Review
Biochemistry & Molecular Biology
Edoardo Troncone, Irene Marafini, Carmine Stolfi, Giovanni Monteleone
Summary: The TGF-beta 1/Smad signaling pathway plays a crucial role in inflammatory bowel diseases, with defective signaling observed in patients with Crohn's disease and ulcerative colitis. Over-expression of Smad7 exacerbates colitis, while pharmacological inhibition of Smad7 restores TGF-beta 1 function and reduces inflammatory responses in patients with IBD. Smad7 is also implicated in colon carcinogenesis and its polymorphisms could potentially influence cancer prognosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jun Li, Ruoshui Li, Izabela Tuleta, Silvia C. Hernandez, Claudio Humeres, Anis Hanna, Bijun Chen, Nikolaos G. Frangogiannis
Summary: The role of macrophage Smad7 in regulating inflammation and repair after myocardial infarction is limited. The anti-inflammatory effects of TGF-beta in macrophages are not restrained by endogenous Smad7 induction.
Article
Oncology
Claudia Maresca, Giulia Di Maggio, Carmine Stolfi, Federica Laudisi, Marco Colella, Teresa Pacifico, Antonio Di Grazia, Davide Di Fusco, Daniele Congiu, Andrea Martina Guida, Giuseppe Sica, Ivan Monteleone, Giovanni Monteleone
Summary: The study reveals a novel positive feedback loop involving Smad7 and Stat3 in CRC cells, suggesting therapeutic targeting of Smad7 in patients with colorectal cancer.
Article
Chemistry, Multidisciplinary
Yang Sun, Zi-jian Li
Summary: TGF-beta is a critical polypeptide involved in regulating various cellular functions and physiological processes. Dysregulation of TGF-beta signalling leads to disorders such as cardiovascular diseases, cancer, and immunological diseases. The study reveals a new mechanism by which HIP-55 regulates TGF-beta signalling, providing potential novel strategies for treating TGF-beta signalling-related human diseases.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Pharmacology & Pharmacy
Xu Shi, Wenyan Jiang, Xiaoguang Yang, Heming Ma, Zhongfeng Wang, Qing Ai, Yutong Dong, Yingyu Zhang, Ying Shi
Summary: This study identified Aucubin as a natural compound with potential anti-liver fibrosis effects. Aucubin inhibited the progression of liver fibrosis by upregulating Smad7 and blocking TGF-β signaling, leading to the inhibition of hepatic stellate cell activation. In an in-vivo mouse model, Aucubin efficiently improved liver fibrosis progression.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Immunology
Changliang Liu, Jiahui Wu, Ming Li, Rui Gao, Xueying Zhang, Shixin Ye-Lehmann, Jiangning Song, Tao Zhu, Chan Chen
Summary: This study found that elevated Smad7 in the hippocampal CA1 region can enhance neuroinflammation and apoptosis, leading to learning and memory impairment after surgery. Therefore, Smad7 may be a potential therapeutic target for the treatment of memory impairment after anesthesia surgery.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Biochemistry & Molecular Biology
Weifeng Wu, Xiao R. Huang, Yongke You, Liang Xue, Xiao-Jing Wang, Xiaoming Meng, Xiang Lin, Jiangang Shen, Xueqing Yu, Hui-Yao Lan, Haiyong Chen
Summary: The study demonstrates that overexpression of latent TGF-beta 1 can protect against the development of DKD in mice, reducing microalbuminuria and inhibiting renal fibrosis and inflammation, without altering blood glucose levels. This protective effect may be associated with the prevention of Arkadia-mediated Smad7 ubiquitin degradation, suggesting a potential mechanism for the inhibition of DKD by latent TGF-beta 1.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Xiaohong Wu, Haiyan Wang, Huamu Chen, Hongrong Lin, Min Li, Zhihui Yue, Liangzhong Sun
Summary: This study revealed that NPHP1 defects activate the TGF-beta/Smad signaling pathway and EMT in MDCK cells, characterized by decreased expression of E-cadherin and beta-catenin, and increased expression of alpha-SMA and FSP1. These factors may contribute to the pathogenesis of interstitial fibrosis in NPHP.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Oncology
Liang Wang, Xiaonan Guan, Qingtao Hu, Zhen Wu, Wei Chen, Lairong Song, Ke Wang, Kaibing Tian, Chunwei Cao, Dake Zhang, Junpeng Ma, Xiangjun Tong, Bo Zhang, Junting Zhang, Changqing Zeng
Summary: Chordoma is a rare bone tumor with downregulation of TGFB3 and upregulation of miR-29 family. Zebrafish experiments highlight the inactivation mechanism of TGFB3 in tumor formation. The retention of negative feedback regulation may maintain the suppressor role of TGF-beta in chordoma cells.
Article
Pharmacology & Pharmacy
Giovanni Monteleone, Carmine Stolfi
Summary: In Crohn's disease and ulcerative colitis, the tissue-damaging inflammatory response involves elevated levels of Smad7, an inhibitor of TGF-beta 1. Previous studies showed that knocking down Smad7 with an antisense oligonucleotide reduced inflammation, leading to the development of mongersen as a potential treatment. Initial studies demonstrated the safety and effectiveness of mongersen in inducing remission in active CD patients. However, a phase 3 trial was prematurely discontinued due to no observed effect of mongersen on CD activity. Recent data suggests that the chemical composition of mongersen batches used in the phase 3 study differed from previous trials, highlighting the need for consistent manufacturing requirements and quality control.
Article
Respiratory System
Guoping Li, Guoliang Liao, Jinbao Xie, Bo Liu, Xu Li, Minglian Qiu
Summary: This study demonstrated the high efficacy and resistance of EGFR-SMAD7-CAR-T in non-small cell lung cancer treatment, through overexpression of the SMAD7 gene.
Article
Biotechnology & Applied Microbiology
Jiewen Su, Dawei Chen, Yi Ruan, Yuan Tian, Kaiji Lv, Xinhua Zhou, Dongjian Ying, Yeting Lu
Summary: Studies have shown that lncRNA MBNL1-AS1 participates in the progression of gastric cancer by regulating the miR-424-5p/Smad7 axis, thus activating the TGF-beta/EMT pathways. This finding may provide a potential marker for gastric cancer patients.
Article
Gastroenterology & Hepatology
Xianjun Xu, Yuecheng Guo, Xin Luo, Zhenyang Shen, Zhongshang Sun, Bo Shen, Cui Zhou, Junjun Wang, Jingyi Lu, Qingqing Zhang, Yanping Ye, Ying Luo, Ying Qu, Xiaobo Cai, Hui Dong, Lungen Lu
Summary: Hydronidone ameliorates liver fibrosis by inhibiting HSCs activation via Smad7-mediated TGF beta RI degradation. It is a potential drug candidate for the treatment of liver fibrosis.
LIVER INTERNATIONAL
(2023)
Article
Pharmacology & Pharmacy
Tao Wang, Yali Zhang, Hanyue Cheng, Ling Li, Lu Xu
Summary: The emergence of acquired resistance to EGFR TKIs, such as osimertinib, limits their long-term efficacy in treating EGFR-mutant lung cancer, necessitating a deeper understanding of the underlying molecular mechanisms. A newly discovered TGF beta 1/integrin beta 3 loop has been identified as a key contributor to the development of acquired resistance. Intervening in this positive feedback loop significantly delays resistance and improves the effectiveness of EGFR TKIs in treating EGFR-mutant lung cancer.
JOURNAL OF DRUG TARGETING
(2023)
Article
Medicine, Research & Experimental
Minmin Gong, Yujin Guo, Hui Dong, Wenbin Wu, Fan Wu, Fuer Lu
Summary: This study demonstrates that trigonelline can attenuate tubular epithelial-mesenchymal transition and renal fibrosis in diabetic mice, potentially by upregulating Smad7 in proximal tubule epithelial cells. These findings suggest the potential of trigonelline as a promising medicine against diabetic kidney disease.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Monireh Khordadmehr, Hamed Ezzati, Amirali Shahbazfar, Farinaz Jigari-Asl, Behzad Baradaran, Elham Baghbani, Saeed Noorolyai
Summary: The overexpression of miR-451a can enhance the chemosensitivity of breast cancer cells to carboplatin therapy, which may provide a beneficial strategy for future cancer therapy.
PHARMACEUTICAL SCIENCES
(2023)
Article
Oncology
Farid Ghorbaninezhad, Hajar Alemohammad, Basira Najafzadeh, Javad Masoumi, Mahdi Abdoli Shadbad, Mohammad Shahpouri, Hossein Saeedi, Omid Rahbarfarzam, Behzad Baradaran
Summary: Dexosomes released by dendritic cells can stimulate CD8+ and CD4+ T cell responses, leading to effective anti-tumoral immune responses. Combining dexosomes vaccination with other treatment approaches can significantly increase tumor-specific T cell responses.
Article
Genetics & Heredity
Noora Karim Ahangar, Mohammad Khalaj-Kondori, Nazila Alizadeh, Ahad Mokhtarzadeh, Amir Baghbanzadeh, Mahdi Abdoli Shadbad, Katayoun Dolatkhah, Behzad Baradaran
Summary: This study found that tumor-intrinsic HHLA2 knockdown increases the anti-tumoral effect of paclitaxel on MG-63 cells and enhances the chemosensitivity of MG-63 cells to paclitaxel.
Article
Oncology
Elaheh Mohammadali, Reza Safaralizadeh, Arash Poursheikhani, Tooraj Asvadi, Behzad Baradaran, Shahram Teimourian
Summary: This study aimed to evaluate the expression of lncRNA TMPO-AS1 in Iranian patients with gastric cancer (GC). Results showed that TMPO-AS1 was overexpressed in cancerous tissues and could serve as a biomarker to distinguish tumor tissues from normal ones. However, further research is needed to confirm its potential application in the diagnosis, prognosis, and treatment of GC.
INTERNATIONAL JOURNAL OF CANCER MANAGEMENT
(2023)
Article
Oncology
Seyed Samad Hosseini, Paria Nazifi, Mohammad Amini, Felor Zargari, Amir Hossein Yari, Behzad Baradaran, Soltanali Mahboob, Ahad Mokhtarzadeh
Summary: The study showed that crocin decreases cell viability in colorectal cancer cells by upregulating miR-143/145 expression and decreasing KRAS and RREB1 expression dose-dependently. Furthermore, crocin treatment also led to the inactivation of AKT by decreasing its phosphorylation, suggesting a potential inhibitory effect on CRC cell proliferation.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Behnaz Mansoori, Shiva Kiani, Alireza Ashrafi Mezajin, Pouyan Zandi, Homadokht Banaie, Davoud Rostamzadeh, William C. Cho, Pascal H. G. Duijf, Behzad Mansoori, Behzad Baradaran
Summary: MiR-143-5p expression is lower in breast cancer tissues compared to normal tissues and low expression is associated with poor prognosis in ER-positive breast cancer patients. Restoration of miR-143-5p suppresses metastasis, reduces cell proliferation, stemness, and promotes apoptosis in ER-positive breast cancer cells through direct targeting of HMGA2. Restoring miR-143-5p could be a promising therapeutic approach for ER-positive breast cancer.
CLINICAL BREAST CANCER
(2023)
Review
Immunology
Sepideh Sohrabi, Javad Masoumi, Bahar Naseri, Farid Ghorbaninezhad, Shiva Alipour, Tohid Kazemi, Javad Ahmadian Heris, Leili Aghebati Maleki, Pedram Basirjafar, Raziyeh Zandvakili, Mohammad Amin Doustvandi, Behzad Baradaran
Summary: This review focuses on the importance of STAT transcription factors' signaling pathways in different subtypes of dendritic cells, and highlights their potential applications in improving immunotherapies based on dendritic cells according to the type of STAT transcription factor and its specific activating or inhibitory agent.
INTERNATIONAL REVIEWS OF IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Negin Riazi-Tabrizi, Mohammad Khalaj-Kondori, Sahar Safaei, Mohammad Amini, Hamidreza Hassanian, Mohadeseh Maghsoudi, Shima Hasani, Behzad Baradaran
Summary: Combination therapy of NRF2 siRNA with paclitaxel can significantly reduce NRF2 gene expression in pancreatic cancer cells, inhibiting cell migration, inducing apoptosis and autophagy, and arresting the cell cycle. NRF2 siRNA can also enhance the sensitivity of Miapaca-2 cells to paclitaxel, showing potential therapeutic efficacy in treating pancreatic cancer.
MOLECULAR BIOTECHNOLOGY
(2023)
Review
Pathology
Vahid Asghariazar, Mahtab Kadkhodayi, Mehdi Sarailoo, Amir Ghaffari Jolfayi, Behzad Baradaran
Summary: This review outlines the impact of miR-143 expression levels on cancer progression, discussing its roles as a tumor suppressor or an oncogene, and explores its target genes and relevant signaling pathways.
PATHOLOGY RESEARCH AND PRACTICE
(2023)
Review
Materials Science, Biomaterials
Zahra Ghahramanipour, Shiva Alipour, Javad Masoumi, Arman Rostamlou, Amirhossein Hatami-Sadr, Javad Ahmadian Heris, Bahar Naseri, Mahdi Jafarlou, Behzad Baradaran
Summary: A functional immune system is crucial for protecting us from infections, tumors, or autoimmune disorders. Micronutrients, particularly vitamins, play important roles in maintaining immune system balance. This review focuses on the roles of vitamins (D, E, A, C) and dendritic cells' subsets in immune processes, including functions, maturation, and cytokine production. Current studies show significant benefits of these vitamins, such as the control of dendritic cells' function and maturation by vitamin E, and the immunoregulatory and anti-inflammatory role of vitamin D. The metabolite of vitamin A, retinoic acid, influences T cell differentiation, and vitamin C has antioxidant effects on dendritic cells. The correlation between vitamin levels and allergic diseases or autoimmunity disorders is also discussed based on previous research.
Article
Oncology
Mohammad Heiat, Ehsan Rezaei, Javad Gharechahi, Masoumeh Abbasi, Javad Behroozi, Mohammad Ali Abyazi, Behzad Baradaran
Summary: Silencing SIX4 inhibits the survival, migration, and invasion ability of pancreatic cancer cells, increases apoptosis and autophagy rates, and reduces mitochondrial membrane potential. Furthermore, knockdown of SIX4 affects the expression of genes related to apoptosis and metastasis. Overall, SIX4 plays a critical role in the development of pancreatic cancer.
Article
Pharmacology & Pharmacy
Nadia Bolandi, Mohammad Hassan Khadem Ansari, Yousef Rasmi, Behzad Baradaran
Summary: The aim of this study was to evaluate the effect of B7-H7 suppression using small interference RNA (siRNA) in combination with docetaxel on gastric cancer cells. The results showed that B7-H7 suppression increased the chemo-sensitivity of MKN-45 cells to docetaxel, reduced cell migration and colony formation rate, arrested the cell cycle at the G2-M phase, and induced apoptosis by modulating the expression of apoptotic target genes. Therefore, B7-H7 suppression, in combination with docetaxel, may be a promising therapeutic approach in treating gastric cancer.
ADVANCED PHARMACEUTICAL BULLETIN
(2023)
Article
Pharmacology & Pharmacy
Souzan Najafi, Zohreh Rahimi, Behzad Mansoori, Ali Mohammadi, Fatemeh Mohammadnejad, Mohammad Amini, Ahad Mokhtazadeh, Zahra Asadzadeh, William Chi-Shing Cho, Behzad Baradaran
Summary: The present study aimed to examine the simultaneous therapeutic effect of CD44 silencing and 5-fluorouracil (5-FU) on in vitro tumorigenesis of colorectal cancer (CRC) cells. CD44 was significantly overexpressed in CRC tissues. Suppression of CD44 considerably promoted the chemosensitivity of CRC cells to 5-FU by inducing apoptosis. Additionally, CD44 suppression, separately or in combination with 5-FU, hindered stemness properties and inhibited cell migration.
ADVANCED PHARMACEUTICAL BULLETIN
(2023)
Article
Pharmacology & Pharmacy
Monireh Khordadmehr, Reyhaneh Matin, Behzad Baradaran, Elham Baghbani, Farinaz Jigari-Asl, Saeed Noorolyai
Summary: This study investigated the effect of miR-4800 restoration on the growth and migration inhibition of human breast cancer cells. The restoration of miR-4800 resulted in decreased expression levels of CXCR4, ROCK1, CD44, and vimentin genes, as well as reduced cell viability and migration ability. Therefore, miR-4800 can act as a tumor suppressor miRNA in breast cancer and may serve as a potential therapeutic target.
ADVANCED PHARMACEUTICAL BULLETIN
(2023)
Review
Pharmacology & Pharmacy
Mina Afrashteh Nour, Farid Ghorbaninezhad, Zahra Asadzadeh, Amir Baghbanzadeh, Hamidreza Hassanian, Patrizia Leone, Mahdi Jafarlou, Nazila Alizadeh, Vito Racanelli, Behzad Baradaran
Summary: Auto-immune diseases are chronic disorders where the immune system destroys the body's cells due to a loss of tolerance to self-antigens. Systemic lupus erythematosus (SLE) is an example of these diseases and is characterized by the production of autoantibodies in different body parts. Genetic and epigenetic factors, including alterations in noncoding RNAs (ncRNAs), play a crucial role in the pathogenesis of SLE.
THERAPEUTIC ADVANCES IN CHRONIC DISEASE
(2023)