Naunyn-Schmiedeberg's archives of pharmacology最新文献

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Saikosaponin D suppresses esophageal squamous cell carcinoma via the PI3K-AKT signaling pathway.
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2024-12-05 DOI: 10.1007/s00210-024-03676-6
Qiong Duan, Mingxiao Wang, Zhenting Cui, Jianxin Ma
{"title":"Saikosaponin D suppresses esophageal squamous cell carcinoma via the PI3K-AKT signaling pathway.","authors":"Qiong Duan, Mingxiao Wang, Zhenting Cui, Jianxin Ma","doi":"10.1007/s00210-024-03676-6","DOIUrl":"https://doi.org/10.1007/s00210-024-03676-6","url":null,"abstract":"<p><p>Saikosaponin D is the saikosaponin with the highest biological activity in Bupleurum chinense DC, which has anti-tumor effects on a variety of human tumors. In this study, we aimed to explore the SSD-induced apoptosis mechanism in ESCC cells. We predicted the targets of SSD and ESCC through several databases and analyzed the intersecting targets to identify the connections and possible pathways between proteins. We evaluated the binding activity between proteins and SSD through molecular docking. Based on the network pharmacology results, different concentrations of SSD were used to treat Eca-109 alongside Te-10 cells. The CCK-8, colony formation, wound healing, transwell, apoptosis, and western blot assays were performed to verify the inhibitory SSD impact on Eca-109 and Te-10 cells. Network pharmacology predicted 186 potential targets of SSD, and 500 targets of ESCC, along with 31 common targets, 5 core protein targets, and 94 potential pathways. Depending on molecular docking findings, SSD was closely bound to five core targets. Cellular experiments showed that SSD suppressed the Eca-109 and Te-10 cell proliferation and metastasis and enhanced apoptosis via the PI3K-AKT signaling. This study suggests SSD inhibited Eca-109 and Te-10 cell proliferation and migration by inhibiting the PI3K-AKT pathway and promoting apoptosis.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785303","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}
引用次数: 0
Anti-diabetic drug pioglitazone reduces Islet amyloid aggregation overload in the Drosophila neuronal cells.
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2024-12-05 DOI: 10.1007/s00210-024-03632-4
Khushboo Sharma, Pooja Rai, Shashank Kumar Maurya, Madhu G Tapadia
{"title":"Anti-diabetic drug pioglitazone reduces Islet amyloid aggregation overload in the Drosophila neuronal cells.","authors":"Khushboo Sharma, Pooja Rai, Shashank Kumar Maurya, Madhu G Tapadia","doi":"10.1007/s00210-024-03632-4","DOIUrl":"https://doi.org/10.1007/s00210-024-03632-4","url":null,"abstract":"<p><p>Amyloid-proteinopathy is observed in type 2 diabetes, where Islet amyloid polypeptide is secreted atypically and impedes cellular homeostasis. The thiazolidinediones family is reported to influence amyloid-beta aggregations. However, research on drug-based stimulation of insulin signaling to alleviate Islet amyloid aggregations is lacking. To understand the impact of pioglitazone on islet amyloid aggregation, we conducted an in vivo and in silico analysis. For in vivo analysis, we generated a transgenic Drosophila harboring the preproform of human Islet amyloid polypeptide (IAPP) that can be ectopically expressed in a spatio-temporal manner. We show that the unprocessed form of IAPP also has the propensity to form aggregates and cause degeneration. Pioglitazone feeding effectively reduces the burden of Islet amyloid aggregations in the larval brain. In silico analysis shows that there is a higher protein-ligand binding energy for IAPP with pioglitazone than amyloid-beta. These results suggests that pioglitazone might be repurposed as a drug to cure islet amyloidogenesis.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786279","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}
引用次数: 0
Phytochemical compounds for treating hyperuricemia associated with gout: a systematic review.
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2024-12-05 DOI: 10.1007/s00210-024-03686-4
Santenna Chenchula, Mohan Krishna Ghanta, Munirah Alhammadi, Arifullah Mohammed, Kuttiappan Anitha, Poojith Nuthalapati, Ganji Seeta Rama Raju, Yun Suk Huh, Lvks Bhaskar
{"title":"Phytochemical compounds for treating hyperuricemia associated with gout: a systematic review.","authors":"Santenna Chenchula, Mohan Krishna Ghanta, Munirah Alhammadi, Arifullah Mohammed, Kuttiappan Anitha, Poojith Nuthalapati, Ganji Seeta Rama Raju, Yun Suk Huh, Lvks Bhaskar","doi":"10.1007/s00210-024-03686-4","DOIUrl":"https://doi.org/10.1007/s00210-024-03686-4","url":null,"abstract":"<p><p>Gout is a prevalent metabolic disorder characterized by increased uric acid (UA) synthesis or decreased UA clearance from the bloodstream, leading to the formation of urate crystals in joints and surrounding tissues. Hyperuricemia (HUA), the underlying cause of gout, poses a growing challenge for healthcare systems in developed and developing countries. Currently, the most common therapeutic approaches for gouty HUA primarily involve the use of allopathic or modern medicine. However, these treatments are often accompanied by adverse effects and may not be universally effective for all patients. Therefore, this systematic review aims to provide a comprehensive outline of phytochemical compounds that have emerged as alternative treatments for HUA associated with gout and to examine their specific mechanisms of action. A systematic search was conducted to identify phytochemicals that have previously been evaluated for their effectiveness in reducing HUA. From a review of > 800 published articles, 100 studies reporting on 50 phytochemicals associated with the management of HUA and gout were selected for analysis. Experimental models were used to investigate the effects of these phytochemicals, many of which exhibited multiple mechanisms beneficial for managing HUA. This review offers valuable insights for identifying and developing novel compounds that are safer and more effective for treating HUA associated with gout.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786325","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}
引用次数: 0
Allopurinol abates hepatocellular carcinoma in rats via modulation of NLRP3 inflammasome and NF-κB pathway.
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2024-12-05 DOI: 10.1007/s00210-024-03666-8
Heba A Bahriz, Rania R Abdelaziz, Dalia H El-Kashef
{"title":"Allopurinol abates hepatocellular carcinoma in rats via modulation of NLRP3 inflammasome and NF-κB pathway.","authors":"Heba A Bahriz, Rania R Abdelaziz, Dalia H El-Kashef","doi":"10.1007/s00210-024-03666-8","DOIUrl":"https://doi.org/10.1007/s00210-024-03666-8","url":null,"abstract":"<p><p>The present research was performed to examine the possible capability of allopurinol to prevent developing hepatocellular carcinoma (HCC) and to explore the fundamental mechanisms that control the hepatoprotective effect considering the enormous impact of HCC on patients' quality of life. Male Sprague Dawely rats were given i.p. injection of thioacetamide (TAA) (200 mg/kg) twice a week for 16 weeks in order to induce HCC. The histological analysis and assessment of the serum levels of liver function indicators verified the development of HCC. Two regimens of allopurinol (100 mg/kg, p.o.) were used; the first involved giving it concurrently with TAA from week 13 to week 16, and the second regimen started from week 9 to week 16. Chronic TAA damage was associated with considerable overexpression of the profibrogenic cytokine TGF-β, degradation and nuclear translocation of NF-κB, which released a number of inflammatory mediators, and upregulation of the NLRP3/caspase1 pathway. Administration of allopurinol demonstrated considerable enhancements in liver function and oxidative balance. Moreover, pathological characteristics like cirrhosis, dysplastic changes, and HCC nodules were greatly diminished. Allopurinol via suppressing TGF-β expression, inhibiting NF-κB nuclear translocation, and restricting inflammatory NLRP3/caspase1/IL-1β pathway was able to protect against TAA-induced liver damage, and it could be a promising therapy for HCC.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786240","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}
引用次数: 0
Unlocking the biological potential of methyl antcinate A: a new frontier in cancer and inflammation application.
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2024-12-04 DOI: 10.1007/s00210-024-03544-3
Maria Sharif, Muhammad Irfan, Kafila Kousar, Assem Mamurova, Lorena Duarte-Peña, Hector Hernández-Parra, Hernán Cortés, Sheila I Peña-Corona, Khushbukhat Khan, Solomon Habtemariam, Gerardo Leyva-Gómez, Javad Sharifi-Rad
{"title":"Unlocking the biological potential of methyl antcinate A: a new frontier in cancer and inflammation application.","authors":"Maria Sharif, Muhammad Irfan, Kafila Kousar, Assem Mamurova, Lorena Duarte-Peña, Hector Hernández-Parra, Hernán Cortés, Sheila I Peña-Corona, Khushbukhat Khan, Solomon Habtemariam, Gerardo Leyva-Gómez, Javad Sharifi-Rad","doi":"10.1007/s00210-024-03544-3","DOIUrl":"https://doi.org/10.1007/s00210-024-03544-3","url":null,"abstract":"<p><p>Antrodia camphorata is a valued and scarce parasitic mushroom that exclusively proliferates on the inner cavity wall of the endangered tree Cinnamomum kanehirai Hay (Lauraceae), endemic to Taiwan. Historically, this fungus has been utilized in traditional medicine to treat liver cancer, diarrhea, abdominal pain, hypertension, and food and drug intoxication, among other ailments. Literature searches were performed in scientific databases. The results were compiled from peer-reviewed studies; the search was refreshed through January 2024 to incorporate the most recent research. In vitro studies have revealed that Antrodia camphorata possesses various pharmacological properties that prevent cancer, reduce inflammation, and improve liver function. This medicinal mushroom contains unique ergostane-type triterpenoids known as antcins, which exhibit numerous pharmacological properties. Seven naturally occurring methyl analogs of antcins have been identified so far. In this article, we reviewed and analyzed the properties of methyl antcinate A (MAA), a constituent of Antrodia camphorata and methyl derivative of antcin A. MAA has demonstrated important anti-apoptotic, anti-inflammatory, and gastro-protective properties, as well as significant anti-tumor, anti-cancer, and cytotoxic activities. The anti-cancer effect of MAA in various cancers is attributed to its ability to modulate signaling cascades in apoptotic pathways. A significant challenge is to initiate preclinical and clinical trials to assess its anti-tumor action in vivo, as this data is currently missing. Additionally, future research on the structure-activity relationship of antcins and their derivatives is expected to support their development as therapeutic agents for clinical use.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770530","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}
引用次数: 0
Edaravone's reno-protective effects against chronic heat-stress exposure.
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2024-12-03 DOI: 10.1007/s00210-024-03685-5
Laiali T Alquraan, Karem H Alzoubi, Sanaa Jaber, Omar F Khabour, Bahaa Al-Trad, Aseel Al-Shwaheen, Ghada Alomari, Suzie Y Rababa'h, Majed M Masadeh
{"title":"Edaravone's reno-protective effects against chronic heat-stress exposure.","authors":"Laiali T Alquraan, Karem H Alzoubi, Sanaa Jaber, Omar F Khabour, Bahaa Al-Trad, Aseel Al-Shwaheen, Ghada Alomari, Suzie Y Rababa'h, Majed M Masadeh","doi":"10.1007/s00210-024-03685-5","DOIUrl":"https://doi.org/10.1007/s00210-024-03685-5","url":null,"abstract":"<p><p>Edaravone (EDV) is a potent antioxidant with anti-inflammatory properties. It is used to treat various diseases, especially neurodegenerative diseases. This study aims to examine EDV's potential renal protective effects on kidney injury induced by heat stress in rats. Male Wistar rats were segregated into four distinct groups (n = 16/group): control (Ctr), heat stress (HS), edaravone (EDV), and HS+EDV groups. Heat stress was applied 6 days a week for 30 min for 8 weeks, and EDV treatment (6 mg/kg. IP) was administered simultaneously in the HS+EDV group. After the experiment, blood and kidney tissue samples were gathered for subsequent analysis. Compared to the control group, the HS group exhibited a significant increase in serum creatinine and urea levels (P < 0.05). Additionally, malondialdehyde level and catalase activity, tumor necrosis factor-α (TNF-α), and interleukin-1 beta (IL-1β) mRNA expression were increased in the kidney tissue during HS. The renal tissues of the heat-stressed animal showed noticeable histological alterations compared to the control group. However, in the HS+EDV and EDV groups, the creatinine and urea concentrations in the blood were markedly reduced compared to the HS group (P < 0.05). In addition, renal oxidative stress biomarkers were normalized (malondialdehyde levels and catalase activity; P < 0.05). The histopathological alterations in the renal tissues of the groups treated with EDV were markedly diminished. In addition, the renal mRNA expression levels of IL-1β and TNF-α were markedly reduced in the HS+EDV group compared to the HS group (P < 0.05). EDV treatment in a heat-stress rat model demonstrated a protective effect on renal tissue, most likely due to its antioxidant and anti-inflammatory properties.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770299","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}
引用次数: 0
Bibliometric comparison of Nobel Prize laureates: a few suggestions.
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2024-12-03 DOI: 10.1007/s00210-024-03648-w
Waseem Hassan, Fred Paas
{"title":"Bibliometric comparison of Nobel Prize laureates: a few suggestions.","authors":"Waseem Hassan, Fred Paas","doi":"10.1007/s00210-024-03648-w","DOIUrl":"https://doi.org/10.1007/s00210-024-03648-w","url":null,"abstract":"<p><p>This study offers insights into a paper by the esteemed editor-in-chief, who conducted a bibliometric comparison of Nobel laureates in physiology, medicine, and chemistry to examine the substantial influence these scientists have had on their respective fields (Naunyn-Schmiedeberg's Arch Pharmacol, 397, 2024, 7169-7185). Analyzing metrics such as laureates' nationalities, ages at productivity peaks, H-index, and age-adjusted H-index, the research highlights distinct career patterns among these distinguished scientists. The present study addresses the limitations of traditional metrics, like the H-index, which may undervalue early-career contributions or multidisciplinary impacts due to its focus on cumulative citations. Alternative indicators such as the H-upper, H-center, and H-tail indices are proposed to capture more balanced aspects of scholarly influence, highlighting top-cited, moderately cited, and broadly influential work, respectively. This study also suggests the value of incorporating composite indices such as the HG-composite and Q2 indices in relevant future studies. A list of other indicators is also provided, which may be employed in similar studies. In the same vein, altmetrics, such as social media engagement, download counts, and mentions in digital and traditional media, further complement these metrics by illustrating the broader, more immediate societal relevance of Nobel laureates' work. The present study proposes a multi-dimensional approach for evaluating research impact, integrating various metrics, and highlighting the need for cross-database comparisons to ensure accurate assessments.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770385","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}
引用次数: 0
Oxyresveratrol and/or Dapagliflozin Attenuate Doxorubicin-Induced Nephrotoxicity via Modulation of PPAR-γ/Nrf-2/HO-1, NF-κB/TNF-α/Keap-1, and Bcl-2/Caspase-3/ATG-5 signaling pathways in rats.
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2024-12-03 DOI: 10.1007/s00210-024-03608-4
Waleed S M El-Sawy, Marwa M Khalaf, Ali H El-Bahrawy, Basim A S Messiha, Ramadan A M Hemeida
{"title":"Oxyresveratrol and/or Dapagliflozin Attenuate Doxorubicin-Induced Nephrotoxicity via Modulation of PPAR-γ/Nrf-2/HO-1, NF-κB/TNF-α/Keap-1, and Bcl-2/Caspase-3/ATG-5 signaling pathways in rats.","authors":"Waleed S M El-Sawy, Marwa M Khalaf, Ali H El-Bahrawy, Basim A S Messiha, Ramadan A M Hemeida","doi":"10.1007/s00210-024-03608-4","DOIUrl":"https://doi.org/10.1007/s00210-024-03608-4","url":null,"abstract":"<p><strong>Purpose: </strong>Among the most undesirable effects that lead to the restriction of doxorubicin (DOX) use in chemotherapy is kidney damage. This research aimed to assess the possible defenses against DOX-induced nephrotoxicity offered by oxyresveratrol (ORES) and/or dapagliflozin (DAPA).</p><p><strong>Methods: </strong>Five groups of eight male Swiss albino rats each were created from a total of sixty-four. One intravenous injection of DOX (10 mg/kg) was given into the tail vein on the fourteenth day of the experiment; in the meantime, ORES (80 mg/kg) and DAPA (10 mg/kg) were given orally 14 days prior to the DOX injection and 2 days following the DOX injection.</p><p><strong>Results: </strong>In rats given DOX, ORES and/or DAPA both successfully reduced the kidney weight, kidney/bodyweight ratio, and blood levels of creatinine, uric acid, and urea. They also increased final body weight and albumin serum levels. Additionally, lower serum concentrations of TNF-α and IL-6 were noted, along with a lower kidney content of caspase-3. Furthermore, the expression of the Bcl-2 gene was upregulated, as were the Nrf-2, PPAR-γ, and HO-1 proteins, and there was a downregulation of the ATG-5, Keap-1, and NF-κB renal gene expression. These findings support a decrease in oxidative stress and relief of histopathological alterations.</p><p><strong>Conclusion: </strong>The current study's findings suggest that ORES and/or DAPA pretreatment could be a viable therapeutic approach to ameliorate DOX-induced nephrotoxicity.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770489","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}
引用次数: 0
Evaluation of the toxicity potential of exercise and atorvastatin/metformin combination therapy on STZ-diabetic rats.
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2024-12-03 DOI: 10.1007/s00210-024-03663-x
Merve Tunçyürekli, Yasin Tülüce, Ferzan Lermioglu Erciyas
{"title":"Evaluation of the toxicity potential of exercise and atorvastatin/metformin combination therapy on STZ-diabetic rats.","authors":"Merve Tunçyürekli, Yasin Tülüce, Ferzan Lermioglu Erciyas","doi":"10.1007/s00210-024-03663-x","DOIUrl":"https://doi.org/10.1007/s00210-024-03663-x","url":null,"abstract":"<p><p>Exercise is recommended for individuals with diabetes, and metformin and atorvastatin are commonly prescribed to diabetic patients. However, these two drugs have potential effects that may lead to toxicity in the skeletal muscle system. Therefore, the effects and potential interactions of combining these two drugs on skeletal muscle performance and structure were investigated in vivo in an experimental diabetes model. Male Wistar rats were divided into six groups: a sedentary control group (N) and five treatment groups-exercise (C), diabetes (D), diabetes with metformin (MET), diabetes with atorvastatin (ATO), and diabetes with metformin and atorvastatin (MET + ATO). In the diabetes model experimentally created with streptozotocin (STZ; 45 mg/kg, i.p.) and metformin (300 mg/kg/day), atorvastatin (10 mg/kg/day) was administered to drug groups by gavage during the 4-week study period. The rats were allowed to run (at moderate level) for 30 min, 5 days a week, on the treadmill. At the end of the study, blood samples and gastrocnemius muscle tissues of the rats were obtained under ketamine anesthesia (100 mg/kg; i.p). The effects of combining exercise and medication on skeletal muscle were assessed by examining the levels of significant biomarkers including PGC-1α, UCP-3, and MyHCs, as well as analyzing oxidative stress/antioxidant capacity parameters in muscle tissue samples. Additionally, relevant biochemical indicators were determined in serum samples. The quantity and morphology of mitochondria in muscle tissue were assessed using transmission electron microscopy. It was observed in the study that some toxic effects associated with the use of drugs alone were reduced by combination therapy. It is thought that this study will contribute to the literature in the evaluation of the effects of drugs and their combined use in Type 1 diabetes under exercise conditions.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770303","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}
引用次数: 0
ADAMDEC1 promotes cervical squamous cell carcinoma by enhancing the JAK/STAT signaling pathway through modulation of TYMP.
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2024-12-03 DOI: 10.1007/s00210-024-03680-w
Beibei Wang, Qingsong Zhang, Lihua Wang, Huiwen Su, Li Zhou, Rong Zhang, Qiangkun Wan
{"title":"ADAMDEC1 promotes cervical squamous cell carcinoma by enhancing the JAK/STAT signaling pathway through modulation of TYMP.","authors":"Beibei Wang, Qingsong Zhang, Lihua Wang, Huiwen Su, Li Zhou, Rong Zhang, Qiangkun Wan","doi":"10.1007/s00210-024-03680-w","DOIUrl":"https://doi.org/10.1007/s00210-024-03680-w","url":null,"abstract":"<p><p>Cervical squamous cell carcinoma (CSCC) poses a significant health challenge, especially in developing countries. Identifying novel prognostic biomarkers and potential drug targets is crucial for improving CSCC management. We analyzed ADAMDEC1 expression patterns in CSCC using various bioinformatic datasets. Clinical samples from CSCC patients were evaluated for ADAMDEC1 and TYMP levels through Western blot and qRT-PCR. Multiple in vitro techniques, including flow cytometry, CCK-8, Transwell, Western blot, wound healing assays, and Co-IP, were employed to investigate the role and molecular pathways associated with ADAMDEC1. Our findings reveal that ADAMDEC1 is significantly overexpressed in CSCC tissues compared to adjacent healthy tissues. Functional assays demonstrated that ADAMDEC1 overexpression significantly enhances cell proliferation, migration, and invasion in vitro, while concurrently inhibiting apoptosis. Conversely, the knockdown of ADAMDEC1 reversed these effects, leading to reduced cell proliferation and increased apoptosis. Mechanistically, we identified a direct interaction between ADAMDEC1 and TYMP, which activates the JAK/STAT signaling pathway in CSCC cells. This activation was confirmed through Western blot analysis, indicating increased phosphorylation of JAK1 and STAT3 in response to ADAMDEC1 overexpression. ADAMDEC1 promotes CSCC progression by modulating the JAK/STAT pathway through regulation of TYMP. These findings suggest that ADAMDEC1 could serve as a molecular biomarker for early diagnosis and targeted therapy in CSCC.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770366","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}
引用次数: 0
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