Cell. Physiol. Biochem. [JOURNAL]
Sun
200 papers
HIF-O-Glcnac Axis - Implications for Breast Cancer Metastasis.
Kozal KA, Jarosiewicz M, Szustka AE … +4 more , Mądrecki M, Jankowski M, Jóźwiak PJ, Krześlak A
Cell Physiol Biochem · 2025 Jun · PMID 40598910 · Publisher ↗
BACKGROUND/AIMS: Hypoxia-inducible factor isoforms HIF1 and HIF2 are crucial in the hypoxia response but might also support cancer progression, including breast cancer. O-GlcNAcylation, a post-translational modification...
BACKGROUND/AIMS: Hypoxia-inducible factor isoforms HIF1 and HIF2 are crucial in the hypoxia response but might also support cancer progression, including breast cancer. O-GlcNAcylation, a post-translational modification regulated by the OGT enzyme, is also emerging as a contributor to breast cancer malignancy. This study aimed to elucidate the role of HIF1 and HIF2 in breast cancer progression and their relationship to O-GlcNAcylation. METHODS: We analyzed clinical breast cancer samples, assessing HIF1, HIF2, OGT, and the total O-GlcNAcylation levels by the Western Blot method and their association with clinicopathological characteristics. Additionally, we employed silencing of OGT, HIF1, and HIF2 in breast cancer cell lines (MCF-7 and MDA-MB-231) to examine their effects on genes expression and cell migration (wound healing assay). A p-value < 0.05 was considered to indicate a statistically significant difference. RESULTS: In breast cancer samples, both HIF isoform levels were elevated in tumors, but HIF2 was associated with lymph node metastasis. A negative correlation was found between HIF2 and O-GlcNAcylation. Silencing HIF2 slowed cell migration, increased O-GlcNAcylation, and decreased the expression of metastasis-related genes. Silencing HIF1 or OGT resulted in the increased expression of these genes, potentially due to increased levels of HIF2. CONCLUSION: Our findings suggest that the HIF-O-GlcNAc axis plays a critical role in breast cancer progression and metastasis, with HIF1 and HIF2 exhibiting distinct functions.
Inactivation of the Reactive Oxygen Species-Dependent PI3K/Akt/Mtor Signaling Pathway by Phloroglucinol Contributes to Cytotoxicity in Hep3B Human Hepatocellular Carcinoma Cells.
Kim SY, Hwangbo H, Kim GY … +1 more , Choi YH
Cell Physiol Biochem · 2025 Jun · PMID 40539241 · Publisher ↗
BACKGROUND/AIMS: Phloroglucinol is a phenolic derivative isolated from brown algae and reportedly has the potential to induce apoptosis in cancer cells, but its mechanism is unclear. This study aimed to elucidate the com...
BACKGROUND/AIMS: Phloroglucinol is a phenolic derivative isolated from brown algae and reportedly has the potential to induce apoptosis in cancer cells, but its mechanism is unclear. This study aimed to elucidate the complete anticancer mechanism of phloroglucinol in Hep3B human hepatocellular carcinoma (HCC) cells. METHODS: We investigated whether phloroglucinol inhibits the proliferation of Hep3B cells by inducing DNA damage and apoptosis, and conducted a study on the mechanism involved. We also explored whether phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway is involved in phloroglucinol-induced apoptosis. In addition, we evaluated whether reactive oxygen species (ROS) was involved in the anticancer activity of phloroglucinol. RESULTS: Our results revealed that phloroglucinol disrupted mitochondrial integrity and induced caspase-dependent apoptosis by altering the expression of Bcl-2 family proteins and increasing the cytosolic release of cytochrome . Phloroglucinol also inactivated the PI3K/Akt/mTOR signaling pathway, and pretreatment with a PI3K inhibitor remarkably augmented the phloroglucinol-induced cytotoxic effect in Hep3B cells. In addition, phloroglucinol significantly stimulated generation of ROS and reduced glutathione ratios. However, a ROS scavenger attenuated phloroglucinol-induced oxidative stress, DNA damage, and apoptosis, thus restoring the reduced cellular viability by blockading phloroglucinol-mediated inactivation of PI3K/Akt/mTOR signaling. CONCLUSION: Our findings support a mechanism in which phloroglucinol enhances Hep3B cell apoptosis by inactivating the ROS-dependent PI3K/Akt/mTOR pathway, which implies that ROS generation acts as an inducer of phloroglucinol-mediated anticancer activity. Taken together, our findings support further research on the potential of phloroglucinol as a candidate for treating HCC.
Association of IL4 (Rs2243250) Gene Variant and Mycoplasma Pneumoniae Infection with Asthma Susceptibility in an Iraqi Population.
Al-Zamali SKS, Mohammed SS, Radhi SH … +2 more , Hassan SA, Abdulridha GAO
Cell Physiol Biochem · 2025 May · PMID 40420775 · Publisher ↗
BACKGROUND/AIMS: Asthma is a multifactorial disease influenced by both genetic and environmental factors. This study aimed to investigate the association between the IL4 gene polymorphism (rs2243250) and asthma susceptib...
BACKGROUND/AIMS: Asthma is a multifactorial disease influenced by both genetic and environmental factors. This study aimed to investigate the association between the IL4 gene polymorphism (rs2243250) and asthma susceptibility, along with serum IL-4 levels. Additionally, it explored infection as a potential risk factor for asthma. METHODS: A total of 118 individuals were enrolled, including 60 asthma patients and 58 healthy controls. Genotyping for IL4 rs2243250 was performed using allele-specific PCR (AS-PCR). Previous infection was assessed serologically, and serum IL-4 levels were measured using ELISA. RESULTS: No significant differences were observed between groups in terms of age, sex, or residence. Smoking (OR: 7.85, = 0.001) and family history of asthma (OR: 5.33, = 0.004) were identified as significant risk factors. infection was significantly more prevalent in asthma patients (41.7%) than in controls, with a strong association with asthma risk (OR: 8.75, < 0.0001). Genotype frequencies of rs2243250 differed significantly: CC (36.7% vs. 68.9%), CT (41.7% vs. 24.2%), and TT (21.6% vs. 6.9%) in patients versus controls, respectively. The T allele was more frequent among patients (42.5%) than controls (18.97%), increasing asthma risk (OR: 3.16, = 0.0001). Both CT (OR: 3.25) and TT (OR: 5.91) genotypes were strongly associated with asthma. Moreover, individuals with the TT genotype had significantly higher serum IL-4 levels ( < 0.001). CONCLUSION: The IL4 rs2243250 polymorphism is associated with increased asthma susceptibility and elevated serum IL-4 levels in the Iraqi population. infection also appears to be a significant contributing factor. Larger-scale studies are warranted to confirm these findings and further explore the role of this infection in asthma pathogenesis.
The P53 Mutation Plays a Regulatory Role in Osteosarcoma Metastasis Via the Cholesterol-Hedgehog Pathway.
Lulin W, Jiawei L, Shuojie Z … +4 more , Xiaoli X, Hui W, Jia J, Juhua D
Cell Physiol Biochem · 2025 May · PMID 40420741 · Publisher ↗
BACKGROUND/AIMS: Osteosarcoma is the most common primary bone cancer affecting children and adolescents worldwide. Although many treatments for osteosarcoma have been explored, the overall survival rate for patients with...
BACKGROUND/AIMS: Osteosarcoma is the most common primary bone cancer affecting children and adolescents worldwide. Although many treatments for osteosarcoma have been explored, the overall survival rate for patients with metastatic osteosarcoma is only 20% due to the lack of understanding of the biological mechanisms by which osteosarcoma metastasis occurs. Therefore, it is important to uncover the molecular mechanism of metastasis in osteosarcoma. METHODS: We compared the migration ability of primary osteosarcoma cells from p53 knockout (p53null) and p53 knock-in (p53S) mice. Furthermore, via RNA-sequencing (RNA-seq) data from mouse embryonic fibroblast (MEF) cells, we explored the mechanism by which p53S regulates the cholesterol synthesis pathway and the Hedgehog signaling pathway in primary osteosarcoma cells. RESULTS: We found that the migration ability of primary tumor cells from p53S mice was increased both and . Further investigations revealed that the cholesterol content in p53S sarcoma tissue and primary cells was increased following the upregulation of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). We subsequently observed that elevated cholesterol levels can regulate the Hedgehog (HH) pathway and lead to tumor metastasis. We subsequently treated p53S sarcoma cells with the cholesterol neutralizer methyl-β-cyclodextrin (MβCD) and an HH pathway inhibitor; consequently, we reported that total cholesterol levels reduced both Hedgehog pathway activity and cell migration, whereas HH pathway activity reduced only cell migration. CONCLUSION: In summary, we confirmed the enhanced metastatic ability of p53S sarcoma primary cells via and experiments and preliminarily confirmed the mechanism by which p53S promotes cholesterol synthesis and further activates the HH signaling pathway, thus leading to sarcoma metastasis. This study provides a theoretical basis for further revealing the function and mode of action of p53 mutations in the process of sarcoma metastasis, thereby providing a new potential target for the targeted diagnosis and treatment of sarcoma.
Exosome-Mediated Mechanisms of Drug Resistance in Lung Cancer: Molecular Mechanisms and Therapeutic Strategies.
Havryliuk V, Wojtowicz K, Gagat M … +1 more , Żuryń A
Cell Physiol Biochem · 2025 May · PMID 40420738 · Publisher ↗
Lung cancer, one of the leading causes of cancer-related deaths globally, is notorious for its poor prognosis and limited response to conventional therapies. Despite advancements in chemotherapy, targeted therapies, and...
Lung cancer, one of the leading causes of cancer-related deaths globally, is notorious for its poor prognosis and limited response to conventional therapies. Despite advancements in chemotherapy, targeted therapies, and immunotherapy, the efficacy of these treatments is often undermined by the development of resistance, particularly multidrug resistance (MDR). MDR in lung cancer is primarily driven by various mechanisms, including the overexpression of ATP-binding cassette (ABC) transporters like P-glycoprotein (ABCB1), which actively pump chemotherapeutic drugs out of cancer cells, reducing their intracellular concentration and effectiveness. Additionally, genetic mutations, enhanced DNA repair mechanisms, and alterations in drug targets contribute to this phenomenon. The complexity of MDR not only complicates treatment regimens but also contributes to the high mortality rate associated with lung cancer. Understanding the underlying mechanisms of MDR and developing strategies to overcome this resistance are critical for improving patient outcomes. The objective of this review is to present a comprehensive summary of the current knowledge on conventional and emerging mechanisms of drug resistance, with a particular focus on the involvement of exosomes and exosome-mediated factors that mediate drug resistance in lung cancer. Exosomes, tiny vesicles secreted by cells, play a critical role in drug resistance, especially in lung cancer. They carry genetic material and proteins that can alter the behavior of recipient cells, promoting resistance. In lung cancer, exosomes transfer miRNAs and other molecules that enhance survival pathways and inhibit cell death, contributing to chemoresistance. Recent research highlights the potential of targeting exosomal pathways to develop new therapeutic strategies.
Effect of Lychee Peel and Seed Flour Consumption on the Anti/Pro-Oxidant System and Cardiomyocyte Contractile Function.
Coelho PM, Simmer LM, Madureira AR … +7 more , Torezani-Sales S, Cardoso JC, Santos KCC, Kitagawa RR, Pezzin MF, Leopoldo AS, Lima-Leopoldo AP
Cell Physiol Biochem · 2025 May · PMID 40384382 · Publisher ↗
BACKGROUND/AIMS: Type 2 diabetes mellitus (T2DM) represents a high risk for developing cardiovascular diseases, with alterations in contractile function and calcium (Ca2+) handling. In addition, there is an increase of r...
BACKGROUND/AIMS: Type 2 diabetes mellitus (T2DM) represents a high risk for developing cardiovascular diseases, with alterations in contractile function and calcium (Ca2+) handling. In addition, there is an increase of reactive oxygen species in T2DM, with the pathways of altered glucose metabolism, oxidative damage to pancreatic β-cells, and endothelial dysfunction being involved in this process. Studies have shown that both the extract and lychee peel and seed flour are rich in antioxidant phenolic compounds, which could be beneficial in preventing and/or reversing oxidative stress (OS) in obesity associated with type 2 diabetes mellitus (T2DMOb). However, the relationship between oxidative stress in T2DMOb and the involvement of lychee peel and seed flour is still not well understood. This study aimed to evaluate the effect of lychee peel and seed flour consumption on the anti/pro-oxidant system and cardiomyocyte contractile function in obese rats induced to T2DM. METHODS: Obesity in Wistar rats (n = 38) was induced by a high-fat diet and, later, they were induced to T2DM. The experimental protocol consisted of a total period of 17 weeks and was divided into four moments (Figure 1): 1) obesity induction (4 weeks); 2) maintenance of obesity (8 weeks); 3) induction of T2DM (12th week) in obese (Ob) rats and redistribution of groups; and 4) obesity and T2DM maintenance and treatments with lychee peel and seed flours (5 weeks). After 12 weeks, the Ob rats were randomized into T2DMOb (n = 8), T2DMOb treated with lychee peel flour (T2DMObPF, n = 10), and T2DMOb treated with lychee seed flour (T2DMObSF, n = 10). Analyzes of the nutritional and metabolic profiles, cardiac remodeling, and OS biomarkers were evaluated. Contractile function by isolated cardiomyocyte analysis and Ca2+ handling was determined. RESULTS: Treatments with lychee peel and seed flour were not able to change body weight, adiposity, biochemical and cardiac morphological parameters, or OS biomarkers in relation to T2DMOb animals. Lychee treatments did not accentuate the elevation of fractional shortening visualized in T2DMOb. Regarding relaxation, the maximum rate of relaxation was higher in the T2DMOb group compared to the Ob group, but the lychee treatments did not promote positive alterations in this parameter. In addition, the time to 50% relaxation was also longer in the presence of T2DM (T2DMOb > Ob); the treatments with lychee peel flour favored a reduction in the time to 50% relaxation. T2DMOb rats presented an increase in diastolic Ca2+ in relation to the Ob group; the treatment with lychee seed flour reduced this parameter, despite not improving the time to 50% decay Ca2+ and, consequently, relaxation. Furthermore, the treatments with lychee peel and seed flour did not change the sensitivity of myofilaments to Ca2+ in T2DMOb animals. CONCLUSION: The treatments with lychee peel and seed flour showed no significant effects on anti/pro-oxidant parameters. However, lychee peel flour demonstrated notable effectiveness in reducing myocardial relaxation time in a T2DMOb model. These results suggest that while the antioxidant properties of lychee seed and peel flours were not significantly altered, lychee peel flour may have specific therapeutic potential to improve cardiac function in T2DMOb.
Impact of Micronutrients and Macronutrients on NK Cells Immunity.
Hamdan TA
Cell Physiol Biochem · 2025 May · PMID 40384360 · Publisher ↗
Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system. Along with their cardinal role in eliminating virally infected and cancerous cells, they are considered as a bridge between innate and adap...
Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system. Along with their cardinal role in eliminating virally infected and cancerous cells, they are considered as a bridge between innate and adaptive immunity. Nutrition is linked to the effective immune response, and it is known that nutrition is among the environmental factors that influence the immune function and physiology. The function of nutrients, which are dissected into micronutrients (e.g. vitamins and minerals) and macronutrients (e.g. fat, protein and carbohydrates), is to maintain the metabolism and energy which are prime to fuel NK cells. In this review, we are going to recapitulate the recent findings and available data regarding the effect of common micro and macronutrients` examples on the NK cells development and function to provide an insight into diet-immune system crosstalk.
Negative Impact of Caloric Restriction on Atherosclerosis in Young ApoE/LDLr Mice.
Kostogrys RB, Franczyk-Żarów M, Gurgul A … +6 more , Jasielczuk I, Żaczek A, Hubalewska-Mazgaj M, Lichołai S, Manterys A, Wybrańska I
Cell Physiol Biochem · 2025 May · PMID 40384342 · Publisher ↗
BACKGROUND/AIMS: Caloric restriction (CR) has proven to be the most effective dietary intervention for reducing cardiovascular disease (CVD) associated with obesity. Depending on the age of the mice the effect of caloric...
BACKGROUND/AIMS: Caloric restriction (CR) has proven to be the most effective dietary intervention for reducing cardiovascular disease (CVD) associated with obesity. Depending on the age of the mice the effect of caloric restriction was diverse. Therefore, the effect of CR on the development of atherosclerosis in young and adult ApoE/LDLr mice was evaluated. METHODS: Eight-week-old and 20-week-old male mice received a control diet. Young mice were fed for eight weeks, whereas adult mice for 5 weeks. To assess whether individual housing influenced the tested parameters, control animals were housed in colony cages (AL) or individually (stressAL; sAL) and fed . Individually housed caloric restriction (CR) mice received a 30% less diet compared to AL group. RESULTS: The body weight of CR mice was significantly lower compared to the AL and sAL groups. TCh and LDL levels were significantly increased in young CR mice. No differences in adult animals were observed. TAG levels significantly decreased in both young and adult CR mice. CR induced atherosclerosis in young mice. The gene was upregulated in young animals. Microbiota composition changed. At the genus level, compared to the control, CR group exhibited a higher relative abundance of the , and a lower relative abundance of the (P< 0.05) genera. CONCLUSION: Caloric restriction exacerbated atherosclerosis in young ApoE/LDLr mice.
Ligament Cell Biology: Effect of Mechanical Loading.
Stańczak M, Biały M, Hagner-Derengowska M
Cell Physiol Biochem · 2025 Apr · PMID 40336361 · Publisher ↗
Ligaments are biomechanically specialized connective tissues that maintain joint stability and guide motion under complex loading conditions. At the cellular and molecular levels, ligament homeostasis is governed by fibr...
Ligaments are biomechanically specialized connective tissues that maintain joint stability and guide motion under complex loading conditions. At the cellular and molecular levels, ligament homeostasis is governed by fibroblast-like cells (ligamentocytes) embedded in an intricately organized ECM composed predominantly of type I collagen, with contributions from type III collagen, elastin, proteoglycans, and glycoproteins. These cells continuously sense and respond to mechanical stimuli-tension, compression, and shear-through mechanotransduction pathways involving integrins, focal adhesions, cytoskeletal remodeling, and mechanosensitive ion channels. Downstream signaling cascades, including MAPKs and PI3K/AKT, integrate biomechanical cues with growth factor and cytokine signaling to fine-tune gene expression, collagen fibrillogenesis, and ECM turnover. Distinct from tendons, ligaments must adapt to multidirectional loads, resulting in unique ECM compositions and cellular phenotypes. Appropriate mechanical loading maintains collagen alignment, promotes ECM integrity, and stabilizes the ligament cell phenotype. By contrast, insufficient or excessive load alters the molecular balance, triggering catabolic processes, inflammation, and disorganized ECM assembly. This delicate equilibrium also underlies the ligamentization observed in ACL graft remodeling, where controlled mechanical environments and molecular interventions accelerate the acquisition of ligamentous properties. Emerging insights into transcriptional and epigenetic regulation, growth factor-mediated cues, and cytokine-driven responses offer avenues to engineer ligament-like tissues and optimize recovery strategies. By leveraging molecular knowledge of cell-matrix interactions, growth factor profiles, and genetic/epigenetic modulators, clinicians and researchers can design tailored loading protocols, biomimetic scaffolds, and regenerative therapies. These approaches aim to restore ligament functionality, enhance graft integration, and prevent degenerative changes, ultimately improving patient outcomes in ligament injury repair and reconstruction.
Dapagliflozin, An SGLT2 Inhibitor, Improves Endothelial Cell Energy Metabolism Through Enhanced Mitochondrial Respiration.
Walczak I, Braczko A, Paterek A … +9 more , Rolski F, Urbanowicz K, Tarnawska M, Knapczyk R, Parzuchowska A, Smoleński RT, Hellmann M, Mączewski M, Kutryb-Zając B
Cell Physiol Biochem · 2025 Apr · PMID 40310878 · Publisher ↗
BACKGROUND/AIMS: Flozins (sodium-glucose cotransporter 2 inhibitors, SGLT2i) are a new class of antidiabetic drugs that reduce cardiovascular mortality and hospitalization rates in heart failure, regardless of type 2 dia...
BACKGROUND/AIMS: Flozins (sodium-glucose cotransporter 2 inhibitors, SGLT2i) are a new class of antidiabetic drugs that reduce cardiovascular mortality and hospitalization rates in heart failure, regardless of type 2 diabetes status. Besides lowering glycemia by inhibiting renal glucose reabsorption, SGLT2 inhibitors may exert sodium-dependent hemodynamic effects and improve cardiomyocyte energy metabolism, substrate preference, and mitochondrial function. However, their impact on endothelial cells remains largely unknown. This study aimed to analyse the effects and mechanisms of SGLT2i on endothelial cell metabolism and function. METHODS: Mouse cardiac endothelial cells (H5V) were used to test the impact of dapagliflozin on endothelial cell metabolism and function in the presence of hypoxia-mimicking conditions. The concentration of intracellular nucleotides was measured using high-performance liquid chromatography. Mitochondrial and glycolytic activity were assessed using Seahorse XFp, while nitric oxide (NO) production was determined by 4-Amino-5-Methylamino-2',7'-Difluorofluorescein (DAF-FM) fluorescence staining. The effects of dapagliflozin treatment on endothelial NO synthesis were also analysed in patients with chronic heart failure and left ventricular ejection fraction above 40% and C57Bl/6J mice. RESULTS: Dapagliflozin augmented adenosine triphosphate (ATP) levels and the ATP/ADP (adenosine diphosphate) ratio in cultured endothelial cells correlated to increased NO production. Dapagliflozin-treated endothelial cells produced ATP through both mitochondrial respiration and glycolysis. Interestingly, mitochondrial respiration was enhanced, while glycolysis was unaffected in endothelial cells after in vitro dapagliflozin treatment. In a murine model, dapagliflozin doubled the rate of coronary NO synthesis and tended to improve coronary capillary density. In humans with chronic heart failure, 3-month treatment with dapagliflozin revealed many metabolic effects, suggesting potential mechanisms related to nitric oxide homeostasis, mitochondrial function, and L-arginine metabolism. CONCLUSION: This study demonstrated the beneficial effect of dapagliflozin on endothelial cell metabolism and function. Regulation of endothelial cell bioenergetics may be an undervalued mechanism of SGLT2i to delay heart failure progression and support cardiac regeneration. These may accelerate endothelial-targeted strategies to support heart failure treatment.
Combined Effects of Toxic Metals and Oxidative Stress on the Development and Health of Sea Trout (Salmo Trutta L.).
Kurhaluk N, Kamiński P, Tkaczenko H
Cell Physiol Biochem · 2025 Apr · PMID 40310875 · Publisher ↗
BACKGROUND/AIMS: Contaminants in the environment pose a considerable threat to biodiversity, ecological balance, and the health of both wildlife and humans, particularly through the transfer of these harmful substances v...
BACKGROUND/AIMS: Contaminants in the environment pose a considerable threat to biodiversity, ecological balance, and the health of both wildlife and humans, particularly through the transfer of these harmful substances via fish in the food chain. METHODS: This study focused on the developmental stages of sea trout ( L.) in both riverine and Baltic Sea environments, with the aim of exploring how chemical element accumulation influences oxidative stress biomarkers in these species. RESULTS: The findings revealed notable age- and tissue-specific patterns in the accumulation of chemical elements in sea trout. Specifically, higher levels of lead (Pb), arsenic (As), mercury (Hg), and tin (Sn) were detected in the muscle tissues of adult trout, while cadmium (Cd) primarily accumulated in the gills, particularly in smolts. These results underscore the influence of both age and tissue type on the bioaccumulation of contaminants in the trout, highlighting how the accumulation of toxic elements contributes to increased oxidative stress in the fish. This oxidative stress, reflected by increased lipid peroxidation (TBARS) and carbonyl derivatives of oxidatively modified proteins, was closely related to the presence of contaminants such as Cd, Pb, As, Hg, and Sn. Gills, which are directly exposed to waterborne pollutants, exhibited significantly higher levels of oxidative damage compared to muscle tissue, consistent with the greater accumulation of metals in this organ. Despite higher total antioxidant status (TAS) in muscle tissue, both muscle and gill tissues of adult trout showed signs of considerable oxidative stress, indicating the cumulative effects of prolonged exposure to these contaminants. CONCLUSION: The study highlights the detrimental consequences of chemical element contamination on the health of trout, with a particular emphasis on oxidative damage, and calls for effective environmental management to protect aquatic species from the long-term effects of exposure to contaminants. Furthermore, the correlation and regression analysis conducted revealed significant patterns, demonstrating positive correlations between the accumulation of Cd, Pb, and As in the gills of adult trout, and between Pb and oxidative stress markers in smolts. Additionally, the analysis indicated that mercury contributes significantly to oxidative damage.
Methylglyoxal Reshapes Hepatic and Adipose Tissue Metabolism and Increases Viability of Lymphocytes.
Lucredi NC, Saavedra LPJ, Piovan S … +11 more , Lima EP, Godoy MAF, Marchiosi R, Vicentini VEP, Mathias PCF, Sá-Nakanishi AB, Bracht L, Chini CCS, Chini EN, Bracht A, Comar JF
Cell Physiol Biochem · 2025 Apr · PMID 40265308 · Publisher ↗
BACKGROUND/AIMS: Methylglyoxal (MG) is associated with the development of metabolic disorders that modify the hepatic energetic metabolism in different ways. However, not much is known about the effects of MG on energy m...
BACKGROUND/AIMS: Methylglyoxal (MG) is associated with the development of metabolic disorders that modify the hepatic energetic metabolism in different ways. However, not much is known about the effects of MG on energy metabolism in healthy liver cells. Therefore, this study investigated the effects of daily MG administration to Wistar rats on hepatic and fat tissue energetic metabolism. METHODS: Rats received MG intraperitoneally at doses of 100 or 200 mg/kg for seven consecutive days in acute approach or at a dose of 25 mg/kg for one month in the chronic approach. Metabolic pathways were measured in isolated perfused livers (glycogen catabolism, gluconeogenesis and ketogenesis) as well in adipose tissue. Activities and mRNA expressions of gluconeogenic enzymes were assessed in the liver and the viability of human lymphocytes were evaluated . RESULTS: MG displayed systemic inflammation and the metabolic changes were similar to those of widespread catabolic diseases. MG and advanced glycation end-products stimulated lymphocyte proliferation, and MG increased the hepatic interleukin-6 expression. Rats that received MG developed insulin resistance. Gluconeogenesis was diminished and glycolysis was stimulated in livers of rats that received MG. Two factors contribute to this outcome: a deficiency in mitochondrial energy supply and a much more significant downregulation of gluconeogenic enzymes. The adipose tissue metabolism was modified in a way that the AMPK-induced lipolysis was increased in the retroperitoneal fat, but not in the mesenteric fat. Ketogenesis was increased and triglycerides content was decreased in the liver. CONCLUSION: To what degree the modifications in hepatic metabolism found in MG-exposed rats can be translated to patients with a high-grade inflammation and cirrhosis is uncertain. However, it is unlikely that the strong catabolic state induced by MG would not contribute in some way to the hepatic dysfunction in advanced liver diseases.
Enhancing Cellular Immunity Through Epitope Peptides of SARS-Cov-2 in Individuals with Specific HLA Allele.
Huang X, Wu Y, Yu F … +2 more , Dong B, Yang Z
Cell Physiol Biochem · 2025 Apr · PMID 40230208 · Publisher ↗
BACKGROUND/AIMS: This research explores the effectiveness of a new cytotoxic T-cell epitope peptide specific for HLA-A2402 in enhancing cellular immune responses to SARS-CoV-2 infections. HLA molecules play a key role in...
BACKGROUND/AIMS: This research explores the effectiveness of a new cytotoxic T-cell epitope peptide specific for HLA-A2402 in enhancing cellular immune responses to SARS-CoV-2 infections. HLA molecules play a key role in presenting antigenic epitopes to T cells, with genetic polymorphisms resulting in varying immune responses among individuals. The study aimed to investigate whether loading this epitope peptide into dendritic cells (DCs) from HLA-A2402(+) individuals could improve immune responses. METHODS: DCs were sensitized with varying doses of the peptide (2-12 µg/mL), with optimal results observed at 8 µg/mL. T-cell responses, proliferation, differentiation, Th cytokine secretion, CTL function, and apoptotic response were compared among the HLA-A2402(+), HLA-A2402(-), PBS control, DC only, and epitope-only groups. RESULTS: A significant enhancement in DC maturation, antigen presentation, T-cell activation, and proliferation was observed in the HLA-A2402(+) group compared to the HLA-A2402(-) control. CONCLUSION: These findings suggest that HLA-A2402-restricted epitope peptides can enhance cellular immunity, offering potential for improving allele-specific SARS-CoV-2 vaccines and other molecular therapies, advancing precision medicine for infectious diseases.
ACE2 Expression in the Kidneys of Pregnant and Postpartum Rats: Physiological and Pathological Significance During Pregnancy.
Kikuta Y, Kazama I
Cell Physiol Biochem · 2025 Apr · PMID 40230194 · Publisher ↗
BACKGROUND/AIMS: Pregnancy is associated with changes in renal hemodynamics, such as increases in renal blood flow and the glomerular filtration rate (GFR). Angiotensin-converting enzyme 2 (ACE2), a transmembrane glycopr...
BACKGROUND/AIMS: Pregnancy is associated with changes in renal hemodynamics, such as increases in renal blood flow and the glomerular filtration rate (GFR). Angiotensin-converting enzyme 2 (ACE2), a transmembrane glycoprotein involved in vasodilation, also acts as a receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during coronavirus disease 2019 (COVID-19). METHODS: Using rats on pregnancy day 16 and postpartum day 5, we examined the histopathological changes in rat kidneys during and after pregnancy. The expressional changes in renal angiotensin-converting enzyme 2 (ACE2) and angiotensin (1-7) (Ang (1-7)) were examined, together with those of transmembrane protease serine 2 (TMPRSS2). RESULTS: examined, together with those of transmembrane protease serine 2 (TMPRSS2). Results: In pregnant rats, the renal arterioles and venules as well as the glomerular capillaries were markedly dilated, indicating renal vasodilation. Immunohistochemistry demonstrated increased ACE2 and Ang (1-7) expression within the proximal renal tubules during pregnancy, which then returned to the virgin levels in the postpartum period. Additionally, the proximal tubular expression of ACE2 and TMPRSS2 was similarly enhanced during pregnancy. CONCLUSION: As ACE2 and Ang (1-7) exert vasodilatory properties, they were considered responsible for renal vasodilation and the subsequent increase in GFR. Further, the similar distribution and enhanced expression of ACE2 and TMPRSS2 in the proximal renal tubules during pregnancy suggested their roles in the development of acute kidney injury (AKI) following COVID-19 in pregnancy. This study highlights the physiological and pathological significance of ACE2 during pregnancy.
Microbial Desalination Cells: Sustainable Water Desalination Application and Wastewater Management.
Mudher I, Ali SA
Cell Physiol Biochem · 2025 Mar · PMID 40152186 · Publisher ↗
BACKGROUND/AIMS: Microbial desalination cells (MDCs) are bioelectrochemical systems using electroactive bacteria to generate energy simultaneously cleaning wastewater and desalinating water. This sustainable technology a...
BACKGROUND/AIMS: Microbial desalination cells (MDCs) are bioelectrochemical systems using electroactive bacteria to generate energy simultaneously cleaning wastewater and desalinating water. This sustainable technology addresses pollution issues and water shortage using an environmentally friendly solution that aids in desalination as well as wastewater treatment. This research focuses on the effectiveness of microbial desalination cells (MDCs) in concurrently treating wastewater and removing salt from water. The study seeks to determine whether MDCs offer a viable, environmentally friendly method for purifying water while generating energy. METHODS: The MDC setup incorporated three distinct chambers: anode, desalination, and cathode. Wastewater samples were placed in the anode and cathode compartments, while the desalination chamber contained saline water. A digital multimeter was employed to regularly monitor and log the generated voltages. The microbial community was examined through 16S rRNA gene sequencing techniques. Organic matter elimination was quantified by measuring total organic carbon (TOC) levels. The MDC operated for 30 days continuously. RESULTS: The microbial desalination cell (MDC) produced bioelectricity, effectively desalinated water, and broke down organic molecules during its 30-day running. This suggests that since the voltage generation peaked at 638 mV and then stabilized at 460 mV, the electrochemical activity has been constant. From 46.2 mS/cm to 10.1 mS/cm, the desalination chamber's electrical conductivity (EC) fell drastically, clearly removing the ions. A decline in sodium chloride (NaCl) concentration-from 29 mg/L to 7 mg/L-also proved a sign of effective desalination. Better organic degradation was shown by the cathode chamber reaching 99.9% while the anode chamber attained a total organic carbon (TOC) removal rate of 97.2%. Desalination mostly depends on selective ion exchange across cation and anion membranes; microbial biofilm adaptation helped in the slow development of voltage. These findings suggest that since they efficiently mix the processes of wastewater treatment, desalination, and power generation, MDCs are a reasonably sustainable technology. The Microbial Desalination Cell (MDC) effectively desalinated water and treated wastewater having a peak voltage of 638 mV and a drop in NaCl concentration from 29 mg/L to 7 mg/L. With TOC removal in the anode at 97.2% and the cathode at 99.9%, the system proved excellent in both desalination and organic matter degradation. Furthermore, found to be unique from NCBI-recognized species was the microbiome found in Iraqi municipal effluent. CONCLUSION: Microbial Desalination Cells (MDCs) have many advantages over conventional desalination techniques like reverse osmosis, including being able to cleanse wastewater and simultaneously generate renewable electricity with far reduced energy usage. Constant challenges are improving ion exchange efficiency, honing interactions between microbial communities, and increasing technological scale. Improving MDC performance and incorporating it into whole energy and water management systems is the main emphasis of research nowadays. This could be a perfect choice for encouraging more environmentally friendly energy sources and lessening the consequences of world water shortage.
Optimized Protocol For DNA Extraction from Human Whole Blood.
Brodzka S, Kamiński P, Baszyński J … +7 more , Mroczkowski S, Rektor K, Stanek E, Kwiecińska-Piróg J, Grochowalska R, Kurhaluk N, Tkaczenko H
Cell Physiol Biochem · 2025 Jan · PMID 40079913 · Publisher ↗
BACKGROUND/AIMS: DNA isolation is the initial process in genetic research. The product is used in many PCR reactions (PCR-RFLP, Real-Time PCR, multiplex PCR). That is why it is important to optimize DNA isolation protoco...
BACKGROUND/AIMS: DNA isolation is the initial process in genetic research. The product is used in many PCR reactions (PCR-RFLP, Real-Time PCR, multiplex PCR). That is why it is important to optimize DNA isolation protocol to obtain a good quality of DNA. Our first attempts at isolation, conducted using Purification Kit, did not result in sufficient concentration (6.414 ng*μL) and purity (A-260/280) of 0.764 of isolated DNA. METHODS: We used twice the recommended amount of tissue and cell lysis solution to get more effective cell lysis. We extend the time of vortexing, centrifugation and incubation at critical steps. We manipulated the speed and temperatures of centrifugation. We used cold iso-propanol to get white strands of DNA faster. When rinsing with ethanol we used cold alcohol. We tested efficiency of two methods of drying of ethanol to achieve optimal DNA pureness. We leave the isolated DNA for 20 minutes to evaporate the ethanol and then resuspend nucleic acid in TE Buffer. RESULTS: Our modifications resulted in the improvement of isolation efficiency. After optimization we achieved DNA concentration (in range of 50-150 ng*μL) and purity (A 260/280) of 1.735. Similar results for DNA parameters were achieved from the whole blood frozen for 2-3 months (concentration in the range of 125.762 ng*μL, pureness: 1.761) and from blood frozen for 18 months (117.94 ng*μL and 1.7194, respectively). We performed electrophoresis after each isolation to confirm the effectiveness of optimized procedure. The refinements we used in DNA isolation are more efficient than those recommended in DNA Purification Kits. CONCLUSION: Our results confirm that optimized DNA protocol fulfills the conditions of good extraction technique: it is relatively fast and easy to perform yet it guarantees a high reproducibility, specificity and sensitivity. There are also no dangerous or harmful steps. Our paper demonstrates innovative and effective approach. It confirms a high effectiveness of method regardless of duration of sample freezing, as well as introduce important modifications (timing, temperature conditions, drying details, absence of K-proteinase) that make overall procedure more productive and relatively fast.
Effective Treatment of Cartilage Abnormalities in Middle-Aged Individuals (Aged 45-60): Bounding Molecular Biology with Microfracture and Hyalofast Membrane Approach Show Positive Outcomes.
Kacprzak B, Rosińska K, Stańczak M
Cell Physiol Biochem · 2025 Feb · PMID 40033938 · Publisher ↗
BACKGROUND/AIMS: In recent years, significant progress has been made in treating cartilage lesions, leading to various techniques aimed at articular surface regeneration. However, the impact of patient age on treatment o...
BACKGROUND/AIMS: In recent years, significant progress has been made in treating cartilage lesions, leading to various techniques aimed at articular surface regeneration. However, the impact of patient age on treatment outcomes remains understudied, despite its recognized influence on effectiveness. Many studies impose upper age limits, resulting in limited data on middle-aged patients, a group frequently undergoing cartilage repair. Age-related physiological changes, including a decline in regenerative capacity and alterations in proteoglycan composition, are believed to affect treatment success. This study investigates the clinical outcomes of cartilage repair in patients aged 45 to 60, specifically evaluating the effectiveness of microfracture combined with Hyalofast membrane implantation. METHODS: Patients aged 45-60 undergoing microfracture with Hyalofast membrane implantation were evaluated. Short- and medium-term outcomes were assessed using the KOOS and SF-36 questionnaires preoperatively and at 6- and 12-month follow-ups. Functional evaluations and MRI analyses were conducted by expert reviewers. Additionally, an intensive rehabilitation program was initiated immediately post-surgery. Statistical analysis was performed using a one-way repeated-measures ANOVA to compare preoperative, 6-month, and 12-month results, with Tukey's post-hoc test applied for multiple comparisons. Clinical significance was assessed using Cohen's d effect size, with standard thresholds for small, medium, and large effects. RESULTS: The combined microfracture and Hyalofast membrane approach, along with early rehabilitation, yielded promising results. Key benefits included reduced inflammation, improved membrane integration, and decreased subchondral edema. CONCLUSION: These findings support the feasibility of this treatment strategy, highlighting its potential to enhance joint function, alleviate pain, and improve the overall quality of life in middle-aged patients.
Synergistic Activity of Indolicidin and Tigecycline Against Multidrug-Resistant Acinetobacter Baumannii Clinical Isolates.
ALtameemi R, Ghareeb AM, Rahal BS
Cell Physiol Biochem · 2025 Feb · PMID 40033934 · Publisher ↗
BACKGROUND/AIMS: Acinetobacter baumannii is a ubiquitous opportunistic microorganism associated with high morbidity and mortality Particularly among burn patients and immunocompromised individuals. This study aimed to as...
BACKGROUND/AIMS: Acinetobacter baumannii is a ubiquitous opportunistic microorganism associated with high morbidity and mortality Particularly among burn patients and immunocompromised individuals. This study aimed to assess the time-dependent antimicrobial effectiveness of indolicidin in combination with tigecycline against multidrug-resistant (MDR) A. baumannii isolates from patients with wound infections. METHODS: The antimicrobial synergy between indolicidin and tigecycline was evaluated using the checkerboard broth microdilution method And anti-biofilm activity was assessed using the crystal violet assay. Ten isolates resistant to multiple antibiotics were identified and confirmed using the API 20-NE system. RESULTS: Fractional inhibitory concentration (FIC) values ranged from 0.97 to 250 µg/ml. The results demonstrated that the inhibitory activity of indolicidin and tigecycline was significantly enhanced when combined With FIC values between 0.046 and 0.312 µg/ml. The MIC of indolicidin for isolate A4 decreased from 62.5 to 0.97 µg/ml • While the MIC of tigecycline decreased from 500 to 15.6 µg/ml • Indicating a strong synergistic effect. Additionally The combination therapy led to a 78% reduction in biofilm formation. CONCLUSION: This study suggests a novel combination therapy for treating wound infections caused by MDR A. baumannii • Demonstrating significant efficacy in both bacterial inhibition and biofilm reduction.
Can Metabolic Biomarkers of Oxygen- Dependent Processes Determine Health Status of Pigeon Columba Livia F. Urbana?
Kurhaluk N, Hetmański T, Kamiński P … +1 more , Tkaczenko H
Cell Physiol Biochem · 2025 Feb · PMID 39957605 · Publisher ↗
BACKGROUND/AIMS: Anthropogenic impact is irreversibly changing natural habitats of birds. Changes caused by the bioaccumulation of trace metals can lead to the development of oxidative stress and affect oxygen-dependent...
BACKGROUND/AIMS: Anthropogenic impact is irreversibly changing natural habitats of birds. Changes caused by the bioaccumulation of trace metals can lead to the development of oxidative stress and affect oxygen-dependent metabolic pathways in bird tissues, which can be used as effective bioindicators in these conditions. The objectives of our study were (a) to investigate the tissue-specific activity of key enzymes involved in metabolic changes and energy production, including Krebs cycle enzymes, as well as variations in metabolites associated with oxygen-dependent processes; and (b) to apply multivariate regression analysis, using beta and correlation coefficients, to elucidate the mechanisms of adaptive responses in pigeons to environmental changes in lead-contaminated areas. METHODS: This study investigates the ecotoxicological effects on feral pigeons (Columba livia f. urbana) in their natural habitats. It examines the influence of key environmental factors, sex, and biochemical alterations across five tissues (liver, kidney, heart, muscle, and brain). The analysis includes the combined effects of these variables on biochemical biomarkers related to energy metabolism, oxidative stress, and antioxidant defenses, considering the levels of chemical elements present in the pigeons. The analyses involved two groups of pigeons, namely, 7 females and 10 males (n = 17) in the group sampled in Słupsk and 7 females and 7 males, (n = 14) in Szpęgawa that living in two areas in central part of Northern Poland, which differed in the level of anthropopressure. RESULTS: We report significant values of lead bioaccumulation in feathers of pigeons and the impact of this metal on the activities of Krebs cycle enzymes (succinate dehydrogenase, pyruvate dehydrogenase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase), biomarkers of oxygen-dependent processes (lactate dehydrogenase activity, lactate and pyruvate levels, and their ratio), and aminotransferases in different tissues of pigeons. CONCLUSION: Biomarkers of oxygen-dependent processes in five tissues of pigeons are depending on sex and environment. Pigeons from lead-exposed areas exhibited decreased antioxidant defence by biochemical alterations in tissues. Analytical model of oxidative stress biomarkers, Krebs cycle enzymes, and chemical elements is significant. Using multivariate regression analysis with beta- and correlative coefficients, relationships were shown for the optimal development of adaptation alterations in biochemical reactions in pigeons in response to the modification of their environments. Research on Columba livia f. urbana provides valuable insights into understanding the effects of anthropogenic pollution on bird physiology and offers practical methods for assessing environmental health.
MOTS-c Impact on Muscle Cell Differentiation and Metabolism Across Fiber Types.
Leciejewska N, Pruszyńska-Oszmałek E, Kołodziejski P … +3 more , Szczepankiewicz D, Nogowski L, Sassek M
Cell Physiol Biochem · 2025 Jan · PMID 39876762 · Publisher ↗
BACKGROUND/AIMS: MOTS-c belongs to a group of mitochondrial peptides involved in metabolic processes in the body. This peptide has garnered increasing attention since its discovery in 2015 because of its potential to ame...
BACKGROUND/AIMS: MOTS-c belongs to a group of mitochondrial peptides involved in metabolic processes in the body. This peptide has garnered increasing attention since its discovery in 2015 because of its potential to ameliorate metabolic parameters in animals with diabetes or insulin resistance. MOTS-c is involved in muscle metabolism; however, little is known about its role in fiber differentiation. METHODS: We conducted a study to explore the effect of MOTS-c on cellular processes using the C2C12 and L6 cell lines, representing different metabolic types of muscle fibers. The research methods were real-time PCR, Western blot, and lipid accumulation measurement. RESULTS: Notably, our investigations revealed that MOTS-c increased the survival of C2C12 cells at doses of 10 and 100 nM (p<0.01) and stimulated the phosphorylation of extracellular signal-regulated kinase within 5 min of incubation (p<0.05). Remarkably, these effects were not observed in L6 cells; however, both cell lines showed a reduced rate of proliferation. Furthermore, MOTS-c promotes the differentiation of C2C12 cells by increasing the expression of muscle regulatory factors, but it does not produce such an effect in L6 cells. Additionally, cells were treated with physiological concentrations of free fatty acids and MOTS-c, unveiling an augmentation in lipid accumulation observed in L6 cells and a decrease in lipid accumulation in C2C12 cells. CONCLUSION: In conclusion, our findings have suggested a diverse response to MOTS-c depending on the type of muscle fibers, particularly in the domains of survival, cell differentiation, and lipid accumulation.
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