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Brain-derived neurotrophic factor (BDNF), or abrineurin, is a member of the neurotrophin family of growth factors that acts on both the central and peripheral nervous systems. BDNF is also well known for its cardinal role in normal neural maturation. It binds to at least two receptors at the cell surface known as tyrosine kinase B (TrkB) and p75NTR. Additional neurotrophins that are anatomically linked with BDNF include neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), and nerve growth factor (NGF). It is evident that BDNF levels in patients with Alzheimer’s disease (AD) are altered. AD is a progressive disorder and a form of dementia, where the mental function of an elderly person is disrupted. It is associated with a progressive decline in cognitive function, which mainly targets the thinking, memory, and behavior of the person. The degeneration of neurons occurs in the cerebral cortex region of brain. The two major sources responsible for neuronal degeneration are protein fragment amyloid-beta (Aβ), which builds up in the spaces between the nerve cells, known as plaques, disrupting the neuron signaling pathway and leading to dementia, and neurofibrillary tangles (NFTs), which are the twisted fibers of proteins that build up inside the cells. AD is highly prevalent, with recent data indicating nearly 5.8 million Americans aged 65 and older with AD in 2020, and with 80% of patients 75 and older. AD is recognized as the sixth leading cause of death in the USA, and its prevalence is predicted to increase exponentially in the coming years. As AD worsens over time, it becomes increasingly important to understand the exact pathophysiology, biomarkers, and treatment. In this article, we focus primarily on the controversial aspect of BDNF in AD, including its influence on various other proteins and enzymes and the current treatments associated with BDNF, along with future perspectives.

Depression is a well-known disabling mental illness characterized by sadness, loss of interest in activities, and decreased energy. The symptoms of depression are usually recurrent in vulnerable individuals, and persistence of symptoms significantly impairs individuals’ quality of life. The exact pathophysiology of depression remains ambiguous, though many hypotheses have been proposed. Brain-derived neurotrophic factor (BDNF) has recently been reported to play a vital role in the pathophysiology of depression. BDNF is an important neurotrophic factor found in the human brain and is involved in neuronal growth and proliferation, synaptic neurotransmission, and neuroplasticity. The neurotrophic theory of depression proposes that depression results from reduced BDNF levels in the brain, which can be treated with antidepressants to alleviate depressive behavior and increase BDNF levels. The aim of this review is to provide broad insight into the role of BDNF in the pathogenesis of depression and in antidepressant therapy. The studies mentioned in this review article greatly support the role of BDNF in the pathogenesis of depression and treatment of this disorder with antidepressants. Since abnormalities in BDNF levels lead to the production of diverse insults that amplify the development or progression of depression, it is important to study and explore BDNF impairment in relation to depression, neuroplasticity, and neurogenesis, and increasing BDNF levels through antidepressant therapy, showing positive response in the management of depression.

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease of unknown etiology, primarily affecting the joints, then extra-articular manifestations can occur. Due to its complexity, which is based on an incompletely elucidated pathophysiological mechanism, good RA management requires a multidisciplinary approach. The clinical status of RA patients has improved in recent years due to medical advances in diagnosis and treatment, that have made it possible to reduce disease activity and prevent systemic complications. The most promising results were obtained by developing disease-modifying anti-rheumatic drugs (DMARDs), the class to which conventional synthetic, biologic, and targeted synthetic drugs belong. Furthermore, ongoing drug development has led to obtaining molecules with improved efficacy and safety profiles, but further research is needed until RA turns into a curable pathology. In the present work, we offer a comprehensive perspective on the management of RA, by centralizing the existing data provided by significant literature, emphasizing the importance of an early and accurate diagnosis associated with optimal personalized treatment in order to achieve better outcomes for RA patients. In addition, this study suggests future research perspectives in the treatment of RA that could lead to higher efficacy and safety profiles and lower financial costs.

In the past few decades, polymeric nanocarriers have been recognized as promising tools and have gained attention from researchers for their potential to efficiently deliver bioactive compounds, including drugs, proteins, genes, nucleic acids, etc., in pharmaceutical and biomedical applications. Remarkably, these polymeric nanocarriers could be further modified as stimuli-responsive systems based on the mechanism of triggered release, i.e., response to a specific stimulus, either endogenous (pH, enzymes, temperature, redox values, hypoxia, glucose levels) or exogenous (light, magnetism, ultrasound, electrical pulses) for the effective biodistribution and controlled release of drugs or genes at specific sites. Various nanoparticles (NPs) have been functionalized and used as templates for imaging systems in the form of metallic NPs, dendrimers, polymeric NPs, quantum dots, and liposomes. The use of polymeric nanocarriers for imaging and to deliver active compounds has attracted considerable interest in various cancer therapy fields. So-called smart nanopolymer systems are built to respond to certain stimuli such as temperature, pH, light intensity and wavelength, and electrical, magnetic and ultrasonic fields. Many imaging techniques have been explored including optical imaging, magnetic resonance imaging (MRI), nuclear imaging, ultrasound, photoacoustic imaging (PAI), single photon emission computed tomography (SPECT), and positron emission tomography (PET). This review reports on the most recent developments in imaging methods by analyzing examples of smart nanopolymers that can be imaged using one or more imaging techniques. Unique features, including nontoxicity, water solubility, biocompatibility, and the presence of multiple functional groups, designate polymeric nanocues as attractive nanomedicine candidates. In this context, we summarize various classes of multifunctional, polymeric, nano-sized formulations such as liposomes, micelles, nanogels, and dendrimers.

Cisplatin (CDDP) may induce nephrotoxicity through oxidative stress, DNA damage, and inflammation. This study was performed to evaluate the antioxidant and anti-inflammatory effects of allicin and ascorbic acid (AA) and investigate the nephroprotective efficacy of their combination against CDDP-induced intoxication. Rats were divided into seven groups: control, allicin (10 mg/kg for 14 days), AA (20 mg/kg for 14 days), CDDP (7 mg/kg as a single dose on the seventh experimental day), CDDP-allicin, CDDP-AA, and CDDP-allicin-AA (at the aforementioned doses). The administration of CDDP induced marked body weight loss and renal damage, manifested by significant increases ( p  < 0.05) in serum creatinine, urea, and uric acid levels and significant reductions in serum Na, Ca, and phosphorus concentrations, in addition to severe alterations in serum and renal tissue levels of tumor necrosis factor-α in comparison with control rats. Moreover, CDDP-intoxicated rats exhibited significantly ( p  < 0.05) higher lipid peroxidation, as well as lower levels of reduced glutathione and activities of glutathione peroxidase, superoxide dismutase, and catalase enzymes in the renal tissue, compared with control rats. The administration of allicin or AA significantly reduced ( p  < 0.05) the CDDP-induced changes in all the aforementioned parameters. Interestingly, allicin achieved comparable nephroprotection to AA in most assessed parameters; however, the restoration of normal serum and renal tissue concentrations of these parameters was more frequent in the CDDP-AA group. In conclusion, both allicin and AA showed significant nephroprotective effects against CDDP intoxication and their combination exhibited better protection than either agent alone. These results are probably mediated by their antioxidant and anti-inflammatory activities.

Despite not being utilized as considerably as other antidepressants in the therapy of depression, the monoamine oxidase inhibitors (MAOIs) proceed to hold a place in neurodegeneration and to have a somewhat broad spectrum in respect of the treatment of neurological and psychiatric conditions. Preclinical and clinical studies on MAOIs have been developing in recent times, especially on account of rousing discoveries manifesting that these drugs possess neuroprotective activities. The altered brain levels of monoamine neurotransmitters due to monoamine oxidase (MAO) are directly associated with various neuropsychiatric conditions like Alzheimer’s disease (AD). Activated MAO induces the amyloid-beta (Aβ) deposition via abnormal cleavage of the amyloid precursor protein (APP). Additionally, activated MAO contributes to the generation of neurofibrillary tangles and cognitive impairment due to neuronal loss. No matter the attention of researchers on the participation of MAOIs in neuroprotection has been on monoamine oxidase-B (MAO-B) inhibitors, there is a developing frame of proof indicating that monoamine oxidase-A (MAO-A) inhibitors may also play a role in neuroprotection. The therapeutic potential of MAOIs alongside the complete understanding of the enzyme’s physiology may lead to the future advancement of these drugs.

Compounds derived from plants have several anticancer properties. In the current study, one guaiane-type sesquiterpene dimer, vieloplain F, isolated from Xylopia vielana species, was tested against B-Raf kinase protein (PDB: 3OG7), a potent target for melanoma. A comprehensive in silico analysis was conducted in this research to understand the pharmacological properties of a compound encompassing absorption, distribution, metabolism, excretion, and toxicity (ADMET), bioactivity score predictions, and molecular docking. During ADMET estimations, the FDA-approved medicine vemurafenib was hepatotoxic, cytochrome-inhibiting, and non-cardiotoxic compared to the vieloplain F. The bioactivity scores of vieloplain F were active for nuclear receptor ligand and enzyme inhibitor. During molecular docking experiments, the compound vieloplain F has displayed a higher binding potential with −11.8 kcal/mol energy than control vemurafenib −10.2 kcal/mol. It was shown that intermolecular interaction with the B-Raf complex and the enzyme’s active gorge through hydrogen bonding and hydrophobic contacts was very accurate for the compound vieloplain F, which was then examined for MD simulations. In addition, simulations using MM-GBSA showed that vieloplain F had the greatest propensity to bind to active site residues. The vieloplain F has predominantly represented a more robust profile compared to control vemurafenib, and these results opened the road for vieloplain F for its utilization as a plausible anti-melanoma agent and anticancer drug in the next era.

Forkhead box-O (FoxO) transcriptional factors perform essential functions in several physiological and biological processes. Recent studies have shown that FoxO is implicated in the pathophysiology of depression. Changes in the upstream mediators of FoxOs including brain-derived neurotrophic factor (BDNF) and protein kinase B have been associated with depressive disorder and the antidepressant agents are known to alter the phosphorylation of FoxOs. Moreover, FoxOs might be regulated by serotonin or noradrenaline signaling and the hypothalamic-pituitary-adrenal (HPA)-axis,both of them are associated with the development of the depressive disorder. FoxO also regulates neural morphology, synaptogenesis, and neurogenesis in the hippocampus, which accounts for the pathogenesis of the depressive disorder. The current article underlined the potential functions of FoxOs in the etiology of depressive disorder and formulate few essential proposals for further investigation. The review also proposes that FoxO and its signal pathway might establish possible therapeutic mediators for the management of depressive disorder.

Oxidative stress and inflammation play a critical role in the initiation and progression of age-related ocular abnormalities as cataract, glaucoma, diabetic retinopathy, and macular degeneration. Therefore, phytochemicals with proven antioxidant and anti-inflammatory activities, such as carotenoids and polyphenols, could be of benefit in these diseases. We searched PubMed and Web of Science databases for original studies investigating the benefits of different carotenoids and polyphenols in age-related ophthalmic diseases. Our results showed that several polyphenols (such as anthocyanins, Ginkgo biloba, quercetin, and resveratrol) and carotenoids (such as lutein, zeaxanthin, and mezoxanthin) have shown significant preventive and therapeutic benefits against the aforementioned conditions. The involved mechanisms in these findings include mitigating the production of reactive oxygen species, inhibiting the tumor necrosis factor-α and vascular endothelial growth factor pathways, suppressing p53-dependent apoptosis, and suppressing the production of inflammatory markers, such as interleukin- (IL-) 8, IL-6, IL-1a, and endothelial leucocyte adhesion molecule-1. Consumption of products containing these phytochemicals may be protective against these diseases; however, adequate human data are lacking. This review discusses the role and mechanisms of polyphenols and carotenoids and their possible synergistic effects on the prevention and treatment of age-related eye diseases that are induced or augmented by oxidative stress and inflammation.

Traditionally, herbal compounds have been the focus of scientific interest for the last several centuries, and continuous research into their medicinal potential is underway. Berberine (BBR) is an isoquinoline alkaloid extracted from plants that possess a broad array of medicinal properties, including anti-diarrheal, anti-fibrotic, antidiabetic, anti-inflammatory, anti-obesity, antihyperlipidemic, antihypertensive, antiarrhythmic, antidepressant, and anxiolytic effects, and is frequently utilized as a traditional Chinese medicine. BBR promotes metabolisms of glucose and lipids by activating adenosine monophosphate-activated protein kinase, stimulating glycolysis and inhibiting functions of mitochondria; all of these ameliorate type 2 diabetes mellitus. BBR has also been shown to have benefits in congestive heart failure, hypercholesterolemia, atherosclerosis, non-alcoholic fatty liver disease, Alzheimer’s disease, and polycystic ovary syndrome. BBR has been investigated as an interesting pharmacophore with the potential to contribute significantly to the research and development of novel therapeutic medicines for a variety of disorders. Despite its enormous therapeutic promise, the clinical application of this alkaloid was severely limited because of its unpleasant pharmacokinetic characteristics. Poor bioavailability, limited absorption, and poor water solubility are some of the obstacles that restricted its use. Nanotechnology has been suggested as a possible solution to these problems. The present review aims at recent updates on important therapeutic activities of BBR and different types of nanocarriers used for the delivery of BBR in different diseases.