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Pathophysiology, Volume 32, Issue 1 (March 2025) – 9 articles

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24 pages, 4240 KiB  
Review
Mitochondrial Dysfunction in Diabetes: Shedding Light on a Widespread Oversight
by Franklyn Nonso Iheagwam, Amarachi Joy Joseph, Eniola Deborah Adedoyin, Olawumi Toyin Iheagwam and Samuel Akpoyowvare Ejoh
Pathophysiology 2025, 32(1), 9; https://doi.org/10.3390/pathophysiology32010009 - 13 Feb 2025
Abstract
Diabetes mellitus represents a complicated metabolic condition marked by ongoing hyperglycemia arising from impaired insulin secretion, inadequate insulin action, or a combination of both. Mitochondrial dysfunction has emerged as a significant contributor to the aetiology of diabetes, affecting various metabolic processes critical for [...] Read more.
Diabetes mellitus represents a complicated metabolic condition marked by ongoing hyperglycemia arising from impaired insulin secretion, inadequate insulin action, or a combination of both. Mitochondrial dysfunction has emerged as a significant contributor to the aetiology of diabetes, affecting various metabolic processes critical for glucose homeostasis. This review aims to elucidate the complex link between mitochondrial dysfunction and diabetes, covering the spectrum of diabetes types, the role of mitochondria in insulin resistance, highlighting pathophysiological mechanisms, mitochondrial DNA damage, and altered mitochondrial biogenesis and dynamics. Additionally, it discusses the clinical implications and complications of mitochondrial dysfunction in diabetes and its complications, diagnostic approaches for assessing mitochondrial function in diabetics, therapeutic strategies, future directions, and research opportunities. Full article
(This article belongs to the Collection Feature Papers in Pathophysiology)
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10 pages, 1497 KiB  
Article
Low Serum Methylglyoxal Levels Correlate with Psoriasis Severity and Inflammatory Response Indices
by Aleksandra Damasiewicz-Bodzek, Agnieszka Nowak, Maciej Maciejczyk, Sławomir Waligóra and Brygida Przywara-Chowaniec
Pathophysiology 2025, 32(1), 8; https://doi.org/10.3390/pathophysiology32010008 - 3 Feb 2025
Abstract
Psoriasis is a multifactorial inflammatory disease. Methylglyoxal (MG) is a highly reactive dicarbonyl compound responsible for dicarbonyl stress in some inflammatory conditions, and it may play a role in the etiopathogenesis of psoriasis. Methods: A total of 50 patients with psoriasis and 35 [...] Read more.
Psoriasis is a multifactorial inflammatory disease. Methylglyoxal (MG) is a highly reactive dicarbonyl compound responsible for dicarbonyl stress in some inflammatory conditions, and it may play a role in the etiopathogenesis of psoriasis. Methods: A total of 50 patients with psoriasis and 35 healthy individuals participated in this study. The following indices were assessed in patients: Body Surface Area (BSA), Psoriasis Area and Severity Index (PASI), and Dermatology Life Quality Index (DLQI). MG concentration was evaluated in blood samples. The following inflammatory response indices were calculated: Systemic Inflammation Response Index (SIRI), Systemic Immuno-inflammation Index (SII), and Aggregate Index of Systemic Inflammation (AISI). Results: An analysis of the obtained data showed a statistically significant decrease in the mean serum MG concentration in patients with psoriasis when compared to the healthy individuals (1.19 ± 0.4 μg/mL vs. 1.75 ± 0.6 μg/mL; p = 0.000002). In the patients, MG concentration correlated negatively with psoriasis disease severity indicators (BSA and PASI), C-reactive protein (CRP) concentration, and inflammatory response indicators (SII and AISI). Conclusions: The decreased concentration of MG may be attributed to an increased accumulation of its derivatives (advanced glycation end-products) in the inflamed skin and/or scavenging by polyamines. Full article
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15 pages, 294 KiB  
Article
Overweight-Related Hypertension in Middle-Aged Men Is Linked to Elevated Leptin, TNF-α, IL-6, Cholesterol, and Reduced Testosterone
by Shalan Alaamri, Abdulhalim S. Serafi, Zahir Hussain, Shouq K. Bafail, Mohammed A. Bafail, Lusine Demirkhanyan, Christopher S. Gondi and Sumera Sohail
Pathophysiology 2025, 32(1), 7; https://doi.org/10.3390/pathophysiology32010007 - 2 Feb 2025
Abstract
Background/Objectives: One of the major causes of hypertension (HT) is the transition of normal weight (NW) status to overweight (OW) status and obesity in a population, which leads to cardiovascular disease (CVD) and other disorders. A variety of factors/variables are involved in the [...] Read more.
Background/Objectives: One of the major causes of hypertension (HT) is the transition of normal weight (NW) status to overweight (OW) status and obesity in a population, which leads to cardiovascular disease (CVD) and other disorders. A variety of factors/variables are involved in the development of HT and OW-related hypertension (OHT). However, we planned to investigate the pathophysiological role of serum leptin (Lep), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), total cholesterol (TC) and serum testosterone (ST) in OHT in middle-aged men. Methods: We consulted three groups of middle-aged men (age: 51–60 years)—an HT group (n: 97, high normal weight (HNW), body mass index (BMI): 23–24.9 kg/m2); an OHT group (n: 97, high overweight (HOW), BMI: 28–29.9 kg/m2) and a normal control group (NC, n: 98, HNW)—to investigate the variations in and correlations of Lep, IL-6, TNF-α, ST, TC and other variables. Results: Significant variations were obtained for the comparisons of TNF-α, Lep, ST and TC for the patient groups. OHT vs. NC showed a significant difference for ST. OHT vs. NC and OHT vs. HT had significant variations for IL-6. Significant changes were obtained for the serum levels of TNF-α, Lep, IL-6, ST and TC among groups. Significant and positive linear associations were obtained for TNF-α, Lep, TC and IL-6. Significant and negative linear associations were found for ST plotted against Lep, TNF-α and IL-6. Conclusions: The current report provides pathophysiological evidence of the interactive role of serum Lep, TNF-α, ST, TC and IL-6 in middle-aged men with HT and OHT. We suggest that the changes we noted in the present study would be helpful for further BMI-based studies in various subcategories of NW, OW and obese subjects with/without HT. Full article
16 pages, 1363 KiB  
Systematic Review
Association Between Vitamin D Receptor BsmI Polymorphism and Low Bone Mineral Density in Postmenopausal Women in the MENA Region
by Tara Al-Barazenji, Asma Allouch, Nedhal Al Husaini, Sondos Yousef, Wisam Nabeel Ibrahim, Amal Al-Haidose, Hatem Zayed and Atiyeh M. Abdallah
Pathophysiology 2025, 32(1), 6; https://doi.org/10.3390/pathophysiology32010006 - 1 Feb 2025
Abstract
Background/Objectives: Low bone mineral density increases the risk of bone fractures, and this condition is especially common in postmenopausal women. Genetic factors significantly influence bone mineral density. This meta-analysis examined the relationship between vitamin D receptor (VDR) gene polymorphisms (BsmI, ApaI, and TaqI) [...] Read more.
Background/Objectives: Low bone mineral density increases the risk of bone fractures, and this condition is especially common in postmenopausal women. Genetic factors significantly influence bone mineral density. This meta-analysis examined the relationship between vitamin D receptor (VDR) gene polymorphisms (BsmI, ApaI, and TaqI) and bone mineral density in postmenopausal women in the Middle East and North Africa (MENA) region. Methods: The PubMed, Embase, Scopus, and Web of Science databases were searched from inception to March 2024 for case–control studies on VDR BsmI, ApaI, and TaqI polymorphisms and their relationship with low bone density. Associations with low bone mineral density were tested with respect to different genetic models (dominant, recessive, allelic) using RevMan v5.3. Results: The meta-analysis included seven studies for BsmI, six for ApaI, and seven for TaqI, representing 704/689 cases/controls for BsmI, 914/711 for ApaI, and 974/895 for TaqI. No significant association was found between VDR polymorphisms and low bone mineral density in postmenopausal women, except in the dominant model (CC + CG vs. GG) for the BsmI variant (OR = 1.27, 95% CI: 1.01–1.59, p = 0.04). Conclusions: We found a modest association between the BsmI polymorphism and increased risk of low bone mineral density (BMD) in postmenopausal women from the MENA region, suggesting its potential as a biomarker. No associations were observed for ApaI or TaqI. These findings highlight the complex genetic–environmental interactions influencing BMD. Full article
(This article belongs to the Section Metabolic Disorders)
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12 pages, 1791 KiB  
Article
Evolocumab Reduces Oxidative Stress and Lipid Peroxidation in Obese Zucker Rats
by Martina Cebova, Radoslava Bulkova and Olga Pechanova
Pathophysiology 2025, 32(1), 5; https://doi.org/10.3390/pathophysiology32010005 - 21 Jan 2025
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Abstract
Background/Objectives: Evolocumab inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) binding to low-density lipoprotein (LDL) receptors, thus allowing more LDL receptors to remove LDL cholesterol from the blood. We aimed to determine the effects of evolocumab on the plasma lipid profile, reactive oxygen [...] Read more.
Background/Objectives: Evolocumab inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) binding to low-density lipoprotein (LDL) receptors, thus allowing more LDL receptors to remove LDL cholesterol from the blood. We aimed to determine the effects of evolocumab on the plasma lipid profile, reactive oxygen species (ROS), and nitric oxide (NO) generation in the heart of adult male obese Zucker rats. Methods: The rats were divided into lean and obese controls and obese rats treated with evolocumab subcutaneously at a dose of 10 mg/kg every two weeks. After 6 weeks, the lipid profile was determined in the plasma, and NO synthase (NOS) activity, thiobarbituric acid reactive substance (TBARS), conjugated diene (CD) concentration, and protein expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, nuclear factor kappaB (NF-κB), endothelial NOS (eNOS), and phosphorylated eNOS (peNOS) were measured in the heart. Results: Evolocumab treatment did not reduce body weight, relative heart weight, or systolic blood pressure in obese Zucker rats. Evolocumab treatment, however, reduced plasma LDL levels, TBARS, and CD concentrations along with decreasing expression of NADPH oxidase and NF-kappaB proteins in the heart. On the other hand, evolocumab had no effect on NOS activity or eNOS and peNOS protein expression. Conclusions: Besides its lipid-lowering effect, evolocumab may exert antioxidant properties and protect cardiomyocytes from lipid peroxidation while not affecting NO production. Full article
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3 pages, 2071 KiB  
Correction
Correction: Yamarthi et al. Sepia pharaonis Ink Mitigates Dehydroepiandrosterone-Induced Insulin Resistance in Mouse Model of Polycystic Ovarian Syndrome. Pathophysiology 2024, 31, 408–419
by Prathyusha Yamarthi, Rama Satyasri Kotipalli, Samatasai Patnaik, Kv Veena, Muralidharan Kathirvel, Rajkumar Vutukuri and Manjula Bhanoori
Pathophysiology 2025, 32(1), 4; https://doi.org/10.3390/pathophysiology32010004 - 20 Jan 2025
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Abstract
Error in Figure [...] Full article
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13 pages, 4891 KiB  
Case Report
Cause of Death Analysis in a 9½-Year-Old with COVID-19 and Dravet Syndrome
by Vedashree R. Meher, Richard J. Huntsman, Francis H. Y. Green, Jill C. Wooff and Roland N. Auer
Pathophysiology 2025, 32(1), 3; https://doi.org/10.3390/pathophysiology32010003 - 10 Jan 2025
Viewed by 605
Abstract
Background: Cause of death analysis is fundamental to forensic pathology. We present the case of a 9½-year-old girl with a genetically confirmed diagnosis of Dravet syndrome who died in her sleep with no evidence of motor seizure. She also had a lifelong [...] Read more.
Background: Cause of death analysis is fundamental to forensic pathology. We present the case of a 9½-year-old girl with a genetically confirmed diagnosis of Dravet syndrome who died in her sleep with no evidence of motor seizure. She also had a lifelong history of recurrent pneumonias and, along with her family, had tested positive for COVID-19 10 days before death. Methods: Long-term clinical history of Dravet Syndrome and respiratory infections were obtained from patient’s medical charts and radiology reports. A Rapid-Antigen Test was used to confirm SARS-CoV2 infection days prior to death. At autopsy, brain, heart and lung tissues were obtained. Paraffin-embedded tissues were double-stained with H&E, and immunohistochemically stained using various antibodies. Results: Autopsy revealed evidence of previous seizure activity in the brain and cellular interstitial thickening in the lung. The brain showed edema and fibrillary gliosis without neuronal loss in neocortex and hippocampus. The lung showed inflammatory interstitial thickening with histiocytes, megakaryocytes, B-lymphocytes, and T-lymphocytes, including helper/suppressor cells and cytotoxic T-lymphocytes. Diffuse alveolar damage was observed as alveolar flooding with proteinaceous fluid. Conclusions: The cause of death may be attributed to Sudden Unexpected Death in Epilepsy (SUDEP) in Dravet syndrome, sudden death in viral pneumonia, or some combination of the two. When two independent risk factors for sudden unexpected death are identified due to co-pathology, it may not be possible to determine a single cause of death beyond a reasonable doubt. Full article
(This article belongs to the Topic Human Anatomy and Pathophysiology, 2nd Volume)
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14 pages, 4162 KiB  
Article
Evaluation of Creatine Monohydrate Supplementation on the Gastrocnemius Muscle of Mice with Muscular Dystrophy: A Preliminary Study
by Victor Augusto Ramos Fernandes, Gabriela Pereira dos Santos, Amilton Iatecola, Daniela Vieira Buchaim, Ionaly Judith Faria Garcia, Carlos Henrique Bertoni Reis, Lívia Maluf Menegazzo Bueno, Bruna Trazzi Pagani, Rogerio Leone Buchaim and Marcelo Rodrigues da Cunha
Pathophysiology 2025, 32(1), 2; https://doi.org/10.3390/pathophysiology32010002 - 6 Jan 2025
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Abstract
Background/Objectives: Duchenne muscular dystrophy (DMD) is a genetic disease characterized by a lack of dystrophin caused by mutations in the DMD gene, and some minor cases are due to decreased levels of dystrophin, leading to muscle weakness and motor impairment. Creatine supplementation has [...] Read more.
Background/Objectives: Duchenne muscular dystrophy (DMD) is a genetic disease characterized by a lack of dystrophin caused by mutations in the DMD gene, and some minor cases are due to decreased levels of dystrophin, leading to muscle weakness and motor impairment. Creatine supplementation has demonstrated several benefits for the muscle, such as increased strength, enhanced tissue repair, and improved ATP resynthesis. This preliminary study aimed to investigate the effects of creatine on the gastrocnemius muscle in dystrophy muscle (MDX) and healthy C57BL/10 mice. Methods: Twenty MDX and C57Bl/10 mice were organized into groups and supplemented or not with creatine in a dosage of 0.3 mg for 8 weeks. Gastrocnemius tissue was analyzed using histomorphology and histomorphometric techniques. Results: The results demonstrated potential anti-inflammatory effects of creatine, with less observation of inflammatory infiltrates, the preservation of intramuscular glycogen, and reduction in tissue fibrosis in supplemented animals. Conclusions: These findings suggest that creatine may enhance tissue function and slow the progression of DMD. However, further research, with more analysis, is needed to elucidate molecular mechanisms underlying creatine’s effects on reducing mononuclear leukocytes and its role in mitigating tissue fibrosis. Full article
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14 pages, 3540 KiB  
Article
Hepatic Estrogen Receptor Alpha Overexpression Protects Against Hepatic Insulin Resistance and MASLD
by Ester S. Alves, Jessica D. M. Santos, Alessandra G. Cruz, Felipe N. Camargo, Carlos H. Z. Talarico, Anne R. M. Santos, Carlos A. A. Silva, Henrique J. N. Morgan, Sandro L. Matos, Layanne C. C. Araujo and João Paulo Camporez
Pathophysiology 2025, 32(1), 1; https://doi.org/10.3390/pathophysiology32010001 - 3 Jan 2025
Viewed by 591
Abstract
Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with cardiometabolic risk. Although studies have shown that estradiol positively contributes to energy metabolism via estrogen receptor alpha (ERα), its role specifically in the liver is not defined. Therefore, this study aimed to evaluate [...] Read more.
Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with cardiometabolic risk. Although studies have shown that estradiol positively contributes to energy metabolism via estrogen receptor alpha (ERα), its role specifically in the liver is not defined. Therefore, this study aimed to evaluate the effects of ERα overexpression, specifically in the liver in mice fed a high-fat diet (HFD). Methods: Male C57BL/6J mice were divided into four groups, vehicle fed with regular chow (RC) (RC-Vehicle); vehicle fed an HFD (HFD-Vehicle); AAV-treated fed with RC (RC-AAV); and AAV-treated fed an HFD (HFD-AAV), for 6 weeks (8–10 mice per group). AAV was administered intravenously to induce ERα overexpression. Results: We demonstrate that overexpression of ERα in RC-fed mice reduces body fat (28%). These mice show increased oxygen consumption in cultured primary hepatocytes, both in basal (19%) and maximal respiration (34%). In HFD-fed mice, we showed a decrease in hepatic TAG content (43%) associated with improved hepatic insulin sensitivity (145%). Conclusions: From this perspective, our results prove that hepatic ERα signaling is responsible for some of the metabolic protective effects of estrogen in mice. Overexpression of ERα improves hepatocyte mitochondrial function, consequently reducing hepatic lipid accumulation and protecting animals from hepatic steatosis and hepatic insulin resistance. Further investigations will be needed to determine the exact molecular mechanism by which ERα improves hepatic metabolic health. Full article
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