{"title":"Recent Advances in Immunotherapy and Targeted Therapy of Triple Negative Breast Cancer.","authors":"Harshada Shewale, Abhishek Kanugo","doi":"10.2174/0113892010303244240718075729","DOIUrl":"10.2174/0113892010303244240718075729","url":null,"abstract":"<p><p>The truancy of representation of the estrogen, progesterone, and human epidermal growth factor receptors occurs during TNBC. TNBC is recognized for the upper reappearance and has a poorer diagnosis compared with rest breast cancer (BC) types. Presently, as such, no targeted therapy is approved for TNBC and treatment options are subjected to chemotherapy and surgery, which have high mortality rates. Hence, the current article focuses on the scenario of TNBC vital pathways and discusses the latest advances in TNBC treatment, including immune checkpoint inhibitors (ICIs), PARP suppressors, and cancer vaccines. Immunotherapy and ICIs, like PD 1 and PD L1 suppressors, displayed potential in clinical trials (CTs). These suppressors obstruct the mechanisms which allow tumor cells to evade the system thereby boosting the body's defense against TNBC. Immunotherapy, either alone or combined with chemotherapy has demonstrated patient outcomes such as increased survival rates and reduced treatment-related side effects. Additionally, targeted therapy approaches include BRCA/2 mutation poly ribose polymerase inhibitors, Vascular Endothelial Growth Factor Receptor (VEGFR) inhibitors, Epidermal growth factor receptor inhibitors, Fibroblast growth factor inhibitors, Androgen Receptor inhibitors, PIK3/AKT/mTOR pathway inhibitors, Cyclin-dependent kinase (CDK) inhibitors, Notch signaling pathway inhibitors, Signal transducer and activator of transcription 3 (STAT3) signaling pathway inhibitors, Chimeric antigen receptor T (CAR-T) cell therapy, Transforming growth factor (TGF) -β inhibitors, Epigenetic modifications (EPM), Aurora Kinase inhibitors and antibody-drug conjugates. We also highlight ongoing clinical trials and potential future directions for TNBC therapy. Despite the challenges in treating TNBC, recent developments in understanding the molecular and immune characteristics of TNBC have opened up new opportunities for targeted therapies, which hold promise for improving outcomes in this aggressive disease.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"365-391"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874436","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}
{"title":"Expression and Function of FAM72A Gene in Multiple MyelomaFAM72A.","authors":"Wenyu Gao, Yanping Ma","doi":"10.2174/0113892010311258240729080309","DOIUrl":"10.2174/0113892010311258240729080309","url":null,"abstract":"<p><strong>Aims: </strong>This study aims to comprehensively investigate the role of Family Member A with sequence similarity 72-A (FAM72A) in multiple myeloma.</p><p><strong>Background: </strong>Multiple myeloma poses significant challenges. This study delves into FAM72A's impact on key cellular processes, shedding light on potential therapeutic targets and enhancing our understanding of multiple myeloma progression.</p><p><strong>Objectives: </strong>Investigate the impact of FAM72A on the proliferation, apoptosis, and bortezomib sensitivity of multiple myeloma cell line U266.</p><p><strong>Methods: </strong>qRT-PCR analyzed FAM72A expression levels in bone marrow samples from 30 patients with multiple myeloma and 10 healthy donors at the Second Hospital of Shanxi Medical University. Cell lines overexpressing FAM72A were constructed, and Cell Counting Kit 8 (CCK-8) and flow cytometry were used to assess U266 cell proliferation, apoptosis, and sensitivity to bortezomib. Biological predictions for FAM72A were performed to find transcription factors binding to the FAM72A promoter region, verified using a luciferase assay. U266 cells were transfected with si-POU2F2 (POU class 2 homeobox 2), and the impact on cell proliferation was validated. Western blot analysis detected the expression of downstream proteins in the p53 signaling pathway. In vivo, experiments established a xenograft mouse model further to study the role of FAM72A in multiple myeloma.</p><p><strong>Results: </strong>FAM72A was upregulated in multiple myeloma bone marrow tissues. Compared to the OE-NC group, the OE-FAM72A group showed increased Mouse Double Minute 2 homolog (MDM2) expression, decreased p53 expression, increased cell proliferation, and decreased apoptosis. POU2F2 was identified as the upstream transcription factor for FAM72A. Compared to the si-NC group, the si-POU2F2 group exhibited decreased MDM2 expression, increased p53 expression, slowed cell proliferation, and increased apoptosis. Silencing POU2F2 could reverse the pro-proliferative effect of over-expressing FAM72A in U266 cells. <i>In vivo</i> experiments in a xenograft mouse model further studied the role of FAM72A in multiple myeloma.</p><p><strong>Conclusion: </strong>Overexpression of FAM72A promotes U266 cell proliferation, inhibits apoptosis, and reduces sensitivity to bortezomib by regulating the POU2F2/FAM72A/p53 signaling pathway.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"455-464"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916304","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}
Seyed Reza Taha, Andarz Fazlollahpour-Naghibi, Mahdieh Shariat Zadeh, Kimia Bagheri, Hamed Rahmani Youshanlouei, Reza Mosaddeghi-Heris, Seyyed Sina Hejazian, Amirreza Khalaji, Seyedeh Shaghayegh Alavi, Payam Fattahi, Saba Mehrtabar
{"title":"The Hepatoprotective Effects of Ginsenoside from Ginseng: A Review of Molecular Mechanisms and Therapeutic Potentials.","authors":"Seyed Reza Taha, Andarz Fazlollahpour-Naghibi, Mahdieh Shariat Zadeh, Kimia Bagheri, Hamed Rahmani Youshanlouei, Reza Mosaddeghi-Heris, Seyyed Sina Hejazian, Amirreza Khalaji, Seyedeh Shaghayegh Alavi, Payam Fattahi, Saba Mehrtabar","doi":"10.2174/0113892010291326240214095327","DOIUrl":"10.2174/0113892010291326240214095327","url":null,"abstract":"<p><p>Treatment of hepatic diseases presents a significant challenge due to their diverse nature. Ginsenosides, bioactive compounds derived from the root of Panax ginseng and widely used in traditional Chinese medicine, offer multifaceted protection to various organs in the body. Their versatile effects, including antioxidant, anti-inflammatory, anti-apoptotic and more, make them a promising approach for addressing hepatic disorders. This review explores the intricate molecular mechanisms and properties of ginsenosides in the prevention and treatment of liver ailments, from mild conditions to severe damage and liver fibrosis. Given the increasing prevalence of hepatic disorders, this article sheds light on the significant pharmaceutical potential of ginsenosides in the realm of hepatic disease management.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"957-971"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995882","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}
Guoliang Mao, Wuqin Xu, Muhammad Jamil, Wei Zhang, Nanlin Jiao, Yinhua Liu
{"title":"Exploring the Diagnostic and Prognostic Predictive Values of Ferroptosis-related Markers in Lung Adenocarcinoma.","authors":"Guoliang Mao, Wuqin Xu, Muhammad Jamil, Wei Zhang, Nanlin Jiao, Yinhua Liu","doi":"10.2174/0113892010293337240312051931","DOIUrl":"10.2174/0113892010293337240312051931","url":null,"abstract":"<p><strong>Background: </strong>Lung Adenocarcinoma (LUAD), a common and aggressive form of lung cancer, poses significant treatment challenges due to its low survival rates.</p><p><strong>Aim: </strong>To better understand the role of ferroptosis driver genes in LUAD, this study aimed to explore their diagnostic and prognostic significance, as well as their impact on treatment approaches and tumor immune function in LUAD.</p><p><strong>Methods: </strong>To accomplish the defined goals, a comprehensive methodology incorporating both <i>in silico</i> and wet lab experiments was employed. A comprehensive analysis was conducted on a total of 233 ferroptosis driver genes obtained from the FerrDB database. Utilizing various TCGA databases and the RT-qPCR technique, the expression profiles of 233 genes were examined. Among them, TP53, KRAS, PTEN, and HRAS were identified as hub genes with significant differential expression. Notably, TP53, KRAS, and HRAS exhibited substantial up-regulation, while PTEN demonstrated significant down-regulation at both the mRNA and protein levels in LUAD samples. The dysregulation of hub genes was further associated with poor overall survival in LUAD patients. Additionally, targeted bisulfite-sequencing (bisulfite-seq) analysis revealed aberrant promoter methylation patterns linked to the dysregulation of hub genes.</p><p><strong>Results & discussion: </strong>Furthermore, hub genes were found to participate in diverse oncogenic pathways, highlighting their involvement in LUAD tumorigenesis. By leveraging the diagnostic and prognostic potential of ferroptosis driver hub genes (TP53, KRAS, PTEN, and HRAS), significant advancements can be made in the understanding and management of LUAD pathogenesis.</p><p><strong>Conclusion: </strong>Therapeutic targeting of these genes using specific drugs holds great promise for revolutionizing drug discovery and improving the overall survival of LUAD patients.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"411-427"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140206444","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}
Manaf AlMatar, Isil Var, Selin Saglam, Osman Albarri
{"title":"The Effectiveness of LISTEX<sup>TM</sup> P100 in Reducing the Biofilm of <i>Listeria</i> spp. on Steel, Plastic, and Galvanised Surfaces.","authors":"Manaf AlMatar, Isil Var, Selin Saglam, Osman Albarri","doi":"10.2174/0113892010299925240507063431","DOIUrl":"10.2174/0113892010299925240507063431","url":null,"abstract":"<p><strong>Background: </strong>Eliminating and managing <i>L. monocytogenes, L. welshimeri</i>, and <i>L. ivanovii</i> biofilms is a significant problem for food safety, as listeriosis is among the worst foodborne illnesses.</p><p><strong>Methods: </strong>The Listex P100 bacteriophage's bactericidal and inhibitory properties have been investigated in relation to varying strains of vegetative cells and biofilms of <i>L. monocytogenes, L. welshimeri</i>, and <i>L. ivanovii</i>.</p><p><strong>Results: </strong>The phage concentrations of 10<sup>9</sup> and 10<sup>10</sup> PFU/ml showed strong antibacterial activity against <i>L. monocytogenes, L. welshimeri</i>, and <i>L. ivanovii</i> at both 10°C and 30°C (P<0.05). In 96- well microplate experiments, bacteriophage treatment inhibited biofilm development and reduced biofilm by up to 57.6% (P ≤ 0.05). When compared to controls, Listex P100 bacteriophage significantly reduced the populations of <i>L. monocytogenes, L. welshimeri</i>, and <i>L. ivanovii</i> biofilms on the surfaces of galvanised, stainless steel, and plastic surfaces where holes were produced and the structure of Listeria spp. was disturbed.</p><p><strong>Conclusion: </strong>This study clearly demonstrated that <i>L. monocytogenes, L. welshimeri</i>, and <i>L. ivanovii</i> biofilms on galvanised, stainless steel, and plastic surfaces might be removed by using Listex P100 bacteriophage.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"539-549"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080778","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}
Nai-Fang Chang, Pey-Shiuan Wu, Hsiang-Ju Yang, Ya-Min Zheng, Chih-Chien Lin
{"title":"Preparation and Evaluation of Nanoemulsion Formulation Containing Kojic Acid and Kojyl 3-aminopropylphosphonic Acid.","authors":"Nai-Fang Chang, Pey-Shiuan Wu, Hsiang-Ju Yang, Ya-Min Zheng, Chih-Chien Lin","doi":"10.2174/0113892010310230240615112928","DOIUrl":"10.2174/0113892010310230240615112928","url":null,"abstract":"<p><strong>Background: </strong>The kojyl 3-aminopropylphosphonic acid (KAP) was synthesized by kojic acid (KA) with a 3-aminopropylphosphonic acid. Which is more stable than KA and showed better skin penetration and anti-pigmentation efficacy in melanocytes. However, up till now, there have been no studies aimed at incorporating KAP into an emulsion system and evaluating its effectiveness.</p><p><strong>Objective: </strong>We develop a novel skin-lightening agent using KAP as the active ingredient and a low-cytotoxic nanoemulsion as the delivery system in this study.</p><p><strong>Method: </strong>The sorbitan monooleate and polysorbate surfactants with polyethylene glycol (PEG) co-surfactant were used to generate a nanoemulsion system.</p><p><strong>Result: </strong>The transparency and particle size stability over various storage times indicate that the formulated nanoemulsions are suitable for long-term storage. Besides, results demonstrate that the anti-pigmentation function of KA and KAP-containing nanoemulsions (NE-KA and NEKAP) evidently outperformed that of the non-packed KA and KAP group. Despite having the lowest concentration among other treatments, NE-KAP was able to reduce melanin content to approximately 80% of the blank.</p><p><strong>Conclusion: </strong>Our findings suggest that this newly developed nanoemulsion containing KAP could potentially serve as a sustainable alternative to hydroquinone for treating dermal hyperpigmentation disorders in future applications.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"608-616"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562897","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}
{"title":"A Comprehensive Review on Preclinical Alzheimer's Disease Models: Evaluating their Clinical Relevance.","authors":"Virendra Kushwaha, Kantrol Kumar Sahu","doi":"10.2174/0113892010331845240802073645","DOIUrl":"10.2174/0113892010331845240802073645","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurological disorder that increases with age and must be treated immediately by worldwide healthcare systems. Internal neurofibrillary tau tangles and extracellular amyloid accumulation have been widely recognized as the primary causes of Alzheimer's disease. These degenerative age-related ailments are expected to proliferate exponentially as life expectancy rises. Experimental models of AD are essential for acquiring a deep knowledge of its pathogenesis and determining the viability of novel therapy options. Although there isn't a model that encompasses all the characteristics of real AD, these models are nonetheless highly helpful for the research of various modifications associated with it, even though they are only partially indicative of the disease circumstances being studied. Better knowledge of the advantages and disadvantages of each of the different models, as well as the use of more than one model to evaluate potential medications, would increase the effectiveness of therapy translation from preclinical research to patients. We outline the pathogenic characteristics and limitations of the main experimental models of AD in this review, including transgenic mice, transgenic rats, primates and non-primate models along with <i>in-vitro</i> cell culture models in humans. Additionally, it highlights the possible future of experimental modeling of AD and includes the co-morbid models.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"186-207"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003826","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}
{"title":"Potential Serotonin 5-HT2A Receptor Agonist of Psychoactive Components of <i>Silene undulata</i> Aiton: LC-MS/MS, ADMET, and Molecular Docking Studies.","authors":"Maram B Alhawarri, Suleiman Olimat","doi":"10.2174/0113892010299804240324140017","DOIUrl":"10.2174/0113892010299804240324140017","url":null,"abstract":"<p><strong>Background: </strong>Silene undulata is historically used for inducing vivid and prophetic lucid dreams, but limited information exists on its phytochemical composition and potential pharmacological properties.</p><p><strong>Objective: </strong>This study aimed to investigate the phytochemical composition of <i>S. undulata</i> through LC-MS/MS analysis and explore its potential serotonergic activity, which could support and confirm the traditional use of <i>S. undulata</i> as a dream-inducing plant.</p><p><strong>Methods: </strong>LC-MS/MS analysis was conducted on <i>S. undulata</i> extract, identifying 51 phytochemicals, including norharman, harmalol, harmaline, harmine, and ibogaine alkaloids. ADMET and Molecular docking investigations were employed to assess the serotonergic potential of these compounds.</p><p><strong>Results: </strong>The analysis revealed the presence of <i>β</i>-carboline alkaloids, such as norharman, harmalol, harmaline, harmine, and ibogaine, within <i>S. undulata</i> extract. ADMET analysis showed that these compounds have a favourable pharmacokinetic properties. In addition, molecular docking investigations showed that harmaline (-8.90 Kcal/mol), harmalol (-8.56 Kcal/mol), and ibogaine (-8.75 Kcal/mol) exhibited binding affinities comparable to the control molecule, LSD (-9.14 Kcal/mol), indicating potential agonistic activity at serotonin 5-HT2A receptor.</p><p><strong>Conclusion: </strong>These findings provide insights into the potential therapeutic benefits of <i>S. undulata</i>, supporting its traditional use as a psychoactive plant. This study investigated the chemical constituents and potential serotonergic agonist activity of <i>S. undulata</i> for the first time. While promising, further research is necessary to uncover additional medicinal properties associated with the identified phytochemical components.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"260-275"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335067","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}
{"title":"Protective Effects of Curcumin and Nanomicelle Curcumin on Chlorpyrifos-induced Oxidative Damage and Inflammation in the Uterus, Ovary and Brain of Rats.","authors":"Maryam Nazarian, Hamed Aramjoo, Babak Roshanravan, Saeed Samarghandian, Tahereh Farkhondeh","doi":"10.2174/0113892010297408240319073735","DOIUrl":"10.2174/0113892010297408240319073735","url":null,"abstract":"<p><strong>Background and aims: </strong>Chlorpyrifos (CPF), which is classified as an Organophosphorus Pesticide (OP), has been identified as a toxic agent for the reproductive system due to its capacity to induce oxidative stress and inflammation. Curcumin (CUR) has been reported as a natural antioxidant and anti-inflammatory agent that could combat toxicity in various tissues. This study aims to examine the protective effects of CUR and its nanoformulation against reproductive impairment induced by CPF.</p><p><strong>Methods: </strong>Forty-eight female Wistar albino rats were randomly allocated to six groups (n=8): control (0.5 mL of corn oil, the solvent for CPF), CPF (10 mg/kg), CPF + CUR 100 mg/kg/day, CPF + CUR 300 mg/kg/day, CPF + nano-micelle curcumin (NMC) 2.5 mg/kg/day, and CPF + NMC 5 mg/kg/day. The experimental treatment was performed for 30 days. Then, brain, ovary and uterus tissues were collected for measuring oxidative stress and inflammatory indices.</p><p><strong>Results: </strong>MDA, NO, IL-6, and TNF-α concentrations significantly increased in the brain, ovary and uterus of the CPF group versus the control group (p < 0.001). The levels of GSH and SOD in the uterus, ovaries, and brain exhibited a significant decrease in the CPF group compared to the control group (p < 0.05). However, CUR (300 mg/kg) and NMC (5 mg/kg) significantly decreased MDA, NO, TNF-α, and Il-6 and increased SOD and GSH levels in the uterus, ovaries and brain of the CPF-exposed animals versus the CPF-exposed non-treated animals (p < 0.001).</p><p><strong>Conclusion: </strong>Our findings indicated that CUR and NMC could be effective in alleviating CPFinduced reproductive toxicity.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"490-496"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335068","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}
{"title":"TP508 Promotes Bone Regeneration on Distraction Osteogenesis <i>via</i> the Activation of Wnt/β-catenin Signaling Pathway.","authors":"Kehan Li, Linan Liu, Jingyi Zhang, Chenyu Liao, Jian Hu, Jian Song","doi":"10.2174/0113892010289575240306033011","DOIUrl":"10.2174/0113892010289575240306033011","url":null,"abstract":"<p><strong>Introduction: </strong>TP508 is a thrombin peptide that participates in the inflammatory response and wound healing. Its role in the molecular mechanism of distraction osteogenesis remains unclear. This study established a tibia distraction osteogenesis (DO) model in rats and investigated the role and mechanism of TP508 in bone regeneration during DO.</p><p><strong>Method: </strong>Micro-computed tomography (Micro-CT) and hematoxylin-eosin (HE) staining were used to track osteogenesis. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to measure the expression of osteoblast-related factors, Wnt/β- catenin signaling-related proteins and genes. Immunohistochemistry was used to measure the expression of β-catenin in the cytoplasm and nucleus.</p><p><strong>Results: </strong>TP508 accelerated bone regeneration increased the expression of the osteoblast-related factors Alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN). After the Wnt signaling was inhibited by LGK974, the expression of osteoblastrelated factors was downregulated, leading to a decrease in bone regeneration ability. More importantly, TP508 upregulated β-catenin and its target CYCLIN-D1 and could reverse the decreased osteogenic ability caused by LGK974.</p><p><strong>Conclusion: </strong>In conclusion, TP508 promotes bone regeneration in DO by activating the Wnt/β- catenin signaling pathway.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"402-410"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101238","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}