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Frontiers in Pharmacology 2024Tetrandrine (Tet) is the main pharmacological component of S. Moore, which is a well-documented traditional Chinese medicine known for its diuretic and antihypertensive...
INTRODUCTION
Tetrandrine (Tet) is the main pharmacological component of S. Moore, which is a well-documented traditional Chinese medicine known for its diuretic and antihypertensive properties. Unraveling the specific targets and mechanisms of Tet involved in inducing diuresis and mitigating hypertension can provide valuable insights into its therapeutic effects. This study aimed to explore the diuretic and antihypertensive targets and mechanisms of Tet using chemical biology coupled with activity analyses and .
METHODS
The diuretic effects of Tet were evaluated using a water-loaded mouse model. The direct target proteins for the diuretic and antihypertensive effects of Tet were determined using chemical biology. Furthermore, the molecular mechanism of Tet binding to target proteins was analyzed using a multidisciplinary approach based on the structure and function of the proteins. Finally, the effects of the Tet-targeted protein on downstream signaling pathways and blood pressure were evaluated in hypertensive model rats.
RESULTS
Tet exhibited significant antihypertensive and potassium-preserving diuretic effects. The mechanism underlying these effects involves the modulation of the enzyme activity by covalent binding of Tet to Cys423 of CYP11A1. This interaction alters the stability of heme within CYP11A1, subsequently impeding electron transfer and inhibiting aldosterone biosynthesis.
DISCUSSION
This study not only revealed the mechanism of the diuretic and antihypertensive effects of Tet but also discovered a novel covalent inhibitor of CYP11A1. These findings contribute significantly to our understanding of the therapeutic potential of Tet and provide a foundation for future research in the development of targeted treatments for hypertension.
PubMed: 38948468
DOI: 10.3389/fphar.2024.1387756 -
Frontiers in Pharmacology 2024The management of neurological disorders heavily relies on neurotherapeutic drugs, but notable concerns exist regarding their possible negative effects on reproductive... (Review)
Review
The management of neurological disorders heavily relies on neurotherapeutic drugs, but notable concerns exist regarding their possible negative effects on reproductive health. Traditional preclinical models often fail to accurately predict reprotoxicity, highlighting the need for more physiologically relevant systems. Organoid models represent a promising approach for concurrently studying neurotoxicity and reprotoxicity, providing insights into the complex interplay between neurotherapeutic drugs and reproductive systems. Herein, we have examined the molecular mechanisms underlying neurotherapeutic drug-induced reprotoxicity and discussed experimental findings from case studies. Additionally, we explore the utility of organoid models in elucidating the reproductive complications of neurodrug exposure. Have discussed the principles of organoid models, highlighting their ability to recapitulate neurodevelopmental processes and simulate drug-induced toxicity in a controlled environment. Challenges and future perspectives in the field have been addressed with a focus on advancing organoid technologies to improve reprotoxicity assessment and enhance drug safety screening. This review underscores the importance of organoid models in unraveling the complex relationship between neurotherapeutic drugs and reproductive health.
PubMed: 38948466
DOI: 10.3389/fphar.2024.1412188 -
Mycobiology 2024The species within the family Cunninghamellaceae during an investigation of soil microfungi in Korea, in which three strains were isolated from Gangwon, Chungbuk, and...
The species within the family Cunninghamellaceae during an investigation of soil microfungi in Korea, in which three strains were isolated from Gangwon, Chungbuk, and Gyeongbuk provinces, designated as KNUF-22-121A, KNUF-22-126A, and KNUF-22-316, respectively. Because the morphological and molecular analyses of these three strains were identical, KNUF-22-316 underwent further detailed study. Phylogenetic analyses based on the concatenated nucleotide sequences of the internal transcribed spacer region and the large subunit 28S rRNA gene revealed that the strain belonged to the genus , but occupied a distinct phylogenetic position. The strain KNUF-22-316 was compared with closely related species CGMCC 3.16257 and CGMCC 3.16259, morphologically different with shorter sporangiophores, smaller sporangia and columellae, and the consistent presence of collars. Here, we provide a detailed description and images of this proposed new species, which we have named sp. nov.
PubMed: 38948449
DOI: 10.1080/12298093.2024.2366047 -
World Journal of Hepatology Jun 2024Hepatocellular carcinoma (HCC) is a primary contributor to cancer-related mortality on a global scale. However, the underlying molecular mechanisms are still poorly...
BACKGROUND
Hepatocellular carcinoma (HCC) is a primary contributor to cancer-related mortality on a global scale. However, the underlying molecular mechanisms are still poorly understood. Long noncoding RNAs are emerging markers for HCC diagnosis, prognosis, and therapeutic target. No study of LINC01767 in HCC was published.
AIM
To conduct a multi-omics analysis to explore the roles of LINC01767 in HCC for the first time.
METHODS
DESeq2 Package was used to analyze different gene expressions. Receiver operating characteristic curves assessed the diagnostic performance. Kaplan-Meier univariate and Cox multivariate analyses were used to perform survival analysis. The least absolute shrinkage and selection operator (LASSO)-Cox was used to identify the prediction model. Subsequent to the validation of LINC01767 expression in HCC fresh frozen tissues through quantitative real time polymerase chain reaction, next generation sequencing was performed following LINC01767 over expression (GSE243371), and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes/Gene Set Enrichment Analysis/ingenuity pathway analysis was carried out. experiment in Huh7 cell was carried out.
RESULTS
LINC01767 was down-regulated in HCC with a log fold change = 1.575 and was positively correlated with the cancer stemness. LINC01767 was a good diagnostic marker with area under the curve (AUC) [0.801, 95% confidence interval (CI): 0.751-0.852, = 0.0106] and an independent predictor for overall survival (OS) with hazard ratio = 1.899 (95%CI: 1.01-3.58, = 0.048). LINC01767 nomogram model showed a satisfied performance. The top-ranked regulatory network analysis of LINC01767 showed the regulation of genes participating various pathways. LASSO regression identified the 9-genes model showing a more satisfied performance than 5-genes model to predict the OS with AUC > 0.75. LINC01767 was down-expressed obviously in tumor than para-tumor tissues in our cohort as well as in cancer cell line; the over expression of LINC01767 inhibit cell proliferation and clone formation of Huh7 .
CONCLUSION
LINC01767 was an important tumor suppressor gene in HCC with good diagnostic and prognostic performance.
PubMed: 38948436
DOI: 10.4254/wjh.v16.i6.932 -
World Journal of Experimental Medicine Jun 2024Aortic aneurysm (AA) refers to the persistent dilatation of the aorta, exceeding three centimeters. Investigating the pathophysiology of this condition is important for... (Review)
Review
Aortic aneurysm (AA) refers to the persistent dilatation of the aorta, exceeding three centimeters. Investigating the pathophysiology of this condition is important for its prevention and management, given its responsibility for more than 25000 deaths in the United States. AAs are classified based on their location or morphology. various pathophysiologic pathways including inflammation, the immune system and atherosclerosis have been implicated in its development. Inflammatory markers such as transforming growth factor β, interleukin-1β, tumor necrosis factor-α, matrix metalloproteinase-2 and many more may contribute to this phenomenon. Several genetic disorders such as Marfan syndrome, Ehler-Danlos syndrome and Loeys-Dietz syndrome have also been associated with this disease. Recent years has seen the investigation of novel management of AA, exploring the implication of different immune suppressors, the role of radiation in shrinkage and prevention, as well as minimally invasive and newly hypothesized surgical methods. In this narrative review, we aim to present the new contributing factors involved in pathophysiology of AA. We also highlighted the novel management methods that have demonstrated promising benefits in clinical outcomes of the AA.
PubMed: 38948412
DOI: 10.5493/wjem.v14.i2.91408 -
Data in Brief Aug 2024Over a period of 30,000 to 40,000 years, high-altitude Tibetans have physiologically and genetically adapted to conditions such as hypoxia, low temperature, and...
Over a period of 30,000 to 40,000 years, high-altitude Tibetans have physiologically and genetically adapted to conditions such as hypoxia, low temperature, and high-intensity ultraviolet radiation. Based on the unique physiological and morphological characteristics of the Tibetan people, they have outstanding hypoxia adaptation skills and can continue to thrive in plateau hypoxia. The placenta of high-altitude Tibetans is protected from oxidative stress during delivery; however, little is known about changes in placental protein expression during vaginal delivery. In this study, we aimed to reveal these adaptive mechanisms by studying changes in placental protein expression during vaginal delivery in high-altitude Tibetans, low-altitude Tibetans, and low-altitude Han populations. Studying the changing mechanisms of maternal responses to hypoxia at high altitudes can reveal the molecular mechanisms of maternal and fetal adaptation to hypoxia at high altitudes and provide theories for preventing and treating maternal hypoxia and intrauterine growth and development restriction caused by other diseases.
PubMed: 38948405
DOI: 10.1016/j.dib.2024.110542 -
Asian Journal of Pharmaceutical Sciences Jun 2024Autophagy and mitophagy pose unresolved challenges in understanding the pathology of diabetic heart condition (DHC), which encompasses a complex range of cardiovascular... (Review)
Review
Autophagy and mitophagy pose unresolved challenges in understanding the pathology of diabetic heart condition (DHC), which encompasses a complex range of cardiovascular issues linked to diabetes and associated cardiomyopathies. Despite significant progress in reducing mortality rates from cardiovascular diseases (CVDs), heart failure remains a major cause of increased morbidity among diabetic patients. These cellular processes are essential for maintaining cellular balance and removing damaged or dysfunctional components, and their involvement in the development of diabetic heart disease makes them attractive targets for diagnosis and treatment. While a variety of conventional diagnostic and therapeutic strategies are available, DHC continues to present a significant challenge. Point-of-care diagnostics, supported by nanobiosensing techniques, offer a promising alternative for these complex scenarios. Although conventional medications have been widely used in DHC patients, they raise several concerns regarding various physiological aspects. Modern medicine places great emphasis on the application of nanotechnology to target autophagy and mitophagy in DHC, offering a promising approach to deliver drugs beyond the limitations of traditional therapies. This article aims to explore the potential connections between autophagy, mitophagy and DHC, while also discussing the promise of nanotechnology-based theranostic interventions that specifically target these molecular pathways.
PubMed: 38948399
DOI: 10.1016/j.ajps.2024.100927 -
Journal of Multidisciplinary Healthcare 2024Despite over 30 years of microbiome and skeletal muscle research, no quantitative analysis of sarcopenia and the microbiome literature had been conducted. Our... (Review)
Review
Despite over 30 years of microbiome and skeletal muscle research, no quantitative analysis of sarcopenia and the microbiome literature had been conducted. Our bibliometric study examined research status, hotspots, and future trends. We utilized bibliometric techniques to search the Science Citation Index Extended Database on February 27, 2023, using the Bibliometrix package in R to create a map displaying scientific production and subject categories. Collaborative network maps between countries/regions were visualized using Scimago Graphica, while VOSviewer explored collaboration modes among individuals and institutions. We analyzed the top 25 emerging keywords, top co-occurring keyword networks, and co-occurring keyword clusters using CiteSpace. A total of 997 articles were retrieved for sarcopenia and microbiome, of which 633 papers were analyzed. Both the number of publications and total citation frequency had been continuously increasing. The United States had the highest total citation frequency, while China had the highest number of publications. Research on the impact of the microbiome on sarcopenia was in its nascent stage and spans multiple disciplines, including nutrition, microbiology, geriatrics, immunology, endocrinology and metabolism, molecular biology, and sports medicine. The University of Copenhagen contributed the most to the number of publications (n=16), with Tibbett M (n=7) and Hulver MW (n=7) among the top authors. The most published journal was "Nutrients" (n=24). Analysis of keywords and clusters revealed new research hotspots in microbes and sarcopenia, such as malnutrition, dietary fiber, signaling pathways, frailty, and intestinal permeability. Research on the impact of the microbiome on sarcopenia is in its infancy and spans multiple disciplines. Malnutrition, dietary fiber, signaling pathways, frailty, and intestinal microbes are currently research hotspots. Furthermore, the visual atlas analysis of research on microbes and sarcopenia helps to track the knowledge structure in research fields related to sarcopenia and microbes, providing direction for future research.
PubMed: 38948393
DOI: 10.2147/JMDH.S469747 -
Frontiers in Genetics 2024The Euchromatic Histone Methyl Transferase Protein 2 (EHMT2), also known as G9a, deposits transcriptionally repressive chromatin marks that play pivotal roles in the...
The Euchromatic Histone Methyl Transferase Protein 2 (EHMT2), also known as G9a, deposits transcriptionally repressive chromatin marks that play pivotal roles in the maturation and homeostasis of multiple organs. Recently, we have shown that inactivation in the mouse pancreas alters growth and immune gene expression networks, antagonizing Kras-mediated pancreatic cancer initiation and promotion. Here, we elucidate the essential role of Ehmt2 in maintaining a transcriptional landscape that protects organs from inflammation. Comparative RNA-seq studies between normal postnatal and young adult pancreatic tissue from conditional knockout animals ( ) targeted to the exocrine pancreatic epithelial cells ( and ), reveal alterations in gene expression networks in the whole organ related to injury-inflammation-repair, suggesting an increased predisposition to damage. Thus, we induced an inflammation repair response in the pancreas and used a data science-based approach to integrate RNA-seq-derived pathways and networks, deconvolution digital cytology, and spatial transcriptomics. We also analyzed the tissue response to damage at the morphological, biochemical, and molecular pathology levels. The pancreas displays an enhanced injury-inflammation-repair response, offering insights into fundamental molecular and cellular mechanisms involved in this process. More importantly, these data show that conditional inactivation in exocrine cells reprograms the local environment to recruit mesenchymal and immunological cells needed to mount an increased inflammatory response. Mechanistically, this response is an enhanced injury-inflammation-repair reaction with a small contribution of specific Ehmt2-regulated transcripts. Thus, this new knowledge extends the mechanisms underlying the role of the Ehmt2-mediated pathway in suppressing pancreatic cancer initiation and modulating inflammatory pancreatic diseases.
PubMed: 38948355
DOI: 10.3389/fgene.2024.1412767 -
Clinical Ophthalmology (Auckland, N.Z.) 2024To investigate the influence of laser trabeculoplasty (LTP) on subsequent surgery with combined phacoemulsification/Kahook Dual Blade goniotomy (phaco-KDB) in patients...
PURPOSE
To investigate the influence of laser trabeculoplasty (LTP) on subsequent surgery with combined phacoemulsification/Kahook Dual Blade goniotomy (phaco-KDB) in patients with open-angle glaucoma or intraocular hypertension.
PATIENTS AND METHODS
Patients undergoing phaco-KDB between 2019 and 2021 were divided into previously LTP treated and previously non-LTP treated, and LTP-treatment included argon laser trabeculoplasty (ALT) and selective laser trabeculoplasty (SLT). The primary goal was to investigate if previous LTP influenced later surgical outcome of phaco-KDB. The secondary goal was to investigate if the outcome of LTP could be predictive of the outcome of subsequent phaco-KDB. We also compared IOP- and medication reductions between LTP and non-LTP treated patients.
RESULTS
A total of 111 LTP treated patients were compared to 139 non-LTP treated patients. In LTP treated patients, surgical success of phaco-KDB was 82.9%, compared to 88.5% in non-LTP treated patients (P=0.20). Reductions in IOP and medications were similar between groups. Furthermore, within the LTP group, patients with successful LTP-treatment had a subsequent surgical success of phaco-KDB in 80.7%, compared to 83.0% in patients with unsuccessful LTP-treatment (P=0.765).
CONCLUSION
Previous LTP treatment does not predict the outcome of phaco-KDB. Furthermore, no correlation was found between the LTP effect and a later surgical success of phaco-KDB.
PubMed: 38948342
DOI: 10.2147/OPTH.S468809