Trophic Properties Research Articles

Residence time and ultrastructural effects of a new formulation of multiple‐action tear substitute: Preliminary results at scanning electron microscopy (SEM) examination

Aims/Purpose: The aim of the study is to evaluate with SEM the residence time and ultrastructural effects on the ocular surface cells in patients suffering from dry eye disease (DED) treated with a multiple‐acting tear substitute based on 0.15% cross‐linked HA, cationic liposomes and 3% trehalose (Trimix®, Offhealth SpA, Firenze, Italy).Methods: We examined 10 eyes of 10 patients with previous clininal diagnosis of DED (Schirmer test 1 < 10 mm, TBUT < 10 s, OSDI > 13). Exclusion criteria: topical or systemic therapies in the previous 30 days; allergic conjunctivitis; infections and other ocular surface diseases in the last 3 months; previous herpetic keratitis; corneal opacities and ulcers; pregnancy and breastfeeding, age < 18 years.All patients were treated for 30 days BID with Trimix®. At the baseline (T0) and 1h (T1), 6h (T2) and 12h (T3) after the end of the treatment, a cytological sampling of the bulbar conjunctiva with an impression procedure was performed. The cytological smear was examined with SEM for the evaluation of the microvilli, using a preset scale (Del Prete, 2017), and of the persistence of Trimix®, preliminarily identified by SEM on a slide. The results were compared with a control group (CTR) of 10 patients with the same grades of inflammation of DED group, treated with BID balanced salt solution.Results: At T0 6 DED patients presented mild/moderate inflammation (grade 1‐2 of microvillar alteration); 4 medium/severe inflammation, with grade 3‐4 on the microvillar evaluation. At T1 8/10 eyes (80%) showed a complete restoration of the microvillar surface (p < 0.001), 2/10 (20%) an improvement at stage 1 (p < 0.001). The persistence of the Trimix® molecules was detected at T1 and T2 in all cases; in 9 of them (90%) Trimix® partially enveloped the microvilli at T3. No significant microvillar changes were found in CTR group (p > 0.05). The tear substitute resulted well tolerated as no patient reported any significant side effects.Conclusions: Microvilli express the vitality of epithelial cells. Their significant improvement or complete recovery after treatment with Trimix® indicates strong trophic and protective properties of the product, that could continue even 12 hours after the instillation, as confirmed by the high residence time. This could suggest a high effectiveness even when administered twice daily.

Mesenchymal Stem Cell-Sourced Exosomes as Potentially Novel Remedies for Severe Dry Eye Disease.

Severe dry eye disease (DED) is an inflammatory condition characterized by a lack of sufficient moisture or lubrication on the surface of the eye, significantly impacting the quality of life and visual function. Since detrimental immune response is crucially responsible for the development and aggravation of DED, therapeutic agents which modulate phenotype and function of eye-infiltrated inflammatory immune cells could be used for the treatment of severe DED. Due to their potent immunomodulatory properties, mesenchymal stem cells (MSCs) represent potentially new remedies for the treatment of inflammatory eye diseases. The majority of MSC-sourced bioactive factors are contained within MSC-derived exosomes (MSC-Exos), nano-sized extracellular vesicles which, due to their nanosize dimension and lipid envelope, easily by pass all biological barriers in the body and deliver their cargo directly into the target immune cells. MSC-Exos contain a variety of bioactive proteins (growth factors, immunoregulatory molecules, cytokines, and chemokines) lipids, and microRNAs (miRNAs) which affect viability, proliferation, phenotype, and function of eye-infiltrated immune cells. Accordingly, MSC-Exos may modulate the progression of inflammatory eye diseases, including DED. Therefore, in this review article, we summarized the current knowledge regarding molecular and cellular mechanisms which were responsible for trophic, anti-inflammatory, immunoregulatory, and regenerative properties of MSC-Exos in the treatment of severe DED. For this purpose, an extensive literature review was carried out in February 2024 across several databases (Medline, Embase, and Google Scholar), from 2000 to the present. Eligible studies delineated molecular and cellular mechanisms responsible for the MSC-Exos-based modulation of immune cell-driven eye inflammation in DED, and their findings were analyzed in this review. Results obtained in these studies demonstrated beneficial effects of MSC-Exos in the treatment of severe DED, paving the way for their future clinical use in ophthalmology. Trial Registration: ClinicalTrials.gov identifier: NCT04213248, NCT06475027, NCT06543667, NCT05738629.

Neurotrophic Hypothesis of Development of Depression

Currently, depression is a widespread mental disorder in modern society and is associated with significant impairments in the quality of life of patients. The review examines the main representatives of neurotrophic factors belonging to various families, in particular nerve growth factor, transforming growth factor beta, neurokines and non-neuronal factors. Neurotrophins, being large polypeptides, play an integrative role, fulfilling the signaling mission of intermediaries in a wide range of physiological processes. At the moment, a large number of studies have been carried out in order to understand the interaction between factors of various directions, including biological, psychological and environmental factors that determine the etiopathogenesis of this pathology. Based on the data obtained, one of the main hypotheses for the development of depression is considered - neurotrophic, which most fully explains the emerging pathogenetic changes. According to this hypothesis, the leading role in the etiology of depression is played by neurotrophic factors that ensure the maintenance of normal neuron-glial interaction, the processes of neurogenesis, angiogenesis, and synaptic plasticity. Neurotrophins have a high physiological activity due to the presence of several binding groups for different cell receptors and the regulatory ability to express other signaling molecules, the ability to penetrate the blood-brain barrier, showing trophic, anti-inflammatory, growth, mediator and effector properties. To date, the mechanisms of the onset of depression, despite the widespread prevalence of this pathology, remain largely unclear, hindering a directed search for targets for the development of effective therapy. The revealed disorders of neurotrophic factors in depression make it reasonable to consider neurotrophins as therapeutic agents in a multitarget approach to the treatment of depressive disorders.

The Cytokine Levels of Cord Blood- and Wharton's Jelly-Derived Mesenchymal Stem Cells from Early to Late Passages.

Mesenchymal stem cells (MSCs) are promising for clinical studies owing to their self-renewal, multipotency, trophic, and immunomodulatory properties. This study aimed to investigate the cytokine levels of human umbilical cord blood (CB) and Wharton's Jelly-(WJ) derived MSCs relevant to immune modulation on different passage levels in vitro. Umbilical CB MSCs were isolated using the ficoll-paque gradient method, and WJ-MSCs were isolated by the explant method. After isolation, the MSCs were characterized using flow cytometry. The supernatant cytokine levels (interferon-gamma (IFN-γ), interleukin 4 (IL-4), interleukin 17 (IL-17)) of MSCs at each passage were evaluated using the ELISA assay. MSCs exhibited different cytokine levels with each passage number. In WJ-MSC culture supernatants, IL-17 levels significantly increased at P4 and P5 compared to the first passage (p < 0.005), while the other passages showed a decrease. IFN-γ levels increased at passage P1 and P4 and decreased at other passages (p < 0.005). IL-4 levels significantly increased only at passage P3 (p < 0.005). In CB-MSC culture supernatants, IL-17 and IL-4 cytokines decreased compared to P0, while IFN-γ cytokine increased from P0 (p < 0.005). The changing ratio of cytokine levelsfor both CB-MSCs and WJ-MSCs were similarly maintained from early to late passages. More research is needed to understand the immunomodulatory functions of MSCs.

Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders.

Pregnane neuroactive steroids, notably allopregnanolone and pregnenolone, exhibit efficacy in mitigating inflammatory signals triggered by toll-like receptor (TLR) activation, thus attenuating the production of inflammatory factors. Clinical studies highlight their therapeutic potential, particularly in conditions like postpartum depression (PPD), where the FDA-approved compound brexanolone, an intravenous formulation of allopregnanolone, effectively suppresses TLR-mediated inflammatory pathways, predicting symptom improvement. Additionally, pregnane neurosteroids exhibit trophic and anti-inflammatory properties, stimulating the production of vital trophic proteins and anti-inflammatory factors. Androstane neuroactive steroids, including estrogens and androgens, along with dehydroepiandrosterone (DHEA), display diverse effects on TLR expression and activation. Notably, androstenediol (ADIOL), an androstane neurosteroid, emerges as a potent anti-inflammatory agent, promising for therapeutic interventions. The dysregulation of immune responses via TLR signaling alongside reduced levels of endogenous neurosteroids significantly contributes to symptom severity across various neuropsychiatric disorders. Neuroactive steroids, such as allopregnanolone, demonstrate efficacy in alleviating symptoms of various neuropsychiatric disorders and modulating neuroimmune responses, offering potential intervention avenues. This review emphasizes the significant therapeutic potential of neuroactive steroids in modulating TLR signaling pathways, particularly in addressing inflammatory processes associated with neuropsychiatric disorders. It advances our understanding of the complex interplay between neuroactive steroids and immune responses, paving the way for personalized treatment strategies tailored to individual needs and providing insights for future research aimed at unraveling the intricacies of neuropsychiatric disorders.

Biochemical state of brain-liver axis of rats under restraint-induced stress and 2-oxoglutarate impact

Environmental factors play a significant role in affecting the overall health of organisms, with stress being a notable contributor. The process of urbanization and globalization in modern society introduces additional stressors, exacerbating population health issues. Consequently, there is a need for thorough examination, analysis, and exploration of strategies to mitigate the adverse effects of stress. 2-Oxoglutarate, an essential intracellular metabolite and mediator with metabolite trophic properties, emerges as a promising candidate for intervention. In this study, we aimed to evaluate the combined impact of restraint-induced stress and 2-oxoglutarate on the oxidative-reducing balance, antioxidant system effectiveness, and the functional status of the liver and brain in rats. Restraint-induced stress was found to elevate oxidative stress levels, as evidenced by increased concentrations of malonic dialdehyde and oxidative-modified proteins, particularly in the brain. Additionally, signs of lactic acidosis were observed in the liver, indicating physiological changes in response to stress. Furthermore, restraint-induced stress significantly altered bioenergy components, with decreased superoxide dismutase activity and increased cytochrome C concentration, potentially indicating mitochondrial dysfunction and increased membrane permeability. The incorporation of a 2% solution of 2-oxoglutarate into the diet demonstrated a reduction in malonic dialdehyde and carbonylated protein formation, leading to more effective restoration of oxidative-reducing balance in the brain compared to the liver. Additionally, normalization of the lactate/pyruvate concentration ratio and decreased lactate dehydrogenase activity, alongside elevated alanine aminotransferase levels, suggested a decrease in oxidative stress in the liver. Moreover, exogenous 2-oxoglutarate exhibited a positive effect on superoxide dismutase activity and cytochrome C concentration, indicating a reduction in oxidative tension in the liver and progressive mitochondrial function recovery. Based on these findings, exogenous 2-oxoglutarate emerges as a promising metabolitotrope and adaptogen for managing oxidative stress and improving mitochondrial function.

Niche width and overlap of benthic invertebrates in surf zones increase with distance from the estuarine source of organic matter

Benthic invertebrates in the surf zone of exposed sandy beaches represent important links for energy circulation between benthic and pelagic food webs. This work assesses the trophic ecology of co-occurring epi- and hyper-benthic invertebrates inhabiting the surf zone of sandy beaches located close to an estuarine mouth. It illustrates that different sources of organic matter induce changes in resource utilization. The trophic positions, and the niche width and overlap of species were described using δ13C and δ15N stable isotope analysis. The contribution of different sources to the particulate organic matter was quantified through stable isotopes analysis and fatty acids profiles. Shifts in the trophic niches of dominant species reflected a decrease in the contribution of estuarine carbon to the diets along the coast. This change in contribution of estuarine carbon also influenced trophic niche properties: more diverse resources availability resulted in narrower niches without overlap while less diverse resources resulted in broad isotopic niches and a highest overlap. Results show that spatial variations in the availability of resources can modify carbon pathways and trophic interactions in coastal food webs. Whenever resources are abundant, species display a more specialized diet while food scarcity leads to broader diets, a pattern consistent with the optimal foraging theory. This resource maximization behavior commonly observed in nature is also occurring in surf zone ecosystems.

A Nonenzymatic Procedure to Obtain Human Mesenchymal Stromal Cells from the Dermis.

Human mesenchymal stromal cells (MSCs) have gained significant interest as cell-based therapeutics for organ restoration in the field of regenerative medicine. More recently, substantial attention has been directed toward cell-free therapy, achieved through the utilization of soluble factors possessing trophic and immunomodulatory properties present in the MSC secretome. This collection of soluble factors can be found either freely in the secretome or packed within its vesicular fraction, known as extracellular vesicles (EVs). MSCs can be derived from various tissue sources, each involving different extraction methods and yielding varying cell amounts. In this study, we describe a nonenzymatic procedure for a straightforward isolation of MSCs from the fetal dermis and the adult dermis. The results demonstrate the isolation of a cell population with a uniform MSC immunophenotype from the earliest passages (approximately 90% positive for the classical MSC markers CD90, CD105, and CD73, while negative for the hematopoietic markers CD34 and CD45, as well as HLA-DR). Additionally, we describe the procedures for cell expansion, banking, and secretome collection.

TMT-Based Quantitative Proteomics Analysis Reveals Differentially Expressed Proteins between Different Sources of hMSCs.

Mesenchymal stem cells (MSCs) are an attractive therapeutic tool for tissue engineering and regenerative medicine owing to their regenerative and trophic properties. The best-known and most widely used are bone marrow MSCs, which are currently being harvested and developed from a wide range of adult and perinatal tissues. MSCs from different sources are believed to have different secretion potentials and production, which may influence their therapeutic effects. To confirm this, we performed a quantitative proteomic analysis based on the TMT technique of MSCs from three different sources: Wharton's jelly (WJ), dental pulp (DP), and bone marrow (BM). Our analysis focused on MSC biological properties of interest for tissue engineering. We identified a total of 611 differentially expressed human proteins. WJ-MSCs showed the greatest variation compared with the other sources. WJ produced more extracellular matrix (ECM) proteins and ECM-affiliated proteins and proteins related to the inflammatory and immune response processes. BM-MSCs expressed more proteins involved in osteogenic, adipogenic, neuronal, or muscular differentiation and proteins involved in paracrine communication. Compared to the other sources, DP-MSCs overexpressed proteins involved in the exocytosis process. The results obtained confirm the existence of differences between WJ, DP, and BM-MSCs and the need to select the MSC origin according to the therapeutic objective sought.

Taxonomic and ecophysiological characteristics of actinobacteria in soils of the dry steppe zone of the Selenga Highlands (Western Transbaikalia).

Arid habitats have recently attracted increasing attention in terms of biodiversity research and the discovery of new bacterial species. These habitats are among the target ecosystems suitable for isolating new strains of actinobacteria that are likely to produce new metabolites. This paper presents the results on the isolation of actinobacteria from soils of the dry steppe zone of the Selenga Highlands, the characterization of their taxonomic diversity, as well as ecological and trophic properties. The bacterial counts on ISP 4 medium ranged from 6.6 × 105 to 7.1 × 106 CFU/g. The highest bacterial counts were observed in the subsurface and middle horizons of the studied soils. 28 strains of Gram-positive bacteria represented by thin-branched mycelium, coccoid and bacilliform forms were isolated. According to the results of 16S rRNA gene analysis, the isolated strains were representatives of Streptomyces, Arthrobacter, Glycomyces, Kocuria, Microbacterium, Micromonospora, Nocardioides, Pseudarthrobacter, and Rhodococcus (Actinomycetota). One isolate that showed low 16S rRNA gene sequence similarity with previously isolated and validly described species was a new species of the genus Glycomyces. It was shown that all tested strains are mesophilic, prefer neutral or slightly alkaline conditions, have growth limits in the temperature range of 5-45 °C and pH 6-9. The optimal NaCl concentration for growth of most strains was 0-1 %. The strains under study were capable of utilizing a wide range of mono- and disaccharides and polyatomic alcohols as a carbon source. The isolated strains were capable of using both organic (proteins and amino acids) and inorganic (ammonium salts and nitrates) compounds as nitrogen sources. The examinations of extracellular enzymes showed that all isolates were capable of producing catalase and amylase; 78.6 % of the total number of isolates produced protease and lipase; 53.6 %, cellulase; and 28.6 %, urease. The data obtained expand current knowledge about the diversity of microbial communities in soils of the Selenga Highlands and also confirm the potential of searching for new actinobacteria species in these soils.

Cerebrospinal Fluid Biomarkers Associated with Intrathecal Cell Therapy in Patients with Progressive Multiple Sclerosis (P1-3.001)

<h3>Objective:</h3> To identify cerebrospinal fluid (CSF) biomarkers of clinical response to intrathecal (IT) mesenchymal stem cell-neural progenitor (MSC-NP) treatment in patients with progressive multiple sclerosis (MS). <h3>Background:</h3> MSC-NPs are a bone marrow-derived population of cells with trophic and immunomodulatory properties with therapeutic potential in MS. A phase II randomized, double-blind, placebo-controlled clinical trial was performed to investigate whether multiple intrathecal (IT) injections of autologous MSC-NPs was associated with clinical efficacy. Study subjects received either 6 IT injections of autologous MSC-NPs or 6 placebo injections spaced 2 months apart. In the crossover study design, subjects treated with placebo in the first year were treated with MSC-NPs in the second year, and vice versa. Safety and clinical efficacy will be reported elsewhere. <h3>Design/Methods:</h3> For biomarker discovery, CSF was collected from 36 study subjects at the time of their first and sixth IT-MSC-NP treatment reflecting pre-treatment and post-treatment timepoints, respectively. CSF supernatants were analyzed using SOMAScan multiplex proteomic assay. Differentially expressed proteins were identified using a multivariate linear mixed effect model. Biomarkers were validated using ELISA/Luminex assays. Treatment responders were defined by improvement in any of the following outcomes: EDSS, timed 25-foot walk, 9-hole peg test, 6-minute walk test, or muscle strength. <h3>Results:</h3> Proteomic analysis of CSF identified matrix metalloproteinase-9 (MMP-9), complement C3a and the chemokine CCL2 as potential biomarkers of IT-MSC-NP treatment. MMP-9 was significantly increased post-treatment and was observed independent of clinical response. Relative concentration of C3a, C3 and C3b were decreased post-treatment and subgroup analysis demonstrated significance only in the responder group. CCL2 was significantly decreased post-treatment with higher significance associated with clinical response. Decreased CCL2 was validated in an independent cohort of patients treated with IT-MSC-NPs. <h3>Conclusions:</h3> These results identify multiple CSF biomarkers of IT-MSC-NP treatment that may correlate with therapeutic response to this novel cell therapy in MS. <b>Disclosure:</b> Miss Kizilbash has nothing to disclose. Ms. Carlson has nothing to disclose. Violaine K. Harris, PhD has nothing to disclose. Dr. Sadiq has nothing to disclose.

Efficacy of Intrathecal Mesenchymal Stem Cell-Neural Progenitor Therapy in Progressive MS: Results from a Phase II Clinical Trial (S16.005)

<h3>Objective:</h3> To determine safety and efficacy of intrathecal (IT) mesenchymal stem cell-neural progenitor (MSC-NP) treatment in patients with progressive multiple sclerosis (MS). <h3>Background:</h3> MSC-NPs are bone marrow-derived cells with trophic and immunomodulatory properties with therapeutic potential in MS. In an open-label phase I clinical study in 20 progressive MS subjects, the safety and tolerability of the treatment was demonstrated, and was associated with functional neurological improvement, particularly in ambulatory patients. <h3>Design/Methods:</h3> A phase II randomized, double-blind, placebo-controlled clinical trial was performed to investigate the clinical efficacy of multiple intrathecal (IT) injections of autologous MSC-NPs s associated with clinical efficacy. Study subjects (n=54) were stratified according to EDSS (3.0–6.5) and disease subtype (SPMS/PPMS) and randomized into either treatment or placebo group to receive 6 IT injections of MSC-NPs or placebo every 2 months. In year 2, subjects crossed over into the opposite group. The primary outcome was improvement in either EDSS, timed 25-foot walk or 9-hole peg test (EDSS Plus). Secondary outcomes included 6-minute walk test (6MWT), brain volume, and muscle strength. <h3>Results:</h3> Subjects were randomized into treatment (n=24) or placebo (n=27) groups and 3 subjects dropped out of the study. There were 9 serious adverse events, none of which were related to the study intervention. There were no significant differences in the primary endpoint between the two groups in year 1. In the 6MWT, the placebo group showed significant worsening in distance walked compared to the MSC-NP group, specifically in subjects with higher EDSS (6.0–6.5). Overall, 50% of SPMS subjects in the MSC-NP group demonstrated improved muscle strength compared to 33% of SPMS in the placebo group. Preliminary results from the crossover group in year 2 show similar trends in muscle strength and 6MWT after MSC-NP treatment. <h3>Conclusions:</h3> These results suggest that IT-MSC-NP treatment may correlate with therapeutic response in a subgroup of MS patients. <b>Disclosure:</b> Ms. Roche has nothing to disclose. Miss Malin has nothing to disclose. Dr. Stark has nothing to disclose. Dr. Williams has nothing to disclose. Violaine K. Harris, PhD has nothing to disclose. Dr. Sadiq has nothing to disclose.

Immunomodulatory Mechanisms and Therapeutic Potential of Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) are regarded as highly promising cells for allogeneic cell therapy, owing to their multipotent nature and ability to display potent and varied functions in different diseases. The functions of MSCs, including native immunomodulation, high self-renewal characteristic, and secretory and trophic properties, can be employed to improve the immune-modulatory functions in diseases. MSCs impact most immune cells by directly contacting and/or secreting positive microenvironmental factors to influence them. Previous studies have reported that the immunomodulatory role of MSCs is basically dependent on their secretion ability from MSCs. This review discusses the immunomodulatory capabilities of MSCs and the promising strategies to successfully improve the potential utilization of MSCs in clinical research.

An Innovative Surgical Technique to Obtain an Adipose-Derived Stromal Cell-Rich Graft for the Treatment of Osteoarthritis: Technical Note

Osteoarthritis (OA) is one of the main causes of disability worldwide and is caused by the progressive degeneration of joint tissues, ultimately leading to chronic pain and loss of function. Intraarticular delivery of mesenchymal stromal cells, such as adipose-derived stromal cells (ASCs), is being actively investigated due to their trophic properties observed in both preclinical and clinical studies. However, cell expansion and handling involve costly and time-consuming processes that limit their application. Recently, several devices and kits have been developed to isolate and process the stromal vascular fraction (SVF), a high biologically active compound of the adipose tissue, right at the patient’s bedside. In this study, we introduce a novel technique to obtain an SVF graft with a high content of ASCs for intraarticular injection directly from liposuction and with minimal equipment. In this technical note, we describe in detail the steps of the surgical technique as well as strategies to avoid common pitfalls and complications.

Umbilical cord mesenchymal stromal cells transplantation delays the onset of hyperglycemia in the RIP-B7.1 mouse model of experimental autoimmune diabetes through multiple immunosuppressive and anti-inflammatory responses.

Type 1 diabetes mellitus (T1DM) is an autoimmune disorder specifically targeting pancreatic islet beta cells. Despite many efforts focused on identifying new therapies able to counteract this autoimmune attack and/or stimulate beta cells regeneration, TD1M remains without effective clinical treatments providing no clear advantages over the conventional treatment with insulin. We previously postulated that both the inflammatory and immune responses and beta cell survival/regeneration must be simultaneously targeted to blunt the progression of disease. Umbilical cord-derived mesenchymal stromal cells (UC-MSC) exhibit anti-inflammatory, trophic, immunomodulatory and regenerative properties and have shown some beneficial yet controversial effects in clinical trials for T1DM. In order to clarify conflicting results, we herein dissected the cellular and molecular events derived from UC-MSC intraperitoneal administration (i.p.) in the RIP-B7.1 mouse model of experimental autoimmune diabetes. Intraperitoneal (i.p.) transplantation of heterologous mouse UC-MSC delayed the onset of diabetes in RIP-B7.1 mice. Importantly, UC-MSC i. p. transplantation led to a strong peritoneal recruitment of myeloid-derived suppressor cells (MDSC) followed by multiple T-, B- and myeloid cells immunosuppressive responses in peritoneal fluid cells, spleen, pancreatic lymph nodes and the pancreas, which displayed significantly reduced insulitis and pancreatic infiltration of T and B Cells and pro-inflammatory macrophages. Altogether, these results suggest that UC-MSC i. p. transplantation can block or delay the development of hyperglycemia through suppression of inflammation and the immune attack.

Application of Caenorhabditis elegans in the evaluation of food nutrition: A review

AbstractAt present, more and more people are suffering from various diseases and it is particularly important to find a suitable biological model to evaluate the prevention and treatment effects of various drugs and active ingredients on diseases. In all biological models, Caenorhabditis elegans is a kind of organism that is easy to observe and cultivate, has a clear genetic background and a high degree of signal pathway conservation with humans. A variety of active ingredients such as polyphenols, polysaccharides, polypeptides, and vitamins exist from natural products, which has extremely high physiological functions and medicinal values. It is highly reliable to evaluate the trophic and functional properties of the active ingredients from natural products in C. elegans. The functional properties of the active ingredients from natural products such as antiaging, anti‐oxidation, regulating lipid metabolism, preventing and treating Alzheimer's disease in C. elegans were clarified in this review. At the same time, its possible pathways were summarized. The literature revealed that it had great effect to evaluate the nutrition and functionality of the active ingredients from natural products in C. elegans. Finally, the shortcomings in this field and suggestions for further improvement in this field have been emphasized.

Micro-fragmented and nanofat adipose tissue derivatives: In vitro qualitative and quantitative analysis.

Introduction: Adipose tissue is widely exploited in regenerative medicine thanks to its trophic properties, mainly based on the presence of adipose-derived stromal cells. Numerous devices have been developed to promote its clinical use, leading to the introduction of one-step surgical procedures to obtain minimally manipulated adipose tissue derivatives. However, only a few studies compared their biological properties. This study aimed to characterize micro-fragmented (MAT) and nanofat adipose tissue (NAT) obtained with two different techniques. Methods: MAT, NAT and unprocessed lipoaspirate were collected from surgical specimens. RNA extraction and collagenase isolation of stromal vascular fraction (SVF) were performed. Tissue sections were analysed by histological and immunohistochemical (collagen type I, CD31, CD34 and PCNA) staining to assess tissue morphology and cell content. qPCR was performed to evaluate the expression of stemness-related (SOX2, NANOG and OCT3/4), extracellular matrix (COL1A1) and inflammatory genes (IL1β, IL6 and iNOS). Furthermore, multilineage differentiation was assessed following culture in adipogenic and osteogenic media and staining with Oil Red O and Alizarin red. ASC immunophenotype was assessed by flow cytometric analysis of CD90, CD105, CD73 and CD45. Results: Histological and immunohistochemical results showed an increased amount of stroma and a reduction of adipocytes in MAT and NAT, with the latter displaying the highest content of collagen type I, CD31, CD34 and PCNA. From LA to MAT and NAT, an increasing expression of NANOG, SOX2, OCT3/4, COL1A1 and IL6 was noted, while no significant differences in terms of IL1β and iNOS emerged. No statistically significant differences were noted between NAT and SVF in terms of stemness-related genes, while the latter demonstrated a significantly higher expression of stress-related markers. SVF cells derived from all three samples (LA, MAT, and NAT) showed a similar ASC immunoprofile as well as osteogenic and adipogenic differentiation. Discussion: Our results showed that both MAT and NAT techniques allowed the rapid isolation of ASC-rich grafts with a high anabolic and proliferative potential. However, NAT showed the highest levels of extracellular matrix content, replicating cells, and stemness gene expression. These results may provide precious clues for the use of adipose tissue derivatives in the clinical setting.

Trophic and Microbial Patterns in the Ross Sea Area (Antarctica): Spatial Variability during the Summer Season

In open regions of the Ross Sea, the role of the microbial community in the turnover of organic matter has scarcely been investigated; indeed, very little is known on how microbial distribution and functional diversity respond to environmental conditions and hydrographic structures. During the austral summer of 2017, two pelagic areas of the Ross Sea [the Drygalski Ice Tongue and the nearby Terra Nova Bay polynya (A area), and the continental Shelf Break area near Cape Adare (C area)] were studied at selected depths [surface, Deep Chlorophyll Maximum (DCM), Circumpolar Deep Water (CDW), deep waters]. Trophic properties [nutrient concentrations, particulate (POC), dissolved organic carbon (DOC) and its optically significant fraction (CDOM) were measured, together with the main hydrological variables. Microbial community abundance [total prokaryotes, living, dead, and actively respiring fraction, high- and low nucleic acid cells (HNA and LNA), pico- and nano-eukaryotes, culturable heterotrophic bacteria], composition, and metabolism (as whole community and as isolated bacteria) were also assessed. Through a multidisciplinary dataset, this study highlighted the variable response of microbial abundance, diversity, and metabolism of the microbial community to the changing local environmental conditions of the Ross Sea. Different forces, such as organic matter inputs (mostly of detrital nature) released from the Drygalski glacier in the A area, and a coastal-to-offshore gradient in the C area, coexisted within this extreme ecosystem. This resulted in a significant spatial segregation of the edaphic parameters, and of the microbial community distribution and metabolic activity patterns.

Ecosystem approach of artificial reef through trophic web modelling

Along the French coast of the Atlantic and English Channel in a high tidal regime, only a limited number of Artificial Reefs (ARs) had been immerged in very few localities in the aim to increase the local production of fisheries of such hard artificial substratum. Moreover, ARs design have been planned to increase the diversity, abundance and biomass of benthic species associated to hard-bottom. Does the deployment of such artificial structure improve the production and ecological functioning on such equipped areas? Trophic models describing the interaction between species at different trophic levels and based on the quantification of energy flow and matter in ecosystems are able to respond to this question. They allow the application of numerical methods for the characterization of emergent properties of the ecosystem, also called Ecological Network Analysis (ENA). Usually, these indices have been proposed as ecosystem health indicators as they have been demonstrated to be sensitive to different impacts on marine ecosystems. Here, Ecopath ecosystem models composed of 23 compartments, from phytoplankton to mammals, are built to describe the situation “Before” and “After” the implantation of ARs in two areas: the Rade of Cherbourg in the central part of the English Channel along the French coast, and in the south of the Bay of Biscay along the Landes coast. In addition, ENA indices are calculated for the two periods, “before” and “after” the implantation of artificial reefs to compare network functioning and the overall structural trophic web properties. In both areas, increase of benthic and fish compartments insure an increase of the system maturity; nevertheless, the high surge of planktinovorous fishes on the Landes AR showed a protection role of such AR than changes of planktonic preys.

Bioscreening and pre-clinical evaluation of the impact of bioactive molecules from Ptychotis verticillata on the multilineage potential of mesenchymal stromal cells towards immune- and inflammation-mediated diseases.

Mesenchymal stromal cells (MSCs) are currently used in cell reparative medicine due to their trophic and ant-inflammatory properties. The modulation of stem cell properties by phytochemicals has been suggested as a tool to empower their tissue repair capacity. In vitro, MSCs are characterized by their tri-lineage potential that holds great interest for tissue regeneration. Ptychotis Verticillata (PV), an aromatic and medicinal plant, may be thus used to modulate the in vitro multilineage potential of MSCs. We screened the impact of PV-derived essential oil and their bioactive molecules (thymol and carvacrol) on the in vitro multilineage potential of MSCs. Different concentrations and incubation times of these compounds were assessed during the osteogenesis and adipogenesis of MSCs. The analysis of 75 conditions indicates that these compounds are biologically active by promoting two major differentiation lineages from MSCs. In a time- and dose-dependent manner, thymol and carvacrol increased the osteogenesis and adipogenesis. According to these preliminary observations, the addition of PV extract may stimulate the tissue regenerative and repair functions of MSCs. Further optimization of compound extraction and characterization from PV as well as cell treatment conditions should increase their therapeutic value in combination with MSCs.