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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.

Breast cancer is the second leading cause of death for women worldwide. The heterogeneity of this disease presents a big challenge in its therapeutic management. However, recent advances in molecular biology and immunology enable to develop highly targeted therapies for many forms of breast cancer. The primary objective of targeted therapy is to inhibit a specific target/molecule that supports tumor progression. Ak strain transforming, cyclin-dependent kinases, poly (ADP-ribose) polymerase, and different growth factors have emerged as potential therapeutic targets for specific breast cancer subtypes. Many targeted drugs are currently undergoing clinical trials, and some have already received the FDA approval as monotherapy or in combination with other drugs for the treatment of different forms of breast cancer. However, the targeted drugs have yet to achieve therapeutic promise against triple-negative breast cancer (TNBC). In this aspect, immune therapy has come up as a promising therapeutic approach specifically for TNBC patients. Different immunotherapeutic modalities including immune-checkpoint blockade, vaccination, and adoptive cell transfer have been extensively studied in the clinical setting of breast cancer, especially in TNBC patients. The FDA has already approved some immune-checkpoint blockers in combination with chemotherapeutic drugs to treat TNBC and several trials are ongoing. This review provides an overview of clinical developments and recent advancements in targeted therapies and immunotherapies for breast cancer treatment. The successes, challenges, and prospects were critically discussed to portray their profound prospects.

Alzheimer’s disease (AD) is a neurodegenerative disorder, and its pathogenesis is not fully known. Although there are several hypotheses, such as neuroinflammation, tau hyperphosphorylation, amyloid-β plaques, neurofibrillary tangles, and oxidative stress, none of them completely explain the origin and progression of AD. Emerging evidence suggests that gut microbiota and epigenetics can directly influence the pathogenesis of AD via their effects on multiple pathways, including neuroinflammation, oxidative stress, and amyloid protein. Various gut microbes such as Actinobacteria, Bacteroidetes, E. coli, Firmicutes, Proteobacteria, Tenericutes, and Verrucomicrobia are known to play a crucial role in the pathogenesis of AD. These microbes and their metabolites modulate various physiological processes that contribute to AD pathogenesis, such as neuroinflammation and other inflammatory processes, amyloid deposition, cytokine storm syndrome, altered BDNF and NMDA signaling, impairing neurodevelopmental processes. Likewise, epigenetic markers associated with AD mainly include histone modifications and DNA methylation, which are under the direct control of a variety of enzymes, such as acetylases and methylases. The activity of these enzymes is dependent upon the metabolites generated by the host’s gut microbiome, suggesting the significance of epigenetics in AD pathogenesis. It is interesting to know that both gut microbiota and epigenetics are dynamic processes and show a high degree of variation according to diet, stressors, and environmental factors. The bidirectional relation between the gut microbiota and epigenetics suggests that they might work in synchrony to modulate AD representation, its pathogenesis, and progression. They both also provide numerous targets for early diagnostic biomarkers and for the development of AD therapeutics. This review discusses the gut microbiota and epigenetics connection in the pathogenesis of AD and aims to highlight vast opportunities for diagnosis and therapeutics of AD.

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.

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.

This article is an extensive collection of scientific literature related to the impact of fertilizers on soil microbial and enzymatic activity. Due to the significance of technology in quantitative and qualitative evaluation of agricultural production, this is a basic problem for the present and future of mankind, where the scientific data being of utmost importance related to the topic. The comparison, including pedo-enzymological evaluation of minerals along with organic fertilization, highlights significant differences between mineral and organic fertilizers, confirming the superiority of complex mineral-organic fertilization. Enzymatic indicators that describe and define the soil quality resulted from enzymatic activities value and provide valuable information regarding the soil fertility status. Moreover, soil enzyme responds to soil management as well as to environmental pollutants. Changes of environmental conditions and pollutants like heavy metals and other toxic substances result in a shift in the biological activity of the soil. These changes can destabilize the soil system and cause a decrease in the nutrient pools. To ensure the improvement of fertilization techniques, the properties of nanoparticles are exploited that can efficiently release nutrients to plant cells. Numerous researches were performed in order to follow the long-term effects of incorporating nanofertilizers into the soil, obtaining an exhaustive overview of this new technology over the development of sustainable agriculture.

The occurrence of Alzheimer’s disease (AD) worldwide has been progressively accelerating at an alarming rate, without any successful therapeutic strategy for the disease mitigation. The complexity of AD pathogenesis needs to be targeted with an alternative approach, as provided by the superfamily of ATP-binding cassette (ABC) transporters, which constitutes an extensive range of proteins, capable of transporting molecular entities across biological membranes. These protein moieties have been implicated in AD, based upon their potential in lipid transportation, resulting in maintenance of cholesterol homeostasis. These transporters have been reported to target the primary hallmark of AD pathogenesis, namely, beta-amyloid hypothesis, which is associated with accumulation of beta-amyloid (Aβ) plaques in AD patients. The ABC transporters have been observed to be localized to the capillary endothelial cells of the blood-brain barrier and neural parenchymal cells, where they exhibit different roles, consequently influencing the neuronal expression of Aβ peptides. The review highlights different families of ABC transporters, ABCB1 (P-glycoprotein), ABCA (ABCA1, ABCA2, and ABCA7), ABCG2 (BCRP; breast cancer resistance protein), ABCG1 and ABCG4, as well as ABCC1 (MRP; multidrug resistance protein) in the CNS, and their interplay in regulating cholesterol metabolism and Aβ peptide load in the brain, simultaneously exerting protective effects against neurotoxic substrates and xenobiotics. The authors aim to establish the significance of this alternative approach as a novel therapeutic target in AD, to provide the researchers an opportunity to evaluate the potential aspects of ABC transporters in AD treatment.

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.

Alzheimer's disease (AD) is one of the most prevailing neurodegenerative disorders of elderly humans associated with cognitive damage. Biochemical, epigenetic, and pathophysiological factors all consider a critical role of extracellular amyloid-beta (Aß) plaques and intracellular neurofibrillary tangles (NFTs) as pathological hallmarks of AD. In an endeavor to describe the intricacy and multifaceted nature of AD, several hypotheses based on the roles of Aß accumulation, tau hyperphosphorylation, impaired cholinergic signaling, neuroinflammation, and autophagy during the initiation and advancement of the disease have been suggested. However, in no way do these theories have the potential of autonomously describing the pathophysiological alterations located in AD. The complex pathological nature of AD has hindered the recognition and authentication of successful biomarkers for the progression of its diagnosis and therapeutic strategies. There has been a significant research effort to design multi-target-directed ligands for the treatment of AD, an approach which is developed by the knowledge that AD is a composite and multifaceted disease linked with several separate but integrated molecular pathways.