scholarly journals Skin Pigmentation Abnormalities and Their Possible Relationship with Skin Aging

2021 ◽  
Vol 22 (7) ◽  
pp. 3727
Author(s):  
Ai-Young Lee
Keyword(s):  
Molecular Mechanisms ◽  
Skin Pigmentation ◽  
Skin Aging ◽  
Premature Aging ◽  
Common Symptom ◽  
Hormonal Changes ◽  
Inherited Disorders ◽  
Therapeutic Modalities ◽  
Dna Mutations ◽  
Abnormal Pigmentation

Skin disorders showing abnormal pigmentation are often difficult to manage because of their uncertain etiology or pathogenesis. Abnormal pigmentation is a common symptom accompanying aging skin. The association between skin aging and skin pigmentation abnormalities can be attributed to certain inherited disorders characterized by premature aging and abnormal pigmentation in the skin and some therapeutic modalities effective for both. Several molecular mechanisms, including oxidative stress, mitochondrial DNA mutations, DNA damage, telomere shortening, hormonal changes, and autophagy impairment, have been identified as involved in skin aging. Although each of these skin aging-related mechanisms are interconnected, this review examined the role of each mechanism in skin hyperpigmentation or hypopigmentation to propose the possible association between skin aging and pigmentation abnormalities.

Role of Resveratrol in Modulating microRNAs in Human Diseases: From Cancer to Inflammatory Disorder

2020 ◽  
Vol 28 (2) ◽  
pp. 360-376 ◽  
Author(s):  
Atefeh Amiri ◽  
Maryam Mahjoubin-Tehran ◽  
Zatollah Asemi ◽  
Alimohammad Shafiee ◽  
Sarah Hajighadimi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Antioxidant Activities ◽  
Natural Compounds ◽  
Therapeutic Effects ◽  
Inflammatory Disorder ◽  
Inflammatory Disorders ◽  
Therapeutic Modalities ◽  
Anti Cancer ◽  
Current Therapies ◽  
Anti Inflammatory

: Cancer and inflammatory disorders are two important public health issues worldwide with significant socio.economic impacts. Despite several efforts, the current therapeutic platforms are associated with severe limitations. Therefore, developing new therapeutic strategies for the treatment of these diseases is a top priority. Besides current therapies, the utilization of natural compounds has emerged as a new horizon for the treatment of cancer and inflammatory disorders as well. Such natural compounds could be used either alone or in combination with the standard cancer therapeutic modalities such as chemotherapy, radiotherapy, and immunotherapy. Resveratrol is a polyphenolic compound that is found in grapes as well as other foods. It has been found that this medicinal agent displays a wide pharmacological spectrum, including anti-cancer, anti-inflammatory, anti-microbial, and antioxidant activities. Recently, clinical and pre-clinical studies have highlighted the anti-cancer and anti-inflammatory effects of resveratrol. Increasing evidence revealed that resveratrol exerts its therapeutic effects by targeting various cellular and molecular mechanisms. Among cellular and molecular targets that are modulated by resveratrol, microRNAs (miRNAs) have appeared as key targets. MiRNAs are short non-coding RNAs that act as epigenetic regulators. These molecules are involved in many processes that are involved in the initiation and progression of cancer and inflammatory disorders. Herein, we summarized various miRNAs that are directly/indirectly influenced by resveratrol in cancer and inflammatory disorders.

scholarly journals Signal Transducer and Activator of Transcription 3 (STAT3) Suppresses STAT1/Interferon Signaling Pathway and Inflammation in Senescent Preadipocytes

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 334
Author(s):  
Aisha Y. Madani ◽  
Yasser Majeed ◽  
Houari B. Abdesselem ◽  
Maha V. Agha ◽  
Muneera Vakayil ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Adenosine Monophosphate ◽  
Human Adipose Tissue ◽  
Premature Aging ◽  
Guanosine Monophosphate ◽  
Negative Regulator ◽  
Signal Transducer ◽  
Interferon Signaling

Obesity promotes premature aging and dysfunction of white adipose tissue (WAT) through the accumulation of cellular senescence. The senescent cells burden in WAT has been linked to inflammation, insulin-resistance (IR), and type 2 diabetes (T2D). There is limited knowledge about molecular mechanisms that sustain inflammation in obese states. Here, we describe a robust and physiologically relevant in vitro system to trigger senescence in mouse 3T3-L1 preadipocytes. By employing transcriptomics analyses, we discovered up-regulation of key pro-inflammatory molecules and activation of interferon/signal transducer and activator of transcription (STAT)1/3 signaling in senescent preadipocytes, and expression of downstream targets was induced in epididymal WAT of obese mice, and obese human adipose tissue. To test the relevance of STAT1/3 signaling to preadipocyte senescence, we used Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein 9 (CRISPR/Cas9) technology to delete STAT1/3 and discovered that STAT1 promoted growth arrest and cooperated with cyclic Guanosine Monophosphate-Adenosine Monophosphate (GMP-AMP) synthase-stimulator of interferon genes (cGAS-STING) to drive the expression of interferon β (IFNβ), C-X-C motif chemokine ligand 10 (CXCL10), and interferon signaling-related genes. In contrast, we discovered that STAT3 was a negative regulator of STAT1/cGAS-STING signaling—it suppressed senescence and inflammation. These data provide insights into how STAT1/STAT3 signaling coordinates senescence and inflammation through functional interactions with the cGAS/STING pathway.

Mitochondrial Disorders of DNA Polymerase γ Dysfunction: From Anatomic to Molecular Pathology Diagnosis

2011 ◽  
Vol 135 (7) ◽  
pp. 925-934
Author(s):  
Linsheng Zhang ◽  
Sherine S. L. Chan ◽  
Daynna J. Wolff
Keyword(s):  
Dna Polymerase ◽  
Molecular Mechanisms ◽  
Clinical Laboratory ◽  
Laboratory Diagnosis ◽  
Molecular Study ◽  
Mitochondrial Disorders ◽  
Definitive Diagnosis ◽  
Inherited Disorders ◽  
Cooperative Effort ◽  
Dna Polymerase Γ

Abstract Context.—Primary mitochondrial dysfunction is one of the most common causes of inherited disorders predominantly involving the neuromuscular system. Advances in the molecular study of mitochondrial DNA have changed our vision and our approach to primary mitochondrial disorders. Many of the mitochondrial disorders are caused by mutations in nuclear genes and are inherited in an autosomal recessive pattern. Among the autosomal inherited mitochondrial disorders, those related to DNA polymerase γ dysfunction are the most common and the best studied. Understanding the molecular mechanisms and being familiar with the recent advances in laboratory diagnosis of this group of mitochondrial disorders are essential for pathologists to interpret abnormal histopathology and laboratory results and to suggest further studies for a definitive diagnosis. Objectives.—To help pathologists better understand the common clinical syndromes originating from mutations in DNA polymerase γ and its associated proteins and use the stepwise approach of clinical, laboratory, and pathologic diagnosis of these syndromes. Data Sources.—Review of pertinent published literature and relevant Internet databases. Conclusions.—Mitochondrial disorders are now better recognized with the development of molecular tests for clinical diagnosis. A cooperative effort among primary physicians, diagnostic pathologists, geneticists, and molecular biologists with expertise in mitochondrial disorders is required to reach a definitive diagnosis.

scholarly journals Identification of Key Genes and Pathways Associated with Differences of Subchondral Bone in Osteoarthritis

2020 ◽  
Author(s):  
Yiyuan Zhang ◽  
Rongguo Yu ◽  
Jiayu Zhang ◽  
Eryou Feng ◽  
Haiyang Wang ◽  
...  
Keyword(s):  
Subchondral Bone ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Hub Genes ◽  
Common Chronic Disease ◽  
Drug Candidates ◽  
Therapeutic Modalities ◽  
Pathogenic Genes

Abstract BackgroundOsteoarthritis (OA) is a common chronic disease worldwide. Subchondral bone is an important pathological change in OA and responds more rapidly to adverse loading and events compared to cartilage. However, the pathogenic genes and pathways of subchondral bone are largely unclear.ObjectiveThis study aimed to identify signature differences in genes involved in knee lateral tibial (LT) and medial tibial (MT) plateaus of subchondral bone tissue while exploring their potential molecular mechanisms via bioinformatics analysis.MethodsFirst, the gene expression data of GSE51588 was downloaded from the GEO database. Differentially expressed genes (DEGs) between knee LT and MT were identified, and functional enrichment analyses were performed. Then, a protein-protein interactive network was constructed in order to acquire the hub genes, and modules analysis was conducted using STRING and Cytoscape for further analysis. The enriched hub genes were queried in DGIdb database to find suitable drug candidates in OA.ResultsA total of 202 DEGs (112 upregulated genes and 84 downregulated genes) were determined. In the PPI network, ten hub genes were identified. Five significant modules were identified using the MCODE plugin unit. Functional enrichment analysis revealed the most important signaling pathways. Six of the ten hub genes were targetable by a total of 35 drugs, suggesting their possible therapeutic use for OA .ConclusionsThe identified hub genes and functional enrichment pathways were implicated in the development and progression of subchondral bone in OA, thus improving our understanding of OA and offering molecular targets for future therapeutic modalities.

scholarly journals THE PATTERN OF ACUTE INTESTINAL OBSTRUCTION: A HOSPITAL BASED. STUDY..

2019 ◽  
pp. 1-3
Author(s):  
Sunil Kumar Patanaik ◽  
Chaitali Pattanayak*
Keyword(s):  
Intestinal Obstruction ◽  
Age Groups ◽  
Operative Management ◽  
Acute Intestinal Obstruction ◽  
Common Symptom ◽  
Common Procedure ◽  
Therapeutic Modalities ◽  
Study Results ◽  
Obstructed Hernia ◽  
Subacute Intestinal Obstruction

BACKGROUND: Intestinal obstruction is a surgical emergency that causes confusion both in the diagnosis and the management. It is related by important disease and mortality. The goal of this study was to classify the etiology, to analyse the methods of performance of acute duodenal obstruction in different age groups, various therapeutic modalities of treatment, to accomplish operative management, anticipate the post-operative complications and outcomes of patients with acute intestinal obstruction. MATERIAL& METHODS: 82 patients of all age groups (except infants) presenting with acute intestinal obstruction were studied between June 2017 and December 2018 in a multispeciality hospital in Eastern India. Patients with history of subacute intestinal obstruction and paralytic ileus were excluded from this study. RESULTS: Males were found to be affected much more than females. Pain abdomen was the most common symptom found in 94% cases followed by distension and vomiting in 86.6% and 68.3% cases respectively. Most common etiology of intestinal obstruction was due to adhesion and bands (40.3%) followed by obstructed hernia (22%) and malignancy (17%). The most common procedure done in intestinal obstruction in present study was release of adhesions and bands (37.8%) followed by resection and anastomosis (26.8%). CONCLUSION: Bowel obstruction continues to be one of the most common abdominal problems faced by general surgeons. Success in the treatment of intestinal obstruction depends largely upon early diagnosis, skilful management and treating the pathological effects of the obstruction just as much as the cause itself.

MOLECULAR MECHANISMS OF RETARDATION OF SKIN AGING UNDER INFLUENCE 0F HUMAN PLACENTA HYDROLYSATE

2019 ◽  
Vol 17 (2) ◽  
Author(s):  
I.M. Kvetnoy ◽  
A.O. Drobintseva ◽  
T.S. Kleimenova ◽  
V.O. Polyakova ◽  
К.А. Turkadze
Keyword(s):  
Human Placenta ◽  
Molecular Mechanisms ◽  
Skin Aging

scholarly journals Autophagy Declines with Premature Skin Aging resulting in Dynamic Alterations in Skin Pigmentation and Epidermal Differentiation

2020 ◽  
Vol 21 (16) ◽  
pp. 5708
Author(s):  
Daiki Murase ◽  
Ayumi Kusaka-Kikushima ◽  
Akira Hachiya ◽  
Rachel Fullenkamp ◽  
Anita Stepp ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Skin Pigmentation ◽  
Skin Aging ◽  
Epidermal Differentiation ◽  
Protein Homeostasis ◽  
Extrinsic Factors ◽  
Traffic System ◽  
Skin Integrity ◽  
Barrier Defect ◽  
Cellular Components

Autophagy is a membrane traffic system that provides sustainable degradation of cellular components for homeostasis, and is thus considered to promote health and longevity, though its activity declines with aging. The present findings show deterioration of autophagy in association with premature skin aging. Autophagy flux was successfully determined in skin tissues, which demonstrated significantly decreased autophagy in hyperpigmented skin such as that seen in senile lentigo. Furthermore, an exacerbated decline in autophagy was confirmed in xerotic hyperpigmentation areas, accompanied by severe dehydration and a barrier defect, which showed correlations with skin physiological conditions. The enhancement of autophagy in skin ex vivo ameliorated skin integrity, including pigmentation and epidermal differentiation. The present results indicate that the restoration of autophagy can contribute to improving premature skin aging by various intrinsic and extrinsic factors via the normalization of protein homeostasis.

scholarly journals Ion Channels: New Actors Playing in Chemotherapeutic Resistance

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 376 ◽  
Author(s):  
Philippe Kischel ◽  
Alban Girault ◽  
Lise Rodat-Despoix ◽  
Mohamed Chamlali ◽  
Silviya Radoslavova ◽  
...  
Keyword(s):  
Ion Channels ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Breast Cancers ◽  
Altered Expression ◽  
Acquired Drug Resistance ◽  
Therapeutic Modalities ◽  
Channel Expression ◽  
Systemic Agents ◽  
Resistance To Chemotherapy

In the battle against cancer cells, therapeutic modalities are drastically limited by intrinsic or acquired drug resistance. Resistance to therapy is not only common, but expected: if systemic agents used for cancer treatment are usually active at the beginning of therapy (i.e., 90% of primary breast cancers and 50% of metastases), about 30% of patients with early-stage breast cancer will have recurrent disease. Altered expression of ion channels is now considered as one of the hallmarks of cancer, and several ion channels have been linked to cancer cell resistance. While ion channels have been associated with cell death, apoptosis and even chemoresistance since the late 80s, the molecular mechanisms linking ion channel expression and/or function with chemotherapy have mostly emerged in the last ten years. In this review, we will highlight the relationships between ion channels and resistance to chemotherapy, with a special emphasis on the underlying molecular mechanisms.

scholarly journals Targeted Metabolomic Analysis of a Mucopolysaccharidosis IIIB Mouse Model Reveals an Imbalance of Branched-Chain Amino Acid and Fatty Acid Metabolism

2020 ◽  
Vol 21 (12) ◽  
pp. 4211 ◽  
Author(s):  
Valeria De Pasquale ◽  
Marianna Caterino ◽  
Michele Costanzo ◽  
Roberta Fedele ◽  
Margherita Ruoppolo ◽  
...  
Keyword(s):  
Amino Acids ◽  
Fatty Acid ◽  
Amino Acid ◽  
Mouse Model ◽  
Molecular Mechanisms ◽  
Clinical Manifestations ◽  
Neurological Impairment ◽  
Genetic Mutation ◽  
Inherited Disorders ◽  
Branched Chain

Mucopolysaccharidoses (MPSs) are inherited disorders of the glycosaminoglycan (GAG) metabolism. The defective digestion of GAGs within the intralysosomal compartment of affected patients leads to a broad spectrum of clinical manifestations ranging from cardiovascular disease to neurological impairment. The molecular mechanisms underlying the progression of the disease downstream of the genetic mutation of genes encoding for lysosomal enzymes still remain unclear. Here, we applied a targeted metabolomic approach to a mouse model of PS IIIB, using a platform dedicated to the diagnosis of inherited metabolic disorders, in order to identify amino acid and fatty acid metabolic pathway alterations or the manifestations of other metabolic phenotypes. Our analysis highlighted an increase in the levels of branched-chain amino acids (BCAAs: Val, Ile, and Leu), aromatic amino acids (Tyr and Phe), free carnitine, and acylcarnitines in the liver and heart tissues of MPS IIIB mice as compared to the wild type (WT). Moreover, Ala, Met, Glu, Gly, Arg, Orn, and Cit amino acids were also found upregulated in the liver of MPS IIIB mice. These findings show a specific impairment of the BCAA and fatty acid catabolism in the heart of MPS IIIB mice. In the liver of affected mice, the glucose-alanine cycle and urea cycle resulted in being altered alongside a deregulation of the BCAA metabolism. Thus, our data demonstrate that an accumulation of BCAAs occurs secondary to lysosomal GAG storage, in both the liver and the heart of MPS IIIB mice. Since BCAAs regulate the biogenesis of lysosomes and autophagy mechanisms through mTOR signaling, impacting on lipid metabolism, this condition might contribute to the progression of the MPS IIIB disease.

scholarly journals Molecular Mechanisms of Premature Aging in Hemodialysis: The Complex Interplay between Innate and Adaptive Immune Dysfunction

2020 ◽  
Vol 21 (10) ◽  
pp. 3422
Author(s):  
Vincenzo Losappio ◽  
Rossana Franzin ◽  
Barbara Infante ◽  
Giulia Godeas ◽  
Loreto Gesualdo ◽  
...  
Keyword(s):  
Immune System ◽  
Adaptive Response ◽  
Molecular Mechanisms ◽  
B Lymphocyte ◽  
Treatment Guidelines ◽  
Immune Dysfunction ◽  
Premature Aging ◽  
Immune System Dysfunction ◽  
Wide Range ◽  
End Stage

Hemodialysis (HD) patient are known to be susceptible to a wide range of early and long-term complication such as chronic inflammation, infections, malnutrition, and cardiovascular disease that significantly affect the incidence of mortality. A large gap between the number of people with end-stage kidney disease (ESKD) and patients who received kidney transplantation has been identified. Therefore, there is a huge need to explore the underlying pathophysiology of HD complications in order to provide treatment guidelines. The immunological dysregulation, involving both the innate and adaptive response, plays a crucial role during the HD sessions and in chronic, maintenance treatments. Innate immune system mediators include the dysfunction of neutrophils, monocytes, and natural killer (NK) cells with signaling mediated by NOD-like receptor P3 (NLRP3) and Toll-like receptor 4 (TLR4); in addition, there is a significant activation of the complement system that is mediated by dialysis membrane-surfaces. These effectors induce a persistent, systemic, pro-inflammatory, and pro-coagulant milieu that has been described as inflammaging. The adaptive response, the imbalance in the CD4+/CD8+ T cell ratio, and the reduction of Th2 and regulatory T cells, together with an altered interaction with B lymphocyte by CD40/CD40L, have been mainly implicated in immune system dysfunction. Altogether, these observations suggest that intervention targeting the immune system in HD patients could improve morbidity and mortality. The purpose of this review is to expand our understanding on the role of immune dysfunction in both innate and adaptive response in patients undergoing hemodialysis treatment.

Sign in / Sign up

Export Citation Format

Share Document