scholarly journals Epidermolysis Bullosa-Associated Squamous Cell Carcinoma: From Pathogenesis to Therapeutic Perspectives

2019 ◽  
Vol 20 (22) ◽  
pp. 5707 ◽  
Author(s):  
Angelo Giuseppe Condorelli ◽  
Elena Dellambra ◽  
Elena Logli ◽  
Giovanna Zambruno ◽  
Daniele Castiglia
Keyword(s):  
Squamous Cell ◽  
Epidermolysis Bullosa ◽  
Genetic Determinants ◽  
Therapeutic Approaches ◽  
Molecular Events ◽  
Genes Encoding ◽  
Skin Fragility ◽  
Serious Disease ◽  
Almost All

Epidermolysis bullosa (EB) is a heterogeneous group of inherited skin disorders determined by mutations in genes encoding for structural components of the cutaneous basement membrane zone. Disease hallmarks are skin fragility and unremitting blistering. The most disabling EB (sub)types show defective wound healing, fibrosis and inflammation at lesional skin. These features expose patients to serious disease complications, including the development of cutaneous squamous cell carcinomas (SCCs). Almost all subjects affected with the severe recessive dystrophic EB (RDEB) subtype suffer from early and extremely aggressive SCCs (RDEB-SCC), which represent the first cause of death in these patients. The genetic determinants of RDEB-SCC do not exhaustively explain its unique behavior as compared to low-risk, ultraviolet-induced SCCs in the general population. On the other hand, a growing body of evidence points to the key role of tumor microenvironment in initiation, progression and spreading of RDEB-SCC, as well as of other, less-investigated, EB-related SCCs (EB-SCCs). Here, we discuss the recent advances in understanding the complex series of molecular events (i.e., fibrotic, inflammatory, and immune processes) contributing to SCC development in EB patients, cross-compare tumor features in the different EB subtypes and report the most promising therapeutic approaches to counteract or delay EB-SCCs.

scholarly journals Autophagy Intertwines with Different Diseases—Recent Strategies for Therapeutic Approaches

Diseases ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 15 ◽  
Author(s):  
Janani Ramesh ◽  
Larance Ronsard ◽  
Anthony Gao ◽  
Bhuvarahamurthy Venugopal
Keyword(s):  
Inflammatory Diseases ◽  
Therapeutic Strategies ◽  
Open Reading Frames ◽  
Signaling Cascades ◽  
Progression Rate ◽  
Therapeutic Approaches ◽  
Genes Encoding ◽  
Novel Therapeutic Strategies ◽  
Reading Frames

Autophagy is a regular and substantial “clear-out process” that occurs within the cell and that gets rid of debris that accumulates in membrane-enclosed vacuoles by using enzyme-rich lysosomes, which are filled with acids that degrade the contents of the vacuoles. This machinery is well-connected with many prevalent diseases, including cancer, HIV, and Parkinson’s disease. Considering that autophagy is well-known for its significant connections with a number of well-known fatal diseases, a thorough knowledge of the current findings in the field is essential in developing therapies to control the progression rate of diseases. Thus, this review summarizes the critical events comprising autophagy in the cellular system and the significance of its key molecules in manifesting this pathway in various diseases for down- or upregulation. We collectively reviewed the role of autophagy in various diseases, mainly neurodegenerative diseases, cancer, inflammatory diseases, and renal disorders. Here, some collective reports on autophagy showed that this process might serve as a dual performer: either protector or contributor to certain diseases. The aim of this review is to help researchers to understand the role of autophagy-regulating genes encoding functional open reading frames (ORFs) and its connection with diseases, which will eventually drive better understanding of both the progression and suppression of different diseases at various stages. This review also focuses on certain novel therapeutic strategies which have been published in the recent years based on targeting autophagy key proteins and its interconnecting signaling cascades.

A Comprehensive Study of miRNAs in Parkinson’s Disease: Diagnostics and Therapeutic Approaches

2022 ◽  
Vol 21 ◽  
Author(s):  
Saima Owais ◽  
Yasir Hasan Siddique
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lewy Bodies ◽  
Alpha Synuclein ◽  
Therapeutic Approaches ◽  
Molecular Events ◽  
Disease Diagnostics ◽  
Therapeutic Molecules ◽  
Comprehensive Study

Abstract: Parkinson’s disease (PD) is the second most debilitating neurodegenerative movement disorder. It is characterized by the presence of fibrillar alpha-synuclein amassed in the neurons, known as Lewy bodies. Certain cellular and molecular events are involved leading to the degeneration of dopaminergic neurons. However, the origin and implication of such events are still uncertain. Nevertheless, the role of microRNAs (miRNAs) as important biomarkers and therapeutic molecules is unquestionable. The most challenging task by far in PD treatment has been its late diagnosis followed by therapeutics. miRNAs are an emerging hope to meet the need of early diagnosis, thereby promising an improved movement symptom and prolonged life of the patients. The continuous efforts in discovering the role of miRNAs could be made possible by the utilisation of various animal models of PD. These models help us to understand insights into the mechanism of the disease. Moreover, miRNAs have been surfaced as therapeutically important molecules with distinct delivery systems enhancing their success rate. This review aims at providing an outline of different miRNAs implicated in either PD-associated gene regulation or involved in therapeutics.

Differentiating haemostasis from thrombosis for therapeutic benefit

2013 ◽  
Vol 110 (11) ◽  
pp. 859-867 ◽  
Author(s):  
James D. McFadyen ◽  
Shaun P. Jackson
Keyword(s):  
Arterial Thrombosis ◽  
Platelet Reactivity ◽  
Thrombus Formation ◽  
Bleeding Risk ◽  
Therapeutic Benefit ◽  
Therapeutic Approaches ◽  
Molecular Events ◽  
Heterogeneous Nature ◽  
Flow Changes

SummaryThe central role of platelets in the formation of the primary haemostatic plug as well as in the development of arterial thrombosis is well defined. In general, the molecular events underpinning these processes are broadly similar. Whilst it has long been known that disturbances in blood flow, changes in platelet reactivity and enhanced coagulation reactions facilitate pathological thrombus formation, the precise details underlying these events remain incompletely understood. Intravital microscopy studies have highlighted the dynamic and heterogeneous nature of thrombus development and demonstrated that there are considerable spatiotemporal differences in the activation states of platelets within a forming thrombus. In this review we will consider the factors regulating the activation state of platelets in a developing thrombus and discuss how specific prothrombotic factors may influence this process, leading to excessive thrombus propagation. We will also discuss some potentially novel therapeutic approaches that may reduce excess thrombus development whilst minimising bleeding risk.

scholarly journals Immunotherapy in head and neck squamous cell carcinoma and rare head and neck malignancies

2021 ◽  
Vol 2 (6) ◽  
Author(s):  
Stefano Cavalieri ◽  
Daria Maria Filippini ◽  
Arianna Ottini ◽  
Cristiana Bergamini ◽  
Carlo Resteghini ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Checkpoint Inhibitors ◽  
Neck Squamous Cell Carcinoma ◽  
Therapeutic Approaches ◽  
Dismal Prognosis ◽  
Genomic Landscape

The dismal prognosis of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) prompted recent advances in the field of therapeutic approaches beyond cytotoxic cancer therapy. In recent years, the deeper and increasing knowledge on the genomic landscape and the upcoming new data on immunotherapy enacted by HNSCCs have led to successful therapeutic targeting of the immune system. Immune checkpoint inhibitors (ICIs) have changed state of the art in R/M patients and could have a potential role even in early disease. The purpose of this work is to summarize the role of immunotherapy for R/M HNSCC in clinical practice, with insights about future perspectives. Updated immunotherapy results in other R/M head and neck cancers such as thyroid, salivary glands, nasopharynx, sinonasal cancers, and nuclear protein in testis (NUT) are presented.

scholarly journals Genetically modified animal models and Osteoimmunology

2017 ◽  
Vol 61 (3) ◽  
pp. 236
Author(s):  
E. DOUNI (Ε.ΝΤΟΥΝΗ)
Keyword(s):  
Mouse Models ◽  
Dna Sequences ◽  
Mouse Genome ◽  
Genetically Modified ◽  
Therapeutic Approaches ◽  
Pathogenic Mechanisms ◽  
Technological Advances ◽  
Continuous Interaction ◽  
Almost All

The completion of the human and mouse genome DNA sequences easily enabled chromosomal localization for each gene, whereas the role of each gene remains largely unknown. Functional Genomics constitutes the new area of Molecular Biology that aims to identify the function(s) of each gene in order to understand the pathogenic mechanisms in various human diseases. The mouse has been extensively used more than any other animal organism in biomedical research, because, except for the similarities it displays with humans, its genome can be genetically modified rather easily. During the last two decades, technological advances enable almost all kinds of mutations in the mouse genome. More specifically, the study of genetically modified mice revealed the continuous interaction between various systems within the organism, such as the interplay between the skeletal and the immune system, introducing the interdisciplinary area of Osteoimmunology. The cytokine RANKL constitutes the key molecule in Osteoimmunology, by regulating osteoclastogenesis, while deregulation of RANKL expression leads to diseases such as osteopetrosis or osteoporosis. In our laboratory we have recently generated, using state-of-the-art technologies, unique mouse models of RANKL-induced osteopetrosis or osteoporosis. These mouse models constitute excellent systems for the study of underlying pathogenic mechanisms and for the evaluation of novel therapeutic approaches at the preclinical level.

scholarly journals Role of Karanja Tail Matra Basti in Purishaja Krimi – A Case Study

2020 ◽  
Vol 8 (06) ◽  
Author(s):  
Prajakta A. Pasarkar
Keyword(s):  
Modern Science ◽  
Public Health Problem ◽  
Treatment Method ◽  
Personal Hygiene ◽  
Ancient Time ◽  
Separate Branch ◽  
Serious Disease ◽  
Almost All

There are lots of patient come in the clinic complaining serious disease like Apsmara, Unmanda, pandu, hridroga, jirnapratishyaya, skin disease ,and many more .we started treating them with hetu, nidan parivarjan, sampramti bhanga basics. but some while we have to think about krimi. In ancient time Concept of Krumi and their relation in the development of disease is described in almost all ayurvedic  samhita. Acharyas  also describe  Krumi as an etiological factor in various diseases. Recent global estimates indicate that more than a quarter of the world’s population are infected with parasitic infestation. Krimi is a serious public health problem and is widely prevalent in developing countries due to low environmental quality and people of low nutritional status and poor personal hygiene. Medicinal Plants has been utilized as medicine from ancient time. Traditional Knowldge of Ayurveda medicinal plant and their treatment method are rooted in classical literatures and unscripted dialets of people in India. Krimi in Ayurveda in broad sense is all worms and microbes whether visible or invisible; pathogenic and nonpathogenic subtle organisms and microorganism. As in modern science there is separate branch of helminthology and microbiology.

scholarly journals Insights Into Genetics and Pathophysiology of Arrhythmogenic Cardiomyopathy

2021 ◽  
Author(s):  
Brenda Gerull ◽  
Andreas Brodehl
Keyword(s):  
Ventricular Arrhythmias ◽  
Disease Onset ◽  
Therapeutic Approaches ◽  
Arrhythmogenic Cardiomyopathy ◽  
Preclinical Research ◽  
Cellular Junctions ◽  
Genes Encoding ◽  
Life Threatening ◽  
Apparently Healthy

Abstract Purpose of Review Arrhythmogenic cardiomyopathy (ACM) is a genetic disease characterized by life-threatening ventricular arrhythmias and sudden cardiac death (SCD) in apparently healthy young adults. Mutations in genes encoding for cellular junctions can be found in about half of the patients. However, disease onset and severity, risk of arrhythmias, and outcome are highly variable and drug-targeted treatment is currently unavailable. Recent Findings This review focuses on advances in clinical risk stratification, genetic etiology, and pathophysiological concepts. The desmosome is the central part of the disease, but other intercalated disc and associated structural proteins not only broaden the genetic spectrum but also provide novel molecular and cellular insights into the pathogenesis of ACM. Signaling pathways and the role of inflammation will be discussed and targets for novel therapeutic approaches outlined. Summary Genetic discoveries and experimental-driven preclinical research contributed significantly to the understanding of ACM towards mutation- and pathway-specific personalized medicine.

scholarly journals TMPRSS2 As an Influential Human Gene for COVID-19

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Sepideh Abdollahi ◽  
Pantea Izadi
Keyword(s):  
Risk Factors ◽  
Clinical Symptoms ◽  
Epidemiological Studies ◽  
Therapeutic Approaches ◽  
Diverse Range ◽  
Angiotensin Converting Enzyme 2 ◽  
Clinical Presentations ◽  
Health System Efficiency ◽  
Almost All

: In December 2019, the new virus, COVID-19, emerged and led to a pandemic respiratory acute disease. Almost all countries have experienced different rates of morbidity and mortality. These differences can be attributed to factors such as a diagnostic test capacity for COVID-19 and the health system efficiency. Besides the differences between countries related to the COVID-19 management, different patients represent a diverse range of clinical symptoms, from outpatient to patients admitted to the intensive care unit (ICU) due to the severity of symptoms. To gain deeper insights into such disparities in the severity of COVID-19 clinical presentations, epidemiological studies have reported risk factors such as old age, male sex, underlying chronic diseases such as diabetes, inflammatory and cardiovascular diseases, which have a bearing on susceptibility to COVID-19. In addition to these risk factors, the molecular mechanism involved in the virus entry process has been under investigation. Apart from a well-known protein called ACE2 (angiotensin-converting enzyme 2), which plays the receptor role for COVID-19, another essential protein in this pathway is TMPRSS2 (transmembrane protease, serine 2). This protease has a crucial role in effective membrane integration between the virus and the target cell. This process can affect the severity of the infection and the mortality rate of the disease. Thus, it seems that understanding the role of TMPRSS2 in COVID-19 infection can help better management by designing TMPRSS2 inhibitors drugs. Given the variants of the TMPRSS2 gene, which are associated with the severity of symptoms, people exposed to severe forms of this disease can be identified before the deterioration of the disease to adopt appropriate therapeutic approaches. Therefore, this study focused on the different levels of the TMPRSS2 interactions with COVID-19 virus and disease severity.

scholarly journals Multiple Skin Squamous Cell Carcinomas in Junctional Epidermolysis Bullosa Due to Altered Laminin-332 Function

2020 ◽  
Vol 21 (4) ◽  
pp. 1426
Author(s):  
Paola Fortugno ◽  
Angelo Giuseppe Condorelli ◽  
Elena Dellambra ◽  
Liliana Guerra ◽  
Francesca Cianfarani ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Epidermolysis Bullosa ◽  
Proteolytic Processing ◽  
Disulphide Bond ◽  
Structural Element ◽  
Junctional Epidermolysis Bullosa ◽  
Skin Fragility ◽  
Gene Expression Studies ◽  
Laminin 332

Variably reduced expression of the basement membrane component laminin-332 (α3aβ3γ2) causes junctional epidermolysis bullosa generalized intermediate (JEB-GI), a skin fragility disorder with an increased susceptibility to squamous cell carcinoma (SCC) development in adulthood. Laminin-332 is highly expressed in several types of epithelial tumors and is central to signaling pathways that promote SCC tumorigenesis. However, laminin-332 mutations and expression in individuals affected by JEB-GI and suffering from recurrent SCCs have been poorly characterized. We studied a JEB-GI patient who developed over a hundred primary cutaneous SCCs. Molecular analysis combined with gene expression studies in patient skin and primary keratinocytes revealed that the patient is a functional hemizygous for the p.Cys1171* mutant allele which is transcribed in a stable mRNA encoding for a β3 chain shortened of the last two C-terminal amino acids (Cys1171-Lys1172). The lack of the Cys1171 residue involved in the C-terminal disulphide bond to γ2 chain did not prevent assembly, secretion, and proteolytic processing of the heterotrimeric molecule. Immunohistochemistry of SCC specimens revealed accumulation of mutant laminin-332 at the epithelial-stromal interface of invasive front. We conclude that the C-terminal disulphide bond is a structural element crucial for laminin-332 adhesion function in-vivo. By saving laminin-332 amount, processing, and signaling role the p.Cys1171* mutation may allow intrinsic pro-tumorigenic properties of the protein to be conveyed, thus contributing to invasiveness and recurrence of SCCs in this patient.

scholarly journals Advances in understanding the molecular basis of skin fragility

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 279 ◽  
Author(s):  
Cristina Has
Keyword(s):  
Epidermolysis Bullosa ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Genetic Disorders ◽  
Scientific Progress ◽  
Mechanical Trauma ◽  
Therapeutic Approaches ◽  
New Genes ◽  
Inherited Epidermolysis Bullosa ◽  
Skin Fragility

Skin fragility refers to a large group of conditions in which the ability of the skin to provide protection against trivial mechanical trauma is diminished, resulting in the formation of blisters, erosions, wounds, or scars. Acquired and physiological skin fragility is common; genetic disorders are rare but give insight into the molecular mechanisms ensuring skin stability. The paradigm is represented by inherited epidermolysis bullosa. This review is focused on recent advances in understanding the molecular basis of genetic skin fragility, including emerging concepts, controversies, unanswered questions, and opinions of the author. In spite of the advanced knowledge on the genetic causes of skin fragility, the molecular pathology is still expanding. Open questions in understanding the molecular basis of genetic skin fragility are the following: what are the causes of phenotypes which remain genetically unsolved, and what are the molecular modifiers which might explain phenotypic differences among individuals with similar mutations?  New mutational mechanisms and new genes have recently been discovered and are briefly described here. Comprehensive next-generation sequencing-based genetic testing improved mutation detection and facilitated the identification of the genetic basis of unclear and new phenotypes. Characterization of the biochemical and cell biological consequences of the genetic variants is challenging and laborious but may represent the basis for personalized therapeutic approaches. Molecular modifiers of skin fragility have been uncovered in particular animal and genetic models but not in larger cohorts of patients. This scientific progress is the basis for revisions of the epidermolysis bullosa classification and for innovative therapeutic approaches designed for this intractable condition.

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