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1.
Noncoding RNA Res ; 9(4): 1222-1234, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39036600

ABSTRACT

Ferroptosis, a form of regulated cell death, has emerged as a crucial process in diverse pathophysiological states, encompassing cancer, neurodegenerative ailments, and ischemia-reperfusion injury. The glutathione (GSH)-dependent lipid peroxidation pathway, chiefly governed by glutathione peroxidase 4 (GPX4), assumes an essential part in driving ferroptosis. GPX4, as the principal orchestrator of ferroptosis, has garnered significant attention across cancer, cardiovascular, and neuroscience domains over the past decade. Noteworthy investigations have elucidated the indispensable functions of ferroptosis in numerous diseases, including tumorigenesis, wherein robust ferroptosis within cells can impede tumor advancement. Recent research has underscored the complex regulatory role of non-coding RNAs (ncRNAs) in regulating the GSH-GPX4 network, thus influencing cellular susceptibility to ferroptosis. This exhaustive review endeavors to probe into the multifaceted processes by which ncRNAs control the GSH-GPX4 network in ferroptosis. Specifically, we delve into the functions of miRNAs, lncRNAs, and circRNAs in regulating GPX4 expression and impacting cellular susceptibility to ferroptosis. Moreover, we discuss the clinical implications of dysregulated interactions between ncRNAs and GPX4 in several conditions, underscoring their capacity as viable targets for therapeutic intervention. Additionally, the review explores emerging strategies aimed at targeting ncRNAs to modulate the GSH-GPX4 pathway and manipulate ferroptosis for therapeutic advantage. A comprehensive understanding of these intricate regulatory networks furnishes insights into innovative therapeutic avenues for diseases associated with perturbed ferroptosis, thereby laying the groundwork for therapeutic interventions targeting ncRNAs in ferroptosis-related pathological conditions.

2.
Pathol Res Pract ; 260: 155430, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-39038389

ABSTRACT

Due to the increasing incidence of cancer and the difficulties in determining the safety profile of existing therapeutic approaches, cancer research has recently become heavily involved in the search for new therapeutic approaches. The therapeutic significance of natural substances, especially flavonoids, against the onset and progression of cancer has been emphasized in traditional food-based medicine. Interestingly, the flavone luteolin possesses biological effects that have been linked to its anti-inflammatory, antioxidant, and anticancer effects. Luteolin interacts with several downstream chemicals and signaling pathways, including those involved in apoptosis, autophagy, cell cycle progression, and angiogenesis, to exert its anticancer effects on various cancerous cells. A complete understanding of both intrinsic and extrinsic apoptotic pathways, autophagy, and, most critically, the nanodelivery of luteolin in liver cancer is provided in the current review.

3.
Heliyon ; 10(13): e32755, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39027624

ABSTRACT

The involvement of neuroinflammation in the pathogenesis of neurodegenerative disorders (NDs) is very significant. Currently, only symptomatic treatments exist, and there are no drugs that modify the progression of Alzheimer's disease (AD) or other NDs. Consequently, there is increasing attention on addressing AD-related neuroinflammation using anti-inflammatory compounds and antioxidants. Currently, there is a growing exploration of dietary phytochemicals as potential therapeutic agents for treating inflammation. Citral, a monoterpene, is under increasing investigation due to its neuroprotective effects. The dysregulation of iron homeostasis is a crucial factor in supporting neuroinflammation, underscoring the significance of proper iron balance. Human transferrin (htf) is a major player involved in iron homeostasis. In this study, we examined binding and dynamics of htf-citral complex through diverse experimental methods. Molecular docking studies revealed that citral binds to crucial residues of htf, forming a stable complex. UV-visible spectroscopy demonstrated binding of citral with htf with good affinity, evident from binding constant of 1.48 × 105 M-1. Further, fluorescence spectroscopy entrenched a stable htf-citral complex formation; citral demonstrates an excellent binding affinity to htf with a binding constant of 106 M-1. Moreover, fluorescence binding assay at various temperatures deciphered htf-citral complex to be driven by both static and dynamic quenching. The analysis of enthalpy change (ΔH) and entropy change (ΔS) demonstrated that htf-citral complex formation was driven mainly by hydrophobic interactions.The current work gives a platform to develop innovative therapeutic strategies targeting neuroinflammation through citral, particularly iron homeostasis.

4.
Explor Target Antitumor Ther ; 5(3): 477-494, 2024.
Article in English | MEDLINE | ID: mdl-38966181

ABSTRACT

In recent times, there have been notable advancements in comprehending the potential anti-cancer effects of chrysin (CH), a naturally occurring flavonoid compound found abundantly in various plant sources like honey, propolis, and certain fruits and vegetables. This active compound has garnered significant attention due to its promising therapeutic qualities and minimal toxicity. CH's ability to combat cancer arises from its multifaceted mechanisms of action, including the initiation of apoptosis and the inhibition of proliferation, angiogenesis, metastasis, and cell cycle progression. CH also displays potent antioxidant and anti-inflammatory properties, effectively counteracting the harmful molecules that contribute to DNA damage and the development of cancer. Furthermore, CH has exhibited the potential to sensitize cancer cells to traditional chemotherapy and radiotherapy, amplifying the effectiveness of these treatments while reducing their negative impact on healthy cells. Hence, in this current review, the composition, chemistry, mechanisms of action, safety concerns of CH, along with the feasibility of its nanoformulations. To conclude, the recent investigations into CH's anti-cancer effects present a compelling glimpse into the potential of this natural compound as a complementary therapeutic element in the array of anti-cancer approaches, providing a safer and more comprehensive method of combating this devastating ailment.

5.
Front Pharmacol ; 15: 1424175, 2024.
Article in English | MEDLINE | ID: mdl-39005934

ABSTRACT

Histone deacetylase 3 (HDAC3) is a member of the histone deacetylase family that has emerged as a crucial target in the quest for novel therapeutic interventions against various complex diseases, including cancer. The repositioning of FDA-approved drugs presents a promising avenue for the rapid discovery of potential HDAC3 inhibitors. In this study, we performed a structure-based virtual screening of FDA-approved drugs obtained from DrugBank. Candidate hits were selected based on their binding affinities and interactions with HDAC3. These promising hits were then subjected to a comprehensive assessment of their biological properties and drug profiles. Our investigation identified two FDA-approved drugs, Imatinib and Carpipramine, characterized by their exceptional affinity and specificity for the binding pocket of HDAC3. These molecules demonstrated a strong preference for HDAC3 binding site and formed interactions with functionally significant residues within the active site pocket. To gain deeper insights into the binding dynamics, structural stability, and interaction mechanisms, we performed molecular dynamics (MD) simulations spanning 300 nanoseconds (ns). The results of MD simulations indicated that Imatinib and Carpipramine stabilized the structure of HDAC3 and induced fewer conformational changes. Taken together, the findings from this study suggest that Imatinib and Carpipramine may offer significant therapeutic potential for treating complex diseases, especially cancer.

7.
EXCLI J ; 23: 570-599, 2024.
Article in English | MEDLINE | ID: mdl-38887390

ABSTRACT

Cancer poses intricate challenges to treatment due to its complexity and diversity. Ferroptosis and circular RNAs (circRNAs) are emerging as innovative therapeutic avenues amid the evolving landscape of cancer therapy. Extensive investigations into circRNAs reveal their diverse roles, ranging from molecular regulators to pivotal influencers of ferroptosis in cancer cell lines. The results underscore the significance of circRNAs in modulating molecular pathways that impact crucial aspects of cancer development, including cell survival, proliferation, and metastasis. A detailed analysis delineates these pathways, shedding light on the molecular mechanisms through which circRNAs influence ferroptosis. Building upon recent experimental findings, the study evaluates the therapeutic potential of targeting circRNAs to induce ferroptosis. By identifying specific circRNAs associated with the etiology of cancer, this analysis paves the way for the development of targeted therapeutics that exploit vulnerabilities in cancer cells. This review consolidates the existing understanding of ferroptosis and circRNAs, emphasizing their role in cancer therapy and providing impetus for ongoing research in this dynamic field. See also the graphical abstract(Fig. 1).

8.
Diabetes Metab Syndr Obes ; 17: 2293-2301, 2024.
Article in English | MEDLINE | ID: mdl-38859997

ABSTRACT

Background: The objective of this study was to determine the prevalence of anemia in patients with type 2 diabetes mellitus and to identify the set of anthropometric and biochemical factors that jointly influence the diabetic and anemic patients including body mass index and kidney function. . Methods: A retrospective cross-sectional design study that was carried out in a private medical center in Palestine. The study included a total of 453 patients with type 2 diabetes. Inclusion criteria included all patients (18 years or older) suffering from type 2 Diabetes mellitus attended the diabetic clinic from the 1st of January 2018, till 30th of December 2018. . Results: A total number of 453 diabetic patients were recruited in the study. Male constituted 48.5% (n=220) of the study sample and 51.4% (n=233) were female. Of total 453 diabetic patients, 38.4% (95% CI, 34%-43%) had anemia. The results of statistical modeling showed that female gender (AOR 18.5; 95% CI 9.35-21.97), presence of hypertension (AOR 2.11; 95% CI 1.98- 4.25), high BMI (AOR 1.101; 95% CI 1.045-1.159), high Serum Creatinine (AOR 1.72; 95% CI 1.22-2.13), high BUN level (AOR 1.22; 95% CI 1.145-1.301) and low e-GFR (AOR 0.571; 95% CI 0.271-0.872) are strong determents of anemia in type 2 diabetic patients. . Conclusion: The results of the current study revealed a high prevalence of Anemia among type 2 diabetes Mellitus patients. A significant association was reported between Anemia, kidney functions and body mass index. .

9.
J Alzheimers Dis ; 100(2): 475-485, 2024.
Article in English | MEDLINE | ID: mdl-38875044

ABSTRACT

Background: HMGCS2 (mitochondrial 3-hydroxy-3-methylglutaryl-COA synthase 2) plays a pivotal role as a control enzyme in ketogenesis, and its association with the amyloid-ß protein precursor (AßPP) in mitochondria implicates a potential involvement in Alzheimer's disease (AD) pathophysiology. Objective: Our study aimed at identifying repurposed drugs using the DrugBank database capable of inhibiting HMGCS2 activity. Methods: Exploiting the power of drug repurposing in conjunction with virtual screening and molecular dynamic (MD) simulations against 'HMGCS2', we present new in-silico insight into structure-based drug repurposing. Results: The initial molecules were screened for their binding affinity to HMGCS2. Subsequent interaction analyses and extensive 300 ns MD simulations were conducted to explore the conformational dynamics and stability of HMGCS2 in complex with the screened molecules, particularly Penfluridol and Lurasidone. Conclusions: The study revealed that HMGCS2 forms stable protein-ligand complexes with Penfluridol and Lurasidone. Our findings indicate that Penfluridol and Lurasidone competitively bind to HMGCS2 and warrant their further exploration as potential repurposed molecules for anti-Alzheimer's drug development.


Subject(s)
Alzheimer Disease , Drug Repositioning , Hydroxymethylglutaryl-CoA Synthase , Molecular Dynamics Simulation , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Drug Repositioning/methods , Humans , Hydroxymethylglutaryl-CoA Synthase/metabolism , Drug Evaluation, Preclinical/methods , Molecular Docking Simulation
10.
J Multidiscip Healthc ; 17: 2563-2576, 2024.
Article in English | MEDLINE | ID: mdl-38803617

ABSTRACT

Background: Providing accurate and sufficient information is a crucial requirement for delivering effective diabetes care, making it essential for community pharmacists to possess adequate knowledge of diabetes mellitus (DM) and its management. Objective: To investigate community pharmacists' level of expertise and engagement in providing counseling and health promotion services for individuals with DM in the United Arab Emirates (UAE). Methods: A cross-sectional study design was used. The community Pharmacies were chosen via random sampling and researchers then conducted face-to-face interviews with them using the structured questionnaire. The questionnaire included demographic data, 14 questions on the knowledge and 9 questions about the practice concerning pharmaceutical care for Diabetes Mellitus. Results: The average age ± SD was 31 ± 6.3. Of the total 516 community pharmacists recruited in the study, 37.2% (n=192) were male and 62.8% (n=324) were female. The average knowledge score about DM prevention and management was 9.7 with a 95% confidence interval (CI) [9.5, 9.9] and the average practice score about DM prevention and management was 7.1 with a 95% confidence interval (CI) [6.9, 7.2]. Better knowledge scores were observed in chief pharmacists (OR 1.29; 95% CI 1.08-1.56), pharmacists with 6-10 Years of experience (OR 6.92; 95% CI 3.43-8.86), pharmacist with > 10 years of experience (OR 1.99; 95% CI 1.67-2.36), when the number of patients the pharmacist serve is 5-10 (OR 1.27; 95% CI 1.06-1.53) and being trained on DM prevention and management (OR 2.18; 95% CI 1.92-2.47). Similarly, better practice scores were observed in older participants (OR1.02; 95% CI 1.001-1.03), chain pharmacies (OR 1.42; 95% CI 1.20-1.68), chief pharmacists (OR 1.56; 95% CI 1.18-2.06), when the number of patients the pharmacists serve was 5-10 (OR 12.26; 95% CI 7.26-16.19), when the number of patients the pharmacists serve was 11-20 (OR 4.23; 95% CI 3.54-5.06) and being trained on DM prevention and management (OR 1.33; 95% CI 1.11-1.59). The most commonly reported barriers to providing counseling and health promotion services for diabetes mellitus (DM) in community pharmacies include a lack of coordination with other healthcare professionals (77%) and insufficient knowledge or clinical skills (68.7%). Conclusion: Our study revealed that community pharmacy staff members displayed a noteworthy level of involvement in providing pharmaceutical care services for patients with diabetes mellitus. Based on these findings, it is recommended to enhance pharmacy education by incorporating more advanced, evidence-based training and curricula focusing on disease management and appropriate therapies, particularly for diabetes.

11.
Front Pharmacol ; 15: 1397332, 2024.
Article in English | MEDLINE | ID: mdl-38799161

ABSTRACT

In present times, vanillin stands out as a promising therapeutic molecule that can be implicated in the treatment of neurodegenerative disorders (NDs), notably Alzheimer's disease (AD). This can be attributed to the highly potent scavenging activity of vanillin against reactive oxygen species (ROS). Oxidative stress leads to generation of ROS that serves a critical role in AD's pathological progression. It is apparent from various studies that diets rich in polyphenols prevent oxidative stress associated with AD development, implying the crucial role of vanillin in AD therapeutics. It is crucial to maintain iron balance to manage AD associated oxidative stress, unveiling the significance of human transferrin (hTf) that maintains iron homeostasis. Here, we have performed an integrated study of spectroscopic and computational approaches to get insight into the binding mechanism of vanillin with hTf. In the preliminary study, molecular docking deciphered that vanillin primarily occupies the hTf binding pocket, forming multiple interactions with its key residues. Moreover, the binding mechanism was evaluated at an atomistic level employing comprehensive molecular dynamic (MD) simulation. MD analysis demonstrated that binding of vanillin to hTf stabilizes its structure, without inducing any significant alterations in its native conformation. The docked complex was maintained throughout the simulations without changing its original conformation. Essential dynamics analysis further confirms that hTf achieved a stable conformation with vanillin. The outcomes were further supplemented by fluorescence spectroscopy which confirms the formation of stable hTf-vanillin complex. Taken together, the current study unveils the interaction mechanism of vanillin with hTf and providing a platform to use vanillin in AD therapeutics in the context of iron homeostasis.

12.
J Mol Model ; 30(6): 170, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38753123

ABSTRACT

CONTEXT: In the pursuit of novel therapeutic possibilities, repurposing existing drugs has gained prominence as an efficient strategy. The findings from our study highlight the potential of repurposed drugs as promising candidates against receptor for advanced glycation endproducts (RAGE) that offer therapeutic implications in cancer, neurodegenerative conditions and metabolic syndromes. Through careful analyses of binding affinities and interaction patterns, we identified a few promising candidates, ultimately focusing on sertindole and temoporfin. These candidates exhibited exceptional binding affinities, efficacy, and specificity within the RAGE binding pocket. Notably, they displayed a pronounced propensity to interact with the active site of RAGE. Our investigation further revealed that sertindole and temoporfin possess desirable pharmacological properties that highlighted them as attractive candidates for targeted drug development. Overall, our integrated computational approach provides a comprehensive understanding of the interactions between repurposed drugs, sertindole and temoporfin and RAGE that pave the way for future experimental validation and drug development endeavors. METHODS: We present an integrated approach utilizing molecular docking and extensive molecular dynamics (MD) simulations to evaluate the potential of FDA-approved drugs, sourced from DrugBank, against RAGE. To gain deeper insights into the binding mechanisms of the elucidated candidate repurposed drugs, sertindole and temoporfin with RAGE, we conducted extensive all-atom MD simulations, spanning 500 nanoseconds (ns). These simulations elucidated the conformational dynamics and stability of the RAGE-sertindole and RAGE-temoporfin complexes.


Subject(s)
Drug Repositioning , Imidazoles , Indoles , Molecular Docking Simulation , Molecular Dynamics Simulation , Receptor for Advanced Glycation End Products , Receptor for Advanced Glycation End Products/metabolism , Receptor for Advanced Glycation End Products/chemistry , Humans , Indoles/chemistry , Indoles/pharmacology , Imidazoles/chemistry , Imidazoles/pharmacology , Protein Binding , Neoplasms/drug therapy , Neoplasms/metabolism , Metabolic Diseases/drug therapy , Metabolic Diseases/metabolism , Binding Sites
13.
CNS Neurosci Ther ; 30(5): e14763, 2024 May.
Article in English | MEDLINE | ID: mdl-38790149

ABSTRACT

BACKGROUND: Parkinson's disease (PD) is a degenerative neurological condition marked by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta. The precise etiology of PD remains unclear, but emerging evidence suggests a significant role for disrupted autophagy-a crucial cellular process for maintaining protein and organelle integrity. METHODS: This review focuses on the role of non-coding RNAs (ncRNAs) in modulating autophagy in PD. We conducted a comprehensive review of recent studies to explore how ncRNAs influence autophagy and contribute to PD pathophysiology. Special attention was given to the examination of ncRNAs' regulatory impacts in various PD models and patient samples. RESULTS: Findings reveal that ncRNAs are pivotal in regulating key processes associated with PD progression, including autophagy, α-synuclein aggregation, mitochondrial dysfunction, and neuroinflammation. Dysregulation of specific ncRNAs appears to be closely linked to these pathogenic processes. CONCLUSION: ncRNAs hold significant therapeutic potential for addressing autophagy-related mechanisms in PD. The review highlights innovative therapeutic strategies targeting autophagy-related ncRNAs and discusses the challenges and prospective directions for developing ncRNA-based therapies in clinical practice. The insights from this study underline the importance of ncRNAs in the molecular landscape of PD and their potential in novel treatment approaches.


Subject(s)
Autophagy , Parkinson Disease , RNA, Untranslated , Humans , Parkinson Disease/genetics , Parkinson Disease/pathology , Parkinson Disease/metabolism , Autophagy/physiology , Autophagy/genetics , RNA, Untranslated/genetics , Animals
15.
Chem Biol Interact ; 394: 111002, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38604395

ABSTRACT

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.


Subject(s)
Asthma , Bronchitis , Formaldehyde , Pulmonary Fibrosis , Formaldehyde/toxicity , Formaldehyde/adverse effects , Humans , Asthma/chemically induced , Pulmonary Fibrosis/chemically induced , Bronchitis/chemically induced , Animals , Environmental Exposure/adverse effects , Lung/drug effects , Lung/pathology , Pneumonia/chemically induced , Oxidative Stress/drug effects , Inflammation/chemically induced
16.
ACS Omega ; 9(14): 16089-16096, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38617645

ABSTRACT

Human transferrin (Htf) is vital in maintaining iron within the brain cells; any disruption results in the development of neurodegenerative diseases (NDs) and other related pathologies, especially Alzheimer's disease (AD). Ellagic acid (EA), a naturally occurring phenolic antioxidant, possesses neuroprotective potential and is present in a broad variety of fruits and vegetables. The current work explores the binding mechanism of dietary polyphenol, EA, with Htf by a combination of experimental and computational approaches. Molecular docking studies unveiled the binding of EA to Htf with good affinity. Molecular dynamic (MD) simulation further provided atomistic details of the binding process, demonstrating a stable Htf-EA complex formation without causing substantial alterations to the protein's conformation. Furthermore, fluorescence binding measurements indicated that EA forms a high-affinity interaction with Htf. Isothermal titration calorimetric measurements advocated the spontaneous nature of binding and also revealed the binding process to be exothermic. In conclusion, the study deciphered the binding mechanism of EA with Htf. The results demonstrated that EA binds with Htf with an excellent affinity spontaneously, thereby laying the groundwork for potential applications of EA in the realm of therapeutics for NDs in the context of iron homeostasis.

17.
Life Sci ; 345: 122613, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38582393

ABSTRACT

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.


Subject(s)
Brain Neoplasms , Glioblastoma , MicroRNAs , Humans , ErbB Receptors/metabolism , Glioblastoma/drug therapy , Glioblastoma/genetics , Glioblastoma/metabolism , Signal Transduction , MicroRNAs/metabolism , RNA, Untranslated/genetics , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Brain Neoplasms/metabolism
18.
Pathol Res Pract ; 257: 155282, 2024 May.
Article in English | MEDLINE | ID: mdl-38608371

ABSTRACT

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.


Subject(s)
Neoplasms , RNA, Long Noncoding , Receptors, Notch , Signal Transduction , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Neoplasms/genetics , Neoplasms/pathology , Neoplasms/therapy , Neoplasms/metabolism , Receptors, Notch/metabolism , Receptors, Notch/genetics , Signal Transduction/genetics , Gene Expression Regulation, Neoplastic/genetics , Animals
19.
Front Pharmacol ; 15: 1348128, 2024.
Article in English | MEDLINE | ID: mdl-38495092

ABSTRACT

Human transferrin (htf) plays a crucial role in regulating the balance of iron within brain cells; any disruption directly contributes to the development of Neurodegenerative Diseases (NDs) and other related pathologies, especially Alzheimer's Disease (AD). In recent times, a transition towards natural compounds is evident to treat diseases and this shift is mainly attributed to their broad therapeutic potential along with minimal side effects. Capsaicin, a natural compound abundantly found in red and chili peppers, possess neuroprotective potential. The current work targets to decipher the interaction mechanism of capsaicin with htf using experimental and computational approaches. Molecular docking analysis revealed that capsaicin occupies the iron binding pocket of htf, with good binding affinity. Further, the binding mechanism was investigated atomistically using Molecular dynamic (MD) simulation approach. The results revealed no significant alterations in the structure of htf implying the stability of the complex. In silico observations were validated by fluorescence binding assay. Capsaicin binds to htf with a binding constant (K) of 3.99 × 106 M-1, implying the stability of the htf-capsaicin complex. This study lays a platform for potential applications of capsaicin in treatment of NDs in terms of iron homeostasis.

20.
Clin Med Insights Endocrinol Diabetes ; 17: 11795514241235514, 2024.
Article in English | MEDLINE | ID: mdl-38495947

ABSTRACT

Background: The use of ChatGPT and artificial intelligence (AI) in the management of metabolic and endocrine disorders presents both significant opportunities and notable risks. Objectives: To investigate the benefits and risks associated with the application of ChatGPT in managing diabetes and metabolic illnesses by exploring the perspectives of endocrinologists and diabetologists. Methods and materials: The study employed a qualitative research approach. A semi-structured in-depth interview guide was developed. A convenience sample of 25 endocrinologists and diabetologists was enrolled and interviewed. All interviews were audiotaped and verbatim transcribed; then, thematic analysis was used to determine the themes in the data. Results: The findings of the thematic analysis resulted in 19 codes and 9 major themes regarding the benefits of implementing AI and ChatGPT in managing diabetes and metabolic illnesses. Moreover, the extracted risks of implementing AI and ChatGPT in managing diabetes and metabolic illnesses were categorized into 7 themes and 14 codes. The benefits of heightened diagnostic precision, tailored treatment, and efficient resource utilization have potential to improve patient results. Concurrently, the identification of potential challenges, such as data security concerns and the need for AI that can be explained, enables stakeholders to proactively tackle these issues. Conclusions: Regulatory frameworks must evolve to keep pace with the rapid adoption of AI in healthcare. Sustained attention to ethical considerations, including obtaining patient consent, safeguarding data privacy, ensuring accountability, and promoting fairness, remains critical. Despite its potential impact on the human aspect of healthcare, AI will remain an integral component of patient-centered care. Striking a balance between AI-assisted decision-making and human expertise is essential to uphold trust and provide comprehensive patient care.


Regulatory frameworks must evolve to keep pace with the rapid adoption of AI in healthcare. Sustained attention to ethical considerations, including obtaining patient consent, safeguarding data privacy, ensuring accountability, and promoting fairness, remains critical. Despite its potential impact on the human aspect of healthcare, AI will remain an integral component of patient-centered care. The use of ChatGPT in the management of metabolic and endocrine disorders presents both significant opportunities and notable risks. The benefits of heightened diagnostic precision, tailored treatment, and efficient resource utilization have potential to improve patient results. Concurrently, the identification of potential challenges, such as data security concerns and the need for AI that can be explained, enables stakeholders to proactively tackle these issues. Regulatory frameworks must evolve to keep pace with the rapid adoption of AI in healthcare. Sustained attention to ethical considerations, including obtaining patient consent, safeguarding data privacy, ensuring accountability, and promoting fairness, remains critical. Despite its potential impact on the human aspect of healthcare, AI will remain an integral component of patient-centered care. Striking a balance between AI-assisted decision-making and human expertise is essential to uphold trust and provide comprehensive patient care.

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