Detection of sFas, sCD137, and IL-27 Cytokines as Potential Biomarkers for Hepatocellular Carcinoma Diagnosis.

Purpose: Hepatocellular carcinoma (HCC), a prevalent type of liver cancer, is mainly diagnosed in the advanced stage, leading to a high mortality rate. Recent advances have identified peripheral cytokines as a potential tool to predict disease outcomes and inform therapeutic decisions. Hence, in this study, we aim to build a predictive model for HCC based on serum levels of different cytokines. Patients and Methods: We used immunoassay to quantify the concentrations of IL-27, MIP-1ß, Perforin, sCD137, sFas, and TNF-α in the serum of 38 HCC patients and 15 healthy controls. Logistic regression was then used to construct classification models detecting HCC based on these cytokines. A nomogram of the best-performing model was generated to visualize HCC prediction. Results: sFas and MIP-1ß were found to be significantly higher in HCC patients compared to controls. Predictive models based on cytokine levels combining sFas, sCD137, and IL-27 performed the best in distinguishing HCC patients from healthy controls. This model has a bias-corrected area under the receiver operating characteristic (ROC) curve (AUC) of 0.948, a sensitivity of 92.11%, a specificity of 93.33%, and an accuracy of 0.925. Conclusion: Our findings suggest that serum cytokines have the potential to be utilized in HCC screening to improve detection rates.

Cytokine-primed umbilical cord mesenchymal stem cells enhanced therapeutic effects of extracellular vesicles on osteoarthritic chondrocytes.

In recent years, extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) have emerged as a potential cell-free therapy against osteoarthritis (OA). Thus, we investigated the therapeutic effects of EVs released by cytokine-primed umbilical cord-derived MSCs (UCMSCs) on osteoarthritic chondrocyte physiology. Priming UCMSCs individually with transforming growth factor beta (TGFß), interferon alpha (IFNα), or tumor necrosis factor alpha (TNFα) significantly reduced the sorting of miR-181b-3p but not miR-320a-3p; two negative regulators of chondrocyte regeneration, into EVs. However, the EV treatment did not show any significant effect on chondrocyte proliferation. Meanwhile, EVs from both non-priming and cytokine-primed UCMSCs induced migration at later time points of measurement. Moreover, TGFß-primed UCMSCs secreted EVs that could upregulate the expression of chondrogenesis markers (COL2 and ACAN) and downregulate fibrotic markers (COL1 and RUNX2) in chondrocytes. Hence, priming UCMSCs with cytokines can deliver selective therapeutic effects of EV treatment in OA and chondrocyte-related disorders.

Polyphasic evaluation and cytotoxic investigation of isolated cyanobacteria with an emphasis on potent activities of a Scytonema strain.

Cyanobacteria are phototrophic organisms widely found in most types of natural habitats in the tropical regions of the world. In this study, we isolated and identified cyanobacterial strains from paddy soil in Hanoi (Vietnam) and investigated their cytotoxic activities. Five isolated cyanobacterial strains showed distinctive profiles of gene sequences (rRNA 16S and rbcL), phylogenetic placements, and morphological characteristics. Based on the polyphasic evaluation, they were classified as Scytonema bilaspurense NK13, Hapalosiphon welwitschii MD2411, Aulosira sp. XN1103, Desikacharya sp. NS2000, and Desmonostoc sp. NK1813. The cytotoxic screening revealed that the extract of strain Scytonema bilaspurense NK13 exhibited potent cytotoxic activities against four human cell lines of HeLa cells, OVCAR-8 cells, HaCaT cells, and HEK-293T cells, with IC50 values of 3.8, 34.2, 21.6, and 0.6 µg/mL, respectively. This is the first time a well-classified Scytonema strain from tropical habitat in Southeast Asia has been recognized as a potential producer of cytotoxic compounds.

Effects of Extracellular Vesicles Secreted by TGFß-Stimulated Umbilical Cord Mesenchymal Stem Cells on Skin Fibroblasts by Promoting Fibroblast Migration and ECM Protein Production.

Umbilical cord-derived mesenchymal stem cells (UCMSCs) have been illustrated for their roles in immunological modulation and tissue regeneration through the secretome. Additionally, culture conditions can trigger the secretion of extracellular vesicles (EVs) into extracellular environments with significant bioactivities. This study aims to investigate the roles of three EV sub-populations released by UCMSCs primed with transforming growth factor ß (TGFß) and their capacity to alter dermal fibroblast functions for skin aging. Results show that three EV sub-populations, including apoptotic bodies (ABs), microvesicles (MVs), and exosomes (EXs), were separated from conditioned media. These three EVs carried growth factors, such as FGF-2, HGF, and VEGF-A, and did not express noticeable effects on fibroblast proliferation and migration. Only EX from TGFß-stimulated UCMSCs exhibited a better capacity to promote fibroblasts migrating to close scratched wounds than EX from UCMSCs cultured in the normal condition from 24 h to 52 h. Additionally, mRNA levels of ECM genes (COL I, COL III, Elastin, HAS II, and HAS III) were detected with lower levels in fibroblasts treated with EVs from normal UCMSCs or TGFß-stimulated UCMSCs compared to EV-depleted condition. On the contrary, the protein levels of total collagen and elastin released by fibroblasts were greater in the cell groups treated with EVs compared to EV-depleted conditions; particularly elastin associated with TGFß-stimulated UCMSCs. These data indicate the potential roles of EVs from UCMSCs in protecting skin from aging by promoting ECM protein production.

Mesenchymal Stem Cell-Derived Extracellular Vesicles for Osteoarthritis Treatment: Extracellular Matrix Protection, Chondrocyte and Osteocyte Physiology, Pain and Inflammation Management.

Osteoarthritis (OA) is a common degenerative disease that can lead to persistent pain and motion restriction. In the last decade, stem cells, particularly mesenchymal stem cells (MSCs), have been explored as a potential alternative OA therapy due to their regenerative capacity. Furthermore, it has been shown that trophic factors enveloped in extracellular vesicles (EVs), including exosomes, are a crucial aspect of MSC-based treatment for OA. Evidently, EVs derived from different MSC sources might rescue the OA phenotype by targeting many biological processes associated with cartilage extracellular matrix (ECM) degradation and exerting protective effects on different joint cell types. Despite this advancement, different studies employing EV treatment for OA have revealed reverse outcomes depending on the EV cargo, cell source, and pathological condition. Hence, in this review, we aim to summarize and discuss the possible effects of MSC-derived EVs based on recent findings at different stages of OA development, including effects on cartilage ECM, chondrocyte biology, osteocytes and bone homeostasis, inflammation, and pain management. Additionally, we discuss further strategies and technical advances for manipulating EVs to specifically target OA to bring the therapy closer to clinical use.

Environmentally relevant fungicide levels modify fungal community composition and interactions but not functioning.

Aquatic hyphomycetes (AHs), a group of saprotrophic fungi adapted to submerged leaf litter, play key functional roles in stream ecosystems as decomposers and food source for higher trophic levels. Fungicides, controlling fungal pathogens, target evolutionary conserved molecular processes in fungi and contaminate streams via their use in agricultural and urban landscapes. Thus fungicides pose a risk to AHs and the functions they provide. To investigate the impacts of fungicide exposure on the composition and functioning of AH communities, we exposed four AH species in monocultures and mixed cultures to increasing fungicide concentrations (0, 5, 50, 500, and 2500 µg/L). We assessed the biomass of each species via quantitative real-time PCR. Moreover, leaf decomposition was investigated. In monocultures, none of the species was affected at environmentally relevant fungicide levels (5 and 50 µg/L). The two most tolerant species were able to colonize and decompose leaves even at very high fungicide levels (≥500 µg/L), although less efficiently. In mixed cultures, changes in leaf decomposition reflected the response pattern of the species most tolerant in monocultures. Accordingly, the decomposition process may be safeguarded by tolerant species in combination with functional redundancy. In all fungicide treatments, however, sensitive species were displaced and interactions between fungi changed from complementarity to competition. As AH community composition determines leaves' nutritional quality for consumers, the data suggest that fungicide exposures rather induce bottom-up effects in food webs than impairments in leaf decomposition.

Serum adipocytokines are related to lipodystrophy and metabolic disorders in HIV-infected men under antiretroviral therapy.

OBJECTIVES: Adipocytokines, secreted by adipose tissue, may regulate fat metabolism, lipid and glucose homeostasis and insulin sensitivity. We analysed the relations between circulating concentrations of adiponectin, leptin, interleukin-6, tumor necrosis factor alpha and its soluble receptors sTNFR1 and R2, lipodystrophic phenotypes and metabolic alterations in patients under highly active antiretroviral therapy (HAART). METHODS: We studied 131 consecutive HIV-infected males under protease inhibitor (PI)-based HAART, with body mass index < 27 kg/m2 and C-reactive protein (CRP) < 10 mg/l. Patients were classified in four groups according to clinical examination: no lipodystrophy (NL), lipohypertrophy (LH), lipoatrophy (LA) and mixed lipodystrophy (ML). In addition to adipocytokines, we measured plasma fasting levels of triglycerides, cholesterol, cardiovascular risk markers (high-sensitivity CRP and apolipoproteins B/A1 ratio), fasted and 2 h post-glucose loading glycemia and insulinemia and calculated the quantitative insulin sensitivity check index. RESULTS: The patients were HIV-infected and PI-treated for a mean of 8.2 and 1.6 years respectively; 74% presented lipodystrophy, 38% altered glucose tolerance and 42% hypertriglyceridemia. Insulin sensitivity correlated positively with adiponectin and negatively with leptin and interleukin-6. Adiponectin, but not leptin, negatively correlated with all metabolic parameters. Insulin resistance, metabolic defects and cardiovascular risk markers were strongly negatively correlated with the adiponectin/leptin ratio (A/L), and positively with sTNFR1. LA patients had a longer duration of infection but ML patients presented the most severe metabolic alterations, insulin resistance and A/L decrease. CONCLUSIONS: These results suggest that adiponectin and the TNFalpha system are related to lipodystrophy, insulin resistance and metabolic alterations in patients under PI-based HAART. A/L and sTNFR1 could predict insulin sensitivity and potential cardiovascular risk in these patients.

Relationship between levels of indinavir in hair and virologic response to highly active antiretroviral therapy.

BACKGROUND: Suboptimal levels of antiretroviral drugs result in virologic failure in HIV-infected patients treated with highly active antiretroviral therapy (HAART). OBJECTIVE: To assess the relationship between levels of indinavir in hair and virologic outcome. DESIGN: Cross-sectional study. SETTING: 7 AIDS clinics in France. PATIENTS: 89 HIV-infected patients who received HAART that included indinavir. MEASUREMENTS: Patients were classified as responders or nonresponders on the basis of viremia at the time of hair collection. In nonresponders, levels of indinavir in hair and resistance mutations in the protease gene were assessed at baseline and at the time of indinavir measurement. RESULTS: Mean indinavir levels (+/-SD) were significantly higher in the 65 responders than in the 24 nonresponders (24.4 +/- 16 microg/g vs. 12.9 +/- 8.6 microg/g) (P < 0.001). Nonresponders with intermediate levels of indinavir in hair had more mutations in the protease gene than did nonresponders with low levels of indinavir in hair. CONCLUSION: Indinavir levels in hair are associated with virologic outcome in patients receiving HAART.