According to the latest report in 2024 by the World Health Organization, based on global data from 2021, Alzheimer’s disease (AD) and other forms of dementia rank seventh among the leading causes of death worldwide, with an estimated 1.8 million deaths. This alarming number underscores the urgent requirement for effective treatments. AD and other dementias also severely affect the global economy. Unfortunately, no cure has been found, and effective treatments remain limited. Over the past two decades, thousands of disease-modifying drugs have been developed for AD treatment. However, most have failed to progress beyond phase I clinical trials, with only a few reaching phase III. To date, lecanemab (sold under the brand name Leqembi) is the only drug to receive full approval from the United States Food and Drug Administration for slowing AD progression. This drug is specifically designed to target and clear amyloid-beta (Aβ) plaques. Apart from targeting Aβ aggregation and tau tangles, neuroinflammatory regulatory pathways have emerged as promising therapeutic targets. With advancing research, neuroinflammation has been considered one of the core characteristics of AD and the third major pathological hallmark of the disease after Aβ plaques and neurofibrillary tau tangles. In this review, we summarize key research findings in neuroinflammatory regulation of AD and related dementias that are promising for treatments. We also provide an overview of clinical trials targeting the immune system or neuroinflammatory regulatory pathways, analyzing their challenges and potential successes.

The foraging of honey bees is one of the most well-organized and admirable behaviors that exist among social insects. In behavioral studies, these beautiful insects have been extensively used for understanding time–space learning, landmark use, and the concept of learning. Highly organized behaviors such as social interaction and communication are systematically well-organized behavioral components of honey bee foraging. Over the last two decades, understanding the regulatory mechanisms underlying honey bee foraging at the cellular and molecular levels has been increasingly interested to several researchers. Upon the search of regulatory genes of brain and behavior, immediate early (IE) genes are considered as a good tool to begin the search investigation. Our two recent studies have demonstrated three IE genes, namely,Egr-1, Hr38, andKakusei, playing a role in the daily foraging of bees and their association with learning and memory during foraging. These studies further evidence that IE genes can be used as a tool in finding the specific molecular/cellular players of foraging in honey bees and its behavioral components such as learning, memory, social interaction, and social communication. In this article, we provide the details of the method of sample collection at different times during foraging to investigate the foraging regulatory molecules.

Neuroinflammation is considered one of the major causing factors of neuronal dysfunction leading to dementia associated with Alzheimer disease (AD) or AD related dementias (ADRD). Several published articles have reported potential involvement of microglia, astrocytes, oligodendrocyte, B-cell and T-cell linked with different neuroinflammatory signaling pathways. This article is intended to provide a summary of various published papers in this area and show the neuroinflammatory pathways that associates with the imbalanced level microglia, astrocytes, oligodendrocyte, B-cell and T-cell leading to neuronal dysfunction, dementia or cognitive decline of neurological diseases like AD and ADRD. Several drugs have been designed and tested, yet unable to find an appropriate drug for treatment. Therefore, further attention is essential for deeper understanding the underlying mechanism of these diseases for finding an appropriate drug target and in this review, we provide the importance of cellular neuroinflammatory pathways that induce neuronal dysfunction leading the dementia or cognitive deficits in AD and ADRD.

The leaf crude extract of Oroxylum indicum (L.) Kurz induces genomic DNA fragmentation, comet formation, and the inhibition of cell proliferation in the prostate cancer cell line PC3, as assessed by agarose gel electrophoresis, comet assay and MTT assay, respectively. The bioactive compound was purified through bioassay-guided fractionation using preparative HPLC and MTT assay. The light brown and water-soluble compound was characterized using 1H and 13C nuclear magnetic resonance (NMR), Fourier transform infrared (FT-IR), and electrospray ionization (ESI) mass spectrometry. The compound was identified as a glycosylated hydroquinone derivative, 2-[p-(2-Carboxyhydrazino)phenoxy]-6-(hydroxymethyl) tetrahy-dro-2H-pyran-3,4,5-triol (molecular formula, C13H18N2O8; molecular mass = 330). The identified phytocompound has not been reported earlier elsewhere. Therefore, the common name of the novel anticancer phytocompound isolated from Oroxylum indicum in this current study is oroxyquinone. The half-maximal inhibitory concentration (IC₅₀) of oroxyquinone on PC3 cells was 58.9 µM (95% CI = 54.5 to 63.7 µM). Treatment of PC3 cells with oroxyquinone induced genomic DNA fragmentation and chromatin condensation, increased in the annexin-V positive cells, arrested the cell cycle at S phases, and inhibited the cell migration; as assessed by comet assay, DAPI staining, flow cytometry and a wound healing assay, respectively. On the investigation of the molecular mechanism of the induction of apoptosis, the results indicated that oroxyquinone induced caspase-3 and PARP independent apoptosis but through the p38 pathway and the localization of AIF into the nucleus. The present study identifies a novel anticancer molecule and provides scientific evidence supporting the therapeutic potency of Oroxylum indicum for ethnomedicinal uses.

According to latest report of 2024 by World Health Organization (WHO) based on global data of 2021, Alzheimer’s disease (AD) and other forms of dementia is placed at seventh position among the leading cause of death, that accounts for killing of 1.8 million lives by the disease; and stroke causes highest number of deaths in the world ("World Health Organisation (WHO) The top 10 causes of death https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death ", 2024) Similarly, Centers for Disease Control and Prevention (CDC) National Center for Health Statistics in 2024 also reported AD to be seventh leading cause of death in the United States, based on data from 2021 to 2022 accounting 1.2 millions of deaths.("CDC’s National Center for Health Statistics, Leading Causes of Death https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm," 2024). This alarming number of deaths due to AD is the call for the urgent need to find proper treatment or cure of the disease. AD also severely affects the global economy. However, there is no appropriate treatment or cure available. In the past two decades thousands of disease modifying drugs have been developed to treat dementia of AD, however most of the drugs could not pass phase I clinical trial and only a few could reach phase II and phase III stage. This review is determined to provide the status of various clinical trials, failures and progress of success of various drugs that have been designed to tread dementia of AD.