Editorial Material
Immunology
Travis E. Faust, Dorothy P. Schafer
Summary: The study reveals that the pro-inflammatory cytokine IL-6 specifically increases synaptogenesis in immature excitatory neurons through downstream neuronal STAT3-dependent transcriptional regulation of Rgs4.
Article
Biochemistry & Molecular Biology
Elizabeta Georgieva, Stefan L. Leber, Cora Wex, Christoph Garbers
Summary: The study reveals that perturbation of the actin cytoskeleton is not sufficient to induce NF-kappa B activation and IL-6 secretion, but it reduces IL-6-induced activation of STAT3 in Hep3B cells. Additionally, IL-6 receptor proteolysis by ADAM10 is not dependent on the integrity of the actin cytoskeleton.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Rossella Salemi, Giuseppe Gattuso, Barbara Tomasello, Alessandro Lavoro, Agostino Gaudio, Massimo Libra, Salvatore Santo Signorelli, Saverio Candido
Summary: This study investigated the involvement of IL-6 trans-signaling in DVT and found a strong correlation between the Asp358Ala variant and sIL6-R levels. The high frequency of the Asp358Ala mutation and elevated IL-6 levels in DVT patients may explain the association between IL-6 overactivation and DVT outcome. These findings provide a proof of concept for targeting IL-6 trans-signaling as a new strategy for DVT adjuvant therapy.
Review
Cell Biology
Laura Forcina, Claudio Franceschi, Antonio Musaro
Summary: IL-6 is a pleiotropic cytokine with dual and sometimes opposite actions, depending on its intensity and duration of release. It can have anti-inflammatory, antioxidant, and pro-myogenic effects at low levels but can induce pro-inflammatory, pro-oxidant, and pro-fibrotic responses at increased systemic concentrations. The role of IL-6 in aging-related diseases and its involvement in the switch from physiological aging to age-related diseases, such as chronic inflammation and oxidative stress, is not fully understood.
AGEING RESEARCH REVIEWS
(2022)
Article
Medical Laboratory Technology
Kun Chen, Xiangyu Li, Di Wang, Yanchun Ma, Bobin Chen, Qingping Wang, Jingjing Ma, Ming Guan
Summary: Aqueous humor can serve as a potential sample type for the diagnosis of intraocular lymphoma when detecting IL-6 and IL-10, showing higher diagnostic value and lower operating risk compared to vitreous specimens.
CLINICA CHIMICA ACTA
(2021)
Review
Biochemistry & Molecular Biology
Yanxia Li, Jing Zhao, Yuan Yin, Ke Li, Chenchen Zhang, Yajuan Zheng
Summary: Fibrosis is a detrimental outcome of most chronic inflammatory disorders, and IL-6 plays a significant role in these diseases.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Immunology
Joanna Kaminska, Violetta Dymicka-Piekarska, Robert Chrzanowski, Karol Sawicki, Anna J. Milewska, Justyna Zinczuk, Marzena Tylicka, Marek Jadeszko, Zenon Mariak, Ewa M. Kratz, Joanna Matowicka-Karna, Johannes Kornhuber, Piotr Lewczuk, Olga M. Koper-Lenkiewicz
Summary: Research has shown that in patients with un-ruptured brain aneurysms, both the IL-6 Quotient and CSF IL-6 concentration are significantly higher, especially in those with multiple aneurysms. This indicates that IL-6 may serve as a biomarker for UIA formation.
JOURNAL OF INFLAMMATION RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Birte Weber, Ramona Sturm, Dirk Henrich, Ludmila Lupu, Katrin Rottluff, Ingo Marzi, Liudmila Leppik
Summary: Trauma is a major cause of death and disability, and accurate diagnosis is crucial for polytraumatized patients to prevent complications. This study suggests that cytokines in exosomes have a longer half-life and can be used as diagnostic and prognostic markers in these patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Isak W. Tengesdal, Alberto Dinarello, Nicholas E. Powers, Matthew A. Burchill, Leo A. B. Joosten, Carlo Marchetti, Charles A. Dinarello
Summary: This study reveals that in melanoma, IL-1 beta-induced inflammation is linked to the expansion of immunosuppressive cells, and inhibition of NLRP3 can reduce STAT3 signaling, preventing the expression of immunosuppressive genes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Silvia Selene Moreno-Guerrero, Arturo Ramirez-Pacheco, Luz Maria Rocha-Ramirez, Gabriela Hernandez-Pliego, Pilar Eguia-Aguilar, Maria Argelia Escobar-Sanchez, Alfonso Reyes-Lopez, Luis Enrique Juarez-Villegas, Juan Jose Luis Sienra-Monge
Summary: Neuroblastoma (NB) is a heterogeneous disease with varying characteristics, and genetic variants of cytokines such as IL-6 and IL-8 may influence tumor progression and metastasis. Elevated levels of IL-6 and IL-8 could potentially serve as biomarkers for predicting poor outcomes in NB patients. The study suggests that genetic polymorphisms and serum levels of IL-6 and IL-8 play a significant role in the prognosis of NB patients, particularly in Mexican children.
Article
Medicine, General & Internal
Xudong Su, Yuelong Chen, Qian Zhan, Bo Zhu, Li Chen, Chen Zhao, Jianye Yang, Li Wei, Zhenghao Xu, Keyu Wei, Wei Huang, Leilei Qin, Ning Hu
Summary: Analyzing the IL-6/IL-4 ratio in the joint fluid can improve the diagnostic accuracy for prosthetic joint infection (PJI), with high sensitivity and specificity.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Microbiology
Xia Zhu, Yongtao Liu, Ning Xu, Xiaohui Ai, Yibin Yang
Summary: In this study, homologous compounds of IL-10 and IL-6 were identified in channel catfish, and their immune responses were analyzed. The expression of IL-10 and IL-6 genes was observed in multiple tissues, with IL-10 highly expressed in the liver and IL-6 highly expressed in the spleen, heart, and gonad. The results suggest that IL-10 and IL-6 are involved in the immune response against pathogens.
Article
Endocrinology & Metabolism
Danny Luan, Benyamin Dadpey, Jessica Zaid, Pania E. Bridge-Comer, Julia H. DeLuca, Wenmin Xia, Joshua Castle, Shannon M. Reilly
Summary: The bidirectional interaction between adipocytes and adipose tissue immune cells is crucial for regulating adipose function, inflammation, and insulin responsiveness. Obesity reduces cAMP-driven IL-6 secretion from adipocytes, but restoring their catecholamine sensitivity can stimulate IL-6 secretion and activate macrophages to promote an anti-inflammatory gene expression pattern.
Article
Medicine, Research & Experimental
Yang Mei, Kehan Ren, Yijie Liu, Annabel Ma, Zongjun Xia, Xu Han, Ermin Li, Hamza Tariq, Haiyan Bao, Xinshu Xie, Cheng Zou, Dingxiao Zhang, Zhaofeng Li, Lili Dong, Amit Verma, Xinyan Lu, Yasmin Abaza, Jessica K. Altman, Madina Sukhanova, Jing Yang, Peng Ji
Summary: This study reveals that age-related MDS can transform into AML, and the cytokine IL-6 plays a significant role in this transformation. By studying a double knockout mouse model and high-risk MDS patients, blocking IL-6 signaling was found to significantly ameliorate AML progression, indicating the clinical significance of targeting IL-6 signaling in treating high-risk MDS.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Review
Biochemistry & Molecular Biology
Jurgen Scheller, Julia Ettich, Christoph Wittich, Silke Pudewell, Doreen M. M. Floss, Puyan Rafii
Summary: IL-6-type cytokines play important roles in immunomodulation and homeostasis. Synthetic biology approaches including mutations, fusion proteins, and inter-cytokine swapping have resulted in IL-6-type cytokines with altered properties. These synthetic cytokines show potential for clinical applications such as aiding type 2 diabetes and brain injuries.
Article
Biochemistry & Molecular Biology
Matthew K. Boag, Angus Roberts, Vladimir N. Uversky, Linlin Ma, Des R. Richardson, Dean L. Pountney
Summary: A major hallmark of Parkinson's disease is the destruction of dopaminergic neurons in the substantia nigra pars compacta. This destruction is preceded by the formation of Lewy bodies, composed of alpha-synuclein aggregates. The accumulation of alpha-synuclein, iron, and mitochondrial dysfunction affects the nigral neurons. The mechanisms underlying iron accumulation are not well understood. This review explores the relationship between iron regulation and alpha-synuclein and discusses the potential therapeutic targets in the context of Parkinson's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Amir Ajoolabady, Yaguang Bi, David J. McClements, Gregory Y. H. Lip, Des R. Richardson, Russel J. Reiter, Daniel J. Klionsky, Jun Ren
Summary: Atherosclerosis is a chronic proinflammatory anomaly that can lead to various cardiovascular diseases. Pharmacotherapies and adjuvants such as melatonin have shown promise in alleviating inflammation and improving the condition of the disease.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
O. Yu. Selyutina, P. A. Kononova, V. E. Koshman, E. A. Shelepova, M. Gholam Azad, R. Afroz, M. Dharmasivam, Paul V. Bernhardt, N. E. Polyakov, D. R. Richardson
Summary: Ascorbate-driven redox cycling enhances the anti-proliferative activity of Dp44mT and Emodin.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2022)
Article
Chemistry, Medicinal
D. R. Richardson, M. Gholam Azad, R. Afroz, V Richardson, M. Dharmasivam
Summary: This article discusses the development of compounds that target the bidirectional oncogenic signaling between pancreatic cancer cells and pancreatic stellate cells. It also explores the discovery of additional pathways involved in this signaling and highlights the therapeutic opportunity presented by suppressing bidirectional signaling between cell types.
FUTURE MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
William Gang Miao, Thanh Nguyen, Jamila Iqbal, Gregory K. Pierens, Linlin Ma, Des R. Richardson, Stephen A. Wood, George D. Mellick, Ronald J. Quinn, Yunjiang Feng
Summary: This study evaluated the effects of natural compounds from Ligusticum chuanxiong on Parkinson's Disease (PD) cells, and found that 34 compounds strongly affected the staining of multiple cellular organelles, which are closely related to the pathogenesis of PD. The results helped rationalize the traditional use of Ligusticum chuanxiong in PD treatment, and these compounds can serve as chemical probes to study the molecular pathways of PD.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Medicine, Research & Experimental
Tereza Brogyanyi, Robert Kaplanek, Zdenek Kejik, Bozena Hosnedlova, Veronika Antonyova, Nikita Abramenko, Katerina Vesela, Pavel Martasek, Martin Vokurka, Des R. Richardson, Milan Jakubek
Summary: This study tested novel iron chelators for their cytotoxicity against pancreatic cancer cells, showing high toxicity and selectivity. The mechanism of action of the chelators may be associated with mitophagy induction.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Tiffany M. Russell, Des R. Richardson
Summary: GSTs are versatile proteins that play important roles in detoxification and cellular nitric oxide metabolism. They have the ability to convert organic nitrates into nitric oxide, thereby regulating vasodilation. GSTs are also considered suitable targets for pharmaceutical development, particularly in the field of anti-cancer drugs.
Article
Chemistry, Medicinal
Mahendiran Dharmasivam, Busra Kaya, Tharushi Wijesinghe, Mahan Gholam Azad, Miguel A. Gonzalvez, Mohammad Hussaini, Jason Chekmarev, Paul Bernhardt, Des R. Richardson
Summary: A novel and selective antitumor agent, 3-thiosemicarbazone (PPP44mT), and its analogues with distinctive properties were synthesized and characterized. The inclusion of a styrene moiety prevented the oxidation of oxy-myoglobin or oxy-hemoglobin, which is different from other potent thiosemicarbazones such as DpC or Dp44mT. PPP44mT and its Cu(II) complexes exhibited immediate cytotoxicity against SK-N-MC tumor cells, while [Zn(PPP44mT)2] showed delayed antiproliferative efficacy and superior inhibition of cyclin D1 expression compared to DpC or Dp44mT.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Tiffany M. Russell, Des R. Richardson
Summary: Glutathione-S-transferases (GSTs) are isozymes that play important roles in both detoxification and redox stress suppression by conjugating glutathione (GSH) to xenobiotics and interacting with cytotoxic nitric oxide (NO). The interactions between NO and GSTs involve binding and storage of NO as dinitrosyl-dithiol iron complexes (DNICs). GSTP1 can inhibit inducible nitric oxide synthase (iNOS) and suppress c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NF-kappa B) pathways, leading to decreased apoptosis and modulating NO-mediated ROS generation. These studies highlight the innovative role of GSTs in NO metabolism and their interactions with multiple effector proteins.
Review
Biochemistry & Molecular Biology
Xiao Zhao, Des R. Richardson
Summary: Breast cancer is the leading cause of cancer death in women, and there are different clinical subtypes based on hormone receptor and HER2 status. Targeted therapies exist for ER-α positive and HER2 overexpressing tumors, but resistance and metastasis remain problems, while TNBC lacks suitable targets.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)
Review
Pharmacology & Pharmacy
Zhao Deng, Des R. Richardson
Summary: This review explores the interactions between Myc proteins and other molecules, focusing on the relationship between N-Myc and NDRG1 and potential therapeutic interventions. These findings provide important insights into the understanding and treatment of neuroblastoma.
PHARMACOLOGICAL REVIEWS
(2023)
Review
Pharmacology & Pharmacy
Xiaoyi Chen, Yunjiang Feng, Ronald J. Quinn, Dean L. Pountney, Des R. Richardson, George D. Mellick, Linlin Ma
Summary: Parkinson's disease is a neurode-generative disorder caused by the loss of dopaminergic neurons in the midbrain, leading to motor symptoms. Understanding the biological targets and pathways involved in the disease is crucial for developing effective treatments. Ion channels, particularly potassium channels, play important roles in neuronal function and neuroinflammation, making them potential therapeutic targets. This review discusses the role of specific potassium channel subfamilies in Parkinson's disease pathogenesis and their potential as targets for neuroprotective drugs.
PHARMACOLOGICAL REVIEWS
(2023)
Article
Pharmacology & Pharmacy
Faten Shehadeh-Tout, Heloisa H. Milioli, Suraya Roslan, Patric J. Jansson, Mahendiran Dharmasivam, Dinny Graham, Robin Anderson, Tharushi Wijesinghe, Mahan Gholam Azad, Des R. Richardson, Zaklina Kovacevic
Summary: This study investigates a new class of anti-cancer agents for the treatment of ER-positive breast cancer. These agents inhibit multiple growth factor receptors and down-stream signaling, leading to decreased expression of hormone receptors and key resistance pathways. In vivo experiments demonstrate that these agents effectively inhibit ER-positive breast cancer growth. This represents an innovative non-hormonal, multi-modal therapeutic approach.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Mahendiran Dharmasivam, Busra Kaya, Tharushi P. Wijesinghe, Vera Richardson, Jeffrey R. Harmer, Miguel A. Gonzalvez, William Lewis, Mahan Gholam Azad, Paul V. Bernhardt, Des R. Richardson
Summary: This study investigates the synthesis and characterization of metal complexes of the Dp4e4mT analog, revealing their distinct effects and off-target activities in cancer treatment, with a key role played by differential transmetallation.
Article
Chemistry, Medicinal
D. R. Richardson, M. Gholam Azad, R. Afroz, V Richardson, M. Dharmasivam
Summary: This article discusses the development of a therapeutic opportunity to overcome the development of dense stroma in pancreatic cancer by suppressing bidirectional signaling between cells.
FUTURE MEDICINAL CHEMISTRY
(2022)
