Despite considering vast majority of the transcribed molecules as merely noise RNA in the last decades, recent advances in the field of molecular biology revealed the mysterious role of long ...non-coding RNAs (lncRNAs), as a massive part of functional non-protein-coding RNAs. As a crucial lncRNA, HOX antisense intergenic RNA (HOTAIR) has been shown to participate in different processes of normal cell development. Aberrant overexpression of this lncRNA contributes to breast cancer progression, through different molecular mechanisms. In this review, we briefly discuss the structure of HOTAIR in the context of genome and impact of this lncRNA on normal human development. We subsequently summarize the potential role of HOTAIR overexpression on different processes of breast cancer development. Ultimately, the relationship of this lncRNA with different therapeutic approaches is discussed.
Inflammatory Bowel Disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract. Though the pathogenesis of IBD remains unclear, diet is increasingly recognized as a ...pivotal factor influencing its onset and progression. Fatty acids, essential components of dietary lipids, play diverse roles in IBD, ranging from anti-inflammatory and immune-regulatory functions to gut-microbiota modulation and barrier maintenance. Short-chain fatty acids (SCFAs), products of indigestible dietary fiber fermentation by gut microbiota, have strong anti-inflammatory properties and are seen as key protective factors against IBD. Among long-chain fatty acids, saturated fatty acids, trans fatty acids, and ω-6 polyunsaturated fatty acids exhibit pro-inflammatory effects, while oleic acid and ω-3 polyunsaturated fatty acids display anti-inflammatory actions. Lipid mediators derived from polyunsaturated fatty acids serve as bioactive molecules, influencing immune cell functions and offering both pro-inflammatory and anti-inflammatory benefits. Recent research has also highlighted the potential of medium- and very long-chain fatty acids in modulating inflammation, mucosal barriers, and gut microbiota in IBD. Given these insights, dietary intervention and supplementation with short-chain fatty acids are emerging as potential therapeutic strategies for IBD. This review elucidates the impact of various fatty acids and lipid mediators on IBD and delves into potential therapeutic avenues stemming from these compounds.
The intra‐ and extracellular functions of ASC specks Franklin, Bernardo S; Latz, Eicke; Schmidt, Florian Ingo
Immunological reviews,
January 2018, 2018-Jan, 2018-01-00, 20180101, Volume:
281, Issue:
1
Journal Article
Peer reviewed
Summary
Inflammasomes are the central signaling hubs of the inflammatory response. They process cytosolic evidence of infection, cell damage, or metabolic disturbances, and elicit a pro‐inflammatory ...response mediated by members of the interleukin‐1 family of cytokines and pyroptotoic cell death. On the molecular level, this is accomplished by the sensor‐nucleated recruitment and oligomerization of the adapter protein ASC. Once a tunable threshold is reached, cooperative assembly of ASC into linear filaments and their condensation into macromolecular ASC specks promotes an all‐or‐none response. These structures are highly regulated and provide a unique signaling platform or compartment to control the activity of caspase‐1 and likely other effectors. Emerging evidence indicates that ASC specks are also released from inflammasome‐activated cells and accumulate in inflamed tissues, where they can continue to mature cytokines or be internalized by surrounding cells to further nucleate ASC specks in their cytosol. Little is known about the mechanisms governing ASC speck release, uptake, and endosomal escape, as well as its contribution to inflammation and disease. Here, we describe the different outcomes of inflammasome activation and discuss the potential function of extracellular ASC specks. We highlight gaps in our understanding of this central process of inflammation, which may have direct consequences on the modulation of host responses and chronic inflammation.
The epidermis, the outermost layer of the skin, serves as a protective barrier against external factors. Epidermal differentiation, a tightly regulated process essential for epidermal homeostasis, ...epidermal barrier formation and skin integrity maintenance, is orchestrated by several players, including signaling molecules, calcium gradient and junctional complexes such as gap junctions (GJs). GJ proteins, known as connexins facilitate cell-to-cell communication between adjacent keratinocytes. Connexins can function as either hemichannels or GJs, depending on their interaction with other connexons from neighboring keratinocytes. These channels enable the transport of metabolites, cAMP, microRNAs, and ions, including Ca
, across cell membranes. At least ten distinct connexins are expressed within the epidermis and mutations in at least five of them has been linked to various skin disorders. Connexin mutations may cause aberrant channel activity by altering their synthesis, their gating properties, their intracellular trafficking, and the assembly of hemichannels and GJ channels. In addition to mutations, connexin expression is dysregulated in other skin conditions including psoriasis, chronic wound and skin cancers, indicating the crucial role of connexins in skin homeostasis. Current treatment options for conditions with mutant or altered connexins are limited and primarily focus on symptom management. Several therapeutics, including non-peptide chemicals, antibodies, mimetic peptides and allele-specific small interfering RNAs are promising in treating connexin-related skin disorders. Since connexins play crucial roles in maintaining epidermal homeostasis as shown with linkage to a range of skin disorders and cancer, further investigations are warranted to decipher the molecular and cellular alterations within cells due to mutations or altered expression, leading to abnormal proliferation and differentiation. This would also help characterize the roles of each isoform in skin homeostasis, in addition to the development of innovative therapeutic interventions. This review highlights the critical functions of connexins in the epidermis and the association between connexins and skin disorders, and discusses potential therapeutic options.
Apresentações e palestras feitas no Simpósio Internacional sobre Doença De Hodgkin, realizado no Instituto Nacional de Câncer no Rio de Janeiro — 16 a 20 de Janeiro de 1967.
•Spotlight on key advances in our understanding of molecular dysfunction and HD.•Description of novel pathways influencing intracellular levels of mutant huntingtin.•Exciting new therapeutic ...strategies involving gene silencing and small molecules.•Emphasis on molecular similarities between HD and other neurological disorders.
Huntington's disease (HD) is a progressive neurodegenerative disorder for which no disease modifying treatments exist. Many molecular changes and cellular consequences that underlie HD are observed in other neurological disorders, suggesting that common pathological mechanisms and pathways may exist. Recent findings have enhanced our understanding of the way cells regulate and respond to expanded polyglutamine proteins such as mutant huntingtin. These studies demonstrate that in addition to effects on folding, aggregation, and clearance pathways, a general transcriptional mechanism also dictates the expression of polyglutamine proteins. Here, we summarize the key pathways and networks that are important in HD in the context of recent therapeutic advances and highlight how their interplay may be of relevance to other protein folding disorders.
Since the COVID-19 pandemic alarm was made by the severe acute respiratory syndrome (SARS)-coronavirus (CoV) 2, several institutions and agencies have pursued to clarify the viral virulence and ...infectivity. The fast propagation of this virus leads to an unprecedented rise in the number of cases worldwide. COVID-19 virus is exceptionally contagious that spreads through droplets, respiratory secretions, and direct contact. The enveloped, single-stranded RNA virus has a specific envelop region called (S) region encoding (S protein) that specifically binds to the host cell receptor. Viral infection requires receptors' participation on the host cell membrane's surface, a key- step for the viral invasion of susceptible cells. Recently, the Italian alpha 1 antitrypsin Registry results showed a close geographic distribution of positive cases like the one recorded for SARS -CoV-2 infection. AAT deficient patients presented with the highest infection rates. They were giving attention to alpha 1 antitrypsin AAT's role in COVID-19 infection. Alpha 1 antitrypsin deficiency (AATD) is undoubtedly the most common genetic condition in adults. AATD is characterized by decreased serum levels or impaired AAT action, raising the risk of developing many diseases, particularly pulmonary emphysema cirrhosis of the liver. This review will discuss the main immunological properties that AAT has as a protective agent against the infection and possible therapeutic application.
Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the BCR-ABL oncoprotein, known to drive leukemogenesis by orchestrating multiple signaling pathways ultimately ...involved in cell survival. Despite successful response rates of CML patients to tyrosine kinase inhibitors (TKIs), resistance eventually arises due to BCR-ABL-dependent and independent mechanisms. Survivin is an inhibitor of apoptosis protein acting in the interface between apoptosis deregulation and cell cycle progression. In CML, high levels of survivin have been associated with late stages of disease and therapy resistance. In this review, we provide an overview of important aspects concerning survivin subcellular localization and expression pattern in CML patients and cell lines. Moreover, we highlight the relevance of molecular networks involving survivin for disease progression and treatment resistance. Finally, we discuss the mechanisms accounting for survivin overexpression, as well as novel therapeutic interventions that have been designed to counteract survivin-associated malignancy in CML.
To determine the functional impact of oral Vitamin A supplementation in patients with intermediate age-related macular degeneration (iAMD) with and without reticular pseudodrusen (RPD) demonstrating ...dysfunction in dark adaptation (DA).
Five patients with iAMD and without RPD (AMD group; mean ± SD age 78.0 ± 4.7 years) and seven with RPD (RPD group; age 74.1 ± 11.2 years) were supplemented with 16,000 IU of Vitamin A palmitate for 8 weeks. Assessment at baseline, 4, 8 and 12 weeks included scotopic thresholds, dark adaptation, best-corrected and low luminance visual acuities and the low-luminance quality of life questionnaire.
In the linear mixed model, RIT improved significantly in the AMD group (mean95% CI change -1.1 min -1.8; -0.5 after 4 weeks (p<0.001) and -2.2 min-2.9; 1.6 after 8 weeks of Vitamin A supplementation (p<0.001). The DA cone plateau also significantly improved (i.e. more sensitive cone threshold) at 4 and 8 weeks (p=0.026 and p=0.001). No other parameters improved in the AMD group and there was no significant improvement in any parameter in the RPD group despite significantly elevated serum Vitamin A levels measurable in both groups after supplementation (p=0.024 and p=0.013).
Supplementation with 16,000IU Vitamin A, a lower dose than used in previous studies, partially overcomes the pathophysiologic functional changes in AMD eyes. The lack of improvement in the RPD group may indicate structural impediments to increasing vitamin A availability in these patients, and/or may reflect the higher variability observed in the functional parameters for this group.
The physiological balance between excitation and inhibition in the brain is significantly affected in Alzheimer's disease (AD). Several neuroactive compounds and their signaling pathways through ...various types of receptors are crucial in brain homeostasis, among them glutamate and γ-aminobutyric acid (GABA). Activation of microglial receptors regulates the immunological response of these cells, which in AD could be neuroprotective or neurotoxic. The novel research approaches revealed the complexity of microglial function, including the interplay with other cells during neuroinflammation and in the AD brain. The purpose of this review is to describe the role of several proteins and multiple receptors on microglia and neurons, and their involvement in a communication network between cells that could lead to different metabolic loops and cell death/survival. Our review is focused on the role of glutamatergic, GABAergic signaling in microglia-neuronal cross-talk in AD and neuroinflammation. Moreover, the significance of AD-related neurotoxic proteins in glutamate/GABA-mediated dialogue between microglia and neurons was analyzed in search of novel targets in neuroprotection, and advanced pharmacological approaches.
PDF
