The role of caspase family in acute brain injury: the potential therapeutic targets in the future

2021 ◽  
Vol 19 ◽  
Author(s):  
Anke Zhang ◽  
Zeyu Zhang ◽  
Yibo Liu ◽  
Cameron Lenahan ◽  
Houshi Xu ◽  
...  
Keyword(s):  
Brain Injury ◽  
Biological Function ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Acute Brain Injury ◽  
Therapeutic Effects ◽  
Caspase Inhibitors ◽  
Caspase Family ◽  
Translational Strategies

: The caspase family is commonly involved in the pathophysiology of acute brain injury (ABI) through complex apoptotic, pyroptotic, and inflammatory pathways. Current translational strategies for caspase modulation in ABI primarily focus on caspase inhibitors. Because there are no caspase-inhibiting drugs approved for clinical use on the market, the development of caspase inhibitors remains an attractive challenge for researchers and clinicians. Therefore, we conducted the present review with the aim of providing a comprehensive introduction of caspases in ABI. In this review, we summarized the available evidence and potential mechanisms regarding the biological function of caspases. We also reviewed the therapeutic effects of caspase inhibitors on ABI and its subsequent complications. However, various important issues remain unclear, prompting further verification of the efficacy and safety regarding clinical application of caspase inhibitors. We believe that our work will be helpful to further understand the critical role of the caspase family, and will provide novel therapeutic potential for ABI treatment.

scholarly journals The Inflammatory Role of Pro-Resolving Mediators in Endometriosis: An Integrative Review

2021 ◽  
Vol 22 (9) ◽  
pp. 4370
Author(s):  
Cássia de Fáveri ◽  
Paula M. Poeta Fermino ◽  
Anna P. Piovezan ◽  
Lia K. Volpato
Keyword(s):  
Intracellular Signaling ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Integrative Review ◽  
Inflammatory Factors ◽  
Resolvin D1 ◽  
Endogenous Factors

The pathogenesis of endometriosis is still controversial, although it is known that the inflammatory immune response plays a critical role in this process. The resolution of inflammation is an active process where the activation of endogenous factors allows the host tissue to maintain homeostasis. The mechanisms by which pro-resolving mediators (PRM) act in endometriosis are still little explored. Thus, this integrative review aims to synthesize the available content regarding the role of PRM in endometriosis. Experimental and in vitro studies with Lipoxin A4 demonstrate a potential inhibitory effect on endometrial lesions’ progression, attenuating pro-inflammatory and angiogenic signals, inhibiting proliferative and invasive action suppressing intracellular signaling induced by cytokines and estradiol, mainly through the FPR2/ALX. Investigations with Resolvin D1 demonstrated the inhibition of endometrial lesions and decreased pro-inflammatory factors. Annexin A1 is expressed in the endometrium and is specifically present in women with endometriosis, although the available studies are still inconsistent. Thus, we believe there is a gap in knowledge regarding the PRM pathways in patients with endometriosis. It is important to note that these substances’ therapeutic potential is evident since the immune and abnormal inflammatory responses play an essential role in endometriosis development and progression.

scholarly journals Regulation of Phosphorylated State of NMDA Receptor by STEP61 Phosphatase after Mild-Traumatic Brain Injury: Role of Oxidative Stress

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1575
Author(s):  
Francisco J. Carvajal ◽  
Waldo Cerpa
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Tyrosine Phosphatase ◽  
Critical Role ◽  
Synaptic Function ◽  
Fyn Kinase ◽  
Impact Device ◽  
Traumatic Lesions ◽  
Early Biomarker

Traumatic Brain Injury (TBI) mediates neuronal death through several events involving many molecular pathways, including the glutamate-mediated excitotoxicity for excessive stimulation of N-methyl-D-aspartate receptors (NMDARs), producing activation of death signaling pathways. However, the contribution of NMDARs (distribution and signaling-associated to the distribution) remains incompletely understood. We propose a critical role of STEP61 (Striatal-Enriched protein tyrosine phosphatase) in TBI; this phosphatase regulates the dephosphorylated state of the GluN2B subunit through two pathways: by direct dephosphorylation of tyrosine-1472 and indirectly via dephosphorylation and inactivation of Fyn kinase. We previously demonstrated oxidative stress’s contribution to NMDAR signaling and distribution using SOD2+/− mice such a model. We performed TBI protocol using a controlled frontal impact device using C57BL/6 mice and SOD2+/− animals. After TBI, we found alterations in cognitive performance, NMDAR-dependent synaptic function (decreased synaptic form of NMDARs and decreased synaptic current NMDAR-dependent), and increased STEP61 activity. These changes are reduced partially with the STEP61-inhibitor TC-2153 treatment in mice subjected to TBI protocol. This study contributes with evidence about the role of STEP61 in the neuropathological progression after TBI and also the alteration in their activity, such as an early biomarker of synaptic damage in traumatic lesions.

scholarly journals Selonsertib Alleviates the Progression of Rat Osteoarthritis: An in vitro and in vivo Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiyuan Yan ◽  
Yingchi Zhang ◽  
Gaohong Sheng ◽  
Bowei Ni ◽  
Yifan Xiao ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Cartilage Damage ◽  
Cartilage Degradation ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Therapeutic Effects ◽  
Exact Role

Osteoarthritis (OA) is a prevalent degenerative joint disease. Its development is highly associated with inflammatory response and apoptosis in chondrocytes. Selonsertib (Ser), the inhibitor of Apoptosis Signal-regulated kinase-1 (ASK1), has exhibited multiple therapeutic effects in several diseases. However, the exact role of Ser in OA remains unclear. Herein, we investigated the anti-arthritic effects as well as the potential mechanism of Ser on rat OA. Our results showed that Ser could markedly prevent the IL-1β-induced inflammatory reaction, cartilage degradation and cell apoptosis in rat chondrocytes. Meanwhile, the ASK1/P38/JNK and NFκB pathways were involved in the protective roles of Ser. Furthermore, intra-articular injection of Ser could significantly alleviate the surgery induced cartilage damage in rat OA model. In conclusion, our work provided insights into the therapeutic potential of Ser in OA, indicating that Ser might serve as a new avenue in OA treatment.

scholarly journals The Role of Cyclodextrins in the Design and Development of Triterpene-Based Therapeutic Agents

2022 ◽  
Vol 23 (2) ◽  
pp. 736
Author(s):  
Alexandra Prodea ◽  
Alexandra Mioc ◽  
Christian Banciu ◽  
Cristina Trandafirescu ◽  
Andreea Milan ◽  
...  
Keyword(s):  
Water Solubility ◽  
Therapeutic Potential ◽  
Underlying Mechanism ◽  
Biological Behavior ◽  
Therapeutic Effects ◽  
Practical Applications ◽  
Starch Derivatives ◽  
Solubility Enhancers ◽  
Low Solubility

Triterpenic compounds stand as a widely investigated class of natural compounds due to their remarkable therapeutic potential. However, their use is currently being hampered by their low solubility and, subsequently, bioavailability. In order to overcome this drawback and increase the therapeutic use of triterpenes, cyclodextrins have been introduced as water solubility enhancers; cyclodextrins are starch derivatives that possess hydrophobic internal cavities that can incorporate lipophilic molecules and exterior surfaces that can be subjected to various derivatizations in order to improve their biological behavior. This review aims to summarize the most recent achievements in terms of triterpene:cyclodextrin inclusion complexes and bioconjugates, emphasizing their practical applications including the development of new isolation and bioproduction protocols, the elucidation of their underlying mechanism of action, the optimization of triterpenes’ therapeutic effects and the development of new topical formulations.

scholarly journals MicroRNA in Pancreatic Cancer: From Biology to Therapeutic Potential

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 752 ◽  
Author(s):  
Rawat ◽  
Kadian ◽  
Gupta ◽  
Kumar ◽  
Chain ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Mirna Biogenesis ◽  
Effective Management ◽  
Future Directions ◽  
Novel Therapeutic Strategies ◽  
Conclusion Section

Pancreatic cancer is one of the most aggressive malignancies, accounting for more than 45,750 deaths annually in the U.S. alone. The aggressive nature and late diagnosis of pancreatic cancer, coupled with the limitations of existing chemotherapy, present the pressing need for the development of novel therapeutic strategies. Recent reports have demonstrated a critical role of microRNAs (miRNAs) in the initiation, progression, and metastasis of cancer. Furthermore, aberrant expressions of miRNAs have often been associated with the cause and consequence of pancreatic cancer, emphasizing the possible use of miRNAs in the effective management of pancreatic cancer patients. In this review, we provide a brief overview of miRNA biogenesis and its role in fundamental cellular process and miRNA studies in pancreatic cancer patients and animal models. Subsequent sections narrate the role of miRNA in, (i) cell cycle and proliferation; (ii) apoptosis; (iii) invasions and metastasis; and (iv) various cellular signaling pathways. We also describe the role of miRNA’s in pancreatic cancer; (i) diagnosis; (ii) prognosis and (iii) therapeutic intervention. Conclusion section describes the gist of review with future directions.

scholarly journals c-Cbl: An Important Regulator and a Target in Angiogenesis and Tumorigenesis

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 498 ◽  
Author(s):  
Chimera L. Lyle ◽  
Mostafa Belghasem ◽  
Vipul C. Chitalia
Keyword(s):  
Therapeutic Potential ◽  
Critical Role ◽  
Modular Function ◽  
Signaling Cascades ◽  
Solid Organ ◽  
Multifunctional Protein ◽  
Ubiquitin E3 Ligase ◽  
Important Regulator ◽  
B Lineage

Casitas B lineage lymphoma (c-Cbl) is a multifunctional protein with a ubiquitin E3 ligase activity capable of degrading diverse sets of proteins. Although previous work had focused mainly on c-Cbl mutations in humans with hematological malignancies, recent emerging evidence suggests a critical role of c-Cbl in angiogenesis and human solid organ tumors. The combination of its unique structure, modular function, and ability to channelize cues from a rich network of signaling cascades, empowers c-Cbl to assume a central role in these disease models. This review consolidates the structural and functional insights based on recent studies that highlight c-Cbl as a target with tantalizing therapeutic potential in various models of angiogenesis and tumorigenesis.

scholarly journals Extracellular vesicles in diagnosis and therapy of kidney diseases

2016 ◽  
Vol 311 (5) ◽  
pp. F844-F851 ◽  
Author(s):  
Wei Zhang ◽  
Xiangjun Zhou ◽  
Hao Zhang ◽  
Qisheng Yao ◽  
Yutao Liu ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Cross Talk ◽  
Cultured Cells ◽  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Cell Communication ◽  
Therapeutic Effects ◽  
Glomerular Diseases ◽  
The Cross

Extracellular vesicles (EV) are endogenously produced, membrane-bound vesicles that contain various molecules. Depending on their size and origins, EVs are classified into apoptotic bodies, microvesicles, and exosomes. A fundamental function of EVs is to mediate intercellular communication. In kidneys, recent research has begun to suggest a role of EVs, especially exosomes, in cell-cell communication by transferring proteins, mRNAs, and microRNAs to recipient cells as nanovectors. EVs may mediate the cross talk between various cell types within kidneys for the maintenance of tissue homeostasis. They may also mediate the cross talk between kidneys and other organs under physiological and pathological conditions. EVs have been implicated in the pathogenesis of both acute kidney injury and chronic kidney diseases, including renal fibrosis, end-stage renal disease, glomerular diseases, and diabetic nephropathy. The release of EVs with specific molecular contents into urine and plasma may be useful biomarkers for kidney disease. In addition, EVs produced by cultured cells may have therapeutic effects for these diseases. However, the role of EVs in kidney diseases is largely unclear, and the mechanism underlying EV production and secretion remains elusive. In this review, we introduce the basics of EVs and then analyze the present information about the involvement, diagnostic value, and therapeutic potential of EVs in major kidney diseases.

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