Dr Badr S Qasem | Uniwersytet Przyrodniczy we Wrocławiu (original) (raw)

Papers by Dr Badr S Qasem

Research paper thumbnail of Trodusquemine (MSI-1436) Restores Metabolic Flexibility and Mitochondrial Dynamics in Insulin-Resistant Equine Hepatic Progenitor Cells (HPCs

Cells, 2024

Equine metabolic syndrome (EMS) is a significant global health concern in veterinary medicine. Th... more Equine metabolic syndrome (EMS) is a significant global health concern in veterinary medicine. There is increasing interest in utilizing molecular agents to modulate hepatocyte function for potential clinical applications. Recent studies have shown promising results in inhibiting protein tyrosine phosphatase (PTP1B) to maintain cell function in various models. In this study, we investigated the effects of the inhibitor Trodusquemine (MSI-1436) on equine hepatic progenitor cells (HPCs) under lipotoxic conditions. We examined proliferative activity, glucose uptake, and mitochondrial morphogenesis. Our study found that MSI-1436 promotes HPC entry into the cell cycle and protects them from palmitate-induced apoptosis by regulating mitochondrial dynamics and biogenesis. MSI-1436 also increases glucose uptake and protects HPCs from palmitate-induced stress by reorganizing the cells' morphological architecture. Furthermore, our findings suggest that MSI-1436 enhances 2-NBDG uptake by increasing the expression of SIRT1, which is associated with liver insulin sensitivity. It also promotes mitochondrial dynamics by modulating mitochondria quantity and morphotype as well as increasing the expression of PINK1, MFN1, and MFN2. Our study provides evidence that MSI-1436 has a positive impact on equine hepatic progenitor cells, indicating its potential therapeutic value in treating EMS and insulin dysregulation.

Research paper thumbnail of Cyclosporine A Delivery Platform for Veterinary Ophthalmology—A New Concept for Advanced Ophthalmology

Biomolecules, Oct 20, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Trodusquemine (MSI-1436) restores metabolic flexibility and mitochondrial dynamics in insulin-resistant equine hepatic progenitor cells (HPCs)

Equine metabolic syndrome (EMS) is a major health threat in veterinary endocrinology medicine wor... more Equine metabolic syndrome (EMS) is a major health threat in veterinary endocrinology medicine worldwide, and there is growing interest in utilizing molecular agents for modulation of hepatocyte function for potential clinical applications with recent studies showing promising results in the inhibition of PTP1B on adipose-derived stromal cells. In this study, we investigated the effects of MSI-1436 on equine hepatic progenitor cells (HPCs) in terms of their proliferative activity, glucose uptake, and mitochondrial morphogenesis under lipotoxic condition. Our study found that MSI-1436 promotes the entry of HPCs in the cell cycle and rescues them from palmitate-induced apoptosis by regulating mitochondrial dynamics and biogenesis. MSI-1436 also increases glucose uptake and protects HPCs from palmitate-induced stress by reorganizing the morphological architecture of the cells. Additionally, our findings suggest that MSI-1436 enhances the 2-NBDG internalization by increasing the expression of SIRT1, which is associated with liver insulin sensitivity, and promotes mitochondrial dynamics by modulating their number and morphotype through PINK1, MFN1, and MFN2 increased expression. Our study provides evidence that MSI-1436 has a positive impact on equine hepatic progenitor cells, indicating its potential therapeutic value in the treatment of EMS and insulin dysregulation.

Research paper thumbnail of Brain-Dead and Coma Patients Exhibit Different Serum Metabolic Profiles: A Novel Diagnostic Approach in Neurocritical Care

There is a clear difference between severe brain damage and brain death. However, in clinical pra... more There is a clear difference between severe brain damage and brain death. However, in clinical practice, the differentiation of these states can be challenging. Currently, there are no laboratory tools that facilitate brain death diagnosis. The aim of our study was to evaluate the utility of serum metabolomic analysis in differentiating coma patients (CP) from individuals with brain death (BD). Serum samples were collected from 23 adult individuals with established diagnosis of brain death and 24 patients in coma with Glasgow Coma Scale 3 or 4, with no other clinical symptoms of brain death for at least 7 days after sample collection. Serum metabolomic pro les were investigated using proton nuclear magnetic resonance (NMR) spectroscopy. The results obtained were examined by univariate and multivariate data analysis (PCA, PLS-DA, and OPLS-DA). Metabolic pro ling allowed us to quantify 43 resonance signals, of which 34 were identi ed. Multivariate statistical modeling revealed a highly signi cant separation between coma patients and brain-dead individuals, as well as strong predictive potential. The ndings not only highlight the potential of the metabolomic approach for distinguishing patients in coma from those in the state of brain death but also may provide an understanding of the pathogenic mechanisms underlying these conditions.

Research paper thumbnail of Post hoc analysis of fecal samples from responders and non-responders to Lactobacillus reuteri DSM 17938 intervention

Acta Biochimica Polonica, Sep 18, 2020

We compared fecal samples from responders and nonresponders to administration of Lactobacillus re... more We compared fecal samples from responders and nonresponders to administration of Lactobacillus reuteri DSM 17938. Data for this post hoc analysis were collected from an RCT assessing the efficacy of L. reuteri for the management of acute gastroenteritis. Responders were defined as subjects with diarrhea lasting no longer than 48 h. 44 children (17 responders and 27 non-responders) were analyzed. There were no differences in clinical characteristics and gut colonization between both groups. In the responder group, there were significantly lower levels of five metabolites before beginning of the intervention: lactate, choline, ethanol, creatine, and formate. The fecal calprotectin level did not differ between groups prior to the intervention, but its level was significantly lower after intervention in the responder group. Possibly, the responder group with a "metabolic niche", including lower level of metabolites, especially lactate, that are potential products of Lactobacillus genus, would determine the response to probiotic treatment. These findings need to be confirmed, but identification of some differences in the fecal metabolomics and the calprotectin level suggests that further studies are warranted.

Research paper thumbnail of Disease Differentiation and Monitoring of Anti-TNF Treatment in Rheumatoid Arthritis and Spondyloarthropathies

International Journal of Molecular Sciences, Jul 9, 2021

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Precision Nutrition in NAFLD: Effects of a High-Fiber Intervention on the Serum Metabolome of NAFD Patients—A Pilot Study

Nutrients, Dec 16, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of PLDLA/TPU Matrix Enriched with Cyclosporine A as a Therapeutic Platform for Immune-Mediated Keratitis (IMMK) in Horses

International Journal of Molecular Sciences, Mar 17, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Sex hormone-binding globulin (SHBG) mitigates ER stress and improves viability and insulin sensitivity in adipose-derived mesenchymal stem cells (ASC) of equine metabolic syndrome (EMS)-affected horses

Cell Communication and Signaling

Background Equine metabolic syndrome (EMS), which encompasses insulin resistance, low-grade infla... more Background Equine metabolic syndrome (EMS), which encompasses insulin resistance, low-grade inflammation and predisposition to laminitis is a critical endocrine disorder among the most prevalent conditions affecting horses from different breeds. According to the most recent research, low human sex hormone-binding globulin (SHBG) serum levels correlate with an increased risk of obesity, insulin resistance and diabetes, and may contribute to overall metabolic dysregulations. This study aimed to test whether exogenous SHBG could protect EMS affected adipose-derived stromal stem cells (EqASCEMS) from apoptosis, oxidative stress, ER stress and thus improve insulin sensitivity. Methods EqASCEMS wells were treated with two different concentrations (50 and 100 nM) of exogenous SHBG, whose biocompatibility was tested after 24, 48 and 72 h of incubation. Several parameters including cell viability, apoptosis, cell cycle, reactive oxygen species levels, ER stress, Pi3K/MAPK activation and insu...

Research paper thumbnail of Sex hormone-binding globulin (SHBG) mitigates ER stress and improves viability and insulin sensitivity in adipose-derived mesenchymal stem cells (ASC) of equine metabolic syndrome (EMS)-affected horses

Cell Communication and Signaling, 2023

Background Equine metabolic syndrome (EMS), which encompasses insulin resistance, low-grade infla... more Background Equine metabolic syndrome (EMS), which encompasses insulin resistance, low-grade inflammation and predisposition to laminitis is a critical endocrine disorder among the most prevalent conditions affecting horses from different breeds. According to the most recent research, low human sex hormone-binding globulin (SHBG) serum levels correlate with an increased risk of obesity, insulin resistance and diabetes, and may contribute to overall metabolic dysregulations. This study aimed to test whether exogenous SHBG could protect EMS affected adiposederived stromal stem cells (EqASC EMS) from apoptosis, oxidative stress, ER stress and thus improve insulin sensitivity. Methods EqASC EMS wells were treated with two different concentrations (50 and 100 nM) of exogenous SHBG, whose biocompatibility was tested after 24, 48 and 72 h of incubation. Several parameters including cell viability, apoptosis, cell cycle, reactive oxygen species levels, ER stress, Pi3K/MAPK activation and insulin transducers expression were analysed. Results Obtained data demonstrated that exogenous SHBG treatment significantly promoted ASCs cells proliferation, cell cycle and survival with reduced expression of p53 and p21 pro-apoptotic mediators. Furthermore, SHBG alleviated the oxidative stress caused by EMS and reduced the overaccumulation of intracellular ROS, by reducing ROS + cell percentage and regulating gene expression of endogenous antioxidant enzymes (Sod 1, Cat, GPx), SHBG treatment exhibited antioxidant activity by modulating total nitric oxide (NO) levels in EMS cells as well. SHBG treatment dampened the activation of ER stress sensors and effectors in EqASC EMS cells via the upregulation of MiR-7a-5p, the decrease in the expression levels of ATF-6, CHOP and eiF2A and the restoration of PDIA3 chaperone protein levels. As a consequence, SHBG application substantially improved insulin sensitivity through the modulation of Pi3K/Akt/ Glut4 insulin signalling cascades. Conclusion Our results suggest that the SHBG is endowed with crucial beneficial effects on ASCs metabolic activities and could serve as a valuable therapeutic target for the development of efficient EMS treatment protocols.

Research paper thumbnail of Trodusquemine (MSI-1436) restores metabolic flexibility and mitochondrial dynamics in insulin-resistant equine hepatic progenitor cells (HPCs)

Equine metabolic syndrome (EMS) is a major health threat in veterinary endocrinology medicine wor... more Equine metabolic syndrome (EMS) is a major health threat in veterinary endocrinology medicine worldwide, and there is growing interest in utilizing molecular agents for modulation of hepatocyte function for potential clinical applications with recent studies showing promising results in the inhibition of PTP1B on adipose-derived stromal cells. In this study, we investigated the effects of MSI-1436 on equine hepatic progenitor cells (HPCs) in terms of their proliferative activity, glucose uptake, and mitochondrial morphogenesis under lipotoxic condition. Our study found that MSI-1436 promotes the entry of HPCs in the cell cycle and rescues them from palmitate-induced apoptosis by regulating mitochondrial dynamics and biogenesis. MSI-1436 also increases glucose uptake and protects HPCs from palmitate-induced stress by reorganizing the morphological architecture of the cells. Additionally, our findings suggest that MSI-1436 enhances the 2-NBDG internalization by increasing the expressi...

Research paper thumbnail of PLDLA/TPU Matrix Enriched with Cyclosporine A as a Therapeutic Platform for Immune-Mediated Keratitis (IMMK) in Horses

International Journal of Molecular Sciences

The purpose of this study was to describe the use of PLDLA/TPU matrix enriched with cyclosporine ... more The purpose of this study was to describe the use of PLDLA/TPU matrix enriched with cyclosporine A (CsA) as a therapeutic platform in horses with immune-mediated keratitis (IMMK) with an in vitro evaluation CsA release and degradation of the blend as well as determination of the safety and efficacy of that platform used in the animal model. The kinetics of the CsA release from matrices constructed of thermoplastic polyurethane (TPU) polymer and a copolymer of L-lactide with DL-lactide (PLDLA) (80:20) in the TPU (10%) and a PLDL (90%) polymer blend were studied. Moreover, we used the STF (Simulated Tear Fluid) at 37 °C as a biological environment to assess the CsA release and its degradation. Additionally, the platform described above was injected subconjunctival in the dorsolateral quadrant of the globe after standing sedation of horses with diagnosed superficial and mid-stromal IMMK. The obtained results indicated that the CsA release rate in the fifth week of the study increased s...

Research paper thumbnail of Precision Nutrition in NAFLD: Effects of a High-Fiber Intervention on the Serum Metabolome of NAFD Patients—A Pilot Study

Nutrients

Non-alcoholic fatty liver disease (NAFLD) is associated with dysfunction of the intestinal microb... more Non-alcoholic fatty liver disease (NAFLD) is associated with dysfunction of the intestinal microbiota and its metabolites. We aimed to assess whether replacing bread with high-fiber buns beneficially changes the metabolome in NAFLD patients. This study involved 27 adult patients with NAFLD validated by FibroScan® (CAP ≥ 234 dB/m). Patients were asked to replace their existing bread for two meals with high-fiber buns. In this way, the patients ate two rolls every day for 2 months. The following parameters were analysed (at the beginning and after 2 months): the anthropometric data (BIA), eating habits (24 h food recalls), gut barrier markers (lipopolysaccharide S and liposaccharide binding protein (LPS, LBP)), serum short-chain fatty acids (SCFAs) and branched chain fatty acids (BCFAs) by GC/MS chromatography, as well as serum metabolites (by 1H NMR spectroscopy). After 2 months of high-fiber roll consumption, the reduction of liver steatosis was observed (change Fibroscan CAP values...

Research paper thumbnail of PLDLA/TPU Matrix Enriched with Cyclosporine A as a Therapeutic Platform for Immune-Mediated Keratitis (IMMK) in Horses

International Journal of Molecular Sciences, 2023

The purpose of this study was to describe the use of PLDLA/TPU matrix enriched with cyclosporine ... more The purpose of this study was to describe the use of PLDLA/TPU matrix enriched with cyclosporine A (CsA) as a therapeutic platform in horses with immune-mediated keratitis (IMMK) with an in vitro evaluation CsA release and degradation of the blend as well as determination of the safety and efficacy of that platform used in the animal model. The kinetics of the CsA release from matrices constructed of thermoplastic polyurethane (TPU) polymer and a copolymer of L-lactide with DL-lactide (PLDLA) (80:20) in the TPU (10%) and a PLDL (90%) polymer blend were studied. Moreover, we used the STF (Simulated Tear Fluid) at 37 • C as a biological environment to assess the CsA release and its degradation. Additionally, the platform described above was injected subconjunctival in the dorsolateral quadrant of the globe after standing sedation of horses with diagnosed superficial and mid-stromal IMMK. The obtained results indicated that the CsA release rate in the fifth week of the study increased significantly by the value of 0.3% compared to previous weeks. In all of the cases, the TPU/PLA doped with 12 mg of the CsA platform effectively reduced the clinical symptoms of keratitis, leading to the complete remission of the corneal opacity and infiltration four weeks post-injection. The results from this study showed that the PLDLA/TPU matrix enriched with the CsA platform was well tolerated by the equine model and effective in treating superficial and mid-stromal IMMK.

Research paper thumbnail of Precision Nutrition in NAFLD: Effects of a High-Fiber Intervention on the Serum Metabolome of NAFD Patients-A Pilot Study

Nutrients, 2022

Non-alcoholic fatty liver disease (NAFLD) is associated with dysfunction of the intestinal microb... more Non-alcoholic fatty liver disease (NAFLD) is associated with dysfunction of the intestinal microbiota and its metabolites. We aimed to assess whether replacing bread with high-fiber buns beneficially changes the metabolome in NAFLD patients. This study involved 27 adult patients with NAFLD validated by FibroScan® (CAP  234 dB/m). Patients were asked to replace their existing bread for two meals with high-fiber buns. In this way, the patients ate two rolls every day for 2 months. The following parameters were analysed (at the beginning and after 2 months): the anthropometric data (BIA), eating habits (24 h food recalls), gut barrier markers (lipopolysaccharide S and liposaccharide binding protein (LPS, LBP)), serum short-chain fatty acids (SCFAs) and branched chain fatty acids (BCFAs) by GC/MS chromatography, as well as serum metabolites (by 1H NMR
spectroscopy). After 2 months of high-fiber roll consumption, the reduction of liver steatosis was observed (change Fibroscan CAP values from 309–277 dB/m). In serum propionate, acetate, isovaleric, and 2-methylbutyric decrease was observed. Proline, choline and one unknown molecule had higher relative concentration in serum at endpoint. A fiber-targeted dietary approach may be helpful in the treatment of patients with NAFLD, by changing the serum microbiota metabolome.

Research paper thumbnail of Cyclosporine A Delivery Platform for Veterinary Ophthalmology—A New Concept for Advanced Ophthalmology

Biomolecules

Cyclosporine A (CsA) is a selective and reversible immunosuppressant agent that is widely used as... more Cyclosporine A (CsA) is a selective and reversible immunosuppressant agent that is widely used as a medication for a wide spectrum of diseases in humans such as graft versus host disease, non-infectious uveitis, rheumatoid arthritis, psoriasis, and atopic dermatitis. Furthermore, the CsA is used to treat keratoconjunctivitis sicca, chronic superficial keratitis, immune-mediated keratitis and equine recurrent uveitis in animals. The selective activity of Cyclosporine A (CsA) was demonstrated to be an immunomodulation characteristic of T-lymphocyte proliferation and inhibits cytokine gene expression. Moreover, the lipophilic characteristics with poor bioavailability and low solubility in water, besides the side effects, force the need to develop new formulations and devices that will provide adequate penetration into the anterior and posterior segments of the eye. This review aims to summarize the effectiveness and safety of cyclosporine A delivery platforms in veterinary ophthalmology.

Research paper thumbnail of Post hoc analysis of fecal samples from responders and non-responders to Lactobacillus reuteri DSM 17938 intervention

Acta Biochimica Polonica, 2020

We compared fecal samples from responders and non-responders to administration of Lactobacillus r... more We compared fecal samples from responders and non-responders to administration of Lactobacillus reuteri DSM 17938. Data for this post hoc analysis were collected from an RCT assessing the efficacy of L. reuteri for the management of acute gastroenteritis. Responders were defined as subjects with diarrhea lasting no longer than 48 h. 44 children (17 responders and 27 non-responders) were analyzed. There were no differences in clinical characteristics and gut colonization between both groups. In the responder group, there were significantly lower levels of five metabolites before beginning of the intervention: lactate, choline, ethanol, creatine, and formate. The fecal calprotectin level did not differ between groups prior to the intervention, but its level was significantly lower after intervention in the responder group. Possibly, the responder group with a “metabolic niche”, including lower level of metabolites, especially lactate, that are potential products of Lactobacillus genus...

Research paper thumbnail of The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts

The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts... more The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts. June 4-7, 2019, Szczyrk, Polan

Research paper thumbnail of Effect of Protoberberine-Rich Fraction of Chelidonium majus L. on Endometriosis Regression

Pharmaceutics, 2021

Endometriosis is a gynecological disease defined by the presence of endometrial tissue outside th... more Endometriosis is a gynecological disease defined by the presence of endometrial tissue outside the uterus. To date, the effective treatment of this disease is still based on invasive surgery or laparoscopy. Chelidonium majus L. (Papaveraceae) belongs to medicinal, latex-bearing plants. Extracts from the plant are a rich source of pharmacologically active agents. Protoberberine compounds derived from C. majus possess anticancer and antiproliferative activities. In the present study of a rat model of endometriosis, we investigated the influence of the plant protoberberine-rich fraction (BBR) obtained from the medicinal plant C. majus on the development of endometriosis. To understand of BBR therapeutic potential for endometriosis, metabolomics has been applied to study. BBR was prepared from an ethanolic extract of dry plants C. majus. Rats (n = 16) with confirmed endometriosis were treated with BBR administered orally (1 g/kg) for 14 days. Blood serum samples were collected from all ...

Research paper thumbnail of Disease Differentiation and Monitoring of Anti-TNF Treatment in Rheumatoid Arthritis and Spondyloarthropathies

International Journal of Molecular Sciences, 2021

Rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) are compreh... more Rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) are comprehensive immunological disorders. The treatment of these disorders is limited to ameliorating the symptoms and improving the quality of life of patients. In this study, serum samples from RA, AS, and PsA patients were analyzed with metabolomic tools employing the 1H NMR method in combination with univariate and multivariate analyses. The results obtained in this study showed that the changes in metabolites were the highest for AS > RA > PsA. The study demonstrated that the time until remission or until low disease activity is achieved is shortest (approximately three months) for AS, longer for RA and longest for PsA. The statistically common metabolite that was found to be negatively correlated with the healing processes of these disorders is ethanol, which may indicate the involvement of the gut microflora and/or the breakdown of malondialdehyde as a cell membrane lipid peroxide pro...

Research paper thumbnail of Trodusquemine (MSI-1436) Restores Metabolic Flexibility and Mitochondrial Dynamics in Insulin-Resistant Equine Hepatic Progenitor Cells (HPCs

Cells, 2024

Equine metabolic syndrome (EMS) is a significant global health concern in veterinary medicine. Th... more Equine metabolic syndrome (EMS) is a significant global health concern in veterinary medicine. There is increasing interest in utilizing molecular agents to modulate hepatocyte function for potential clinical applications. Recent studies have shown promising results in inhibiting protein tyrosine phosphatase (PTP1B) to maintain cell function in various models. In this study, we investigated the effects of the inhibitor Trodusquemine (MSI-1436) on equine hepatic progenitor cells (HPCs) under lipotoxic conditions. We examined proliferative activity, glucose uptake, and mitochondrial morphogenesis. Our study found that MSI-1436 promotes HPC entry into the cell cycle and protects them from palmitate-induced apoptosis by regulating mitochondrial dynamics and biogenesis. MSI-1436 also increases glucose uptake and protects HPCs from palmitate-induced stress by reorganizing the cells' morphological architecture. Furthermore, our findings suggest that MSI-1436 enhances 2-NBDG uptake by increasing the expression of SIRT1, which is associated with liver insulin sensitivity. It also promotes mitochondrial dynamics by modulating mitochondria quantity and morphotype as well as increasing the expression of PINK1, MFN1, and MFN2. Our study provides evidence that MSI-1436 has a positive impact on equine hepatic progenitor cells, indicating its potential therapeutic value in treating EMS and insulin dysregulation.

Research paper thumbnail of Cyclosporine A Delivery Platform for Veterinary Ophthalmology—A New Concept for Advanced Ophthalmology

Biomolecules, Oct 20, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Trodusquemine (MSI-1436) restores metabolic flexibility and mitochondrial dynamics in insulin-resistant equine hepatic progenitor cells (HPCs)

Equine metabolic syndrome (EMS) is a major health threat in veterinary endocrinology medicine wor... more Equine metabolic syndrome (EMS) is a major health threat in veterinary endocrinology medicine worldwide, and there is growing interest in utilizing molecular agents for modulation of hepatocyte function for potential clinical applications with recent studies showing promising results in the inhibition of PTP1B on adipose-derived stromal cells. In this study, we investigated the effects of MSI-1436 on equine hepatic progenitor cells (HPCs) in terms of their proliferative activity, glucose uptake, and mitochondrial morphogenesis under lipotoxic condition. Our study found that MSI-1436 promotes the entry of HPCs in the cell cycle and rescues them from palmitate-induced apoptosis by regulating mitochondrial dynamics and biogenesis. MSI-1436 also increases glucose uptake and protects HPCs from palmitate-induced stress by reorganizing the morphological architecture of the cells. Additionally, our findings suggest that MSI-1436 enhances the 2-NBDG internalization by increasing the expression of SIRT1, which is associated with liver insulin sensitivity, and promotes mitochondrial dynamics by modulating their number and morphotype through PINK1, MFN1, and MFN2 increased expression. Our study provides evidence that MSI-1436 has a positive impact on equine hepatic progenitor cells, indicating its potential therapeutic value in the treatment of EMS and insulin dysregulation.

Research paper thumbnail of Brain-Dead and Coma Patients Exhibit Different Serum Metabolic Profiles: A Novel Diagnostic Approach in Neurocritical Care

There is a clear difference between severe brain damage and brain death. However, in clinical pra... more There is a clear difference between severe brain damage and brain death. However, in clinical practice, the differentiation of these states can be challenging. Currently, there are no laboratory tools that facilitate brain death diagnosis. The aim of our study was to evaluate the utility of serum metabolomic analysis in differentiating coma patients (CP) from individuals with brain death (BD). Serum samples were collected from 23 adult individuals with established diagnosis of brain death and 24 patients in coma with Glasgow Coma Scale 3 or 4, with no other clinical symptoms of brain death for at least 7 days after sample collection. Serum metabolomic pro les were investigated using proton nuclear magnetic resonance (NMR) spectroscopy. The results obtained were examined by univariate and multivariate data analysis (PCA, PLS-DA, and OPLS-DA). Metabolic pro ling allowed us to quantify 43 resonance signals, of which 34 were identi ed. Multivariate statistical modeling revealed a highly signi cant separation between coma patients and brain-dead individuals, as well as strong predictive potential. The ndings not only highlight the potential of the metabolomic approach for distinguishing patients in coma from those in the state of brain death but also may provide an understanding of the pathogenic mechanisms underlying these conditions.

Research paper thumbnail of Post hoc analysis of fecal samples from responders and non-responders to Lactobacillus reuteri DSM 17938 intervention

Acta Biochimica Polonica, Sep 18, 2020

We compared fecal samples from responders and nonresponders to administration of Lactobacillus re... more We compared fecal samples from responders and nonresponders to administration of Lactobacillus reuteri DSM 17938. Data for this post hoc analysis were collected from an RCT assessing the efficacy of L. reuteri for the management of acute gastroenteritis. Responders were defined as subjects with diarrhea lasting no longer than 48 h. 44 children (17 responders and 27 non-responders) were analyzed. There were no differences in clinical characteristics and gut colonization between both groups. In the responder group, there were significantly lower levels of five metabolites before beginning of the intervention: lactate, choline, ethanol, creatine, and formate. The fecal calprotectin level did not differ between groups prior to the intervention, but its level was significantly lower after intervention in the responder group. Possibly, the responder group with a "metabolic niche", including lower level of metabolites, especially lactate, that are potential products of Lactobacillus genus, would determine the response to probiotic treatment. These findings need to be confirmed, but identification of some differences in the fecal metabolomics and the calprotectin level suggests that further studies are warranted.

Research paper thumbnail of Disease Differentiation and Monitoring of Anti-TNF Treatment in Rheumatoid Arthritis and Spondyloarthropathies

International Journal of Molecular Sciences, Jul 9, 2021

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Precision Nutrition in NAFLD: Effects of a High-Fiber Intervention on the Serum Metabolome of NAFD Patients—A Pilot Study

Nutrients, Dec 16, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of PLDLA/TPU Matrix Enriched with Cyclosporine A as a Therapeutic Platform for Immune-Mediated Keratitis (IMMK) in Horses

International Journal of Molecular Sciences, Mar 17, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Sex hormone-binding globulin (SHBG) mitigates ER stress and improves viability and insulin sensitivity in adipose-derived mesenchymal stem cells (ASC) of equine metabolic syndrome (EMS)-affected horses

Cell Communication and Signaling

Background Equine metabolic syndrome (EMS), which encompasses insulin resistance, low-grade infla... more Background Equine metabolic syndrome (EMS), which encompasses insulin resistance, low-grade inflammation and predisposition to laminitis is a critical endocrine disorder among the most prevalent conditions affecting horses from different breeds. According to the most recent research, low human sex hormone-binding globulin (SHBG) serum levels correlate with an increased risk of obesity, insulin resistance and diabetes, and may contribute to overall metabolic dysregulations. This study aimed to test whether exogenous SHBG could protect EMS affected adipose-derived stromal stem cells (EqASCEMS) from apoptosis, oxidative stress, ER stress and thus improve insulin sensitivity. Methods EqASCEMS wells were treated with two different concentrations (50 and 100 nM) of exogenous SHBG, whose biocompatibility was tested after 24, 48 and 72 h of incubation. Several parameters including cell viability, apoptosis, cell cycle, reactive oxygen species levels, ER stress, Pi3K/MAPK activation and insu...

Research paper thumbnail of Sex hormone-binding globulin (SHBG) mitigates ER stress and improves viability and insulin sensitivity in adipose-derived mesenchymal stem cells (ASC) of equine metabolic syndrome (EMS)-affected horses

Cell Communication and Signaling, 2023

Background Equine metabolic syndrome (EMS), which encompasses insulin resistance, low-grade infla... more Background Equine metabolic syndrome (EMS), which encompasses insulin resistance, low-grade inflammation and predisposition to laminitis is a critical endocrine disorder among the most prevalent conditions affecting horses from different breeds. According to the most recent research, low human sex hormone-binding globulin (SHBG) serum levels correlate with an increased risk of obesity, insulin resistance and diabetes, and may contribute to overall metabolic dysregulations. This study aimed to test whether exogenous SHBG could protect EMS affected adiposederived stromal stem cells (EqASC EMS) from apoptosis, oxidative stress, ER stress and thus improve insulin sensitivity. Methods EqASC EMS wells were treated with two different concentrations (50 and 100 nM) of exogenous SHBG, whose biocompatibility was tested after 24, 48 and 72 h of incubation. Several parameters including cell viability, apoptosis, cell cycle, reactive oxygen species levels, ER stress, Pi3K/MAPK activation and insulin transducers expression were analysed. Results Obtained data demonstrated that exogenous SHBG treatment significantly promoted ASCs cells proliferation, cell cycle and survival with reduced expression of p53 and p21 pro-apoptotic mediators. Furthermore, SHBG alleviated the oxidative stress caused by EMS and reduced the overaccumulation of intracellular ROS, by reducing ROS + cell percentage and regulating gene expression of endogenous antioxidant enzymes (Sod 1, Cat, GPx), SHBG treatment exhibited antioxidant activity by modulating total nitric oxide (NO) levels in EMS cells as well. SHBG treatment dampened the activation of ER stress sensors and effectors in EqASC EMS cells via the upregulation of MiR-7a-5p, the decrease in the expression levels of ATF-6, CHOP and eiF2A and the restoration of PDIA3 chaperone protein levels. As a consequence, SHBG application substantially improved insulin sensitivity through the modulation of Pi3K/Akt/ Glut4 insulin signalling cascades. Conclusion Our results suggest that the SHBG is endowed with crucial beneficial effects on ASCs metabolic activities and could serve as a valuable therapeutic target for the development of efficient EMS treatment protocols.

Research paper thumbnail of Trodusquemine (MSI-1436) restores metabolic flexibility and mitochondrial dynamics in insulin-resistant equine hepatic progenitor cells (HPCs)

Equine metabolic syndrome (EMS) is a major health threat in veterinary endocrinology medicine wor... more Equine metabolic syndrome (EMS) is a major health threat in veterinary endocrinology medicine worldwide, and there is growing interest in utilizing molecular agents for modulation of hepatocyte function for potential clinical applications with recent studies showing promising results in the inhibition of PTP1B on adipose-derived stromal cells. In this study, we investigated the effects of MSI-1436 on equine hepatic progenitor cells (HPCs) in terms of their proliferative activity, glucose uptake, and mitochondrial morphogenesis under lipotoxic condition. Our study found that MSI-1436 promotes the entry of HPCs in the cell cycle and rescues them from palmitate-induced apoptosis by regulating mitochondrial dynamics and biogenesis. MSI-1436 also increases glucose uptake and protects HPCs from palmitate-induced stress by reorganizing the morphological architecture of the cells. Additionally, our findings suggest that MSI-1436 enhances the 2-NBDG internalization by increasing the expressi...

Research paper thumbnail of PLDLA/TPU Matrix Enriched with Cyclosporine A as a Therapeutic Platform for Immune-Mediated Keratitis (IMMK) in Horses

International Journal of Molecular Sciences

The purpose of this study was to describe the use of PLDLA/TPU matrix enriched with cyclosporine ... more The purpose of this study was to describe the use of PLDLA/TPU matrix enriched with cyclosporine A (CsA) as a therapeutic platform in horses with immune-mediated keratitis (IMMK) with an in vitro evaluation CsA release and degradation of the blend as well as determination of the safety and efficacy of that platform used in the animal model. The kinetics of the CsA release from matrices constructed of thermoplastic polyurethane (TPU) polymer and a copolymer of L-lactide with DL-lactide (PLDLA) (80:20) in the TPU (10%) and a PLDL (90%) polymer blend were studied. Moreover, we used the STF (Simulated Tear Fluid) at 37 °C as a biological environment to assess the CsA release and its degradation. Additionally, the platform described above was injected subconjunctival in the dorsolateral quadrant of the globe after standing sedation of horses with diagnosed superficial and mid-stromal IMMK. The obtained results indicated that the CsA release rate in the fifth week of the study increased s...

Research paper thumbnail of Precision Nutrition in NAFLD: Effects of a High-Fiber Intervention on the Serum Metabolome of NAFD Patients—A Pilot Study

Nutrients

Non-alcoholic fatty liver disease (NAFLD) is associated with dysfunction of the intestinal microb... more Non-alcoholic fatty liver disease (NAFLD) is associated with dysfunction of the intestinal microbiota and its metabolites. We aimed to assess whether replacing bread with high-fiber buns beneficially changes the metabolome in NAFLD patients. This study involved 27 adult patients with NAFLD validated by FibroScan® (CAP ≥ 234 dB/m). Patients were asked to replace their existing bread for two meals with high-fiber buns. In this way, the patients ate two rolls every day for 2 months. The following parameters were analysed (at the beginning and after 2 months): the anthropometric data (BIA), eating habits (24 h food recalls), gut barrier markers (lipopolysaccharide S and liposaccharide binding protein (LPS, LBP)), serum short-chain fatty acids (SCFAs) and branched chain fatty acids (BCFAs) by GC/MS chromatography, as well as serum metabolites (by 1H NMR spectroscopy). After 2 months of high-fiber roll consumption, the reduction of liver steatosis was observed (change Fibroscan CAP values...

Research paper thumbnail of PLDLA/TPU Matrix Enriched with Cyclosporine A as a Therapeutic Platform for Immune-Mediated Keratitis (IMMK) in Horses

International Journal of Molecular Sciences, 2023

The purpose of this study was to describe the use of PLDLA/TPU matrix enriched with cyclosporine ... more The purpose of this study was to describe the use of PLDLA/TPU matrix enriched with cyclosporine A (CsA) as a therapeutic platform in horses with immune-mediated keratitis (IMMK) with an in vitro evaluation CsA release and degradation of the blend as well as determination of the safety and efficacy of that platform used in the animal model. The kinetics of the CsA release from matrices constructed of thermoplastic polyurethane (TPU) polymer and a copolymer of L-lactide with DL-lactide (PLDLA) (80:20) in the TPU (10%) and a PLDL (90%) polymer blend were studied. Moreover, we used the STF (Simulated Tear Fluid) at 37 • C as a biological environment to assess the CsA release and its degradation. Additionally, the platform described above was injected subconjunctival in the dorsolateral quadrant of the globe after standing sedation of horses with diagnosed superficial and mid-stromal IMMK. The obtained results indicated that the CsA release rate in the fifth week of the study increased significantly by the value of 0.3% compared to previous weeks. In all of the cases, the TPU/PLA doped with 12 mg of the CsA platform effectively reduced the clinical symptoms of keratitis, leading to the complete remission of the corneal opacity and infiltration four weeks post-injection. The results from this study showed that the PLDLA/TPU matrix enriched with the CsA platform was well tolerated by the equine model and effective in treating superficial and mid-stromal IMMK.

Research paper thumbnail of Precision Nutrition in NAFLD: Effects of a High-Fiber Intervention on the Serum Metabolome of NAFD Patients-A Pilot Study

Nutrients, 2022

Non-alcoholic fatty liver disease (NAFLD) is associated with dysfunction of the intestinal microb... more Non-alcoholic fatty liver disease (NAFLD) is associated with dysfunction of the intestinal microbiota and its metabolites. We aimed to assess whether replacing bread with high-fiber buns beneficially changes the metabolome in NAFLD patients. This study involved 27 adult patients with NAFLD validated by FibroScan® (CAP  234 dB/m). Patients were asked to replace their existing bread for two meals with high-fiber buns. In this way, the patients ate two rolls every day for 2 months. The following parameters were analysed (at the beginning and after 2 months): the anthropometric data (BIA), eating habits (24 h food recalls), gut barrier markers (lipopolysaccharide S and liposaccharide binding protein (LPS, LBP)), serum short-chain fatty acids (SCFAs) and branched chain fatty acids (BCFAs) by GC/MS chromatography, as well as serum metabolites (by 1H NMR
spectroscopy). After 2 months of high-fiber roll consumption, the reduction of liver steatosis was observed (change Fibroscan CAP values from 309–277 dB/m). In serum propionate, acetate, isovaleric, and 2-methylbutyric decrease was observed. Proline, choline and one unknown molecule had higher relative concentration in serum at endpoint. A fiber-targeted dietary approach may be helpful in the treatment of patients with NAFLD, by changing the serum microbiota metabolome.

Research paper thumbnail of Cyclosporine A Delivery Platform for Veterinary Ophthalmology—A New Concept for Advanced Ophthalmology

Biomolecules

Cyclosporine A (CsA) is a selective and reversible immunosuppressant agent that is widely used as... more Cyclosporine A (CsA) is a selective and reversible immunosuppressant agent that is widely used as a medication for a wide spectrum of diseases in humans such as graft versus host disease, non-infectious uveitis, rheumatoid arthritis, psoriasis, and atopic dermatitis. Furthermore, the CsA is used to treat keratoconjunctivitis sicca, chronic superficial keratitis, immune-mediated keratitis and equine recurrent uveitis in animals. The selective activity of Cyclosporine A (CsA) was demonstrated to be an immunomodulation characteristic of T-lymphocyte proliferation and inhibits cytokine gene expression. Moreover, the lipophilic characteristics with poor bioavailability and low solubility in water, besides the side effects, force the need to develop new formulations and devices that will provide adequate penetration into the anterior and posterior segments of the eye. This review aims to summarize the effectiveness and safety of cyclosporine A delivery platforms in veterinary ophthalmology.

Research paper thumbnail of Post hoc analysis of fecal samples from responders and non-responders to Lactobacillus reuteri DSM 17938 intervention

Acta Biochimica Polonica, 2020

We compared fecal samples from responders and non-responders to administration of Lactobacillus r... more We compared fecal samples from responders and non-responders to administration of Lactobacillus reuteri DSM 17938. Data for this post hoc analysis were collected from an RCT assessing the efficacy of L. reuteri for the management of acute gastroenteritis. Responders were defined as subjects with diarrhea lasting no longer than 48 h. 44 children (17 responders and 27 non-responders) were analyzed. There were no differences in clinical characteristics and gut colonization between both groups. In the responder group, there were significantly lower levels of five metabolites before beginning of the intervention: lactate, choline, ethanol, creatine, and formate. The fecal calprotectin level did not differ between groups prior to the intervention, but its level was significantly lower after intervention in the responder group. Possibly, the responder group with a “metabolic niche”, including lower level of metabolites, especially lactate, that are potential products of Lactobacillus genus...

Research paper thumbnail of The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts

The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts... more The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts. June 4-7, 2019, Szczyrk, Polan

Research paper thumbnail of Effect of Protoberberine-Rich Fraction of Chelidonium majus L. on Endometriosis Regression

Pharmaceutics, 2021

Endometriosis is a gynecological disease defined by the presence of endometrial tissue outside th... more Endometriosis is a gynecological disease defined by the presence of endometrial tissue outside the uterus. To date, the effective treatment of this disease is still based on invasive surgery or laparoscopy. Chelidonium majus L. (Papaveraceae) belongs to medicinal, latex-bearing plants. Extracts from the plant are a rich source of pharmacologically active agents. Protoberberine compounds derived from C. majus possess anticancer and antiproliferative activities. In the present study of a rat model of endometriosis, we investigated the influence of the plant protoberberine-rich fraction (BBR) obtained from the medicinal plant C. majus on the development of endometriosis. To understand of BBR therapeutic potential for endometriosis, metabolomics has been applied to study. BBR was prepared from an ethanolic extract of dry plants C. majus. Rats (n = 16) with confirmed endometriosis were treated with BBR administered orally (1 g/kg) for 14 days. Blood serum samples were collected from all ...

Research paper thumbnail of Disease Differentiation and Monitoring of Anti-TNF Treatment in Rheumatoid Arthritis and Spondyloarthropathies

International Journal of Molecular Sciences, 2021

Rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) are compreh... more Rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) are comprehensive immunological disorders. The treatment of these disorders is limited to ameliorating the symptoms and improving the quality of life of patients. In this study, serum samples from RA, AS, and PsA patients were analyzed with metabolomic tools employing the 1H NMR method in combination with univariate and multivariate analyses. The results obtained in this study showed that the changes in metabolites were the highest for AS > RA > PsA. The study demonstrated that the time until remission or until low disease activity is achieved is shortest (approximately three months) for AS, longer for RA and longest for PsA. The statistically common metabolite that was found to be negatively correlated with the healing processes of these disorders is ethanol, which may indicate the involvement of the gut microflora and/or the breakdown of malondialdehyde as a cell membrane lipid peroxide pro...

Research paper thumbnail of BIOACTIVITY SAMPLES WITH SiO 2 -Y 2 O 3 CERAMIC LAYERS PRODUCED BY SOL-GEL METHOD

ENGINEERING OF BIOMATERIALS, 2020

316L stainless steel is widely used in implantology, although biological complications may result... more 316L stainless steel is widely used in implantology, although biological complications may result from its insufficient mechanical properties and low corrosion resistance in the human body. In order to improve the corrosion resistance of 316L steel and its bioactivity,
coatings are applied, e.g. ceramic layers that can improve the proliferation of living cells and barrier protection in the human body