Pathophysiology最新文献

{"title":"The Pathophysiological Mechanisms and Pattern of Dyslipidemia Associated with Iodine Deficiency and Subclinical Hypothyroidism in Pregnant Normotensive and Preeclamptic Central African Women.","authors":"Charles Bitamazire Businge, Benjamin Longo-Mbenza","doi":"10.3390/pathophysiology32020018","DOIUrl":"https://doi.org/10.3390/pathophysiology32020018","url":null,"abstract":"<p><strong>Background: </strong>Pregnancy simulates a metabolic syndrome-like state and predisposes to iodine deficiency and hypothyroidism through increased iodine renal loss and transplacental transfer to the fetus. Iodine deficiency is thought to predispose to dyslipidemia through elevation of serum TSH. Obesity, dyslipidemia, and hypothyroidism are established risk factors of preeclampsia. Hence, pregnant women with iodine deficiency are likely to be at increased risk of dyslipidemia and preeclampsia. We investigated the pattern of dyslipidemia among preeclamptic and normotensive pregnant women with and without iodine deficiency.</p><p><strong>Methods: </strong>The pathophysiological mechanisms linking iodine deficiency and dyslipidemia were delineated using bivariate correlations, logistic regression, and exploratory factor analysis of anthropometric, lipid profile, urine iodine concentration (UIC), and thyroid function data from 240 women with preeclampsia and 120 normotensive pregnant controls at term who attended Lomo Medical Centre, Democratic Republic of Congo (DRC).</p><p><strong>Results: </strong>Preeclamptic women with iodine deficiency had significantly lower HDL-C but higher triglyceride levels than those with sufficient iodine intake. Both normotensive and preeclamptic participants with elevated TSH had high serum oxidized LDL-C but low NO, <i>p</i> < 0.001.</p><p><strong>Conclusions: </strong>SCH, secondary to iodine deficiency, is associated with elevated serum oxidized LDL and decreased Nitric Oxide (NO) among both normotensive and preeclamptic women, while insufficient iodine nutrition among preeclamptic women predisposes to reduced HDL-C and increased serum Triglycerides, which are risk factors of atherosclerosis and cardiovascular disease.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"32 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatoprotective and Antiatherosclerotic Effects of Oleoylethanolamide-Based Dietary Supplement in Dietary-Induced Obesity in Mice.","authors":"Darya Ivashkevich, Arina Ponomarenko, Igor Manzhulo, Anastasia Egoraeva, Inessa Dyuizen","doi":"10.3390/pathophysiology32020016","DOIUrl":"https://doi.org/10.3390/pathophysiology32020016","url":null,"abstract":"<p><p><b>Background:</b> Metabolic effects of oleoylethanolamide-based dietary supplement (OEA-DS) were studied in a model of dietary-induced obesity in mice. Obesity was induced by a 2-month high-fat, high-cholesterol diet, resulting in significant morphological changes in liver tissues and elevated cholesterol levels in the animals' blood serum. Elevated levels of proinflammatory cytokines, oxidative stress, and hepatocyte apoptosis were also observed in the liver tissue. The aim of this study was to examine the mechanisms through which an OEA-based dietary supplement (OEA-DS) exerts a comprehensive influence on multiple aspects of the pathogenesis of MASLD, thereby demonstrating a robust hepatoprotective effect. <b>Methods:</b> mice were fed a high-fat, high-cholesterol diet with or without OEA-DS supplementation. Liver tissues and blood serum were analyzed for cholesterol levels, inflammatory markers (CD68, Iba-1, CD163, IL-1β, IL-6, TNFα), apoptotic markers (Bad, Bax, Bcl-2), nuclear receptors (PPAR-α, PPAR-γ, AdipoR1), and enzymes involved in lipolysis (Acox1, Cpt1a) and cholesterol metabolism (Ldlr, Furin, Pcsk9). Immunohistochemistry, Western blotting, and RT-PCR were used to assess protein expression and gene transcription. <b>Results:</b> administration of OEA-DS normalized cholesterol levels, decreased expression of inflammatory markers (CD68 and Iba-1), pro-apoptotic markers (Bad, Bax) and levels of pro-inflammatory cytokines (IL-1β, IL-6, TNFα). In parallel, the expression of nuclear receptors PPAR-α and PPAR-γ, adiponectin receptor 1 (AdipoR1), and anti-inflammatory (CD163) and anti-apoptotic (Bcl-2) markers have risen. OEA-DS administration induced the expression of liver lipolysis enzymes (Acox1, Cpt1a) and cholesterol metabolism factors (Ldlr, Furin), while simultaneously reducing the transcription of the proatherogenic factor Pcsk9. <b>Conclusions:</b> The results of this study suggest a complex action of OEA-DS in obesity-associated liver damage, which includes reduction of systemic inflammation.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"32 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunological Disorders: Gradations and the Current Approach in Laboratory Diagnostics.","authors":"Anna A Starshinova, Andrey An Savchenko, Alexander Borisov, Igor Kudryavtsev, Artem Rubinstein, Irina Dovgalyuk, Anastasia Kulpina, Leonid P Churilov, Polina Sobolevskaia, Tamara Fedotkina, Dmitry Kudlay, Evgeny V Shlyakhto","doi":"10.3390/pathophysiology32020017","DOIUrl":"https://doi.org/10.3390/pathophysiology32020017","url":null,"abstract":"<p><p>Currently, understanding the immune response, its abnormalities, and its diagnostic possibilities is a key point in the management of patients with various diseases, from infectious to oncological ones. The aim of this review was to analyze the data presented in the current literature on immune disorders and the possibility of their laboratory diagnostics in combination with clinical manifestations. We have performed a systematic analysis of the literature presented in international databases over the last ten years. We have presented data on the possibility of diagnosing immunopathological processes due to changes in immune cells and soluble molecules involved in the pathogenesis of a wide range of diseases, as well as the determination of antibodies to detect autoimmune processes. By applying laboratory techniques such as hematology, flow cytometry, ELISA, etc., available to most clinical laboratories worldwide, clinical data on immune system dysfunction in a wide range of diseases are being collected. This process is unfortunately still very far from being completed. However, with all the diversity of accumulated knowledge, we can currently state that the pathogenesis of the vast majority of immune-mediated diseases is not yet known. At the same time, the current success in dividing immune-mediated diseases into distinct clusters based on different types of inflammatory responses that are based on the involvement of different populations of T helper cells and cytokine molecules represents significant progress. Further research in this direction seems very promising, as it allows the identification of new target cells and target molecules for both improved diagnostics and targeted therapies.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"32 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Immunoglobulin and Proteoglycan Synthesis in Resected Hippocampal Tissue Predicts Post-Surgical Seizure Recurrence in Human Temporal Lobe Epilepsy.","authors":"Michael F Hammer, Martin E Weinand","doi":"10.3390/pathophysiology32020015","DOIUrl":"https://doi.org/10.3390/pathophysiology32020015","url":null,"abstract":"<p><p><b>Background/Objectives:</b> For patients with medically refractory temporal lobe epilepsy (TLE), surgery is an effective strategy. However, post-operative seizure recurrence occurs in 20-30% of patients, and it remains challenging to predict outcomes solely based on clinical variables. Here, we ask to what extent differences in gene expression in epileptic tissue can predict the outcome after resective epilepsy surgery. <b>Methods:</b> We performed RNAseq on hippocampal tissue resected from eight patients who underwent anterior temporal lobectomy with amygalohippocampectomy (ATL/AH), half of whom became seizure free (SF) or non-seizure free (NSF). <b>Results:</b> Bioinformatic analyses revealed 1548 differentially expressed genes and statistical enrichment analyses identified a distinct set of pathways in NSF and SF cohorts that were associated with neuroinflammation, neurotransmission, synaptic plasticity, and extracellular matrix (ECM) reorganization. Resected tissue exhibiting strong pro-inflammatory processes are associated with better post-surgery seizure outcomes than patients exhibiting cellular signaling processes related to ECM reorganization, autoantibody production, and neural circuit formation. <b>Conclusions:</b> The results suggest that post-operative targeting of both inhibitory aspects of the ECM remodeling and the autoimmune/inflammatory components may be helpful in promoting repair and preventing the recurrence of seizures.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"32 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frequency of Tumor Necrosis Factor-α, Interleukin-6, and Interleukin-10 Gene Polymorphisms in Mexican Patients with Diabetic Retinopathy and Diabetic Kidney Disease.","authors":"Patricia Elvira Sánchez-Valencia, Juan Daniel Díaz-García, Margarita Leyva-Leyva, Fabiola Sánchez-Aguillón, Nelly Raquel González-Arenas, Jesús Guillermo Mendoza-García, Erika Karina Tenorio-Aguirre, Mercedes Piedad de León-Bautista, Aurora Ibarra-Arce, Pablo Maravilla, Angélica Olivo-Díaz","doi":"10.3390/pathophysiology32020014","DOIUrl":"https://doi.org/10.3390/pathophysiology32020014","url":null,"abstract":"<p><strong>Background/objectives: </strong>Two of the microvascular complications in type 2 diabetes (T2D) are diabetic retinopathy (DR), which is the most common cause of non-traumatic blindness, and diabetic kidney disease (DKD); the latter generally requires renal replacement therapy. The aim of the present study was to determine the frequency of polymorphisms of Tumor Necrosis Factor-α, interleukin-6, and interleukin-10 (<i>TNF-α</i>, <i>IL-10,</i> and <i>IL-6</i>), as well as to describe the clinical and laboratory characteristics of T2D association with these microvascular complications.</p><p><strong>Methods: </strong>This study included 203 patients with T2D, of which 102 had microvascular complications: 95 with DR, 50 with DKD, and 15 with diabetic neuropathy (the latter were not included in the statistical analysis); those with T2D without confirmed microvascular complications were considered as controls. Clinical and laboratory data were collected from the patient's medical records. Polymorphism typing of <i>TNF-α</i> rs361525 and rs1800629 and <i>IL-10</i> rs1800872 and rs1800871 were obtained using MALDI-TOF MS. <i>IL-10</i> rs1800896 and <i>IL-6</i> rs1800795 were typed using a quantitative real-time polymerase chain reaction.</p><p><strong>Results: </strong>The results of age, HbA1c, fasting glucose, and arterial hypertension are significantly associated in every group. The <i>TNF-α</i> rs1800629A allele and <i>TNF-α</i> rs1800629G/A genotype were associated with microvascular complications and DR. For <i>IL-10</i>-rs1800896, all the models were associated in DKD. The <i>TNF-α</i> rs361525-rs1800629GA haplotype was associated with microvascular complications and DR, while the <i>IL-10</i> haplotype, rs1800872-rs1800871-rs1800896 GGC, showed susceptibility in every group.</p><p><strong>Conclusions: </strong>Our results show the contributions of the variants of these cytokines to these microvascular complications, but more studies are required to reach relevant conclusions.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"32 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholesteryl Ester Species but Not Serum Proprotein Convertase Subtilisin/Kexin Type 9 Levels Decline in Male Patients with Active Inflammatory Bowel Disease.","authors":"Angelika Hettenbach, Tanja Elger, Muriel Huss, Gerhard Liebisch, Marcus Höring, Johanna Loibl, Arne Kandulski, Martina Müller, Hauke Christian Tews, Christa Buechler","doi":"10.3390/pathophysiology32020013","DOIUrl":"https://doi.org/10.3390/pathophysiology32020013","url":null,"abstract":"<p><strong>Background/objectives: </strong>Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates serum cholesterol levels and inflammation, both of which are dysregulated in inflammatory bowel disease (IBD). Free cholesterol (FC) and the various types of cholesteryl ester (CE) have different functions in the body. However, it is not yet known whether these lipids undergo parallel changes in male and female patients with active IBD, nor whether PCSK9 correlates with these lipids and disease severity in either sex. The present study measured the serum levels of PCSK9, FC, and 15 CE species in IBD patients, focusing on the associations of these molecules with sex, each other, and with disease severity.</p><p><strong>Methods: </strong>The serum PCSK9 levels of 80 IBD patients (42 males and 38 females) and 24 controls (12 males and 12 females) were measured by enzyme-linked immunosorbent assay. In addition, FC and 15 CE species levels of 53 randomly selected IBD patients and 16 controls were determined by direct flow injection analysis (FIA) using a high-resolution hybrid quadrupole-orbitrap mass spectrometer (FIA-FTMS).</p><p><strong>Results: </strong>Serum PCSK9 levels in controls and IBD patients were comparable and did not correlate with disease severity in IBD patients. There was no discernible difference in serum PCSK9, FC, and CE levels between patients with Crohn's disease (CD) and those with ulcerative colitis (UC). FC and almost all CE species decreased in male patients with active IBD but were not related to disease severity in the female patients. The decrease in different CE species in male IBD patients with diarrhea compared to those with normal stool consistency appears to be related to IBD severity. Bile acids regulate serum cholesterol levels, and FC and CE levels were positively correlated with fecal levels of secondary bile acids in the patients with UC but not CD. This association also existed in male UC patients and could not be evaluated in women due to the small sample size.</p><p><strong>Conclusions: </strong>In active IBD, a reduction in FC and almost all CE species was observed only in males, while serum PCSK9 levels remained within normal ranges in both sexes. It can be hypothesized that blocking PCSK9 may further reduce serum cholesterol levels, which may have adverse effects in male patients with active IBD.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"32 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Chronic Hyperinsulinemia Induces Remodelling of Vascular Smooth Muscle Cells from Young Men and Women in a Sex Hormone Independent Manner.","authors":"Ashley Jazzar, Danielle Jacques, Amira Abou-Aichi, Ghassan Bkaily","doi":"10.3390/pathophysiology32010012","DOIUrl":"10.3390/pathophysiology32010012","url":null,"abstract":"<p><p>Elevated circulating insulin levels between 80 and 100 µU/mL characterize hyperinsulinemia, which often leads to metabolic disorders such as obesity, insulin resistance, and type 2 diabetes (T2D). Elevated circulating insulin levels can directly affect vascular function and contribute to the pathophysiology of the cardiovascular system, including secondary arterial hypertension (SAH) and atherosclerosis. It is well known that hyperinsulinemia induced remodeling of the heart. However, there is no information on whether intrinsic differences exist between human vascular smooth muscle cells (VSMCs) and if in vitro mimicking hyperinsulinemia induces human VSMCs morphological and intracellular homeostasis remodeling in a sex- and sex hormones-dependent manner. Our in vitro cultured human VSMCs, coupled with quantitative 3D confocal imaging results, show that intrinsic differences exist between VSMCs from young men and women. Chronic hyperinsulinemia (80 µU/mL, 48 h treatment) increases cell and nuclear volumes associated with increased intracellular calcium (Ca²⁺) and ROS and decreased glutathione. In the absence of hyperinsulinemia, pretreatment with testosterone in VSMCs from men and oestradiol in VSMCs from women had no effect. Both sex hormones partially but not completely prevented hyperinsulinemia-induced remodeling of VSMCs from young men and women. The increase in VSMC volume may increase the thickness of the tunica media, leading to a decrease in the lumen of the blood vessel, which promotes the development of SAH and atherosclerosis in a sex-dependent manner.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"32 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRI Voxel Morphometry Shows Brain Volume Changes in Breast Cancer Survivors: Implications for Treatment.","authors":"Alexandra Nikolaeva, Maria Pospelova, Varvara Krasnikova, Albina Makhanova, Samvel Tonyan, Aleksandr Efimtsev, Anatoliy Levchuk, Gennadiy Trufanov, Mark Voynov, Matvey Sklyarenko, Konstantin Samochernykh, Tatyana Alekseeva, Stephanie E Combs, Maxim Shevtsov","doi":"10.3390/pathophysiology32010011","DOIUrl":"10.3390/pathophysiology32010011","url":null,"abstract":"<p><p>Chemotherapy-related cognitive impairment termed «chemobrain» is a prevalent complication in breast cancer survivors that requires early detection for the development of novel therapeutic approaches. Magnetic resonance voxel morphometry (MR morphometry), due to its high sensitivity, might be employed for the evaluation of the early changes in the volumes of brain structures in order to explore the «chemobrain» condition.</p><p><strong>Methods: </strong>The open, prospective, single-center study enrolled 86 breast cancer survivors (43.3 ± 4.4 years) and age-matched 28 healthy female volunteers (44.0 ± 5.68). Conventional MR sequences (T1- and T2-weighted, TIRM, DWI, MPRAGE) were obtained in three mutually perpendicular planes to exclude an organ pathology of the brain. Additionally, the MPRAGE sequence was performed for subsequent MR morphometry of the volume of brain structures using the open VolBrain program. The evaluation was performed at two follow-up visits 6 months and 3 years after the completion of BC treatment.</p><p><strong>Results: </strong>According to the MR morphometry, breast cancer survivors presented with significantly decreased volumes of brain structures (including total brain volume, cerebellum volume, subcortical gray matter, etc.) as compared to healthy volunteers. Evaluation over the follow-up period of 3 years did not show the restoration of brain volume structures.</p><p><strong>Conclusions: </strong>The data obtained employing MR morphometry revealed significant reductions (that were not detected on the conventional MR sequences) in both gray and white matter in breast cancer survivors following chemotherapy. This comprehensive analysis indicated the utility of MR morphometry in detecting subtle yet statistically significant neuroanatomical changes associated with cognitive and motor impairments in patients, which can in turn provide valuable insights into the extent of structural brain alterations, helping to identify specific regions that are most affected by treatment.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"32 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered Production and Cellular Levels of Hydrogen Sulfide (H₂S) in Placental Trophoblasts from Pregnancies Affected by Pre-Eclampsia.","authors":"Xiaodan Chu, Jie Xu, Xinggui Shen, Wenji Sheng, Jingxia Sun, Yang Gu, David F Lewis, Danielle Cooper, Dani Zoorob, Yuping Wang","doi":"10.3390/pathophysiology32010010","DOIUrl":"10.3390/pathophysiology32010010","url":null,"abstract":"<p><strong>Background/objectives: </strong>Hydrogen sulfide (H₂S) is a vasorelaxant gas and exerts anti-oxidative, anti-inflammatory, and cytoprotective effects. H₂S has been implicated in regulating placental vaso-activity and angiogenesis. It is believed that abnormal trophoblast production of vasodilators and angiogenic factors contributes to pre-eclampsia development. However, little is known about whether aberrant H₂S production is present in placental trophoblasts from pre-eclamptic pregnancies.</p><p><strong>Methods: </strong>Trophoblasts were isolated from normal and pre-eclamptic placentas. After incubation, cell production of H₂S in the culture medium and the cellular levels of H₂S were analyzed by reversed phase high-performance liquid chromatography (RP-HPLC). Expression levels of the three key H₂S converting enzymes, cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), were determined by immunohistochemistry. The protein expression of CBS and CSE was assessed by Western blot analysis.</p><p><strong>Results: </strong>(1) Trophoblast production and cellular levels of H₂S were significantly reduced in cells from pre-eclamptic vs. normal placentas; (2) free H₂S production was increased in a time-dependent manner in cultured trophoblasts from normal, but not from pre-eclamptic, placentas; and (3) strong CBS and CSE expression was seen in trophoblasts from normal, as opposed to pre-eclamptic, placentas. Reduced CBS and CSE expression in trophoblasts from pre-eclamptic vs. normal placentas were confirmed by Western blot analysis; and (4) 3-MST expression was undetachable in both normal and pre-eclamptic placentas, but 3-MST expression was strongly expressed in the first and second trimester placentas.</p><p><strong>Conclusions: </strong>These data provide plausible evidence that downregulation of CBS and CSE, but not 3-MST, expression may be responsible for reduced free H₂S production and decreased cellular H₂S levels in pre-eclamptic placentas. Our data provide further evidence that expression of 3-MST in placental trophoblasts is likely gestational age (developmental)-dependent.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"32 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Dysfunction in Diabetes: Shedding Light on a Widespread Oversight.","authors":"Franklyn Nonso Iheagwam, Amarachi Joy Joseph, Eniola Deborah Adedoyin, Olawumi Toyin Iheagwam, Samuel Akpoyowvare Ejoh","doi":"10.3390/pathophysiology32010009","DOIUrl":"10.3390/pathophysiology32010009","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"32 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}