ABSTRACT
Coriander (Coriandrum sativum L.) is a member of the Umbelliferae/Apiaceae family and one of the well-known essential oil-containing plants, in which the seeds are used in traditional medicine, and as flavoring in food preparation. Knowing the diverse chemical components of different parts of the plant, this work aims to investigate the antioxidant, the anti-inflammatory, and the immunostimulatory modulator effects of the Jordanian C. sativum's seed extracted essential oil (JCEO). Coriander oil extract was prepared by hydro-distillation method using the Clevenger apparatus. Different concentrations of coriander oil were examined by using DPPH radical scavenging assay, MTT assay, pro-inflammatory cytokine (Tumor Necrosis Factor-TNF-alpha) production in RAW264.7 murine macrophages in addition, scratch-wound assessment, NO level examination, Th1/Th2 assay, phagocytosis assay, and fluorescence imaging using DAPI stain were conducted. JCEO had a potential metabolic enhancer effect at a concentration of 0.3 mg/mL on cell viability with anti-inflammatory activities via increasing cytokines like IL-10, IL-4, and limiting NO, INF-γ, and TNF-α release into cell supernatant. Antioxidant activity was seen significantly at higher concentrations of JCEO reaching 98.7% when using 100mg/mL and minimally reaching 50% at 12.5mg/mL of the essential oil. Treated macrophages were able to attain full scratch closure after 48-hrs at concentrations below 0.3mg/mL. The seed-extracted JCEO showed significant free radical scavenging activity even at lower dilutions. It also significantly induced an anti-inflammatory effect via an increase in the release of cytokines but reduced the LPS-induced NO and TNF-α production at 0.16-0.3mg/mL. In summary, coriander essential oil demonstrated antioxidant, anti-inflammatory, and immunostimulatory effects, showcasing its therapeutic potential at specific concentrations. The findings underscore its safety and metabolic enhancement properties, emphasizing its promising role in promoting cellular health.
Subject(s)
Anti-Inflammatory Agents , Antioxidants , Coriandrum , Macrophages , Oils, Volatile , Seeds , Animals , Mice , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Seeds/chemistry , Antioxidants/pharmacology , Coriandrum/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Macrophages/drug effects , Macrophages/metabolism , RAW 264.7 Cells , Tumor Necrosis Factor-alpha/metabolism , Cell Survival/drug effects , Nitric Oxide/metabolism , Phagocytosis/drug effects , Cytokines/metabolism , JordanABSTRACT
Parkinson's disease (PD) is a widely seen neurodegenerative condition recognized by misfolded α-synuclein (αSyn) protein, a prominent indicator for PD and other synucleinopathies. Motor symptoms like stiffness, akinesia, rest tremors, and postural instability coexist with nonmotor symptoms that differ from person to person in the development of PD. These symptoms arise from a progressive loss of synapses and neurons, leading to a widespread degenerative process in multiple organs. Implementing medical and surgical interventions, such as deep brain stimulation, has enhanced individuals' overall well-being and long-term survival with PD. It should be mentioned that these treatments cannot stop the condition from getting worse. The complicated structure of the brain and the existence of a semi-permeable barrier, commonly known as the BBB, have traditionally made medication delivery for the treatment of PD a challenging endeavor. The drug's low lipophilic nature, enormous size, and peculiarity for various ATP-dependent transport mechanisms hinder its ability to enter brain cells. This article delves into the potential of drug delivery systems based on chitosan (CS) to treat PD.
ABSTRACT
The microbiota-gut-brain axis (MGBA) represents a sophisticated communication network between the brain and the gut, involving immunological, endocrinological, and neural mediators. This bidirectional interaction is facilitated through the vagus nerve, sympathetic and parasympathetic fibers, and is regulated by the hypothalamic-pituitary-adrenal (HPA) axis. Evidence shows that alterations in gut microbiota composition, or dysbiosis, significantly impact neurological disorders (NDs) like anxiety, depression, autism, Parkinson's disease (PD), and Alzheimer's disease (AD). Dysbiosis can affect the central nervous system (CNS) via neuroinflammation and microglial activation, highlighting the importance of the microbiota-gut-brain axis (MGBA) in disease pathogenesis. The microbiota influences the immune system by modulating chemokines and cytokines, impacting neuronal health. Synbiotics have shown promise in treating NDs by enhancing cognitive function and reducing inflammation. The gut microbiota's role in producing neurotransmitters and neuroactive compounds, such as short-chain fatty acids (SCFAs), is critical for CNS homeostasis. Therapeutic interventions targeting the MGBA, including dietary modulation and synbiotic supplementation, offer potential benefits for managing neurodegenerative disorders. However, more in-depth clinical studies are necessary to fully understand and harness the therapeutic potential of the MGBA in neurological health and disease.
ABSTRACT
Understanding the underlying mechanisms of breast cancer metastasis is of vital importance for developing treatment approaches. This review emphasizes contemporary breakthrough studies with special focus on breast cancer brain metastasis. Acquired mutational changes in metastatic lesions are often distinct from the primary tumor, suggesting altered mutagenesis pathways. The concept of micrometastases and heterogeneity within the tumors unravels novel therapeutic targets at genomic and molecular levels through epigenetic and proteomic profiling. Several pre-clinical studies have identified mechanisms involving the immune system, where tumor associated macrophages are key players. Expression of cell proteins like Syndecan1, fatty acid-binding protein 7 and tropomyosin kinase receptor B have been implicated in aiding the transmigration of breast cancer cells to the brain. Changes in the proteomic landscape of the blood-brain-barrier show altered permeability characteristics, supporting entry of cancer cells. Findings from laboratory studies pave the path for the emergence of new biomarkers, especially blood-based miRNA and circulating tumor cell markers for prognostic staging. The constantly evolving therapeutics call for clinical trials backing supportive evidence of efficacies of both novel and existing approaches. The challenge lying ahead is discovering innovative techniques to replace use of human samples and optimize small-scale patient recruitment in trials.
Subject(s)
Brain Neoplasms , Breast Neoplasms , Humans , Breast Neoplasms/pathology , Brain Neoplasms/secondary , Brain Neoplasms/pathology , Female , Biomarkers, Tumor/metabolism , AnimalsABSTRACT
Lung cancer (LC) is the leading cause of cancer-related mortality, and it is caused by many factors including cigarette smoking. Despite numerous treatment strategies for LC, its five-year survival is still poor (<20â¯%), attributable to treatment resistance and lack of early diagnosis and intervention. Importantly, LC incidence is higher in patients affected by chronic respiratory diseases (CRDs) such as asthma and chronic obstructive pulmonary disorder (COPD), and LC shares with other CRDs common pathophysiological features including chronic inflammation, oxidative stress, cellular senescence, and airway remodelling. Remodelling is a complex process resulting from the aberrant activation of tissue repair secondary to chronic inflammation, oxidative stress, and tissue damage observed in the airways of CRD patients, and it is characterized by irreversible airway structural and functional alterations, concomitantly with tissue fibrosis, epithelial-to-mesenchymal transition (EMT), excessive collagen deposition, and thickening of the basement membrane. Many processes involved in remodelling, particularly EMT, are also fundamental for LC pathogenesis, highlighting a potential connection between CRDs and LC. This provides rationale for the development of novel treatment strategies aimed at targeting components of the remodelling pathways. In this study, we tested the in vitro therapeutic activity of rat fecal microbiome extract (FME) on A549 human lung adenocarcinoma cells. We show that treatment with FME significantly downregulates the expression of six proteins whose function is at the forefront between airway remodelling and LC development: Snail, SPARC, MUC-1, Osteopontin, MMP-2, and HIF-1α. The results of this study, if confirmed by further investigations, provide proof-of-concept for a novel approach in the treatment of LC, focused on tackling the airway remodelling mechanisms underlying the increased susceptibility to develop LC observed in CRD patients.
Subject(s)
Airway Remodeling , Down-Regulation , Lung Neoplasms , Airway Remodeling/drug effects , Humans , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Animals , Rats , A549 Cells , Feces/microbiology , Epithelial-Mesenchymal Transition/drug effects , Microbiota/drug effects , Gastrointestinal Microbiome/drug effectsABSTRACT
Lung cancer remains the leading cause of cancer-related deaths worldwide. According to the American Cancer Society (ACS), it ranks as the second most prevalent type of cancer globally. Recent findings have highlighted bidirectional gut-lung interactions, known as the gut-lung axis, in the pathophysiology of lung cancer. Probiotics are live microorganisms that boost host immunity when consumed adequately. The immunoregulatory mechanisms of probiotics are thought to operate through the generation of various metabolites that impact both the gut and distant organs (e.g., the lungs) through blood. Several randomized controlled trials have highlighted the pivotal role of probiotics in gut health especially for the prevention and treatment of malignancies, with a specific emphasis on lung cancer. Current research indicates that probiotic supplementation positively affects patients, leading to a suppression in cancer symptoms and a shortened disease course. While clinical trials validate the therapeutic benefits of probiotics, their precise mechanism of action remains unclear. This narrative review aims to provide a comprehensive overview of the present landscape of probiotics in the management of lung cancer.
ABSTRACT
Chronic respiratory diseases (CRDs) represent a significant proportion of global health burden, with a wide spectrum of varying, heterogenic conditions largely affecting the pulmonary system. Recent advances in immunology and respiratory biology have highlighted the systemic impact of these diseases, notably through the elucidation of the lung-eye axis. The current review focusses on understanding the pivotal role of the lung-eye axis in the pathogenesis and progression of chronic respiratory infections and diseases. Existing literature published on the immunological crosstalk between the eye and the lung has been reviewed. The various roles of the ocular microbiome in lung health are also explored, examining the eye as a gateway for respiratory virus transmission, and assessing the impact of environmental irritants on both ocular and respiratory systems. This novel concept emphasizes a bidirectional relationship between respiratory and ocular health, suggesting that respiratory diseases may influence ocular conditions and vice versa, whereby this conception provides a comprehensive framework for understanding the intricate axis connecting both respiratory and ocular health. These aspects underscore the need for an integrative approach in the management of chronic respiratory diseases. Future research should further elucidate the in-depth molecular mechanisms affecting this axis which would pave the path for novel diagnostics and effective therapeutic strategies.
Subject(s)
Eye , Lung , Humans , Lung/microbiology , Lung/physiopathology , Eye/microbiology , Eye Diseases/physiopathology , Eye Diseases/etiology , Animals , Respiratory Tract Diseases/physiopathology , Respiratory Tract Diseases/microbiology , Respiratory Tract Diseases/virology , Microbiota/physiologyABSTRACT
Hepatocellular carcinoma (HCC) is among the primary reasons for fatalities caused by cancer globally, highlighting the need for comprehensive knowledge of its molecular aetiology to develop successful treatment approaches. The PI3K/Akt system is essential in the course of HCC, rendering it an intriguing candidate for treatment. Non-coding RNAs (ncRNAs), such as long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are important mediators of the PI3K/Akt network in HCC. The article delves into the complex regulatory functions of ncRNAs in influencing the PI3K/Akt system in HCC. The study explores how lncRNAs, miRNAs, and circRNAs impact the expression as well as the function of the PI3K/Akt network, either supporting or preventing HCC growth. Additionally, treatment strategies focusing on ncRNAs in HCC are examined, such as antisense oligonucleotide-based methods, RNA interference, and small molecule inhibitor technologies. Emphasizing the necessity of ensuring safety and effectiveness in clinical settings, limitations, and future approaches in using ncRNAs as therapies for HCC are underlined. The present study offers useful insights into the complex regulation system of ncRNAs and the PI3K/Akt cascade in HCC, suggesting possible opportunities for developing innovative treatment approaches to address this lethal tumor.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , RNA, Untranslated , Signal Transduction , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Humans , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , Phosphatidylinositol 3-Kinases/metabolism , Phosphatidylinositol 3-Kinases/genetics , Signal Transduction/genetics , RNA, Untranslated/genetics , Gene Expression Regulation, Neoplastic/genetics , RNA, Circular/genetics , RNA, Circular/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolismABSTRACT
Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorder (ND), affecting more than 44 million individuals globally as of 2023. It is characterized by cognitive dysfunction and an inability to perform daily activities. The progression of AD is associated with the accumulation of amyloid beta (Aß), the formation of neurofibrillary tangles (NFT), increased oxidative stress, neuroinflammation, mitochondrial dysfunction, and endoplasmic reticulum stress. Presently, various phytomedicines and their bioactive compounds have been identified for their neuroprotective effects in reducing oxidative stress, alleviating neuroinflammation, and mitigating the accumulation of Aß and acetylcholinesterase enzymes in the hippocampus and cerebral cortex regions of the brain. However, despite demonstrating promising anti-Alzheimer's effects, the clinical utilization of phytoconstituents remains limited in scope. The key factor contributing to this limitation is the challenges inherent in traditional drug delivery systems, which impede their effectiveness and efficiency. These difficulties encompass insufficient drug targeting, restricted drug solubility and stability, brief duration of action, and a lack of control over drug release. Consequently, these constraints result in diminished bioavailability and insufficient permeability across the blood-brain barrier (BBB). In response to these challenges, novel drug delivery systems (NDDS) founded on nanoformulations have emerged as a hopeful strategy to augment the bioavailability and BBB permeability of bioactive compounds with poor solubility. Among these systems, nanoemulsion (NE) have been extensively investigated for their potential in targeting AD. NE offers several advantages, such as ease of preparation, high drug loading, and high stability. Due to their nanosize droplets, NE also improves gut and BBB permeability leading to enhanced permeability of the drug in systemic circulation and the brain. Various studies have reported the testing of NE-based phytoconstituents and their bioactives in different animal species, including transgenic, Wistar, and Sprague-Dawley (SD) rats, as well as mice. However, transgenic mice are commonly employed in AD research to analyze the effects of Aß. In this review, various aspects such as the neuroprotective role of various phytoconstituents, the challenges associated with conventional drug delivery, and the need for NDDS, particularly NE, are discussed. Various studies involving phytoconstituent-based NE for the treatment of AD are also discussed.
ABSTRACT
Tobacco smoking is a leading cause of preventable mortality, and it is the major contributor to diseases such as COPD and lung cancer. Cigarette smoke compromises the pulmonary antiviral immune response, increasing susceptibility to viral infections. There is currently no therapy that specifically addresses the problem of impaired antiviral response in cigarette smokers and COPD patients, highlighting the necessity to develop novel treatment strategies. 18-ß-glycyrrhetinic acid (18-ß-gly) is a phytoceutical derived from licorice with promising anti-inflammatory, antioxidant, and antiviral activities whose clinical application is hampered by poor solubility. This study explores the therapeutic potential of an advanced drug delivery system encapsulating 18-ß-gly in poly lactic-co-glycolic acid (PLGA) nanoparticles in addressing the impaired antiviral immunity observed in smokers and COPD patients. Exposure of BCi-NS1.1 human bronchial epithelial cells to cigarette smoke extract (CSE) resulted in reduced expression of critical antiviral chemokines (IP-10, I-TAC, MIP-1α/1ß), mimicking what happens in smokers and COPD patients. Treatment with 18-ß-gly-PLGA nanoparticles partially restored the expression of these chemokines, demonstrating promising therapeutic impact. The nanoparticles increased IP-10, I-TAC, and MIP-1α/1ß levels, exhibiting potential in attenuating the negative effects of cigarette smoke on the antiviral response. This study provides a novel approach to address the impaired antiviral immune response in vulnerable populations, offering a foundation for further investigations and potential therapeutic interventions. Further studies, including a comprehensive in vitro characterization and in vivo testing, are warranted to validate the therapeutic efficacy of 18-ß-gly-PLGA nanoparticles in respiratory disorders associated with compromised antiviral immunity.
Subject(s)
Glycyrrhetinic Acid , Nanoparticles , Humans , Glycyrrhetinic Acid/pharmacology , Glycyrrhetinic Acid/analogs & derivatives , Antiviral Agents/pharmacology , Smoke/adverse effects , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Cell Line , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/immunology , Epithelial Cells/drug effects , Epithelial Cells/virology , Cigarette Smoking/adverse effectsABSTRACT
The escalating prevalence of lung diseases underscores the need for innovative therapies. Dysbiosis in human body microbiome has emerged as a significant factor in these diseases, indicating a potential role for synbiotics in restoring microbial equilibrium. However, effective delivery of synbiotics to the target site remains challenging. Here, we aim to explore suitable nanoparticles for encapsulating synbiotics tailored for applications in lung diseases. Nanoencapsulation has emerged as a prominent strategy to address the delivery challenges of synbiotics in this context. Through a comprehensive review, we assess the potential of nanoparticles in facilitating synbiotic delivery and their structural adaptability for this purpose. Our review reveals that nanoparticles such as nanocellulose, starch, and chitosan exhibit high potential for synbiotic encapsulation. These offer flexibility in structure design and synthesis, making them promising candidates for addressing delivery challenges in lung diseases. Furthermore, our analysis highlights that synbiotics, when compared to probiotics alone, demonstrate superior anti-inflammatory, antioxidant, antibacterial and anticancer activities. This review underscores the promising role of nanoparticle-encapsulated synbiotics as a targeted and effective therapeutic approach for lung diseases, contributing valuable insights into the potential of nanomedicine in revolutionizing treatment strategies for respiratory conditions, ultimately paving the way for future advancements in this field.
Subject(s)
Lung Diseases , Synbiotics , Humans , Lung Diseases/drug therapy , Nanostructures/chemistry , Lung/drug effects , Lung/pathology , Animals , Nanoparticles/chemistryABSTRACT
Probiotics are a mixture of beneficial live bacteria and/or yeasts that naturally exist in our bodies. Recently, numerous studies have focused on the immunostimulatory effects of single-species or killed multi-species probiotic conditioned mediums on macrophages. This study investigates the immunostimulatory effect of commercially available active, multi-species probiotic conditioned medium (CM) on RAW264.7 murine macrophages. The probiotic CM was prepared by culturing the commercially available probiotic in a cell-culture medium overnight at 37 °C, followed by centrifugation and filter-sterilization to be tested on macrophages. The immunostimulatory effect of different dilution percentages (50%, 75%, 100%) of CM was examined using the MTT assay, proinflammatory cytokine (tumor necrosis factor TNF-alpha) production in macrophages, migration, and phagocytosis assays. For all the examined CM ratios, the percentages of cell viability were > 80%. Regarding the migration scratch, TNF-alpha and phagocytosis assays, CM demonstrated a concentration-dependent immunostimulatory effect. However, the undiluted CM (100%) showed a significant (p-value < 0.05) stimulatory effect compared to the positive and negative controls. The findings suggest that the secretions and products of probiotics, as measured in the CM, may be closely associated with their immune-boosting effects. Understanding this relationship between probiotic secretions and immune function is crucial for further exploring the potential benefits of probiotics in enhancing overall health and well-being.
Subject(s)
Probiotics , Tumor Necrosis Factor-alpha , Mice , Animals , Culture Media, Conditioned/pharmacology , Tumor Necrosis Factor-alpha/pharmacology , Macrophages , Immunity , Probiotics/pharmacologyABSTRACT
The gut microbiome is involved in the pathogenesis of many diseases including polycystic ovarian syndrome (PCOS). Modulating the gut microbiome can lead to eubiosis and treatment of various metabolic conditions. However, there is no proper study assessing the delivery of microbial technology for the treatment of such conditions. The present study involves the development of guar gum-pectin-based solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing curcumin (CCM) and fecal microbiota extract (FME) for the treatment of PCOS. The optimized S-SNEDDS containing FME and CCM was prepared by dissolving CCM (25 mg) in an isotropic mixture consisting of Labrafil M 1944 CS, Transcutol P, and Tween-80 and solidified using lactose monohydrate, aerosil-200, guar gum, and pectin (colon-targeted CCM solid self-nanoemulsifying drug delivery system [CCM-CT-S-SNEDDS]). Pharmacokinetic and pharmacodynamic evaluation was carried out on letrozole-induced female Wistar rats. The results of pharmacokinetic studies indicated about 13.11 and 23.48-fold increase in AUC of CCM-loaded colon-targeted S-SNEDDS without FME (CCM-CT-S-SNEDDS (WFME)) and CCM-loaded colon-targeted S-SNEDDS with FME [(CCM-CT-S-SNEDDS (FME)) as compared to unprocessed CCM. The pharmacodynamic study indicated excellent recovery/reversal in the rats treated with CCM-CT-S-SNEDDS low and high dose containing FME (group 13 and group 14) in a dose-dependent manner. The developed formulation showcasing its improved bioavailability, targeted action, and therapeutic activity in ameliorating PCOS can be utilized as an adjuvant therapy for developing a dosage form, scale-up, and technology transfer.
ABSTRACT
Chronic Obstructive Pulmonary Disease (COPD), a chronic lung disease that causes breathing difficulties and obstructs airflow from the lungs, has a significant global health burden and affects millions of people worldwide. The use of pharmaceuticals in COPD treatment is aimed to alleviate symptoms, improve lung function, prevent exacerbations, and enhance the overall quality of life for patients. Nanotechnology holds great promise to alleviate the burden of COPD. The main goal of this review is to present the full spectrum of therapeutics based on nanostructures for the treatment and management of COPD, including nanoparticles, polymeric nanoparticles, polymeric micelles, solid-lipid nanoparticles, liposomes, exosomes, nanoemulsions, nanosuspensions, and niosomes. Nanotechnology is just one of the many areas of research that may contribute to the development of more effective and personalized treatment modalities for COPD patients in the future. Future studies may be focused on enhancing the therapeutic effectiveness of nanocarriers by conducting extensive mechanistic investigations to translate current scientific knowledge for the effective management of COPD with little or no adverse effects.
ABSTRACT
Chronic Obstructive Pulmonary Disease (COPD) is a dilapidating condition which is characterized by inflammation, an excess in free radical generation and airway obstruction. Currently, the drugs commercially available for the management of COPD pose several limitations such as systemic adverse effects, including bone density loss and an increased risk of developing pneumonia. Moreover, another limitation includes the need for regular and frequent dosing regimens; which can affect the adherence to the therapy. Furthermore, these current treatments provide symptomatic relief; however, they cannot stop the progression of COPD. Comparatively, nanoparticles (NPs) provide great therapeutic potential to treat COPD due to their high specificity, biocompatibility, and higher bioavailability. Furthermore, the NP-based drug delivery systems involve less frequent dosing requirements and in smaller doses which assist in minimizing side effects. In this review, the benefits and limitations of conventional therapies are explored, while providing an in-depth insight on advanced applications of NP-based systems in the treatment of COPD.
ABSTRACT
Tumour suppressor genes play a cardinal role in the development of a large array of human cancers, including lung cancer, which is one of the most frequently diagnosed cancers worldwide. Therefore, extensive studies have been committed to deciphering the underlying mechanisms of alterations of tumour suppressor genes in governing tumourigenesis, as well as resistance to cancer therapies. In spite of the encouraging clinical outcomes demonstrated by lung cancer patients on initial treatment, the subsequent unresponsiveness to first-line treatments manifested by virtually all the patients is inherently a contentious issue. In light of the aforementioned concerns, this review compiles the current knowledge on the molecular mechanisms of some of the tumour suppressor genes implicated in lung cancer that are either frequently mutated and/or are located on the chromosomal arms having high LOH rates (1p, 3p, 9p, 10q, 13q, and 17p). Our study identifies specific genomic loci prone to LOH, revealing a recurrent pattern in lung cancer cases. These loci, including 3p14.2 (FHIT), 9p21.3 (p16INK4a), 10q23 (PTEN), 17p13 (TP53), exhibit a higher susceptibility to LOH due to environmental factors such as exposure to DNA-damaging agents (carcinogens in cigarette smoke) and genetic factors such as chromosomal instability, genetic mutations, DNA replication errors, and genetic predisposition. Furthermore, this review summarizes the current treatment landscape and advancements for lung cancers, including the challenges and endeavours to overcome it. This review envisages inspired researchers to embark on a journey of discovery to add to the list of what was known in hopes of prompting the development of effective therapeutic strategies for lung cancer.
Subject(s)
Lung Neoplasms , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Loss of Heterozygosity , Genes, Tumor Suppressor , Mutation/genetics , Cell Transformation, Neoplastic/geneticsABSTRACT
The impact of the coronavirus disease 2019 (COVID-19) pandemic on the everyday livelihood of people has been monumental and unparalleled. Although the pandemic has vastly affected the global healthcare system, it has also been a platform to promote and develop pioneering applications based on autonomic artificial intelligence (AI) technology with therapeutic significance in combating the pandemic. Artificial intelligence has successfully demonstrated that it can reduce the probability of human-to-human infectivity of the virus through evaluation, analysis, and triangulation of existing data on the infectivity and spread of the virus. This review talks about the applications and significance of modern robotic and automated systems that may assist in spreading a pandemic. In addition, this study discusses intelligent wearable devices and how they could be helpful throughout the COVID-19 pandemic.
ABSTRACT
Calcium is a ubiquitous second messenger that is indispensable in regulating neurotransmission and memory formation. A precise intracellular calcium level is achieved through the concerted action of calcium channels, and calcium exerts its effect by binding to an array of calcium-binding proteins, including calmodulin (CAM), calcium-calmodulin complex-dependent protein kinase-II (CAMK-II), calbindin (CAL), and calcineurin (CAN). Calbindin orchestrates a plethora of signaling events that regulate synaptic transmission and depolarizing signals. Vitamin D, an endogenous fat-soluble metabolite, is synthesized in the skin upon exposure to ultraviolet B radiation. It modulates calcium signaling by increasing the expression of the calcium-sensing receptor (CaSR), stimulating phospholipase C activity, and regulating the expression of calcium channels such as TRPV6. Vitamin D also modulates the activity of calcium-binding proteins, including CAM and calbindin, and increases their expression. Calbindin, a high-affinity calcium-binding protein, is involved in calcium buffering and transport in neurons. It has been shown to inhibit apoptosis and caspase-3 activity stimulated by presenilin 1 and 2 in AD. Whereas CAM, another calcium-binding protein, is implicated in regulating neurotransmitter release and memory formation by phosphorylating CAN, CAMK-II, and other calcium-regulated proteins. CAMK-II and CAN regulate actin-induced spine shape changes, which are further modulated by CAM. Low levels of both calbindin and vitamin D are attributed to the pathology of Alzheimer's disease. Further research on vitamin D via calbindin-CAMK-II signaling may provide newer insights, revealing novel therapeutic targets and strategies for treatment.
Subject(s)
Alzheimer Disease , Vitamin D , Humans , Calcium Signaling , Calbindins , Calmodulin , Calcium , Calcium-Binding Proteins , Calcium Channels , Calcineurin , Calcium-Calmodulin-Dependent Protein Kinase Type 2ABSTRACT
Piceatannol is a naturally occurring hydroxylated resveratrol analogue that can be found in a variety of fruits and vegetables. It has been documented to have a wide range of beneficial effects, including anti-inflammatory, antioxidant, anti-aging, anti-allergic, antidiabetic, neuroprotective, cardioprotective, and chemopreventive properties. Piceatannol has significantly higher antioxidant activity than resveratrol. Piceatannol has been shown in preclinical studies to have the ability to inhibit or reduce the growth of cancers in various organs such as the brain, breast, lung, colon, cervical, liver, prostate, and skin. However, the bioavailability of Piceatannol is comparatively lower than resveratrol and other stilbenes. Several approaches have been reported in recent years to enhance its bioavailability and biological activity, and clinical trials are required to validate these findings. This review focuses on several aspects of natural stilbene Piceatannol, its chemistry, and its mechanism of action, and its promising therapeutic potential for the prevention and treatment of a wide variety of complex human diseases.