Cell. Physiol. Biochem. [JOURNAL]
Sun
200 papers
Environmental Cues Facilitate Maturation and Patterning of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
Coca E, Cho S, Kauffman C … +3 more , Cook AD, Tristani-Firouzi M, Torres NS
Cell Physiol Biochem · 2024 Oct · PMID 39370954 · Full text
BACKGROUND/AIMS: Advances in induced pluripotent stem cell (iPSC) technology allow for reprogramming of adult somatic cells into stem cells from which patient- and disease-specific cardiomyocytes (CMs) can be derived. Ye...
BACKGROUND/AIMS: Advances in induced pluripotent stem cell (iPSC) technology allow for reprogramming of adult somatic cells into stem cells from which patient- and disease-specific cardiomyocytes (CMs) can be derived. Yet, the potential of iPSC technology to revolutionize cardiovascular research is limited, in part, by the embryonic nature of these cells. Here, we test the hypothesis that decellularized porcine left ventricular extracellular cardiac matrix (ECM) provides environmental cues that promote transcriptional maturation and patterning of iPSC-CMs in culture. METHODS: Cardiac progenitor cells were plated on ECM or standard tissue plates (2D monolayer) for 30 days, after which CM orientation and single cell transcriptomics were evaluated using confocal imaging and singe cell RNA-sequencing, respectively. RESULTS: Cardiac progenitors differentiated on left ventricular ECM formed longitudinal fibers that differed quantitatively from progenitors differentiated in standard 2D conditions. Unsupervised clustering of single cell transcriptomics identified a CM cluster expressing a higher level of genes related to CM maturation. CMs differentiated on ECM were overrepresented in this cluster, indicating a bias toward CM maturation, compared to cells differentiated in standard 2D monolayer conditions. CONCLUSION: Our data suggest that environmental cues related to the left ventricular ECM may promote differentiation to a more mature CM state compared to cells differentiated on a standard 2D monolayer, while facilitating organization into longitudinal micro-fibers. Our study highlights the utility of ECM as a differentiation substrate to promote CM maturation and fiber orientation .
Change in Nfkb/Nrf2/Bax Levels by High Monomeric Polyphenols Berries Extract (HMPBE) in Acute and Chronic Secondary Brain Damage.
Modafferi S, Molinari F, Interdonato L … +13 more , Fusco R, Impellizzeri D, Siracusa R, D'Amico R, Abdelhameed AS, Wenzel U, Jacobs U, Fritsch T, Osakabe N, Cuzzocrea S, Calabrese V, Paola RD, Cordaro M
Cell Physiol Biochem · 2024 Oct · PMID 39370950 · Publisher ↗
BACKGROUND/AIMS: High Monomeric Polyphenols Berries Extract (HMPBE) is a formula highly rich in polyphenols clinically proven to enhance learning and memory. It is currently used to enhances cognitive performance includi...
BACKGROUND/AIMS: High Monomeric Polyphenols Berries Extract (HMPBE) is a formula highly rich in polyphenols clinically proven to enhance learning and memory. It is currently used to enhances cognitive performance including accuracy, working memory and concentration. METHODS: Here, we investigated for the first time the beneficial effects of HMPBE in a mouse model of acute and chronic traumatic brain injury (TBI). RESULTS: HMPBE, at the dose of 15 mg/kg was able to reduce histological alteration as well as inflammation and lipid peroxidation. HMPBE ameliorate TBI by improving Nrf-2 pathway, reducing Nf-kb nuclear translocation and apoptosis, and ameliorating behavioral alteration such as anxiety and depression. Moreover, in the chronic model of TBI, HMPBE administration restored the decline of Tyrosine Hydroxylase (TH) and dopamine transporter (DAT) and the accumulation of a-synuclein into the midbrain region. This finding correlates the beneficial effect of HMPBE administration with the onset of parkinsonism related to traumatic brain damage. CONCLUSION: The data may open a window for developing new support strategies to limit the neuroinflammation event of acute and chronic TBI.
Peroxyredoxin 6 Protects RIN-M5F Pancreatic Beta Cells Against Streptozotocin-Induced Senescence.
Novoselova EG, Glushkova OV, Khrenov MO … +4 more , Lunin SM, Novoselova TV, Sharapov MG, Parfenyuk SB
Cell Physiol Biochem · 2024 Sep · PMID 39348523 · Publisher ↗
BACKGROUND/AIMS: There are evidences that a decrease in the functional activity of pancreatic β-cells under type 2 diabetes conditions may be associated with their senescence, therefore, senotherapy may be a prospective...
BACKGROUND/AIMS: There are evidences that a decrease in the functional activity of pancreatic β-cells under type 2 diabetes conditions may be associated with their senescence, therefore, senotherapy may be a prospective strategy for the diabetes treatment. METHODS: The senotherapeutic potential of peroxiredoxin 6 (PRDX6) was studied in RIN-m5F pancreatic β-cells with streptozotocin-induced senescence by measuring markers, associated with senescence. RESULTS: Exposure to streptozotocin (STZ) resulted in the senescence of the β-cells. The addition of PRDX6 to the culture medium of RIN-m5F β-cells before treatment with STZ decreased the levels of the following senescence markers: the percentage of SA-β-Gal-positive cells, the phosphorylation of histone H2AX and p21 proteins, and the secretion of the proinflammatory cytokine IL-6 but not the anti-inflammatory cytokine IL-10. These effects were accompanied by a decrease in the production of reactive oxygen species (ROS) and the restoration of impaired NF-κB activation. In addition, PRDX6 altered the production of the heat shock protein HSP90: the production of the constitutive form of HSP90-beta decreased, while the level of inducible HSP90-alpha increased. CONCLUSION: PRDX6 prevented the senescence of RIN-m5F cells in response to the DNA damage-inducing agent streptozotocin, indicating a potential protective role of PRDX6 in type 2 diabetes mellitus.
GNAS, not a Highly Mutated Gene, Has Prognostic Significance and Carcinogenic Effects in Osteosarcoma.
Qi J, Huang Y, Bian Y
Cell Physiol Biochem · 2024 Sep · PMID 39305132 · Publisher ↗
BACKGROUND/AIMS: Osteosarcoma is a prevalent and aggressive primary malignant bone tumor affecting children and adolescents. Despite advancements in sequencing technologies, there remains a lack of reliable prognostic bi...
BACKGROUND/AIMS: Osteosarcoma is a prevalent and aggressive primary malignant bone tumor affecting children and adolescents. Despite advancements in sequencing technologies, there remains a lack of reliable prognostic biomarkers and effective targeted therapies for osteosarcoma. This study focuses on identifying key prognostic genes, particularly the role of GNAS, in osteosarcoma progression. METHODS: Bioinformatics analyses were performed on osteosarcoma datasets from the Gene Expression Omnibus (GEO). Differential gene expression analysis, weighted correlation network analysis (WGCNA), and survival analysis identified potential prognostic hub genes. The expression and function of these genes were validated through immunohistochemistry and animal experiments. Specifically, the role of GNAS was investigated through siRNA-mediated knockdown in osteosarcoma cell lines and nude mice models. RESULTS: Five hub genes (PROP1, GNAS, CYP4F2, LHX3, CNGB1) were identified as significantly related to osteosarcoma prognosis. Among these, GNAS was found to be highly expressed in osteosarcoma tissues compared to normal tissues. Immunohistochemical analysis confirmed the elevated expression of GNAS in osteosarcoma samples. GNAS mutation analysis revealed a low mutation rate in osteosarcoma, suggesting its oncogenic role is independent of mutational status. Animal experiments demonstrated that knocking down GNAS significantly inhibited tumor growth and induced apoptosis in osteosarcoma cells. CONCLUSION: GNAS is highly expressed in osteosarcoma and associated with poor prognosis, acting as an oncogene in osteosarcoma progression. Targeting GNAS could be a potential therapeutic strategy for osteosarcoma. Further studies on GNAS-related signaling pathways may provide deeper insights into the molecular mechanisms driving osteosarcoma malignancy.
Analysis of Erythrocyte Parameters in Multiple and Long-Term Blood Donors from Northern Pomerania (Poland).
Kurhaluk N, Gradziuk M, Kamiński P … +1 more , Tkaczenko H
Cell Physiol Biochem · 2024 Sep · PMID 39305131 · Publisher ↗
BACKGROUND/AIMS: Assessment of the levels of vital blood parameters in donors is essential to evaluate their health status, ensure their suitability for donation, preserve the integrity of the circulatory system, and fac...
BACKGROUND/AIMS: Assessment of the levels of vital blood parameters in donors is essential to evaluate their health status, ensure their suitability for donation, preserve the integrity of the circulatory system, and facilitate comprehensive health monitoring. The aim of our study was to analyse the levels of haemoglobin, haematocrit, erythrocyte count, MCV, MCH, and MCHC in 12 groups of first-time donors and experienced donors of both sexes at the John Paul II Regional Blood Donation and Treatment Centre in Słupsk, northern Poland. The donors were divided into three age groups (18-30 years, 31-45 years, and 46-65 years). METHODS: Using MANOVA multivariate significance tests, we examined the main effects of donor-related factors (age, sex, donor stage) on morphological blood parameters to evaluate different haematological parameters, such as Hb, Ht, RBC, MCV, MCH, and MCHC, and identified statistically significant relationships between all variables. RESULTS: The multivariate analysis of these three main factors showed that the variation in haemoglobin (Hb) levels accounted for 46% of the explained dependence in this statistical model. In particular, approximately half of the variability in the multivariate statistical analysis was attributed to the role of Hb and haematocrit (Ht). In addition, the β-coefficient values for Hb and Ht were statistically higher in relation to donor sex and donor type (single versus repeat). These β-coefficient values from our data represent the strength and direction of the relationship between the haematological parameters (Hb and Ht) and the specific donor characteristics. A higher β-coefficient indicates a stronger influence of donor sex and donor type on these parameters, suggesting that these factors contribute significantly to the variation in the Hb and Ht levels. Based on our results, the comprehensive analysis of the entire statistical model of metabolic biomarkers revealed the following hierarchy: Hb > Ht > MCHC > MCV > RBC > MCH. The results obtained showed strong statistical relationships, as indicated by the high values of the key statistical indicators in our analysis. The coefficient of determination (R²) showed that the model explained a significant proportion of the variance in the data, while the F-test statistic confirmed the significance of the predictors. CONCLUSION: These strong statistical dependencies provided a clear justification for selecting this model over others, as it effectively represented the underlying relationships within the data. These statistics help to assess how well the model matches the actual data, thereby helping to reduce the risks associated with blood donation, optimise donor safety, and maintain the quality and efficiency of blood transfusion services.
ASMase is Essential for the Immune Response to Partial-Tumor Radiation Exposure.
Mathieu M, Nepali PR, Russell J … +6 more , Askarifirouzjaei H, Baltaci M, Powell SN, Humm J, Deasy JO, Haimovitz-Friedman A
Cell Physiol Biochem · 2024 Sep · PMID 39248192 · Publisher ↗
BACKGROUND/AIMS: Tumor response to radiation is thought to depend on the direct killing of tumor cells. Our laboratory has called this into question. Firstly, we showed that the biology of the host, specifically the endo...
BACKGROUND/AIMS: Tumor response to radiation is thought to depend on the direct killing of tumor cells. Our laboratory has called this into question. Firstly, we showed that the biology of the host, specifically the endothelial expression of acid sphingomyelinase (ASMase), was critical in determining tumor radiocurability. Secondly, we have shown that the immune system can enhance radiation response by allowing a complete tumor control in hemi-irradiated tumors. In this paper, we focus on the integration of these two findings. METHODS: We used Lewis Lung Carcinoma (LLC) cells, injected in the flank of either: (i) ASMase knockout or (ii) WT of matched background (sv129xBl/6) or (iii) C57Bl/6 mice. Radiation therapy (RT) was delivered to 50% or 100% of the LLC tumor volume. Tumor response, immune infiltration (CD8 T cells), ICAM-1, and STING activation were measured. Radiotherapy was also combined with methyl-cyclodextrin, to inhibit the ASMase-mediated formation of ceramide-enriched lipid rafts. RESULTS: We recapitulated our previous finding, namely that tumor hemi-irradiation was sufficient for tumor control in the LLC/C57Bl/6 model. However, in ASMase KO mice hemi-irradiation was ineffective. Likewise, pharmacological inhibition of ASMase significantly reduced the tumor response to hemi-irradiation. Further, we demonstrated elevated ICAM-1 expression, increased levels of CD8 T cells, ICAM-1, and STING activation in tumors growing in C57Bl/6 mice, as well as the ASMase WT strain. However, no such changes were seen in tumors growing in ASMase KO mice. CONCLUSION: ASMase and ceramide generation are necessary to mediate a radiation-induced anti-tumor immune response STING activation.
Efficacy of Stilbene Derivatives in Sensitizing Breast Cancer Cells to Ionizing Radiation.
Komorowska D, Zaczek A, Kalenik S … +1 more , Rodacka A
Cell Physiol Biochem · 2024 Sep · PMID 39248186 · Publisher ↗
BACKGROUND/AIMS: One of the treatments for breast cancer is surgical resection of the tumour and prevention of recurrence with postoperative radiotherapy. Unfortunately, radiotherapy is not always effective enough due to...
BACKGROUND/AIMS: One of the treatments for breast cancer is surgical resection of the tumour and prevention of recurrence with postoperative radiotherapy. Unfortunately, radiotherapy is not always effective enough due to the low sensitivity of cancer cells to ionising radiation. This study aimed to evaluate the radiosensitising properties of resveratrol, piceatannol and polydatin on breast cancer cells, which differ in the presence of hormonal receptors on their surface. METHODS: The experimental part was carried out on triple-negative breast cancer cells (HCC38) and hormone-dependent cells (MCF7). The study assessed the level of cell death, changes in the expression of genes (BAX, BCL-2) and proteins related to the apoptosis process (CASPASE 3, 8 and P53), changes in the expression of antioxidant enzymes (CATALASE, SOD, GPx1/2) and NRF-2. Additionally, the expression level of RAD51 protein and histone H2AX, which are involved in DNA repair processes, was assessed. Statistical significance was evaluated by a two-way analysis of variance (ANOVA) followed by Tukey's post hoc test (p < 0.05). RESULTS: Ionising radiation in combination with resveratrol or piceatannol activates the apoptosis process by internal and external pathways. Greater sensitivity of MCF7 cells compared to HCC38 cells to ionising radiation in combination with resveratrol is associated with a weaker antioxidant response of cells and reduced intensity of DNA damage repair. DNA repair induced by ionising radiation occurs more effectively in HCC38 cells than in MCF7 cells. CONCLUSION: Resveratrol has the highest radiosensitising potential among the tested stilbene for cells of both lines. The effectiveness of ionizing radiation in combination with resveratrol (to a lesser extent with piceatannol) is more significant in MCF7 than in HCC38 cells.
Expression of Concern.
Cell Physiol Biochem · 2024 Aug · PMID 39230350 · Publisher ↗
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Lemon Juice and Peel Constituents Potently Stabilize Rat Peritoneal Mast Cells.
Sato A, Kikuta Y, Kazama I
Cell Physiol Biochem · 2024 Aug · PMID 39230349 · Publisher ↗
BACKGROUND/AIMS: Lemons ( ) contain various nutrients and are among the most popular citrus fruit. Besides their antioxidant, anticancer, antibacterial, and anti-inflammatory properties, clinical studies have indicated t...
BACKGROUND/AIMS: Lemons ( ) contain various nutrients and are among the most popular citrus fruit. Besides their antioxidant, anticancer, antibacterial, and anti-inflammatory properties, clinical studies have indicated their anti-allergic properties. METHODS: Using the differential-interference contrast (DIC) microscopy, we examined the effects of lemon juice and peel constituents, such as citric acid, ascorbic acid, hesperetin and eriodictyol, on the degranulation from rat peritoneal mast cells. Using fluorescence imaging with a water-soluble dye, Lucifer Yellow, we also examined their effects on the deformation of the plasma membrane. RESULTS: Lemon juice dose-dependently decreased the number of degranulated mast cells. At concentrations equal to or higher than 0.25 mM, citric acid, hesperetin, and eriodictyol significantly reduced the number of degranulating mast cells in a dose-dependent manner, while ascorbic acid required much higher doses to exert significant effects. At 1 mM, citric acid, hesperetin, and eriodictyol almost completely inhibited exocytosis and washed out the Lucifer Yellow trapped on the mast cell surface, while ascorbic acid did not. CONCLUSION: This study provides evidence for the first time that lemon constituents, such as citric acid, hesperetin, and eriodictyol, potently exert mast cell-stabilizing properties. These properties are attributable to their inhibitory effects on plasma membrane deformation in degranulating mast cells.
Evaluation of SK-N-SH Cells as a Model for NMDA Receptor Induced Toxicity.
Goerges G, Disse P, Peischard S … +5 more , Ritter N, Brenker C, Seebohm G, Strutz-Seebohm N, Schreiber JA
Cell Physiol Biochem · 2024 Aug · PMID 39215550 · Publisher ↗
BACKGROUND/AIMS: Over the years, the number of patients with neurodegenerative diseases is constantly rising illustrating the need for new neuroprotective drugs. A promising treatment approach is the reduction of excitot...
BACKGROUND/AIMS: Over the years, the number of patients with neurodegenerative diseases is constantly rising illustrating the need for new neuroprotective drugs. A promising treatment approach is the reduction of excitotoxicity induced by rising ()-glutamate levels and subsequent NMDA receptor overactivation. To facilitate the search for new NMDA receptor inhibitors neuronal cell models are needed. In this study, we evaluated the suitability of human SK-N-SH cells to serve as a cell model for neurodegeneration induced by NMDA receptor overstimulation. METHODS: The cytoprotective effect of the unselective NMDA receptor blocker ketamine as well as the GluN2B-selective inhibitor WMS14-10 was evaluated utilizing different cell viability assays, such as endpoint (LDH, CCK-8, DAPI/FACS) and time dependent methods (bioimpedance). RESULTS: Non-differentiated as well as differentiated SK-N-SH cells express GluN1 and GluN2B subunits. Furthermore, 50 mM ()-glutamate led to an instantaneous decrease in cell survival. Only application of unselective channel blocker ketamine could protect differentiated cells against this effect, while the selective inhibitor WMS14-10 did not significantly increase cell survival. CONCLUSION: SK-N-SH cells show an increased sensitivity to ()-glutamate mediated cytotoxicity with higher differentiation level, that is only partially induced by NMDA receptor overstimulation. Furthermore, we showed that only unselective NMDA receptor inhibition can partially reverse ()-glutamate-induced toxicity.
Anti-Ceramide ScFv Prophylaxis for First Responders to a Limited Nuclear Attack.
Cheng J, Nagesh PKB, Feldman R … +4 more , Shamu T, Zhang Z, Fuks Z, Kolesnick R
Cell Physiol Biochem · 2024 Aug · PMID 39172137 · Full text
BACKGROUND/AIMS: After 9/11, multiple government agencies instituted programs aimed at developing medical radiation countermeasures (MRCs) for two syndromes lethal within weeks of a limited nuclear attack; the hematopoie...
BACKGROUND/AIMS: After 9/11, multiple government agencies instituted programs aimed at developing medical radiation countermeasures (MRCs) for two syndromes lethal within weeks of a limited nuclear attack; the hematopoietic-acute radiation syndrome (H-ARS) and the higher-dose gastrointestinal-acute radiation syndrome (GI-ARS). While re-purposing drugs that enhance marrow repopulation treats H-ARS, no mitigator protects GI tract. METHODS: We recently reported anti-ceramide 6B5 single-chain variable fragment (scFv) pre-treatment abrogates ongoing small intestinal endothelial apoptosis to rescue Lgr5 stem cells, preventing GI-ARS lethality in C57B/L6J mice. Here, with US Department of Defense support, we provide evidence that humanized anti-ceramide scFv (CX-01) is a promising prophylactic MRC for first responders, who risk exposure upon entering a radiation-contaminated site. RESULTS: CX-01, when delivered up to 90 min before irradiation, is highly-effective in preventing small intestinal endothelial apoptosis in mice and lethality in both sexes. Unexpectedly, females require an ~2-fold higher CX-01 dose than males for full protection. CX-01 is effective subcutaneously and intramuscularly, a property critical for battlefield use. Increasing the maximally-effective dose 5-fold does not extend duration of bioeffectiveness. CONCLUSION: While CX-01 prevents GI-ARS lethality, structural modification to extend half-life may be necessary to optimize first responder prophylaxis.
Flour Fortification Using Lablab Purpureus Evaluation with a Biosensor.
Piedra FJ, Z RAR, Vélez MIZ … +9 more , Murillo JPM, Flor FGI, Loor AMA, Alfonso YR, Moreno JAV, Sánchez HC, Sánchez JMV, Vega EP, Brito LDD
Cell Physiol Biochem · 2024 Aug · PMID 39166656 · Publisher ↗
BACKGROUND/AIMS: Due to rapid metabolic and growth rates during the first two years of life, the nutritional needs of young children are high. Given the small portion sizes consumed by children between the ages of 6 and...
BACKGROUND/AIMS: Due to rapid metabolic and growth rates during the first two years of life, the nutritional needs of young children are high. Given the small portion sizes consumed by children between the ages of 6 and 24 months, it is necessary to improve diets to meet the nutritional needs of this age group. Therefore, the analysis of lysine content is an important parameter in the evaluation of enriched foods. METHODS: The utilization of an enzymatic sensor employing lysine-α-oxidase (LOx) as a biorecognition element represents an alternative to the existing methods. This sensor was optimized for quantifying the lysine content in flour mixtures: Quinoa-Lablab purpureus rye - Lablab purpureus, and pole beans - Lablab purpureus, with a maximum ratio of 85g/100g. RESULTS: The addition of lablab purpureus significantly increased the lysine concentration in the enriched samples. When 30 percent was substituted in quinoa, it reached a 143 percent increase. And when 15 percent was substituted in the rye flour, the final concentration of this amino acid increased by 64 percent. In order to quantify the lysine concentration, it was necessary to optimize various parameters during the use of the sensor, e.g. a potentiometric signal was detected upon the depletion of oxygen present during the oxidation of lysine in the samples, and the sensor response was recorded at 2 s. This was possible due to the modification of the pH and the thickness of the membrane. The oxidation of lysine is catalyzed by LOx using molecular oxygen as the electron acceptor. The corresponding acidic compounds and hydrogen peroxide were formed in the reaction medium. CONCLUSION: It was possible to increase and verify the concentration of lysine in all the flours tested through the use of the biosensor, which turned out to be a valid method for controlling the nutritional quality of flours.
Dysregulation of Aquaporin-3 and Glyceryl Glucoside Restoring Action in Hidradenitis Suppurativa in Vitro Models.
Del Vecchio C, Gratton R, Nait-Meddour C … +12 more , Nardacchione EM, Moura R, Sommella E, Moltrasio C, Marzano AV, Ura B, Mentino D, Boniotto M, d'Adamo AP, Calamita G, Crovella S, Tricarico PM
Cell Physiol Biochem · 2024 Aug · PMID 39166549 · Publisher ↗
BACKGROUND/AIMS: Aquaporin-3 (AQP3) is an aquaglyceroporin and peroxiporin that plays a crucial role in skin barrier homeostasis. Dysregulated AQP3 expression has been observed in different inflammatory skin conditions....
BACKGROUND/AIMS: Aquaporin-3 (AQP3) is an aquaglyceroporin and peroxiporin that plays a crucial role in skin barrier homeostasis. Dysregulated AQP3 expression has been observed in different inflammatory skin conditions. Hidradenitis Suppurativa (HS) is an autoinflammatory keratinization disease that typically appears between 10 and 21 years of age, characterized by alteration of skin barrier homeostasis. METHODS: To evaluate the role of AQP3 in the development of HS, we performed real-time PCR and Western blot to analyze gene and protein levels in human keratinocyte cell lines knock-out (KO) for and genes, simulating genetic-associated HS. Additionally, we investigated the impact of Glyceryl Glucoside (GG) on biological processes by performing MTT, scratch, proliferation assays and proteome studies. RESULTS: We detected a significant decrease of the levels of AQP3 gene and protein in KO cell lines. GG effectively elevated the levels of mRNA and protein, significantly decreased the hyperproliferation rate, and enhanced cell migration in our model of genetic Hidradenitis Suppurativa. Pathway enrichment analysis further confirmed GG's role in the migration and proliferation pathways of keratinocytes. CONCLUSION: Our results suggest that AQP3 may act as a new novel actor in HS etio-pathogenesis, and GG could be further explored as potential treatment option for managing HS in patients.
Hybrid Organic-Inorganic Copper and Cobalt Complexes for Antimicrobial Potential Applications.
Al-Jameel SS, Ababutain IM, Alghamdi AI … +9 more , Ben-Ali A, Al-Nasir AH, Alqhtani AH, Aldewely LK, Alhassan MM, Bakhurji RE, AlGhamdi WM, Alzahrani RA, Alrabghi IA
Cell Physiol Biochem · 2024 Aug · PMID 39137299 · Publisher ↗
BACKGROUND/AIMS: The naturally occurring phenolic chemical curcumin (CUR), which was derived from the Curcuma longa plant, has a variety of biological actions, including anti-inflammatory, antimicrobial, antioxidant, and...
BACKGROUND/AIMS: The naturally occurring phenolic chemical curcumin (CUR), which was derived from the Curcuma longa plant, has a variety of biological actions, including anti-inflammatory, antimicrobial, antioxidant, and anticancer activities. Curcumin is known for its restricted bioavailability due to its hydrophobicity, poor intestinal absorption, and quick metabolism. To boost the biological effects of these bioactive molecules, it is necessary to raise both their bioavailability and their solubility in water. Aim: The aim of this study is to synthesize and characterize hybrid organic-inorganic complexes of copper and cobalt, and to evaluate their antimicrobial potential against a range of pathogenic microorganisms. METHODS: The synthesis of metal curcumin complexes (Cu-CUR and Co-CUR) was achieved by mixing curcumin with copper acetate monohydrate. The solid residue was isolated, filtered, and dried in an oven. X-ray diffraction analysis was used to identify the structure and phase of the prepared samples. FTIR spectra were recorded using a Shimadzu 2200 module. The antimicrobial activity of the prepared complexes was evaluated against four bacterial strains and two Candida species. The chemical materials were dissolved in DMSO to a final concentration of 20%, and the plates were incubated at 37°C for 24 hours. The results showed that the prepared complexes had antimicrobial activity against the tested microorganisms. RESULTS: The study compared the Powder X-ray diffraction (XRD) patterns of prepared copper and cobalt complexes to pure curcumin, revealing new, isostructural complexes. The FTIR analysis showed that the Cu-CUR and Co-CUR complexes varied in their inhibitory effect against microorganisms, with Co-CUR being more effective. The results are consistent with previous studies showing the cobalt-curcumin complex was effective against various bacterial genera, with inhibition activity varying depending on the species and strains of microorganisms. CONCLUSION: Copper and cobalt curcumin complexes, synthesized at room temperature, exhibit high crystallinity and antimicrobial activity. Co-CUR, with its superior antibacterial potential, outperforms pure curcumin in inhibiting microbes. Further investigation is needed to understand their interaction mechanisms with bacteria and fungi.
Elucidation of the Role of L-Arginine and N-Nitro-L-Arginine in the Treatment of Rats with Different Levels of Hypoxic Tolerance and Exposure to Lead Nitrate.
Tkaczenko H, Lukash O, Kamiński P … +1 more , Kurhaluk N
Cell Physiol Biochem · 2024 Jul · PMID 39092511 · Publisher ↗
BACKGROUND/AIMS: Individual resistance to hypoxia is an important feature of the physiological profile of an organism, particularly in relation to lead-induced toxicity. METHODS: Our study focused on evaluating parameter...
BACKGROUND/AIMS: Individual resistance to hypoxia is an important feature of the physiological profile of an organism, particularly in relation to lead-induced toxicity. METHODS: Our study focused on evaluating parameters of mitochondrial oxygen consumption, microsomal oxidation, intensity of lipoperoxidation processes and antioxidant defences in the liver of rats with low (LR) and high (HR) resistance to hypoxia to elucidate the mechanisms of action of L-arginine and the NO synthase inhibitor L-NNA before or after exposure to lead nitrate. RESULTS: Our study suggests that the redistribution of oxygen-dependent processes towards mitochondrial processes under the influence of the nitric oxide precursor amino acid L-arginine is an important mechanism for maintaining mitochondrial respiratory chain function during lead nitrate exposure (3.6 mg lead nitrate/kg bw per day for 30 days). Animals were given L-arginine at a dose of 600 mg/kg bw (i.p., 30 min) before and after exposure to lead nitrate or the NO synthase inhibitor N-nitro-L-arginine (L-NNA) at a dose of 35 mg/kg bw (i.p., 30 min) before and after exposure to lead nitrate. Our experiments demonstrated the efficacy of using lead nitrate to simulate lead-related toxic processes via Pb levels in liver tissue; we demonstrated significantly reduced levels of nitrites and nitrates, i.e. stable metabolites of the nitric oxide system, in both LR and HR animals. The effect of the amino acid L-arginine stabilised the negative effects of lead nitrate exposure in both groups of LR and HR rats. We observed the efficiency of mitochondrial energy supply processes and showed a greater vulnerability of NADH-dependent oxidation during lead nitrate exposure in the liver of HR rats. CONCLUSION: L-arginine initiated the processes of oxidation of NADH-dependent substrates in the LR group, whereas in the HR group this directionality of processes was more effective when the role of the nitric oxide system was reduced (use of L-NNA). Our study of key antioxidant enzyme activities in rat liver tissue during lead nitrate exposure revealed changes in the catalase-peroxidase activity ratio. We found different activities of antioxidant enzymes in the liver tissue of rats treated with lead nitrate and L-arginine or L-NNA, with a significant increase in GPx activity in the LR group when L-arginine was administered both before and after exposure to lead nitrate.
The Effect of Oleuropein in AIF and MMP-9 in Traumatic Brain Injury Rat Model.
Mousa A, Dharmajaya R, Reveny J … +6 more , Surbakti KP, Tobing HG, Ilyas S, Sembiring RJ, Arina CA, Riawan W
Cell Physiol Biochem · 2024 Jul · PMID 39092504 · Publisher ↗
BACKGROUND/AIMS: Traumatic brain injury is a significant public problem with an incidence of 10 million people per year, causing the largest deaths and disabilities worldwide. Head injuries can be classified into primary...
BACKGROUND/AIMS: Traumatic brain injury is a significant public problem with an incidence of 10 million people per year, causing the largest deaths and disabilities worldwide. Head injuries can be classified into primary and secondary head injuries. Secondary head injuries can be caused by several factors such as ischemia, cerebral edema, and neuroinflammation. AIF and MMP-9 are two parameters that can be indicators in measuring the effect of Oleuropein on traumatic brain injury in rats. Oleuropein itself has many activities such as antioxidant, anti-apoptotic, antimicrobial, anti-inflammatory, and neuroprotective. METHODS: Adult male Sprague-Dawley rats (250-350 grams) were exposed to head injury, with or without intraperitoneal administration of Oleuropein. Within 24-72 hours brain tissue was isolated for immunohistochemical analysis, ELISA, and TUNEL. AIF, GFAP, MMP-9, and HMGB-1 levels were determined using immunohistochemistry in both the control and treatment groups. Statistical analysis was made using the One-Way Analysis of Variance (ANOVA) and paired t-test. RESULTS: The results showed that Oleuropein was able to reduce AIF and MMP-9 levels in rats with traumatic brain injury. This indicates that Oleuropein has a neuroprotective effect by reducing inflammation and apoptosis. CONCLUSION: Oleuropein has a potential neuroprotective effect in traumatic brain injury by reducing inflammation and apoptosis. Therefore, Oleuropein can be considered as a potential therapeutic agent for traumatic brain injury in the future.
Single-Cell Analysis Reveals That CD47 mRNA Expression Correlates with Immune Cell Activation, Antiviral Isgs, and Cytotoxicity.
Cham LB, Rosas-Umbert M, Lin L … +2 more , Tolstrup M, Søgaard OS
Cell Physiol Biochem · 2024 Jul · PMID 39074350 · Publisher ↗
BACKGROUND/AIMS: Immune cells are reported to upregulate CD47 during infection, however, the role of CD47 in innate and adaptive immune cells remains unclear. METHODS: To bridge this knowledge gap, we analysed our single...
BACKGROUND/AIMS: Immune cells are reported to upregulate CD47 during infection, however, the role of CD47 in innate and adaptive immune cells remains unclear. METHODS: To bridge this knowledge gap, we analysed our single cell (sc)-RNA dataset along with other publicly available sc-RNA datasets from healthy controls, people with HIV-1 (PWH) and COVID-19 patients. We characterized each immune cell based on low, intermediate, and high expression of . RESULTS: Our analyses revealed that pDCs and monocytes exhibited relatively higher expression of IFN-α regulatory genes, antiviral interferon-stimulated genes (ISGs) and MHC-I associated genes compared to and cells. Furthermore, NK and CD8+ T cells showed higher expression of antiviral ISGs, as well as genes encoding for cytotoxic markers like granzyme B, perforin, granulysin, interferon gamma and NKG7. Additionally, CD8+ T cells expressed higher levels of PD-1 and LAG-3 genes. Lastly, we found that B cells had enriched expression of genes involved in cell activation and humoral responses. CONCLUSION: Overall, our analyses revealed that innate and adaptive immune cells expressing elevated activation and functional gene signatures also express higher levels.
Is Salivary Α-Amylase a Reliable Indicator of Psychological Status and Quality of Life in Patients with Oral Lichen Planus: a Case-Control Study.
Glavina A, Zoranić A, Tadin A … +3 more , Cigić L, Šupe-Domić D, Lugović-Mihić L
Cell Physiol Biochem · 2024 Jul · PMID 39012386 · Publisher ↗
BACKGROUND/AIMS: The objectives of our study were to determine salivary α-amylase activity (stress biomarker) and its association with psychological status and quality of life (QoL), disease duration and intensity of sym...
BACKGROUND/AIMS: The objectives of our study were to determine salivary α-amylase activity (stress biomarker) and its association with psychological status and quality of life (QoL), disease duration and intensity of symptoms (pain/burning) in patients with OLP. METHODS: A total of 50 subjects participated in this case-control study: 30 patients with oral lichen planus (OLP); 20 control subjects. Unstimulated whole saliva (UWS) was collected between 9 and 10 am to avoid diurnal fluctuations. Psychological status was assessed using the Croatian validated version of the original Depression, Anxiety and Stress Scale (DASS-21). The impact of oral health on QoL was assessed using the Croatian version of the Oral Health Impact Profile Questionnaire (OHIP-CRO14). RESULTS: There was no statistically significant difference in salivary α-amylase activity between patients with OLP (N=30) and control subjects (N=20) (133813.3 vs. 166815.5 U/L, p=0.314; t-test). Depression, anxiety and stress showed no statistically significant difference between patients with OLP and control subjects (p=0.076, p=0.111, p=0.209; t-test). The patients with OLP had statistically significantly poorer QoL (total) compared to control subjects (p=0.004, t-test). There was a moderate positive correlation between symptom intensity (pain/burning) and poor QoL (total) (r=0.584, p<0.001), the OHIP-CRO14 dimension "physical pain" (r=0.661, p<0.001), "psychological impossibility" (r=0.555, p<0.01), "handicap" (r=0.546, p<0.01). CONCLUSION: Although salivary α-amylase showed no statistically significant difference between patients with OLP and control subjects, the patients with OLP had poorer psychological status (three times higher scores for depression and two times higher scores for anxiety) and poorer QoL compared to the control subjects. Recognising and treating mental disorders in patients with OLP is important in order to break the "vicious circle" and achieve a better QoL in these patients.
Role of Piezo2 in Schwann Cell Volume Regulation and Its Impact on Neurotrophic Release Regulation.
Suttinont C, Maeno K, Yano M … +3 more , Sato-Numata K, Numata T, Tsutsumi M
Cell Physiol Biochem · 2024 Jul · PMID 38973197 · Publisher ↗
BACKGROUND/AIMS: Tactile perception relies on mechanoreceptors and nerve fibers, including c-fibers, Aβ-fibers and Aδ-fibers. Schwann cells (SCs) play a crucial role in supporting nerve fibers, with non-myelinating SCs e...
BACKGROUND/AIMS: Tactile perception relies on mechanoreceptors and nerve fibers, including c-fibers, Aβ-fibers and Aδ-fibers. Schwann cells (SCs) play a crucial role in supporting nerve fibers, with non-myelinating SCs enwrapping c-fibers and myelinating SCs ensheathing Aβ and Aδ fibers. Recent research has unveiled new functions for cutaneous sensory SCs, highlighting the involvement of nociceptive SCs in pain perception and Meissner corpuscle SCs in tactile sensation. Furthermore, Piezo2, previously associated with Merkel cell tactile sensitivity, has been identified in SCs. The goal of this study was to investigate the channels implicated in SC mechanosensitivity and the release process of neurotrophic factor secretion. METHODS: Immortalized IFRS1 SCs and human primary SCs generated two distinct subtypes of SCs: undifferentiated and differentiated SCs. Quantitative PCR was employed to evaluate the expression of differentiation markers and mechanosensitive channels, including TRP channels (TRPV4, TRPM7 and TRPA1) and Piezo channels (Piezo1 and Piezo2). To validate the functionality of specific mechanosensitive channels, Ca imaging and electronic cell sizing experiments were conducted under hypotonic conditions, and inhibitors and siRNAs were used. Protein expression was assessed by Western blotting and immunostaining. Additionally, secretome analysis was performed to evaluate the release of neurotrophic factors in response to hypotonic stimulation, with BDNF, a representative trophic factor, quantified using ELISA. RESULTS: Induction of differentiation increased Piezo2 mRNA expression levels both in IFRS1 and in human primary SCs. Both cell types were responsive to hypotonic solutions, with differentiated SCs displaying a more pronounced response. Gd and FM1-43 effectively inhibited hypotonicity-induced Ca transients in differentiated SCs, implicating Piezo2 channels. Conversely, inhibitors of Piezo1 and TRPM7 (Dooku1 and NS8593, respectively) had no discernible impact. Moreover, Piezo2 in differentiated SCs appeared to participate in regulatory volume decreases (RVD) after cell swelling induced by hypotonic stimulation. A Piezo2 deficiency correlated with reduced RVD and prolonged cell swelling, leading to heightened release of the neurotrophic factor BDNF by upregulating the function of endogenously expressed Ca-permeable TRPV4. CONCLUSION: Our study unveils the mechanosensitivity of SCs and implicates Piezo2 channels in the release of neurotrophic factors from SCs. These results suggest that Piezo2 may contribute to RVD, thereby maintaining cellular homeostasis, and may also serve as a negative regulator of neurotrophic factor release. These findings underscore the need for further investigation into the role of Piezo2 in SC function and neurotrophic regulation.
Retraction.
Cell Physiol Biochem · 2024 Jun · PMID 38958399 · Publisher ↗
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