Pub Date : 2024-09-03DOI: 10.2174/0113862073306093240820113714
Yang Huang, Lili Zhong, Jing Yang, Qiaomei Dai, Li Zhao, Mengdi Zhang, Hong Liu
Introduction: Sex hormones are important factors in maintaining brain function and acting as brain protectors. Recent research suggests that neuronal damage in brain aging may be linked to the methylation of the estrogen receptor α (ERα). However, the mechanism of Zuogui Pills (ZGW) in brain-aging ERα DNA methylation and neuronal repair remains unknown.
Materials and methods: D-galactose-induced ovary removal mice were used as a model of aging. Changes in estrous cycle were detected in mice by vaginal cell smear. Animal behavior tests, including the Morris water maze (MWM) and new object recognition (NOR) test, were conducted. Hematoxylin-eosin (HE) and Nissl-staining were carried out to assess hippocampal neurogenesis. Enzyme-linked immunosorbent assay (ELISA) was performed for 5- methylcytosine methylation levels, and immunohistochemistry (IHC) and western blotting (WB) experiments were performed to assess ERα/DNA methyltransferase 1 (DNMT1) expression after ZGW treatment. Finally, bisulfite sequencing PCR (BSP) analysis was performed to identify methylated differentially expressed estrogen receptor 1 (ESR1) gene in D-gal-induced senescent neurons before and after ZGW treatment.
Results: We found that ERα methylation was involved in the delayed brain ageing process of ZGW. Mechanistically, ZGW can improve the learning and memory ability of brain-aging mice, reduce the expression of 5-methylcytosine (5-mc) in serum, increase the amount of ERα, inhibit the expression of DNMT1, and significantly reduce methylated expression of the ESRI gene.
Conclusion: Our data suggested that ZGW slowed down D-gal-induced brain aging in mice, and these results showed that ZGW is beneficial for aging. It may be used for neuronal protection in aging.
{"title":"Zuogui Pills Improve the Learning and Memory Ability of Brain-Aging Mice through the Estrogen Receptor ERα Methylation Pathway.","authors":"Yang Huang, Lili Zhong, Jing Yang, Qiaomei Dai, Li Zhao, Mengdi Zhang, Hong Liu","doi":"10.2174/0113862073306093240820113714","DOIUrl":"https://doi.org/10.2174/0113862073306093240820113714","url":null,"abstract":"<p><strong>Introduction: </strong>Sex hormones are important factors in maintaining brain function and acting as brain protectors. Recent research suggests that neuronal damage in brain aging may be linked to the methylation of the estrogen receptor α (ERα). However, the mechanism of Zuogui Pills (ZGW) in brain-aging ERα DNA methylation and neuronal repair remains unknown.</p><p><strong>Materials and methods: </strong>D-galactose-induced ovary removal mice were used as a model of aging. Changes in estrous cycle were detected in mice by vaginal cell smear. Animal behavior tests, including the Morris water maze (MWM) and new object recognition (NOR) test, were conducted. Hematoxylin-eosin (HE) and Nissl-staining were carried out to assess hippocampal neurogenesis. Enzyme-linked immunosorbent assay (ELISA) was performed for 5- methylcytosine methylation levels, and immunohistochemistry (IHC) and western blotting (WB) experiments were performed to assess ERα/DNA methyltransferase 1 (DNMT1) expression after ZGW treatment. Finally, bisulfite sequencing PCR (BSP) analysis was performed to identify methylated differentially expressed estrogen receptor 1 (ESR1) gene in D-gal-induced senescent neurons before and after ZGW treatment.</p><p><strong>Results: </strong>We found that ERα methylation was involved in the delayed brain ageing process of ZGW. Mechanistically, ZGW can improve the learning and memory ability of brain-aging mice, reduce the expression of 5-methylcytosine (5-mc) in serum, increase the amount of ERα, inhibit the expression of DNMT1, and significantly reduce methylated expression of the ESRI gene.</p><p><strong>Conclusion: </strong>Our data suggested that ZGW slowed down D-gal-induced brain aging in mice, and these results showed that ZGW is beneficial for aging. It may be used for neuronal protection in aging.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: In the ongoing fight against bacterial resistance to antibiotics, this study focuses on synthesizing and evaluating 1,2,4-triazole derivatives to explore their potential as new antibacterial agents. 1,2,4-Triazole compounds are promising drug candidates with a wide range of therapeutic effects, including pain relief, antiseptic, antimicrobial, antioxidant, antiurease, anti-inflammatory, diuretic, anticancer, anticonvulsant, antidiabetic, and antimigraine properties.
Method: The structures of all the synthesized compounds were identified using their physicochemical properties and spectral techniques, such as IR and NMR. These compounds were then evaluated in molecular docking studies against antimicrobial activity in vitro and further supported by molecular dynamics studies.
Result: Compound 7, featuring a 6-chloro group on the phenyl ring, emerged as the most effective against Gram-positive S. aureus compared to the standard antibiotic ciprofloxacin. Docking studies revealed high and comparable affinities for all ten ligands, with compounds 4 and 6 showing the best-docked activity against Penicillin Acylase mutants. Further, compounds 6 and 10 displayed significant affinity against D-alanine-D-alanine ligase (DDL) from Yersinia pestis during 100 ns MD simulation.
Conclusion: Notably, compound 7 demonstrated the highest binding score to the 5C1P protein, suggesting its potential as a lead molecule for the development of potent and safer antimicrobial agents. This research contributes valuable insights into addressing the escalating challenge of bacterial resistance.
{"title":"In Silico Molecular Docking and Molecular Dynamics Analysis of Antimicrobial Triazole Derivatives: Insights from Synthesis, Computational and In Vitro Studies.","authors":"Shikha Sharma, Naveen Kumawat, Suraj N Mali, Monika Meghani, Nitin Kumar, Bijo Mathew, Sunil Kumar","doi":"10.2174/0113862073314430240730095615","DOIUrl":"https://doi.org/10.2174/0113862073314430240730095615","url":null,"abstract":"<p><strong>Introduction: </strong>In the ongoing fight against bacterial resistance to antibiotics, this study focuses on synthesizing and evaluating 1,2,4-triazole derivatives to explore their potential as new antibacterial agents. 1,2,4-Triazole compounds are promising drug candidates with a wide range of therapeutic effects, including pain relief, antiseptic, antimicrobial, antioxidant, antiurease, anti-inflammatory, diuretic, anticancer, anticonvulsant, antidiabetic, and antimigraine properties.</p><p><strong>Method: </strong>The structures of all the synthesized compounds were identified using their physicochemical properties and spectral techniques, such as IR and NMR. These compounds were then evaluated in molecular docking studies against antimicrobial activity in vitro and further supported by molecular dynamics studies.</p><p><strong>Result: </strong>Compound 7, featuring a 6-chloro group on the phenyl ring, emerged as the most effective against Gram-positive S. aureus compared to the standard antibiotic ciprofloxacin. Docking studies revealed high and comparable affinities for all ten ligands, with compounds 4 and 6 showing the best-docked activity against Penicillin Acylase mutants. Further, compounds 6 and 10 displayed significant affinity against D-alanine-D-alanine ligase (DDL) from Yersinia pestis during 100 ns MD simulation.</p><p><strong>Conclusion: </strong>Notably, compound 7 demonstrated the highest binding score to the 5C1P protein, suggesting its potential as a lead molecule for the development of potent and safer antimicrobial agents. This research contributes valuable insights into addressing the escalating challenge of bacterial resistance.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-28DOI: 10.2174/0113862073333880240819105537
Jun Cao, Shijia Zhang, Kehui Zhou, Xiaochun Mao, Ming Zhao, Jinbiao Shang, Xiabin Lan
background: Cuproptosis is a novel type of cell death mediated by protein lipoylation,and is closely related to mitochondrial metabolism. Clinical association of cuproptosis-related genes(CRGs)in thyroid cancer, however, remains unclear. In this study, we systematically evaluated the differential expression and genetic alterations of CRGs in papillary thyroid cancer (PTC) and constructed a CRG signature to predict the prognosis of PTC patients. method: We integrated the data of The Cancer Genome Atlas (TCGA) database and analyzed the expression of 10 CRGs in PTC. CRG signature was constructed by univariate Cox analysis and selection operator (LASSO) Cox regression. In addition, the signature-related molecular features were validated by a combination of functional enrichment, Cox regression, and immune infiltration analysis. Independent validation cohort data and quantitative real-time polymerase chain reaction (qRT-PCR) were used to validate the expression of differentially expressed CRG (CDKN2A). result: Thyroid cancer patients could be divided into two subtypes (low and high CRG score groups) and we found that overall survival (OS) of patients was lower in high CRG score group (HCSG) than in low CRG score group (LCSG) (p &amp;lt; 0.001). And the area under the curve (AUC) values for 3 years, 5 years, and 8 years were 0.872, 0.941, and 0.976, respectively. Cox regression analysis showed that the CRG score could be used as an independent prognostic indicator for PTC. Functional enrichment analysis indicated that the CRG prognostic signature was also associated with the tumor immune microenvironment. In HCSG, the immune suppression type cell score is significantly higher than in LCSG. In addition, we identified the expression of CRG (CDKN2A) by qRT-PCR, and the results were consistent with the TCGA database. conclusion: Our CRG signature has a good predictive ability for the prognosis of PTC patients. CRGs may play an important role in tumorigenesis and could be used to predict immunotherapy efficacy of PTC.
{"title":"A Novel Cuproptosis-Related Gene Signature Predicts Prognosis in Papillary Thyroid Carcinoma Patients","authors":"Jun Cao, Shijia Zhang, Kehui Zhou, Xiaochun Mao, Ming Zhao, Jinbiao Shang, Xiabin Lan","doi":"10.2174/0113862073333880240819105537","DOIUrl":"https://doi.org/10.2174/0113862073333880240819105537","url":null,"abstract":"background: Cuproptosis is a novel type of cell death mediated by protein lipoylation,and is closely related to mitochondrial metabolism. Clinical association of cuproptosis-related genes(CRGs)in thyroid cancer, however, remains unclear. In this study, we systematically evaluated the differential expression and genetic alterations of CRGs in papillary thyroid cancer (PTC) and constructed a CRG signature to predict the prognosis of PTC patients. method: We integrated the data of The Cancer Genome Atlas (TCGA) database and analyzed the expression of 10 CRGs in PTC. CRG signature was constructed by univariate Cox analysis and selection operator (LASSO) Cox regression. In addition, the signature-related molecular features were validated by a combination of functional enrichment, Cox regression, and immune infiltration analysis. Independent validation cohort data and quantitative real-time polymerase chain reaction (qRT-PCR) were used to validate the expression of differentially expressed CRG (CDKN2A). result: Thyroid cancer patients could be divided into two subtypes (low and high CRG score groups) and we found that overall survival (OS) of patients was lower in high CRG score group (HCSG) than in low CRG score group (LCSG) (p &amp;amp;lt; 0.001). And the area under the curve (AUC) values for 3 years, 5 years, and 8 years were 0.872, 0.941, and 0.976, respectively. Cox regression analysis showed that the CRG score could be used as an independent prognostic indicator for PTC. Functional enrichment analysis indicated that the CRG prognostic signature was also associated with the tumor immune microenvironment. In HCSG, the immune suppression type cell score is significantly higher than in LCSG. In addition, we identified the expression of CRG (CDKN2A) by qRT-PCR, and the results were consistent with the TCGA database. conclusion: Our CRG signature has a good predictive ability for the prognosis of PTC patients. CRGs may play an important role in tumorigenesis and could be used to predict immunotherapy efficacy of PTC.","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142176454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26DOI: 10.2174/0113862073285839240808113152
Menghai Wu, Huaxin Qi, Jun Li, Periyannan Velu, Xia Han
Background: A major factor in type 1 diabetes mortality is Ischemic Heart Disease (IHD). In order to treat IHD, blood flow must be restored to the heart, which results in myocardial ischemia-reperfusion (MI/R) damage. While rosmanol inhibits MI/R damage, its role in diabetic- MI/R (D-MI/R) injury remains unclear. Both microRNA (miR) 126 and the PI3K/AKT signaling pathway have been linked to preventing MI/R damage.
Objective: The objective of the present study was to investigate whether rosmanol inhibits DMI/ R-injury in diabetic rats and whether miR-126-phosphatidylinositol 3-kinase (PI3K)/ protein kinase B axis (miR-126-PI3K/AKT) is implicated in this protective effect.
Methods: For 30 days, diabetic rats received either distilled water or the drug rosmanol (40 mg/kg, orally) before being subjected to MI/R.
Results: The findings from the current study demonstrated how rosmanol reduced MI/R damage in rats with diabetes caused by streptozotocin (STZ). Using spectrophotometry, it was possible to measure the decrease in myocardial enzyme levels, the rise in cardiac viability, the inhibition of myocardial oxidative stress, the increase in cardiac function, and the detection of these changes using a hemodynamic monitoring system. In addition, rosmanol augmented the miR- 126-PI3K/AKT in the hearts of ischemic rats. After stimulating the myocardial miR-126- PI3K/AKT axis, our results showed that rosmanol protected the heart against MI/R in STZinduced diabetic rats.
Conclusion: According to the most recent research, rosmanol may be a useful tool in the therapy of diabetic IHD since it is an effective agent against D-MI/R damage.
{"title":"Rosmanol Alleviates Myocardial Ischemia-Reperfusion Injury by Enhancing the Myocardial miR-126/VEGF/PI3K/AKT Signaling in STZ-Induced Diabetic Rats.","authors":"Menghai Wu, Huaxin Qi, Jun Li, Periyannan Velu, Xia Han","doi":"10.2174/0113862073285839240808113152","DOIUrl":"https://doi.org/10.2174/0113862073285839240808113152","url":null,"abstract":"<p><strong>Background: </strong>A major factor in type 1 diabetes mortality is Ischemic Heart Disease (IHD). In order to treat IHD, blood flow must be restored to the heart, which results in myocardial ischemia-reperfusion (MI/R) damage. While rosmanol inhibits MI/R damage, its role in diabetic- MI/R (D-MI/R) injury remains unclear. Both microRNA (miR) 126 and the PI3K/AKT signaling pathway have been linked to preventing MI/R damage.</p><p><strong>Objective: </strong>The objective of the present study was to investigate whether rosmanol inhibits DMI/ R-injury in diabetic rats and whether miR-126-phosphatidylinositol 3-kinase (PI3K)/ protein kinase B axis (miR-126-PI3K/AKT) is implicated in this protective effect.</p><p><strong>Methods: </strong>For 30 days, diabetic rats received either distilled water or the drug rosmanol (40 mg/kg, orally) before being subjected to MI/R.</p><p><strong>Results: </strong>The findings from the current study demonstrated how rosmanol reduced MI/R damage in rats with diabetes caused by streptozotocin (STZ). Using spectrophotometry, it was possible to measure the decrease in myocardial enzyme levels, the rise in cardiac viability, the inhibition of myocardial oxidative stress, the increase in cardiac function, and the detection of these changes using a hemodynamic monitoring system. In addition, rosmanol augmented the miR- 126-PI3K/AKT in the hearts of ischemic rats. After stimulating the myocardial miR-126- PI3K/AKT axis, our results showed that rosmanol protected the heart against MI/R in STZinduced diabetic rats.</p><p><strong>Conclusion: </strong>According to the most recent research, rosmanol may be a useful tool in the therapy of diabetic IHD since it is an effective agent against D-MI/R damage.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.2174/0113862073252534231122073045
Gaber El-Saber Batiha, Hayder M Al-Kuraishy, Omnia Momtaz Al-Fakhrany, Engy Elekhnawy
The manuscript has been withdrawn upon author request.
Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.
The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php
Bentham science disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure, or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Additionally, plagiarism is strictly forbidden, and by submitting the article for publication, the authors agree that the publishers have the legal right to take appropriate action against the authors if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.
{"title":"WITHDRAWN: Comparative Experimental Study of using Tramadol and Nefopam in Pain Management","authors":"Gaber El-Saber Batiha, Hayder M Al-Kuraishy, Omnia Momtaz Al-Fakhrany, Engy Elekhnawy","doi":"10.2174/0113862073252534231122073045","DOIUrl":"10.2174/0113862073252534231122073045","url":null,"abstract":"<p><p>The manuscript has been withdrawn upon author request.</p><p><p>Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.</p><p><p>The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php</p><p><strong>Bentham science disclaimer: </strong>It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously\u0000submitted or published elsewhere. Furthermore, any data, illustration, structure, or table that has been published elsewhere\u0000must be reported, and copyright permission for reproduction must be obtained. Additionally, plagiarism is strictly forbidden,\u0000and by submitting the article for publication, the authors agree that the publishers have the legal right to take appropriate action\u0000against the authors if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the\u0000copyright of their article is transferred to the publishers if and when the article is accepted for publication.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-21DOI: 10.2174/0113862073335953240820075044
Zhaoyi Li, Yi Cao, Hui Li, Sihua Le, Libo Yin
Ethnopharmacological relevance: Dispel-Scar Ointment is used in Traditional Chinese Medicine to treat scarred tissue and increasing evidence has shown that DSO has potent therapeutic; however, its exact mechanism remains unexplored.
Aim of the study: This study explored the molecular mechanisms of action of DSO in scarring using network pharmacology, molecular docking, and experimental validation.
Materials and methods: Public databases were used to predict the bioactive ingredients and putative targets of DSO against scars. A compounds-targets network was constructed using the Cytoscape software. Enrichment analysis was performed using ClueGo and FunRich to specify the biological functions and associated pathways of hub targets. Molecular docking was used to verify the correlation between the major active components and hub targets, visualised using PyMol 2.3. Experimental validations were conducted to elucidate the influence of DSO on keloid fibroblast cells using the CCK-8, wound-scratch, cell reactive oxygen species, and western blot assays. Results:Network pharmacological analysis of DSO for scar treatment identified 146 ingredients and 1078 gene targets. Major targets included, prostaglandin-endoperoxide synthase 2 matrix metallopeptidases, and nitric oxide synthase 2. ClueGo analysis revealed 29 pathways (p&amp;lt;0.05) and FunRich 345 pathways (p&amp;lt;0.05), mainly toll-like receptor, TGF-β, interleukin-4/13, glypican, and tumour necrosis factor-related apoptosis-inducing ligand pathways. Molecular docking showed MMP2-flavoxanthin, MMP9-luteolin and MMP-9-kaempferol bound best to DSO. DSO could inhibit the proliferation and migration of scar fibroblasts and promote their apoptosis in a concentration-dependent manner. DSO also decreased TGF-β1, -βR2, pSMAD2, pSMAD3, SMAD4, CoL1a1, and MMP2 expression.
Conclusions: Network pharmacology, molecular docking, and experimental validation showed DSO&#039;s potential in treating scars. It may inhibit scars via the TGF-β1/SMADs/MMPs signalling pathway, providing a basis for DSO&#039;s scar treatment application.
{"title":"Network Pharmacology, Molecular Docking Analysis and Experiment Validations on Molecular Targets and Mechanisms of the Dispel-Scar Ointment in Scar Treatment.","authors":"Zhaoyi Li, Yi Cao, Hui Li, Sihua Le, Libo Yin","doi":"10.2174/0113862073335953240820075044","DOIUrl":"https://doi.org/10.2174/0113862073335953240820075044","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Dispel-Scar Ointment is used in Traditional Chinese Medicine to treat scarred tissue and increasing evidence has shown that DSO has potent therapeutic; however, its exact mechanism remains unexplored.</p><p><strong>Aim of the study: </strong>This study explored the molecular mechanisms of action of DSO in scarring using network pharmacology, molecular docking, and experimental validation.</p><p><strong>Materials and methods: </strong>Public databases were used to predict the bioactive ingredients and putative targets of DSO against scars. A compounds-targets network was constructed using the Cytoscape software. Enrichment analysis was performed using ClueGo and FunRich to specify the biological functions and associated pathways of hub targets. Molecular docking was used to verify the correlation between the major active components and hub targets, visualised using PyMol 2.3. Experimental validations were conducted to elucidate the influence of DSO on keloid fibroblast cells using the CCK-8, wound-scratch, cell reactive oxygen species, and western blot assays. Results:Network pharmacological analysis of DSO for scar treatment identified 146 ingredients and 1078 gene targets. Major targets included, prostaglandin-endoperoxide synthase 2 matrix metallopeptidases, and nitric oxide synthase 2. ClueGo analysis revealed 29 pathways (p&amp;amp;lt;0.05) and FunRich 345 pathways (p&amp;amp;lt;0.05), mainly toll-like receptor, TGF-β, interleukin-4/13, glypican, and tumour necrosis factor-related apoptosis-inducing ligand pathways. Molecular docking showed MMP2-flavoxanthin, MMP9-luteolin and MMP-9-kaempferol bound best to DSO. DSO could inhibit the proliferation and migration of scar fibroblasts and promote their apoptosis in a concentration-dependent manner. DSO also decreased TGF-β1, -βR2, pSMAD2, pSMAD3, SMAD4, CoL1a1, and MMP2 expression.</p><p><strong>Conclusions: </strong>Network pharmacology, molecular docking, and experimental validation showed DSO&amp;#039;s potential in treating scars. It may inhibit scars via the TGF-β1/SMADs/MMPs signalling pathway, providing a basis for DSO&amp;#039;s scar treatment application.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-19DOI: 10.2174/0113862073304276240606102447
D M Danuri Savindi Dissanayake, I G Sahasra Heshani, Sadhana Hassan, Anchala I Kuruppu
Tropical fruits are often studied to determine their content of bioactive compounds that contain health-enhancing properties and are often identified to hold a rich nutritional composition. Their bioactive compounds are classified through their phenolic, flavonoid, and antioxidant properties, while some tropical fruits are known to have other properties such as anticancer and anti-inflammatory activity. Sri Lanka is an island with abundant resources. One such resource is exotic fruits. Exotic fruits are known as edible fruits, which are not necessarily native but consist of a unique flavor profile, fragrance, shape, or appearance. Exotic fruits are usually consumed on their own or consumed as beverages, pickles, jams, salads, and desserts. The market-friendly tropical fruits in Sri Lanka include a vast number, and some of them are mango, Ceylon olives, durian, jackfruit, rambutan, soursop, passion fruit, and star fruit. These fruits contribute to the rice culinary heritage of Sri Lanka, and most of them are exported worldwide. At present, the traditional medicine system is quite popular among the public due to its less toxic nature and easy access. This review is aimed at evaluating the antioxidant, cytotoxic, anticancer, and anti-inflammatory properties of eight selected exotic fruits mentioned above and their traditional usage, which is based on the literature of various scientific studies conducted on these tropical fruits.
{"title":"Exploring the Bioactive Potential of Exotic Fruits from Sri Lanka: A Treasure Trove of Medicinal Properties.","authors":"D M Danuri Savindi Dissanayake, I G Sahasra Heshani, Sadhana Hassan, Anchala I Kuruppu","doi":"10.2174/0113862073304276240606102447","DOIUrl":"https://doi.org/10.2174/0113862073304276240606102447","url":null,"abstract":"<p><p>Tropical fruits are often studied to determine their content of bioactive compounds that contain health-enhancing properties and are often identified to hold a rich nutritional composition. Their bioactive compounds are classified through their phenolic, flavonoid, and antioxidant properties, while some tropical fruits are known to have other properties such as anticancer and anti-inflammatory activity. Sri Lanka is an island with abundant resources. One such resource is exotic fruits. Exotic fruits are known as edible fruits, which are not necessarily native but consist of a unique flavor profile, fragrance, shape, or appearance. Exotic fruits are usually consumed on their own or consumed as beverages, pickles, jams, salads, and desserts. The market-friendly tropical fruits in Sri Lanka include a vast number, and some of them are mango, Ceylon olives, durian, jackfruit, rambutan, soursop, passion fruit, and star fruit. These fruits contribute to the rice culinary heritage of Sri Lanka, and most of them are exported worldwide. At present, the traditional medicine system is quite popular among the public due to its less toxic nature and easy access. This review is aimed at evaluating the antioxidant, cytotoxic, anticancer, and anti-inflammatory properties of eight selected exotic fruits mentioned above and their traditional usage, which is based on the literature of various scientific studies conducted on these tropical fruits.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The plant kingdom offers a wealth of molecules with potential efficacy against various human, animal, and plant crop infections and illnesses. Cannabis sativa L. has garnered significant attention in recent decades within the scientific community due to its broad biological activity. Key bioactive compounds such as cannabinoids and phenolic compounds have been isolated from this plant, driving its bioactivity. Numerous studies have highlighted the impact of different agronomic practices, particularly fertilization, on the phytochemical composition, notably altering the percentage of various chemical groups. This review aims to present updated fertilization recommendations, crop requirements, and their implications for the chemical composition of C. sativa plants, along with major biological properties documented in the literature over the past five years. Various databases were utilized to summarize information on fertilization and crop requirements, chemical composition, bioassays employed, natural products (extracts or isolated compounds), and bioactivity results. Through this review, it is evident that C. sativa holds promise as a source of novel molecules for treating diverse human diseases. Nonetheless, careful consideration of agronomic practices is essential to optimize chemical composition and maximize therapeutic potential.
{"title":"Correlation between Chemical Fertilization Practices, Phytochemical Response, and Biological Activities of Cannabis sativa L.","authors":"Marianela Simonutti, Gisela Seimandi, Geraldina Richard, Juan Marcelo Zabala, Marcos Derita","doi":"10.2174/0113862073319590240801112332","DOIUrl":"https://doi.org/10.2174/0113862073319590240801112332","url":null,"abstract":"<p><p>The plant kingdom offers a wealth of molecules with potential efficacy against various human, animal, and plant crop infections and illnesses. Cannabis sativa L. has garnered significant attention in recent decades within the scientific community due to its broad biological activity. Key bioactive compounds such as cannabinoids and phenolic compounds have been isolated from this plant, driving its bioactivity. Numerous studies have highlighted the impact of different agronomic practices, particularly fertilization, on the phytochemical composition, notably altering the percentage of various chemical groups. This review aims to present updated fertilization recommendations, crop requirements, and their implications for the chemical composition of C. sativa plants, along with major biological properties documented in the literature over the past five years. Various databases were utilized to summarize information on fertilization and crop requirements, chemical composition, bioassays employed, natural products (extracts or isolated compounds), and bioactivity results. Through this review, it is evident that C. sativa holds promise as a source of novel molecules for treating diverse human diseases. Nonetheless, careful consideration of agronomic practices is essential to optimize chemical composition and maximize therapeutic potential.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.2174/0113862073311689240730112355
Hao-Yun Luo, Jun-Ming Feng, Jun Luo, Tian Tian
Background: Current evidence highlights clear cell renal carcinoma (ccRCC) as the most prevalent form of kidney cancer despite ongoing challenges in treating advanced-stage disease. Integrin subunit beta 3 (ITGB3) has recently emerged as a critical player in tumorigenesis, prompting our investigation into its role in ccRCC. This study aimed to elucidate the mechanisms responsible for ITGB3 downregulation and evaluate its clinical significance, particularly regarding its impact on the immune landscape within ccRCC.
Methods: We first conducted analyses utilizing data from both TCGA and GEO datasets to explore ITGB3 expression in ccRCC tissues. Subsequently, we evaluated the association between ITGB3 expression levels and patient prognosis and pathological staging. Pathway and functional enrichment analyses were performed to assess correlations between ITGB3 and immune and methylation-related pathways. Additionally, we examined the relationship between ITGB3 transcriptional expression and DNA hypermethylation. A prognostic risk model was developed using LASSO-based analysis on selected ITGB3-associated DNA methylation probes. Immunohistochemistry (IHC) analysis, alongside TIMER and ssGSEA results, was utilized to investigate ITGB3 expression and its association with immune cell infiltration.
Results: Our analyses revealed significant downregulation of ITGB3 mRNA expression in ccRCC tissues compared to other members of the ITGB family, consistent across TCGA and GEO datasets. Higher ITGB3 expression correlated with improved prognosis and lower pathological stage in ccRCC patients. Pathway and functional enrichment analyses demonstrated positive correlations between ITGB3 and immune and methylation-related pathways, while ITGB3 transcriptional expression showed a negative correlation with DNA hypermethylation. The established prognostic risk model identified a high-risk group with poorer survival probabilities than the low-risk group. Immunohistochemical quantification revealed a positive correlation between CD4+ and CD8+ immune cell infiltration and ITGB3 expression.
Conclusion: Overall, our study provides compelling evidence supporting the significant role of ITGB3 in ccRCC immunity. The downregulation of ITGB3, coupled with its association with better prognosis and immune activation, suggests its potential as a therapeutic target and prognostic marker for this patient population.
{"title":"ITGB3 is a Novel Prognostic Biomarker and Correlates with Aberrant Methylation and Tumor Immunity in Clear Cell Renal Cell Carcinoma.","authors":"Hao-Yun Luo, Jun-Ming Feng, Jun Luo, Tian Tian","doi":"10.2174/0113862073311689240730112355","DOIUrl":"https://doi.org/10.2174/0113862073311689240730112355","url":null,"abstract":"<p><strong>Background: </strong>Current evidence highlights clear cell renal carcinoma (ccRCC) as the most prevalent form of kidney cancer despite ongoing challenges in treating advanced-stage disease. Integrin subunit beta 3 (ITGB3) has recently emerged as a critical player in tumorigenesis, prompting our investigation into its role in ccRCC. This study aimed to elucidate the mechanisms responsible for ITGB3 downregulation and evaluate its clinical significance, particularly regarding its impact on the immune landscape within ccRCC.</p><p><strong>Methods: </strong>We first conducted analyses utilizing data from both TCGA and GEO datasets to explore ITGB3 expression in ccRCC tissues. Subsequently, we evaluated the association between ITGB3 expression levels and patient prognosis and pathological staging. Pathway and functional enrichment analyses were performed to assess correlations between ITGB3 and immune and methylation-related pathways. Additionally, we examined the relationship between ITGB3 transcriptional expression and DNA hypermethylation. A prognostic risk model was developed using LASSO-based analysis on selected ITGB3-associated DNA methylation probes. Immunohistochemistry (IHC) analysis, alongside TIMER and ssGSEA results, was utilized to investigate ITGB3 expression and its association with immune cell infiltration.</p><p><strong>Results: </strong>Our analyses revealed significant downregulation of ITGB3 mRNA expression in ccRCC tissues compared to other members of the ITGB family, consistent across TCGA and GEO datasets. Higher ITGB3 expression correlated with improved prognosis and lower pathological stage in ccRCC patients. Pathway and functional enrichment analyses demonstrated positive correlations between ITGB3 and immune and methylation-related pathways, while ITGB3 transcriptional expression showed a negative correlation with DNA hypermethylation. The established prognostic risk model identified a high-risk group with poorer survival probabilities than the low-risk group. Immunohistochemical quantification revealed a positive correlation between CD4+ and CD8+ immune cell infiltration and ITGB3 expression.</p><p><strong>Conclusion: </strong>Overall, our study provides compelling evidence supporting the significant role of ITGB3 in ccRCC immunity. The downregulation of ITGB3, coupled with its association with better prognosis and immune activation, suggests its potential as a therapeutic target and prognostic marker for this patient population.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: In this study, we used immune repertoire (IR) sequencing technology to profile the diversity of peripheral blood T cell receptors and used transcriptomics to profile the gene expression of peripheral blood neutrophil mRNA in patients with mild-moderate knee osteoarthritis (KOA) before and after electroacupuncture (EA) treatment.
Methods: An 8-week intervention with EA was performed on 3 subjects with KOA. IR sequencing of complementarity determining region 3 (CDR3) was performed using RNA extracted from peripheral blood T cells of KOA subjects prior to and at the end of the intervention, as well as healthy volunteers (controls) who matched the subjects in sex and age. Neutrophils were extracted from the plasma of healthy individuals, pretreatment patients, and posttreatment patients for further transcriptome sequencing.
Results: The D50, diversity index (DI), and Shannon entropy values of circulatory T-cells were significantly lower in pretreatment KOA patients compared to healthy controls. Posttreatment KOA samples displayed significant decreases in serum proinflammatory factors, IL-8 and IL-18 (P < 0.01), as well as a substantial reduction in serum matrix MMP-3 and MMP-13 (P < 0.01, P < 0.05). Transcriptome analysis revealed that the expression of CXCL2, IRF8, and PEAR1 (P < 0.05) was significantly higher in patients before the treatment than in the healthy population and was significantly down-regulated after the treatment. In contrast, the expression of SMPD3 (P < 0.05) showed the opposite trend.
Conclusion: EA may alleviate KOA by rebalancing T-cell homeostasis and improving systemic inflammation. At the same time, EA treatment can significantly enhance TCR diversity, reduce levels of proinflammatory factors, and increase levels of anti-inflammatory factors, thereby achieving therapeutic effects.
研究背景在这项研究中,我们利用免疫复合物(IR)测序技术分析了外周血T细胞受体的多样性,并利用转录组学分析了轻中度膝骨关节炎(KOA)患者在电针(EA)治疗前后外周血中性粒细胞mRNA的基因表达:方法:对3名KOA患者进行为期8周的电针干预。方法:对 3 名 KOA 受试者进行了为期 8 周的 EA 干预,并使用干预前和干预结束时从 KOA 受试者以及在性别和年龄上与受试者相匹配的健康志愿者(对照组)的外周血 T 细胞中提取的 RNA 对互补决定区 3(CDR3)进行了 IR 测序。从健康人、治疗前患者和治疗后患者的血浆中提取中性粒细胞,进一步进行转录组测序:结果:与健康对照组相比,KOA治疗前患者循环T细胞的D50、多样性指数(DI)和香农熵值明显较低。治疗后的 KOA 样本显示血清促炎因子 IL-8 和 IL-18 明显降低(P < 0.01),血清基质 MMP-3 和 MMP-13 也大幅降低(P < 0.01,P < 0.05)。转录组分析显示,治疗前,患者体内的CXCL2、IRF8和PEAR1(P<0.05)的表达明显高于健康人群,治疗后则明显下调。相比之下,SMPD3(P < 0.05)的表达则呈相反趋势:结论:EA 可通过重新平衡 T 细胞平衡和改善全身炎症来缓解 KOA。结论:EA 可通过重新平衡 T 细胞稳态和改善全身炎症来缓解 KOA,同时,EA 治疗可显著提高 TCR 多样性,降低促炎因子水平,提高抗炎因子水平,从而达到治疗效果。
{"title":"Electroacupuncture Ameliorates Knee Osteoarthritis By Rebalancing T Cell Homeostasis as Revealed By Immune Repertoire (IR) Sequencing.","authors":"Wenrui Jia, Yunan Zhang, Tianqi Wang, Cunzhi Liu, Jianfeng Tu, Guangxia Shi, LingYi Cai, Jingwen Yang, Guangrui Huang","doi":"10.2174/0113862073303471240805061026","DOIUrl":"https://doi.org/10.2174/0113862073303471240805061026","url":null,"abstract":"<p><strong>Background: </strong>In this study, we used immune repertoire (IR) sequencing technology to profile the diversity of peripheral blood T cell receptors and used transcriptomics to profile the gene expression of peripheral blood neutrophil mRNA in patients with mild-moderate knee osteoarthritis (KOA) before and after electroacupuncture (EA) treatment.</p><p><strong>Methods: </strong>An 8-week intervention with EA was performed on 3 subjects with KOA. IR sequencing of complementarity determining region 3 (CDR3) was performed using RNA extracted from peripheral blood T cells of KOA subjects prior to and at the end of the intervention, as well as healthy volunteers (controls) who matched the subjects in sex and age. Neutrophils were extracted from the plasma of healthy individuals, pretreatment patients, and posttreatment patients for further transcriptome sequencing.</p><p><strong>Results: </strong>The D50, diversity index (DI), and Shannon entropy values of circulatory T-cells were significantly lower in pretreatment KOA patients compared to healthy controls. Posttreatment KOA samples displayed significant decreases in serum proinflammatory factors, IL-8 and IL-18 (P < 0.01), as well as a substantial reduction in serum matrix MMP-3 and MMP-13 (P < 0.01, P < 0.05). Transcriptome analysis revealed that the expression of CXCL2, IRF8, and PEAR1 (P < 0.05) was significantly higher in patients before the treatment than in the healthy population and was significantly down-regulated after the treatment. In contrast, the expression of SMPD3 (P < 0.05) showed the opposite trend.</p><p><strong>Conclusion: </strong>EA may alleviate KOA by rebalancing T-cell homeostasis and improving systemic inflammation. At the same time, EA treatment can significantly enhance TCR diversity, reduce levels of proinflammatory factors, and increase levels of anti-inflammatory factors, thereby achieving therapeutic effects.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}