Morphological Changes Research Articles

Doxophylline, a Non-Selective Phosphodiesterase Inhibitor, Protects Against Chronic Fatigue-Induced Neurobehavioral, Biochemical, and Mitochondrial Alterations.

Chronic fatigue stress (CFS) is a multisystem disorder which exhibits multiple signs of neurological complications like brain fog, cognitive deficits and oxidative stress with no specific treatment. Doxophylline, a non-selective phosphodiesterase inhibitor (PDEI), has anti-inflammatory properties with enhanced blood-brain barrier penetration and tissue specificity. We have evaluated the neuroprotective potential of doxophylline in a murine model of forced swim test (FST) induced CFS and in H2O2 (hydrogen peroxide) induced oxidative stress in PC12 cells. An FST model to induce a state of CFS in mice was induced by forcing them to swim daily for 6min for 15 days. The drug was administered daily 30min prior to FST. The immobility period was compared for day 1 and day 15. Animals were sacrificed on day 16 for biochemical, mitochondrial, and histopathological estimations in the brain. Cytotoxicity assay, reactive oxygen species (ROS) and nuclear morphology determination were carried out in PC12 cells. A significant increase in immobility has been observed on the 15th day in CFS-induced mice compared to doxophylline treated group. Neurobehavioral studies revealed hypo locomotion, anxiety, motor incoordination, and memory deficit. Biochemical analysis showed a significant change in oxidative stress markers (superoxide dismutase (SOD), reduced glutathione (GSH), catalase, lipid peroxidation (LPO) and nitrite levels) and acetylcholinesterase enzyme activity (AChE) in brain homogenates. Doxophylline pre-treatment protects against these impairments. In PC12 cell lines, doxophylline exhibits alleviation against H2O2-induced oxidative stress, intracellular ROS generation, and changes in nuclear morphology. Doxophylline could be promising and possess therapeutic potential in CFS treatment. Further research is needed to test if doxophylline can be repurposed for neurological disorders.

Study on the biosafety and targeting efficiency of Escherichia coli outer membrane vesicles in breast tumor.

To seek out the targeting of Escherichia coli outer membrane vesicles (E. coli OMVs) in breast tumor-bearing mice and their biosafety in healthy mice. Ultrafiltration in conjunction with ultracentrifugation was utilized to concentrate E. coli OMVs, and characterize them. Subcutaneous breast tumors were induced in BALB/c mice to serve as an experimental model, and the biodistribution of E. coli OMVs in both tumor-bearing and healthy mice was monitored using an in vivo fluorescence imaging system. Utilizing frozen sections, the infiltration of E. coli OMVs in tumor tissues was appraised at the 24-hour post-injection. Healthy BALB/c mice were randomly divided into control group and vesicles group. Following the intravenous injection of E. coli OMVs, monitoring encompassed variations in body weight, blood routine indices, serum levels of AST, ALT, and BUN, organ indices (heart, liver, spleen, lung, and kidney), along with tissue histopathology over a 14-day period. The spherical E. coli OMVs had a diameter of (155.8 ± 3.1) nm and exhibited the expression of outer membrane proteins OmpA and OmpC. Upon assessment, it was evident that the E. coli OMVs persisted in the tumor tissues even 24h post-injection. An evident decrease in the body weight of the vesicles group, distinct from the control group, was observed on the second day after injection (P < 0.001); in contrast, no considerable differences were noted at subsequent time points (P > 0.05). Following the injection, the vesicles group displayed notable reductions in WBC and PLT as relative to the control group (P < 0.0001) on the initial day, however, there were no noteworthy distinctions as opposed to the control group for other hematological indices; No notable variances in hematological indices between the two groups were observed on the seventh and fourteenth day (P > 0.05). Over the 14 days, no substantial differences were observed in the serum levels of BUN, AST, ALT, and organ indices within the vesicles group as opposed to the control group (P > 0.05). Furthermore, there were no obvious abnormal changes in tissue morphology. 0.5mg/kg of E. coli OMVs can safely and effectively target 4T1 breast tumor in mice.

Effect of an experimental desensitizer with a hydroxyapatite-capsaicin composite applied before in-office dental bleaching on hydrogen peroxide diffusion, color and surface changes.

To evaluate a prior application of an experimental desensitizer containing a hydroxyapatite-capsaicin composite (HAp-CAP) in different concentrations on hydrogen peroxide (HP) diffusion into the pulp chamber, bleaching efficacy (BE) and on physical and chemical alterations of the enamel surface after in-office bleaching. Forty sound premolars were randomized in five groups according to each experimental condition (n = 8): no bleaching (negative control), only bleaching (positive control), 0.1%, 1% and 5% of HAp-CAP. Four groups were submitted to in-office bleaching (HP 35%) post-desensitizer application. The HP concentration (µg/mL) on the pulp chamber was measured by UV-Vis spectrophotometer. The BE was measured by digital spectrophotometer (ΔEab, ΔE00 and ΔWID) before and after 7 days bleaching. Enamel tooth fragments obtained from twenty molars were submitted to the same experimental conditions and analyzed using FE-SEM and EDS, Vickers microhardness (VHN), Raman spectroscopy, and nanoroughness (Ra) by AFM to evaluate morphologic and chemical changes on enamel surface. All data were submitted to statistical analysis (α = 0.05). The groups treated with HAp-CAP exhibited a lower concentration of HP in the pulp chamber compared to only bleaching group (p < 0.05). There were no significant differences observed in BE between HAp-CAP groups and only bleaching group (p > 0.05). Only HAp-CAP 5% showed no significant differences in VHN values when compared to no bleaching group (p > 0.05). There were no significant differences among any group in Ra values (p > 0.05). The groups submitted to HAp-CAP showed a higher mineral concentration when compared to only bleaching group (p < 0.05). Desensitizers containing HAp-CAP up to 5% effectively reduce HP diffusion into the pulp chamber after in-office bleaching, without interfering to BE and Ra, as well as prevent enamel demineralization. The use of desensitizers containing HAp-CAP during in-office bleaching treatments offers a promising approach to reduce the risk of pulp irritation caused by hydrogen peroxide diffusion, without compromising the bleaching effectiveness or causing surface roughness.

Optical Clearing of Ex Vivo Adipose Tissue.

The paper focuses on the development of technology of adipose tissue optical clearing using different complex hyperosmotic optical clearing agents and tissue permeability enhancers. To quantify optical clearing efficiency, reduced scattering coefficient was estimated from the ex vivo spatially resolved backreflectance measurements using a multi-distant fiber optical device. Tissue morphology modification was monitored with the help of histological studies. Kinetics and efficiency of the optical clearing were evaluated for ex vivo abdominal fat tissue at action of dimethyl sulfoxide, diatrizoic acid, metrizoic acid, sucrose, and fructose solutions accompanied by tissue permeability enhancers, such as various modes of fractional laser microablation and sonophoresis and their combinations. Histological studies allowed us to find agents that cause minimal morphological changes of the adipose tissue. Maximal optical clearing efficiency of 83.5% was observed for the samples subjected to action of the fructose-ethanol solution during 90 min in combination with gentle modes of fractional laser microablation and sonophoresis.

Red Rice Alcohol in Southern China: Two Ways of Traditional Brewing and Their Implications for Archaeological Research

ABSTRACT China has a long history of making alcohol using different cereals. Recent archaeological studies demonstrate that people began producing hongqujiu (red rice alcohol) in the early Neolithic. However, because this product is produced and consumed in limited areas today, there is limited information about how it is made. This article reports ethnographic observations of the process of making hongqujiu in two villages in Zhejiang Province, China, where local people practice two different brewing methods–wet and dry. Samples from an abandoned jiugang vat, used in the production of red rice alcohol by a local villager, were studied microscopically to provide reference data on starches, fungi, and other microresidues. By providing reference information on the traditional alcohol-making processes, circumstances of consumption, and morphological changes of starch and fungal elements, this study will improve our understanding of alcohol making and consuming practices in archaeological contexts in China and beyond.

Single-cell transcriptomics reveals evolutionary reconfiguration of embryonic cell fate specification in the sea urchin Heliocidaris erythrogramma.

Altered regulatory interactions during development likely underlie a large fraction of phenotypic diversity within and between species, yet identifying specific evolutionary changes remains challenging. Analysis of single-cell developmental transcriptomes from multiple species provides a powerful framework for unbiased identification of evolutionary changes in developmental mechanisms. Here, we leverage a "natural experiment" in developmental evolution in sea urchins, where a major life history switch recently evolved in the lineage leading to Heliocidaris erythrogramma, precipitating extensive changes in early development. Comparative analyses of scRNA-seq developmental time courses from H. erythrogramma and Lytechinus variegatus (representing the derived and ancestral states respectively) reveals numerous evolutionary changes in embryonic patterning. The earliest cell fate specification events and the primary signaling center are co-localized in the ancestral dGRN; remarkably, in H. erythrogramma they are spatially and temporally separate. Fate specification and differentiation are delayed in most embryonic cell lineages, although in some cases, these processes are conserved or even accelerated. Comparative analysis of regulator-target gene co-expression is consistent with many specific interactions being preserved but delayed in H. erythrogramma, while some otherwise widely conserved interactions have likely been lost. Finally, specific patterning events are directly correlated with evolutionary changes in larval morphology, suggesting that they are directly tied to the life history shift. Together, these findings demonstrate that comparative scRNA-seq developmental time courses can reveal a diverse set of evolutionary changes in embryonic patterning and provide an efficient way to identify likely candidate regulatory interactions for subsequent experimental validation.

Morphological changes of endometrial tissue in women with infertility who suffered from coronavirus disease anamnesis

The objective: to determine the morphological changes in endometrial samples in women with infertility and post-COVID syndrome.Materials and methods. 80 women with infertility and a history of post-COVID syndrome were examined, as well as 40 women with infertility without having experienced COVID-19.In all patients, endometrial samples were collected in the middle proliferative and middle secretory phases (in different menstrual cycles) by pipel biopsy or during office hysteroscopy, followed by histological and immunohistochemical examination. Antibodies to angiotensin-converting enzyme-2 (ACE2), SARS-CoV-2, CD138, CD56 were used for immunotyping.Results. In women with infertility and a history of post-COVID syndrome plasma cells (р = 0.027), lymphohistiocytic infiltration (р = 0.003), areas of fibrotic stroma (р=0.031) are more often detected during the study of endometrial samples in the middle proliferative phase, and in biosamples of the middle secretory phase – weakly developed stroma (p = 0.033), plasma cells (p = 0.029). When conducting an immunohistochemical study in both cohorts an increase in ACE2 protein expression was found in the middle secretory phase.In the mucous membrane of the uterus in both proliferative and secretory phase, in patients of both cohorts the expression of the CD138 immunomarker was detected, but in the middle secretory phase the signs of the expression of endometrial granulocytes were more often found in women who were diagnosed with infertility and a history of post-CIVOD syndrome (p=0.032). No expression of antibodies to SARS-CoV-2 was observed in the endometrial samples of patients who had coronavirus disease.Conclusions. In women with infertility and post-COVID syndrome the main morphological features in the selected endometrial samples were the presence of plasma cells in both phases of the menstrual cycle, lymphohistiocytic infiltration of the stroma, areas of fibrosis of the stromal component in the middle proliferative phase, impaired decidualization and expression of endometrial granulocytes in the middle secretory phase, and as well as the lack of expression of the SARS-CoV-2 immunomarker.

Effects of electroacupuncture on expression of miR-218 and HMGB1/TLR4 signaling pathway in rats with focal cerebral ischemia

To observe the effect of electroacupuncture (EA) on high mobility group box 1 (HMGB1) / toll-like receptor 4 (TLR4) signaling pathway and inflammatory injury in rats with focal cerebral ischemia (FCI), so as to explore its mechanisms underlying amelioration of ischemic stroke. Male SD rats were randomly divided into sham operation (n=18), model (n=18) and EA (n=18) groups. The FCI model was established according to Longa's method. In the EA group, 24 h after modeling, EA stimulation was applied to "Baihui"(GV20), "Fengfu"(GV16), and "Neiguan" (PC6) and "Xinshu" (BL15) on the left side for 20 min, once a day for 1 week. The neurological deficit severity was evaluated by the modified neurological severity score (mNSS), and the morphological changes of neurons were observed after H.E. staining. The expression of HMGB1 and TLR4 proteins were detected by immunofluorescence staining. The contents of tumor necrosis factor(TNF)-α and interleukin(IL)-6 in the ischemic area tissue of the brain were detected using ELISA. The mRNA expressions of HMGB1 and TLR4 as well as the expression of miR-218 in the ischemic cortex were detected by PCR. Compared with the sham operation group, the mNSS at 2 h, 48 h and 7 day (d), IL-6 and TNF-α contents, HMGB1 and TLR4 immunoactivity and mRNA expression at 48 h and 7 d were significantly increased (P<0.01), while miR-218 expression at 48 h and 7 d was obviously down-regulated (P<0.01) in the model group. In comparison with the model group, the mNSS at 7 d, IL-6 and TNF-α contents, HMGB1 and TLR4 immunoactivity and mRNA expression at 7 d not at 48 h were significantly decreased (P<0.01, P<0.05), while the expression of miR-218 at 7 d was apparently up-regulated (P<0.05) in the EA group. H.E. staining showed that there were signs of neuronal necrosis including blurred outline of the cells, disordered internal structure, dense cytoplasm, shrunk nuclei, etc. in the ischemic area of the brain at 48 h and 7 d in the model group, which was evidently milder on day 7 in the EA group. EA can reduce the inflammatory injury of brain tissue and improve the neurological impairment in rats with FCI, which may be associated with its effects in inhibiting HMGB1/TLR4 signaling and down-regulating the level of pro-inflammatory cytokines.

Scanning Electron Microscopy of the Proboscis and Associated Sensilla in Colias erate (Esper, 1805) (Lepidoptera: Pieridae)

Morphological studies of the proboscis can provide valuable insights into the evolutionary adaptations of Lepidoptera. However, such research is relatively limited for Pieridae, a family that is significant both ecologically and economically. In this study, scanning electron microscopy (SEM) was employed to investigate the proboscis and associated sensilla of adult C. erate, with an emphasis on ultrastructural details and potential sex-specific differences. The proboscis in both sexes exhibits a similar structure, consisting of two elongated maxillary galeae connected by dorsal and ventral legulae. It is divided into three distinct zones based on morphological changes in the dorsal legulae. The outer surface of the proboscis is characterized by spike-like microbumps on transverse ridges, while the inner surface (food canal) is smooth throughout all three zones, with regularly spaced transverse grooves. Three types of sensilla comprising five subtypes were identified: sensilla chaetica (sc), sensilla basiconica (sb1, sb2, and sb3), and sensilla styloconica (ss). The functional implications of these morphological features are also discussed briefly .

Analysis of Optic Disc Morphology and the Peripapillary Retinal and Choroidal Thickness by the Swept Source Optical Coherence Tomography in Patients with Moyamoya Disease

Introduction: Moyamoya Disease (MMD) is a chronic cerebrovascular occlusive disorder. Ocular involvement in patients with MMD has increasingly been recognized and reported in recent years. This study aimed to investigate the changes of optic disc morphology and the peripapillary retinal and choroidal thickness in patients with MMD. Methods: This cross-sectional study included 56 patients diagnosed with idiopathic MMD and 56 healthy controls matched by age and gender. All participants underwent swept-source optical coherence tomography to capture the optic disc morphology as well as the peripapillary retinal and choroidal thickness. Optic disc parameters, including cup area, rim area, cup volume, rim volume, C/D area ratio (CDR), linear CDR, and vertical CDR were measured and compared between the two groups. Additionally, the thickness of the peripapillary whole retina, retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and choroid were evaluated and analyzed across 12 clock-hour segments around the peripapillary region. Results: The rim area in MMD patients was significant less than controls while the CDR in MMD patients was significantly larger than that in the control group. There was no statistically significant difference between the two groups regarding disc area, cup area, cup volume, rim volume, vertical and horizontal diameter of disc. The retinal thickness at the 7 o'clock position was significantly thinner in the MMD group compared to the control group and the temporal RNFL thickness, particularly at the 7 o'clock and 9 o'clock positions, was significantly reduced in the MMD group (p&lt;0.05). The GCL layer at the 7 o'clock position was thinner in the MMD group than in the control group (p&lt;0.05). The MMD group showed a notably reduced average choroidal thickness, particularly in the inferior-temporal region (p&lt;0.05). There was a correlation between peripapillary choroidal and GCL layer thickness in the MMD group, but no significant correlations were found with rim area, CDR, or RNFL. Conclusions: In patients with MMD, there is an increase in the CDR accompanied by a decrease in the rim area. Additionally, there is thinning of the temporal RNFL, GCL, and choroidal thickness, notably in the inferotemporal quadrant of the optic disc.

HABILIDADES MOTORAS E FUNCIONALIDADE CORPORAL NA SAÚDE EQUALIDADE DE VIDA EM IDOSOS PRATICANTES DE EXERCÍCIOS FÍSICOS

Introduction: Aging is a natural and progressive process responsible for several physiological, morphological, functional, biochemical and psychological changes, compromising their autonomy, this process is accompanied by structural and functional changes of the body and mind, and is also associated with cognitive decline that can affect the health and quality of life of the elderly. Objective: To verify motor skills in body functionality and health and quality of life in elderly practitioners of physical exercises. Methods: This is an integrative literature review, carried out in the following databases: Virtual Health Library (VHL), Bireme, Pubmed, Lilacs, Medline, Scientific Electronic Library Online (SciELO). Using the following descriptors alone and/or in combination: Physical exercise and motor skills in the elderly, Physical exercise and motor coordination in the elderly; Physical exercise and balance in the elderly; Physical exercise and functionality in the elderly; Physical exercise, motor coordination and functionality in the elderly; Physical exercise, balance and functionality in the elderly; Physical exercise and quality of life in the elderly. Results: The data showed that maintaining an active lifestyle is essential for the development of motor skills that consequently affects the autonomy, functionality and quality of life of the elderly. Considerations: An active lifestyle stimulates and maintains motor skills, which are fundamental mechanisms for maintaining the functional independence of the elderly. As for the limitations of the research, the theme focused on motor coordination proved to be quite scarce, and studies that deal with the study of skills in a more specific way are suggested.

In the Era of Molecular Pathology, the Role of Morphological Changes in Megakaryocytes in Bone Marrow Aspiration in Cases of Isolated Thrombocytopenia

In the Era of Molecular Pathology, the Role of Morphological Changes in Megakaryocytes in Bone Marrow Aspiration in Cases of Isolated Thrombocytopenia

Cloning and Functional Analysis of Skin Host Defense Peptides from Yakushima Tago’s Brown Frog (Rana tagoi yakushimensis) and Development of Serum Endotoxin Detection System

Background/Objective: Amphibian skin is a valuable source of host defense peptides (HDPs). This study aimed to identify HDPs with novel amino acid sequences from the skin of Rana tagoi yakushimensis and analyze their functions. Methods: cDNAs encoding HDP precursors were cloned and sequenced using RT-PCR and 3′-RACE. The novel HDPs were synthesized to evaluate their antimicrobial activity, antioxidant activity, and cytotoxicity. Antimicrobial activity was evaluated by way of broth microdilution and endotoxin- and β-glucan-binding capacity using an enzyme-linked endotoxin binding assay (ELEBA) and a modified ELEBA, respectively. Results: Nine cDNAs encoding precursors for various HDP families, including temporin, ranatuerin-2, brevinin-1, amurin-9, and a novel yakushimin peptide, were identified. Brevinin-1TYa exhibited antibacterial activity against Staphylococcus aureus, and brevinin-1TYa and amurin-9TYa induced morphological changes in Escherichia coli and S. aureus. Yakushimin-TYa, amurin-9TYa, and brevinin-1TYa showed concentration-dependent antibacterial effects against the plant pathogens Xanthomonas oryzae pv. oryzae and Clavibacter michiganensis subsp. michiganensis. Amurin-9TYa demonstrated strong binding affinity to lipopolysaccharide, lipoteichoic acid, and β-glucan, exhibited antioxidant activity, and lacked cytotoxicity, making it a promising therapeutic candidate. Moreover, brevinin-1TYa showed strong cytotoxicity, whereas yakushimin-TYa exhibited weak cytotoxicity. Conclusions: These findings highlight the potential of these peptides, particularly amurin-9TYa, for future applications as antimicrobial and therapeutic agents.

Characterization of Morphological Brain Changes in Generalized Epilepsy Using Region-based Morphometry

Magnetic Resonance Imaging has been widely involved in detecting morphological brain changes in generalized epilepsy at voxel level. It is believed that region-based morphometry could provide better characterizations for macro structural changes in the brain with comparative advantages than voxel-based morphometry. The aim of this study is to detect regional brain changes associated with generalized epilepsy and to test the potential of regional brain changes in classification of patients with generalized epilepsy and non-epileptic subjects. 45 patients and 46 non-epileptic subjects were scanned using a 3 Tesla MRI scanner and 3D T1 weighted images were obtained. Images were pre-processed and region based structural metrics (grey matter volumes, white matter volumes, cerebrospinal fluid volumes, cortical gyrification, and sulcus depth) were developed using Computational Anatomical Toolbox (CAT12). Two sample t-tests were used to perform the univariate analyses and results were corrected for multiple comparisons (FDR corrected, p &lt; 0.05). Grey matter volume reductions were detected in cerebellum, frontal lobe, temporal lobe, thalamus, and hippocampal region while bilateral white matter volume reductions were reported in cerebellum. In contrast, cerebrospinal fluid volume increments in left lateral ventricle were also detected. Reduced regional gyrification was detected in left posterior ramus of the lateral sulcus and reduced sulcal depths were detected in occipital pole, cuneus, and posterior ramus of the lateral sulcus in patients. Furthermore, pattern analysis revealed that each metric shows different discriminative abilities to distinguish patients with generalized epilepsy and non-epileptic subjects (Classification accuracy: 61.1%, 62.2%, 58.8%, 61.1% and 60% for GMV, WMV, CSFV, Cortical gyrification and sulcal depth respectively). In conclusion, this study provides a comprehensive understanding about regional structural changes (cortical and subcortical) associated with generalized epilepsy under region-based morphometry. However, pattern analyses do not provide adequate discriminative power and therefore the clinical utility of findings is limited.

Prostaglandin F2A Disturbs Oogenesis by Causing Meiotic Spindle Damage

Abstract According to recent data, prostaglandin F2 alpha can have a negative influence on meiosis during oogenesis. Previously, we have found that this prostaglandin may accelerate in a dosage-dependent way the postovulatory aging in ovulated mature oocytes, compromising the integrity of their meiotic spindles. Aim. The study aimed to investigate the effects of prostaglandin F2α on the course and outcome of oocyte meiosis in a mouse model. Materials and Methods. Mouse oocytes were matured in vitro in the presence of prostaglandin F2α in a concentration of 100 ng/ml. Their meiotic stage, spindle morphology and chromosome arrangement were assessed by immunofluorescent labeling of tubulin and fluorescent staining of DNA. Results. We obtained a higher percentage of immature oocytes in metaphase I after the treatment than in untreated control oocytes. In addition, there were specific morphological changes in the meiotic spindles of oocytes exposed to prostaglandin F2α associated with a reduced number of fibers. Conclusion. It is probable that prostaglandin F2α has an impact on the microtubule dynamics of the meiotic spindle that can prevent the transition of maturing oocytes to the second meiotic division, most likely by triggering the spindle assembly checkpoint.

TIMP1 regulates ferroptosis in osteoblasts by inhibiting TFRC ubiquitination: an in vitro and in vivo study

BackgroundIn clinical practice, alterations in the internal environment of type 2 diabetes can significantly affect bone quality. While the increased risk of fractures among diabetic patients is well-established, the precise mechanisms by which hyperglycemia influences bone quality remain largely unclear.MethodsWestern blotting, immunohistochemistry (IHC), and micro-CT were used to examine ferroptosis-related protein expression and bone morphology changes in the bone tissues of type 2 diabetic mice. The CCK8 assay determined the optimal conditions for inducing ferroptosis in osteoblasts by high glucose and high fat (HGHF). Ferroptosis phenotypes in osteoblasts were analyzed using flow cytometry, Western blotting, and two-photon laser confocal microscopy. Transcriptomic sequencing of the control and HGHF groups, followed by bioinformatic analysis, identified and validated key genes. TIMP1 was knocked down in osteoblasts to assess its impact on ferroptosis, while TFRC expression was inhibited and activated to verify the role of TIMP1 in regulating ferroptosis through TFRC. The therapeutic effect of TIMP1 inhibition on osteoporosis was evaluated in a type 2 diabetic mouse model.ResultsThe expression of TIMP1 is increased in type 2 diabetic osteoporosis. In vitro, TIMP1 knockout inhibited ferroptosis in osteoblasts induced by high glucose and high fat (HGHF). However, overexpression of TFRC reversed the ferroptosis inhibition caused by TIMP1 knockout. Suppression of TIMP1 expression alleviated the progression of osteoporosis in type 2 diabetic mice. Mechanistic studies suggest that TIMP1 regulates HGHF-induced ferroptosis in osteoblasts through TFRC.ConclusionThis study demonstrates that TIMP1 expression is increased during type 2 diabetic osteoporosis and that TIMP1 promotes ferroptosis in osteoblasts by regulating TFRC. These findings suggest that TIMP1 is a promising novel therapeutic target for type 2 diabetic osteoporosis.

Evidence of rustrela virus-associated feline staggering disease in Sweden since the 1970s

BackgroundStaggering disease (SD) is a severe neurological disease that has been regularly reported in Swedish cats since the beginning of the 1970s. The aetiology of SD has been debated, but novel rustrela virus (RusV) was recently suggested as the causative agent in Swedish cases dating from 2017 onwards. However, whether RusV was associated with earlier cases of feline SD in Sweden remained unknown. Further, presence of RusV in extraneural tissues of RusV-infected cats and viral transmission routes for RusV are still unknown. Therefore, we investigated the presence of RusV in nervous tissue of historical cases of plausible feline SD in Sweden, dating back to the 1970s, as well as the presence of RusV in selected extraneural tissues.Formalin-fixed, paraffin-embedded brain and spinal cord from 14 encephalitic cats matching the criteria for SD based on clinical and pathological records, and five non-encephalitic control cats were screened for the presence of RusV antigen and RNA using immunohistochemistry (IHC) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively. Extraneural presence of RusV antigen was investigated by IHC in four known RusV-positive cats. Morphologic changes were evaluated using light microscopy. In addition, the 14 encephalitic cats were tested for Borna disease virus 1 (BoDV-1) RNA by RT-qPCR.ResultsMorphologic findings compatible with SD were confirmed in 13 of 14 encephalitic cats. All 13 cats were RusV-positive by IHC and 12 of them also by RT-qPCR. One encephalitic cat, morphologically and clinically untypical of SD, as well as all control cats tested negative for RusV RNA and showed either negative or uncertain RusV immunolabeling. There was no firm evidence of extraneural presence of RusV. All encephalitic cats were negative for BoDV-1.ConclusionsWe show that RusV has infected cats in Sweden as far back as the 1970s, whereas BoDV-1 was not detected in any of the investigated cats. This further strengthens RusV as the causative agent of feline SD. Our findings suggest that RusV is strongly neurotropic in cats and that the cat may represent a dead-end host. Further investigations into the pathogenesis of RusV-associated meningoencephalomyelitis in cats are warranted, including disease transmission, pathophysiologic responses and mechanisms of neuronal dysfunction.

Lidar-Derived Decadal Change in Barrier Morphology: A Case Study of Waisanding, Taiwan

Barrier change is a complex process of evolution of coastal topography, which is related to the interaction of driving forces such as waves, tides and sea level rise (SLR) with beaches. The Waisanding Barrier (WSDB) in Taiwan has suffered from continuous beach erosion in recent decades. Some short-term studies have been carried out to understand the characteristics of the barrier change to provide a reference for future barrier protection. In this paper, the digital elevation model (DEM) measured by LiDAR (Light Detection and Ranging), over nearly two decades was used to analyze the morphological changes, the land area and volume. The changes in the morphology, including the whole shoreline, duneline height, width of forebeach and backbarrier, are investigated. The WSDB’s land area and land volume were analyzed to show a continuous decrease by a rate of −0.418 × 106 m2/year and −3.96 × 105 m3/year, respectively. The corresponding average land volume (LV) decrease in elevation can be estimated to be −0.0286 m/year. The changes in these features are discussed and relate to land subsidence, sea level rise and large waves induced by typhoons passing near WSDB.

Neuronal Cell Rearrangement During Aging: Antioxidant Compounds as a Potential Therapeutic Approach

Aging is a natural process that leads to time-related changes and a decrease in cognitive abilities, executive functions, and attention. In neuronal aging, brain cells struggle to respond to oxidative stress. The structure, function, and survival of neurons can be mediated by different pathways that are sensitive to oxidative stress and age-related low-energy states. Mitochondrial impairment is one of the most noticeable signs of brain aging. Damaged mitochondria are thought to be one of the main causes that feed the inflammation related to aging. Also, protein turnover is involved in age-related impairments. The brain, due to its high oxygen usage, is particularly susceptible to oxidative damage. This review explores the mechanisms underlying neuronal cell rearrangement during aging, focusing on morphological changes that contribute to cognitive decline and increased susceptibility to neurodegenerative diseases. Potential therapeutic approaches are discussed, including the use of antioxidants (e.g., Vitamin C, Vitamin E, glutathione, carotenoids, quercetin, resveratrol, and curcumin) to mitigate oxidative damage, enhance mitochondrial function, and maintain protein homeostasis. This comprehensive overview aims to provide insights into the cellular and molecular processes of neuronal aging and highlight promising therapeutic avenues to counteract age-related neuronal deterioration.

DsbA-L activates TGF-β1/SMAD3 signaling and M2 macrophage polarization by stimulating AKT1 and NLRP3 to promote pulmonary fibrosis

BackgroundPulmonary fibrosis (PF) is a progressive and difficult-to-heal lung disease that poses a significant threat to human life and health. This study aimed to investigate the potential pathological mechanisms of PF and to identify new avenues for the treatment of PF.MethodsClinical samples were collected to assess the effect of disulfide-bond A oxidoreductase-like protein (DsbA-L) on PF. TGF-β1-induced MLE-12 cell model and bleomycin (BLM)-induced mice model were established. Changes in physiological morphology and fibrosis were observed in the lung tissues. The degree of apoptosis and the mitochondrial function was analyzed. The expression of relative cytokines was examined. The CD68+/CD206+ ratio was determined to indicate M2 macrophage polarization.ResultsThe expression of DsbA-L was upregulated in patients with PF and PF-like models. In vitro, DsbA-L overexpression exacerbated TGF-β1-induced the deposition of extracellular matrix (ECM), apoptosis, inflammation, and mitochondrial damage, whereas DsbA-L silencing exerted the opposite effects. DsbA-L silencing inhibited the activation of AKT1, NLRP3, and SMAD3 by TGF-β1. MLE-12 cells silencing DsbA-L limited the polarization of RAW264.7 cells towards the M2 phenotype. AKT1 agonist or NLRP3 agonist reversed the role of DsbA-L silencing in inhibiting the TGF-β1/SMAD3 pathway and M2 macrophage polarization. In vivo, DsbA-L knockout protected mice from PF-like pathological damage caused by BLM.ConclusionDsbA-L exhibited a significant profibrotic effect in lung epithelial cells and mice, which increased the levels of AKT1 and NLRP3 to activate the TGF-β1/SMAD3 pathway and M2 macrophage polarization. These findings could shed light on new clues for comprehension and treatment of PF.