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Keywords = primary progressive MS

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21 pages, 243 KiB  
Article
The Impact of Multiple Sclerosis on Work Productivity: A Preliminary Look at the North American Registry for Care and Research in Multiple Sclerosis
by Ahya Ali, Kottil Rammohan, June Halper, Terrie Livingston, Sara McCurdy Murphy, Lisa Patton, Jesse Wilkerson, Yang Mao-Draayer and on behalf of the NARCRMS Healthcare Economics Outcomes Research Advisory Group
NeuroSci 2025, 6(3), 82; https://doi.org/10.3390/neurosci6030082 - 22 Aug 2025
Abstract
Objective: We aimed to quantify multiple sclerosis (MS)-related work productivity and to illustrate the longitudinal trends for relapses, disease progression, and utilization of health care resources in a nationally representative cohort of working North Americans living with MS. Background: The North American Registry [...] Read more.
Objective: We aimed to quantify multiple sclerosis (MS)-related work productivity and to illustrate the longitudinal trends for relapses, disease progression, and utilization of health care resources in a nationally representative cohort of working North Americans living with MS. Background: The North American Registry for Care and Research in Multiple Sclerosis (NARCRMS) is a multicentered physician-reported registry which prospectively collects clinical information including imaging data over a long period of time from people with MS from sites across the U.S. and Canada. The Health Economics Outcomes Research (HEOR) Advisory Group has also incorporated Health-Related Productivity and Health Resource Utilization questionnaires, which collect information about health care economics of people with MS and its effects on daily life. Design/Methods: This is a prospective observational study utilizing data from NARCRMS. Socio-demographic, clinical, and health economic outcome data were collected through previously validated and structured questionnaires. Logistic regression was used to calculate the relative odds of symptom impact, with a generalized logit link for number of relapses. Cox proportional hazards regression was used to calculate hazard ratios for time to first relapse. Results: Six hundred and eighty-two (682) people with MS were enrolled in NARCRMS and had completed the HEOR questionnaires at the time of the analysis. Among the participants, 61% were employed full-time and 11% were employed part time. Fatigue was the leading symptom reported to impact both work and household chores. Among the employed participants, 13% reported having missed work with a median of 6.8 (IQR: 3.0–9.0) missed hours due to MS symptoms (absenteeism), while 35% reported MS having impacted their work output (presenteeism). The odds of higher disease severity (EDSS 2.0–6.5 vs. 0.0–1.5) were 2.29 (95% CI = 1.08, 4.88; p = 0.011) times higher for participants who identified reduction of work output. Fatigue was the most identified symptom attributed to work output reduction. Among all participants, 33% reported having missed planned household work with a median of 3.0 (IQR: 2.0–5.0) hours. The odds of higher disease severity were 2.49 (95% CI = 1.37, 4.53; p = 0.006) times higher for participants who identified reduction in household work output, and 1.70 (CI = 1.27, 2.49; p = 0.006) times higher for those whose fatigue affected housework output as compared to other symptoms. Conclusions: A preliminary review of the first 682 patients showed that people with MS had reduced work and housework productivity even at an early disease state. Multiple sclerosis (MS) can significantly impair individuals’ ability to function fully at work and at home, with fatigue overwhelmingly identified as the primary contributing factor. The economic value of finding an effective treatment for MS-related fatigue is substantial, underscoring the importance of these findings for policy development, priority setting, and the strategic allocation of healthcare resources for this chronic and disabling condition. Full article
22 pages, 12756 KiB  
Article
The Antidiabetic Mechanisms of Cinnamon Extract: Insights from Network Pharmacology, Gut Microbiota, and Metabolites
by Rong Wang, Kuan Yang, Xuefeng Liu, Yiye Zhang, Yunmei Chen, Nana Wang, Lili Yu, Shaojing Liu, Yaqi Hu and Bei Qin
Curr. Issues Mol. Biol. 2025, 47(7), 543; https://doi.org/10.3390/cimb47070543 - 12 Jul 2025
Viewed by 784
Abstract
The progression of type 2 diabetes mellitus (T2DM) is shaped by a multifaceted interplay among genetic, behavioral, and environmental factors, alongside gut dysbiosis. Cinnamon, being abundant in polyphenols and flavonoids, shows significant antioxidant effects. Studies have substantiated that cinnamon contributes to the management [...] Read more.
The progression of type 2 diabetes mellitus (T2DM) is shaped by a multifaceted interplay among genetic, behavioral, and environmental factors, alongside gut dysbiosis. Cinnamon, being abundant in polyphenols and flavonoids, shows significant antioxidant effects. Studies have substantiated that cinnamon contributes to the management of glucose and lipid metabolism. However, the anti-diabetic efficacy of cinnamon is not completely understood. The objective of this research was to clarify the anti-diabetic mechanism associated with cinnamon extract through a combination of chemical profiling, network pharmacology, and in vivo investigations. The results indicated that 32 chemical ingredients, including quercetin, were identified through UPLC-Q-TOF-MS. Network pharmacology revealed that 471 targets related to 14 compounds were screened. The analysis of GO enrichment revealed that the primary pathways were notably enhanced in the metabolism of insulin and glucose. In vivo analyses showed that cinnamon could effectively alleviate hyperglycemia, insulin resistance, and lipid metabolism abnormalities via increased relative abundance of Akkermansia and Ligilactobacillus at the genus level and a decreased Firmicutes/Bacteroidetes ratio at the phylum level. Moreover, cinnamon reduced the serum levels of lipopolysaccharide (LPS) and proinflammatory cytokines (IL-6 and TNF-α) and significantly increased the colon Zonula occludens-1 (ZO-1) and occludin protein levels. It was also observed that cinnamon improved the fecal SCFA levels (acetic, propionic, butyric, valeric and caproic acid), while also modifying the bile acid (BA) profile and increasing the conjugated-to-unconjugated BA ratio. The Western blotting analysis further demonstrated that cinnamon activated intestinal FXR/FGF15 and hepatic PI3K/AKT signaling pathways. In summary, the finding confirmed that cinnamon ameliorated glucose and lipid metabolism disorders by safeguarding the intestinal barrier and modulating the gut microbiota and metabolites, thereby activating intestinal FXR/FGF15 and hepatic PI3K/AKT signaling pathways. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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30 pages, 14172 KiB  
Article
Synoptic and Dynamic Analyses of an Intense Mediterranean Cyclone: A Case Study
by Ahmad E. Samman
Climate 2025, 13(6), 126; https://doi.org/10.3390/cli13060126 - 15 Jun 2025
Viewed by 683
Abstract
On 3 February 2006, a powerful Mediterranean cyclone instigated a widespread dust storm across Saudi Arabia. Meteorological observations from one station recorded strong westerly to southwesterly winds, with gusts reaching 40 m/s, accompanied by thunderstorms and dust storms. This study delves into the [...] Read more.
On 3 February 2006, a powerful Mediterranean cyclone instigated a widespread dust storm across Saudi Arabia. Meteorological observations from one station recorded strong westerly to southwesterly winds, with gusts reaching 40 m/s, accompanied by thunderstorms and dust storms. This study delves into the formation and development of this significant Mediterranean cyclone, which impacted the Mediterranean basin and the Arabian Peninsula from 26 January to 4 February 2006. Utilizing ECMWF ERA5 reanalysis data, this research analyzes the synoptic and dynamic conditions that contributed to the cyclone’s evolution and intensification. The cyclone originated over the North Atlantic as cold air from higher latitudes and was advected southward, driven by a strong upper-level trough. The initial phase of cyclogenesis was triggered by baroclinic instability, facilitated by an intense upper-level jet stream interacting with a pre-existing low-level baroclinic zone over coastal regions. Upper-level dynamics enhanced surface frontal structures, promoting the formation of the intense cyclone. As the system progressed, low-level diabatic processes became the primary drivers of its evolution, reducing the influence of upper-level baroclinic mechanisms. The weakening of the upper-level dynamics led to the gradual distortion of the low-level baroclinicity and frontal structures, transitioning the system to a more barotropic state during its mature phase. Vorticity analysis revealed that positive vorticity advection and warm air transport toward the developing cyclone played key roles in its intensification, leading to the development of strong low-level winds. Atmospheric kinetic energy analysis showed that the majority of the atmospheric kinetic energy was concentrated at 400 hPa and above, coinciding with intense jet stream activity. The generation of the atmospheric kinetic energy was primarily driven by cross-contour flow, acting as a major energy source, while atmospheric kinetic energy dissipation from grid to subgrid scales served as a major energy sink. The dissipation pattern closely mirrored the generation pattern but with the opposite sign. Additionally, the horizontal flux of the atmospheric kinetic energy was identified as a continuous energy source throughout the cyclone’s lifecycle. Full article
(This article belongs to the Section Weather, Events and Impacts)
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13 pages, 675 KiB  
Article
HLA-DRB1 and DQB1 Allelic Polymorphism and Multiple Sclerosis in a Moroccan Population
by Abir Fguirouche, Yahya Naji, Morad Guennouni, Raja Hazime, Safa Zahlane, Mohamed Chraa, Najib Kissani, Nissrine Louhab and Brahim Admou
Curr. Issues Mol. Biol. 2025, 47(6), 458; https://doi.org/10.3390/cimb47060458 - 13 Jun 2025
Viewed by 735
Abstract
Introduction: Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system (CNS) that leads to inflammation and demyelination, manifesting in either a relapsing–remitting or progressive form. As a multifactorial disease, MS involves both genetic and environmental factors, with a [...] Read more.
Introduction: Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system (CNS) that leads to inflammation and demyelination, manifesting in either a relapsing–remitting or progressive form. As a multifactorial disease, MS involves both genetic and environmental factors, with a known significant contribution from human leukocyte antigen (HLA) genes, mainly represented by the HLA-DRB1 and HLA-DQB1 loci, which have been linked to either susceptibility or protection, but variably across populations and ethnic groups. We aimed to study the distribution and polymorphism of HLA-DRB1 and HLA-DQB1 alleles in a population with MS from the southern Moroccan region, in comparison with healthy controls. Materials and Methods: A cross-sectional study was conducted over a period of 2 years (2022–2024) in a MS cohort including 40 patients and 100 healthy controls. DRB1 and DQB1 HLA genotyping was performed using a high-resolution reverse sequence-specific oligonucleotide (SSO) method, based on the Luminex system (xMAP technology, One lambda®). Data were analyzed using SPSS 26; differences in allele frequencies were evaluated by the Chi-square test and Fisher’s exact test. OR (95% CI) was calculated, and FDR corrections were applied for multiple testing. Results: Among the various HLA-DRB1 and DQB1 alleles studied, including those considered as predisposing to MS, the DQB1*02:01 and DRB1*15:01 alleles were more prevalent in MS patients, with 40% and 8.8% vs. 16% and 4.08% in controls respectively, although these differences were not statistically significant (p = 0.06 and p = 0.12). Likewise, the DRB1*15:01-DQB1*06:02 association was significantly more prevalent in the MS group (9%, p = 0.004). In contrast, the DRB1*07:01 allele, linked to protection against MS in many populations, was significantly predominant in controls (17%, p = 0.004). Similarly, the DRB1*07:01–DQB*02:01 combination was rather more frequent in controls (12%, p = 0.01). Confronted to MS clinical forms, we remarkably noted that the DRB1*13:03 allele was found only among relapsing–remitting MS (RRMS) patients (6%, p = 0.003), while DQB1*02:01 was significantly associated with RRMS (42.1%) and primary progressive MS (41%, p = 0.001), with an intermediate Expanded Disability Status Scale (EDSS) score, which may indicate a possible link with disease progression and severity. Conclusions: The results of our study highlighted particular HLA alleles, DRB1 and DQB1, alone or in combination, as potential immunogenic factors of susceptibility to MS in a population from southern Morocco, while other alleles seem rather to protect against the disease. This HLA polymorphism is also reflected in the clinical forms of the disease, showing a tendency toward severity for certain alleles. However, such preliminary results need to be consolidated and confirmed by studies carried out on a larger population sample, and compared with others on a national scale. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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12 pages, 1695 KiB  
Communication
Mercury Bioaccumulation in Female Breast Cancer Is Associated to CXCR4 Expression
by Francesca Servadei, Rita Bonfiglio, Renata Sisto, Stefano Casciardi, Erica Giacobbi, Maria Paola Scioli, Valeria Palumbo, Claudio Oreste Buonomo, Gerry Melino, Alessandro Mauriello and Manuel Scimeca
Int. J. Mol. Sci. 2025, 26(9), 4427; https://doi.org/10.3390/ijms26094427 - 7 May 2025
Viewed by 751
Abstract
The growing incidence of breast cancer over time suggests that environmental factors might contribute to the underlying causes of the disease. Mercury, a toxic metal classified as a Substance of Very High Concern, accumulates in the body through contaminated food, air, water, and [...] Read more.
The growing incidence of breast cancer over time suggests that environmental factors might contribute to the underlying causes of the disease. Mercury, a toxic metal classified as a Substance of Very High Concern, accumulates in the body through contaminated food, air, water, and soil, raising concerns about its role in tumor biology. The main aim of this study was to identify the possible associations between in situ mercury bioaccumulation and the molecular features of breast cancer. To achieve this, a total of 26 breast cancer cases were analyzed using an integrated approach that combined DNA and RNA sequencing, histological analysis, and inductively coupled plasma mass spectrometry (ICP-MS) to assess mercury bioaccumulation. Mercury was detected in 72% of the cases. A significant positive correlation was found between mercury bioaccumulation and CXCR4 expression in breast cancer tissues. Bioinformatic analysis further revealed that CXCR4 expression was significantly higher in metastatic tissues compared to primary tumors. These findings suggest that mercury accumulation may influence tumor biology through the CXCR4-CXCL12 signaling pathway, highlighting a potential mechanism by which mercury contributes to breast cancer progression. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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12 pages, 3852 KiB  
Article
Screening and Isolating Acetylcholinesterase Inhibitors from Olea europaea L. Fruit Using Ultrafiltration–Liquid Chromatography Coupled with High-Speed Counter-Current Chromatography
by Xingcui Wang, Yingshan Zhang, Jules Muhire, Duolong Di, Xinyi Huang and Dong Pei
Separations 2025, 12(4), 96; https://doi.org/10.3390/separations12040096 - 12 Apr 2025
Viewed by 497
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative condition and one of the most prevalent types of dementia in older adults. Currently, the primary drugs used to treat AD are acetylcholinesterase (AChE) inhibitors. The development of natural substances has become a research hotspot due [...] Read more.
Alzheimer’s disease (AD) is a progressive neurodegenerative condition and one of the most prevalent types of dementia in older adults. Currently, the primary drugs used to treat AD are acetylcholinesterase (AChE) inhibitors. The development of natural substances has become a research hotspot due to the high number of adverse effects of synthetic drugs. In this study, a new assay based on ultrafiltration–liquid chromatography–high-speed counter-current chromatography (UF-HPLC-HSCCC) was developed for the rapid screening and identification of AChE inhibitors from Olea europaea L. fruit. In this research, we screened and isolated two AChE inhibitors from O. europaea fruit extracts, identified by EI-MS and NMR as secologanoside and oleuroside-11-methyl ester. These compounds were identified for the first time from O. europaea and found to possess AChE inhibitory activity using an in vitro AChE inhibition assay and molecular docking. The IC50 values of the two compounds were 0.76 ± 0.04 mM and 1.08 ± 0.05 mM. The results demonstrated that secologanoside showed better AChE inhibition activity than oleuroside-11-methyl ester, suggesting that this compound is a promising AChE inhibitor. At the same time, the results showed that the combination of UF-HPLC- HSCCC provides a powerful tool for screening and isolating AChE inhibitors in complex samples. Full article
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23 pages, 5327 KiB  
Article
Protect Effects of Perilla Seed Extract and Its Active Ingredient Luteolin Against Inflammatory Bowel Disease Model via the PI3K/AKT Signal Pathway In Vivo and In Vitro
by Jin Zhang, Linlu Zhao, Jieyi He, Huining Wu, Mengru Guo, Zhichao Yu, Xingbin Ma, Yanhong Yong, Youquan Li, Xianghong Ju and Xiaoxi Liu
Int. J. Mol. Sci. 2025, 26(8), 3564; https://doi.org/10.3390/ijms26083564 - 10 Apr 2025
Cited by 1 | Viewed by 815
Abstract
The purpose of this study was to investigate the anti-inflammatory effects of Perilla Seed Extract (PSE) and its active ingredient on Inflammatory Bowel Disease (IBD) in vitro and in vivo. Thirty-two C57/BL mice were randomly divided into four groups (n = 8): [...] Read more.
The purpose of this study was to investigate the anti-inflammatory effects of Perilla Seed Extract (PSE) and its active ingredient on Inflammatory Bowel Disease (IBD) in vitro and in vivo. Thirty-two C57/BL mice were randomly divided into four groups (n = 8): control group (CON), PBS group, LPS group (LPS 3.5 mg/kg given intraperitoneally [ip] on day 7 of the study only), and PSE group (100 mg/kg orally daily + LPS ip at 3.5 mg/kg on day 7). Mice were euthanized 24 h after LPS administration. MODE-K cells were divided into five groups: control group (CON), LPS group (50 μg/mL LPS for 2 h), and PSE group (low dose, 25 μg/mL PSE + LPS; middle dose, 50 μg/mL PSE + LPS; high dose, 100 μg/mL PSE + LPS). In vivo, compared with the CON group, LPS revealed a significant decrease in the villus length-to-crypt depth ratio (p < 0.01) and goblet cell density per unit area (p < 0.01). Conversely, PSE administration resulted in a significant increase in the villus length-to-crypt depth ratio (p < 0.01) and goblet cell density (p < 0.01). LPS significantly increased the ROS content (p < 0.01), the secretion of inflammatory cytokines of IL-6 (p < 0.01), TNF-α (p < 0.01), and the mRNA expressions of HO-1 (p < 0.01). LPS significantly decreased the mRNA expressions of Occludin (p < 0.01) and Claudin1 (p < 0.01). In contrast, PSE treatment led to a marked decrease in ROS levels (p < 0.01), along with a reduction in the secretion of inflammatory factors IL-6 (p < 0.01) and TNF-α(p < 0.05), as well as the mRNA expressions of HO-1 (p < 0.01). Concurrently, PSE significantly increased the mRNA expressions of Occludin (p < 0.05) and Claudin1 (p < 0.01). In vitro, PSE treatment also significantly reversed LPS-induced inflammation, oxidation and tight junction–related factors. Network pharmacology identified 97 potential targets for PSE in treating IBD, while transcriptomics analysis revealed 342 differentially expressed genes (DEGs). Network pharmacology and transcriptomics analysis indicated that significant pathways included the PI3K-Akt signaling pathway, MAPK signaling pathway, and TNF signaling pathway, of which the PI3K-AKT pathway may represent the primary mechanism. In an in vivo setting, compared with the CON group, LPS led to a significant increase in the protein expression of p-PI3K/PI3K (p < 0.01) and p-AKT1/AKT1 (p < 0.01). Conversely, PSE resulted in a significant decrease in the protein expression of p-PI3K/PI3K (p < 0.01) and p-AKT1/AKT1 (p < 0.01). In vitro, compared with the LPS group, PSE also significantly blocked the protein expression of p-PI3K/PI3K (p < 0.01) and p-AKT1/AKT1 (p < 0.01). The chemical composition of PSE was analyzed using UPLC-MS/MS, which identified six components including luteolin (content 0.41%), rosmarinic acid (content 0.27%), α-linolenic acid (content 1.2%), and oleic acid (content 0.2%). Molecular docking found that luteolin could establish stable binding with eight targets, and luteolin significantly decreased the p-AKT1/AKT1 ratio (p < 0.01) compared to the LPS group in MODE-K cells. In summary, PSE demonstrates efficacy against IBD progression by enhancing intestinal barrier function and inhibiting inflammatory responses and oxidative stress via the PI3K/AKT signaling pathway, and luteolin’s inhibition of AKT1 protein phosphorylation appears to play a particularly crucial role in this therapeutic mechanism. Full article
(This article belongs to the Special Issue Characterization and Biological Function of Plant Extracts)
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20 pages, 309 KiB  
Review
Kinesiotherapeutic Possibilities and Molecular Parameters in Multiple Sclerosis
by Katarzyna Wiszniewska, Małgorzata Wilk, Małgorzata Wiszniewska, Joanna Poszwa, Oliwia Szymanowicz, Wojciech Kozubski and Jolanta Dorszewska
Sclerosis 2025, 3(2), 13; https://doi.org/10.3390/sclerosis3020013 - 3 Apr 2025
Viewed by 651
Abstract
Multiple sclerosis (MS) is a chronic and incurable neurological disease of the central nervous system. Three main forms of the disease have been distinguished: relapsing–remitting form (RRMS), secondary progressive form (SPMS), and primary progressive form (PPMS). Currently, in patients with MS, in addition [...] Read more.
Multiple sclerosis (MS) is a chronic and incurable neurological disease of the central nervous system. Three main forms of the disease have been distinguished: relapsing–remitting form (RRMS), secondary progressive form (SPMS), and primary progressive form (PPMS). Currently, in patients with MS, in addition to pharmacotherapy, neurorehabilitation is indicated to improve the motor function of the body and action in the most physiological movement patterns possible. In this therapy, work on lost or incorrect functions is used to provide the patient with self-sufficiency in everyday life. Kinesiotherapy is used as part of neurorehabilitation. This therapy for MS includes coordination exercises aimed at facilitating movement, strengthening exercises and resistance training, balance exercises, improving stability during everyday activities stretching and relaxation exercises, improving tissue elasticity, reducing tension, and breathing exercises. In this article, we present various possibilities for using kinesiotherapy in patients with MS at various stages of disease development. Moreover, we would like to draw attention to the benefits of physical activity leading to a significant improvement in the quality of life in MS patients. We believe that a regular exercise program should be part of the neurorehabilitation program in these patients in the future. Full article
17 pages, 2755 KiB  
Article
Acylcarnitine and Free Fatty Acid Profiles in Primary Biliary Cholangitis: Associations with Fibrosis and Inflammation
by Magdalena Rogalska, Agnieszka Błachnio-Zabielska, Piotr Zabielski, Jacek Robert Janica, Kamila Roszczyc-Owsiejczuk, Karolina Pogodzińska, Aleksandra Andrzejuk, Andrzej Dąbrowski, Robert Flisiak and Paweł Rogalski
Nutrients 2025, 17(7), 1097; https://doi.org/10.3390/nu17071097 - 21 Mar 2025
Cited by 1 | Viewed by 1152
Abstract
Background: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by bile duct destruction, cholestasis, and fibrosis. Acylcarnitines are esters of carnitine responsible for the transport of long-chain fatty acids into mitochondria for β-oxidation, playing a crucial role in energy metabolism [...] Read more.
Background: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by bile duct destruction, cholestasis, and fibrosis. Acylcarnitines are esters of carnitine responsible for the transport of long-chain fatty acids into mitochondria for β-oxidation, playing a crucial role in energy metabolism and lipid homeostasis. This study aimed to assess acylcarnitine and free fatty acid (FFA) profiles in PBC patients and their associations with fibrosis severity and inflammation. Methods: This cross-sectional study included 46 PBC patients and 32 healthy controls. Acylcarnitines and FFAs were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and enzymatic assays, respectively. Liver stiffness was measured by point shear wave elastography (ElastPQ), and fibrosis was assessed using APRI and FIB-4 scores. Inflammatory markers (IL-6, IL-1β) were also analyzed. Results: PBC patients had significantly higher levels of C18:1-acylcarnitine (median: 165.1 ng/mL) compared with the controls (152.4 ng/mL, p = 0.0036). Similarly, the FFA levels were markedly elevated in the PBC patients (median: 0.46 mM/L) compared with the controls (0.26 mM/L, p < 0.0001). Patients with higher liver stiffness (ElastPQ > 5.56 kPa) had significantly elevated C18:1-acylcarnitine (p = 0.0008) and FFA levels (p = 0.00098). Additionally, FFAs were significantly increased in patients with higher APRI and FIB-4 scores and were associated with elevated inflammatory markers (IL-6, IL-1β) and liver injury markers. Multivariate regression analysis confirmed C18:1-acylcarnitine (OR = 1.031, 95% CI: 1.007–1.057, p = 0.013) and FFAs (OR = 2.25 per 0.1 mM/L increase, 95% CI: 1.20–4.22, p = 0.012) as independent predictors of fibrosis severity in PBC. Conclusions: C18:1-acylcarnitine and FFAs are significantly elevated in PBC and are strongly associated with fibrosis severity and inflammation. These findings suggest a link between lipid metabolism disturbances and PBC. Both metabolites may potentially serve as non-invasive biomarkers of fibrosis progression in PBC, warranting further investigation. Full article
(This article belongs to the Section Lipids)
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15 pages, 7382 KiB  
Article
Pharmacological Inhibition of Microglial Proliferation Supports Blood–Brain Barrier Integrity in Experimental Autoimmune Encephalomyelitis
by Nozha Borjini, Mercedes Fernandez, Luciana Giardino, Lydia Sorokin and Laura Calzà
Cells 2025, 14(6), 414; https://doi.org/10.3390/cells14060414 - 12 Mar 2025
Cited by 1 | Viewed by 1189
Abstract
Blood–brain barrier dysfunction (BBB) is a primary characteristic of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). We have previously shown that blocking microglial proliferation using GW2580, a selective inhibitor of CSF1R (Colony stimulating factor 1 receptor), reduced disease progression [...] Read more.
Blood–brain barrier dysfunction (BBB) is a primary characteristic of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). We have previously shown that blocking microglial proliferation using GW2580, a selective inhibitor of CSF1R (Colony stimulating factor 1 receptor), reduced disease progression and severity and prevented the relapse phase. However, whether this was due to effects of GW2580 on the functional integrity of the BBB was not determined. Therefore, here, we examine BBB properties in rats during EAE under GW2580 treatment. Our data suggest that blocking early microglial proliferation through selective targeting of CSF1R signaling has a therapeutic effect in EAE by protecting BBB integrity and reducing peripheral immune cell infiltration. Taken together, our results identify a novel mechanism underlying the effects of GW2580, which could offer a novel therapy for MS. Full article
(This article belongs to the Special Issue Emerging Roles of Glial Cells in Human Health and Disease)
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12 pages, 242 KiB  
Article
Metabolomic Profiling of Disease Progression Following Radiotherapy for Breast Cancer
by Alexandra N. McMahon, Isildinha M. Reis, Cristiane Takita, Jean L. Wright and Jennifer J. Hu
Cancers 2025, 17(5), 891; https://doi.org/10.3390/cancers17050891 - 5 Mar 2025
Viewed by 1075
Abstract
Background: This study aims to explore metabolic biomarkers and pathways in breast cancer prognosis. Methods: We performed a global post-radiotherapy (RT) urinary metabolomic analysis of 120 breast cancer patients: 60 progression-free (PF) patients as the reference and 60 with progressive disease (PD: recurrence, [...] Read more.
Background: This study aims to explore metabolic biomarkers and pathways in breast cancer prognosis. Methods: We performed a global post-radiotherapy (RT) urinary metabolomic analysis of 120 breast cancer patients: 60 progression-free (PF) patients as the reference and 60 with progressive disease (PD: recurrence, second primary, metastasis, or death). UPLC-MS/MS (Metabolon Inc.) identified 1742 biochemicals (1258 known and 484 unknown structures). Following normalization to osmolality, log transformation, and imputation of missing values, a Welch’s two-sample t-test was used to identify biochemicals and metabolic pathways that differed between PF and PD groups. Data analysis and visualization were performed with MetaboAnalyst. Results: Metabolic biomarkers and pathways that significantly differed between the PD and PF groups were the following: amino acid metabolism, including phenylalanine, tyrosine, and tryptophan biosynthesis (impact value (IV) = 1.00; p = 0.0007); histidine metabolism (IV = 0.60; p < 0.0001); and arginine and proline metabolism (IV = 0.70; p = 0.0035). Metabolites of carbohydrate metabolism, including glucose (p = 0.0197), sedoheptulose (p = 0.0115), and carboxymethyl lysine (p = 0.0098), were elevated in patients with PD. Gamma-glutamyl amino acids, myo-inositol, and oxidative stress biomarkers, including 7-Hydroxyindole Sulfate and sulfate, were elevated in patients who died (p ≤ 0.05). Conclusions: Amino acid metabolism emerged as a key pathway in breast cancer progression, while carbohydrate and oxidative stress metabolites also showed potential utility as biomarkers for breast cancer progression. These findings demonstrate applications of metabolomics in identifying metabolic biomarkers and pathways as potential targets for predicting breast cancer progression. Full article
(This article belongs to the Section Cancer Therapy)
14 pages, 3219 KiB  
Article
Analysis of Potential Markers of Pork Freshness Based on Volatile Organic Compounds
by Wu Wang, Yujing Wang, Peilin Weng, Yixin Zhang, Jiali Peng, Fei Ma and Hui Zhou
Foods 2025, 14(5), 832; https://doi.org/10.3390/foods14050832 - 28 Feb 2025
Cited by 1 | Viewed by 1189
Abstract
Bacteria and endogenous enzymes generate volatile organic compounds (VOCs), which are posited to be the primary source of undesirable flavors in spoilt pork. Headspace solid-phase microextraction–gas chromatography–mass spectrometry (HS-SPME-GC-MS) was employed to assess the fluctuations in VOC concentrations in pork stored under tray [...] Read more.
Bacteria and endogenous enzymes generate volatile organic compounds (VOCs), which are posited to be the primary source of undesirable flavors in spoilt pork. Headspace solid-phase microextraction–gas chromatography–mass spectrometry (HS-SPME-GC-MS) was employed to assess the fluctuations in VOC concentrations in pork stored under tray packaging at 6–8 °C for 10 days, while total volatile basic nitrogen (TVB-N) and total viable counts (TVCs) were used to determine the quality of the pork. During storage, TVCs steadily increased, reflecting the growth of spoilage-related microorganisms, while TVB-N levels surpassed the spoilage threshold early, indicating an acceleration of the degradation process. Nine VOCs associated with pork spoilage were found by partial least squares discriminant analysis (PLS-DA), fold change (FC), and t-tests. The substances comprised ethyl acetate, acetoin, 3-methyl-1-butanol, 3-methylbutanal, 1-octen-3-ol, hexanal, vinyl acetate, 2-methylaziridine, and heptanal. A univariate linear regression analysis revealed a strong positive correlation (p < 0.001) between the gaseous total volatile basic nitrogen (G-TVBN) and the storage duration. Given that G-TVBN accurately reflects changes in pork freshness and the progression of spoilage, these results highlight the potential for dynamically monitoring the freshness and spoilage processes of pork. Full article
(This article belongs to the Section Food Security and Sustainability)
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25 pages, 1205 KiB  
Review
Clinical Management in Multiple Sclerosis
by Ana Victoria Arredondo-Robles, Karen Paola Rodríguez-López and Rodolfo Daniel Ávila-Avilés
Neuroglia 2025, 6(1), 6; https://doi.org/10.3390/neuroglia6010006 - 5 Feb 2025
Cited by 1 | Viewed by 4044
Abstract
This review aims to provide a comprehensive overview of the main types, subtypes, clinical manifestations, and current therapeutic strategies for multiple sclerosis, emphasizing recent advancements and clinical challenges. Multiple Sclerosis (MS) is a demyelinating, chronic, autoimmune, and inflammatory disease that affects the Central [...] Read more.
This review aims to provide a comprehensive overview of the main types, subtypes, clinical manifestations, and current therapeutic strategies for multiple sclerosis, emphasizing recent advancements and clinical challenges. Multiple Sclerosis (MS) is a demyelinating, chronic, autoimmune, and inflammatory disease that affects the Central Nervous System (CNS). Its classification has the following subtypes: Relapsing-Remitting (RRMS), Secondary-Progressive (SPMS), and Primary-Progressive (PPMS), including rarer subtypes such as Clinically Isolated Syndrome (CIS), Radiologically Isolated Syndrome (RIS), Balo’s Concentric Sclerosis (BCS), Schilder’s Disease (SD), and Progressive-Relapsing MS (PRMS). This article divides the various treatments for MS into the following three categories: acute relapse management, symptomatic treatments, and Disease-Modifying Treatments (DMTs). The latter represents revolutionary research in MS, since they are the drugs considered as the best treatment alternatives for this disease. Full article
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17 pages, 781 KiB  
Review
Eye-Tracking Metrics as a Digital Biomarker for Neurocognitive Disorders in Multiple Sclerosis: A Scoping Review
by Sonja Cecchetti, Andrew T. Duchowski and Marco Cavallo
Brain Sci. 2025, 15(2), 149; https://doi.org/10.3390/brainsci15020149 - 31 Jan 2025
Viewed by 2770
Abstract
Multiple sclerosis (MS) is an autoimmune disease classified as neurodegenerative because it can be associated with the more or less progressive development of neurological symptoms and cognitive deficits. In recent years, various studies have started to investigate eye movements in relation to cognitive [...] Read more.
Multiple sclerosis (MS) is an autoimmune disease classified as neurodegenerative because it can be associated with the more or less progressive development of neurological symptoms and cognitive deficits. In recent years, various studies have started to investigate eye movements in relation to cognitive impairment in persons with MS by means of eye-tracking equipment. However, the high heterogeneity of the paradigms used in different studies, as well as the different methodologies included, makes it difficult to provide a complete and precise picture of this important research and clinical issue. The purpose of the present in-depth scoping review was to map the existing literature in this field to determine which metrics may be relevant when dealing with the neurocognitive profile of people with MS. From the analyses of the included studies, the anti-saccade latency and errors were the most frequently proposed metrics. Correlation analyses between these metrics and cognitive measures showed significant associations between them, calling for a deeper investigation of this promising research and clinical field. The results of the present scoping review strongly suggest that eye tracking may play a crucial role in clinical practice during the early detection of neurocognitive disorders. There is a great need for primary research that addresses the full complexity of MS in its different phenotypes and the disease-related variables from a multidisciplinary perspective. Future research should clarify whether oculomotor dysfunction in MS follows or precedes cognitive deficits. Full article
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11 pages, 543 KiB  
Article
Clinical Characteristics of Early-Onset and Late-Onset Multiple Sclerosis in Patients from Lithuania
by Emilija Šlajūtė, Naglis Vičkačka, Tautvydas Klėgėris, Ingrida Ulozienė and Renata Balnytė
Medicina 2025, 61(1), 107; https://doi.org/10.3390/medicina61010107 - 13 Jan 2025
Viewed by 954
Abstract
Background and Objectives: Early-onset MS (EOMS) and late-onset MS (LOMS) differ in terms of symptom presentation, disease progression, and disability outcomes. This study aims to evaluate the clinical characteristics of patients with EOMS and LOMS in Lithuania. Materials and Methods: A retrospective analysis [...] Read more.
Background and Objectives: Early-onset MS (EOMS) and late-onset MS (LOMS) differ in terms of symptom presentation, disease progression, and disability outcomes. This study aims to evaluate the clinical characteristics of patients with EOMS and LOMS in Lithuania. Materials and Methods: A retrospective analysis of patients’ medical records was conducted at the Lithuanian University of Health Sciences, Kaunas Clinics Department of Neurology. This study included 97 patients with multiple sclerosis, of which 34 were diagnosed with EOMS and 63 with LOMS. Results: The female/male ratio did not differ significantly in the EOMS group (1.26:1), while in the LOMS group, the female-to-male ratio was 2:1. All EOMS patients were diagnosed with relapsing–remitting multiple sclerosis (RRMS), while in the LOMS group, RRMS was observed in 55.6%, secondary progressive multiple sclerosis (SPMS) was observed in 27%, and primary progressive multiple sclerosis (PPMS) was observed in 17.4% of patients (p < 0.001). The most common initial symptoms in the EOMS group were brainstem dysfunction (50%), and sensory (38.2%) and visual (26.5%) disorders, whereas LOMS patients predominantly experienced brainstem dysfunction (50.8%) and motor impairments (47.6%). The EOMS group experienced more clinical relapses in the first year after diagnosis, along with more frequent radiological signs of disease activity compared to LOMS (p < 0.001). Both groups demonstrated a significant increase in Expanded Disability Status Scale (EDSS) score at the last follow-up visit compared to the baseline, while the LOMS group had higher EDSS scores both at the baseline and at the last follow-up compared to the EOMS group (p < 0.001). Only LOMS patients had an increase in Multiple Sclerosis Severity Score (MSSS) at the last follow-up compared to the baseline (p = 0.028), and MSSS was higher than in EOMS patients both at the baseline (p = 0.004) and the last follow-up (p < 0.001). Conclusions: There was no significant gender difference in the EOMS group, whereas in the LOMS group, females were predominant. Both groups had RRMS as the most common disease course. At the onset of MS, brainstem dysfunction was the most common symptom in both patient groups. EOMS patients had a more active disease course, in contrast to LOMS patients, who exhibited higher levels of disability, suggesting a progressive disease. Full article
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