Temperature-Dependent Products in Gallium Flux Reactions of Cerium and Transition Metals.

Reactions of cerium and transition metals in excess molten gallium were carried out, exploring the formation of different cerium intermetallics as the flux reaction is cooled. Ce/T/Ga reactions with T = Ni, Cu, Pd, Ag, and Zn produce a high-temperature product, which converts into a low-temperature product in the flux. The phases present in the flux mixture were determined by quenching identical reactions at 750 and 300 °C and identifying the isolated products using elemental analysis and X-ray diffraction. The compounds CeGa2, CeCu0.37Ga3.63, CePd0.32Ga3.68, Ce5Ag1.76Ga17.29, and Ce5Zn1.37Ga17.73 were isolated by quenching at 750 °C. Upon cooling to 300 °C, the corresponding reactions instead yielded CeGa6, Ce2CuGa12, Ce2PdGa12, Ce2Ag0.7Ga9.1, and CeZnxGa7-x. All of these structures contain cerium in the ThCr2Si2-related layers. Large crystals of high-temperature products CeCu0.37Ga3.63, CePd0.32Ga3.68, Ce5Ag1.76Ga17.29, and Ce5Zn1.37Ga17.73 were used for magnetic susceptibility measurements. All of these materials show highly anisotropic ferromagnetic ordering of Ce3+ moments below 8 K, which is in contrast to the antiferromagnetism seen for the compounds that were isolated at 300 °C.

Epigenetics of glioblastoma multiforme: From molecular mechanisms to therapeutic approaches.

Glioblastoma multiforme (GBM) is the most common form of brain cancer and one of the most aggressive cancers found in humans. Most of the signs and symptoms of GBM can be mild and slowly aggravated, although other symptoms might demonstrate it as an acute ailment. However, the precise mechanisms of the development of GBM remain unknown. Due to the improvement of molecular pathology, current researches have reported that glioma progression is strongly connected with different types of epigenetic phenomena, such as histone modifications, DNA methylation, chromatin remodeling, and aberrant microRNA. Furthermore, the genes and the proteins that control these alterations have become novel targets for treating glioma because of the reversibility of epigenetic modifications. In some cases, gene mutations including P16, TP53, and EGFR, have been observed in GBM. In contrast, monosomies, including removals of chromosome 10, particularly q23 and q25-26, are considered the standard markers for determining the development and aggressiveness of GBM. Recently, amid the epigenetic therapies, histone deacetylase inhibitors (HDACIs) and DNA methyltransferase inhibitors have been used for treating tumors, either single or combined. Specifically, HDACIs are served as a good choice and deliver a novel pathway to treat GBM. In this review, we focus on the epigenetics of GBM and the consequence of its mutations. We also highlight various treatment approaches, namely gene editing, epigenetic drugs, and microRNAs to combat GBM.

Inflammation-targeted nanomedicine against brain cancer: From design strategies to future developments.

Brain cancer is an aggressive type of cancer with poor prognosis. While the immune system protects against cancer in the early stages, the tumor exploits the healing arm of inflammatory reactions to accelerate its growth and spread. Various immune cells penetrate the developing tumor region, establishing a pro-inflammatory tumor milieu. Additionally, tumor cells may release chemokines and cytokines to attract immune cells and promote cancer growth. Inflammation and its associated mechanisms in the progression of cancer have been extensively studied in the majority of solid tumors, especially brain tumors. However, treatment of the malignant brain cancer is hindered by several obstacles, such as the blood-brain barrier, transportation inside the brain interstitium, inflammatory mediators that promote tumor growth and invasiveness, complications in administering therapies to tumor cells specifically, the highly invasive nature of gliomas, and the resistance to drugs. To resolve these obstacles, nanomedicine could be a potential strategy that has facilitated advancements in diagnosing and treating brain cancer. Due to the numerous benefits provided by their small size and other features, nanoparticles have been a prominent focus of research in the drug-delivery field. The purpose of this article is to discuss the role of inflammatory mediators and signaling pathways in brain cancer as well as the recent advances in understanding the nano-carrier approaches for enhancing drug delivery to the brain in the treatment of brain cancer.

Production of high molecular-ordered stilbene oligomers for the study of their biological activity: total synthesis, bio-catalyzed synthesis and production by plant systems.

Though the iconic stilbene resveratrol and its related dimers constitute a top storyline in the field of natural product research, resveratrol oligomers (condensation >2) have been left aside despite their higher biological activity compared to that of the monomers. This situation largely results from the difficulty of getting them in sufficient quantities to enable evaluation of their biological properties in vivo. We present here a synthetic and critical analysis of the methods used for the production of high molecular-ordered stilbene oligomers of potential biomedical interest, gathering the most salient data regarding the approaches employed to prepare them by total synthesis, use of biomimetic approaches or through plant systems.

Role of melatonin in Alzheimer's disease: From preclinical studies to novel melatonin-based therapies.

Melatonin and novel melatonin-based therapies such as melatonin-containing hybrid molecules, melatonin analogues, and melatonin derivatives have been investigated as potential therapeutics against Alzheimer's disease (AD) pathogenesis. In this review, we examine the developmental trends of melatonin therapies for AD from 1997 to 2021. We then highlight the neuroprotective mechanisms of melatonin therapy derived from preclinical studies. These mechanisms include the alleviation of amyloid-related burden, neurofibrillary tangle accumulation, oxidative stress, neuroinflammation, apoptosis, mitochondrial dysfunction, and impaired neuroplasticity and neurotransmission. We further illustrate the beneficial effects of melatonin on behavior in animal models of AD. Next, we discuss the clinical effects of melatonin on sleep, cognition, behavior, psychiatric symptoms, electroencephalography findings, and molecular biomarkers in patients with mild cognitive impairment and AD. We then explore the effectiveness of novel melatonin-based therapies. Lastly, we discuss the limitations of current melatonin therapies for AD and suggest two emerging research themes for future study.

Microglia in Alzheimer's Disease: A Favorable Cellular Target to Ameliorate Alzheimer's Pathogenesis.

Microglial cells serve as molecular sensors of the brain that play a role in physiological and pathological conditions. Under normal physiology, microglia are primarily responsible for regulating central nervous system homeostasis through the phagocytic clearance of redundant protein aggregates, apoptotic cells, damaged neurons, and synapses. Furthermore, microglial cells can promote and mitigate amyloid ß phagocytosis and tau phosphorylation. Dysregulation of the microglial programming alters cellular morphology, molecular signaling, and secretory inflammatory molecules that contribute to various neurodegenerative disorders especially Alzheimer's disease (AD). Furthermore, microglia are considered primary sources of inflammatory molecules and can induce or regulate a broad spectrum of cellular responses. Interestingly, in AD, microglia play a double-edged role in disease progression; for instance, the detrimental microglial effects increase in AD while microglial beneficiary mechanisms are jeopardized. Depending on the disease stages, microglial cells are expressed differently, which may open new avenues for AD therapy. However, the disease-related role of microglial cells and their receptors in the AD brain remain unclear. Therefore, this review represents the role of microglial cells and their involvement in AD pathogenesis.

Phytostilbenes as agrochemicals: biosynthesis, bioactivity, metabolic engineering and biotechnology.

Covering: 1976 to 2020. Although constituting a limited chemical family, phytostilbenes represent an emblematic group of molecules among natural compounds. Ever since their discovery as antifungal compounds in plants and their ascribed role in human health and disease, phytostilbenes have never ceased to arouse interest for researchers, leading to a huge development of the literature in this field. Owing to this, the number of references to this class of compounds has reached the tens of thousands. The objective of this article is thus to offer an overview of the different aspects of these compounds through a large bibliography analysis of more than 500 articles. All the aspects regarding phytostilbenes will be covered including their chemistry and biochemistry, regulation of their biosynthesis, biological activities in plants, molecular engineering of stilbene pathways in plants and microbes as well as their biotechnological production by plant cell systems.

Deciphering the Interacting Mechanisms of Circadian Disruption and Alzheimer's Disease.

Alzheimer's disease (AD) is one of the crucial causative factors for progressive dementia. Neuropathologically, AD is characterized by the extracellular accumulation of amyloid beta plaques and intracellular neurofibrillary tangles in cortical and limbic regions of the human brain. The circadian system is one of the many affected physiological processes in AD, the dysfunction of which may reflect in the irregularity of the sleep/wake cycle. The interplay of circadian and sleep disturbances inducing AD progression is bidirectional. Sleep-associated pathological alterations are frequently evident in AD. Understanding the interrelation between circadian disruption and AD may allow for earlier identification of AD pathogenesis as well as better suited approaches and potential therapies to combat dementia. In this article, we examine the existing literature related to the molecular mechanisms of the circadian clock and interacting mechanisms of circadian disruption and AD pathogenesis.

Biological evidence of gintonin efficacy in memory disorders.

Gintonin is a novel glycolipoprotein, which has been abundantly found in the root of Korean ginseng. It holds lysophosphatidic acids (LPAs), primarily identified LPA C18:2, and is an exogenous agonist of LPA receptors (LPARs). Gintonin maintains blood-brain barrier integrity, and it has recently been studied in several models of neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD), Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. Gintonin demonstrated neuroprotective activity by providing action against neuroinflammation-, apoptosis- and oxidative stress-mediated neurodegeneration. Gintonin showed an emerging role as a modulator of synaptic transmission and neurogenesis and also potentially regulated autophagy in primary cortical astrocytes. It also ameliorated the toxic agent-induced and genetic models of cognitive deficits in experimental NDDs. As a novel agonist of LPARs, gintonin regulated several G protein-coupled receptors (GPCRs) including GPR40 and GPR55. However, further study needs to be investigated to understand the underlying mechanism of action of gintonin in memory disorders.

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.

Molecular Mechanisms of Astaxanthin as a Potential Neurotherapeutic Agent.

Neurological disorders are diseases of the central and peripheral nervous system that affect millions of people, and the numbers are rising gradually. In the pathogenesis of neurodegenerative diseases, the roles of many signaling pathways were elucidated; however, the exact pathophysiology of neurological disorders and possible effective therapeutics have not yet been precisely identified. This necessitates developing multi-target treatments, which would simultaneously modulate neuroinflammation, apoptosis, and oxidative stress. The present review aims to explore the potential therapeutic use of astaxanthin (ASX) in neurological and neuroinflammatory diseases. ASX, a member of the xanthophyll group, was found to be a promising therapeutic anti-inflammatory agent for many neurological disorders, including cerebral ischemia, Parkinson's disease, Alzheimer's disease, autism, and neuropathic pain. An effective drug delivery system of ASX should be developed and further tested by appropriate clinical trials.

Anti-Alzheimer's Molecules Derived from Marine Life: Understanding Molecular Mechanisms and Therapeutic Potential.

Alzheimer's disease (AD) is a devastating neurodegenerative disease and the most common cause of dementia. It has been confirmed that the pathological processes that intervene in AD development are linked with oxidative damage to neurons, neuroinflammation, tau phosphorylation, amyloid beta (Aß) aggregation, glutamate excitotoxicity, and cholinergic deficit. Still, there is no available therapy that can cure AD. Available therapies only manage some of the AD symptoms at the early stages of AD. Various studies have revealed that bioactive compounds derived from marine organisms and plants can exert neuroprotective activities with fewer adverse events, as compared with synthetic drugs. Furthermore, marine organisms have been identified as a source of novel compounds with therapeutic potential. Thus, there is a growing interest regarding bioactive compounds derived from marine sources that have anti-AD potentials. Various marine drugs including bryostatin-1, homotaurine, anabaseine and its derivative, rifampicins, anhydroexfoliamycin, undecylprodigioisin, gracilins, 13-desmethyl spirolide-C, and dictyostatin displayed excellent bioavailability and efficacy against AD. Most of these marine drugs were found to be well-tolerated in AD patients, along with no significant drug-associated adverse events. In this review, we focus on the drugs derived from marine life that can be useful in AD treatment and also summarize the therapeutic agents that are currently used to treat AD.

Mesoporous Carbon: A Versatile Material for Scientific Applications.

Mesoporous carbon is a promising material having multiple applications. It can act as a catalytic support and can be used in energy storage devices. Moreover, mesoporous carbon controls body's oral drug delivery system and adsorb poisonous metal from water and various other molecules from an aqueous solution. The accuracy and improved activity of the carbon materials depend on some parameters. The recent breakthrough in the synthesis of mesoporous carbon, with high surface area, large pore-volume, and good thermostability, improves its activity manifold in performing functions. Considering the promising application of mesoporous carbon, it should be broadly illustrated in the literature. This review summarizes the potential application of mesoporous carbon in many scientific disciplines. Moreover, the outlook for further improvement of mesoporous carbon has been demonstrated in detail. Hopefully, it would act as a reference guidebook for researchers about the putative application of mesoporous carbon in multidimensional fields.

Role of Phenolic Compounds in Human Disease: Current Knowledge and Future Prospects.

Inflammation is a natural protective mechanism that occurs when the body's tissue homeostatic mechanisms are disrupted by biotic, physical, or chemical agents. The immune response generates pro-inflammatory mediators, but excessive output, such as chronic inflammation, contributes to many persistent diseases. Some phenolic compounds work in tandem with nonsteroidal anti-inflammatory drugs (NSAIDs) to inhibit pro-inflammatory mediators' activity or gene expression, including cyclooxygenase (COX). Various phenolic compounds can also act on transcription factors, such as nuclear factor-κB (NF-κB) or nuclear factor-erythroid factor 2-related factor 2 (Nrf-2), to up-or downregulate elements within the antioxidant response pathways. Phenolic compounds can inhibit enzymes associated with the development of human diseases and have been used to treat various common human ailments, including hypertension, metabolic problems, incendiary infections, and neurodegenerative diseases. The inhibition of the angiotensin-converting enzyme (ACE) by phenolic compounds has been used to treat hypertension. The inhibition of carbohydrate hydrolyzing enzyme represents a type 2 diabetes mellitus therapy, and cholinesterase inhibition has been applied to treat Alzheimer's disease (AD). Phenolic compounds have also demonstrated anti-inflammatory properties to treat skin diseases, rheumatoid arthritis, and inflammatory bowel disease. Plant extracts and phenolic compounds exert protective effects against oxidative stress and inflammation caused by airborne particulate matter, in addition to a range of anti-inflammatory, anticancer, anti-aging, antibacterial, and antiviral activities. Dietary polyphenols have been used to prevent and treat allergy-related diseases. The chemical and biological contributions of phenolic compounds to cardiovascular disease have also been described. This review summarizes the recent progress delineating the multifunctional roles of phenolic compounds, including their anti-inflammatory properties and the molecular pathways through which they exert anti-inflammatory effects on metabolic disorders. This study also discusses current issues and potential prospects for the therapeutic application of phenolic compounds to various human diseases.

Multifarious roles of mTOR signaling in cognitive aging and cerebrovascular dysfunction of Alzheimer's disease.

Age-related cognitive failure is a main devastating incident affecting even healthy people. Alzheimer's disease (AD) is the utmost common form of dementia among the geriatric community. In the pathogenesis of AD, cerebrovascular dysfunction is revealed before the beginning of the cognitive decline. Mounting proof shows a precarious impact of cerebrovascular dysregulation in the development of AD pathology. Recent studies document that the mammalian target of rapamycin (mTOR) acts as a crucial effector of cerebrovascular dysregulation in AD. The mTOR contributes to brain vascular dysfunction and subsequence cerebral blood flow deficits as well as cognitive impairment. Furthermore, mTOR causes the blood-brain barrier (BBB) breakdown in AD models. Inhibition of mTOR hyperactivity protects the BBB integrity in AD. Furthermore, mTOR drives cognitive defect and cerebrovascular dysfunction, which are greatly prevalent in AD, but the central molecular mechanisms underlying these alterations are obscure. This review represents the crucial and current research findings regarding the role of mTOR signaling in cognitive aging and cerebrovascular dysfunction in the pathogenesis of AD.

Exploring the Therapeutic Potentials of Highly Selective Oxygenated Chalcone Based MAO-B Inhibitors in a Haloperidol-Induced Murine Model of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder of dopaminergic, noradrenergic, and serotonergic systems, in which dopamine, noradrenaline, and serotonin levels are depleted and lead to the development of motor and non-motor symptoms such as tremor, bradykinesia, weight changes, fatigue, depression, and visual hallucinations. Therapeutic strategies place much focus on dopamine replacement and the inhibition of dopamine metabolism. The present study was based on the known abilities of chalcones to act as molecular scaffolds that selectively inhibit MAO-B with the added advantage of binding reversibly. Recently, we synthesized a series of 26 chalcone compounds, amongst which (2E)-1-(2H-1,3-benzodioxol-5-yl)-3-(4-fluorophenyl)prop-2-en-1-one (O10) and (2E)-1-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-(4-fluorophenyl)prop-2-en-1-one (O23) most inhibited MAO-B. Hence, the present study was performed to explore the molecular mechanisms responsible for the neuroprotective effect of O10 and O23 at varying doses such as 10, 20, and 30 mg/kg each in a haloperidol-induced murine model of PD. Both compounds were effective (though O23 was the more effective) at ameliorating extrapyramidal and non-motor symptoms in the model and improved locomotory and exploratory behaviors, reduced oxidative stress markers, and enhanced antioxidant marker and neurotransmitter levels. Furthermore, histopathological studies showed O10 and O23 both reduced neurofibrillary tangles and plaques to almost normal control levels.

Sesquiterpenes and their derivatives-natural anticancer compounds: An update.

Sesquiterpenes belong to the largest group of plant secondary metabolites, which consist of three isoprene building units. These compounds are widely distributed in various angiosperms, a few gymnosperms and bryophytes. Sesquiterpenes and their allied derivatives are bio-synthesized in various plant parts including leaves, fruits and roots. These plant-based metabolites are predominantly identified in the Asteraceae family, wherein up to 5000 complexes have been documented to date. Sesquiterpenes and their derivatives are characteristically associated with plant defence mechanisms owing to their antifungal, antibacterial and antiviral activities. Over the last two decades, these compounds have been reportedly demonstrated health promoting perspectives against a wide range of metabolic syndromes i.e. hyperglycemia, hyperlipidemia, cardiovascular complications, neural disorders, diabetes, and cancer. The high potential of sesquiterpenes and their derivatives against various cancers like breast, colon, bladder, pancreatic, prostate, cervical, brain, liver, blood, ovarium, bone, endometrial, oral, lung, eye, stomach and kidney are the object of this review. Predominantly, it recapitulates the literature elucidating sesquiterpenes and their derivatives while highlighting the mechanistic approaches associated with their potent anticancer activities such as modulating nuclear factor kappa (NF-kB) activity, inhibitory action against lipid peroxidation and retarding the production of reactive oxygen & nitrogen species (ROS&RNS).

Molecular insights into therapeutic promise of targeting of Wnt/ß-catenin signaling pathway in obesity.

Obesity is a curable disorder which is a global health concern, linked to an excess amount of fat. It is caused by inherited and environmental factors and can be grim to maintain through dieting only. The importance of peculiar Wnt/ß-catenin signaling has directed considerable efforts in the future production of therapeutic approaches in metabolic complications, including obesity. The article aims to examine the prospects of Wnt/ß-catenin signaling cascade in obesity via directing effects of Wnt/ß-catenin cascade in regulating appetite. A deep research on the literature available to date, for Wnt/ß-catenin cascade in obesity is conducted using various medical databases like PubMed, MEDLINE from the internet. The articles published in English language were mainly preferred. Obesity has developed endemic worldwide, which initiates various obesity-related comorbidities. Obesity is implied by excessive deposition of fat primarily in the adipose tissue. Numerous studies have shown the vital impact of the Wnt/ß-catenin signaling pathway in the growth of body part and biological homeostasis, while latent data illustrate the inherited variations in the Wnt/ß-catenin cascade, correlating to several complications. The current article enlightens the stimulation of the Wnt/ß-catenin cascade in obesity, mainly depot-explicit impact among adipose tissue during high caloric intake regulation and WAT browning event. Taken all together these data illustrate Wnt/ß-catenin signaling cascade subsidizes to obesity promoted insulin resistance independent proliferation of adipose tissue.

Correlation Between Subjective Happiness and Pleasant Activities at Workplace in Nursing Staff for Older Individuals in Japan.

The purpose of this study was to investigate the correlations between nursing staff's mental health, number of years worked, night shifts performed, and pleasant activities at the workplace. One hundred forty-three subjects who had no missing data were analyzed. Questions consisted of basic attributes, subjective happiness scale (SHS), and pleasant activities conducted at the workplace. Denouements of SHS indicated a significant trend for the main effect, with more pleasant activities in the high SHS group than the low SHS group. The interaction was significant, with fewer pleasant activities in participants in the low SHS group who worked the night shift compared with those who worked the night shift regardless of work experience. The outcomes of this study suggest that it is essential to expand the repertoire of pleasant activities at the workplace to increase the subjective happiness of nursing staff for older individuals.

Revisiting the Amyloid Cascade Hypothesis: From Anti-Aß Therapeutics to Auspicious New Ways for Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder related to age, characterized by the cerebral deposition of fibrils, which are made from the amyloid-ß (Aß), a peptide of 40-42 amino acids. The conversion of Aß into neurotoxic oligomeric, fibrillar, and protofibrillar assemblies is supposed to be the main pathological event in AD. After Aß accumulation, the clinical symptoms fall out predominantly due to the deficient brain clearance of the peptide. For several years, researchers have attempted to decline the Aß monomer, oligomer, and aggregate levels, as well as plaques, employing agents that facilitate the reduction of Aß and antagonize Aß aggregation, or raise Aß clearance from brain. Unluckily, broad clinical trials with mild to moderate AD participants have shown that these approaches were unsuccessful. Several clinical trials are running involving patients whose disease is at an early stage, but the preliminary outcomes are not clinically impressive. Many studies have been conducted against oligomers of Aß which are the utmost neurotoxic molecular species. Trials with monoclonal antibodies directed against Aß oligomers have exhibited exciting findings. Nevertheless, Aß oligomers maintain equivalent states in both monomeric and aggregation forms; so, previously administered drugs that precisely decrease Aß monomer or Aß plaques ought to have displayed valuable clinical benefits. In this article, Aß-based therapeutic strategies are discussed and several promising new ways to fight against AD are appraised.