Metabolic Activity Research Articles

Loss of the histone chaperone UNC-85/ASF1 inhibits the epigenome-mediated longevity and modulates the activity of one-carbon metabolism.

Histone H3/H4 chaperone anti-silencing function 1 (ASF1) is a conserved factor mediating nucleosomal assembly and disassembly, playing crucial roles in processes such as replication, transcription, and DNA repair. Nevertheless, its involvement in aging has remained unclear. Here, we utilized the model organism Caenorhabditis elegans to demonstrate that the loss of UNC-85, the homolog of ASF1, leads to a shortened lifespan in a multicellular organism. Furthermore, we show that UNC-85 is required for epigenome-mediated longevity, as knockdown of the histone H3 lysine K4 methyltransferase ash-2 does not extend the lifespan of unc-85 mutants. In this context, we found that the longevity-promoting ash-2 RNA interference enhances UNC-85 activity by increasing its nuclear localization. Finally, our data indicate that the loss of UNC-85 increases the activity of one-carbon metabolism, and that downregulation of the one-carbon metabolism component dao-3/MTHFD2 partially rescues the short lifespan of unc-85 mutants. Together, these findings reveal UNC-85/ASF1 as a modulator of the central metabolic pathway and a factor regulating a pro-longevity response, thus shedding light on a mechanism of how nucleosomal maintenance associates with aging.

Effect of immersion time on bacterial community structure and sulfur metabolism in biofilm on concrete surface in sewer environment

This study focuses on an overlooked but critical issue: the composition and functional expression of microbial communities on the concrete surface in different areas of sewer pipes. Three immersion conditions were applied to simulate the duration of concrete in different areas ofsewers exposed to sewage, including short-term (L1), long-term (L2) and permanent immersion (L3). The properties of concrete under different immersion conditions and the bacterial diversity and functional capabilities in biofilms on the concrete surface were analyzed. Results showed that the L1 group was dominated by Halothiobacillus, whereas Desulfomicrobium was prominent in the L3 group. Significant differences in the predominant functional microbial communities and metabolic functional genes further confirmed the strong impact of immersion time on the pathways of microbial sulfur metabolism and concrete performance in sewer environment. Compared with the L2 and L3 groups, the decreased sewage immersion time resulted in an increase in the abundance and metabolic activity of sulfur-oxidizing bacteria in the L1 group. Hence, greater mass loss and gypsum production of concrete was found in the L1 group. The structural and functional differentiation of bacterial communities on the concrete surface observed in this study contributes to a better understanding of the uneven corrosion in real sewer pipes.

Antagonistic effects of a COX1/2 inhibitor drug in human HepG2 cells exposed to an environmental carcinogen

Understanding interactions between legacy and emerging environmental contaminants has important implications for risk assessment, especially when involving mutagens and carcinogens whose critical effects are chronic and therefore difficult to predict. The current work aimed to investigate potential interactions between benzo[a]pyrene (B[a]P), a carcinogenic polycyclic aromatic hydrocarbon and legacy pollutant, and diclofenac (DFC), a non-steroidal anti-inflammatory drugs and pollutant of emerging concern and how DFC affects B[a]P toxicity. Exposure to binary mixtures of these chemicals resulted in substantially reduced cytotoxicity in human HepG2 cells compared to single-chemical exposures. Significant antagonistic effects were observed in response to high concentrations of B[a]P in combination with DFC at IC50 and ⅕ IC50. While additive effects were found on levels of intracellular reactive oxygen species, antagonistic mixture effects were observed for genotoxicity. B[a]P induced DNA strand breaks, γH2AX activation, and micronuclei formation at ½ IC50 concentrations or lower while DFC only induced low levels of DNA strand breaks. Their mixture caused significantly lower levels of genotoxicity by all three endpoints compared to those expected based on concentration additivity. In addition, antagonistic mixture effects on CYP1 enzyme activity suggested that the observed reduced genotoxicity of B[a]P was due to its reduced metabolic activation as a result of enzymatic inhibition by DFC. Overall, the findings further support the increasing concern that co-exposure to environmental toxicants and their non-additive interactions can be a confounding factor that should not be neglected in environmental and human health risk assessment.

Using rice straw-augmented ecological floating beds to enhance nitrogen removal in carbon-limited wastewater

Agricultural biomass used as solid carbon substrates in ecological floating beds (EFBs) has been proven to be applicable in nitrogen removal for carbon-limited wastewater treatment. However, the subtle interactions among plants, rhizosphere microorganisms, and supplementary carbon sources have not been thoroughly studied. This study combined rice straw mats with different aquatic macrophytes in EFBs to investigate denitrification efficiency in carbon-limited eutrophic waters. Results showed that rice straw significantly enhanced the nitrogen removal efficiency of EFBs, while enriching nitrogen-fixing and denitrifying bacteria (such as Rhizobium, Rubrivivax, and Rhodobacter, etc.). Additionally, during the denitrification process in EFBs, rice straw can release humic acid-like fraction as electron donors to support the metabolic activities of microorganisms, while aquatic macrophytes provide a more diverse range of dissolved organic matters, facilitating a sustainable denitrification process. These findings help to understand the synergistic effect of denitrification processes within wetland ecosystems using agricultural biomass.

Impact of donor pool size on the variability of platelet lysate-derived extracellular vesicles for regenerative medicine

Aim: The objective of the present study was to determine the variability of platelet lysate-derived extracellular vesicles (pEV), in terms of characteristics and functionality through wound healing assays, when isolated either from platelet concentrates (PC, obtained from 5 donors) or from multiple PC (MPC, that is 50 donors). Methods: pEV were isolated under GMP-like conditions in a clean room using Size Exclusion Chromatography (SEC). The differential characteristics between pEV obtained from PC (PC-EV) or MPC (MPC-EV) were evaluated by means of protein concentration, Nanoparticle Tracking Analysis (NTA), Transmission Electron Microscopy (TEM), and flow cytometry using the MACSPlex™ arrays for surface analysis profiling of EV. The functionality of the isolated pEV was determined in cell culture by metabolic activity and LDH activity determination and through a wound healing assay after 24 h treatment. Results: No significant differences were observed in the pEV characteristics evaluated, whether isolated from PC or MPC. As regards functionality, a higher wound closure percentage was obtained in those pEV pools isolated from PC (5 donors). No differences in the coefficient of variation (CV) were found when comparing all the evaluated variables of pEV derived either from PC (5 donors) or from MPC (50 donors). Conclusion: Our findings challenge the necessity of a larger donor pool for pEV isolation, revealing no significant variations in the analyzed variables of MPC-EV and PC-EV. Notably, our results suggest that, unlike platelet concentrates, a high number of donors is not required to reduce the variability of pEV, showing that the pool of only 5 donors can provide a consistent and reliable therapeutic product.

In vitro screening of the impact of dietary prebiotic components, probiotic strains, and their symbiotic combinations on colonic microbiota in children with cystic fibrosis.

Children with Cystic Fibrosis (CF) are more likely to have intestinal dysbiosis due to recurrent antibiotic therapy and the conventional hypercaloric diet administered to them. This study aimed at evaluating the effect of isolated prebiotic components and probiotic strains, and their combinations as potential synbiotics, on the intestinal microbiota of CF children. A static in vitro colonic fermentation model was used by colonizing vials with faecal inoculum, a culture medium, and the substrates to be tested. Post treatment, aliquots were taken to determine ammonium, lactate, and short-chain fatty acids production and to profile the microbiota composition by 16s rRNA sequencing. At genus level, Escherichia-Shigella decreased (15.8%) with the treatment pectin + L. rhamnosus, followed by the beta-glucan + L. salivarius (15.5%). Inversely, the most increase in Bacteroides (44%) was obtained by the treatment with Pectin + L. reuteri. Lactate and acetic acid production was significantly increased with prebiotics and their combinations with L. rhamnosus and L. salivarius. In conclusion, the use of beta-glucan and pectin in combination with probiotic strains from the Lactobacillaceae family suggest potential to modulate dysbiosis and metabolic activity on CF colonic microbiota, encouraging further studies in animal studies or clinical settings to confirm the findings in vivo.

Single-cell transcriptome reveals the heterogeneity of malignant ductal cells and the prognostic value of REG4 and SPINK1 in primary pancreatic ductal adenocarcinoma

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related deaths, with very limited therapeutic options available. This study aims to comprehensively depict the heterogeneity and identify prognostic targets for PDAC with single-cell RNA sequencing (scRNA-seq) analysis. Methods ScRNA-seq analysis was performed on 16 primary PDAC and three adjacent lesions. A series of analytical methods were applied for analysis in cell clustering, gene profiling, lineage trajectory analysis and cell-to-cell interactions. In vitro experiments including colony formation, wound healing and sphere formation assay were performed to assess the role of makers. Results A total of 32,480 cells were clustered into six major populations, among which the ductal cell cluster expressing high copy number variants (CNVs) was defined as malignant cells. Malignant cells were further subtyped into five subgroups which exhibited specific features in immunologic and metabolic activities. Pseudotime trajectory analysis indicated that components of various oncogenic pathways were differentially expressed along tumor progression. Furthermore, intensive substantial crosstalk between ductal cells and stromal cells was identified. Finally, genes (REG4 and SPINK1) screened out of differentially expressed genes (DEGs) were upregulated in PDAC cell lines. Silencing either of them significantly impaired proliferation, invasion, migration and stemness of PDAC cells. Conclusions Our findings offer a valuable resource for deciphering the heterogeneity of malignant ductal cells in PDAC. REG4 and SPINK1 are expected to be promising targets for PDAC therapy.

Induced CD8α identifies human NK cells with enhanced proliferative fitness and modulates NK cell activation.

The surface receptor CD8α is present on 20-80% of human (but not mouse) NK cells, yet its function on NK cells remains poorly understood. CD8α expression on donor NK cells was associated with a lack of therapeutic responses for leukemia patients in prior studies, thus we hypothesized that CD8α may impact critical NK cell functions. Here, we discovered that CD8α- NK cells had improved control of leukemia in xenograft models, compared to CD8α+ NK cells, likely due to an enhanced capacity for proliferation. Unexpectedly, CD8α expression was induced on approximately 30% of previously CD8α- NK cells following IL-15 stimulation. These 'induced' CD8α+ ('iCD8α+') NK cells had the greatest proliferation, responses to IL-15 signaling, and metabolic activity, compared to those that sustained existing CD8α expression ('sustained CD8α+) or those that remained CD8α- ('persistent CD8α-'). These iCD8α+ cells originated from an IL-15Rβ high NK cell population, with CD8α expression dependent on the transcription factor RUNX3. Moreover, CD8A CRISPR/Cas9 deletion resulted in enhanced responses through the activating receptor NKp30, possibly by modulating KIR inhibitory function. Thus, CD8α status identifies human NK cell capacity for IL-15-induced proliferation and metabolism in a time-dependent fashion and exhibits a suppressive effect on NK cell activating receptors.

Single-Cell Data Analysis Reveals Critical Hepatic Cells Subpopulations in the Progression of Non-alcoholic Fatty Liver Disease to Non-Alcoholic Steatohepatitis.

The aim of this study was to reveal the hepatic cell landscape and function in the progression of NAFLD to NASH. Non-alcoholic steatohepatitis (NASH) is the progressive form and turning point of nonalcoholic fatty liver disease (NAFLD), which severely causes irreversible cirrhosis as well as hepatocellular carcinoma. The mechanism underlying the progression of NAFLD to NASH has not been revealed. Unraveling the mechanism of action of NAFLD-NASH is an important goal in improving the survival of patients with liver disease. The aim of this study is to discover heterogeneous hepatic cells during the progression of NAFLD to NASH. Single-nucleus RNA-seq (snRNA-seq) data containing NASH in NAFLD samples were obtained from the Gene Expression Omnibus (GEO) database. Cell types in liver tissues from NASH and NAFLD were identified after dimensionality reduction analysis, cluster analysis, and cell annotation. The cell pathways in which differences existed were identified by analyzing metabolic pathways in Hepatic cells. We also identified cell subpopulations in Hepatic cells. The developmental trajectories of Hepatic cells were characterized by pseudotime trajectory analysis. Single-cell regulatory network inference and clustering analysis identified key transcription factors and gene regulatory networks in Hepatic cells. Moreover, cell communication analysis determined the potential interactions between Hepatic cells and immune cells, and heapatic stellate cells. Seven cell types were identified in NAFLD and NASH. The proportion of Hepatic cells was lower in NASH and showed greater energy metabolism and glucose metabolism activity. Hepatic cells exhibited heterogeneity, showing two cell subpopulations, Hepatic cells 1 and Hepatic cells 2. Dysregulation of lipid metabolism in Hepatic Cell 2 resulted in lipid accumulation in the liver, which might be involved in the progression of NAFLD. Four key transcription factors, BHLHE40, NFEL2L, RUNX1, and INF4A, were primarily found in Hepatic cells 2. The transcription factors within the hepatic cells 2 subpopulation mainly regulated genes related to lipid metabolism, energy metabolism, and inflammatory response. The cell communication analysis showed that hepatocyte interactions with immune cells were associated with inflammatory responses, while interactions with hepatic astrocytes were associated with liver injury and hepatocyte fibrosis. The hepatic cells 2 might promote the progression of NAFLD to NASH by regulating metabolic activity, which might contribute to liver injury through inflammation.

Acibenzolar-S-methyl promotes wound healing of harvested sweet potatoes (Ipomoea batatas) by regulation of reactive oxygen species metabolism and phenylpropanoid pathway.

Rapid wound healing is crucial in protecting sweet potatoes (Ipomoea batatas ) against infection, water loss and quality deterioration during storage. The current study investigated how acibenzolar-S-methyl (ASM) treatment influenced wound healing in harvested sweet potatoes by investigating the underlying mechanism. It was found that ASM treatment of wounded sweet potatoes induced a significant accumulation of lignin at the wound sites, which effectively suppressed weight loss. After 4days of healing, the lignin content of ASM-treated sweet potatoes was 41.8% higher than that of untreated ones, and the weight loss rate was 20.4% lower. Moreover, ASM treatment increased the ability of sweet potatoes to defend against wounding stress through enhancing processes such as increased production of reactive oxygen species (ROS), activation of enzymes involved in the ROS metabolism (peroxidase, superoxide dismutase and catalase) and phenylpropanoid pathway (phenylalanine ammonia lyase, cinnamate-4-hydroxylase, 4-coumarate-CoA ligase and cinnamyl alcohol dehydrogenase), and intensive synthesis of phenolics and flavonoids. These results suggest that treating harvested sweet potatoes with ASM promotes wound healing through the activation of the ROS metabolism and phenylpropanoid pathway.

Deciphering of the morpho-physiological traits of two native grasses from Argentina with contrasting drought resistance strategies

Context Semiarid environments, such as the Patagonian shrublands, are characterised by having shrubby patches surrounded by grasses with different ecophysiological strategies to tolerate long dry periods. Aims We hypothesised that coexisting grasses of the Patagonian rangeland, already classified as drought-escaping or drought-tolerant, have different traits according to the season and the annual rainfall events. Methods Two dominant native grasses were selected: Pappostipa speciosa (evergreen) and Poa ligularis (deciduous). Samples were collected in the four seasons for the term of 1 year. Rainfall events and soil water content of each season were determined. Spring was the wettest season and autumn the driest. Physiological (relative water content, pigments, hormones), biochemical (polyphenols, antioxidant activity) and morphological traits were measured in the four seasons. Key results P. speciosa was characterised by keeping evergreen leaves with high production of polyphenols as secondary metabolites with high antioxidant capacity during the dry autumn and winter seasons. P. ligularis was characterised by high contents of gibberellin (GA1), auxin (IAA), total phenols, total flavonoids and tartaric acid esters, and high antioxidant capacity in roots during the autumn dry season. In addition, P. ligularis leaves had higher content of carotenoids and polyphenols than P. speciosa during the summer dry season. Conclusions The major adaptive strategy to tolerate dry periods is the high activity of the secondary metabolism, mainly in leaves in P. speciosa (a drought-tolerant grass) and in roots in P. ligularis (a drought-escaping grass). Implications Rainfall variations during a year can affect the phenological growth stages and the metabolism of two native grasses from Argentina characterised by different drought resistance mechanisms.

LncRNA TUG1 mediates microglial inflammatory activation by regulating glucose metabolic reprogramming

Microglia are natural immune cells in the central nervous system, and the activation of microglia is accompanied by a reprogramming of glucose metabolism. In our study, we investigated the role of long non-coding RNA taurine-upregulated gene 1 (TUG1) in regulating microglial glucose metabolism reprogramming and activation. BV2 cells were treated with Lipopolysaccharides (LPS)/Interferon-γ (IFN-γ) to establish a microglial activation model. The glycolysis inhibitor 2-Deoxy-D-glucose (2-DG) was used as a control. The expression levels of TUG1 mRNA and proinflammatory cytokines such as Interleukin-1β (IL-1β), Interleukin -6, and Tumor Necrosis Factor-α mRNA and anti-inflammatory cytokines such as IL-4, Arginase 1(Arg1), CD206, and Ym1 were detected by RT-qPCR. TUG1 was silenced using TUG1 siRNA and knocked out using CRISPR/Cas9. The mRNA and protein expression levels of key enzymes involved in glucose metabolism, such as Hexokinase2, Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Lactate dehydrogenase, Glucose 6 phosphate dehydrogenase, and Pyruvate dehydrogenase (PDH), were determined by RT-qPCR and Western blotting. The glycolytic rate of microglial cells was measured using Seahorse. Differential metabolites were determined by metabolomics, and pathway enrichment was performed using these differential metabolites. Our findings revealed that the expression of TUG1 was elevated in proinflammatory-activated microglia and positively correlated with the levels of inflammatory factors. The expression of anti-inflammatory cytokines such as IL-4, Arg1, CD206, and Ym1 were decreased when induced with LPS/IFN-γ. However, this decrease was reversed by the treatment with 2-DG. Silencing of GAPDH led to an increase in the expression of TUG1 and inflammatory factors. TUG1 knockout (TUG1KO) inhibited the expression of glycolytic key enzymes and promoted the expression of oxidative phosphorylation key enzymes, shifting the metabolic profile of activated microglia from glycolysis to oxidative phosphorylation. Additionally, TUG1KO reduced the accumulation of metabolites, facilitating the restoration of the tricarboxylic acid cycle and enhancing oxidative phosphorylation in microglia. Furthermore, the downregulation of TUG1 was found to reduce the expression of both proinflammatory and anti-inflammatory cytokines under normal conditions. Interestingly, when induced with LPS/IFN-γ, TUG1 downregulation showed a potentially beneficial effect on microglia in terms of inflammation. Downregulation of TUG1 expression inhibits glycolysis and facilitates the shift of microglial glucose metabolism from glycolysis to oxidative phosphorylation, promoting their transformation towards an anti-inflammatory phenotype and exerting anti-inflammatory effects in BV2.

Antiviral Activity of Physta®, Standardised Water Extract of Eurycoma longifolia against SARS-CoV-2: An in vitro Study

Eurycoma longifolia Jack (Simaroubaceae) root extract is known to exhibit antiinflammatory, antiviral and immunomodulatory activities. Therefore, E. longifolia, through a multimodal approach could potentially be used in COVID-19 management. However, to date there has been no investigation into the antiviral activity of E. longifolia root extract against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The objective of the study is to investigate the antiviral activity of Physta® (a standardised water extract of E. longifolia) against SARS-CoV-2. A mitochondrial metabolic activity assay using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) was used to determine the cytotoxicity of the Physta® extract in Vero cells, with concentrations ranging from 1.95 µg/mL to 1,000 µg/mL. Physta® was tested for antiviral activity at six different concentrations, ranging from 3.12 µg/mL to 50 µg/mL. The half maximal cytotoxic concentration (CC50) value of Physta® against Vero cells was estimated at 1,117 µg/mL and the maximum non-toxic dose (MNTD) value was estimated at 60 µg/mL. Physta® inhibited SARS-CoV-2 replication in a dose-dependent manner, and the half maximal inhibition concentration (IC50) was estimated to be 36.3 µg/mL. This study has demonstrated the antiviral activity of Physta® against SARS-CoV-2. Future evaluations in animal and clinical settings should be conducted to determine whether Physta® can be used alone or in combination with other antiviral agents to alleviate COVID-19.

Seasonal shift in trophic status induced by bacterial metabolic activity in tropical mangrove-dominated estuaries of Southwest India

Seasonal shift in trophic status induced by bacterial metabolic activity in tropical mangrove-dominated estuaries of Southwest India

The Metabolic and Antioxidant Activity Profiles of Aged Greek Grape Marc Spirits

The Metabolic and Antioxidant Activity Profiles of Aged Greek Grape Marc Spirits

Paraná basin basalt powder: A multinutrient soil amendment for enhancing soil chemistry and microbiology

This study evaluated the effects of Paraná Basin basalt powder, a mining byproduct from southern Brazil, on the macro- and micronutrient content of two soil types, Oxisol (OX) and Typic Quartzipsamment (TQ), as well as the metabolic activity of soil microorganisms. Basalt powder doses were determined based on CaO levels required to correct Ca2+ levels in each soil, ranging from 0 to 4 times the recommended amount. Soil samples were collected for analysis after 60 and 170 days of incubation to assess soil attributes. Additionally, a laboratory study examined soil basal respiration (SBR) after 168 days of greenhouse incubation. The results revealed that higher doses of basalt powder application led to increased pH, P, K+, Ca2+, Mg2+, Cu, B, and Si levels in OX, while decreasing Al3+ levels in the same soil. In TQ soils, the effects were more limited, showing specific increases in pH, P, S–SO42-, and Si levels. Moreover, there was a 21% increase in SBR in OX with higher basalt rates. These findings suggest that basalt powder has the potential to serve as an environmentally friendly solution for soil fertilization, positively impacting its chemical and biological properties.

Coexistence of cardiac sarcoidosis and genetic cardiomyopathies: a conundrum

Abstract Introduction Cardiac sarcoidosis (CS) is a chronic inflammatory disease characterized histologically by the formation of non-caseating granuloma in the myocardium, however, causes remain largely unknown. Genetic arrhythmogenic cardiomyopathy (ACM) is an important differential diagnosis of CS. Until now, few data are available about the coexistence of CS in a patient with genetic ACM harboring a desmoglein-2 (DSG2) variant. Purpose We report a case series of patients who demonstrate coexistence of histologically proven CS and genetic ACM. Methods This is a multicentric study, which included patients from four high-volume cardiology referral centres for heart failure and ACM in Switzerland, Italy, and Austria. Patients with both a biopsy-proven diagnosis of sarcoidosis with cardiac involvement (according to the 2014 HRS criteria) also harboring a pathogenic/likely pathogenic (P/LP) variant for cardiomyopathy-associated genes were 1:1 matched for age, gender and genetic variant with patients with genetic ACM without CS (Gen-only). Clinical and imaging data (echocardiography (TTE), cardiac magnetic resonance (CMR) and positron-emission tomography (18FFDG-PET/CT) were collected. Results Each group included 5 patients (Gen+CS: age 48 ± 11 years, Gen only: age 52 ± 13.7 years, n=3 (60%) female in both groups). For each group, the following genes with P/LP variants were found: PKP2: n=2 (40%), DSG2: n=1 (20%), DSP: n=1 (20%), TTN: n=1 (20%). In patients with Gen+CS, atrio-ventricular block (AVB) I° (80% vs 20%, p=0.05) and paroxysmal atrial fibrillation (80% vs 0%, p=0.004) were more frequent, and median NT-proBNP levels (1346ng/l, IQR:103-4276 vs. 214ng/l, IQR:131-326, p=0.046), as well as high-sensitive C-reactive protein levels were higher (3.1g/dl, IQR:1.1-24.2 vs. 0.7g/dl, IQR:0.3-0.95, p=0.016). On imaging, Gen+CS patients were more likely to have septal involvement (60% vs 0%, p=0.021), as highlighted by positive late-gadolinium enhancement on CMR, metabolic activity on PET, or focal wall motion anomalies on TTE. Conclusions CS and genetic ACM can coexist. Hence, detection of a P/LP genetic variant associated with ACM should not lead to exclusion of CS, which more frequently presents with AVB, septal involvement, heart failure, and metabolic activity on imaging. On the contrary, CS can be associated with genetic variants in cardiomyopathy-associated genes.FDG-PET/CT

A Cellular Model of Amyotrophic Lateral Sclerosis to Study the Therapeutic Effects of Extracellular Vesicles from Adipose Mesenchymal Stem Cells on Microglial Activation

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of upper and lower motor neurons (MNs) in the brain and spinal cord, leading to progressive paralysis and death. Increasing evidence indicates that neuroinflammation plays an important role in ALS’s pathogenesis and disease progression. Neuroinflammatory responses, primarily driven by activated microglia and astrocytes, and followed by infiltrating peripheral immune cells, contribute to exacerbate/accelerate MN death. In particular, the role of the microglia in ALS remains unclear, partly due to the lack of experimental models that can fully recapitulate the complexity of ALS’s pathology. In this study, we developed and characterized a microglial cell line, SIM-A9-expressing human mutant protein Cu+/Zn+ superoxide dismutase_1 (SIM-A9hSOD1(G93A)), as a suitable model in vitro mimicking the microglia activity in ALS. The expression of hSOD1(G93A) in SIM-A9 cells induced a change in their metabolic activity, causing polarization into a pro-inflammatory phenotype and enhancing reactive oxygen species production, which is known to activate cell death processes and apoptosis. Afterward, we used our microglial model as an experimental set-up to investigate the therapeutic action of extracellular vesicles isolated from adipose mesenchymal stem cells (ASC-EVs). ASC-EVs represent a promising therapeutic treatment for ALS due to their neuroprotective and immunomodulatory properties. Here, we demonstrated that treatment with ASC-EVs is able to modulate activated ALS microglia, reducing their metabolic activity and polarizing their phenotype toward an anti-inflammatory one through a mechanism of reduction of reactive oxygen species.

Potassium Nutrition Induced Salinity Mitigation in Mungbean [Vigna radiata (L.) Wilczek] by Altering Biomass and Physio-Biochemical Processes

The present investigation was conducted to explore the role of potassium nutrition in improving biomass and physio-chemical alterations to reduce the adverse effects of salinity in mungbean. A sand-culture experiment was carried out under different salinity levels (0, 50, and 100 mM NaCl) with two levels of potassium (0 and 50 mM K2SO4) and two mungbean cultivars (NM-92 and Ramzan), and the alterations in mungbean biomass and metabolic activities were investigated. The results suggested that salinity significantly reduced the biomass, nitrate reductase activity (NRA), nitrite reductase activity (NiRA), total soluble proteins, chlorophyll a, chlorophyll b, total chlorophyll, nitrogen, potassium, calcium, magnesium, and phosphorous contents in both mungbean cultivars in comparison to the control. However, K2SO4 at 50 mM significantly improved all the parameters in both mungbean cultivars except for the sodium content. A significant increase in the total free amino acids, carotenoids, and sodium content in both mungbean cultivars was observed due to salt stress. Moreover, principal component analysis and heatmaps were developed individually for both mungbean cultivars to assess the variability and correlation among the studied attributes under all applied treatments. Under saline conditions, the mungbean ‘Ramzan’ showed more marked reductions in almost all the growth parameters as compared to ‘NM-92’. The results suggest that the application of K2SO4 ameliorates the adverse effects of salinity by regulating osmolyte production, NRA, and NiRA, thus promoting plant growth and productivity.

18F]FDG PET and CT findings at therapy completion of pulmonary tuberculosis: comparison between HIV-positive and HIV-negative patients and impact on treatment response assessment

Abstract Background [18F]FDG-PET/CT is a sensitive non-invasive tool for assessing treatment response in patients with pulmonary tuberculosis. The data on the performance of [18F]FDG-PET/CT for response assessment among patients infected with the human immunodeficiency virus (HIV) is limited. Here, we investigated the differences between PET and CT lung findings on end-of-treatment [18F]FDG-PET/CT among HIV-positive versus HIV-negative patients who completed anti-tuberculous therapy for pulmonary tuberculosis. Methods Patients who completed anti-tuberculous therapy for pulmonary tuberculosis and declared cured based on negative clinical and laboratory assessments for active pulmonary tuberculosis were prospectively recruited to undergo [18F]FDG-PET/CT. Patients were classified as having residual metabolic activity if PET metabolic activity was demonstrated in the lung parenchyma or complete metabolic response if there was no abnormally increased [18F]FDG avidity in the lungs and compared the CT features. We identified 10 CT lung changes, five were associated with active pulmonary tuberculosis (nodules, micronodules in tree-in-bud pattern, consolidation, pleural effusion, and [18F]FDG-avid mediastinal/hilar lymphadenopathy) and the rest were associated with inactive sequelae of prior pulmonary tuberculosis (cysts, cavities, fibrosis, bronchiectasis, and calcifications and compared their incidence between HIV-positive and HIV-negative patients. Results Seventy-five patients were included with a mean age of 36.09 ± 10.49 years. There were fifty HIV-positive patients, all of whom were on antiretroviral therapy and with a median CD4 + T-cell of 255 cells/µL (IQR: 147–488). Fifteen HIV-positive patients had detectable HIV viremia with a median viral load of 12,497 copies/mL (IQR: 158–38,841). There was a significant difference in the incidence of residual metabolic activity and complete metabolic response between HIV-positive and HIV-negative patients. (P = 0.003) HIV-positive patients were more likely to have [18F]FDG-avid lymphadenopathy and HIV-negative patients had a higher incidence of cystic lung changes. The pattern of CT lung changes was otherwise not different between HIV-positive and HIV-negative patients. (P > 0.05) Conclusions The incidence of residual metabolic activity and complete metabolic response on end-of-treatment [18F]F-FDG-PET/CT are similar between HIV-positive and HIV-negative patients. The incidence of [18F]FDG-avid mediastinal/hilar lymphadenopathy is more prevalent among HIV-positive patients. The pattern of lung changes was largely similar between HIV-positive and HIV-negative patients, indicating that the presence of HIV coinfection may not influence the interpretation of end-of-treatment [18F]F-FDG-PET/CT obtained for pulmonary tuberculosis treatment response assessment.