Anti-degenerative effect of melatonin on intervertebral disc: protective contribution against inflammation, oxidative stress, apoptosis, and autophagy

Intervertebral disc (IVD) degeneration is a leading cause of lower back pain. Although the etiology of IVD degeneration (IVDD) is unclear, excessive oxidative stress, inflammation and apoptosis and disruption of autophagy play important role in the pathogenesis of IVDD. Therefore, finding a solution to mitigate these processes could stop or reduce the development of IVDD. Melatonin, a powerful antioxidant, plays an important role in regulating cartilage tissue hemostasis. Melatonin inhibits destruction of extracellular matrix (ECM) of disc. Melatonin preserves ECM contents including sox-9, aggrecan, and collagen II through inhibiting matrix degeneration enzymes such as MMP-13. These protective effects may be mediated by the inhibition of oxidative stress, inflammation and apoptosis, and regulation of autophagy in IVD cells.

Targeting mTOR Signaling in Type 2 Diabetes Mellitus and Diabetes Complications

The mechanistic target of rapamycin (mTOR) is a pivotal regulator of cell metabolism and growth. In the form of two different multi-protein complexes, mTORC1 and mTORC2, mTOR integrates cellular energy, nutrient and hormonal signals to regulate cellular metabolic homeostasis. In type 2 diabetes mellitus (T2DM) aberrant mTOR signaling underlies its pathological conditions and end-organ complications. Substantial evidence suggests that two mTOR-mediated signaling schemes, mTORC1-p70S6 kinase 1 (S6K1) and mTORC2-protein kinase B (AKT), play a critical role in insulin sensitivity and that their dysfunction contributes to development of T2DM. This review summaries our current understanding of the role of mTOR signaling in T2DM and its associated complications, as well as the potential use of mTOR inhibitors in treatment of T2DM.

Directing hypoxic tumor microenvironment and HIF to illuminate cancer immunotherapy's existing prospects and challenges in drug targets

Cancer is now also reflected as a disease of the tumor microenvironment, primarily supposed to be a decontrolled genetic and cellular expression disease. Over the past two decades, significant and rapid progress has been made in recognizing the dynamics of the tumor's microenvironment and its contribution to influencing the response to various anti-cancer therapies and drugs. Modulations in the tumor microenvironment and immune checkpoint blockade are interesting in cancer immunotherapy and drug targets. Simultaneously, the immunotherapeutic strategy can be done by modulating the immune regulatory pathway; however, the tumor microenvironment plays an essential role in suppressing the antitumor's immunity by its substantial heterogeneity. Hypoxia inducible factor (HIF) is a significant contributor to solid tumor heterogeneity and a key stressor in the tumor microenvironment to drive adaptations to prevent immune surveillance. Checkpoint inhibitors here halt the ability of cancer cells to stop the immune system from activating, and in turn, amplify your body's immune system to help destroy cancer cells. Common checkpoints that these inhibitors affect are the PD-1/PD-L1 and CTLA-4 pathways and important drugs involved are Ipilimumab and Nivolumab, mainly along with other drugs in this group. Targeting the hypoxic tumor microenvironment may provide a novel immunotherapy strategy, break down traditional cancer therapy resistance, and build the framework for personalized precision medicine and cancer drug targets. We hope that this knowledge can provide insight into the therapeutic potential of targeting Hypoxia and help to develop novel combination approaches of cancer drugs to increase the effectiveness of existing cancer therapies, including immunotherapy.

HPV-mediated Cervical Cancer: A Systematic review on Immunological Basis, Molecular Biology and Immune evasion mechanisms

Background: Human papillomavirus (HPV), one of the most frequently transmitted viruses globally, causing several malignancies including cervical cancer Aim: Owing to their unique pathogenicity HPV viruses can persist in the host organism for a longer duration than other virus types, to complete their lifecycle. During its association with the host, HPV causes various pathological conditions affecting the immune system by evading the host immune- mechanisms leading to the progression of various diseases, including cance Method: To date, ~ 150 serotypes were identified, and certain high-risk HPV types are known to be associated with genital warts and cervical cancer. As of now, two prophylactic vaccines are in use for the treatment of HPV infection, however, no effective antiviral drug is available for HPV-associated disease/infections. Numerous clinical and laboratory studies are being investigated to formulate an effective and specific vaccine again HPV infections and associated diseases Result: As the immunological basis of HPV infection and associated disease progress persist indistinctly, deeper insights on immune evasion mechanism and molecular biology of disease would aid in developing an effective vaccine. Conclusion: Thus this review focuses, aiming a systematic review on the immunological aspects of HPV-associated cervical cancer by uncovering immune evasion strategies adapted by HPV.

Current Role of Nanotechnology Used in Food Processing Industry to Control Food Additives and Exploring Their Biochemical Mechanisms

Background: With the advent of food additives centuries ago, the human race has found ways to improve and maintain the safety of utility, augment the taste, color, texture, nutritional value, and appearance of the food. Since the 19th century, when the science behind food spoilage was discerned, the use of food additives in food preservation has been increasing worldwide and at a fast pace to get along with modern lifestyles. Although food additives are thought to be used to benefit the food market, some of them are found to be associated with several health issues at an alarming rate. Studies are still going on regarding the mechanisms by which food additives affect public health. Therefore, an attempt has been made to find out the remedies by exploiting technologies that may convey new properties of food additives that can only enhance the quality of food without having any systemic side effects. Thus, this review focuses on the applications of nanotechnology in the production of nano-food additives and evaluates its success regarding reduction in the health-related hazards collaterally maintaining the food nutrient value. Methodology: Ahorough literature study was performed using scientific databases like PubMed, Science Direct, Scopus, Web of Science for determining the design of the study, and each article was checked for citation and referred to formulate the present review article. Conclusion: Nanotechnology can be applied in the food processing industry to control the unregulated use of food additives and to intervene in the biochemical mechanisms at a cellular and physiological level for the ensuring safety of food products. The prospective of nano-additive of chemical origin could be useful to reduce risks of hazards related to human health that are caused majorly due to the invasion of food contaminants (either intentional or non-intentional) into food, though this area still needs scientific validation. Therefore, this review provides comprehensive knowledge on different facets of food contaminants and also serves as a platform of ideas for encountering health risk problems about the design of improved versions of nano-additives.

Regulation of tumor immune microenvironment by sphingolipids and lysophosphatidic acid

: The tumor microenvironment (TME) consists of cancer cells that interact with stromal components such as the extracellular matrix, blood, and lymphatic networks, fibroblasts, adipocytes, and the cells of the immune system. Further, the tumor immune microenvironment, majorly represented by the tumor-infiltrating immune cells (TIIC), plays an important role in cancer therapeutics and patient prognosis. In fact, a high density of TIICs within the tumor microenvironment is known to be associated with better outcomes in several types of cancers. Towards this, two bioactive lipid molecules, lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) regulate the homing of immune cells to the TME. In the present review, we will uncover the role of LPA and S1P signaling in the tumor immune environment, highlighting the latest progress in this field.

A Revisit to Etiopathogenesis and Therapeutic Strategies in Alzheimer’s Disease

: Dementia is a cluster of brain abnormalities that trigger progressive memory deficits and other cognitive abilities such as skills, language, or executive function. Alzheimer’s disease (AD) is the foremost type of age-associated dementia that involves progressive neurodegeneration accompanied by profound cognitive deficits in advanced stages that severely hamper social or occupational abilities with or without the involvement of any other psychiatric condition. The last two decades witnessed a sharp increase (~123%) in mortality due to AD type dementia, typically owing to a very low disclosure rate (~45%) and hence, the prophylactic, as well as the therapeutic cure of AD, has been a huge challenge. Although understanding of AD pathogenesis has witnessed a remarkable growth (e.g., tauopathy, oxidative stress, lipid transport, glucose uptake, apoptosis, synaptic dysfunction, inflammation, and immune system), still a dearth of an effective therapeutic agent in the management of AD prompts the quest for newer pharmacological targets in the purview of its growing epidemiological status. Most of the current therapeutic strategies focus on modulation of a single target, e.g., inhibition of acetylcholinesterase, glutamate excitotoxicity (memantine), or nootropics (piracetam), even though AD is a multifaceted neurological disorder. There is an impedance urgency to find not only symptomatic but effective disease-modifying therapies. The present review focuses on the risk / protective factors and pathogenic mechanisms involved in AD. In addition to the existing symptomatic therapeutic approach, a diverse array of possible targets linked to pathogenic cascades have been re-investigated to envisage the pharmacotherapeutic strategies in AD.