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Amphiregulin (AREG) serves as a ligand for the epidermal growth factor receptor (EGFR) and is involved in vital biological functions, including inflammatory responses, tissue regeneration, and immune system function. Upon interaction with the EGFR, AREG initiates a series of signaling cascades necessary for several physiological activities, such as metabolism, cell cycle regulation, and cellular proliferation. Recent findings have provided evidence for the substantial role of AREG in maintaining the equilibrium of homeostasis in damaged tissues and preserving epithelial cell structure in the context of viral infections affecting the lungs. The development of resistance to influenza virus infection depends on the presence of type 1 cytokine responses. Following the eradication of the pathogen, the lungs are subsequently colonized by several cell types that are linked with type 2 immune responses. These cells contribute to the process of repairing and resolving the tissue injury and inflammation caused by infections. Following influenza infection, the activation of AREG promotes the regeneration of bronchial epithelial cells, enhancing the tissue's structural integrity and increasing the survival rate of infected mice. In the same manner, mice afflicted with influenza experience rapid mortality due to a subsequent bacterial infection in the pulmonary region when both bacterial and viral infections manifest concurrently inside the same host. The involvement of AREG in bacterial infections has been demonstrated. The gene AREG experiences increased transcriptional activity inside host cells in response to bacterial infections caused by pathogens such as Escherichia coli and Neisseria gonorrhea. In addition, AREG has been extensively studied as a mitogenic stimulus in epithelial cell layers. Consequently, it is regarded as a prospective contender that might potentially contribute to the observed epithelial cell reactions in helminth infection. Consistent with this finding, mice that lack the AREG gene exhibit a delay in the eradication of the intestinal parasite Trichuris muris. The observed delay is associated with a reduction in the proliferation rate of colonic epithelial cells compared to the infected animals in the control group. The aforementioned findings indicate that AREG plays a pivotal role in facilitating the activation of defensive mechanisms inside the epithelial cells of the intestinal tissue. The precise cellular sources of AREG in this specific context have not yet been determined. However, it is evident that the increased proliferation of the epithelial cell layer in infected mice is reliant on CD4+ T cells. The significance of this finding lies in its demonstration of the crucial role played by the interaction between immunological and epithelial cells in regulating the AREG-EGFR pathway. Additional research is necessary to delve into the cellular origins and signaling mechanisms that govern the synthesis of AREG and its tissue-protective properties, independent of infection.
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Infecções Bacterianas , Influenza Humana , Animais , Humanos , Camundongos , Anfirregulina/metabolismo , Receptores ErbB/metabolismo , Estudos ProspectivosRESUMO
Cervical cancer (CC) and other malignant malignancies are acknowledged to be primarily caused by persistent human papillomavirus (HPV) infection. Historically, vaccinations against viruses that produce neutralizing antibodies unique to the virus have been an affordable way to manage viral diseases. CC risk is decreased, but not eliminated, by HPV vaccinations. Since vaccinations have been made available globally, almost 90% of HPV infections have been successfully avoided. On the lesions and diseases that are already present, however, no discernible treatment benefit has been shown. As a result, therapeutic vaccines that elicit immune responses mediated by cells are necessary for the treatment of established infections and cancers. mRNA vaccines possess remarkable potential in combating viral diseases and malignancy as a result of their superior industrial production, safety, and efficacy. Furthermore, considering the expeditiousness of production, the mRNA vaccine exhibits promise as a therapeutic approach targeting HPV. Given that the HPV-encoded early proteins, including oncoproteins E6 and E7, are consistently present in HPV-related cancers and pre-cancerous lesions and have crucial functions in the progression and persistence of HPV-related diseases, they serve as ideal targets for therapeutic HPV vaccines. The action mechanism of HPV and HPV-related cancer mRNA vaccines, their recent advancements in clinical trials, and the potential for their therapeutic applications are highlighted in this study, which also offers a quick summary of the present state of mRNA vaccines. Lastly, we highlight a few difficulties with mRNA HPV vaccination clinical practice and provide our thoughts on further advancements in this quickly changing sector. It is expected that mRNA vaccines will soon be produced quickly for clinical HPV prevention and treatment.
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Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Vacinas de mRNA , Humanos , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/imunologia , Vacinas contra Papillomavirus/administração & dosagem , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/terapia , Feminino , Papillomaviridae/imunologia , Papillomaviridae/genética , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem , Proteínas Oncogênicas Virais/imunologia , Proteínas Oncogênicas Virais/genética , Papillomavirus HumanoRESUMO
Brucella infections typically occur in mucosal membranes, emphasizing the need for mucosal vaccinations. This study evaluated the effectiveness of orally administering Lactococcus lactis (L. lactis) for producing the Brucella abortus multi-epitope OMPs peptide. A multi-epitope plasmid was generated through a reverse vaccinology method, and mice were administered the genetically modified L. lactis orally as a vaccine. The plasmid underwent digestion, synthesizing a 39 kDa-sized protein known as OMPs by the target group. The sera of mice that were administered the pNZ8124-OMPs-L. lactis vaccine exhibited a notable presence of IgG1 antibodies specific to outer membrane proteins (OMPs), heightened levels of interferon (IFN-λ) and tumor necrosis factor alpha (TNF-α), and enhanced transcription rates of interleukin 4 (IL-4) and interleukin 10 (IL-10). The spleen sections from the pNZ8124-OMPs-L. lactis and IRIBA group had less morphological damage associated with inflammation, infiltration of lymphocytes, and lesions to the spleen. The findings present a novel approach to utilizing the food-grade, non-pathogenic L. lactis as a protein cell factory to synthesize innovative immunological candidate OMPs. This approach offers a distinctive way to evaluate experimental medicinal items' practicality, safety, affordability, and long-term sustainability.
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Vacina contra Brucelose , Brucella abortus , Brucelose , Lactococcus lactis , Camundongos Endogâmicos BALB C , Animais , Brucella abortus/imunologia , Brucelose/prevenção & controle , Brucelose/imunologia , Lactococcus lactis/genética , Lactococcus lactis/imunologia , Vacina contra Brucelose/imunologia , Vacina contra Brucelose/administração & dosagem , Vacina contra Brucelose/genética , Camundongos , Feminino , Proteínas da Membrana Bacteriana Externa/imunologia , Proteínas da Membrana Bacteriana Externa/genética , Epitopos/imunologia , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Baço/imunologia , Vetores Genéticos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Citocinas/metabolismoRESUMO
One of the most prevalent types of cancer worldwide today is gastric intestinal (GI) tumors. To guarantee their lives, people with a developed GI require palliative care. This covers the application of targeted medicines in addition to chemotherapy treatments including cisplatin, 5-fluorouracil, oxaliplatin, paclitaxel, and pemetrexed. Because of the evidence of drug resistance emerging in poor patient outcomes and prognoses, determining the exact process of medication resistance is motivated. Besides, it is noteworthy that exosomes and noncoding RNAs, like microRNAs and long non-coding RNAs (lncRNAs), produced from tumor cells are implicated in both GI medication resistance and the carcinogenesis and development of GI disease. Biochemical events related to the cell cycle, differentiation of cells, growth, and pluripotency, in addition to gene transcription, splicing, and epigenetics, are all regulated by noncoding RNAs (ncRNAs). Therefore, it should come as a wonder that several ncRNAs have been connected in recent years to drug susceptibility and resistance as well as tumorigenesis. Additionally, through communicating directly with medications, altering the transcriptome of tumor cells, and affecting the immune system, exosomes may govern treatment resistance. Because of this, exosomal lncRNAs often act as a competitive endogenous RNA (ceRNA) of miRNAs to carry out its role in modifying drug resistance. In light of this, we provide an overview of the roles and processes of ncRNA-enriched exosomes in GI medication resistance.
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The first line of defense against viral infection of the host cell is the cellular lipid membrane, which is also a crucial first site of contact for viruses. Lipids may sometimes be used as viral receptors by viruses. For effective infection, viruses significantly depend on lipid rafts during the majority of the viral life cycle. It has been discovered that different viruses employ different lipid raft modification methods for attachment, internalization, membrane fusion, genome replication, assembly, and release. To preserve cellular homeostasis, cells have potent antioxidant, detoxifying, and cytoprotective capabilities. Nuclear factor erythroid 2-related factor 2 (NRF2), widely expressed in many tissues and cell types, is one crucial component controlling electrophilic and oxidative stress (OS). NRF2 has recently been given novel tasks, including controlling inflammation and antiviral interferon (IFN) responses. The activation of NRF2 has two effects: it may both promote and prevent the development of viral diseases. NRF2 may also alter the host's metabolism and innate immunity during viral infection. However, its primary function in viral infections is to regulate reactive oxygen species (ROS). In several research, the impact of NRF2 on lipid metabolism has been examined. NRF2 is also involved in the control of lipids during viral infection. We evaluated NRF2's function in controlling viral and lipid infections in this research. We also looked at how lipids function in viral infections. Finally, we investigated the role of NRF2 in lipid modulation during viral infections.
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Metabolismo dos Lipídeos , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Viroses , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Humanos , Viroses/metabolismo , Viroses/imunologia , Viroses/virologia , Animais , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Microdomínios da Membrana/metabolismo , Imunidade Inata , Interações Hospedeiro-PatógenoRESUMO
Parkinson's disease (PD) is one of the most prevalent diseases of central nervous system that is caused by degeneration of the substantia nigra's dopamine-producing neurons through apoptosis. Apoptosis is regulated by initiators' and executioners' caspases both in intrinsic and extrinsic pathways, further resulting in neuronal damage. In that context, targeting apoptosis appears as a promising therapeutic approach for treating neurodegenerative diseases. Non-coding RNAs-more especially, microRNAs, or miRNAs-are a promising target for the therapy of neurodegenerative diseases because they are essential for a number of cellular processes, including signaling, apoptosis, cell proliferation, and gene regulation. It is estimated that a substantial portion of coding genes (more than 60%) are regulated by miRNAs. These small regulatory molecules can have wide-reaching consequences on cellular processes like apoptosis, both in terms of intrinsic and extrinsic pathways. Furthermore, it was recommended that a disruption in miRNA expression levels could also result in perturbation of typical apoptosis pathways, which may be a factor in certain diseases like PD. The latest research on miRNAs and their impact on neural cell injury in PD models by regulating the apoptosis pathway is summarized in this review article. Furthermore, the importance of lncRNA/circRNA-miRNA-mRNA network for regulating apoptosis pathways in PD models and treatment is explored. These results can be utilized for developing new strategies in PD treatment.
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Colorectal cancer (CRC) remains a major global health concern, necessitating an in-depth exploration of the intricate molecular mechanisms underlying its progression and potential therapeutic interventions. Transforming Growth Factor-ß (TGF-ß) signaling, a pivotal pathway implicated in CRC plays a dual role as a tumor suppressor in the early stages and a promoter of tumor progression in later stages. Recent research has shed light on the critical involvement of noncoding RNAs (ncRNAs) in modulating the TGF-ß signaling pathway, introducing a new layer of complexity to our understanding of CRC pathogenesis. This comprehensive review synthesizes the current state of knowledge regarding the function and therapeutic potential of various classes of ncRNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), in the context of TGF-ß signaling in CRC. The intricate interplay between these ncRNAs and key components of the TGF-ß pathway is dissected, revealing regulatory networks that contribute to the dynamic balance between tumor suppression and promotion. Emphasis is placed on how dysregulation of specific ncRNAs can disrupt this delicate equilibrium, fostering CRC initiation, progression, and metastasis. Moreover, the review provides a critical appraisal of the emerging therapeutic strategies targeting ncRNAs associated with TGF-ß signaling in CRC. The potential of these ncRNAs as diagnostic and prognostic biomarkers is discussed, highlighting their clinical relevance. Additionally, the challenges and prospects of developing RNA-based therapeutics, such as RNA interference and CRISPR/Cas-based approaches, are explored in the context of modulating TGF-ß signaling for CRC treatment. In conclusion, this review offers a comprehensive overview of the intricate interplay between ncRNAs and the TGF-ß signaling pathway in CRC. By unraveling the functional significance of these regulatory elements, we gain valuable insights into the molecular landscape of CRC, paving the way for the development of novel and targeted therapeutic interventions aimed at modulating the TGF-ß signaling cascade through the manipulation of ncRNAs.
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Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Neoplasias Colorretais/metabolismo , RNA não Traduzido/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Transdução de Sinais/genética , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismoRESUMO
During the last decades, the ever-increasing incidence of diseases has led to high rates of mortality throughout the world. On the other hand, the inability and deficiencies of conventional approaches (such as chemotherapy) in the suppression of diseases remain challenging issues. As a result, there is a fundamental requirement to develop novel, biocompatible, bioavailable, and practical nanomaterials to prevent the incidence and mortality of diseases. Chitosan (CS) derivatives and their blends are outstandingly employed as promising drug delivery systems for disease therapy. These biopolymers are indicated more efficient performance against diseases compared with conventional modalities. The CS blends possess improved physicochemical properties, ease of preparation, high affordability, etc. characteristics compared with other biopolymers and even pure CS which result in efficient thermal, mechanical, biochemical, and biomedical features. Also, these blends can be administrated through different routes without a long-term treatment period. Due to the mentioned properties, numerous formulations of CS blends are developed for pharmaceutical sciences to treat diseases. This review article highlights the progressions in the development of CS-based blends as potential drug delivery systems against diseases.
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Quitosana , Sistemas de Liberação de Medicamentos , Quitosana/química , Humanos , Sistemas de Liberação de Medicamentos/métodos , Portadores de Fármacos/química , AnimaisRESUMO
Rheumatoid arthritis (RA) is a multifaceted autoimmune disorder characterized by chronic inflammation and joint destruction. Recent research has elucidated the intricate interplay between gut microbiota and RA pathogenesis, underscoring the role of microbiota-derived metabolites as pivotal contributors to disease development and progression. The human gut microbiota, comprising a vast array of microorganisms and their metabolic byproducts, plays a crucial role in maintaining immune homeostasis. Dysbiosis of this microbial community has been linked to numerous autoimmune disorders, including RA. Microbiota-derived metabolites, such as short-chain fatty acids (SCFAs), tryptophan derivatives, Trimethylamine-N-oxide (TMAO), bile acids, peptidoglycan, and lipopolysaccharide (LPS), exhibit immunomodulatory properties that can either exacerbate or ameliorate inflammation in RA. Mechanistically, these metabolites influence immune cell differentiation, cytokine production, and gut barrier integrity, collectively shaping the autoimmune milieu. This review highlights recent advances in understanding the intricate crosstalk between microbiota metabolites and RA pathogenesis and also discusses the potential of specific metabolites to trigger or suppress autoimmunity, shedding light on their molecular interactions with immune cells and signaling pathways. Additionally, this review explores the translational aspects of microbiota metabolites as diagnostic and prognostic tools in RA. Furthermore, the challenges and prospects of translating these findings into clinical practice are critically examined.
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Artrite Reumatoide , Biomarcadores , Disbiose , Microbioma Gastrointestinal , Humanos , Artrite Reumatoide/microbiologia , Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Biomarcadores/metabolismo , Disbiose/microbiologia , Animais , Ácidos Graxos Voláteis/metabolismoRESUMO
Despite great advances in diagnostic and treatment options for cancer, like chemotherapy surgery, and radiation therapy it continues to remain a major global health concern. Further research is necessary to find new biomarkers and possible treatment methods for cancer. MicroRNAs (miRNAs), tiny non-coding RNAs found naturally in the body, can influence the activity of several target genes. These genes are often disturbed in diseases like cancer, which perturbs functions like differentiation, cell division, cell cycle, apoptosis and proliferation. MiR-146a is a commonly and widely used miRNA that is often overexpressed in malignant tumors. The expression of miR-146a has been correlated with many pathological and physiological changes in cancer cells, such as the regulation of various cell death paths. It's been established that the control of cell death pathways has a huge influence on cancer progression. To improve our understanding of the interrelationship between miRNAs and cancer cell apoptosis, it's necessary to explore the impact of miRNAs through the alteration in their expression levels. Research has demonstrated that the appearance and spread of cancer can be mitigated by moderating the expression of certain miRNA - a commencement of treatment that presents a hopeful approach in managing cancer. Consequently, it is essential to explore the implications of miR-146a with respect to inducing different forms of tumor cell death, and evaluate its potential to serve as a target for improved chemotherapy outcomes. Through this review, we provide an outline of miR-146a's biogenesis and function, as well as its significant involvement in apoptosis. As well, we investigate the effects of exosomal miR-146a on the promotion of apoptosis in cancer cells and look into how it could possibly help combat chemotherapeutic resistance.
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MicroRNAs , Neoplasias , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Apoptose/genética , Neoplasias/genética , BiomarcadoresRESUMO
Aqueous two-phase systems (ATPSs) have long been recognized as versatile and efficient tools for the extraction of biomolecules, including amino acids. Recent advancements in the field have introduced a novel approach by utilizing deep eutectic solvents (DES) to form ATPs. This study aimed to determine the phase diagrams for an ATPS made of polyethylene glycol dimethyl ether 250 and two types of NADESs, namely choline chloride as a hydrogen bond acceptor (HBA), and either sucrose or fructose as a hydrogen bond donor (HBD) with a molar ratio of 1 : 2. The measured tie-line results revealed that the hydrogen bonds of NADES may not be entirely disrupted in aqueous solutions, and thus, these ATPSs act as ternary-like systems. Additionally, the binodal data were fitted using two semi-empirical equations, namely Merchuk and Zafarani-Moattar et al. equations. Furthermore, the ATPSs mentioned above were applied to extract three amino acids, namely l-arginine, l-phenylalanine, and l-tyrosine, and demonstrated good extraction levels. Finally, the Diamond-Hsu equation and its modified version were utilized to correlate the experimental partition coefficients of the amino acids. These advancements pave the way for the development of improved extraction methodologies and the exploration of new applications in the field of biotechnology, pharmaceuticals, and beyond.
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MiRNAs have emerged as crucial modulators of the expression of their target genes, attracting significant attention due to their engagement in various cellular processes, like cancer onset and development. Amidst the extensive repertoire of miRNAs implicated in cancer, miR-136-5p has emerged as an emerging miRNA with diverse roles. Dysregulation of miR-136-5p has been proved in human cancers. Accumulating evidence suggests that miR-136-5p mainly functions as a tumor suppressor. These data proposed that miR-136-5p is engaged in the regulation of various cellular processes, like cell proliferation, migration, invasion, EMT, and apoptosis. In addition, miR-136-5p has demonstrated substantial potential as a prognostic and diagnostic marker in human cancers as well as an effective mediator in cancer chemotherapy. Furthermore, miR-136-5p was shown to be correlated with clinicopathological features of affected patients, proposing that it could be used for cancer staging and patient survival. Therefore, a comprehensive comprehension of the precise molecular basis governing miR-136-5p dysregulation in different cancers is vital for unraveling its therapeutic importance. Here, we have discussed the molecular basis of miR-136-5p as a potential tumor suppressor as well as its importance in cancer diagnosis, prognosis, and chemotherapy. Finally, we have discussed the challenge of using miRNAs as a therapeutic target as well as the prospect regarding the importance of miR-136-5p in human cancers.
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Among the leading causes of death globally has been cancer. Nearly 90% of all cancer-related fatalities are attributed to metastasis, which is the growing of additional malignant growths out of the original cancer origin. Therefore, a significant clinical need for a deeper comprehension of metastasis exists. Beginning investigations are being made on the function of microRNAs (miRNAs) in the metastatic process. Tiny non-coding RNAs called miRNAs have a crucial part in controlling the spread of cancer. Some miRNAs regulate migration, invasion, colonization, cancer stem cells' properties, the epithelial-mesenchymal transition (EMT), and the microenvironment, among other processes, to either promote or prevent metastasis. One of the most well-conserved and versatile miRNAs, miR-155 is primarily distinguished by overexpression in a variety of illnesses, including malignant tumors. It has been discovered that altered miR-155 expression is connected to a number of physiological and pathological processes, including metastasis. As a result, miR-155-mediated signaling pathways were identified as possible cancer molecular therapy targets. The current research on miR-155, which is important in controlling cancer cells' invasion, and metastasis as well as migration, will be summarized in the current work. The crucial significance of the lncRNA/circRNA-miR-155-mRNA network as a crucial regulator of carcinogenesis and a player in the regulation of signaling pathways or related genes implicated in cancer metastasis will be covered in the final section. These might provide light on the creation of fresh treatment plans for controlling cancer metastasis.
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The treatment of diseases, such as cancer, is one of the most significant issues correlated with human beings health. Hydrogels (HGs) prepared from biocompatible and biodegradable materials, especially biopolymers, have been effectively employed for the sort of pharmaceutical and biomedical applications, including drug delivery systems, biosensors, and tissue engineering. Chitosan (CS), one of the most abundant bio-polysaccharide derived from chitin, is an efficient biomaterial in the prognosis, diagnosis, and treatment of diseases. CS-based HGs possess some potential advantages, like high values of bioactive encapsulation, efficient drug delivery to a target site, sustained drug release, good biocompatibility and biodegradability, high serum stability, non-immunogenicity, etc., which made them practical and useful for pharmaceutical and biomedical applications. In this review, we summarize recent achievements and advances associated with CS-based HGs for drug delivery, regenerative medicine, disease detection and therapy.
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Quitosana , Humanos , Quitosana/uso terapêutico , Hidrogéis , Materiais Biocompatíveis/uso terapêutico , Medicina Regenerativa , Engenharia Tecidual , Sistemas de Liberação de MedicamentosRESUMO
In the current twenty years, industrial applications of ionic liquids (ILs) have been of paramount attention due to their indisputable positive characteristics like negligible volatility and chemical/thermal stability. These brilliant advantages open new horizons towards environmentally friendly application of ILs in several industrial activities like membrane-based CO2 separation, electrolyte, bioprocessing, targeted drug delivery and solar panels. The principal intention of this article is to prepare a comprehensive review on the potential efficiency of IL-based absorbents to separate CO2 acidic contaminant from industrial gaseous streams compared to alkanolamine absorbents as the benchmark. For this purpose, a techno-economic evaluation is presented to compare the cost-effectiveness of ILs compared to alkanolamine absorbents. Finally, major environmental impacts of the ILs applications in industries are discussed and future perspectives towards solving the operational challenges are presented in detail.