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Journal of Integrative Neuroscience Jun 2024root, cataloged as "" in the Korean Pharmacopeia, is rich in various anthraquinones known for their anti-inflammatory and antioxidant properties. Formulations...
BACKGROUND
root, cataloged as "" in the Korean Pharmacopeia, is rich in various anthraquinones known for their anti-inflammatory and antioxidant properties. Formulations containing are traditionally employed for treating neurological conditions. This study aimed to substantiate the antiepileptic and neuroprotective efficacy of root extract (RTE) against trimethyltin (TMT)-induced epileptic seizures and hippocampal neurodegeneration.
METHODS
The constituents of RTE were identified by ultra-performance liquid chromatography (UPLC). Experimental animals were grouped into the following five categories: control, TMT, and three TMT+RTE groups with dosages of 10, 30, and 100 mg/kg. Seizure severity was assessed daily for comparison between the groups. Brain tissue samples were examined to determine the extent of neurodegeneration and neuroinflammation using histological and molecular biology techniques. Network pharmacology analysis involved extracting herbal targets for and disease targets for epilepsy from multiple databases. A protein-protein interaction network was built using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and pivotal targets were determined by topological analysis. Enrichment analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool to elucidate the underlying mechanisms.
RESULTS
The RTE formulation was found to contain sennoside A, sennoside B, chrysophanol, emodin, physcion, (+)-catechin, and quercetin-3-O-glucuronoid. RTE effectively inhibited TMT-induced seizures at 10, 30, and 100 mg/kg dosages and attenuated hippocampal neuronal decay and neuroinflammation at 30 and 100 mg/kg dosages. Furthermore, RTE significantly reduced mRNA levels of tumor necrosis factor (), glial fibrillary acidic protein (), and in hippocampal tissues. Network analysis revealed TNF, Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Protein c-fos (FOS), RAC-alpha serine/threonine-protein kinase (AKT1), and Mammalian target of rapamycin (mTOR) as the core targets. Enrichment analysis demonstrated significant involvement of components in neurodegeneration ( = 4.35 × 10-5) and TNF signaling pathway ( = 9.94 × 10-5).
CONCLUSIONS
The and analyses performed in this study suggests that RTE can potentially modulate TMT-induced epileptic seizures and neurodegeneration. Therefore, root is a promising herbal treatment option for antiepileptic and neuroprotective applications.
Topics: Animals; Neuroprotective Agents; Trimethyltin Compounds; Plant Extracts; Rheum; Plant Roots; Male; Anticonvulsants; Epilepsy; Hippocampus; Disease Models, Animal; Neurodegenerative Diseases; Computer Simulation; Network Pharmacology; Protein Interaction Maps; Rats
PubMed: 38940090
DOI: 10.31083/j.jin2306122 -
Molecules (Basel, Switzerland) Jun 2024Ultraviolet B (UVB) exposure can contribute to photoaging of skin. is rich in ursolic acid (UA), which is beneficial to the prevention of photoaging. Because UA is...
Ultraviolet B (UVB) exposure can contribute to photoaging of skin. is rich in ursolic acid (UA), which is beneficial to the prevention of photoaging. Because UA is hardly soluble in water, the extract (COE) was obtained using water as the antisolvent to separate the components containing UA from the crude extract of . The effect of COE on UVB damage was assessed using . The results showed that COE could increase the lifespan and enhance the antioxidant enzyme activity of exposed to UVB while decreasing the reactive oxygen species (ROS) level. At the same time, COE upregulated the expression of antioxidant-related genes and promoted the migration of SKN-1 to the nucleus. Moreover, COE inhibited the expression of the downstream gene and the extension of the lifespan in mutants exposed to UVB, indicating that SKN-1 was required for COE to function. Our findings indicate that COE mainly ameliorates the oxidative stress caused by UVB in via the SKN-1/Nrf2 pathway.
Topics: Animals; Caenorhabditis elegans; Triterpenes; Ursolic Acid; Ultraviolet Rays; Plant Extracts; Caenorhabditis elegans Proteins; Oxidative Stress; Cornus; Antioxidants; Reactive Oxygen Species; Skin Aging; Transcription Factors; DNA-Binding Proteins; Longevity; NF-E2-Related Factor 2
PubMed: 38930783
DOI: 10.3390/molecules29122718 -
Transfusion Medicine (Oxford, England) Jun 2024Having faster plasma thawing devices could be beneficial for transfusion services, as it may improve the rapid availability of thawed plasma for bleeding patients, and...
BACKGROUND
Having faster plasma thawing devices could be beneficial for transfusion services, as it may improve the rapid availability of thawed plasma for bleeding patients, and it might remove the need to have extended pre-thawed plasma: thus, reducing unnecessary plasma wastage.
STUDY DESIGN AND METHODS
The aims of this study were to assess (a) the thawing times and (b) in vitro haemostatic quality of thawed plasma using Barkey Plasmatherm V (PTV) at 37 and 45°C versus Barkey Plasmatherm Classic (PTC) at 37 and 45°C, Sarstedt Sahara-III Maxitherm (SS-III) at 37°C and Helmer Scientific Thermogenesis Thermoline (TT) at 37°C. Haemostatic quality was assessed using LG-Octaplas at three different time points: baseline (5 min), 24 and 120 h after thawing.
RESULTS
The thawing time (SD) of 2 and 4 units was significantly different between different thawers. PTV at 45°C was the fastest method for both 2 and 4 units (7.06 min [0.68], 9.6 min [0.87], respectively). SS-III at 37°C being the slowest method (24.69 min [2.09] and 27.18 min [4.4], respectively) (p = < 0.05). Baseline measurements for all assays showed no significant difference in the prothrombin time, fibrinogen, FII, FV, protein C activity or free protein S antigen between all methods tested. However, at baseline PTV (both 37°C and 45°C) had significantly higher levels of FVII, FVIII and FXI and shortened activated partial thromboplastin time.
DISCUSSION
PTV was the quickest method at thawing plasma at both 37 and at 45°C. The haemostatic quality of plasma thawed at 45 versus 37°C was not impaired. Thawing frozen plasma at 45°C should be considered.
PubMed: 38923078
DOI: 10.1111/tme.13061 -
ELife Jun 2024Cognitive decline is a significant health concern in our aging society. Here, we used the model organism to investigate the impact of the IIS/FOXO pathway on...
Cognitive decline is a significant health concern in our aging society. Here, we used the model organism to investigate the impact of the IIS/FOXO pathway on age-related cognitive decline. The Insulin/IGF-1 receptor mutant exhibits a significant extension of learning and memory span with age compared to wild-type worms, an effect that is dependent on the DAF-16 transcription factor. To identify possible mechanisms by which aging mutants maintain learning and memory with age while wild-type worms lose neuronal function, we carried out neuron-specific transcriptomic analysis in aged animals. We observed downregulation of neuronal genes and upregulation of transcriptional regulation genes in aging wild-type neurons. By contrast, IIS/FOXO pathway mutants exhibit distinct neuronal transcriptomic alterations in response to cognitive aging, including upregulation of stress response genes and downregulation of specific insulin signaling genes. We tested the roles of significantly transcriptionally-changed genes in regulating cognitive functions, identifying novel regulators of learning and memory. In addition to other mechanistic insights, a comparison of the aged vs young neuronal transcriptome revealed that a new set of potentially neuroprotective genes is upregulated; instead of simply mimicking a young state, may enhance neuronal resilience to accumulation of harm and take a more active approach to combat aging. These findings suggest a potential mechanism for regulating cognitive function with age and offer insights into novel therapeutic targets for age-related cognitive decline.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Forkhead Transcription Factors; Transcriptome; Neurons; Cognitive Aging; Aging; Receptor, Insulin; Signal Transduction; Gene Expression Regulation; Memory; Gene Expression Profiling
PubMed: 38922671
DOI: 10.7554/eLife.95621 -
Cells Jun 2024The opioid epidemic continues to be a major public health issue that includes millions of people who inject drugs (PWID). PWID have increased incidence of serious...
The opioid epidemic continues to be a major public health issue that includes millions of people who inject drugs (PWID). PWID have increased incidence of serious infections, including HIV as well as metabolic and inflammatory sequelae. We sought to discern the extent of systemic alterations in humoral immunity associated with injection drug use, including alterations in the plasma proteome and its regulation of B cell responsiveness. Comprehensive plasma proteomics analysis of HIV negative/hepatitis C negative individuals with a history of recent injection heroin use was performed using mass spectrometry and ELISA. The effects of plasma from PWID and healthy controls on the in vitro proliferation and transcriptional profile of B cell responses to stimulation were determined by flow cytometry and RNA-Seq. The plasma proteome of PWID was distinct from healthy control individuals, with numerous immune-related analytes significantly altered in PWID, including complement (C3, C5, C9), immunoglobulin (IgD, IgM, kappa light chain), and other inflammatory mediators (CXCL4, LPS binding protein, C-reactive protein). The plasma of PWID suppressed the in vitro proliferation of B cells. Transcriptome analysis indicated that PWID plasma treatment increased B cell receptor and CD40 signaling and shifted B cell differentiation from plasma cell-like toward germinal center B cell-like transcriptional profiles. These results indicate that the systemic inflammatory milieu is substantially altered in PWID and may impact their B cell responses.
Topics: Humans; B-Lymphocytes; Male; Adult; Female; Cell Proliferation; Substance Abuse, Intravenous; Proteome; Middle Aged
PubMed: 38920641
DOI: 10.3390/cells13121011 -
ACS Applied Bio Materials Jun 2024β-Thalassemia especially transfusion-dependent thalassemia (TDT) associates with a hypercoagulable state, which is the main cause of thromboembolic events (TEE). Plasma...
A Compact Differential Dynamic Microscopy-based Device (cDDM): An Approach Tool for Early Detection of Hypercoagulable State in Transfusion-Dependent-β-Thalassemia Patients.
β-Thalassemia especially transfusion-dependent thalassemia (TDT) associates with a hypercoagulable state, which is the main cause of thromboembolic events (TEE). Plasma viscosity and rheological parameters could be essential markers for determining hypercoagulable state in β-thalassemia patients. The traditional methods for measuring viscosity are often limited by large sample volumes and are impractical for routine clinical monitoring. The compact differential dynamic microscopy-based device (cDDM), an optical microscopy for quantitative rheological assessment, was developed and applied for prognosis of the hypercoagulable state in β-TDT with and without splenectomy. The device was performed plasma viscosity measurement using low plasma volume (8 μL) and revealed a value as modulus of complex viscosity |η(ω)| in 7 min. We also parallelly demonstrated the correlation of the viscosity and related-coagulable parameters: complete blood count, prothrombin time (PT), activated partial thromboplastin time (APTT), protein C (PC), protein S (PS), CD62P and CD63 expression, and platelet aggregation test. The thalassemia plasma exhibited a higher value of |η(ω)| than healthy plasma, which can represent a different viscoelastic property among the groups. Even all related-coagulable parameters indicated hypercoagulable state in both nonsplenectomies and splenectomies β-TDT patients when compared to control, only high platelet numbers significantly correlated to high plasma viscosity in the splenectomy group. However, the other coagulable parameters have shown a trend of positive relationship with high plasma viscosity in all β-1thalassemia TDT patients. The relative results suggested that our device would be an approach tool for early detection of hypercoagulable state in transfusion-dependent-β-thalassemia patients, which can help to prevent TEE and the critical consequent-complications.
PubMed: 38920024
DOI: 10.1021/acsabm.4c00516 -
Naunyn-Schmiedeberg's Archives of... Jun 2024TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that is capable of apoptosis induction selectively in tumor cells. Although TRAIL has...
TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that is capable of apoptosis induction selectively in tumor cells. Although TRAIL has been harnessed in numerous clinical trials, resistance to TRAIL-induced apoptosis is a major challenge ahead of this therapy in various cancer models as well as in leukemia. Since histone deacetylases (HDACs) are known to affect drug resistance in malignant cells, the present study aimed to evaluate the potential of fisetin for sensitization of MOLT-4 and K-562 leukemic cells to TRAIL-induced apoptosis. The MOLT-4 and K-562 cells were treated with increasing concentrations of fisetin and its impact on the growth inhibition and apoptosis induction of TRAIL were evaluated by MTT and Annexin V/7-AAD assays. The impact of fisetin on the mRNA and protein expression levels of apoptosis regulatory genes such as BIRC2/c-IAP1, CFLAR/cFLIP, CASP3, CASP7, CASPP9, TNFRSF10A/DR4, TNFRSF10B/DR5, and BID were examined by PCR array, qRT-PCR, and flow cytometry. Pre-treatment of MOLT-4 and K-562 cells with fisetin reduced the IC50 of TRAIL in growth inhibition along with an improvement in apoptosis induction by TRAIL. The expression of the BIRC2 gene encoding antiapoptotic protein c-IAP1 downregulated in the fisetin-treated cells while the expressions of TNFRSF10A and TNFRSF10B encoding TRAIL death receptors increased. Fisetin demonstrated a potential for alleviating the TRAIL resistance by modulating the apoptosis regulatory factors and improving the expressions of TRAIL receptors that could facilitate the application of TRAIL in cancer therapies.
PubMed: 38918236
DOI: 10.1007/s00210-024-03101-y -
Thrombosis and Haemostasis Jun 2024Venous thromboembolism (VTE) is predisposed by thrombotic mutations in patients with hereditary thrombophilia. Although prothrombin deficiencies caused by homozygous or...
BACKGROUND
Venous thromboembolism (VTE) is predisposed by thrombotic mutations in patients with hereditary thrombophilia. Although prothrombin deficiencies caused by homozygous or compound heterozygous mutations are associated with bleeding diathesis, rare cases have shown a correlation between heterozygous prothrombin mutations and thrombosis.
MATERIAL AND METHODS
We surveyed genetic variants involved in thrombosis and hemostasis in 347 patients with unprovoked VTE or having a positive family history of thrombosis. For patients identified with heterozygous prothrombin mutations, we conducted family investigations and performed thrombin generation test (TGT) to elucidate the thrombotic risk. Novel mutants were expressed and subjected to functional assays to clarify the underlying thrombotic mechanisms.
RESULTS
Heterozygous prothrombin mutations were identified in 3.5% of patients (12/347), including three novel mutations Phe382Ser, Phe382Leu and Asp597Tyr found in one patient each, as well as previously reported Arg541Trp mutation in four patients and Arg596Gln mutation in five patients. A total of 42 mutation carriers were identified within the 12 pedigrees, among whom 64.3% (27/42) had experienced thrombotic events. TGT results demonstrated hypercoagulability for carriers of the five mutations, with Arg596Gln showing the highest thrombin generation potential followed by Arg541Trp. The Phe382-associated mutations severely impaired thrombomodulin binding ability of thrombin, resulting in obviously reduced protein C (PC) activation. The Asp597Tyr mutation exhibited a mild reduction in both antithrombin inhibition and PC activation reactions.
CONCLUSIONS
The presence of heterozygous prothrombin mutations represents a potential genetic predisposition for VTE. All thrombosis associated mutations potentiate coagulation activity by either conferring antithrombin resistance and/or impairing PC pathway activity.
PubMed: 38914130
DOI: 10.1055/a-2350-8338 -
Lipids in Health and Disease Jun 2024Overweight, often known as obesity, is the abnormal and excessive accumulation of fat that exposes the health of a person at risk by increasing the likelihood that they...
BACKGROUND
Overweight, often known as obesity, is the abnormal and excessive accumulation of fat that exposes the health of a person at risk by increasing the likelihood that they may experience many chronic conditions. Consequently, obesity has become a global health threat, presenting serious health issues, and attracting a lot of attention in the healthcare profession and the scientific community.
METHOD
This study aims to explore the anti-adipogenic properties of 7-MEGA™ in an attempt to address obesity, using both in vitro and in vivo research. The effects of 7MEGA™ at three distinct concentrations were investigated in obese mice who were given a high-fat diet (HFD) and 3T3-L1 adipocytes.
RESULTS
7MEGA™ decreased the total fat mass, overall body weight, and the perirenal and subcutaneous white adipose tissue (PWAT and SWAT) contents in HFD mice. Additionally, 7MEGA™ showed promise in improving the metabolic health of individuals with obesity and regulate the levels of insulin hormone, pro-inflammatory cytokines and adipokines. Furthermore, Peroxisome proliferator-activated receptors (PPAR) α and γ, Uncoupling Protein 1 (UCP-1), Sterol Regulatory Element-Binding Protein 1 (SREBP-1), Fatty Acid-Binding Protein 4 (FABP4), Fatty Acid Synthase (FAS), Acetyl-CoA Carboxylase (ACC), Stearoyl-CoA Desaturase-1 (SCD-1) and CCAAT/Enhancer-Binding Protein (C/EBPα) were among the adipogenic regulators that 7MEGA™ could regulate.
CONCLUSION
In summary, this study uncovered that 7MEGA™ demonstrates anti-adipogenic and anti-obesity effects, suggesting its potential in combating obesity.
Topics: Animals; Diet, High-Fat; Adipogenesis; Obesity; Mice; 3T3-L1 Cells; Adipocytes; Mice, Inbred C57BL; Male; PPAR gamma; Sterol Regulatory Element Binding Protein 1; Stearoyl-CoA Desaturase; Mice, Obese; Fatty Acid-Binding Proteins; Adipokines; Anti-Obesity Agents; Uncoupling Protein 1; Adipose Tissue, White; CCAAT-Enhancer-Binding Proteins
PubMed: 38909257
DOI: 10.1186/s12944-024-02175-0 -
Medicina 2024Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is a late onset neurodegenerative disorder. Its genetic basis has recently been identified in...
Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is a late onset neurodegenerative disorder. Its genetic basis has recently been identified in the gene encoding a subunit of the Replication Factor C (RFC1). We present the case of a 62-year-old woman who experienced a history of a biphasic presentation of imbalance and gait disorders, with rapid onset of symptoms followed by slow and progressive neurological deterioration. The diagnostic process was challenging, and numerous tests were conducted to rule out acquired and genetic causes of ataxia, leading to a diagnosis of late-onset idiopathic cerebellar ataxia. Subsequently, vestibular function tests identified severe bilateral vestibulopathy. This led to considering CANVAS among the diagnoses, which was ultimately confirmed through genetic testing (biallelic expansion of the pentanucleotide AAGGG in the RFC1 gene). This case highlights the importance of this new described genetic disease and its subacute presentation variant, emphasizing the relevance of objective vestibular function tests in idiopathic ataxias to achieve proper diagnosis and eventual genetic counseling for offspring.
Topics: Humans; Female; Middle Aged; Cerebellar Ataxia; Bilateral Vestibulopathy; Syndrome; Replication Protein C; Vestibular Function Tests
PubMed: 38907973
DOI: No ID Found