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1.
Front Pharmacol ; 13: 807651, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370667

RESUMO

Overview: The treatment of chronic renal failure (CRF) with traditional Chinese medicine has attracted much attention, but its mechanism is not clear. Network pharmacology is an effective strategy for exploring the interaction mechanisms between Chinese herbs and diseases, however, it still needs to be validated in cell and/or animal experiments due to its virtual screening characteristics. Herein, the anti-CRF mechanism of the Fushengong decoction (FSGD) was investigated using a dual-dimension network pharmacological strategy combined with in vivo experiment. Methods: The traditional Chinese medicine systems pharmacology (TCMSP) database (https://tcmspw.com) and UHPLC-MS/MS technology were used to identify the effective compounds of FSGD in theory and practice, such as quercetin, formononetin, and pachymic acid. The putative targets of FSGD and CRF were obtained from the Swisstarget prediction platform and the Genecards database, respectively. The common target pathways between FSGD and CRF were got from the dual-dimension network pharmacology analysis, which integrated the cross-common targets from the TCMSP components-Swisstarget-Genecards-Venn platform analysis in theory, and the UHPLC-MS/MS identified effective ingredients-Swisstarget screening, such as TNF and PI3K/AKT. Furthermore, system molecular determinations were used to prove the dual-dimension network pharmacology study through CRF rat models, which were constructed using adenine and treated with FSGD for 4 weeks. Results: A total of 121 and 9 effective compounds were obtained from the TCMSP database and UHPLC-MS/MS, respectively. After dual-dimension network pharmacology analysis, the possible mechanism of PTEN/PI3K/AKT/NF-κB pathway was found for FSGD in CRF. In vivo experiments indicated that FSGD can play a role in protecting renal function and reducing fibrosis by regulating the PTEN/PI3K/AKT/NF-κB pathway. These findings provide a reference for FSGD in CRF. Conclusion: Based on the theoretical and practical dual-dimension network pharmacology analysis for FSGD in CRF, the possible molecular mechanism of PTEN/PI3K/AKT/NF-κB was successfully predicted, and these results were verified by in vivo experiments. In this study, the dual-dimension network pharmacology was used to interpret the key signal pathway for FSGD in CRF, which also proved to be a smart strategy for the study of effective substances and pharmacology in FSGD.

2.
Brain Struct Funct ; 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35918458

RESUMO

Inappropriate fear expression and failure of fear extinction are commonly seen in patients with post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD). Among the patients, aberrant and asymmetric activation of the lateral orbitofrontal cortex (lOFC) is reported in some clinical cases. In this study, we aimed to examine the role of lOFC activation in extinction acquisition and explore the potential functional lateralization of lOFC on extinction. We bilaterally or unilaterally activated the lOFC with N-methyl-D-aspartate (NMDA) before fear extinction acquisition in rats. Our data suggested that both left and bilateral lOFC activation interfered with the in-session expression of conditioned fear, whereas activation of the right lOFC did not. In addition, pre-extinction unilateral or bilateral activation of the lOFC, regardless of the side, impaired the acquisition of fear extinction. We also quantified the neuronal activities during the late phase of extinction with immunohistochemical approach. Our data showed that activation of the lOFC increased the neuronal activities on the injection side(s) in the medial prefrontal cortex (mPFC), the lateral amygdala (LA), the basolateral amygdala (BLA; preferentially the non-GABAergic neurons), and the medial intercalated cells (mITC; preferentially the right side). To conclude, aberrant activation of the lOFC during extinction disturbed the excitatory/inhibitory balance of neuronal activities in fear-related brain regions, which interfered with the expression of conditioned fear and impaired the acquisition of fear extinction.

3.
BMC Complement Med Ther ; 22(1): 210, 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35932042

RESUMO

Diabetic nephropathy (DN) is one of the most serious complications of diabetes and the main cause of end-stage renal failure. Rhubarb is a widely used traditional Chinese herb, and it has exhibited efficacy in reducing proteinuria, lowering blood sugar levels and improving kidney function in patients with DN. However, the exact pharmacological mechanism by rhubarb improves DN remain unclear due to the complexity of its ingredients. Hence, we systematically explored the underlying mechanisms of rhubarb in the treatment of DN. We adopted a network pharmacology approach, focusing on the identification of active ingredients, drug target prediction, gene collection, Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes enrichment. Molecular docking technology was used to verify the binding ability between the main active compounds and central therapeutic targets, and screen out the core active ingredients in rhubarb for the treatment of DN. Finally, molecular dynamics simulation was performed for the optimal core protein-ligand obtained by molecular docking using GROMACS software. The network analysis identified 16 active compounds in rhubarb that were linked to 37 possible therapeutic targets related to DN. Through protein-protein interaction analysis, TP53, CASP8, CASP3, MYC, JUN and PTGS2 were identified as the key therapeutic targets. By validation of molecular docking, finding that the central therapeutic targets have good affinities with the main active compounds of rhubarb, and rhein, beta-sitosterol and aloe-emodin were identified as the core active ingredients in rhubarb for the treatment of DN. Results from molecular dynamics simulations showed that TP53 and aloe-emodin bound very stably with a binding free energy of - 26.98 kcal/mol between the two. The results of the gene enrichment analysis revealed that the PI3K-Akt signalling pathway, p53 signalling pathway, AGE-RAGE signalling pathway and MAPK signalling pathway might be the key pathways for the treatment of DN, and these pathways were involved in podocyte apoptosis, glomerular mesangial cell proliferation, inflammation and renal fibrosis. Based on the network pharmacology approach and molecular docking technology, we successfully predicted the active compounds and their respective targets. In addition, we illustrated the molecular mechanisms that mediate the therapeutic effects of rhubarb against DN. These findings provided an important scientific basis for further research of the mechanism of rhubarb in the treatment of DN.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Emodina , Rheum , Nefropatias Diabéticas/tratamento farmacológico , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases/metabolismo , Rheum/química , Rheum/metabolismo , Tecnologia
4.
Front Pharmacol ; 13: 960267, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935817

RESUMO

Background: Similar pathogenesis makes Corona Virus Disease 2019 (COVID-19) associated with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and gouty arthritis (GA), and it is possible to introduce common drugs for the treatment of RA, AS and GA into the treatment of COVID-19. That is, "homotherapy for heteropathy", especially cytokine inhibitors. But little is known about the specific link between the diseases. In addition, "new use of old drugs" is an important short-term strategy for the treatment of COVID-19. Cepharanthine (CEP), a monomer component of traditional Chinese medicine (TCM), is mainly used in the treatment of leukopenia and has recently been proved to have a good therapeutic effect on COVID-19, but its specific molecular mechanism has not been clearly explained. The purpose of this work is to explore the common targets and signaling pathways among COVID-19, RA, AS, and GA by means of network pharmacology (NP), and to infer the potential mechanism of CEP in the treatment of COVID-19. Methods: Firstly, SwissTargetPrediction was used to predict the targets of CEP, and the pathogenic targets of COVID-19, RA, AS and GA were searched in GeneCards, OMIM, TTD, PharmGKB database and literature, respectively. Then, the protein interaction network of CEP and COVID-19 cross targets and the common targets of COVID-19, RA, AS and GA was constructed. Cytosscape 3.7.2 software was used to construct CEP-common targets-signaling pathways-COVID-19 network, module function analysis, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG). Finally, the molecular docking of hub targets and CEP was carried out by AutoDock software. Results: The results showed that the common targets of the four diseases were tumor necrosis factor (TNF), interleukin (IL)-6 and IL-1ß, and involved Coronavirus disease, IL-17 signaling pathway and TNF signaling pathway. CEP has a good binding force with AKT Serine/Threonine Kinase 1 (AKT1), phosphatidylinositol 3-kinase (PIK3) CA, PIK3CD and Angiotensin-converting enzyme 2 (ACE2), and plays a role in the treatment of COVID-19 by regulating PI3K-Akt signaling pathway, Relaxin signaling pathway, VEGF signaling pathway and HIF-1 signaling pathway. Conclusion: Therefore, this study not only confirmed the potential mechanism of CEP in the treatment of COVID-19 at the molecular level, but also found that TNF and IL-17 inhibitors, which are commonly used in the treatment of RA, AS and GA, may also affect the treatment of COVID-19, which provides new clues and theoretical basis for the rapid discovery of effective therapeutic drugs for COVID-19.

6.
Front Pharmacol ; 13: 927488, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935870

RESUMO

Background: Myocardial infarction (MI), characterized by reduced blood flow to the heart, is a coronary artery disorder with the highest morbidity and mortality among cardiovascular diseases. Consequently, there is an urgent need to identify effective drugs to treat MI. Rhizoma Corydalis (RC) is the dry tuber of Corydalis yanhusuo W.T. Wang, and is extensively applied in treating MI clinically in China. Its underlying pharmacological mechanism remains unknown. This study aims to clarify the molecular mechanism of RC on MI by utilizing network pharmacology and experimental verification. Methods: Based on network pharmacology, the potential targets of the RC ingredients and MI-related targets were collected from the databases. Furthermore, core targets of RC on MI were identified by the protein-protein interaction (PPI) network and analyzed with Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was used to validate the binding affinity between the core targets and the bioactive components. Oxygen-glucose deprivation (OGD) was performed on H9c2 cells to mimic MI in vitro. A Cell Counting Kit-8 assay was used to assess the cardioprotective effect of the active ingredient against OGD. Western blot analysis and RT-qPCR were used to measure the cell apoptosis and inflammation level of H9c2 cells. Results: The network pharmacology obtained 60 bioactive components of RC, 431 potential targets, and 1131 MI-related targets. In total, 126 core targets were screened according to topological analysis. KEGG results showed that RC was closely related to the phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (PKB, also called Akt) signaling pathway. The experimental validation data showed that tetrahydropalmatine (THP) pretreatment preserved cell viability after OGD exposure. THP suppressed cardiomyocyte apoptosis and inflammation induced by OGD, while LY294002 blocked the inhibition effect of THP on OGD-induced H9c2 cell injury. Moreover, the molecular docking results indicated that THP had the strongest binding affinity with Akt over berberine, coptisine, palmatine, and quercetin. Conclusion: THP, the active ingredient of RC, can suppress OGD-induced H9c2 cell injury by activating the PI3K/Akt pathway, which in turn provides a scientific basis for a novel strategy for MI therapy and RC application.

7.
Neurotoxicology ; 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35934178

RESUMO

Diazinon (DZN) is a commonly used organophosphorus pesticide that was recently found to cause hippocampal degeneration in rodents. In this study, we elucidated the underlying molecular mechanisms through integrated network pharmacology and in vitro toxicity screening. 37 potential molecular targets of DZN-induced hippocampal neurotoxicity were predicted. Identified targets were then included in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A preliminary protein-protein network (PPI) was constructed using STRING, and the top 10 network hub target genes (Akt1, Mapk3, Tnf, Il6, Ptgs2, Il10, Il2, Il4, Creb1, and Fgf2) were screened for expression changes under DZN treatment. Cell counting kit-8 (CCK8) and lactate dehydrogenase (LDH) assays revealed time- and dose-dependent toxicity of DZN against mouse hippocampus-derived HT22 cells. Acetylcholinesterase (AChE) activity assay suggested that DZN inhibited the AChE activity, and TUNEL staining revealed that DZN increased the apoptotic rate. The mRNA expression levels of 9 hub targets (all except Il10) showed significant changes during DZN treatment, and AChE activity inhibition correlated strongly with Akt1, Mapk3, Il6, Il2, and Fgf2. DZN-induced hippocampal neurotoxicity was associated with the altered activity of multiple signaling pathways (including PI3K-Akt, TNF, and apoptosis signaling). These results provided a theoretical basis for more precise elucidation of DZN neurotoxic mechanisms.

8.
Pharmacol Res ; : 106391, 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35944805

RESUMO

The 2018 marine pharmacology literature review represents a continuation of the previous 11 reviews of a series initiated in 1998. Preclinical marine pharmacology research during 2018 was performed by investigators in 44 countries and contributed novel pharmacology for 195 marine compounds. The peer-reviewed marine natural products pharmacology literature reported antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral activities for 53 compounds, 73 compounds which presented antidiabetic and anti-inflammatory activities as well as affecting the immune and nervous system, while in contrast 69 compounds were reported to show miscellaneous mechanisms of action which may contribute upon further investigation to several pharmacological classes. Thus, in 2018, the preclinical marine natural product pharmacology pipeline continued to report novel pharmacology as well as new lead compounds for the clinical marine pharmaceutical pipeline, which currently contributes to therapeutic strategies for several disease categories. We would like to dedicate this manuscript in memory of Professor Francis Schmitz.

9.
Pharm Nanotechnol ; 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35946098

RESUMO

The eye is a one-of-a-kind sensory organ with intricate anatomy and physiology. It is protected by a variety of barriers, ranging from static barriers to dynamic barriers. Although these barriers are very effective at protecting the eye from exogenous substances and external stress, they are highly compromised by various vision-impairing diseases of both the anterior and the posterior segment of the eye. Due to ocular elimination systems and intricate obstacles that selectively limit drug entry into the eye, effective drug delivery to the posterior segment of the eye (PSE) continues to be a challenge in ophthalmology. Since more than half of the most debilitating eye illnesses are thought to originate in the posterior segment (PS), understanding the physiology and clearance mechanism of the eye could help design improved formulations that could be noninvasive and intended for targeted posterior segment therapeutics. Moreover, the major drawback associated with the conventional drug delivery system to PSE is minimal therapeutic drug concentration in the desired ocular tissue and life-threatening ophthalmic complications. One possible approach that can be implemented to overcome these ocular barriers for efficient ocular therapy, noninvasive and targeted drug action to the posterior tissues is by designing nanomedicines. This review summarizes the recent non-invasive and patient compliant advances in designing nanomedicines targeting PSE. The various routes and pathways of drug administration to the ocular tissue are also summarized.

10.
J Arrhythm ; 38(4): 554-569, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35936037

RESUMO

In the human heart, the rapid delayed rectifier K+ current (I Kr) contributes significantly to ventricular action potential (AP) repolarization and to set the duration of the QT interval of the surface electrocardiogram (ECG). The pore-forming (α) subunit of the I Kr channel is encoded by KCNH2 or human ether-à-go-go-related gene 1 (hERG1). Impairment of hERG function through either gene mutation (congenital) or pharmacological blockade by diverse drugs in clinical use (acquired) can cause a prolongation of the AP duration (APD) reflected onto the surface ECG as a prolonged QT interval or Long QT Syndrome (LQTS). LQTS can increase the risk of triggered activity of ventricular cardiomyocytes and associated life-threatening arrhythmia. Current treatments all focus on reducing the incidence of arrhythmia or terminating it after its onset but there is to date no prophylactic treatment for the pharmacological management of LQTS. A new class of hERG modulators (agonists) have been suggested through direct interaction with the hERG channel to shorten the action potential duration (APD) and/or increase the postrepolarisation refractoriness period (PRRP) of ventricular cardiomyocytes protecting thereby against triggered activity and associated arrhythmia. Although promising drug candidates, there remain major obstacles to their clinical development. The aim of this review is to summarize the latest advances as well as the limitations of this proposed pharmacotherapy.

11.
Mol Divers ; 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35933455

RESUMO

Non-small cell lung cancer (NSCLC) is one of the leading causes of death in the world. Rhubarb, a traditional Chinese medicine, has been widely used in the treatment of inflammatory and autoimmune diseases. This study aimed to investigate the possible mechanism of the rhubarb herb in the treatment of NSCLC by means of network pharmacology and molecular docking and to provide a theoretical basis for experiments and clinical application of traditional Chinese medicine for treating lung cancer. The main active chemical components and targets of rhubarb were screened through Swiss Target Prediction, TargetNet, and Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The protein-protein interaction (PPI) network was built via an in-depth exploration of the relationships between the proteins. The enrichment analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied to predict the potential roles in the pathogenesis of NSCLC via the R package cluster Profiler. Potential targets and active ingredients associated with anti-tumor effects of rhubarb were screened by reverse molecular docking. By searching databases and literature, a total of 295 targets were found for the 21 active ingredients in rhubarb. There were 68 common target genes associated with NSCLC, of which 9 are derived from FDA-approved drugs. GO Gene Set Enrichment Analysis (GSEA) explored up to 1103 biological processes, 62 molecular functions, and 18 cellular components. KEGG GSEA explored 65 basic pathways, and 71 disease pathways. Four key targets (JUN, EGFR, BCL2, and JAK2) were screened through the protein-protein interaction network, target-pathway network, and FDA drug-target network. Molecular docking results showed that these key targets had relatively strong binding activities with rhubarb's active ingredients. The present study explored the potential pharmacological mechanisms of rhubarb on NSCLC, promoting the clinical application of rhubarb in treating NSCLC, and providing references for advanced research.

13.
J Food Biochem ; : e14363, 2022 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-35933696

RESUMO

Since the outbreak of novel Coronavirus Pneumonia 2019 (COVID-19), the role of Almonds (Xingren) in the protection and treatment of COVID-19 is not clear. Network pharmacology and molecular docking were used to explore the potential mechanism and potential key targets of Xingren on COVID-19. A total of nine common targets between them were obtained, and these targets were involved in multiple related processes of GO and KEGG pathway enrichment analysis. Molecular docking showed that licochalcone B has the best binding energy (-9.33 kJ·mol-1 ) to PTGS2. They are maybe the important ingredient and key potential target. Its possible mechanism is to intervene anxiety disorder in the process of disease development, such as regulation of blood pressure, reactive oxygen species metabolic process, leishmaniasis peroxisome, and IL-17 signaling pathway. PRACTICAL APPLICATIONS: Xingren is a traditional Chinese medicine that has been used and developed in China for many years. It contains a variety of active ingredients and also has the functions of relieving cough, relieving asthma, enhancing human immunity, delaying aging, regulating blood lipids, nourishing brain, and improving intelligence. In this article, the possible mechanisms of action and important targets of Xingren in the prevention and treatment of COVID-19 were discussed through network pharmacology and molecular docking. We also found that active ingredient licochalcone B and the potential target PTGS2 are worthy of further research and analysis. At the same time, the study also provides a theoretical basis and reference for the prevention and treatment of COVID-19 and the development of new drugs.

14.
Pediatr Pulmonol ; 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927224

RESUMO

Access to CFTR modulators has been gradually increasing for people with cystic fibrosis, the first of which was ivacaftor, a CFTR potentiator which is part of all clinically available modulator treatments. In this study, we hypothesized that the steady-state concentrations in blood and tissue are highly variable in patients taking ivacaftor in a real-world context, which may have impacts on treatment approach. We collected nasal epithelial cells to estimate target site concentrations and blood samples to estimate pharmacokinetic parameters at steady state. We found that patients on ivacaftor monotherapy have variable concentrations well above the maximal effective concentration and may maintain concentrations necessary for clinical benefit even if dosing is reduced. We also are the first to provide detailed target site concentration data over time, which shows that tissue concentrations do not fluctuate significantly and do not correlate with plasma concentrations. These findings show that some patients may have higher-than-expected concentrations and may benefit from tailored dosing to balance clinical response with side effects or adherence needs. This article is protected by copyright. All rights reserved.

15.
Curr Mol Pharmacol ; 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35927815

RESUMO

BACKGROUND: Cancer is a leading cause of death and a severe threat to global public health. Organoid, as a novel 3D in vitro model, has been applied in various tumor related studies regarding its apparent advantages. The organoid is mainly constructed by Matrigel-depended 3D culture system, Air-Liquid Interface (ALI) culture, and Microfluidic culture or Organ-on-chips platform. For the application in carcinogenesis studies, organoid model may favor depicting initiative hallmarks and identifying potential intervening targets, investigating driver genes of carcinogenesis, and identifying known or unknown risk or protective factors. CONCLUSION: In this review, we discussed different organoid construction methods and their properties. We also noted that tumor organoids can portray initiative hallmarks and identify possible intervening targets, as well as explore carcinogenesis driver genes and uncover known or unknown risk or protective factors. Organoid systems have been used to identify tumor-preventive drugs such as oligomeric proanthocyanidins, Vitamin D, n-3 PUFAs, and pomegranate. The current evidence underscores the organoid model's potential importance in developing innovative tumor-prevention techniques.

16.
Clin Oral Investig ; 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35930141

RESUMO

AIM: This study aimed to identify medications taken by patients before dental appointments and to simulate and characterize their interactions with medications often prescribed by dental surgeons. MATERIALS AND METHODS: A retrospective cross-sectional study evaluated 320 medical records, 118 from the Emergency Service (ES) archives, and 202 from elective appointments at the Dental Clinic (DC) of a university in southern Brazil. Drug interactions were identified and classified according to severity using the Medscape® application into four grades: (1) Minor, (2) Monitor closely, (3) Serious, or (4) Contraindicated. Descriptive and inferential statistical analyses were carried out (α = 5%). RESULTS: Preexisting systemic conditions were noted in 55.9% of the medical records from the ES and 64.35% from the DC. In the ES records, 47.45% contained information on continuous use medication for treatment of systemic conditions and 59.40% of DC records contained such information. A total of 359 potential interactions were found. Drug interactions with analgesics were most frequent, accounting for 50.41% of the sample. CONCLUSIONS: The most prevalent drug interaction severity was grade 2: monitor or use with caution. Many patients take medications to treat systemic conditions and seek dental care, generating a significant possible source of drug interactions. CLINICAL RELEVANCE: Prescribers must carefully analyze the patients' medical histories and obtain accurate data regarding their use of medications to be able to assess the risk-benefit relationships of possible combinations.

17.
Phytomedicine ; 105: 154347, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-35914361

RESUMO

BACKGROUND: With the increasing ages of the general population, the incidence of knee osteoarthritis (KOA) is also rising, and KOA has become a major health problem worldwide. Recently, medicinal plants and their secondary metabolites have gained interest due to their activity in treating KOA. In this paper, a comprehensive systematic review of the literature was performed concerning the effects of medicinal plant extracts and natural compounds against KOA in recent years. The related molecular pathways of natural compounds against KOA were summarized, and the possible crosstalk among components in chondrocytes was discussed to propose possible solutions for the current situation of treating KOA. PURPOSE: This review focused on the molecular mechanisms by which medicinal plants and their secondary metabolites act against KOA. METHODS: Literature searches were performed in the PUBMED, Embase, Science Direct, and Web of Science databases for a 10-year period from 2011 to 2022 with the search terms "medicinal plants," "bioactive compounds," "natural products," "phytochemical," "knee osteoarthritis," "knee joint osteoarthritis," "knee osteoarthritis," "osteoarthritis of the knee," and "osteoarthritis of knee joint." RESULTS: According to the results, substantial plant extracts and secondary metabolites show a positive effect in fighting KOA. Plant extracts and their secondary metabolites can affect the diagnostic and prognostic biomarkers of KOA. Natural products inhibit the expression of MMP1, MMP3, MMP19, syndecan IV, ADAMTS-4, ADAMTS-5, iNOS, COX-2, collagenases, IL-6, IL-1ß, and TNF-α in vitro and in vivo and . Cytokines also upregulate the expression of collagen II and aggrecan. The main signaling pathways affected by the extracts and isolated compounds include AMPK, SIRT, NLRP3, MAPKs, PI3K/AKT, mTOR, NF-κB, WNT/ß-catenin, JAK/STAT3, and NRF2, as well as the cell death modes apoptosis, autophagy, pyroptosis, and ferroptosis. CONCLUSION: The role of secondary metabolites in different signaling pathways supplies a better understanding of their potential to develop further curative options for KOA.

18.
Comput Biol Med ; 148: 105786, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35926267

RESUMO

Synovitis is an essential feature of Osteoarthritis (OA). Increasing evidence demonstrates that synovitis plays a critical role in OA's symptoms and structural progression. However, there is no effective drug for preventing and treating synovitis. Some Chinese herbal formulae have been found to treat clinical OA effectively, however, their mode of action is still unclear. This study investigated the Chinese herbal formulae Zhuanggu Huoxue Tang (ZHT) underlying mechanisms for treating osteoarthritis. Transcriptome data and a network pharmacology analysis were used to investigate the biochemical pathways affected by ZHT during OA treatment with in vitro verification. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were undertaken. The interaction network of the ZHT active constituent targets was determined using Cytoscape 3.7.1 software. Molecular docking of key pathogenic proteins and components of ZHT was performed in silico to confirm the compounds' pharmaceutical activities. The results establish that JUN is a target pathway in the pathogenesis of osteoarthritis. Miltirone, one of the active ingredients of ZHT, demonstrated a suitable binding activity with JUN. Miltirone alleviates the catabolic gene expression induced by IL-1ß and IL-6 in synovial fibroblasts (FLS), validating the use of Miltirone as a therapeutic drug for osteoarthritis.

19.
BMC Womens Health ; 22(1): 333, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931998

RESUMO

BACKGROUND: Abortion is highly restricted in Indonesia; self-administered misoprostol can safely induce an abortion. Brick and mortar pharmacies, a common place to purchase misoprostol off-label in other parts of the world, are monitored closely by the government authority in Indonesia which controls drugs so that they cannot function outside the law without risking arrest and prosecution. An online marketplace has sprung up in response that sells misoprostol through in-country distributors. Such procurement offers a level of safety and anonymity to the buyer and seller. So as to understand online access to misoprostol, we created a protocol to identify the most visible universe of sellers. METHODS: We carried out a mystery client methodology to replicate the experiences of women procuring misoprostol online. Our study consisted of five stages: (1) identify the universe of online sellers using the most common search terms, drawn from multiple platforms to capture diversity in interactions as well as products sold (2) remove duplicates across sites as determined by their telephone numbers (3) draw a roughly probability proportional to size sample (4) contact sellers as mystery clients through text/chat, depending on the platform, and engage with them and (5) attempt to purchase drugs offered by the seller. Descriptive statistics are presented. RESULTS: The listing generated 727 sites: 441 websites, 153 marketplace sellers, and 133 Instagram profiles. After removing duplicate listings, we identified 281 unique sellers. We selected all sellers with greater than 12 listings, 60% of sellers with 4-12 listings, 50% of sellers with 2-3 listings, and 40% of sellers with only one listing. Mystery clients were able to send initial messages to 110 sellers, of which 16 never responded. The interaction progressed to purchasing misoprostol with 76 sellers, 64 of whom sent drugs. CONCLUSIONS: As women seek to terminate unwanted pregnancies in legally restrictive settings, online sales of misoprostol must be considered. With the Covid pandemic constraining movement, the importance of this way of procuring misoprostol will likely become more appealing. Understanding this unregulated landscape is important if we are to try to improve women's ability to safely conduct an abortion in highly restrictive settings.


Assuntos
Abortivos não Esteroides , Aborto Induzido , COVID-19 , Misoprostol , Abortivos não Esteroides/uso terapêutico , Aborto Induzido/métodos , Feminino , Humanos , Indonésia , Gravidez
20.
Phytomedicine ; 105: 154344, 2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35932605

RESUMO

BACKGROUND: Depression is a common psychiatric disorder and has become a growing public health issue. Traditional Chinese medicine (TCM) tonic prescriptions have been clinically proven to be an effective treatment for depression. PURPOSE: This study aimed to identify the core prescription to improve depression among the numerous TCM tonic prescriptions. METHODS AND RESULTS: First, we used meta-analysis to clarify the efficacy and safety of tonic prescriptions in depression among 37 studies and identified 16 effective tonic prescriptions. Second, we conducted data mining to analyze the tonic prescriptions and identified important nourishing herbs. Third, based on the data mining results, we constructed a Delphi experiment to investigate the effects of these important nourishing herbs in depression. Combining the results of Delphi expert questionnaires and weight analysis, a core TCM tonic prescription, Jianpi Tongmai formula (JPTMF) for the treatment of depression, was constructed and was composed of invigorating Spleen qi herbs. Fourth, we verified that JPTMF can improve chronic unpredictable mild stress (CUMS) induced depression-like behaviors in mice. Fifth, we predicted that the mechanism of JPTMF in the treatment of depression was mainly associated with chemical synaptic transmission and neuroinflammation through network pharmacology and determined preliminary confirmation through animal experiments. CONCLUSION: This study was undertaken to evaluate the efficacy of TCM tonic prescriptions on depression and construct a core TCM tonic prescription, JPTMF, through a progressive analysis. Network pharmacology and animal experiments verified the reliability of JPTMF. The proposal of JPTMF is of innovative significance, and may provide far-reaching implications for improving depression by using nourishing herbs. Furthermore, the integrated methods applied in this study provide an innovative paradigm for the standardization and scientific basis of TCM research.

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