scholarly journals Crosstalk Between microRNAs and the Pathological Features of Secondary Lymphedema

2021 ◽  
Vol 9 ◽  
Author(s):  
Khairunnisa’ Md Yusof ◽  
Kira Groen ◽  
Rozita Rosli ◽  
Kelly A. Avery-Kiejda
Keyword(s):  
Immune System ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Lymphatic Vessels ◽  
Pathological Features ◽  
Secondary Lymphedema ◽  
Immune System Dysfunction ◽  
Lymphatic Fluid

Secondary lymphedema is characterized by lymphatic fluid retention and subsequent tissue swelling in one or both limbs that can lead to decreased quality of life. It often arises after loss, obstruction, or blockage of lymphatic vessels due to multifactorial modalities, such as lymphatic insults after surgery, immune system dysfunction, deposition of fat that compresses the lymphatic capillaries, fibrosis, and inflammation. Although secondary lymphedema is often associated with breast cancer, the condition can occur in patients with any type of cancer that requires lymphadenectomy such as gynecological, genitourinary, or head and neck cancers. MicroRNAs demonstrate pivotal roles in regulating gene expression in biological processes such as lymphangiogenesis, angiogenesis, modulation of the immune system, and oxidative stress. MicroRNA profiling has led to the discovery of the molecular mechanisms involved in the pathophysiology of auto-immune, inflammation-related, and metabolic diseases. Although the role of microRNAs in regulating secondary lymphedema is yet to be elucidated, the crosstalk between microRNAs and molecular factors involved in the pathological features of lymphedema, such as skin fibrosis, inflammation, immune dysregulation, and aberrant lipid metabolism have been demonstrated in several studies. MicroRNAs have the potential to serve as biomarkers for diseases and elucidation of their roles in lymphedema can provide a better understanding or new insights of the mechanisms underlying this debilitating condition.

scholarly journals Lymphatic system and adipose tissue: Crosstalk in health and disease

2021 ◽  
Vol 18 (3) ◽  
pp. 336-344
Author(s):  
V. V. Klimontov ◽  
D. M. Bulumbaeva
Keyword(s):  
Endothelial Cells ◽  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Inflammatory Cells ◽  
The Body ◽  
Push Button ◽  
Secondary Lymphedema

The lymphatic system (LS) is one of the main integrative systems of the body, providing protective and transport functions. In recent years, interactions between LS and adipose tissue (AT) have been of particular interest. Lymphatic vessels play an important role in metabolic and regulatory functions of AT, acting as a collector of lipolysis products and adipokines. In its turn, hormones and adipocytokines that produced in adipocytes (including leptin, adiponectin, IL-6, TNF-α, etc.) affect the function of lymphatic endothelial cells and control the growth of lymphatic vessels. Cooperation between LS and AT becomes pathogenetically and clinically important in lymphedema and obesity. It is known that both primary and secondary lymphedema are characterized by increased fat accumulation which is associated with the severity of lymphostasis and inflammation. Similarly, in obesity, the drainage function of LS is impaired, which is accompanied by perilymphatic mononuclear infiltration in the AT. The development of these changes is facilitated by endocrine dysfunction of adipocytes and impaired production of adipocytokines. The increase in the production of inflammatory mediators and the disruption of the traffic of inflammatory cells causes a further deterioration in the outflow of interstitial fluid and exacerbates the inflammation of the AT, thereby forming a vicious circle. The role of lymphangiogenesis in AT remodeling in obesity needs further research. Another promising area of research is the study of the role of intestinal LS in the development of obesity and related disorders. It has been shown that the transport of chylomicrons from the intestine depends on the expression of a number of molecular mediators (VEGF-C, DLL-4, neuropilin-1, VEGFR-1, CD36/FAT, etc.)in the endotheliocytes of the intestinal lymphatic vessels, as well as the functioning of «push-button» and “zippering” junctions between endothelial cells. New approach to the treatment of obesity based on blockade of lymphatic chylomicrontransport has been experimentally substantiated. Further identification of the molecular mechanisms and signaling pathways that determine the remodeling of AT in lymphedema and obesity are likely to provide new approaches to the treatment of these diseases.

Covid-19 In Man: A Very Dangerous Affair.

2021 ◽  
Vol 21 ◽  
Author(s):  
Giuseppe Lisco ◽  
Vito A. Giagulli ◽  
Giovanni De Pergola ◽  
Anna De Tullio ◽  
Edoardo Guastamacchia ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Metabolic Diseases ◽  
Systemic Disease ◽  
Public Health Issue ◽  
Immune System Dysfunction ◽  
Data Support ◽  
Systemic Spread ◽  
The Impact

Background: The novel pandemic of Coronavirus disease 2019 (COVID-19) has becoming a public health issue since March 2020 considering that more than 30 million people were found to be infected worldwide. Particularly, recent evidences suggested that men may be considered as at higher risk of poor prognosis or death once the infection occurred and concerns surfaced in regard of the risk of a possible testicular injury due to SARS-CoV-2 infection. Results: Several data support the existence of a bivalent role of testosterone (T) in driving poor prognosis in patients with COVID-19. On one hand, this is attributable to the fact that T may facilitate SARS-CoV-2 entry in human cells by means of an enhanced expression of transmembrane serine-protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2). At the same time, younger man with normal testicular function compared to women of similar age are prone to develop a blunted immune response against SARS-CoV-2, being exposed to less viral clearance and more viral shedding and systemic spread of the disease. Conversely, low levels of serum T observed in hypogonadal men predispose them to a greater background systemic inflammation, cardiovascular and metabolic diseases, and immune system dysfunction, hence driving harmful consequences once SARS-CoV-2 infection occurred. Finally, SARS-CoV-2, as a systemic disease, may also affect testicles with possible concerns for current and future testicular efficiency. Preliminary data suggested that SARS-CoV-2 genome is not normally found in gonads and gametes, therefore sex transmission could be excluded as a possible way to spread the COVID-19. Conclusion: Most data support a role of T as a bivalent risk factor for poor prognosis (high/normal in younger; lower in elderly) in COVID-19. However, the impact of medical treatment aimed to modify T homeostasis for improving the prognosis of affected patients is unknown in this clinical setting. In addition, testicular damage may be a harmful consequence of the infection even in case it occurred asymptomatically but no long-term evidences are currently available to confirm and quantify this phenomenon. Different authors excluded the presence of SARS-CoV-2 in sperm and oocytes, thus limiting worries about both a potential sexual and gamete-to-embryos transmission of COVID-19. Despite these evidence, long-term and well-designed studies are needed to clarify these issues.

scholarly journals The roles and mechanisms of hypoxia in liver fibrosis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jingyao Cai ◽  
Min Hu ◽  
Zhiyang Chen ◽  
Zeng Ling
Keyword(s):  
Quality Of Life ◽  
Liver Fibrosis ◽  
Theoretical Basis ◽  
Liver Diseases ◽  
Molecular Mechanisms ◽  
Clinical Intervention ◽  
Chronic Liver Injury ◽  
Key Factor

AbstractLiver fibrosis occurs in response to any etiology of chronic liver injury. Lack of appropriate clinical intervention will lead to liver cirrhosis or hepatocellular carcinoma (HCC), seriously affecting the quality of life of patients, but the current clinical treatments of liver fibrosis have not been developed yet. Recent studies have shown that hypoxia is a key factor promoting the progression of liver fibrosis. Hypoxia can cause liver fibrosis. Liver fibrosis can, in turn, profoundly further deepen the degree of hypoxia. Therefore, exploring the role of hypoxia in liver fibrosis will help to further understand the process of liver fibrosis, and provide the theoretical basis for its diagnosis and treatment, which is of great significance to avoid further deterioration of liver diseases and protect the life and health of patients. This review highlights the recent advances in cellular and molecular mechanisms of hypoxia in developments of liver fibrosis.

scholarly journals Neuroinflammation and Its Impact on the Pathogenesis of COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Mohammed M. Almutairi ◽  
Farzane Sivandzade ◽  
Thamer H. Albekairi ◽  
Faleh Alqahtani ◽  
Luca Cucullo
Keyword(s):  
Immune System ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Immune Cell ◽  
Clinical Manifestations ◽  
Cell Infiltration ◽  
Cellular Mechanisms ◽  
Cytokine Levels

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical manifestations of COVID-19 include dry cough, difficult breathing, fever, fatigue, and may lead to pneumonia and respiratory failure. There are significant gaps in the current understanding of whether SARS-CoV-2 attacks the CNS directly or through activation of the peripheral immune system and immune cell infiltration. Although the modality of neurological impairments associated with COVID-19 has not been thoroughly investigated, the latest studies have observed that SARS-CoV-2 induces neuroinflammation and may have severe long-term consequences. Here we review the literature on possible cellular and molecular mechanisms of SARS-CoV-2 induced-neuroinflammation. Activation of the innate immune system is associated with increased cytokine levels, chemokines, and free radicals in the SARS-CoV-2-induced pathogenic response at the blood-brain barrier (BBB). BBB disruption allows immune/inflammatory cell infiltration into the CNS activating immune resident cells (such as microglia and astrocytes). This review highlights the molecular and cellular mechanisms involved in COVID-19-induced neuroinflammation, which may lead to neuronal death. A better understanding of these mechanisms will help gain substantial knowledge about the potential role of SARS-CoV-2 in neurological changes and plan possible therapeutic intervention strategies.

Role of Polyherbal Formulations of Medicinal Plants From Himalayan Regions in the Management of Diabetes

2022 ◽  
pp. 212-229
Author(s):  
Ashfaq Ahmad Shah ◽  
Sumaira Qayoom ◽  
Amit Gupta ◽  
Aqueel Ur Rehman
Keyword(s):  
Quality Of Life ◽  
Oxidative Stress ◽  
Metabolic Diseases ◽  
Polyphenolic Compounds ◽  
Health Concern ◽  
Glucose Measurement ◽  
Diabetes Research ◽  
Cardiovascular Disorders

Current research on phytochemicals is mainly focused on novel phenolic and polyphenolic compounds expressing their potential as therapeutic agents in various diseases like cancer, autoimmune diseases, cardiovascular disorders, diabetes, oxidative stress-related diseases, as well as their properties to inhibit the growth and proliferation of infectious agents. Among the human physiological disorders, one of the most severe endocrine metabolic diseases is Diabetes mellitus which is a clinical disease distinguished by a deficit in the production of insulin or resistance to the action of insulin. Globally, diabetes is an increasing health concern which is now emerging as an epidemic. About 700-800 plants are exhibiting anti-diabetic activity that has been studied. As far as nanotechnology in diabetes research is concerned, it has made possible the buildout of novel glucose measurement as well as insulin delivery modalities that possess the potential to excellently enhance the quality of life of the diabetic patient.

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.

scholarly journals Causes and Mechanisms of Hematopoietic Stem Cell Aging

2019 ◽  
Vol 20 (6) ◽  
pp. 1272 ◽  
Author(s):  
Jungwoon Lee ◽  
Suk Yoon ◽  
Inpyo Choi ◽  
Haiyoung Jung
Keyword(s):  
Immune System ◽  
Molecular Mechanisms ◽  
The Elderly ◽  
Cell Aging ◽  
Extrinsic Factors ◽  
Hematopoietic Stem ◽  
Age Related ◽  
Stem Cell Aging ◽  
Related Stress

Many elderly people suffer from hematological diseases known to be highly age-dependent. Hematopoietic stem cells (HSCs) maintain the immune system by producing all blood cells throughout the lifetime of an organism. Recent reports have suggested that HSCs are susceptible to age-related stress and gradually lose their self-renewal and regeneration capacity with aging. HSC aging is driven by cell-intrinsic and -extrinsic factors that result in the disruption of the immune system. Thus, the study of HSC aging is important to our understanding of age-related immune diseases and can also provide potential strategies to improve quality of life in the elderly. In this review, we delineate our understanding of the phenotypes, causes, and molecular mechanisms involved in HSC aging.

scholarly journals ROLE OF AMALAKYADI RASAYANA IN LOWERING DOWN THE MORBIDITY RATE IN CHILDREN: A REVIEW

2020 ◽  
Vol 11 (5) ◽  
pp. 121-127
Author(s):  
Ajay Kushwaha ◽  
Nisha Kumari Ojha
Keyword(s):  
Immune System ◽  
Experimental Studies ◽  
Anthelmintic Activity ◽  
The Body ◽  
Morbidity Rate ◽  
Tissue Quality ◽  
Tissue Degeneration ◽  
Age Related

Children are more susceptible to various infections because of underdeveloped immune system as compared to adults. Strengthening the immune system is a natural way to help the body fight against the disease-causing pathogens and immunomodulators can play a major role in this context. Various Ayurveda classics and studies published in journals related to Ayurveda drugs for improving immunity are reviewed and analysed. In Ayurveda, the objective of immune enhancement is achieved through the use of the Amalakyadi Rasayana (an Immunomodulators), as it increases longevity of life, memory, intellect, luxture, complexion, voice, strength of the body functions, strength of all senses and provides the resistance to disease, improves glow and power. Analysis of classical references and various experimental studies show that Amalakyadi Rasayana posse immuno-modulatory, Antioxidant, Anti-inflammatory, Antimicrobial, Anthelmintic activity. Present paper is a review to update knowledge on pharmacological properties, therapeutic actions and possible mode of action of the selected formulation, Amalakyadi rasayana from Yogaratnakara (Rasayanadhikara/17) to enhance the immunity in children. Rasayana is an important part of Ayurvedic therapeutics used to improve the quality of life by strengthening the tissue quality and by reducing the age-related tissue degeneration. This study reveals that Amalakyadi Rasayana have potential to improve or strengthen the immune system in children and thereby can lower down the morbidity rate in children.

scholarly journals Sex differences in severity and mortality from COVID-19: are males more vulnerable?

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ajay Pradhan ◽  
Per-Erik Olsson
Keyword(s):  
Sex Differences ◽  
Immune System ◽  
Immune Responses ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Basic Research ◽  
Contributing Factors ◽  
High Infection ◽  
Males And Females

Abstract Coronavirus disease 2019 (COVID-19) has shown high infection and mortality rates all over the world, and despite the global efforts, there is so far no specific therapy available for COVID-19. Interestingly, while the severity and mortality of COVID-19 are higher in males than in females, the underlying molecular mechanisms are unclear. In this review, we explore sex-related differences that may be contributing factors to the observed male-biased mortality from COVID-19. Males are considered the weaker sex in aspects related to endurance and infection control. Studies show that viral RNA clearance is delayed in males with COVID-19. A recent study has indicated that the testis can harbor coronavirus, and consequently, males show delayed viral clearance. However, the role of testis involvement in COVID-19 severity and mortality needs further research. Males and females show a distinct difference in immune system responses with females eliciting stronger immune responses to pathogens. This difference in immune system responses may be a major contributing factor to viral load, disease severity, and mortality. In addition, differences in sex hormone milieus could also be a determinant of viral infections as estrogen has immunoenhancing effects while testosterone has immunosuppressive effects. The sex-specific severity of COVID-19 infections indicates that further research on understanding the sex differences is needed. Inclusion of both males and females in basic research and clinical trials is required to provide critical information on sex-related differences that may help to better understand disease outcome and therapy.

scholarly journals MiR-145-5p Inhibits the Invasion of Prostate Cancer and Induces Apoptosis by Inhibiting WIP1

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jianming Sun ◽  
Linggang Deng ◽  
Ye Gong
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Quantitative Polymerase Chain Reaction ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Luciferase Reporter Gene ◽  
Anticancer Effects ◽  
Polymerase Chain

Prostate cancer (PCa) is a common malignant tumor of the male genitourinary system that seriously affects the quality of life of patients. Studying the pathogenesis and therapeutic targets of PCa is important. In this study, we investigated the role of miR-145-5p in PCa and its potential molecular mechanisms. The expression levels of miR-145-5p in PCa tissues and adjacent control tissues were detected by real-time quantitative polymerase chain reaction. The effects of miR-145-5p overexpression on PCa were studied using cell proliferation, migration, and invasion experiments. Furthermore, WIP1 was the target gene of miR-145-5p through the bioinformatics website and dual-luciferase reporter gene experiment. Further studies found that WIP1 downregulation could inhibit the proliferation, invasion, and cloning of PCa cells. Overexpression of WIP1 reversed the anticancer effects of miR-145. The anticancer effect of miR-145 was achieved by inhibiting the PI3K/AKT signaling pathway and upregulating ChK2 and p-p38MAPK. Taken together, these results confirmed that miR-145-5p inhibited the growth and metastasis of PCa cells by inhibiting the expression of proto-oncogene WIP1, thereby playing a role in tumor suppression in PCa and may become a potential therapeutic target for the treatment of PCa.

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