Manini Bhatt

The mammalian target of rapamycin (mTOR) is a protein kinase that controls cellular metabolism, catabolism, immune responses, autophagy, survival, proliferation, and migration, to maintain cellular homeostasis. The mTOR signaling cascade consists of two distinct multi-subunit complexes named mTOR complex 1/2 (mTORC1/2). mTOR catalyzes the phosphorylation of several critical proteins like AKT, protein kinase C, insulin growth factor receptor (IGF-1R), 4E binding protein 1 (4E-BP1), ribosomal protein S6 kinase (S6K), transcription factor EB (TFEB), sterol-responsive element-binding proteins (SREBPs), Lipin-1, and Unc-51-like autophagy-activating kinases. mTOR signaling plays a central role in regulating translation, lipid synthesis, nucleotide synthesis, biogenesis of lysosomes, nutrient sensing, and growth factor signaling. The emerging pieces of evidence have revealed that the constitutive activation of the mTOR pathway due to mutations/amplification/deletion in either mTOR and its complexes (mTORC1 and mTORC2) or upstream targets is responsible for aging, neurological diseases, and human malignancies. Here, we provide the detailed structure of mTOR, its complexes, and the comprehensive role of upstream regulators, as well as downstream effectors of mTOR signaling cascades in the metabolism, biogenesis of biomolecules, immune responses, and autophagy. Additionally, we summarize the potential of long noncoding RNAs (lncRNAs) as an important modulator of mTOR signaling. Importantly, we have highlighted the potential of mTOR signaling in aging, neurological disorders, human cancers, cancer stem cells, and drug resistance. Here, we discuss the developments for the therapeutic targeting of mTOR signaling with improved anticancer efficacy for the benefit of cancer patients in clinics.

Reactive astrogliosis and inflammation are pathologic hallmarks of spinal cord injury. After injury, dysfunction of glial cells (astrocytes) results in glial scar formation, which limits neuronal regeneration. The blood-spinal cord barrier maintains the structural and functional integrity of the spinal cord and does not allow blood vessel components to leak into the spinal cord microenvironment. After the injury, disruption in the spinal cord barrier causes an imbalance of the immunological microenvironment. This triggers the process of neuroinflammation, facilitated by the actions of microglia, neutrophils, glial cells, and cytokines production. Recent work has revealed two phenotypes of astrocytes, A1 and A2, where A2 has a protective type, and A1 releases neurotoxins, further promoting glial scar formation. Here, we first describe the current understanding of the spinal cord microenvironment, both pre-, and post-injury, and the role of different glial cells in the context of spinal cord injury, which forms the essential update on the cellular and molecular events following injury. We aim to explore in-depth signaling pathways and molecular mediators that trigger astrocyte activation and glial scar formation. This review will discuss the activated signaling pathways in astrocytes and other glial cells and their collaborative role in the development of gliosis through inflammatory responses.

Carbon nanodots are ultra-small carbonaceous nanostructures with excellent photoluminescence and cytocompatibility properties, making them suitable for developing excellent bioimaging probes. They exhibit dual properties, generating and scavenging reactive oxygen species, and are used as photosensitizers to produce reactive oxygen species under light and as photothermal agents that transform light energy into heat. This makes it possible to use them in photothermal and photodynamic therapies to treat cancer. They may enter the body by various means, including inhalation, ingestion, or intravenous injection. Once inside, they travel through the bloodstream, infiltrating tissues where they come into contact with the immune system, similar to infectious agents. These nanodots are identified by several receptors on the surface of innate immune cells, such as monocytes and macrophages, which attempt to engulf these nanodots. This interaction can induce a pro-inflammatory (M1) or anti-inflammatory (M2) response, modulating immune activity. This review explores the immuno-toxic potential of carbon nanodots, focusing on their ability to modulate redox balance by catalase, glutathione peroxidase, and superoxide dismutase, which are examples of antioxidant enzymes. Although carbon nanodots have demonstrated a wide range of applications, their effect on the cellular immune system remains largely unexplored. In this study, we primarily addressed the sophisticated impacts of carbon nanodots on the immune system and their diverse processes, such as the many cellular redox reactions implicated in antibacterial and antiviral treatment, wound healing, drug administration, and tumor therapy. As a result, we outline the benefits and difficulties of carbon nanodots in the biomedical domain and discuss their potential in the future development of clinical medicine.

Spinal cord injuries, whether resulting from traumatic or nontraumatic events, have severe and lasting detrimental effects on individuals, significantly impacting their overall health, mobility, and quality of life. The limited regenerative capacity of the spinal cord is mainly due to neuronal damage, the presence of inhibitory molecules, an impaired immune response, and the formation of glial scars, all of which create a hostile environment for neural repair and functional recovery. The majority of SCIs are caused by traffic accidents and falling objects. The current global treatments used for SCI are surgical methods, steroid medications, physiotherapy, and spinal cord epidural stimulations. However, these approaches offer only temporary relief and have serious adverse effects. Various preclinical approaches have been studied for SCI, including biomaterials, drug delivery, electrical stimulation, and cell-based therapies. Among these, stem cell therapies, such as NSCs, MSCs, and iPSCs, have the potential to significantly improve axonal regrowth, reduce inflammation, and promote neuroprotection. Furthermore, biophysical stimulation methods such as optogenetics, electrical and mechanical stimulation, and biomechanical devices offer encouraging paths toward improving neural plasticity and functional recovery. However, combinational approaches such as biomaterials with cell-based systems, cell-based systems with drug delivery, and biophysical stimulation with biomaterials aim to have more significant potential for functional recovery than a single treatment alone. This review has discussed the current clinical practices for SCI treatment, their limitations, and combinational strategies for spinal cord regeneration. So, this article can give clinicians, bioengineers, and researchers clues to construct preclinical and clinical studies that can have long-term effects on patients.

Carbon nanodots (CNDs) have emerged as a promising class of carbon-based nanomaterials for cancer theranostics, uniquely integrating diagnosis and therapy on a single platform. Their ultrasmall size, high aqueous dispersibility, tunable photoluminescence extending into the near-infrared (NIR) window, and compatibility with green, scalable synthesis enable deep-tissue imaging and targeted intervention with reduced systemic toxicity compared with many conventional nanomaterials. This review summarises recent advances in the top-down and bottom-up fabrication of CNDs, including heteroatom doping and surface functionalisation with ligands or stimuli-responsive linkers, and relates these design parameters to optical performance, tumour selectivity, and responsiveness to the tumour microenvironment. Particular emphasis is placed on CND-based platforms for multimodal imaging (fluorescence, MRI, and photoacoustic), controlled-release drug delivery, gene silencing, and light-activated photodynamic and photothermal therapies, as well as emerging synergistic systems that combine these functions for real-time, image-guided treatment. Remaining challenges, such as batch-to-batch variability, incomplete understanding of long-term biosafety (especially for metal-doped CNDs), and limited clinical-scale manufacturing and regulatory readiness, are critically discussed alongside future opportunities, including NIR-II optimisation, protein-corona-resistant surface engineering, and AI-assisted CND design for personalised cancer theranostics.