ncRNAs and Their Impact on Dopaminergic Neurons: Autophagy Pathways in Parkinson's Disease.

Parkinson's Disease (PD) is a complex neurological illness that causes severe motor and non-motor symptoms due to a gradual loss of dopaminergic neurons in the substantia nigra. The aetiology of PD is influenced by a variety of genetic, environmental, and cellular variables. One important aspect of this pathophysiology is autophagy, a crucial cellular homeostasis process that breaks down and recycles cytoplasmic components. Recent advances in genomic technologies have unravelled a significant impact of ncRNAs on the regulation of autophagy pathways, thereby implicating their roles in PD onset and progression. They are members of a family of RNAs that include miRNAs, circRNA and lncRNAs that have been shown to play novel pleiotropic functions in the pathogenesis of PD by modulating the expression of genes linked to autophagic activities and dopaminergic neuron survival. This review aims to integrate the current genetic paradigms with the therapeutic prospect of autophagy-associated ncRNAs in PD. By synthesizing the findings of recent genetic studies, we underscore the importance of ncRNAs in the regulation of autophagy, how they are dysregulated in PD, and how they represent novel dimensions for therapeutic intervention. The therapeutic promise of targeting ncRNAs in PD is discussed, including the barriers that need to be overcome and future directions that must be embraced to funnel these ncRNA molecules for the treatment and management of PD.

Targeting notch-related lncRNAs in cancer: Insights into molecular regulation and therapeutic potential.

Cancer is a group of diseases marked by unchecked cell proliferation and the ability for the disease to metastasize to different body areas. Enhancements in treatment and early detection are crucial for improved outcomes. LncRNAs are RNA molecules that encode proteins and have a length of more than 200 nucleotides. LncRNAs are crucial for chromatin architecture, gene regulation, and other cellular activities that impact both normal growth & pathological processes, even though they are unable to code for proteins. LncRNAs have emerged as significant regulators in the study of cancer biology, with a focus on their intricate function in the Notch signaling pathway. The imbalance of this pathway is often linked to a variety of malignancies. Notch signaling is essential for cellular functions like proliferation, differentiation, and death. The cellular response is shaped by these lncRNAs through their modulation of essential Notch pathway constituents such as receptors, ligands, and downstream effectors around it. Furthermore, a variety of cancer types exhibit irregular expression of Notch-related lncRNAs, underscoring their potential use as therapeutic targets and diagnostic markers. Gaining an understanding of the molecular processes behind the interaction between the Notch pathway and lncRNAs will help you better understand the intricate regulatory networks that control the development of cancer. This can open up new possibilities for individualized treatment plans and focused therapeutic interventions. The intricate relationships between lncRNAs & the Notch pathway in cancer are examined in this review.

Exploring ncRNA-mediated regulation of EGFR signalling in glioblastoma: From mechanisms to therapeutics.

Glioblastoma (GBM) is the most prevalent and deadly primary brain tumor type, with a discouragingly low survival rate and few effective treatments. An important function of the EGFR signalling pathway in the development of GBM is to affect tumor proliferation, persistence, and treatment resistance. Advances in molecular biology in the last several years have shown how important ncRNAs are for controlling a wide range of biological activities, including cancer progression and development. NcRNAs have become important post-transcriptional regulators of gene expression, and they may affect the EGFR pathway by either directly targeting EGFR or by modifying important transcription factors and downstream signalling molecules. The EGFR pathway is aberrantly activated in response to the dysregulation of certain ncRNAs, which has been linked to GBM carcinogenesis, treatment resistance, and unfavourable patient outcomes. We review the literature on miRNAs, circRNAs and lncRNAs that are implicated in the regulation of EGFR signalling in GBM, discussing their mechanisms of action, interactions with the signalling pathway, and implications for GBM therapy. Furthermore, we explore the potential of ncRNA-based strategies to overcome resistance to EGFR-targeted therapies, including the use of ncRNA mimics or inhibitors to modulate the activity of key regulators within the pathway.

The impact of formaldehyde exposure on lung inflammatory disorders: Insights into asthma, bronchitis, and pulmonary fibrosis.

Lung inflammatory disorders are a major global health burden, impacting millions of people and raising rates of morbidity and death across many demographic groups. An industrial chemical and common environmental contaminant, formaldehyde (FA) presents serious health concerns to the respiratory system, including the onset and aggravation of lung inflammatory disorders. Epidemiological studies have shown significant associations between FA exposure levels and the incidence and severity of several respiratory diseases. FA causes inflammation in the respiratory tract via immunological activation, oxidative stress, and airway remodelling, aggravating pre-existing pulmonary inflammation and compromising lung function. Additionally, FA functions as a respiratory sensitizer, causing allergic responses and hypersensitivity pneumonitis in sensitive people. Understanding the complicated processes behind formaldehyde-induced lung inflammation is critical for directing targeted strategies aimed at minimizing environmental exposures and alleviating the burden of formaldehyde-related lung illnesses on global respiratory health. This abstract explores the intricate relationship between FA exposure and lung inflammatory diseases, including asthma, bronchitis, allergic inflammation, lung injury and pulmonary fibrosis.

Pollutants to pathogens: The role of heavy metals in modulating TGF-ß signaling and lung cancer risk.

Lung cancer is a malignant tumor that develops in the lungs due to the uncontrolled growth of aberrant cells. Heavy metals, such as arsenic, cadmium, mercury, and lead, are metallic elements characterized by their high atomic weights and densities. Anthropogenic activities, such as industrial operations and pollution, have the potential to discharge heavy metals into the environment, hence presenting hazards to ecosystems and human well-being. The TGF-ß signalling pathways have a crucial function in controlling several cellular processes, with the ability to both prevent and promote tumor growth. TGF-ß regulates cellular responses by interacting in both canonical and non-canonical signalling pathways. Research employing both in vitro and in vivo models has shown that heavy metals may trigger TGF-ß signalling via complex molecular pathways. Experiments conducted in a controlled laboratory environment show that heavy metals like cadmium and arsenic may directly bind to TGF-ß receptors, leading to alterations in their structure that enable the receptor to be phosphorylated. Activation of this route sets in motion subsequent signalling cascades, most notably the canonical Smad pathway. The development of lung cancer has been linked to heavy metals, which are ubiquitous environmental pollutants. To grasp the underlying processes, it is necessary to comprehend their molecular effect on TGF-ß pathways. With a particular emphasis on its consequences for lung cancer, this abstract delves into the complex connection between exposure to heavy metals and the stimulation of TGF-ß signalling.

CircRNAs: Pivotal modulators of TGF-ß signalling in cancer pathogenesis.

The intricate molecular landscape of cancer pathogenesis continues to captivate researchers worldwide, with Circular RNAs (circRNAs) emerging as pivotal players in the dynamic regulation of biological functions. The study investigates the elusive link between circRNAs and the Transforming Growth Factor-ß (TGF-ß) signalling pathway, exploring their collective influence on cancer progression and metastasis. Our comprehensive investigation begins by profiling circRNA expression patterns in diverse cancer types, revealing a repertoire of circRNAs intricately linked to the TGF-ß pathway. Through integrated bioinformatics analyses and functional experiments, we elucidate the specific circRNA-mRNA interactions that modulate TGF-ß signalling, unveiling the regulatory controls governing this crucial pathway. Furthermore, we provide compelling evidence of the impact of circRNA-mediated TGF-ß modulation on key cellular processes, including epithelial-mesenchymal transition (EMT), migration, and cell proliferation. In addition to their mechanistic roles, circRNAs have shown promise as diagnostic and prognostic biomarkers, as well as potential molecular targets for cancer therapy. Their ability to modulate critical pathways, such as the TGF-ß signalling axis, underscores their significance in cancer biology and clinical applications. The intricate interplay between circRNAs and TGF-ß is dissected, uncovering novel regulatory circuits that contribute to the complexity of cancer biology. This review unravels a previously unexplored dimension of carcinogenesis, emphasizing the crucial role of circRNAs in shaping the TGF-ß signalling landscape.

MALAT1: A key regulator in lung cancer pathogenesis and therapeutic targeting.

Lung cancer remains a formidable global health burden, necessitating a comprehensive understanding of the underlying molecular mechanisms driving its progression. Recently, lncRNAs have become necessary controllers of various biological functions, including cancer development. MALAT1 has garnered significant attention due to its multifaceted role in lung cancer progression. Lung cancer, among other malignancies, upregulates MALAT1. Its overexpression has been associated with aggressive tumor behavior and poor patient prognosis. MALAT1 promotes cellular proliferation, epithelial-mesenchymal transition (EMT), and angiogenesis in lung cancer, collectively facilitating tumor growth and metastasis. Additionally, MALAT1 enhances cancer cell invasion by interacting with numerous signaling pathways. Furthermore, MALAT1 has been implicated in mediating drug resistance in lung cancer, contributing to the limited efficacy of conventional therapies. Recent advancements in molecular biology and high-throughput sequencing technologies have offered fresh perspectives into the regulatory networks of MALAT1 in lung cancer. It exerts its oncogenic effects by acting as a ceRNA to sponge microRNAs, thereby relieving their inhibitory effects on target genes. Moreover, MALAT1 also influences chromatin remodeling and post-translational modifications to modulate gene expression, further expanding its regulatory capabilities. This review sheds light on the multifaceted roles of MALAT1 in lung cancer progression, underscoring its potential as an innovative therapeutic target and diagnostic biomarker. Targeting MALAT1 alone or combined with existing therapies holds promise to mitigate lung cancer progression and improve patient outcomes.

From LncRNA to metastasis: The MALAT1-EMT axis in cancer progression.

Cancer is a complex disease that causes abnormal genetic changes and unchecked cellular growth. It also causes a disruption in the normal regulatory processes that leads to the creation of malignant tissue. The complex interplay of genetic, environmental, and epigenetic variables influences its etiology. Long non-coding RNAs (LncRNAs) have emerged as pivotal contributors within the intricate landscape of cancer biology, orchestrating an array of multifaceted cellular processes that substantiate the processes of carcinogenesis and metastasis. Metastasis is a crucial driver of cancer mortality. Among these, MALAT1 (Metastasis-Associated Lung Adenocarcinoma Transcript 1) has drawn a lot of interest for its function in encouraging metastasis via controlling the Epithelial-Mesenchymal Transition (EMT) procedure. MALAT1 exerts a pivotal influence on the process of EMT, thereby promoting metastasis to distant organs. The mechanistic underpinning of this phenomenon involves the orchestration of an intricate regulatory network encompassing transcription factors, signalling cascades, and genes intricately associated with the EMT process by MALAT1. Its crucial function in transforming tumor cells into an aggressive phenotype is highlighted by its capacity to influence the expression of essential EMT effectors such as N-cadherin, E-cadherin, and Snail. An understanding of the MALAT1-EMT axis provides potential therapeutic approaches for cancer intervention. Targeting MALAT1 or its downstream EMT effectors may reduce the spread of metastatic disease and improve the effectiveness of already available therapies. Understanding the MALAT1-EMT axis holds significant clinical implications. Therefore, directing attention towards MALAT1 or its downstream mediators could present innovative therapeutic strategies for mitigating metastasis and improving patient prognosis. This study highlights the importance of MALAT1 in cancer biology and its potential for cutting back on metastatic disease with novel treatment strategies.

Unwinding circular RNA's role in inflammatory pulmonary diseases.

Circular RNAs (circRNAs) have emerged as pivotal regulators of gene expression and cellular processes in various physiological and pathological conditions. In recent years, there has been a growing interest in investigating the role of circRNAs in inflammatory lung diseases, owing to their potential to modulate inflammation-associated pathways and contribute to disease pathogenesis. Inflammatory lung diseases, like asthma, chronic obstructive pulmonary disease (COPD), and COVID-19, pose significant global health challenges. The dysregulation of inflammatory responses demonstrates a pivotal function in advancing these diseases. CircRNAs have been identified as important players in regulating inflammation by functioning as miRNA sponges, engaging with RNA-binding proteins, and participating in intricate ceRNA networks. These interactions enable circRNAs to regulate the manifestation of key inflammatory genes and signaling pathways. Furthermore, emerging evidence suggests that specific circRNAs are differentially expressed in response to inflammatory stimuli and exhibit distinct patterns in various lung diseases. Their involvement in immune cell activation, cytokine production, and tissue remodeling processes underscores their possible capabilities as therapeutic targets and diagnostic biomarkers. Harnessing the knowledge of circRNA-mediated regulation in inflammatory lung diseases could lead to the development of innovative strategies for disease management and intervention. This review summarizes the current understanding of the role of circRNAs in inflammatory lung diseases, focusing on their regulatory mechanisms and functional implications.

A review of Glycogen Synthase Kinase-3 (GSK3) inhibitors for cancers therapies.

The intricate molecular pathways governing cancer development and progression have spurred intensive investigations into novel therapeutic targets. Glycogen Synthase Kinase-3 (GSK3), a complex serine/threonine kinase, has emerged as a key player with intricate roles in various cellular processes, including cell proliferation, differentiation, apoptosis, and metabolism. Harnessing GSK3 inhibitors as potential candidates for cancer therapy has garnered significant interest due to their ability to modulate key signalling pathways that drive oncogenesis. The review encompasses a thorough examination of the molecular mechanisms underlying GSK3's involvement in cancer progression, shedding light on its interaction with critical pathways such as Wnt/ß-catenin, PI3K/AKT, and NF-κB. Through these interactions, GSK3 exerts influence over tumour growth, invasion, angiogenesis, and metastasis, rendering it an attractive target for therapeutic intervention. The discussion includes preclinical and clinical studies, showcasing the inhibitors efficacy across a spectrum of cancer types, including pancreatic, ovarian, lung, and other malignancies. Insights from recent studies highlight the potential synergistic effects of combining GSK3 inhibitors with conventional chemotherapeutic agents or targeted therapies, opening avenues for innovative combinatorial approaches. This review provides a comprehensive overview of the current state of research surrounding GSK3 inhibitors as promising agents for cancer treatment.

New horizons in lung cancer management through ATR/CHK1 pathway modulation.

Lung cancer is the leading cause of cancer-related deaths worldwide. Molecular profiling has contributed to a new classification of lung cancer, driving advancements in research and therapy. The ataxia telangiectasia and rad3/checkpoint kinase 1 (ATR/CHK1) pathway plays a crucial role in maintaining genomic stability, and its activation has been linked to the development of lung cancer, drug resistance and poor prognosis. Clinical and preclinical studies have demonstrated promising results in targeting this pathway. ATR and CHK1 are proteins that collaborate to repair DNA damage caused by radiation or chemotherapy. ATR/CHK1 inhibitors are currently under investigation in preclinical and clinical trials. This article explores the ATR/CHK1 pathway and its potential for treating lung cancer.

Uncovering the complex role of interferon-gamma in suppressing type 2 immunity to cancer.

Cancer involves cells' abnormal growth and ability to invade or metastasize to different body parts. Cancerous cells can divide uncontrollably and spread to other areas through the lymphatic or circulatory systems. Tumors form when malignant cells clump together in an uncontrolled manner. In this context, the cytokine interferon-gamma (IFN-γ) is crucial in regulating immunological responses, particularly malignancy. While IFN-γ is well-known for its potent anti-tumor effects by activating type 1 immunity, recent research has revealed its ability to suppress type 2 immunity, associated with allergy and inflammatory responses. This review aims to elucidate the intricate function of IFN-γ in inhibiting type 2 immune responses to cancer. We explore how IFN-γ influences the development and function of immune cells involved in type 2 immunity, such as mast cells, eosinophils, and T-helper 2 (Th2) cells. Additionally, we investigate the impact of IFN-mediated reduction of type 2 immunity on tumor development, metastasis, and the response to immunotherapeutic interventions. To develop successful cancer immunotherapies, it is crucial to comprehend the complex interplay between type 2 and type 1 immune response and the regulatory role of IFN-γ. This understanding holds tremendous promise for the development of innovative treatment approaches that harness the abilities of both immune response types to combat cancer. However, unraveling the intricate interplay between IFN-γ and type 2 immunity in the tumor microenvironment will be essential for achieving this goal.

A comprehensive review on the emerging role of long non-coding RNAs in the regulation of NF-κB signaling in inflammatory lung diseases.

Public health globally faces significant risks from conditions like acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and various inflammatory lung disorders. The NF-κB signaling system partially controls lung inflammation, immunological responses, and remodeling. Non-coding RNAs (lncRNAs) are crucial in regulating gene expression. They are increasingly recognized for their involvement in NF-κB signaling and the development of inflammatory lung diseases. Disruption of lncRNA-NF-κB interactions is a potential cause and resolution factor for inflammatory respiratory conditions. This study explores the therapeutic potential of targeting lncRNAs and NF-κB signaling to alleviate inflammation and restore lung function. Understanding the intricate relationship between lncRNAs and NF-κB signaling could offer novel insights into disease mechanisms and identify therapeutic targets. Regulation of lncRNAs and NF-κB signaling holds promise as an effective approach for managing inflammatory lung disorders. This review aims to comprehensively analyze the interaction between lncRNAs and the NF-κB signaling pathway in the context of inflammatory lung diseases. It investigates the functional roles of lncRNAs in modulating NF-κB activity and the resulting inflammatory responses in lung cells, focusing on molecular mechanisms involving upstream regulators, inhibitory proteins, and downstream effectors.

From nature to therapy: Luteolin's potential as an immune system modulator in inflammatory disorders.

Inflammation is an essential immune response that helps fight infections and heal tissues. However, chronic inflammation has been linked to several diseases, including cancer, autoimmune disorders, cardiovascular diseases, and neurological disorders. This has increased interest in finding natural substances that can modulate the immune system inflammatory signaling pathways to prevent or treat these diseases. Luteolin is a flavonoid found in many fruits, vegetables, and herbs. It has been shown to have anti-inflammatory effects by altering signaling pathways in immune cells. This review article discusses the current research on luteolin's role as a natural immune system modulator of inflammatory signaling mechanisms, such as its effects on nuclear factor-kappa B, mitogen-activated protein kinases, Janus kinase/signal transducer and activator of transcription, and inflammasome signaling processes. The safety profile of luteolin and its potential therapeutic uses in conditions linked to inflammation are also discussed. Overall, the data point to Luteolin's intriguing potential as a natural regulator of immune system inflammatory signaling processes. More research is needed to fully understand its mechanisms of action and possible therapeutic applications.

Unveiling the connection: Long-chain non-coding RNAs and critical signaling pathways in breast cancer.

Breast cancer is a complex and diverse condition that disrupts multiple signaling pathways essential for cell proliferation, survival, and differentiation. Recently, the significant involvement of long-chain non-coding RNAs (lncRNAs) in controlling key signaling pathways associated with breast cancer development has been discovered. This review aims to explore the interaction between lncRNAs and various pathways, including the AKT/PI3K/mTOR, Wnt/ß-catenin, Notch, DNA damage response, TGF-ß, Hedgehog, and NF-κB signaling pathways, to gain a comprehensive understanding of their roles in breast cancer. The AKT/PI3K/mTOR pathway regulates cell growth, survival, and metabolic function. Recent data suggests that specific lncRNAs can influence the functioning of this pathway, acting as either oncogenes or tumor suppressors. Dysregulation of this pathway is commonly observed in breast cancer cases. Moreover, breast cancer development has been associated with other pathways such as Wnt/ß-catenin, Notch, TGF-ß, Hedgehog, and NF-κB. Emerging studies have identified lncRNAs that modulate breast cancer's growth, progression, and metastasis by interacting with these pathways. To advance the development of innovative diagnostic tools and targeted treatment options, it is crucial to comprehend the intricate relationship between lncRNAs and vital signaling pathways in breast cancer. By fully harnessing the therapeutic potential of lncRNAs, there is a possibility of developing more effective and personalized therapy choices for breast cancer patients. Further investigation is necessary to comprehensively understand the role of lncRNAs within breast cancer signaling pathways and fully exploit their therapeutic potential.

The pyroptotic role of Caspase-3/GSDME signalling pathway among various cancer: A Review.

Cytotoxic drugs have long been recognised to kill cancer cells through apoptosis. According to a current study, pyroptosis inhibits cell proliferation and shrinks tumors. Pyroptosis and apoptosis are caspase-dependent programmed cell death (PCD) processes. Inflammasomes activate caspase-1 and latent cytokines, including IL-1ß and IL-18, to cleave gasdermin E (GSDME) and induce pyroptosis. Gasdermin proteins activate caspase-3 to induce pyroptosis, which is associated with tumour genesis, development, and therapy response. These proteins may serve as therapeutic biomarkers for cancer detection, and their antagonists may be a new target. Caspase-3, a crucial protein in both pyroptosis and apoptosis, governs tumour cytotoxicity when activated, and GSDME expression modulates this. Once active caspase-3 cleaves GSDME, its N-terminal domain punches holes in the cell membrane, causing it to expand, burst, and die. To understand the cellular and molecular mechanisms of PCD mediated by caspase-3 and GSDME, we focused on pyroptosis. Hence, caspase-3 and GSDME may be promising targets for cancer treatment.

Galangin as an inflammatory response modulator: An updated overview and therapeutic potential.

Numerous chronic diseases, such as cancer, diabetes, rheumatoid arthritis, cardiovascular disease, and gastrointestinal disorders, all have an inflammation-based etiology. In cellular and animal models of inflammation, flavonols were used to show potent anti-inflammatory activity. The flavonols enhanced the synthesis of the anti-inflammatory cytokines transforming growth factor and interleukin-10 (IL-10) and reduced the synthesis of the prostaglandins IL-6, tumor necrosis factor-alpha (TNF-α), and prostaglandin E2 (PGE2), IL-1. Galangin (GAL), a natural flavonol, has a strong ability to control apoptosis and inflammation. GAL was discovered to suppress extracellular signal-regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)p65 phosphorylation, which results in anti-inflammatory actions. Arthritis, inflammatory bronchitis, stroke, and cognitive dysfunction have all been treated with GAL. The current review aimed to demonstrate the anti-inflammatory properties of GAL and their protective effects in treating various chronic illnesses, including those of the heart, brain, skin, lungs, liver, and inflammatory bowel diseases.