Asem Surindro Singh

Dendritic cells (DCs) are central orchestrators of adaptive immunity, integrating innate immune sensing with antigen‐specific T‐cell activation. While long noncoding RNAs (lncRNAs) have emerged as critical regulators of immune cell fate and function, the lncRNA landscape governing human DC differentiation and effector activity remains incompletely defined. Here, we generated monocyte‐derived dendritic cells (moDCs) from primary human peripheral blood monocytes and performed transcriptome‐wide RNA sequencing to systematically identify previously unannotated lncRNAs associated with DC differentiation. We uncovered an extensive repertoire of novel lncRNA transcripts dynamically regulated during DC development. Among these, MSTRG.479558.1 and MSTRG.582898.5 were prioritized based on robust induction during differentiation, responsiveness to inflammatory stimulation (LPS), and elevated expression in periodontitis. Functional interrogation revealed a selective and non‐redundant role for MSTRG.479558.1 in DC biology. Knockdown of the lncRNA MSTRG.479558.1 but not MSTRG.582898.5 significantly reduced the expression of dendritic cell markers CD1a, CD209, and CDw93, indicating impaired dendritic cell differentiation. Functionally, MSTRG.479558.1 silencing profoundly impaired phagocytic capacity and antigen processing, indicating disruption at the earliest stages of antigen handling. Moreover, loss of MSTRG.479558.1 compromised antigen presentation and significantly attenuated DC‐mediated CD4 ⁺ T‐cell activation, and Th1 related cytokines IFNγ and TNF‐α, suggesting a functional link between this lncRNA and adaptive immune priming. Mechanistically, targeted transcriptional profiling demonstrated coordinated dysregulation of genes implicated in antigen processing and presentation pathways following MSTRG.479558.1 depletion, including components of proteasomal processing, chaperone‐mediated folding, and MHC‐associated peptide loading machinery. These findings support a model in which MSTRG.479558.1 acts as an upstream regulator of a transcriptional network that governs antigen handling and presentation. Collectively, this study defines a previously uncharacterized lncRNA program operative during human DC differentiation and identifies MSTRG.479558.1 as a critical regulator of DC functional competency. By coupling antigen acquisition to T‐cell activation, this lncRNA represents a novel layer of immune regulation with potential implications for inflammatory disease pathogenesis and therapeutic targeting.

Neuroinflammation is considered as one of the core pathogenic factors of neurodegeneration in Alzheimer disease (AD) and related dementias (RD). It is also associated with other two hallmarks of AD dementia, i.e., amyloid beta (Ab) and neurofibrillary tangles (NFT), and increasingly considered as the third hallmark of AD. Abnormality in microglial pathway plays a crucial role in the neuroinflammation of AD and RD. Microglia dysfunction is linked to many neuroinflammatory signaling pathways towards the progress of developing neurodegeneration resulting to cognitive deficits or dementia. Currently, several therapeutic approaches aim to target inflammatory regulators for AD treatment, and microglia is considered as one of the vital targets. In this article we intend to highlight and discuss various microglia mediated signaling pathways that link to chronic neuroinflammation and cognitive dysfunction/dementia in AD and other diseases. This could help us to understand the degree of microglial association with the disease pathophysiology through analyzing various studies in last few decades including the latest reports. We also aim to highlight the pathways that are more and less conclusively established and determine possible pathways which may help in further exploration and narrowing down or expanding the area of studies that requires further research. AD and RD are one of the most leading causes of death in the world and there is no appropriate drug available for cure or prevention of the disease. Further research is an absolute requirement for better understanding the mechanisms underlying the disease pathophysiology and better planning of basic/therapeutic research and clinical trials. We also provide up-to-date clinical trials that used inflammatory targeting drugs and discuss the failures and promising drug targets.

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.

Honeybee foraging is a well-organized behavior that has been studied in detail. During foraging, foraging bees search for food, interact, communicate, and collect food for the colony. Learning, remembering, and locating food source at far distance from the hive and able to communicate with each other and complete the task of food collection would not be simple for these small insects. This mysterious highly intelligent behavior of bees has attracted several scientists and interpretation of honeybee dance language was Nobel prize winning research a thing to be always remembered. To understand further the underlying mechanism is a subsequent excitement. Recent studies have taken great importance on understanding the molecular and cellular modulators of honeybee foraging. Some studies have revealed that immediate early genes (IEGs) can be used as neural markers for understanding honeybee brain functions and its behaviors. Our recent studies have shown that three IEGs Egr-1, Hr38 and Kakusei have potential roles in honeybee foraging and learning and memory (Singh et al., 2018; Singh & Takhellambam, 2021; Singh et al., 2020). This piece of work is an extension of the earlier study and investigate whether gene expression continue to increase for longer time during the food reward foraging. We found that the gene expression level continued to remain upregulated throughout the entire time 3 hours foraging duration revealing the role of Egr-1, Hr38, Kakusei during the entire time of foraging.

Enormous progress has been made towards understanding the pathophysiology of Alzheimer’s disease (AD) over the recent years through the advancement of research in the field of AD research. However, the unavailability of an appropriate drug for treatment raises several questions and scores the lake of thorough understanding the regulatory mechanisms underlying the disease pathophysiology and thereby the needs of further research for deeper understanding and uncover the hidden complexity. Most of the drugs that have been designed and proceed to clinical trials are focused on clearing of the aggregates of amyloid beta and the neurofibrillary tangles that are made of phosphorylated, while the focus on neuroinflammatory pathways is also emerging. Other pathological pathways that have profound regulatory roles underlying AD dementia include APOE mediated cholesterol transportation and metabolism, TREM2 mutation, DNA methylation, histone modification and non-coding RNAs etc. This review is particularly focus on how APOE, TREM2, DNA methylation, histone modification and non-coding RNAs contribute to neuroinflammation and leads to dementia of AD.

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 foraging behavior of honeybees is one of the most systematically composed behaviors among social insects which are admirable to watch. The main purpose of honeybee foraging is to collect food for their colony and since ancient days honeybee products have been used for various medicinal purposes (Singh and Takhellambam, 2021) (1). During foraging, honeybees gather information and transmit to their colony members regarding the location, distance, and profitability of forage sites with the help of unique movements called waggle dance. The capacities of honeybees’ time memory enable the foragers to return to a good food source in anticipation of the time of day. This highly intellectual, dynamic, and well-coordinated behavior of honeybees makes them to be one of the best choices of behavioral model to study various aspects of dynamic behaviors. As a result, vast knowledge in honeybee behavior has been accumulated and several recent studies immerge towards finding the underpinning regulatory biology of honeybee foraging behaviors. Immediate early genes (IE) genes are well documented neural markers and their promising roles in honeybee foraging have been demonstrated. Two of our recent studies showed three IE genes Egr-1, Hr-38 and Kakusei involvement during the daily foraging of honeybees. This finding has provided an avenue to further explore and identify the regulatory genes/proteins and neurons that underlie a specific behavior such as learning, memory, communication, and interaction etc. In this study we further analyze our previous published data to examine interaction of the three genes during the daily foraging of honeybees.

The foraging behavior of honeybees is one of the most systematically composed behaviors among social insects which are admirable to watch. The main purpose of honeybee foraging is to collect food for their colony and since ancient days honeybee products have been used for various medicinal purposes (Singh and Takhellambam 2021). During foraging, honeybees gather information and transmit to their colony members regarding the location, distance, and profitability of forage sites with the help of unique movements called waggle dance. The capacities of honeybees time memory enable the foragers to return to a good food source in anticipation of the time of day. This highly intellectual, dynamic, and well-coordinated behavior of honeybees makes them to be one of the best choices of behavioral model to study various aspects of dynamic behaviors. As a result, vast knowledge in honeybee behavior has been accumulated and several recent studies immerge towards finding the underpinning regulatory biology of honeybee foraging behaviors. Immediate early genes (IE) genes are well documented neural markers and their promising roles in honeybee foraging have been demonstrated. Two of our recent studies showed three IE genes Egr-1, Hr38 and Kakusei involvement during the daily foraging of honeybees. This finding has provided an avenue to further explore and identify the regulatory genes/proteins and neurons that underlie a specific behavior such as learning, memory, communication, and interaction etc. In this study we further analyze our previous published data to examine interaction of the three genes during the daily foraging of honeybees.

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.