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Computers in Biology and Medicine Jun 2024CDD-2103 is an herbal prescription used to treat ulcerative colitis (UC). This study aimed to uncover its mechanism by integrating metabolomics and serum-feces...
BACKGROUND
CDD-2103 is an herbal prescription used to treat ulcerative colitis (UC). This study aimed to uncover its mechanism by integrating metabolomics and serum-feces pharmacochemistry-based network pharmacology.
METHODS
A DSS-induced chronic colitis mice model was used to evaluate the anti-colitis effect of CDD-2103. Serum and feces metabolomics were conducted to identify differential metabolites and pathways. In the serum-feces pharmacochemistry study, biological samples were collected from rats treated with CDD-2103. Then, network pharmacology was utilized to predict the targets of the identified compounds. Critical genes were extracted through the above-integrated analysis. The interactions between targets, CDD-2103, and its compounds were validated through molecular docking, immunoblotting, and enzyme activity assays.
RESULTS
CDD-2103 alleviated ulcerous symptoms and colonic injuries in colitis mice. Metabolomics study identified differential metabolites associated with tryptophan, glycerophospholipid, and linoleic acid metabolisms. The serum-feces pharmacochemistry study revealed twenty-three compounds, which were subjected to network pharmacology analysis. Integration of these results identified three key targets (AHR, PLA2, and PTGS2). Molecular docking showed strong affinities between the compounds and targets. PTGS2 was identified as a hub gene targeted by most CDD-2103 compounds. Immunoblotting and enzyme activity assays provided further evidence that CDD-2103 alleviates UC, potentially through its inhibitory effect on cyclooxygenase-2 (COX-2, encoded by PTGS2), with alkaloids and curcuminoids speculated as crucial anti-inflammatory compounds.
CONCLUSION
This integrated strategy reveals the mechanism of CDD-2103 and provides insights for developing herbal medicine-based therapies for UC.
PubMed: 38941901
DOI: 10.1016/j.compbiomed.2024.108775 -
Medicine Jun 2024Species of the genus Codonopsis (Campanulaceae) have a long history of application, acclaimed for its edible and therapeutic attributes. Scholarly inquiries into... (Review)
Review
Species of the genus Codonopsis (Campanulaceae) have a long history of application, acclaimed for its edible and therapeutic attributes. Scholarly inquiries into Codonopsis span botany, phytochemistry, quality assurance, pharmacodynamics, and toxicity, revealing a rich and comprehensive body of knowledge. This study synthesizes information from esteemed scientific databases like SciFinder, PubMed, China National Knowledge Infrastructure, and Chinese herbal classics to create a thorough scientific conceptual and theoretical framework for Codonopsis research. In this article, the phytochemical composition includes saccharides, polyacetylenes, polyenes, flavonoids, alkaloids, lignans, terpenoids, and organic acids was summarized. To date, over 350 monomeric compounds have been isolated and identified from Codonopsis, with recent studies primarily focusing on polysaccharides, aromatic derivatives, lignans, and polyacetylenes. Codonopsis exhibits broad pharmacological activities across various systems, including immune, blood, cardiovascular, central nervous, and digestive systems, with no significant toxicity or adverse effects reported. The existing research, focusing on various extracts and active parts without identifying specific active molecules, complicates the understanding of the mechanisms of action. There is an urgent need to advance research on the chemical composition and pharmacological effects to fully elucidate its pharmacodynamic properties and the basis of its material composition. Such efforts are crucial for the rational development, utilization, and clinical application of this herb.
Topics: Codonopsis; Humans; Phytochemicals; Drugs, Chinese Herbal; Lignans; Alkaloids
PubMed: 38941387
DOI: 10.1097/MD.0000000000038632 -
Medicine Jun 2024Combining hydromorphone with ropivacaine in ultrasound-guided erector spinae plane blocks enhances postoperative analgesia and reduces interleukin-6 expression in breast... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Combining hydromorphone with ropivacaine in ultrasound-guided erector spinae plane blocks enhances postoperative analgesia and reduces interleukin-6 expression in breast surgery patients.
METHODS
In this study, breast cancer patients undergoing modified radical mastectomy were randomized into 3 groups for anesthesia (30 patients in each group): standard general (group C), Erector Spinae Plane Block (ESPB) with ropivacaine (group R), and ESPB with ropivacaine plus hydromorphone (group HR). Diagnosis: Breast cancer patients. Postsurgery, pain levels, IL-6, anesthetic doses, additional analgesia needs, and recovery milestones were compared to evaluate the efficacy of the ESPB enhancements.
RESULTS
The 3 groups were not significantly different in baseline characteristics, operation time, number of cases with postoperative nausea, and serum IL-6 concentrations at T1 (the time of being returned to the ward after surgery). At T2 (at 6:00 in the next morning after surgery), the serum IL-6 concentration in group HR was significantly lower than that in groups R and C (P < .05); the intraoperative doses of remifentanil, sufentanil, and propofol were significantly lower in groups HR and R than those in group C (P < .05); Groups HR and R had significantly lower visual analog scale scores at T3 (4 hours postoperatively), T4 (12 hours postoperatively), and T5 (24 hours postoperatively) than those in group C (P < .05); the proportions of patients receiving postoperative remedial analgesia were significantly lower in groups HR and R than in group C (P < .05); groups HR and R had significantly lower proportions of patients with postoperative nausea than group C (P < .05); the time to the first anal exhaust and the time to the first ambulation after surgery were significantly shorter in groups HR and R than those in group C (P < .05).
CONCLUSION
Hydromorphone combined with ropivacaine for ESPB achieved a greater postoperative analgesic effect for patients receiving MRM under general anesthesia. The combined analgesia caused fewer adverse reactions and inhibited the expression level of the inflammatory factor IL-6 more effectively, thereby facilitating postoperative recovery. ESPB using hydromorphone with ropivacaine improved pain control post-MRM, reduced adverse effects, and more effectively suppressed IL-6, enhancing recovery.
Topics: Humans; Ropivacaine; Female; Hydromorphone; Middle Aged; Nerve Block; Pain, Postoperative; Prospective Studies; Anesthetics, Local; Breast Neoplasms; Mastectomy, Modified Radical; Analgesics, Opioid; Adult; Interleukin-6; Paraspinal Muscles; Ultrasonography, Interventional; Drug Therapy, Combination; Pain Measurement
PubMed: 38941366
DOI: 10.1097/MD.0000000000038758 -
Medicine Jun 2024Colorectal cancer (CRC) is a significant public health issue owing to its widespread occurrence and substantial morbidity and mortality rates. Recent studies have...
Colorectal cancer (CRC) is a significant public health issue owing to its widespread occurrence and substantial morbidity and mortality rates. Recent studies have highlighted serum uric acid (SUA) level as a probable risk factor for CRC; however, the inconsistency in these findings has created doubt. We performed a Mendelian randomization (MR) study utilizing extensive cohort data from the UK BioBank and the NHGRI-EBI Genome-Wide Association Study (GWAS) Catalog to investigate the causal connection between SUA levels and CRC incidence. Our MR study addresses the constraints of earlier studies, including limited sample sizes and inconsistent results. Considering SUA levels as the exposure and CRC as the outcome, the inverse variance-weighted (IVW) approach in MR showed that the odds ratios (ORs) for CRC for each unit increase in SUA were 0.232 (95% confidence interval [CI] of OR 0.094-0.570; P = .001) and 0.551 (95% CI of OR 0.325-0.934; P = .027). Pleiotropic tests and sensitivity analysis confirmed minimal horizontal pleiotropy and the robustness of causality. Our research deepens the understanding of the association between SUA levels and CRC, offering insights into prevention strategies and patient outcomes prediction.
Topics: Humans; Mendelian Randomization Analysis; Colorectal Neoplasms; Uric Acid; Genome-Wide Association Study; Risk Factors; Male; Female; Polymorphism, Single Nucleotide; Incidence; Middle Aged; Odds Ratio
PubMed: 38941363
DOI: 10.1097/MD.0000000000038722 -
Translational Vision Science &... Jun 2024To compare changes in superficial retinal vascular density (SRVD), deep retinal vascular density (DRVD), and retinal thickness (RT) of the macular zone after repeated... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
PURPOSE
To compare changes in superficial retinal vascular density (SRVD), deep retinal vascular density (DRVD), and retinal thickness (RT) of the macular zone after repeated low-level red light (RLRL) and 0.01% atropine exposure in premyopic schoolchildren.
METHODS
Prospective randomized trial. Sixty-nine schoolchildren with cycloplegic refraction >-0.75 D and ≤0.50 D were randomly assigned to RLRL and 0.01% atropine groups. SRVD, DRVD, and RT were measured using swept-source optical coherence tomography at baseline and six months. The macular zone was divided into three concentric rings (fovea, parafovea, and perifovea) using the Early Treatment Diabetic Retinopathy Study.
RESULTS
After six months, the whole, parafoveal, and perifoveal SRVD significantly increased in the two groups (all P < 0.05). Multivariate regression analyses showed that none of these changes varied significantly between the two groups (all P > 0.05), whereas foveal SRVD remained stable in both groups (all P > 0.05). In the RLRL group, the whole and perifoveal DRVD increased significantly (all P < 0.05), whereas no statistical difference was observed in the foveal and parafoveal DRVD. DRVD remained stable in the 0.01% atropine group (all P > 0.05). No significant differences were observed in RT changes between the two groups (all P > 0.05). In comparison, there were no significant changes in SRVD, DRVD, or RT after six months in the placebo group in our previous study.
CONCLUSIONS
SRVD increased similarly in the RLRL and 0.01% atropine groups, whereas DRVD increased only in the former group. There were no significant RT changes in either group after six months of treatment in premyopic schoolchildren.
TRANSLATIONAL RELEVANCE
This research observed the effects of low-level red light and 0.01% atropine on retinal vasculature, offering valuable insights into myopia progression prevention.
Topics: Humans; Atropine; Male; Female; Child; Prospective Studies; Retinal Vessels; Mydriatics; Tomography, Optical Coherence; Myopia; Ophthalmic Solutions; Phototherapy; Microvascular Density; Red Light
PubMed: 38940757
DOI: 10.1167/tvst.13.6.23 -
Journal of Virology Jun 2024Coronavirus disease 2019 (COVID-19) has claimed millions of lives since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and lung disease...
UNLABELLED
Coronavirus disease 2019 (COVID-19) has claimed millions of lives since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and lung disease appears the primary cause of death in COVID-19 patients. However, the underlying mechanisms of COVID-19 pathogenesis remain elusive, and there is no existing model where human disease can be faithfully recapitulated and conditions for the infection process can be experimentally controlled. Herein we report the establishment of an human precision-cut lung slice (hPCLS) platform for studying SARS-CoV-2 pathogenicity and innate immune responses, and for evaluating the efficacy of antiviral drugs against SARS-CoV-2. We show that while SARS-CoV-2 continued to replicate during the course of infection of hPCLS, infectious virus production peaked within 2 days, and rapidly declined thereafter. Although most proinflammatory cytokines examined were induced by SARS-CoV-2 infection, the degree of induction and types of cytokines varied significantly among hPCLS from individual donors. Two cytokines in particular, IP-10 and IL-8, were highly and consistently induced, suggesting a role in the pathogenesis of COVID-19. Histopathological examination revealed focal cytopathic effects late in the infection. Transcriptomic and proteomic analyses identified molecular signatures and cellular pathways that are largely consistent with the progression of COVID-19 in patients. Furthermore, we show that homoharringtonine, a natural plant alkaloid derived from , not only inhibited virus replication but also production of pro-inflammatory cytokines, and thus ameliorated the histopathological changes caused by SARS-CoV-2 infection, demonstrating the usefulness of the hPCLS platform for evaluating antiviral drugs.
IMPORTANCE
Here, established an human precision-cut lung slice platform for assessing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, viral replication kinetics, innate immune response, disease progression, and antiviral drugs. Using this platform, we identified early induction of specific cytokines, especially IP-10 and IL-8, as potential predictors for severe coronavirus disease 2019 (COVID-19), and uncovered a hitherto unrecognized phenomenon that while infectious virus disappears at late times of infection, viral RNA persists and lung histopathology commences. This finding may have important clinical implications for both acute and post-acute sequelae of COVID-19. This platform recapitulates some of the characteristics of lung disease observed in severe COVID-19 patients and is therefore a useful platform for understanding mechanisms of SARS-CoV-2 pathogenesis and for evaluating the efficacy of antiviral drugs.
PubMed: 38940558
DOI: 10.1128/jvi.00794-24 -
Journal of Complementary & Integrative... Jul 2024The study provides a thorough examination of the rhizomes of Roxb., which is a medicinal substance sometimes referred to as black turmeric and has not been well studied.
OBJECTIVES
The study provides a thorough examination of the rhizomes of Roxb., which is a medicinal substance sometimes referred to as black turmeric and has not been well studied.
METHODS
The study examines the pharmacognostical characteristics, GC-MS profiling, and elemental analysis of the substance to determine its potential for use in medicine. The presence of heavy metal contamination in herbal products is a significant issue, which necessitates the use of Atomic Absorption Spectrophotometry to quantitatively analyze eight elements.
RESULTS
The investigation validates the existence of crucial trace elements while guaranteeing that the levels of heavy metals are within the toxicity limits set by the World Health Organization. This indicates that the rhizome is safe for medicinal purposes. The selection of a solvent has a substantial impact on the efficiency of extraction. Acetone has the highest extraction yield, followed by ethanol and ethyl acetate. The GC-MS analysis uncovers a wide range of phytochemicals, such as alkaloids, flavonoids, phenols, tannins, steroids, and proteins. Additionally, particular solvents exclusively detect specific molecules. Epicurzerenone and zederone are chemicals that show promise for use in reducing inflammation and fighting cancer.
CONCLUSIONS
On the basis of results it can be concluded that rhizome's quality based on acceptable physicochemical characteristics and provides a strong basis for future pharmacological research. The research has potential for the development of novel organic drugs, utilizing the abundant phytochemical composition of Roxb. rhizomes.
PubMed: 38940214
DOI: 10.1515/jcim-2024-0151 -
Annals of Agricultural and... Jun 2024We read with interest the article by Kulesza et al. about a narrative review on the question of whether cannabidiol is really effective in treating lower back pain [1]....
We read with interest the article by Kulesza et al. about a narrative review on the question of whether cannabidiol is really effective in treating lower back pain [1]. After a literature search using suitable search terms and application of inclusion and exclusion criteria, the authors included 10 studies in the analysis [1]. One of the articles included was an editorial and four papers were reviews [1]. Cannabidiol has been found to be ineffective in treating lower back pain and further studies are needed to answer the question of interest. The review is impressive, but several points require discussion.
Topics: Cannabidiol; Humans; Low Back Pain
PubMed: 38940097
DOI: 10.26444/aaem/186635 -
Veterinary Radiology & Ultrasound : the... Jun 2024A 1-year-old Miniature Horse filly was presented for chronic lethargy and hyporexia. Elevated liver enzymes, bile acids, and ammonia were noted on bloodwork. The primary...
A 1-year-old Miniature Horse filly was presented for chronic lethargy and hyporexia. Elevated liver enzymes, bile acids, and ammonia were noted on bloodwork. The primary differential diagnosis was a portosystemic shunt (PSS). Three-phase computed tomographic angiography findings were consistent with a transhepatic portosystemic shunt. Percutaneous liver biopsy confirmed severe diffuse hepatic changes, most likely due to chronic pyrrolizidine alkaloid toxicosis, and medical management was elected. Based on an extensive literature review, this is the first report of a transhepatic portosystemic collateral vessel in a horse. Computed tomographic angiography is feasible and useful for the diagnosis of PSS in miniature horses.
PubMed: 38940068
DOI: 10.1111/vru.13401 -
Frontiers in Bioscience (Landmark... Jun 2024Persistent hyperuricemia can lead to the generation and deposition of monosodium urate (MSU) crystals. This can trigger gouty arthritis (GA), which in turn induces...
BACKGROUND
Persistent hyperuricemia can lead to the generation and deposition of monosodium urate (MSU) crystals. This can trigger gouty arthritis (GA), which in turn induces inflammation. Activation of the Nod-like receptor pyrin domain containing 3 (NLRP3) inflammasome plays a critical role in the onset and progression of GA. Autophagy may have a dual effect on GA with regard to the NLRP3 inflammasome. Therefore, the present study aimed to gain a deeper comprehension of the interaction between autophagy and NLRP3 inflammasome activation is imperative for developing more efficacious treatments for GA.
METHODS
Peripheral blood monocytes (PBMCs) were first isolated from GA patients and healthy controls and underwent bulk RNA sequencing analysis. Overexpression and knockdown of dual specificity phosphatase 1 (DUSP1) was performed in THP-1 monocytes to investigate its role in the immune response and mitochondrial damage. The luciferase assay and Western blot analysis were used to study the interaction between autophagy and NLRP3 inflammasome activation.
RESULTS
Bulk RNA sequencing analysis showed significant upregulation of DUSP1 expression in PBMCs from GA patients compared to healthy controls. This result was subsequently verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR). DUSP1 expression in human THP-1 monocytes was also shown to increase after MSU treatment. Downregulation of DUSP1 expression increased the secretion of inflammatory cytokines after MSU treatment, whereas the overexpression of DUSP1 decreased the secretion levels. Lipopolysaccharides (LPS) combined with adenosine-triphosphate (ATP) led to mitochondrial damage, which was rescued by overexpressing DUSP1. DUSP1 overexpression further increased the level of autophagy following MSU treatment, whereas downregulation of DUSP1 decreased autophagy. Treatment with the autophagy inhibitor 3-Methyladenine (3-MA) restored inflammatory cytokine secretion levels in the DUSP1 overexpression group. MSU caused pronounced pathological ankle swelling . However, DUSP1 overexpression significantly mitigated this phenotype, accompanied by significant downregulation of inflammatory cytokine secretion levels in the joint tissues.
CONCLUSIONS
This study revealed a novel function and mechanism for DUSP1 in promoting autophagy to mitigate the MSU-induced immune response in GA. This finding suggests potential diagnostic biomarkers and anti-inflammatory targets for more effective GA therapy.
Topics: Humans; Autophagy; Dual Specificity Phosphatase 1; Arthritis, Gouty; Uric Acid; NLR Family, Pyrin Domain-Containing 3 Protein; Inflammasomes; THP-1 Cells; Male; Monocytes; Case-Control Studies; Female; Leukocytes, Mononuclear; Middle Aged
PubMed: 38940057
DOI: 10.31083/j.fbl2906222