Article
Biochemistry & Molecular Biology
Katri Vaparanta, Anne Jokilammi, Ilkka Paatero, Johannes A. Merilahti, Juho Heliste, Karthik Amudhala Hemanthakumar, Riikka Kivela, Kari Alitalo, Pekka Taimen, Klaus Elenius
Summary: In this study, it is demonstrated that Neuregulin-1 (NRG-1) regulates myocardial growth through the STAT5b pathway. Disruption of the NRG-1/ERBB4 pathway or inhibition of Dynamin-2 reduces STAT5b activation and cardiomyocyte hypertrophy. Activation of Stat5 is also observed in NRG-1-induced myocardial growth in zebrafish embryos, and knockdown of stat5b leads to reduced myocardial growth and cardiac function. Furthermore, the NRG-1/ERBB4/STAT5b pathway is differentially regulated in patients with pathological cardiac hypertrophy.
Article
Medicine, General & Internal
Malgorzata Galecka, Janusz Szemraj, Kuan-Pin Su, Angelos Halaris, Michael Maes, Aleksandra Skiba, Piotr Galecki, Katarzyna Blizniewska-Kowalska
Summary: This study found that there is increased expression of JAK3 and decreased expression of STAT1 in depressed patients.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biology
Xuelian Chen, Yunzheng Zhang, Junjian He, Yibing Li
Summary: This study identified the importance of STAT5B in endometrial carcinoma (EC) and its correlation with clinical outcomes. STAT5B and STAT6 expression predicted favorable clinical outcomes, while STAT1 and STAT2 expression predicted poor clinical outcomes in EC. The STAT family was found to be involved in apoptosis pathway activation, cell cycle disruption, and epithelial-mesenchymal transition. STAT5B expression was also correlated with clinicopathological characteristics, immune cell infiltration, and specific signaling pathways.
Review
Dermatology
Qi Yin, Albert Wolkerstorfer, Oren Lapid, Frank B. Niessen, Paul P. M. Van Zuijlen, Susan Gibbs
Summary: Keloid tissues contain inflammatory cells and upregulated pro-inflammatory cytokines. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway mediate cellular responses to these cytokines. Preclinical studies indicate a role for the JAK-STAT pathway in keloid pathogenesis and a potential role for JAK-STAT inhibitors in keloid treatment. Further investigation on relevant biomarkers in a human keloid skin model and in clinical studies is needed.
EXPERIMENTAL DERMATOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Ines Roger, Javier Milara, Paula Montero, Julio Cortijo
Summary: Pulmonary hypertension is a group of diseases characterized by an increase in pulmonary vascular resistance, leading to right ventricular failure and premature death. Current treatments for PH are limited to vasodilatory agents, prompting the search for new drugs that target pulmonary artery remodeling. Activation of the JAK/STAT pathway plays a critical role in pulmonary artery remodeling and PH progression, suggesting it as a potential target for future treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Obstetrics & Gynecology
Hiroaki Inui, Takako Kawakita, Misaki Murayama, Tomotaka Nakagawa, Hikari Sasada, Ayaka Shinohara, Ryousuke Aragaki, Tomohiro Kagawa, Yuri Kadota, Takeshi Kato, Masato Nishimura, Takeshi Iwasa
Summary: STAT inhibitors have a therapeutic effect on endometriosis.
REPRODUCTIVE SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Jia Liu, Faping Wang, Fengming Luo
Summary: There are four members of the JAK family and seven of the STAT family in mammals. The JAK/STAT molecular pathway can be activated by various hormones, cytokines, growth factors, etc. The JAK/STAT signaling pathway extensively mediates various biological processes such as cell proliferation, differentiation, migration, apoptosis, and immune regulation.
Article
Cell Biology
Zhihui Min, Jiebai Zhou, Ruolin Mao, Bo Cui, Yunfeng Cheng, Zhihong Chen
Summary: The study found that PQQ can alleviate allergic airway inflammation in mice by improving the immune microenvironment and regulating the JAK-STAT signaling pathway, suggesting its potential as a therapeutic agent for inflammatory diseases, including asthma.
MEDIATORS OF INFLAMMATION
(2022)
Article
Biochemistry & Molecular Biology
Sarah M. M. AL-Qabbaa, Samaher I. I. Qaboli, Tahani K. K. Alshammari, Maha A. A. Alamin, Haya M. M. Alrajeh, Lama A. A. Almuthnabi, Rana R. R. Alotaibi, Asma S. S. Alonazi, Anfal F. F. Bin Dayel, Nawal M. M. Alrasheed, Nouf M. M. Alrasheed
Summary: This study examined the therapeutic effects of sitagliptin, a dipeptidyl peptidase inhibitor, on diabetic nephropathy (DN). The results showed that sitagliptin can reduce inflammation and improve DN by inhibiting PTP1B and modulating the JAK/STAT signaling pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Grace L. Wong, Sara G. Manore, Daniel L. Doheny, Hui-Wen Lo
Summary: Breast cancer is a common and deadly disease in women, and the STAT family of transcription factors, especially STAT3, plays a critical role in its development and progression. Targeting STAT proteins for cancer treatment presents significant opportunities and challenges.
SEMINARS IN CANCER BIOLOGY
(2022)
Review
Genetics & Heredity
Abdolmajid Ghasemian, Hadeel A. Omear, Yaser Mansoori, Pardis Mansouri, Xinpei Deng, Farzaneh Darbeheshti, Elham Zarenezhad, Maryam Kohansal, Babak Pezeshki, Zhangling Wang, Hailin Tang
Summary: Colorectal cancer is a fatal cancer, and lncRNAs play regulatory roles in cell proliferation and immune responses via the JAK/STAT signaling pathway, making them potential biomarkers and therapeutic targets.
FRONTIERS IN GENETICS
(2023)
Review
Cell Biology
Lena Puigdevall, Camille Michiels, Clara Stewardson, Laure Dumoutier
Summary: A subset of cytokines triggers the JAK-STAT pathway to exert various functions such as inflammation and immune responses. There are alternative modes of STAT activation, including association between the tyrosine-free region of cytokine receptors and STATs, and direct interaction between JAK and STAT proteins. These noncanonical mechanisms by cytokine receptors suggest their importance and are discussed in this review.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Review
Immunology
Amr Allam, Marina Yakou, Lokman Pang, Matthias Ernst, Jennifer Huynh
Summary: This article discusses the relationship between cancer-associated fibroblasts (CAFs) and signal transducer and activator of transcription 3 (STAT3) in the tumor microenvironment, as well as their impact on tumor growth, immune suppression, and metastatic spread. Research suggests that CAF-intrinsic STAT3 activity is closely associated with tumor progression.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Plant Sciences
Hyun-Seung Lee, Yong-Jin Kwon, Eun-Bi Seo, Seul-Ki Kim, Haeri Lee, Jin-Tae Lee, Pahn-Shick Chang, Young Jin Choi, Sung-Hyen Lee, Sang-Kyu Ye
Summary: The peel extract of Allium cepa (AP50E) exhibits anti-inflammatory effects in LPS-induced RAW264.7 mouse macrophages by directly inhibiting the JAK-STAT signaling pathway. These findings suggest that AP50E may be a potential candidate for the development of preventive or therapeutic agents against inflammatory diseases.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
N. P. Syamprasad, Nitin Madje, Jayasri Bachannagari, Arun Kumar Jannu, Siddhi Jain, Kalyani Tene, P. A. Shantanu, V. G. M. Naidu, Naveen Chella
Summary: The current therapy for gastrointestinal stromal tumors is limited in its efficacy and resistance. In this study, the potential of the signal transducer and activator of transcription 3 (STAT3) inhibitor, niclosamide, to treat gastrointestinal stromal tumors was explored. Nanocrystals of niclosamide were developed to improve solubility and bioavailability. The study demonstrated that niclosamide induced dose-dependent cytotoxicity, mitochondrial damage, and apoptotic-like cell death in gastrointestinal stromal tumor cells. Niclosamide nanocrystals showed enhanced anticancer activity compared to pure niclosamide. Furthermore, niclosamide nanocrystals exhibited better tumor suppression, indicating higher bioavailability. This study suggests that nanocrystals could be a promising delivery strategy for niclosamide in treating gastrointestinal stromal tumors.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Abisha Crystal Christopher, Vigneshwaran Venkatesan, Karthik V. Karuppusamy, Saranya Srinivasan, Prathibha Babu, Manoj Kumar K. Azhagiri, Karthik Chambayil, Abhirup Bagchi, Vignesh Rajendiran, Nithin Sam Ravi, Sanjay Kumar, Srujan Kumar Marepally, Kumarasamypet Murugesan Mohankumar, Alok Srivastava, Shaji R. Velayudhan, Saravanabhavan Thangavel
Summary: In this study, a combination of small molecules was identified to selectively expand CD34(+)CD133(+)CD90(+) hematopoietic stem cells (HSCs) in ex vivo culture. The preferential expansion enriched the HSCs in culture and significantly increased long-term engraftment in NSG mice. The culture-enriched HSCs also showed a higher responsiveness to gene modification, resulting in a higher frequency of gene-modified HSCs. The yield of gene-modified HSCs obtained through culture enrichment was similar to sort-purification and superior to Cyclosporin-H treatment.
HUMAN GENE THERAPY
(2022)
Article
Biology
Nithin Sam Ravi, Beeke Wienert, Stacia K. Wyman, Henry William Bell, Anila George, Gokulnath Mahalingam, Jonathan T. Vu, Kirti Prasad, Bhanu Prasad Bandlamudi, Nivedhitha Devaraju, Vignesh Rajendiran, Nazar Syedbasha, Aswin Anand Pai, Yukio Nakamura, Ryo Kurita, Muthuraman Narayanasamy, Poonkuzhali Balasubramanian, Saravanabhavan Thangavel, Srujan Marepally, Shaji R. Velayudhan, Alok Srivastava, Mark A. DeWitt, Merlin Crossley, Jacob E. Corn, Kumarasamypet M. Mohankumar
Summary: Inspired by naturally occurring point mutations in sickle cell patients, this study used base editing to identify novel regulatory regions in the HBG promoter and successfully upregulated fetal hemoglobin synthesis.
Article
Pharmacology & Pharmacy
Gokulnath Mahalingam, Hari Krishnareddy Rachamalla, Porkizhi Arjunan, Yogapriya Periyasami, M. Salma, Saravanabhavan Thangavel, Kumarasamypet M. Mohankumar, Mahesh Moorthy, Shaji R. Velayudhan, Alok Srivastava, Srujan Marepally
Summary: Due to the fast mutating nature of SARS-CoV-2, it is crucial to develop new therapeutics and vaccines, as well as evaluate the efficacy of existing ones against mutated strains. Pseudotyped SARS-CoV-2 viruses have been proven to be useful in evaluating therapeutics, and a comprehensive protocol including selecting transfection reagents and validating packaging systems is necessary. In this study, new cationic lipids were designed and synthesized for the efficient delivery of plasmids. The lipids showed comparable transfection efficiencies with a commercial standard and were used for the preparation of lentiviruses and SARS-CoV-2 pseudovirions. The optimized protocol allowed for the generation of pseudovirions, which were characterized for their infectivity and neutralizing properties.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Immunology
Karthik V. Karuppusamy, John Paul Demosthenes, Vigneshwaran Venkatesan, Abisha Crystal Christopher, Prathibha Babu, Manojkumar K. Azhagiri, Annlin Jacob, Veena Vadhini Ramalingam, Sumathi Rangaraj, Mohankumar Kumarasamypet Murugesan, Srujan Kumar Marepally, George M. Varghese, Alok Srivastava, Rajesh Kannangai, Saravanabhavan Thangavel
Summary: This study demonstrates the potential of using CD34(+)CD90(+) hematopoietic stem cells (HSCs) and gene editing technology as an ideal graft for HIV gene therapy. Treatment with a small molecule cocktail improves the in vivo engraftment potential of CD34(+)CD90(+) HSCs, and gene editing of CCR5 generates immune cells resistant to HIV infection.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Divya Saro Varghese, Thilina T. Alawathugoda, Muhammad Abid Sheikh, Anil Kumar Challagandla, Bright Starling Emerald, Suraiya A. Ansari
Summary: Obesity is a multigene disorder with genetic and environmental factors contributing to its development. Human induced pluripotent stem cells (hiPSCs) from individuals with familial obesity or obesogenic genotype could serve as a valuable model to understand the effects of this multigene disorder on organ development and uncover pathologies associated with obesity.
CELL DEATH & DISEASE
(2022)
Article
Biology
Ahmed Sultan, Ernest Adeghate, Bright Starling Emerald, Muhammad A. Qureshi, Saeed Tariq Minhas, Frank Christopher Howarth
Summary: The study found that the amplitude of shortening in ZF rat ventricular myocytes was increased, while resting Ca2+ levels were elevated in ZDF rat myocytes. Additionally, the time for Ca2+ transient half decay was prolonged in ZDF rats and reduced in ZF rats compared to ZL rats. Changes in protein expression and cell structure were also noted.
Article
Biochemistry & Molecular Biology
Bright Starling Emerald, Mohammed A. Al Jailani, Marwa F. Ibrahim, Challagandla Anil Kumar, Mohammed Z. Allouh
Summary: This study suggests that long-term high-fat diet leads to degeneration and atrophy of skeletal muscle, similar to age-related sarcopenia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Michael Pudjihartono, Jo K. Perry, Cris Print, Justin M. O'Sullivan, William Schierding
Summary: This study reviews the research on non-coding mutations and emphasizes the importance of interpreting and prioritizing different regulatory data types to deepen our understanding of novel mechanisms driving cancer.
CLINICAL EPIGENETICS
(2022)
Article
Cell Biology
Hayate Javed, Aishwarya Mary Johnson, Anil Kumar Challagandla, Bright Starling Emerald, Safa Shehab
Summary: Cutaneous injection of resiniferatoxin (RTX) in the rat's hind paw can completely reverse and prevent neuropathic pain induced by L5 nerve injury. RTX injection also downregulates the expression of nociceptive pain markers and suppresses neuronal activity.
Article
Biotechnology & Applied Microbiology
Brijesh Lohchania, Abisha Crystal Christopher, Porkizhi Arjunan, Gokulnath Mahalingam, Durga Kathirvelu, Aishwarya Prasannan, Vigneshwaran Venkatesan, Pankaj Taneja, K. M. Mohan Kumar, Saravanabhavan Thangavel, Srujan Marepally
Summary: The CRISPR/Cas9 system is promising for treating genetic diseases, but faces challenges in controlling the expression of editing factors and achieving high fidelity. Non-viral vectors have been found as a potential solution. In this study, liposomes with diosgenin were shown to effectively deliver Cas9 pDNA and mRNA for genome editing at multiple loci, surpassing the efficacy of liposomes with cholesterol. Mechanistically, diosgenin facilitated the cholesterol-independent and clathrin-mediated endocytosis of lipoplexes, leading to enhanced intracellular delivery.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Review
Oncology
Yue Wang, Stephen M. F. Jamieson, Jo K. Perry
Summary: Published research supports the role of growth hormone in cancer, leading to increasing interest in targeting growth hormone in oncology. Growth hormone receptor antagonists have shown efficacy in xenograft studies as single agents or in combination with other anticancer therapies. However, there are challenges in using growth hormone receptor antagonists in preclinical models, such as identifying predictive biomarkers for selecting patients and monitoring drug efficacy.
ENDOCRINE-RELATED CANCER
(2023)
Article
Medicine, Research & Experimental
Vigneshwaran Venkatesan, Abisha Crystal Christopher, Manuel Rhiel, Manoj Kumar K. Azhagiri, Prathibha Babu, Kaivalya Walavalkar, Bharath Saravanan, Geoffroy Andrieux, Sumathi Rangaraj, Saranya Srinivasan, Karthik Karuppusamy, Annlin Jacob, Abhirup Bagchi, Aswin Anand Pai, Yukio Nakamura, Ryo Kurita, Poonkuzhali Balasubramanian, Rekha Pai, Srujan Kumar Marepally, Kumarasamypet Murugesan Mohankumar, Shaji R. Velayudhan, Melanie Boerries, Dimple Notani, Toni Cathomen, Alok Srivastava, Saravanabhavan Thangavel
Summary: Reactivation of fetal hemoglobin is a common strategy for treating β-hemoglobinopathies. This study identified a specific genetic mutation that can effectively inhibit the production of adult hemoglobin and increase fetal hemoglobin production. Gene editing of patient hematopoietic stem cells resulted in therapeutic levels of fetal hemoglobin and improved the phenotypes of both sickle cell disease and β-thalassemia major.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Cell Biology
Lekha Jain, Mark H. Vickers, Bincy Jacob, Martin J. Middleditch, Daria A. Chudakova, Austen R. D. Ganley, Justin M. O'Sullivan, Jo K. Perry
Summary: Growth hormone (GH) activates downstream signalling by binding to its cell-surface receptor, the GH receptor (GHR). However, nuclear localization of GHR has been observed and linked to increased cancer cell proliferation. In this study, the authors investigated the functional implications of GHR nuclear translocation in two cancer cell lines and identified potential interactions with chromatin factors. The findings suggest that GHR nuclear translocation might mediate GH actions by influencing downstream transcriptional programs.
JOURNAL OF CELL COMMUNICATION AND SIGNALING
(2023)
Review
Cell Biology
Yauhen Statsenko, Nik V. Kuznetsov, Daria Morozova, Katsiaryna Liaonchyk, Gillian Lylian Simiyu, Darya Smetanina, Aidar Kashapov, Sarah Meribout, Klaus Neidl-Van Gorkom, Rifat Hamoudi, Fatima Ismail, Suraiya Anjum Ansari, Bright Starling Emerald, Milos Ljubisavljevic
Summary: Although accelerated aging is a commonly recognized theory, it still has many shortcomings and limitations that require an updated concept.
Article
Biotechnology & Applied Microbiology
Anila George, Nithin Sam Ravi, Kirti Prasad, Lokesh Panigrahi, Sanya Koikkara, Vignesh Rajendiran, Nivedhitha Devaraju, Joshua Paul, Aswin Anand Pai, Yukio Nakamura, Ryo Kurita, Poonkuzhali Balasubramanian, Saravanabhavan Thangavel, Srujan Marepally, Shaji R. Velayudhan, Alok Srivastava, Kumarasamypet M. Mohankumar
Summary: This study developed a modular lentiviral-based prime editor system that efficiently modeled and corrected sickle cell anemia mutations in human erythroid cell lines, resulting in functional restoration of adult hemoglobin without unintended nucleotide changes or indel formations. The off-target effects mediated by the prime editor system were minimal, making it a safe therapeutic option.
FRONTIERS IN GENOME EDITING
(2022)
