Current trends in epigenetic, cellular and molecular pathways in management of rheumatoid arthritis.

Rheumatoid arthritis is a systemic chronic polyarticular autoimmune disorder of joints and joint membrane mainly affecting feet and hands. The pathological manifestation of the disease includes infiltration of immune cells, hyperplasia of the lining of synovium, formation of pannus and bone and cartilage destruction. If left untreated, the appearance of small focal necrosis, adhesion of granulation, and formation of fibrous tissue on the surface of articular cartilage is noted. The disease primarily affects nearly 1% of the population globally, women being more affected than men with a ratio 2:1 and can initiate regardless of any age. The synovial fibroblast in rheumatoid arthritis individuals exhibits an aggressive phenotype which upregulates the manifestation of protooncogenes, adhesive compounds, inflammatory cytokines and matrix-deteriorating enzymes. Apart from the inflammatory effects of cytokines, chemokines are also noted to induce swelling and pain in arthritic individuals by residing in synovial membrane and forming pannus. The current treatment of rheumatoid arthritis includes treatment with non-steroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, treatment with biologics such as inhibitors of TNF-α, interleukins, platelet activating factor, etc. which provides significant relief from symptoms and aids in management of the disease. The current review highlights the pathogenesis involved in the onset of rheumatoid arthritis and also covers epigenetic, cellular and molecular parameters associated with it to aid better and advanced therapeutic approaches for management of the debilitating disease.

Mitochondrial Dysfunction: A Cellular and Molecular Hub in Pathology of Metabolic Diseases and Infection.

Mitochondria are semiautonomous doubly membraned intracellular components of cells. The organelle comprises of an external membrane, followed by coiled structures within the membrane called cristae, which are further surrounded by the matrix spaces followed by the space between the external and internal membrane of the organelle. A typical eukaryotic cell contains thousands of mitochondria within it, which make up 25% of the cytoplasm present in the cell. The organelle acts as a common point for the metabolism of glucose, lipids, and glutamine. Mitochondria chiefly regulate oxidative phosphorylation-mediated aerobic respiration and the TCA cycle and generate energy in the form of ATP to fulfil the cellular energy needs. The organelle possesses a unique supercoiled doubly stranded mitochondrial DNA (mtDNA) which encodes several proteins, including rRNA and tRNA crucial for the transport of electrons, oxidative phosphorylation, and initiating genetic repair processors. Defects in the components of mitochondria act as the principal factor for several chronic cellular diseases. The dysfunction of mitochondria can cause a malfunction in the TCA cycle and cause the leakage of the electron respiratory chain, leading to an increase in reactive oxygen species and the signaling of aberrant oncogenic and tumor suppressor proteins, which further alter the pathways involved in metabolism, disrupt redox balance, and induce endurance towards apoptosis and several treatments which play a major role in developing several chronic metabolic conditions. The current review presents the knowledge on the aspects of mitochondrial dysfunction and its role in cancer, diabetes mellitus, infections, and obesity.

Insights into the Explicit Protective Activity of Herbals in Management of Neurodegenerative and Cerebrovascular Disorders.

The longstanding progressive neurodegenerative conditions of the central nervous system arise mainly due to deterioration, degradation and eventual neuronal cell loss. As an individual ages, the irreversible neurodegenerative disorders associated with aging also begin to develop, and these have become exceedingly prominent and pose a significant burden mentally, socially and economically on both the individual and their family. These disorders express several symptoms, such as tremors, dystonia, loss of cognitive functions, impairment of motor activity leading to immobility, loss of memory and many more which worsen with time. The treatment employed in management of these debilitating neurodegenerative disorders, such as Parkinson's disease (which mainly involves the loss of dopaminergic neurons in the nigrostriatal region), Alzheimer's disease (which arises due to accumulation of Tau proteins causing diffusive atrophy in the brain), Huntington's disease (which involves damage of striatal and spinal neurons, etc.), have several adverse effects, leading to exploration of several lead targets and molecules existing in herbal drugs. The current review highlights the mechanistic role of natural products in the treatment of several neurodegenerative and cerebrovascular diseases such as Parkinson's disease, Alzheimer's disease, ischemic stroke and depression.

Exploration of Multiverse Activities of Endocannabinoids in Biological Systems.

Over the last 25 years, the human endocannabinoid system (ECS) has come into the limelight as an imperative neuro-modulatory system. It is mainly comprised of endogenous cannabinoid (endocannabinoid), cannabinoid receptors and the associated enzymes accountable for its synthesis and deterioration. The ECS plays a proven role in the management of several neurological, cardiovascular, immunological, and other relevant chronic conditions. Endocannabinoid or endogenous cannabinoid are endogenous lipid molecules which connect with cannabinoid receptors and impose a fashionable impact on the behavior and physiological processes of the individual. Arachidonoyl ethanolamide or Anandamide and 2-arachidonoyl glycerol or 2-AG were the endocannabinoid molecules that were first characterized and discovered. The presence of lipid membranes in the precursor molecules is the characteristic feature of endocannabinoids. The endocannabinoids are released upon rapid enzymatic reactions into the extracellular space via activation through G-protein coupled receptors, which is contradictory to other neurotransmitter that are synthesized beforehand, and stock up into the synaptic vesicles. The current review highlights the functioning, synthesis, and degradation of endocannabinoid, and explains its functioning in biological systems.

Targeting Insulin-Like Growth Factor-I in Management of Neurological Disorders.

The degradation of neurons marks as the pathological reason for onset of most of the neurological diseases although the functional deficiencies and symptoms may vary. Insulin-like growth factor-I (IGF-I) boosts regeneration of both motor and sensory neurons and thus presents as a potential treatment in management of neurological disorders. IGF-I is a pleiotropic agent which stimulates the survival and outgrowth of neurons accompanied by their motility as well as myelination by glial cells. This hormone has been found to possess neuroprotective properties which is in association with its antioxidant and mitochondrial protection activity. Studying and exploring the signaling pathways which mediate pleotropic responses intracellularly have elucidated significant therapeutic approach in treatment and management of neurological disorders by IGF-I. The current review highlights the role of IGF-I in management of major neurological disorders such as depression, Parkinson's disease, and Alzheimer's disease and also covers the mechanisms involved in the process.

Biotechnological Innovations from Ocean: Transpiring Role of Marine Drugs in Management of Chronic Disorders.

Marine drugs are abundant in number, comprise of a diverse range of structures with corresponding mechanisms of action, and hold promise for the discovery of new and better treatment approaches for the management of several chronic diseases. There are huge reserves of natural marine biological compounds, as 70 percent of the Earth is covered with oceans, indicating a diversity of chemical entities on the planet. The marine ecosystems are a rich source of bioactive products and have been explored for lead drug molecules that have proven to be novel therapeutic targets. Over the last 70 years, many structurally diverse drug products and their secondary metabolites have been isolated from marine sources. The drugs obtained from marine sources have displayed an exceptional potential in the management of a wide array of diseases, ranging from acute to chronic conditions. A beneficial role of marine drugs in human health has been recently proposed. The current review highlights various marine drugs and their compounds and role in the management of chronic diseases such as cancer, diabetes, neurodegenerative diseases, and cardiovascular disorders, which has led to the development of new drug treatment approaches.

Current Trends in Neurodegeneration: Cross Talks between Oxidative Stress, Cell Death, and Inflammation.

The human body is highly complex and comprises a variety of living cells and extracellular material, which forms tissues, organs, and organ systems. Human cells tend to turn over readily to maintain homeostasis in tissues. However, postmitotic nerve cells exceptionally have an ability to regenerate and be sustained for the entire life of an individual, to safeguard the physiological functioning of the central nervous system. For efficient functioning of the CNS, neuronal death is essential, but extreme loss of neurons diminishes the functioning of the nervous system and leads to the onset of neurodegenerative diseases. Neurodegenerative diseases range from acute to chronic severe life-altering conditions like Parkinson's disease and Alzheimer's disease. Millions of individuals worldwide are suffering from neurodegenerative disorders with little or negligible treatment available, thereby leading to a decline in their quality of life. Neuropathological studies have identified a series of factors that explain the etiology of neuronal degradation and its progression in neurodegenerative disease. The onset of neurological diseases depends on a combination of factors that causes a disruption of neurons, such as environmental, biological, physiological, and genetic factors. The current review highlights some of the major pathological factors responsible for neuronal degradation, such as oxidative stress, cell death, and neuroinflammation. All these factors have been described in detail to enhance the understanding of their mechanisms and target them for disease management.

Exploring the Effect of Terminalia catappa Fruit Extract in Rheumatoid Arthritis: An Evaluation of Behavioural, Hematologiocal and Histopathological Parameters.

BACKGROUND AND OBJECTIVE: Rheumatoid Arthritis (RA) is an autoimmune disease characterized by failure of spontaneous resolution of inflammation with lifetime perseverance, becoming principal cause of inactivity. Many conventional therapies are in use but the side effects associated with them are equally problematic. Therefore, an urge to explore advanced therapeutic approaches with least adverse events has seeded the idea of discovering newer herbal drugs and their respective constituents in management of RA. The current research explores anti-arthritic activity of Terminalia catappa fruits hydroalcoholic extract in CFA induced Wistar rats. METHODS: The fruits were obtained, washed, dried and processed to obtain hydroalcoholic powdered extract which was dissolved in water and given orally to the rats. Wistar rats of either sex were used in the study. The animals were injected with 0.1 ml of complete freund's adjuvant (CFA) in footpad of left hind paw. The treatment was initiated from day 0 by oral dosing of Terminalia catappa fruit extract in doses of 40 mg/kg and 80 mg/kg followed by CFA administration to day 21 and behavioral, hematological parameters besides histopathological screening were assessed simultaneously. RESULTS: The arthritic symptoms were observed to gradually decrease in treatment groups when compared against disease control groups. The parameters like body weight and pain latency were increased whereas paw volume and arthritic score were found to significantly decrease in treatment groups as compared to disease control group. The hematological parameters were also modified and were studied in treatment groups. The histopathological estimation depicted extent of damage in joint tissue of diseased rat comparable to normal, standard and combination therapy group. CONCLUSION: The fruits possess anti-arthritic properties and significantly reduced paw volume, arthritic score and increased pain threshold and body weight gain besides theory hematological effects like increase in Hb and RBC and decrease in WBC, platelets and ESR levels simultaneously. The histopathological estimation confirmed decreased deterioration of joint tissue in treatment groups as compared to disease control group hence proving to be an emerging therapeutic option in management of RA.

Untying the correlation between apolipoproteins and rheumatoid arthritis.

AIM AND OBJECTIVE: The concentration of lipoproteins and apolipoprotein are extremely low in the synovial fluid of any healthy person as compared to the concentrations in plasma. However, in the synovial fluid of any diseased patient the amount of cholesterol and lipids is sharply increased. The current review defines the role of various apolipoproteins and lipoproteins and their constituent subfractions in the synovial fluid embarking its principal role in rheumatoid arthritis. It also explains the need to define synovial fluid lipids, lipoprotein particle subfractions and their constituent apolipoproteins in synovial fluid. MATERIALS AND METHODS: Various research and review articles highlighting the role of apolipoproteins and lipoproteins were procured from medical websites mainly Pubmed, Medline, Science Direct, etc., and studied for the writing of the review paper. CONCLUSION: Mainly apolipoproteins A-1, B and E are prominently increased in chronic inflammatory joint disorders. Several theories have been proposed to understand the source of increase of lipids and apolipoproteins in synovial fluid of the diseased patients compared to healthy individuals, yet the precise mechanism is still not lucid. Lipoproteins are believed to play both functional role and pathological role in the synovial fluid. The activated T-lymphocytes in patients of RA lead to activation of inflammatory cytokines such as tumor necrosis factor and interleukins which embark to be the principal mechanism for induction of the disease. It can be thus concluded that the apolipoproteins prevent the activation of monocytes by blocking their contact of activation and thus play critical role in management of RA by inhibiting the production of proinflammatory cytokines.

Emerging Therapeutic Effects of Herbal Plants in Rheumatoid Arthritis.

Rheumatoid arthritis is a chronic inflammatory autoimmune disease characterized by the failure of spontaneous resolution of inflammation with lifetime perseverance, becoming one of the major causes of disability in millions of people. It is mainly characterized by progressive erosion of cartilage in response to the formation of pannus leading to chronic polyarthritis and joint distortion. Early diagnosis and advances in molecular biology undoubtedly revolutionized therapeutic interventions in the past decade for better disease management. Despite favorable prospects, many patients still fail to respond to the current therapies urging a burning need to develop newer and safer medications. Herbal plants have been utilized since the ancient era and provided the base for massive bioactive compounds with flaunting therapeutic potential, many being advanced to drugs that are consumed worldwide for treating countless ailments. Scientific studies showed the involvement of several cellular mechanisms like oxidative stress suppression, downregulated synthesis of proinflammatory cytokines namely interleukins (IL-1, IL-6), TNF-α, NF-κB, demoted metalloproteinases induced cartilage destruction and augmentation of free radical scavenging and antioxidant activity in the treatment of rheumatoid arthritis. A plethora of active phytoconstituents like flavonoids, saponins, terpenes, alkaloids, lactones, etc, have been isolated from herbal plants with proven curative actions. The present review enlists some of the herbal drugs that can be used to amend the effects of rheumatoid arthritis and impart symptomatic relief to patients.

Understanding the Role of Inflammasomes in Rheumatoid Arthritis.

Inflammasomes are the molecular pathways that activate upon conditions of infection or stress and trigger the activation and maturation of inflammatory cytokines. Immune reactions in conjugation with inflammatory processes play a pivotal role in developing innumerable diseases. An over reactive immune system fabricates many allergic and hypersensitive reactions in response to autoantibodies activated against modified self-epitopes and similar molecules. Rheumatoid arthritis (RA) is a complex autoimmune inflammatory disorder commencing with inflammation in small joints like hands, knees, and wrist eventually entrapping larger joints such as spine. The formation of autoantibodies called rheumatoid factor (RF) and citrullinated proteins against immunoglobulin G symbolizes autoimmune nature of the disease. The presence of autoantibodies embarks principal diagnostic hallmark of the disease. With the advancement of technology, the therapeutic approach is also advancing. A new era of molecules, namely inflammasomes, are activated upon infection or in response to stress and trigger the activation of various proinflammatory cytokines such interleukins which engage in the defense mechanism of the innate immunity. Robust linking among the activity of dysregulated inflammasomes and the heritable acquired inflammatory diseases and disorders emphasizes the significance of this pathway in altering the immune responses. The current review highlights the functioning of inflammasomes and their possible role in disease dysregulation.

Nutraceuticals in Neurological Disorders.

Neurological diseases are one of the major healthcare issues worldwide. Posed lifestyle changes are associated with drastically increased risk of chronic illness and diseases, posing a substantial healthcare and financial burden to society globally. Researchers aim to provide fine treatment for ailing disorders with minimal exposed side effects. In recent decades, several studies on functional foods have been initiated to obtain foods that have fewer side effects and increased therapeutic activity. Hence, an attempt has been made to unravel several extraction techniques to acquire essential bioactive compounds or phytochemicals from therapeutically active food products. This has led to the conception of the term functional foods being meddled with other similar terms like "pharmafoods," "medifoods", "vitafoods", or "medicinal foods". With a dire need to adhere towards healthy options, the demand of nutraceuticals is widely increasing to combat neurological interventions. An association between food habits and the individual lifestyle with neurodegeneration has been manifested, thereby proposing the role of nutraceuticals as prophylactic treatment for neurological interventions. The current review covers some of the major neurological disorders and nutraceutical therapy in the prevention of disease.

Intercalating the Role of MicroRNAs in Cancer: As Enemy or Protector.

OBJECTIVE: The transformation in cells at genetic levels stimulatesthe proliferation of cancer. The current review highlights the role of miRNA in management of cancer by altering processes of body at cellular levels. METHODS: A deep research on the literature available till date for miRNA in cancer was conducted using various medical sites like PubMed, MEDLINE from internet and data was collected. The articles were majorly preferred in English language. RESULTS: The development of normal cells into cancerous cells is a multivalent procedure highlighting numerous responsible factors. During the progression of cancer, the role of oncogene and tumor suppressor genes outshines at different levels of tumorogenesis. Metastasis poses highest threat in cancer progression and fabricates obstacles to clinicians and researchers in preventing formation of tumor on secondary sites. The mesenchymal-epithelial transition (MET) and epithelial mesenchymal transition (EMT) induce dissemination and ultimately progression of cancer. CONCLUSION: A comprehensive knowledge of the altered genes and the mechanism by which they induce formation of tumor is essential as they contribute in proliferating cancer at various stages, aggravating clinical symptoms. Hence miRNAs can be efficiently employed as an emerging treatment therapy for cancer.

Role of HDAC inhibitors in diabetes mellitus.

OBJECTIVE: The role of histone deacetylases has come out as an emerging remedy in control and treatment of various metabolic disorders and cancers. This review highlights their intricate role in diabetes mellitus as well as its associated complications. KEY FINDINGS: Through recent studies and reports the role of various epigenetic markers in treatment of diabetes mellitus has been revealed. HDAC enzyme regulates the structure of chromatin and transcripts genes in the nucleus synthesizing various proteins that control metabolic activities in the body. It mainly acts by removing an acetyl group from its precursor protein thereby modulating gene expression and regulates the metabolic enzyme acetylation in mitochondria and cytosol. SUMMARY: The present review focus on the intrinsic role of HDAC inhibitors as an emerging remedy for diabetes and its complications demonstrating their use in preventing resistance of ß-cells towards insulin, destruction of ß-cells and provide protection against cytokine mediated attack on pancreatic cells.