections to induce hippocampal damage. Rats were treated with ASA and/or CM derived from adipose tissue MSCs every 48 h for 16 days. Behavioral tests (open field test, Morris water maze, novel object recognition, and passive avoidance), oxidative stress, Western blot analysis of brain-derived neurotrophic factor (BDNF) and cerebral dopamine neurotrophic factor (CDNF) expression, and hippocampal histological investigation were conducted. RESULTS: Administration of EB caused impairments in spatial, recognition, and passive avoidance memory, as well as heightened oxidative stress, reduced BDNF/CDNF expression, and pyramidal cell loss in the hippocampal CA1 region. Administration of ASA, CM, or a combination of both mitigated these hippocampal damages and cognitive deficits, elevated BDNF and CDNF levels, and alleviated the CA1 necrosis caused by EB. Moreover, co-administering ASA and CM resulted in greater improvements in spatial memory compared to administering ASA alone, suggesting possible synergistic interactions. CONCLUSIONS: The ability of ASA, CM obtained from adipose tissue-derived MSCs, and their combination therapy to alleviate hippocampal injuries highlights their promising therapeutic potential as a neuroprotection strategy against brain damage. Our findings provide preliminary evidence of the potential synergistic effects of ASA and CM, which warrants further investigations.

The change of epicardial adipose tissue characteristics and vulnerability for atrial fibrillation upon drastic weight loss.

BACKGROUND: Obesity increases the risk of atrial fibrillation (AF). We hypothesize that 'obese' epicardial adipose tissue (EAT) is, regardless of comorbidities, associated with markers of AF vulnerability. METHODS: Patients >40y of age undergoing bariatric surgery and using <2 antihypertensive drugs and no insulin were prospectively included. Study investigations were conducted before and 1y after surgery. Heart rhythm and p-wave duration were measured through ECGs and 7-d-holters. EAT-volume and attenuation were determined on non-enhanced CT scans. Serum markers were quantified by ELISA. RESULTS: Thirty-seven patients underwent surgery (age: 52.1 ± 5.9y; 27 women; no AF). Increased p-wave duration correlated with higher BMI, larger EAT volumes, and lower EAT attenuations (p < 0.05). Post-surgery, p-wave duration decreased from 109 ± 11 to 102 ± 11ms. Concurrently, EAT volume decreased from 132 ± 49 to 87 ± 52ml, BMI from 43.2 ± 5.2 to 28.9 ± 4.6kg/m2, and EAT attenuation increased from -76.1 ± 4.0 to -71.7 ± 4.4HU (p <0.001). Adiponectin increased from 8.7 ± 0.8 to 14.2 ± 1.0 µg/ml (p <0.001). However, decreased p-wave durations were not related to changed EAT characteristics, BMI or adiponectin. CONCLUSION: In this explorative study, longer p-wave durations related to higher BMIs, larger EAT volume, and lower EAT attenuations. P-wave duration and EAT volume decreased, and EAT attenuation increased upon drastic weightloss. However, there was no relation between decreased p-wave duration and changed BMI or EAT characteristics.

MiRNA-132/212 encapsulated by adipose tissue-derived exosomes worsen atherosclerosis progression.

BACKGROUND: Visceral adipose tissue in individuals with obesity is an independent cardiovascular risk indicator. However, it remains unclear whether adipose tissue influences common cardiovascular diseases, such as atherosclerosis, through its secreted exosomes. METHODS: The exosomes secreted by adipose tissue from diet-induced obesity mice were isolated to examine their impact on the progression of atherosclerosis and the associated mechanism. Endothelial apoptosis and the proliferation and migration of vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque were evaluated. Statistical significance was analyzed using GraphPad Prism 9.0 with appropriate statistical tests. RESULTS: We demonstrate that adipose tissue-derived exosomes (AT-EX) exacerbate atherosclerosis progression by promoting endothelial apoptosis, proliferation, and migration of VSMCs within the plaque in vivo. MicroRNA-132/212 (miR-132/212) was detected within AT-EX cargo. Mechanistically, miR-132/212-enriched AT-EX exacerbates palmitate acid-induced endothelial apoptosis via targeting G protein subunit alpha 12 and enhances platelet-derived growth factor type BB-induced VSMC proliferation and migration by targeting phosphatase and tensin homolog in vitro. Importantly, melatonin decreases exosomal miR-132/212 levels, thereby mitigating the pro-atherosclerotic impact of AT-EX. CONCLUSION: These data uncover the pathological mechanism by which adipose tissue-derived exosomes regulate the progression of atherosclerosis and identify miR-132/212 as potential diagnostic and therapeutic targets for atherosclerosis.

Therapeutic potential of mesenchymal stem cell-derived extracellular vesicles in SARS-CoV-2 and H1N1 influenza-induced acute lung injury.

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have shown anti-inflammatory potential in multiple inflammatory diseases. In the March 2022 issue of the Journal of Extracellular Vesicles, it was shown that EVs from human MSCs can suppress severe acute respiratory distress syndrome, coronavirus 2 (SARS-CoV-2) replication and can mitigate the production and release of infectious virions. We therefore hypothesized that MSC-EVs have an anti-viral effect in SARS-CoV-2 infection in vivo. We extended this question to ask whether also other respiratory viral infections could be treated by MSC-EVs. Adipose stem cell-derived EVs (ASC-EVs) were isolated using tangential flow filtration from conditioned media obtained from a multi-flask cell culture system. The effects of the ASC-EVs were tested  in Vero E6 cells in vitro. ASC-EVs were also given i.v. to SARS-CoV-2 infected Syrian Hamsters, and H1N1 influenza virus infected mice. The ASC-EVs attenuated SARS-CoV-2 virus replication in Vero E6 cells and reduced body weight and signs of lung injury in infected Syrian hamsters. Furthermore, ASC-EVs increased the survival rate of influenza A-infected mice and attenuated signs of lung injury. In summary, this study suggests that ASC-EVs can have beneficial therapeutic effects in models of virus-infection-associated acute lung injury and may potentially be developed to treat lung injury in humans.

Subpial transplantation of adipose-derived stem cells alleviates paraplegia in a rat model of aortic occlusion/reperfusion-induced spinal cord infarction.

Background: Thoracoabdominal periprocedural occlusion/reperfusion injury of the spinal cord (SCII/R) can lead to devastating paraplegia, underscoring the critical need for effective interventions. However, our knowledge of optimal medical strategies and their efficacy remains limited. Preclinical investigations have shown promise in harnessing adult stem cells, including pluripotent and multipotent stem cells such as mesenchymal stem cells (MSCs), to address SCII/R by enhancing neuro-inflammation, axonal growth, and myelination. Particularly, growth factors derived from adipose tissue-derived MSCs (ADSCs) have been proposed to facilitate recovery. Despite advancements, achieving complete recovery remains a formidable challenge. Therefore, gaining a more profound insight into the role of ADSCs in alleviating SCII/R-induced paraplegia, including optimizing the delivery systems for therapies, is imperative. Materials and methods: In this study, we assessed the impact of subpial allogeneic rat adipose tissue-derived MSCs (rADSCs) transplantation on paraplegia using a rat SCII/R model induced by ephemeral aortic occlusion, known as the Taira-Marsala model. rADSCs were isolated from adipose tissue of male Sprague-Dawley rats, cultured, characterized, and cryopreserved. One week following the induction of paraplegia, rADSCs (n = 6) or physiological saline (n = 6) were transplanted. Hind limb motor function was evaluated before treatment and at 3-, 7-, and 14-days post-treatment using the Basso-Beattie-Bresnahan scoring system. Results: The rADSC-treated group demonstrated a significant improvement in hind limb motor function compared to the saline-treated group (p < 0.05), with 5 out of 6 rats exhibiting enhanced motor function following treatment. Conclusions: Our findings suggest that subpial rADSC engraftment may enhance SCII/R-induced paraplegia recovery. These initial results drive further research to validate this potential, understand the molecular mechanisms, and optimize therapies.