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25 pages, 2341 KiB  
Article
Lipid-Enriched Cooking Modulates Starch Digestibility and Satiety Hormone Responses in Traditional Nixtamalized Maize Tacos
by Julian de la Rosa-Millan
Foods 2025, 14(15), 2576; https://doi.org/10.3390/foods14152576 - 23 Jul 2025
Abstract
Traditional taco preparation methods, such as oil immersion and steaming, can significantly affect the nutritional and metabolic characteristics of the final product. This study evaluated tacos made with five commercial nixtamalized maize flours and four common fillings (chicharron, beef skirt, potato, and refried [...] Read more.
Traditional taco preparation methods, such as oil immersion and steaming, can significantly affect the nutritional and metabolic characteristics of the final product. This study evaluated tacos made with five commercial nixtamalized maize flours and four common fillings (chicharron, beef skirt, potato, and refried beans), processed using three different methods: Plain, Full-Fat, and Patted-Dry. We assessed their chemical composition, starch digestibility, and thermal properties, and measured satiety-related hormone responses in mice. Fillings had a stronger influence on protein, fat, and moisture content than tortilla type. Full-fat tacos exhibited increased amylose–lipid complex formation and a lower gelatinization enthalpy, whereas plain tacos retained more retrograded starch and a crystalline structure. In vitro digestion revealed that Plain tacos, especially those with plant-based fillings, had the highest resistant starch content and the lowest predicted glycemic index. Hierarchical clustering showed that resistant starch, moisture, and gelatinization onset temperature were closely linked in the Plain samples, whereas lipid-driven variables dominated in the Full-Fat tacos. In mice, tacos with a higher resistant starch content led to greater GLP-1 levels, lower ghrelin levels, and reduced insulin responses, suggesting improved satiety and glycemic control. Patted-Dry tacos showed intermediate hormonal effects, supporting their potential as a balanced, health-conscious alternative. These findings demonstrate how traditional preparation techniques can be leveraged to enhance the nutritional profile of culturally relevant foods, such as tacos. Full article
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23 pages, 1199 KiB  
Review
Dysregulation of Mitochondrial Function in Cancer Cells
by Ahmed Mahmoud Ahmed Mahmoud Awad and Norwahidah Abdul Karim
Int. J. Mol. Sci. 2025, 26(14), 6750; https://doi.org/10.3390/ijms26146750 - 14 Jul 2025
Viewed by 388
Abstract
In addition to their well-known role in ATP production, mitochondria are vital to cancer cell metabolism due to their involvement in redox regulation, apoptosis, calcium signaling, and biosynthesis. This review explores how cancer cells drive the extensive reprogramming of mitochondrial structure and function, [...] Read more.
In addition to their well-known role in ATP production, mitochondria are vital to cancer cell metabolism due to their involvement in redox regulation, apoptosis, calcium signaling, and biosynthesis. This review explores how cancer cells drive the extensive reprogramming of mitochondrial structure and function, enabling malignant cells to survive hostile microenvironments, evade therapy, and proliferate rapidly. While glycolysis (the Warburg effect) was once thought to be the dominant force behind cancer metabolism, recent updates underscore the pivotal contribution of mitochondrial oxidative phosphorylation (OXPHOS) to tumor development. Cancer cells often exhibit enhanced mitochondrial ATP production, metabolic flexibility, and the ability to switch between energy sources such as glucose, glutamine, and pyruvate. Equally important are changes in mitochondrial morphology and dynamics. Due to disruptions in fusion and fission processes, regulated by proteins like Drp1 and MFN1/2, cancer cells often display fragmented mitochondria, which are linked to increased motility, metastasis, and tumor progression. Moreover, structural mitochondrial alterations not only contribute to drug resistance but may also serve as biomarkers for therapeutic response. Emerging evidence also points to the influence of oncometabolites and retrograde signaling in reshaping mitochondrial behavior under oncogenic stress. Collectively, these insights position mitochondria as central regulators of cancer biology and attractive targets for therapy. By unraveling the molecular mechanisms underlying mitochondrial reprogramming—from energy production to structural remodeling—researchers can identify new approaches to disrupt cancer metabolism and enhance treatment efficacy. Full article
(This article belongs to the Special Issue Mitochondria: Central Players in Cancer)
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24 pages, 28055 KiB  
Article
Sequence Stratigraphic and Geochemical Records of Paleo-Sea Level Changes in Upper Carboniferous Mixed Clastic–Carbonate Successions in the Eastern Qaidam Basin
by Yifan Li, Xiaojie Wei, Kui Liu and Kening Qi
J. Mar. Sci. Eng. 2025, 13(7), 1299; https://doi.org/10.3390/jmse13071299 - 2 Jul 2025
Viewed by 281
Abstract
The Upper Carboniferous strata in the eastern Qaidam Basin, comprising several hundred meters of thick, mixed clastic–carbonate successions that have been little reported or explained, provide an excellent geological record of paleoenvironmental and paleo-sea level changes during the Late Carboniferous icehouse period. This [...] Read more.
The Upper Carboniferous strata in the eastern Qaidam Basin, comprising several hundred meters of thick, mixed clastic–carbonate successions that have been little reported or explained, provide an excellent geological record of paleoenvironmental and paleo-sea level changes during the Late Carboniferous icehouse period. This tropical carbonate–clastic system offers critical constraints for correlating equatorial sea level responses with high-latitude glacial cycles during the Late Paleozoic Ice Age. Based on detailed outcrop observations and interpretations, five facies assemblages, including fluvial channel, tide-dominated estuary, wave-dominated shoreface, tide-influenced delta, and carbonate-dominated marine, have been identified and organized into cyclical stacking patterns. Correspondingly, four third-order sequences were recognized, each composed of lowstand, transgressive, and highstand system tracts (LST, TST, and HST). LST is generally dominated by fluvial channels as a result of river juvenation when the sea level falls. The TST is characterized by tide-dominated estuaries, followed by retrogradational, carbonated-dominated marine deposits formed during a period of sea level rise. The HST is dominated by aggradational marine deposits, wave-dominated shoreface environments, or tide-influenced deltas, caused by subsequent sea level falls and increased debris supply. The sequence stratigraphic evolution and geochemical records, based on carbon and oxygen isotopes and trace elements, suggest that during the Late Carboniferous period, the eastern Qaidam Basin experienced at least four significant sea level fluctuation events, and an overall long-term sea level rise. These were primarily driven by the Gondwana glacio-eustasy and regionally ascribed to the Paleo-Tethys Ocean expansion induced by the late Hercynian movement. Assessing the history of glacio-eustasy-driven sea level changes in the eastern Qaidam Basin is useful for predicting the distribution and evolution of mixed cyclic succession in and around the Tibetan Plateau. Full article
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12 pages, 611 KiB  
Article
Cutaneous Allodynia of the Withers in Cattle: An Experimental In Vivo Neuroanatomical Preliminary Investigation of the Dichotomizing Sensory Neurons Projecting into the Reticulum and Skin of the Withers—A Case Study on Two Calves
by Roberto Chiocchetti, Luciano Pisoni, Monika Joechler, Adele Cancellieri, Fiorella Giancola, Giorgia Galiazzo, Giulia Salamanca, Rodrigo Zamith Cunha and Arcangelo Gentile
Animals 2025, 15(12), 1689; https://doi.org/10.3390/ani15121689 - 6 Jun 2025
Viewed by 556
Abstract
The presence of dichotomizing neurons in the dorsal root ganglia (DRG) of cattle, innervating both the reticulum and the withers, may indicate a pre-spinal convergence of visceral and cutaneous sensory information, i.e., that the DRG primary sensory neurons may elaborate the sensory information [...] Read more.
The presence of dichotomizing neurons in the dorsal root ganglia (DRG) of cattle, innervating both the reticulum and the withers, may indicate a pre-spinal convergence of visceral and cutaneous sensory information, i.e., that the DRG primary sensory neurons may elaborate the sensory information coming from two different anatomical areas before reaching the secondary sensory neurons within the spinal cord. This anatomical feature could be the underlying basis for the cutaneous allodynia observed in traumatic reticuloperitonitis, also known as the “Kalchschmidt pain test”. The aim of the study was to identify the DRG primary sensory neurons innervating the reticulum and the withers by using two different retrograde fluorescent tracers, Fast Blue (FB, affinity for cytoplasm) and Diamidino Yellow (DY, affinity for nucleus). In two anesthetized calves, FB and DY were injected into the reticulum and skin of the withers, respectively. At the end of the experimental period, the calves were deeply anesthetized and then euthanatized. The thoracic (T1–T8) DRG were collected and processed to obtain cryosections which were examined on a fluorescent microscope. A large number of neurons localized, especially in the T7 DRG, presented nuclei labeled with DY. On the contrary, only a few neurons localized exclusively in T6 and T7 DRG presented the cytoplasm labeled with FB. No neurons displayed FB and DY simultaneously within the cytoplasm and nucleus, respectively. The absence of double-labeled DRG neurons suggests that the convergence of visceral and somatic sensory inputs underlying the Kalchschmidt pain response likely does not occur at the level of individual DRG neurons. Rather, it may involve higher-order integrative centers, possibly including vagal pathways and brainstem nuclei which integrate the afferent information to coordinate respiratory movements of the diaphragm, intercostal muscles, and larynx. Although limited by the sample size, this case study provides a neuroanatomical basis for further investigation into central mechanisms of referred visceral pain in cattle. Full article
(This article belongs to the Section Cattle)
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10 pages, 453 KiB  
Article
Impact of COVID-19 on Ureteroscopy Management of Urolithiasis: Retrospective Comparative Study Before and After Pandemic
by Shota Iijima, Takanobu Utsumi, Naoki Ishitsuka, Takahide Noro, Yuta Suzuki, Yuka Sugizaki, Takatoshi Somoto, Ryo Oka, Takumi Endo, Naoto Kamiya and Hiroyoshi Suzuki
Appl. Sci. 2025, 15(11), 6101; https://doi.org/10.3390/app15116101 - 28 May 2025
Viewed by 375
Abstract
The COVID-19 pandemic disrupted healthcare delivery worldwide, potentially impacting the management of urolithiasis. This study aimed to evaluate changes in referral patterns, perioperative care, and surgical outcomes among patients undergoing ureteroscopic treatment for upper ureteral stones at a Japanese institution. A retrospective cohort [...] Read more.
The COVID-19 pandemic disrupted healthcare delivery worldwide, potentially impacting the management of urolithiasis. This study aimed to evaluate changes in referral patterns, perioperative care, and surgical outcomes among patients undergoing ureteroscopic treatment for upper ureteral stones at a Japanese institution. A retrospective cohort of 467 patients who underwent ureteroscopic lithotripsy or retrograde intrarenal surgery between March 2018 and May 2022 was analyzed. The patients were divided into pre-pandemic (March 2018–March 2020, n = 244) and post-pandemic (April 2020–May 2022, n = 223) groups. Clinical characteristics and outcomes were compared. Baseline demographics were similar. After the pandemic onset, preoperative ureteral stenting increased (30.3% vs. 42.6%, p = 0.006), while surgical waiting times (36 days vs. 28 days, p = 0.005) and operative durations (77 min vs. 67 min, p = 0.018) decreased. Referral sources shifted (p = 0.045), with fewer primary care referrals and more from emergency or higher-level hospitals. Stone-free rates (65.6% vs. 58.7%, p = 0.128) and postoperative complication rates were comparable. Despite systemic constraints during the pandemic, timely adaptations in scheduling and perioperative management allowed for the continued delivery of safe and effective ureteroscopic treatment. These findings emphasize the importance of flexible clinical strategies during healthcare crises. Full article
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20 pages, 8664 KiB  
Article
Molecular Fingerprint of Endocannabinoid Signaling in the Developing Paraventricular Nucleus of the Hypothalamus as Revealed by Single-Cell RNA-Seq and In Situ Hybridization
by Evgenii O. Tretiakov, Zsófia Hevesi, Csenge Böröczky, Alán Alpár, Tibor Harkany and Erik Keimpema
Cells 2025, 14(11), 788; https://doi.org/10.3390/cells14110788 - 27 May 2025
Viewed by 595
Abstract
The paraventricular nucleus of the hypothalamus (PVN) regulates, among others, the stress response, sexual behavior, and energy metabolism through its magnocellular and parvocellular neurosecretory cells. Within the PVN, ensemble coordination occurs through the many long-range synaptic afferents, whose activity in time relies on [...] Read more.
The paraventricular nucleus of the hypothalamus (PVN) regulates, among others, the stress response, sexual behavior, and energy metabolism through its magnocellular and parvocellular neurosecretory cells. Within the PVN, ensemble coordination occurs through the many long-range synaptic afferents, whose activity in time relies on retrograde neuromodulation by, e.g., endocannabinoids. However, the nanoarchitecture of endocannabinoid signaling in the PVN, especially during neuronal development, remains undescribed. By using single-cell RNA sequencing, in situ hybridization, and immunohistochemistry during fetal and postnatal development in mice, we present a spatiotemporal map of both the 2-arachidonoylglycerol (2-AG) and anandamide (AEA) signaling cassettes, with a focus on receptors and metabolic enzymes, in both molecularly defined neurons and astrocytes. We find type 1 cannabinoid receptors (Cnr1), but neither Cnr2 nor Gpr55, expressed in neurons of the PVN. Dagla and Daglb, which encode the enzymes synthesizing 2-AG, were found in all neuronal subtypes of the PVN, with a developmental switch from Daglb to Dagla. Mgll, which encodes an enzyme degrading 2-AG, was only found sporadically. Napepld and Faah, encoding enzymes that synthesize and degrade AEA, respectively, were sparsely expressed in neurons throughout development. Notably, astrocytes expressed Mgll and both Dagl isoforms. In contrast, mRNA for any of the three major cannabinoid-receptor subtypes could not be detected. Immunohistochemistry validated mRNA expression and suggested that endocannabinoid signaling is configured to modulate the activity of afferent inputs, rather than local neurocircuits, in the PVN. Full article
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22 pages, 6198 KiB  
Article
Engineering a Dual-Function Starch–Cellulose Composite for Colon-Targeted Probiotic Delivery and Synergistic Gut Microbiota Regulation in Type 2 Diabetes Therapeutics
by Ruixiang Liu, Yikang Ding, Yujing Xu, Qifeng Wu, Yanan Chen, Guiming Yan, Dengke Yin and Ye Yang
Pharmaceutics 2025, 17(5), 663; https://doi.org/10.3390/pharmaceutics17050663 - 17 May 2025
Viewed by 779
Abstract
Objectives: This study engineered a colon-targeted drug delivery system (CTDS) using the dual pharmaceutical and edible properties of Pueraria lobata to encapsulate Lactobacillus paracasei for Type 2 diabetes mellitus (T2DM) therapy. Methods: The CTDS was designed as a core–shell composite through microwave–hydrothermal engineering, [...] Read more.
Objectives: This study engineered a colon-targeted drug delivery system (CTDS) using the dual pharmaceutical and edible properties of Pueraria lobata to encapsulate Lactobacillus paracasei for Type 2 diabetes mellitus (T2DM) therapy. Methods: The CTDS was designed as a core–shell composite through microwave–hydrothermal engineering, comprising the following: (1) a retrograded starch shell with acid/enzyme-resistant crystallinity to protect probiotics from gastric degradation; (2) a porous cellulose core derived from Pueraria lobata’s natural microstructure, serving as a colonization scaffold for probiotics. Results: Structural characterization confirmed the shell’s resistance to acidic/pancreatic conditions and the core’s hierarchical porosity for bacterial encapsulation. pH/enzyme-responsive release kinetics were validated via fluorescence imaging, demonstrating targeted probiotic delivery to the colon with minimal gastric leakage. In diabetic models, the CTDS significantly reduced fasting blood glucose and improved dyslipidemia, while histopathological analysis revealed restored hepatic and pancreatic tissue architecture. Pharmacologically, the system acted as both a probiotic delivery vehicle and a microbiota modulator, selectively enriching Allobaculum and other short-chain fatty acid (SCFA)-producing bacteria to enhance SCFA biosynthesis and metabolic homeostasis. The CTDS further exhibited direct compression compatibility, enabling its translation into scalable oral dosage forms (e.g., tablets). Conclusions: By integrating natural material engineering, microbiota-targeted delivery, and tissue repair, this platform bridges the gap between pharmaceutical-grade probiotic protection and metabolic intervention in T2DM. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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9 pages, 9435 KiB  
Brief Report
The Efficiency of FLAIR Images for Hemodynamic Change After STA-MCA Bypass with Moyamoya Disease and Symptomatic Steno-Occlusive Disorder
by Hyun Dong Yoo, Seung Young Chung, Seong Min Kim, Ki Seok Park, Seung Jun Ryu and Jae Guk Kim
J. Clin. Med. 2025, 14(10), 3292; https://doi.org/10.3390/jcm14103292 - 8 May 2025
Cited by 1 | Viewed by 545
Abstract
Background: Hyperintense vessels (HVs) visualized on FLAIR MRI are believed to reflect sluggish antegrade or retrograde flow in leptomeningeal collaterals that develop in response to major intracranial artery stenosis or occlusion. HV is frequently observed in conditions such as Moyamoya disease and [...] Read more.
Background: Hyperintense vessels (HVs) visualized on FLAIR MRI are believed to reflect sluggish antegrade or retrograde flow in leptomeningeal collaterals that develop in response to major intracranial artery stenosis or occlusion. HV is frequently observed in conditions such as Moyamoya disease and symptomatic ICA/MCA steno-occlusion. However, the relationship between HV and cerebral hemodynamics—and the effect of STA-MCA bypass on HV—remains inadequately characterized. This study aimed to investigate the relationship between HV on FLAIR and cerebral vascular hemodynamic status, as measured by SPECT, in patients with Moyamoya disease and symptomatic ICA/MCA occlusion. The secondary goal was to assess the impact of recanalization through STA-MCA bypass surgery on the presence of HV. Methods: We retrospectively analyzed 49 patients with symptomatic ICA or MCA steno-occlusion who underwent STA-MCA bypass between 2015 and 2020. Pre- and postoperative FLAIR MRIs were evaluated, and HV presence was graded as negative (0), minimal (1), or positive (2). SPECT was utilized to assess cerebrovascular reserve (CVR) in regions exhibiting various HV intensities. Follow-up FLAIR imaging was performed 3–14 months postoperatively to correlate HV changes with hemodynamic improvements observed via SPECT. Result: HV was present in 74% (36/49) of affected hemispheres. Regions exhibiting minimal or positive HV demonstrated a significantly lower CVR compared to HV-negative areas, indicating compromised perfusion. Following bypass surgery, HV was reduced or resolved in 65% (32/49) of patients, and this regression corresponded with improved CVR as confirmed by both SPECT and perfusion MRI. Conclusions: HV presence on FLAIR imaging is associated with impaired cerebrovascular hemodynamics in patients with Moyamoya disease or symptomatic large-vessel steno-occlusion. HV-positive territories exhibit reduced CVR, while surgical revascularization via STA-MCA bypass leads to hemodynamic improvement and concurrent HV reduction. These findings support HV as a potential surrogate marker for treatment response. Full article
(This article belongs to the Section Clinical Neurology)
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24 pages, 11888 KiB  
Article
Olfactory Dysfunction in a Novel Model of Prodromal Parkinson’s Disease in Adult Zebrafish
by Nathaniel W. Vorhees, Samantha L. Groenwold, Mackenzie T. Williams, Lexus S. Putt, Nereyda Sanchez-Gama, Grace A. Stalions, Gabriella M. Taylor, Heather E. Van Dort and Erika Calvo-Ochoa
Int. J. Mol. Sci. 2025, 26(10), 4474; https://doi.org/10.3390/ijms26104474 - 8 May 2025
Viewed by 639
Abstract
Olfactory dysfunction is a clinical marker of prodromal Parkinson’s disease (PD), yet the underlying mechanisms remain unclear. To explore this relationship, we developed a zebrafish model that recapitulates the olfactory impairment observed in prodromal PD without affecting motor function. We used zebrafish due [...] Read more.
Olfactory dysfunction is a clinical marker of prodromal Parkinson’s disease (PD), yet the underlying mechanisms remain unclear. To explore this relationship, we developed a zebrafish model that recapitulates the olfactory impairment observed in prodromal PD without affecting motor function. We used zebrafish due to their olfactory system’s similarity to mammals and their unique nervous system regenerative capacity. By injecting 6-hydroxydopamine (6-OHDA) into the dorsal telencephalic ventricle, we observed a significant loss of dopaminergic (DA) periglomerular neurons in the olfactory bulb (OB) and retrograde degeneration of olfactory sensory neurons (OSNs) in the olfactory epithelium (OE). These alterations impaired olfactory responses to cadaverine, an aversive odorant, while responses to alanine remained intact. 6-OHDA also triggered robust neuroinflammatory responses. By 7 days post-injection, dopaminergic synapses in the OB were remodeled, OSNs in the OE appeared recovered, and neuroinflammation subsided, leading to full recovery of olfactory responses to cadaverine. These findings highlight the remarkable neuroplasticity of zebrafish and suggest that this model of olfactory dysfunction associated with dopaminergic loss could provide valuable insights into some features of early PD pathology. Understanding the interplay between dopaminergic loss and olfactory dysfunction in a highly regenerative vertebrate may inform therapeutic strategies for individuals suffering from olfactory loss. Full article
(This article belongs to the Special Issue The Zebrafish Model in Animal and Human Health Research, 2nd Edition)
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14 pages, 3193 KiB  
Case Report
Uncommon Urinary Actinomycosis Mimicking Upper Urinary Tract Urothelial Tumor: Case Report and Literature Review
by Patricia A. Meza-Meneses, Rodrigo Pérez Becerra, Gerardo Garza Sainz, Luis Trujillo Ortiz, Adrián Martinez Correa, Alan Rodrigo Pérez Soriano, Ruben Miguel Angel Santiago González, Aarón Delgado Corral, Omar Vieyra Valdez, Genaro Argüelles Morales, Mario Alberto Toledo Díaz, Alberto Saldivar Luna, Carlos Alberto Castro-Fuentes and Victor Osornio Sánchez
Microorganisms 2025, 13(5), 1033; https://doi.org/10.3390/microorganisms13051033 - 30 Apr 2025
Viewed by 711
Abstract
Urinary actinomycosis is a rare condition, often mimicking a urinary tract tumor. Due to its low prevalence, it can be challenging to diagnose and may be mistaken for malignancies. A 33-year-old female patient with a history of type 2 Diabetes Mellitus and recurrent [...] Read more.
Urinary actinomycosis is a rare condition, often mimicking a urinary tract tumor. Due to its low prevalence, it can be challenging to diagnose and may be mistaken for malignancies. A 33-year-old female patient with a history of type 2 Diabetes Mellitus and recurrent urinary tract infections presented to the emergency room with right renal fossa pain radiating to the right hypochondrium, fever with chills, nausea, and vomiting. Physical examination revealed a positive Giordano sign and tenderness at the ipsilateral middle and upper ureteral points. A contrast-enhanced CT scan showed a mass infiltrating the distal third of the right ureter, causing retrograde dilatation and hydronephrosis. Additionally, a liver injury with both liquid and solid components was observed. Therefore, given the suspicion of a urothelial tumor, a diagnostic cystoscopy and ureteroscopy were performed. Using interventional radiology, an abscessed liver lesion was drained, yielding purulent fluid. The histopathological examination revealed no evidence of malignancy. However, due to the strong suspicion of upper urinary tract urothelial carcinoma, a right radical nephroureterectomy with bladder cuff excision and retroperitoneal lymphadenectomy was performed. Histopathological examination ultimately confirmed urinary actinomycosis. Consequently, antibiotic therapy with oral amoxicillin 2 g every 12 h was initiated, leading to a good clinical response. Despite its low incidence, urinary actinomycosis should be considered as a differential diagnosis in cases suspected of urothelial tumors in the upper urinary tract. Increased awareness of this rare condition may help prevent unnecessary surgical interventions. Full article
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26 pages, 2831 KiB  
Article
Catalpol Protects Against Retinal Ischemia Through Antioxidation, Anti-Ischemia, Downregulation of β-Catenin, VEGF, and Angiopoietin-2: In Vitro and In Vivo Studies
by Howard Wen-Haur Chao, Windsor Wen-Jin Chao and Hsiao-Ming Chao
Int. J. Mol. Sci. 2025, 26(9), 4019; https://doi.org/10.3390/ijms26094019 - 24 Apr 2025
Viewed by 545
Abstract
Retinal ischemic disorders present significant threats to vision, characterized by inadequate blood supply oxygen–glucose deprivation (OGD), oxidative stress, and cellular injury, often resulting in irreversible injury. Catalpol, an iridoid glycoside derived from Rehmannia glutinosa, has demonstrated antioxidative and neuroprotective effects. This study [...] Read more.
Retinal ischemic disorders present significant threats to vision, characterized by inadequate blood supply oxygen–glucose deprivation (OGD), oxidative stress, and cellular injury, often resulting in irreversible injury. Catalpol, an iridoid glycoside derived from Rehmannia glutinosa, has demonstrated antioxidative and neuroprotective effects. This study aimed at investigating the protective effects and mechanisms of catalpol against oxidative stress or OGD in vitro and retinal ischemia in vivo, focusing on the modulation of key biomarkers of retinal ischemia, including HIF-1α, vascular endothelial growth factor (VEGF), angiopoietin-2, MCP-1, and the Wnt/β-catenin pathway. Cellular viability was assessed using retinal ganglion cell-5 (RGC-5) cells cultured in DMEM; a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed. H2O2 (1 mM)/OGD was utilized. Vehicle or different catalpol concentrations were administered 15 min before the ischemic-like insults. The Wistar rat eyes’ intraocular pressure was increased to 120 mmHg for 60 min to induce retinal ischemia. Intravitreous injections of catalpol (0.5 or 0.25 mM), Wnt inhibitor DKK1 (1 μg/4 μL), anti-VEGF Lucentis (40 μg/4 μL), or anti-VEGF Eylea (160 μg/4 μL) were administered to the rats’ eyes 15 min before or after retinal ischemia. Electroretinogram (ERG), fluorogold retrograde labeling RGC, Western blotting, ELISA, RT-PCR, and TUNEL were utilized. In vitro, both H2O2 and OGD models significantly (p < 0.001/p < 0.001; H2O2 and OGD) induced oxidative stress/ischemic-like insults, decreasing RGC-5 cell viability (from 100% to 55.14 ± 2.19%/60.84 ± 4.57%). These injuries were insignificantly (53.85 ± 1.28% at 0.25 mM)/(63.46 ± 3.30% at 0.25 mM) and significantly (p = 0.003/p = 0.012; 64.15 ± 2.41%/77.63 ± 8.59% at 0.5 mM) altered by the pre-administration of catalpol, indicating a possible antioxidative and anti-ischemic effect of 0.5 mM catalpol. In vivo, catalpol had less effect at 0.25 mM for ERG amplitude ratio (median [Q1, Q3] 14.75% [12.64%, 20.48%]) and RGC viability (mean ± SE 63.74 ± 5.13%), whereas (p < 0.05 and p < 0.05) at 0.5 mM ERG’s ratio (35.43% [24.35%, 43.08%]) and RGC’s density (74.34 ± 5.10%) blunted the ischemia-associated significant (p < 0.05 and p < 0.01) reduction in ERG b-wave amplitude (6.89% [4.24%, 10.40%]) and RGC cell viability (45.64 ± 3.02%). Catalpol 0.5 mM also significantly protected against retinal ischemia supported by the increased amplitude ratio of ERG a-wave and oscillatory potential, along with recovering a delayed a-/b-wave response time ratio. When contrasted with DKK1 or Lucentis, catalpol exhibited similar protective effects against retinal ischemia via significantly (p < 0.05) blunting the ischemia-induced overexpression of β-catenin, VEGF, or angiopoietin-2. Moreover, ischemia-associated significant increases in apoptotic cells in the inner retina, inflammatory biomarker MCP-1, and ischemic indicator HIF-1α were significantly nullified by catalpol. Catalpol demonstrated antiapoptotic, anti-inflammatory, anti-ischemic (in vivo retinal ischemia or in vitro OGD), and antioxidative (in vitro) properties, counteracting retinal ischemia via suppressing upstream Wnt/β-catenin and inhibiting downstream HIF-1α, VEGF, and angiopoietin-2, together with its decreasing TUNEL apoptotic cell number and inflammatory MCP-1 concentration. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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17 pages, 21498 KiB  
Article
Multi-Year Global Oscillations in GNSS Deformation and Surface Loading Contributions
by Songyun Wang, Clark R. Wilson, Jianli Chen, Yuning Fu, Weijia Kuang and Ki-Weon Seo
Remote Sens. 2025, 17(9), 1509; https://doi.org/10.3390/rs17091509 - 24 Apr 2025
Viewed by 478
Abstract
Recent studies have identified a near six-year oscillation (SYO) in Global Navigation Satellite Systems (GNSS) surface displacements, with a degree 2, order 2 spherical harmonic (SH) pattern and retrograde motion. The cause is uncertain, with proposals ranging from deep Earth to near-surface sources. [...] Read more.
Recent studies have identified a near six-year oscillation (SYO) in Global Navigation Satellite Systems (GNSS) surface displacements, with a degree 2, order 2 spherical harmonic (SH) pattern and retrograde motion. The cause is uncertain, with proposals ranging from deep Earth to near-surface sources. This study investigates the SYO and possible causes from surface loading. Considering the irregular spatiotemporal distribution of GNSS data and the variety of contributors to surface displacements, we used synthetic experiments to identify optimal techniques for estimating low degree SH patterns. We confirm a reported retrograde SH degree 2, order 2 displacement using GNSS data from the same 35 stations used in a previous study for the 1995–2015 period. We also note that its amplitude diminished when the time span of observations was extended to 2023, and the retrograde dominance became less significant using a larger 271-station set. Surface loading estimates showed that terrestrial water storage (TWS) loads contributed much more to the GNSS degree 2, order 2 SYO, than atmospheric and oceanic loads, but TWS load estimates were highly variable. Four TWS sources—European Centre for Medium-Range Weather Forecasts Reanalysis 5 (ERA5), Modern-Era Retrospective analysis for Research and Applications (MERRA), Global Land Data Assimilation System (GLDAS), and Gravity Recovery and Climate Experiment (GRACE/GRACE Follow-On)—yielded a wide range (24% to 93%) of predicted TWS contributions with GRACE/GRACE Follow-On being the largest. This suggests that TWS may be largely responsible for SYO variations in GNSS observations. Variations in SYO GNSS amplitudes in the extended period (1995–2023) were also consistent with near surface sources. Full article
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25 pages, 7344 KiB  
Article
The Burning Pain Transcriptome in the Mouse Primary Somatosensory Cortex
by Virág Erdei, Zoltán Mészár and Angelika Varga
Int. J. Mol. Sci. 2025, 26(8), 3538; https://doi.org/10.3390/ijms26083538 - 9 Apr 2025
Viewed by 496
Abstract
Our previous research has demonstrated that the spinal cord undergoes epigenetic and molecular alterations following non-severe burn injury (BI). However, the primary somatosensory cortex (S1), crucial for pain perception, remains unexplored in this context. Here, we investigated transcriptomic alterations in the S1 cortex [...] Read more.
Our previous research has demonstrated that the spinal cord undergoes epigenetic and molecular alterations following non-severe burn injury (BI). However, the primary somatosensory cortex (S1), crucial for pain perception, remains unexplored in this context. Here, we investigated transcriptomic alterations in the S1 cortex of mice subjected to BI or formalin application (FA) to the hind paw, utilizing RNA sequencing (RNA-seq) one hour after injury. RNA-seq identified 1116 differentially expressed genes (DEGs) in BI and 136 DEGs in formalin-induced inflammatory pain. Notably, 82.4% of DEGs in BI and 32.4% in FA were downregulated. A total of 42 upregulated and 17 downregulated overlapping DEGs were identified, indicating significant differences in the cortical processing of pain based on its origins. Gene Ontology analysis reveals that BI upregulated mitochondrial functions and ribosome synthesis, whereas axon guidance, synaptic plasticity, and neurotransmission-related processes were downregulated. By contrast, formalin treatment mainly impacted metabolic processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis highlights the significance of retrograde endocannabinoid signaling (REC) in the response to burn injury. These findings demonstrate that transcriptomic remodeling in the S1 cortex is dependent on the sensory modality and suggest that the REC network is activated during acute pain responses following BI. Full article
(This article belongs to the Special Issue Pain: From Molecular Basis to Therapy)
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17 pages, 8689 KiB  
Article
Potential of Process-Induced Modification of Potato Starch to Modulate Starch Digestibility and Levels of Resistant Starch Type III
by Moshit Yaskin Harush, Carmit Shani Levi and Uri Lesmes
Foods 2025, 14(5), 880; https://doi.org/10.3390/foods14050880 - 4 Mar 2025
Cited by 1 | Viewed by 1303
Abstract
Starch digestibility and the content of resistant starch (RS) play a crucial role in human health, particularly in relation to glycemic responses, insulin sensitivity, fat oxidation, and satiety. This study investigates the impact of processing methods on potato starch digestibility and RS content, [...] Read more.
Starch digestibility and the content of resistant starch (RS) play a crucial role in human health, particularly in relation to glycemic responses, insulin sensitivity, fat oxidation, and satiety. This study investigates the impact of processing methods on potato starch digestibility and RS content, focusing on two modification techniques: autoclaving and high hydrostatic pressure (HHP), followed by retrogradation at different temperatures. The research employs a comprehensive approach to characterize structural changes in starch samples using X-ray diffraction (XRD), attenuated total reflectance–Fourier transform infrared (ATR-FTIR) spectroscopy, and scanning electron microscopy (SEM). In turn, semi-dynamic in vitro digestion experiments based on the INFOGEST protocol were conducted to assess starch digestibility, while RS content was evaluated through enzymatic digestion of the non-RS fraction. SEM, XRD, and FTIR measurements reveal thermal processing appreciably affected starch architectures while HHP had a marginal effect. Further, the FTIR 1045/1022R ratio was found to be correlated with RS content measurements while reducing rapidly digestible starch (RDS). The findings led to the stipulation that thermal processing facilitates amylose leaching and granular disruption. In turn, retrogradation enabled the deposition of the amylose onto the disrupted structures which delineated their subsequent liability to enzymatic digestion. Conversely, HHP had minimal effects on granular architectures and amylose leaching. Overall, this research provides valuable insights for processing starch-based food products with the goal of increasing RS content, which may have significant implications for the food industry and nutritional science. Full article
(This article belongs to the Section Food Physics and (Bio)Chemistry)
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14 pages, 520 KiB  
Review
The Role of Adenogenesis Factors in the Pathogenesis of Endometriosis
by Pietro G. Signorile, Alfonso Baldi, Rosa Viceconte and Mariarosaria Boccellino
Int. J. Mol. Sci. 2025, 26(5), 2076; https://doi.org/10.3390/ijms26052076 - 27 Feb 2025
Viewed by 955
Abstract
Endometriosis is a pathological condition characterized by the presence of the endometrial tissue, outside the uterine cavity. It affects nearly 10% of women of reproductive age and is responsible for infertility, chronic pain, and the weakening of the quality of life. Various pathogenetic [...] Read more.
Endometriosis is a pathological condition characterized by the presence of the endometrial tissue, outside the uterine cavity. It affects nearly 10% of women of reproductive age and is responsible for infertility, chronic pain, and the weakening of the quality of life. Various pathogenetic mechanisms have been suggested; however, the essential pathogenesis of endometriosis remains insufficiently comprehended. A comprehensive literature search was conducted in databases such as PubMed, Scopus, and Web of Science up to December 2024. Inclusion criteria encompassed studies investigating the pathogenetic mechanisms of endometriosis, while exclusion criteria included reviews, case reports, and studies lacking primary data. The analyzed studies explored multiple pathogenetic mechanisms, including retrograde menstruation, coelomic metaplasia, embryological defects, stem cell involvement, and epigenetic modifications. Special emphasis was placed on the role of uterine adenogenesis factors in the development and progression of endometriosis. A deeper understanding of the various pathogenetic mechanisms underlying endometriosis is crucial for advancing targeted therapeutic strategies. Further research into uterine adenogenesis factors may provide new insights into the disease’s pathophysiology and pave the way for novel treatment approaches. Full article
(This article belongs to the Special Issue Endometriosis: Focusing on Molecular and Cellular Research)
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