Adiponectin System (Rescue Hormone): The Missing Link between Metabolic and Cardiovascular Diseases.

The adipose tissue, regardless of its role in generating and storing energy, acts as a key player as an endocrine tissue, producing a wide scale of cytokines/hormones called adipokines. Adipokines such as leptin, resistin, visfatin and osteopontin own pro-inflammatory effects on the cardiovascular system in some cases. In contrast, some adipokines have cardioprotective and anti-inflammatory impacts including adiponectin, omentin, and apelin. One of the key adipokines is adiponectin, the abundant peptide regulating hormone that is released mainly by adipocytes and cardiomyocytes as well as by endothelial and skeletal cells. It acts through two main receptors: AdipoR1 and AdipoR2, forming the "Adiponectin system" which effectively exerts its cellular mechanisms and responses in target cells. It regulates various metabolic processes, while adiponectin is the adipocyte hormone known for its cardioprotective impact in clinical and experimental research. It is also a well-effector metabolic adipokine, since weight loss or diet restriction show a link with rises in adiponectin concentrations, which is accompanied with increasing insulin sensitivity, glucose, and lipids-regulation via adiponectin's antioxidant, anti-inflammatory, anti-fibrotic actions. The high adiponectin level made it an attractive player in developing therapeutical treatments for metabolic syndromes and cardiovascular disease. The elevated plasma levels of adiponectin are mostly attributed to its benefits on cardio-metabolism. In some cases, adiponectin has been paradoxically accompanied with elevated risk of cardiovascular disease, so higher adiponectin concentration is a marker of poor prediction. Thus, the adiponectin system is attractive to researchers as a biomarker of heart disease advancement and a predictor of prognosis during the term of some cardiovascular diseases and its mechanical functions in Hypertension and diabetic patients. This review highlights the physiological roles of adiponectin as an anti-inflammatory and cardioprotective hormone as well as how it plays as a biomarker and potential therapeutic tool in the cardiovascular system in adult, children, and adolescents. The adiponectin system may be seen as a rescue hormone aiding in remodeling of the cardiovascular system on both cellular and molecular levels. The paradox role of adiponectin relevant to cardiovascular mortality should be taken into consideration.

Thymus Gland: A Double Edge Sword for Coronaviruses.

The thymus is the main lymphoid organ that regulates the immune and endocrine systems by controlling thymic cell proliferation and differentiation. The gland is a primary lymphoid organ responsible for generating mature T cells into CD4+ or CD8+ single-positive (SP) T cells, contributing to cellular immunity. Regarding humoral immunity, the thymic plasma cells almost exclusively secrete IgG1 and IgG3, the two main complement-fixing effector IgG subclasses. Deformity in the thymus can lead to inflammatory diseases. Hassall's corpuscles' epithelial lining produces thymic stromal lymphopoietin, which induces differentiation of CDs thymocytes into regulatory T cells within the thymus medulla. Thymic B lymphocytes produce immunoglobulins and immunoregulating hormones, including thymosin. Modulation in T cell and naive T cells decrement due to thymus deformity induce alteration in the secretion of various inflammatory factors, resulting in multiple diseases. Influenza virus activates thymic CD4+ CD8+ thymocytes and a large amount of IFNγ. IFNs limit virus spread, enhance macrophages' phagocytosis, and promote the natural killer cell restriction activity against infected cells. Th2 lymphocytes-produced cytokine IL-4 can bind to antiviral INFγ, decreasing the cell susceptibility and downregulating viral receptors. COVID-19 epitopes (S, M, and N proteins) with ≥90% identity to the SARS-CoV sequence have been predicted. These epitopes trigger immunity for antibodies production. Boosting the immune system by improving thymus function can be a therapeutic strategy for preventing virus-related diseases. This review aims to summarize the endocrine-immunoregulatory functions of the thymus and the underlying mechanisms in the prevention of COVID-19.

Emerging trends in the delivery of nanoformulated oxytocin across Blood-Brain barrier.

Neurological diseases are related to the central nervous system disorders and considered as serious cases. Several drugs are used to treat neurological diseases; however, to date the main issue is to design a therapeutic model which can cross the blood-brain-barrier (BBB) easily. The delivery of neuropeptides into the brain lays as one of the important routes for treating neurological disorders. Neuropeptides have been demonstrated as potential therapeutics for neurological disorders. Among numerous neuropeptides, the oxytocin (OT) hormone is of particular interest as it serves as a neurotransmitter in the brain as well as its role as a hormone. OT has a wide-range of activities in the brain and has a key role in cognitive, neuroendocrine, and social functions. However, OT does not cross the BBB readily coupled with its half-life in the blood being too short. The current literature reveals that the delivery of OT by nanoparticle-based drug delivery system (DDS) improves its efficacy. Nanoparticle based DDS are considered important tools for the targeted delivery of drugs to the brain as they lower toxicity of the drug and improve the drug efficacy. Nanoparticles are advantageous candidates for biomedical applications due to their distinctive characteristics such as quantum effects, large surface area and their ability to carry and transport the drug to its target site. OT can be delivered through oral and intranasal routes, but the bioavailability of OT inside the brain can further be enhanced by the delivery using nanoparticles. The application of nano-based delivery system not only improves the penetration of OT inside brain but also increases its half-life by the application of encapsulation and extended release. The aim of current review is to provide an overview of nanoparticle-based drug-delivery systems for the delivery of OT inside brain.

Lirioresinol B dimethyl ether inhibits NF-κB and COX-2 and activates IκBα expression in CCl4-induced hepatic fibrosis.

BACKGROUND: Inflammation is one of the key components in the initiation and progression of hepatic diseases. If not treated, inflammation may cause cell dysplasia, and ultimately cancer. In the current study, we investigated the anti-inflammatory and anti-cancer activities of plant isolated compound Lirioresinol B Dimethyl Ether (LBDE) extracted from the seeds of Magnolia fargesii CHENG (Magnoliaceae) against HepG2 cells as well as in BALB/C male mice. METHODS: We assessed the antioxidant and anti-proliferative effects of plant compounds using DPPH assay and HepG2 cell lines. Carbon tetrachloride (CCl4) and Diethylnitrosamine (DEN) were used to induce liver cell dysplasia followed by hepatocellular carcinoma (HCC) in BALB/C male mice for 12 weeks. We investigated the underlying mechanism by using histopathology and immunoblot experiments. RESULTS: Intraperitoneal injection of LBDE (50 mg/kg body weight/day) inhibited CCl4-induced HCC. Free radical scavenging assay shows the strong anti-oxidant activity of LBDE. Western blot results show that LBDE down-regulated nuclear factor kappa B (NFκB) and cyclooxygenase (COX-2) by preventing the phosphorylation of I kappa B alpha (IκBα) in CCl4 treated group. LBDE also improved liver function by decreasing Alkaline Phosphatase (ALP), aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT) levels. Histopathology results revealed that LBDE decreased granulomas and express normal morphology of hepatocytes. CONCLUSIONS: These preliminary results show that LBDE has the potential to inhibit CCl4-induced liver cell dysplasia and prevents cancer development by regulating NFκB/COX-2 activation.

Application of Three-dimensional (3D) Tumor Cell Culture Systems and Mechanism of Drug Resistance.

The in-vitro experimental model for the development of cancer therapeutics has always been challenging. Recently, the scientific revolution has improved cell culturing techniques by applying three dimensional (3D) culture system, which provides a similar physiologically relevant in-vivo model for studying various diseases including cancer. In particular, cancer cells exhibiting in-vivo behavior in a model of 3D cell culture is a more accurate cell culture model to test the effectiveness of anticancer drugs or characterization of cancer cells in comparison with two dimensional (2D) monolayer. This study underpins various factors that cause resistance to anticancer drugs in forms of spheroids in 3D in-vitro cell culture and also outlines key challenges and possible solutions for the future development of these systems.

Synthesis, characterization and antibacterial activity of silver nanoparticles using Rhazya stricta.

BACKGROUND: Green synthesis of metallic nanoparticles has gained significant attention in the field of nanomedicine as an environment-friendly and cost-effective alternative in comparison with other physical and chemical methods. Several metals such as silver, gold, iron, titanium, zinc, magnesium and copper have been subjected to nanoformulation for a wide range of useful applications. Silver nanoparticles (AgNPs) are playing a major role in the field of nanomedicine and nanotechnology. They are widely used in diagnostics, therapeutic and pharmaceutical industries. Studies have shown potential inhibitory antimicrobial, anti-inflammatory and antiangiogenesis activities of AgNPs. METHODS: AgNPs have been synthesized using silver nitrate and methanolic root extract of Rhazya stricta that belongs to the Apocynaceae family. Stability and dispersion of nanoparticles were improved by adding xylitol. Synthesized nanoparticles were characterized by UV-Vis spectroscopy, scanning electron microscopy, energy dispersive spectroscopy, X-ray diffractometer and Fourier transforms infrared spectroscopy. Furthermore, the antibacterial effect of the plant extract and the nanoparticles were evaluated against gram-positive (Bacillus subtilis) and gram-negative (Escherichia coli) bacteria. RESULTS: The average size of AgNPs synthesized, was 20 nm with the spherical shape. Rhazya stricta based nanoparticles exhibited improved antibacterial activity against both gram-positive and negative strains.