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1.
Cureus ; 16(6): e61879, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38978926

RESUMO

Background Hemophagocytic lymphohistiocytosis (HLH) is an uncommon, potentially fatal condition caused by high immune activation. The present study aimed to identify the clinical manifestations, geographic distribution, and associated pathogenic genetic mutations of HLH in Saudi Arabia. Method A retrospective cross-sectional study was conducted at King Fahad Medical City (KFMC), with a total of 59 patients diagnosed with HLH in the period between 2006 and 2018. All genetic results and clinical and biochemical data were retrieved and statistically analyzed using IBM SPSS Statistics for Windows, Version 25 (Released 2017; IBM Corp., Armonk, New York, United States). Results The results revealed that 48 patients (81.4%) had 15 pathogenic mutations of primary HLH whereas 8 (13.6%) patients had no genetic mutation. The most common variant mutation identified was c.1430C>T of the STXBP2 gene (42.4% of total patients), followed by c.1122G>A of the PRF1 gene (10.2% of patients), which demonstrated a distinctive geographic and tribal association. Patients with RAB27A mutation tend to present at an older age than the others with a median age of presentation of 5.5 months vs 2 months for patients with PRF1 mutations. No significant differences in clinical features were observed among the various groups. Conclusion This study highlights the incidence of genetic mutations among the Saudi population with HLH. The STXBP2 is the most common mutation followed by PRF1 mutations, many mutation variants are associated with a distinctive tribal and geographic association.

2.
Pathol Res Pract ; 260: 155443, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38981348

RESUMO

Glioblastoma (GB) remains a formidable challenge and requires new treatment strategies. The vital part of the Ubiquitin-proteasome system (UPS) in cellular regulation has positioned it as a potentially crucial target in GB treatment, given its dysregulation oncolines. The Ubiquitin-specific proteases (USPs) in the UPS system were considered due to the garden role in the cellular processes associated with oncolines and their vital function in the apoptotic process, cell cycle regulation, and autophagy. The article provides a comprehensive summary of the evidence base for targeting USPs as potential factors for neoplasm treatment. The review considers the participation of the UPS system in the development, resulting in the importance of p53, Rb, and NF-κB, and evaluates specific goals for therapeutic administration using midnight proteasomal inhibitors and small molecule antagonists of E1 and E2 enzymes. Despite the slowed rate of drug creation, recent therapeutic discoveries based on USP system dynamics hold promise for specialized therapies. The review concludes with an analysis of future wanderers and the feasible effects of targeting USPs on personalized GB therapies, which can improve patient hydration in this current and unattractive therapeutic landscape. The manuscript emphasizes the possibility of USP oncogene therapy as a promising alternative treatment line for GB. It stresses the direct creation of research on the medical effectiveness of the approach.

3.
EXCLI J ; 23: 570-599, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38887390

RESUMO

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).

4.
Poult Sci ; 103(8): 103914, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38905757

RESUMO

Delivering natural antioxidants via in ovo feeding holds promise for enhancing the antioxidant status and performance of chickens. Therefore, The objective of this study was to evaluate the impacts of in ovo feeding during early embryonic development using grape pomace extract as a natural antioxidant on hatchability, productive performance, immune response, and antioxidant status in broilers. A total of 900 fertile broiler eggs from the Arbor Acres strain were utilized. Each egg was individually weighed, with egg weights ranging from 61.88 ± 3 g. On the 17.5th d of incubation (DOI), the fertile eggs were divided into 6 groups. The first treatment group was untreated and designated as the control (C). The second group was the sham group (Sh), receiving a simulated injection. The third group, designated as the vehicle group (V), was injected with 100 µl of dimethyl sulfoxide (DMSO). The fourth group received an injection of 100 µL of grape pomace dissolved in DMSO at a concentration of 2 mg (T2). Similarly, the fifth and sixth groups were injected with 100 µL of grape pomace dissolved in DMSO at concentrations of 4 mg and 6 mg, (T4), (T6) respectively. Subsequently, all groups were raised under uniform conditions in terms of management, environment, and nutrition till 5 wk of age. The grape pomace extract (GPE), obtained is rich in total phenolic content (16.07 mg/g), total flavonoid content (7.42 mg/g), and total anthocyanin (8.37 mg/g). Grape pomace extract has exhibited significant antioxidant properties as evidenced by its effectiveness in DPPH scavenging and reducing power assays. Significant improvements in body weight at hatch were observed with in ovo feeding of grape pomace extract, particularly at the 4 mg level, surpassing the effectiveness of the 2 mg and 6 mg grape pomace levels, and this enhancement in body weight continued until the age of 5 wk. GPE injection also led to a significant reduction in cholesterol levels, with the lowest levels recorded for the T4 group. Plasma total Antioxidant Capacity (TAC) levels were significantly elevated in groups treated with T4, T6, and T2 compared to the control group. Conversely, the control group showed a significant increase (P < 0.01) in plasma malondialdehyde (MDA) levels. The immune response of hatched chicks from grape pomace extract-injected groups, especially the T4 group, exhibited improvement through increased IgM and IgG. These findings demonstrate that in ovo feeding of GPE, particularly at a dosage of 4 mg, enhances growth performance, immune response, and antioxidant status in hatched chicks. Thus, administering natural antioxidants, such as grape pomace extract, to developing broiler embryos via in ovo feeding could serve as a valuable strategy for enhancing the subsequent post-hatch productive performance, as well as bolstering the antioxidant and immunological status of broiler chicks.

5.
Brain Res ; 1841: 149089, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38880410

RESUMO

Epilepsy is a prevalent neurological illness which is linked with high worldwide burdens. Oxidative stress (OS) is recognized to be among the contributors that trigger the advancement of epilepsy, affecting neuronal excitability and synaptic transmission. Various types of non-coding RNAs (ncRNAs) are known to serve vital functions in many disease mechanisms, including epilepsy. The current review sought to understand better the mechanisms through which these ncRNAs regulate epilepsy's OS-related pathways. We investigated the functions of microRNAs in controlling gene expression at the post-translatory stage and their involvement in OS and neuroinflammation. We also looked at the different regulatory roles of long ncRNAs, including molecular scaffolding, enhancer, and transcriptional activator, during OS. Circular RNAs and their capability to act as miRNA decoys and their consequential impact on epilepsy development were also explored. Our review aimed to improve the current understanding of novel therapies for epilepsy based on the role of ncRNAs in OS pathways. We also demonstrated the roles of ncRNAs in epilepsy treatment and diagnosis, explaining that these molecules play vital roles that could be used in therapy as biomarkers.

6.
Patient Prefer Adherence ; 18: 1077-1094, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38854480

RESUMO

Objective: Chronic diseases hold the potential to worsen the overall health of patients by limiting their functional status, productivity, and capacity to live well, affecting their overall health-related quality of life (HRQoL). The purpose of the study was to assess the HRQoL of individuals with chronic diseases residing in the Al-Jouf region of Saudi Arabia. Furthermore, the current study also sought to ascertain the impact of multimorbidity and the duration of illness on HRQoL. Material and Methods: A cross-sectional study was conducted among the residents of Al-Jouf region for a period of 6 months. A self-administered EuroQoL (EQ-5D-5L) study tool was used. Appropriate statistical analysis was conducted to ascertain the relationship between various variables and HRQoL. Results: A total of 500 out of 562 participants completed the study, with a response rate of 88.97%. Participants had a mean age of 46.15 ± 16.79 years, and the majority were female (n = 299; 59.80%). A mean HRQoL score of 0.82 ± 0.20 was reported, poorest in patients with kidney failure (0.65 ± 0.26) and highest in hepatitis. However, nearly half of the participants had diabetes mellitus type II (n = 205, 39.20%). Patients aged <30 years (OR: 0.109; p = 0.002), male participants (OR: 0.053; p < 0.001), no disability (OR: 0.143; p = 0.002), and <2 comorbid diseases (0.84 ± 0.18; p < 0.001) reported better QoL. Additionally, comorbid conditions such as DM, prolong the duration of the overall illness (14.19 ± 7.67 years). Overall, imperfect health (n = 390, 78%) was reported by the study participants. Conclusion: The present study provided preliminary data about the current HRQoL status of individuals with imperfect health and lower HRQoL. In the future, large-scale longitudinal studies are required to investigate the most prevalent chronic diseases, their associations, and change in HRQoL, as there is a dearth of information in the Saudi population.

7.
Ageing Res Rev ; 98: 102327, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38734148

RESUMO

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.


Assuntos
Autofagia , Neurônios Dopaminérgicos , Doença de Parkinson , RNA não Traduzido , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Humanos , Autofagia/fisiologia , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , RNA não Traduzido/genética , Animais
8.
ACS Omega ; 9(18): 19741-19755, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38737049

RESUMO

In recent years, the development of biomaterials from green organic sources with nontoxicity and hyposensitivity has been explored for a wide array of biotherapeutic applications. Polyphenolic compounds have unique structural features, and self-assembly by oxidative coupling allows molecular species to rearrange into complex biomaterial that can be used for multiple applications. Self-assembled polyphenolic structures, such as hollow spheres, can be designed to respond to various chemical and physical stimuli that can release therapeutic drugs smartly. The self-assembled metallic-phenol network (MPN) has been used for modulating interfacial properties and designing biomaterials, and there are several advantages and challenges associated with such biomaterials. This review comprehensively summarizes current challenges and prospects of self-assembled polyphenolic hollow spheres and MPN coatings and self-assembly for biomedical applications.

9.
JAAD Case Rep ; 47: 113-114, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38737619
10.
CNS Neurosci Ther ; 30(5): e14763, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38790149

RESUMO

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.


Assuntos
Autofagia , Doença de Parkinson , RNA não Traduzido , Humanos , Doença de Parkinson/genética , Doença de Parkinson/patologia , Doença de Parkinson/metabolismo , Autofagia/fisiologia , Autofagia/genética , RNA não Traduzido/genética , Animais
11.
Pathol Res Pract ; 258: 155329, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38692083

RESUMO

Fibrosarcoma is a challenging cancer originating from fibrous tissues, marked by aggressive growth and limited treatment options. The discovery of non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and small interfering RNAs (siRNAs), has opened new pathways for understanding and treating this malignancy. These ncRNAs play crucial roles in gene regulation, cellular processes, and the tumor microenvironment. This review aims to explore the impact of ncRNAs on fibrosarcoma's pathogenesis, progression, and resistance to treatment, focusing on their mechanistic roles and therapeutic potential. A comprehensive review of literature from databases like PubMed and Google Scholar was conducted, focusing on the dysregulation of ncRNAs in fibrosarcoma, their contribution to tumor growth, metastasis, drug resistance, and their cellular pathway interactions. NcRNAs significantly influence fibrosarcoma, affecting cell proliferation, apoptosis, invasion, and angiogenesis. Their function as oncogenes or tumor suppressors makes them promising biomarkers and therapeutic targets. Understanding their interaction with the tumor microenvironment is essential for developing more effective treatments for fibrosarcoma. Targeting ncRNAs emerges as a promising strategy for fibrosarcoma therapy, offering hope to overcome the shortcomings of existing treatments. Further investigation is needed to clarify specific ncRNAs' roles in fibrosarcoma and to develop ncRNA-based therapies, highlighting the significance of ncRNAs in improving patient outcomes in this challenging cancer.


Assuntos
Fibrossarcoma , RNA não Traduzido , Humanos , Fibrossarcoma/genética , Fibrossarcoma/patologia , RNA não Traduzido/genética , Regulação Neoplásica da Expressão Gênica , Oncogenes/genética , Microambiente Tumoral/genética , Genes Supressores de Tumor/fisiologia , MicroRNAs/genética , MicroRNAs/metabolismo , Animais
12.
Pathol Res Pract ; 258: 155333, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38723325

RESUMO

Long non-coding RNAs (lncRNAs) are a diverse class of RNA molecules that do not code for proteins but play critical roles in gene regulation. One such role involves the modulation of cell cycle progression and proliferation through interactions with cyclin-dependent kinases (CDKs), key regulators of cell division. Dysregulation of CDK activity is a hallmark of cancer, contributing to uncontrolled cell growth and tumor formation. These lncRNA-CDK interactions are part of a complex network of molecular mechanisms underlying cancer pathogenesis, involving various signaling pathways and regulatory circuits. Understanding the interplay between lncRNAs, CDKs, and cancer biology holds promise for developing novel therapeutic strategies targeting these molecular targets for more effective cancer treatment. Furthermore, targeting CDKs, key cell cycle progression and proliferation regulators, offers another avenue for disrupting cancer pathways and overcoming drug resistance. This can open new possibilities for individualized treatment plans and focused therapeutic interventions.


Assuntos
Quinases Ciclina-Dependentes , Progressão da Doença , Neoplasias , RNA Longo não Codificante , Humanos , Neoplasias/genética , Neoplasias/patologia , Neoplasias/enzimologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/metabolismo , Regulação Neoplásica da Expressão Gênica , Animais , Transdução de Sinais/genética , Proliferação de Células/genética , Ciclo Celular/genética , Ciclo Celular/fisiologia
13.
Pathol Res Pract ; 258: 155303, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38728793

RESUMO

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.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , RNA não Traduzido , Transdução de Sinais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Transdução de Sinais/genética , RNA não Traduzido/genética , Regulação Neoplásica da Expressão Gênica/genética , RNA Circular/genética , RNA Circular/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
14.
Adv Exp Med Biol ; 1451: 337-354, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38801589

RESUMO

Poxviruses target innate immunity mediators such as tumor necrosis factors, interleukins, interferons, complement, and chemokines. It also targets adaptive immunity such as CD4+ T cells, CD4+ T cells, and B cells. Emerging of the recent epidemic of monkeypox virus (MPXV), a zoonotic disease native to Central and Western Africa, besides the lack of permitted treatments for poxviruses infections, encouraged researchers to identify effective inhibitors to help in preventing and treating poxviruses infections. Natural bioactive components, particularly polyphenolics, are promising for creating powerful antioxidants, anti-inflammatory, immune-stimulating, and antiviral agents. As a result, they are potentially effective therapies for preventing and treating viral diseases, such as infections caused by poxviruses including the recent pandemic MPXV. Polyphenolics: rosmarinic acid, caffeic acid, resveratrol, quercitrin, myricitrin, gingerol, gallotannin, and propolis-benzofuran A, as well as isoquinoline alkaloids: galanthamine and thalimonine represent prospective antiviral agents against MPXV, they can inhibit MPXV and other poxviruses via targeting different viral elements including DNA Topoisomerase I (TOP1), Thymidine Kinase (TK), serine/threonine protein kinase (Ser/Thr kinase), and protein A48R. The bioactive extracts of different traditional plants including Guiera senegalensis, Larrea tridentata, Sarracenia purpurea, Kalanchoe pinnata (Lam.) Pers., Zingiber officinale Roscoe, Quercus infectoria, Rhus chinensis, Prunella vulgaris L., Salvia rosmarinus, and Origanum vulgare also can inhibit the growth of different poxviruses including MPXV, vaccinia virus (VACV), variola virus, buffalopox virus, fowlpox virus, and cowpox virus. There is an urgent need for additional molecular studies to identify and confirm the anti-poxviruses properties of various natural bioactive components, especially those that showed potent antiviral activity against other viruses.


Assuntos
Antivirais , Infecções por Poxviridae , Poxviridae , Humanos , Infecções por Poxviridae/tratamento farmacológico , Infecções por Poxviridae/virologia , Infecções por Poxviridae/imunologia , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Antivirais/química , Poxviridae/efeitos dos fármacos , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/uso terapêutico , Agentes de Imunomodulação/química , Terapias Complementares/métodos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Produtos Biológicos/química
15.
Life Sci ; 345: 122613, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38582393

RESUMO

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.


Assuntos
Neoplasias Encefálicas , Glioblastoma , MicroRNAs , Humanos , Receptores ErbB/metabolismo , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Transdução de Sinais , MicroRNAs/metabolismo , RNA não Traduzido/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo
16.
Chem Biol Interact ; 394: 111002, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38604395

RESUMO

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.


Assuntos
Asma , Bronquite , Formaldeído , Fibrose Pulmonar , Formaldeído/toxicidade , Formaldeído/efeitos adversos , Humanos , Asma/induzido quimicamente , Fibrose Pulmonar/induzido quimicamente , Bronquite/induzido quimicamente , Animais , Exposição Ambiental/efeitos adversos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pneumonia/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Inflamação/induzido quimicamente
17.
Pathol Res Pract ; 256: 155260, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38493726

RESUMO

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.


Assuntos
Arsênio , Poluentes Ambientais , Neoplasias Pulmonares , Metais Pesados , Humanos , Cádmio/análise , Arsênio/toxicidade , Arsênio/análise , Poluentes Ambientais/toxicidade , Poluentes Ambientais/análise , Ecossistema , Metais Pesados/toxicidade , Metais Pesados/metabolismo , Pulmão/metabolismo
18.
Pathol Res Pract ; 256: 155259, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38503004

RESUMO

Circular RNAs (circRNAs) have been recognized as key components in the intricate regulatory network of the KRAS pathway across various cancers. The KRAS pathway, a central signalling cascade crucial in tumorigenesis, has gained substantial emphasis as a possible therapeutic target. CircRNAs, a subgroup of non-coding RNAs known for their closed circular arrangement, play diverse roles in gene regulation, contributing to the intricate landscape of cancer biology. This review consolidates existing knowledge on circRNAs within the framework of the KRAS pathway, emphasizing their multifaceted functions in cancer progression. Notable circRNAs, such as Circ_GLG1 and circITGA7, have been identified as pivotal regulators in colorectal cancer (CRC), influencing KRAS expression and the Ras signaling pathway. Aside from their significance in gene regulation, circRNAs contribute to immune evasion, apoptosis, and drug tolerance within KRAS-driven cancers, adding complexity to the intricate interplay. While our comprehension of circRNAs in the KRAS pathway is evolving, challenges such as the diverse landscape of KRAS mutant tumors and the necessity for synergistic combination therapies persist. Integrating cutting-edge technologies, including deep learning-based prediction methods, holds the potential for unveiling disease-associated circRNAs and identifying novel therapeutic targets. Sustained research efforts are crucial to comprehensively unravel the molecular mechanisms governing the intricate interplay between circRNAs and the KRAS pathway, offering insights that could potentially revolutionize cancer diagnostics and treatment strategies.


Assuntos
Neoplasias , RNA Circular , Humanos , RNA Circular/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Neoplasias/genética , Processos Neoplásicos
19.
Pathol Res Pract ; 256: 155257, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38537524

RESUMO

Circular RNAs (circRNAs) constitute a recently identified category of closed continuous loop RNA transcripts, serving as a subset of competing endogenous RNAs (ceRNAs) with the capacity to modulate genes by acting as microRNA sponges. In the context of cancer growth, numerous investigations have explored the potential functions of circRNAs, revealing their diverse functions either as oncogenes, promoting cancer progression, or as tumor suppressors, mitigating disease development. Among these, circRNA ADAM9 (Circ-ADAM9) is now recognized as an important player in a variety of mechanisms, both physiological and pathological, especially in cancer. The aberrant expression of Circ-ADAM9 has been observed across multiple human malignancies, implying a significant involvement in tumorigenesis. This comprehensive review aims to synthesize recent findings elucidating the function of Circ-ADAM9 in many malignancies. Additionally, the review explores the possibility of Circ-ADAM9 as a valuable biomarker, offering insights into its prognostic, diagnostic, and therapeutic implications. By summarizing the latest discoveries in this field, the review contributes to our understanding of the multifaceted contribution of Circ-ADAM9 in tumor biology and its potential applications in clinical settings.


Assuntos
MicroRNAs , Neoplasias , Humanos , RNA Circular/genética , Neoplasias/genética , MicroRNAs/genética , Carcinogênese/genética , Transformação Celular Neoplásica , Proteínas de Membrana/genética , Proteínas ADAM
20.
Pathol Res Pract ; 256: 155224, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38452584

RESUMO

Sepsis, a potentially fatal illness caused by an improper host response to infection, remains a serious problem in the world of healthcare. In recent years, the role of ncRNA has emerged as a pivotal aspect in the intricate landscape of cellular regulation. The exploration of ncRNA-mediated regulatory networks reveals their profound influence on key molecular pathways orchestrating pyroptotic responses during septic conditions. Through a comprehensive analysis of current literature, we navigate the diverse classes of ncRNAs, including miRNAs, lncRNAs, and circRNAs, elucidating their roles as both facilitators and inhibitors in the modulation of pyroptotic processes. Furthermore, we highlight the potential diagnostic and therapeutic implications of targeting these ncRNAs in the context of sepsis, aiming to cover the method for novel and effective strategies to mitigate the devastating consequences of septic pathogenesis. As we unravel the complexities of this regulatory axis, a deeper understanding of the intricate crosstalk between ncRNAs and pyroptosis emerges, offering promising avenues for advancing our approach to sepsis intervention. The intricate pathophysiology of sepsis is examined in this review, which explores the dynamic interaction between ncRNAs and pyroptosis, a highly regulated kind of programmed cell death.


Assuntos
MicroRNAs , RNA Longo não Codificante , Sepse , Humanos , Piroptose/fisiologia , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , MicroRNAs/genética , RNA Longo não Codificante/genética
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