Hidden regulators: the emerging roles of lncRNAs in brain development and disease.

Long non-coding RNAs (lncRNAs) have emerged as critical players in brain development and disease. These non-coding transcripts, which once considered as "transcriptional junk," are now known for their regulatory roles in gene expression. In brain development, lncRNAs participate in many processes, including neurogenesis, neuronal differentiation, and synaptogenesis. They employ their effect through a wide variety of transcriptional and post-transcriptional regulatory mechanisms through interactions with chromatin modifiers, transcription factors, and other regulatory molecules. Dysregulation of lncRNAs has been associated with certain brain diseases, including Alzheimer's disease, Parkinson's disease, cancer, and neurodevelopmental disorders. Altered expression and function of specific lncRNAs have been implicated with disrupted neuronal connectivity, impaired synaptic plasticity, and aberrant gene expression pattern, highlighting the functional importance of this subclass of brain-enriched RNAs. Moreover, lncRNAs have been identified as potential biomarkers and therapeutic targets for neurological diseases. Here, we give a comprehensive review of the existing knowledge of lncRNAs. Our aim is to provide a better understanding of the diversity of lncRNA structure and functions in brain development and disease. This holds promise for unravelling the complexity of neurodevelopmental and neurodegenerative disorders, paving the way for the development of novel biomarkers and therapeutic targets for improved diagnosis and treatment.

The Impact of COVID-19 Infection on Patients with Chronic Diseases Admitted to ICU: a Cohort Retrospective Study.

The coronavirus disease (COVID-19) infection is causing significant morbidity and mortality rates worldwide. A comprehensive investigation of the disease characteristics, especially among vulnerable disease groups, could help better manage the disease and reduce the pathogen's effect. This retrospective study examined the impact of COVID-19 infection on three groups of patients with chronic diseases. We investigated the clinical characteristics and outcomes of 535 COVID-19 patients with cardiovascular diseases (CVD), chronic kidney diseases (CKD), and Cancer that were admitted to the Intensive Care Unit (ICU). Of the total cases, 433 patients (80.93%) were discharged from the ICU, and 102 patients (19.06%) were declared dead. Patients' symptoms, their clinical laboratory findings, number and type of medications, length of ICU stay, and outcome were collected and analyzed. Most COVID-19 patients included in our study were associated with other comorbidities such as diabetes mellitus, hypertension, and heart disease and failure. Upon ICU admission, the main COVID-19-related symptoms in CVD, CKD, and cancer patients were cough (55.73, 50.42, and 50.5%, respectively), Shortness of Breath (SOB) (59.38, 43.1, and 43.7%, respectively), and fever (41.15%, 48.75%, and 28.2%, respectively). In terms of lab findings, D-dimer, LDH, and inflammatory markers, in particular, were outside the normal range. Treatment options for patients with COVID-19 in ICU were mainly antibiotics, synthetic glucocorticoids, and Low Molecular Weight Heparin (LMWH). Furthermore, CKD patients had a longer ICU stay (13.93 ± 15.87 days) which illustrates the poorer outcome in this group of patients compared with the others. In conclusion, our results highlighted the significant risk factors among COVID-19 patients within the three groups. This can guide physicians in prioritizing ICU admission and help in the management of critically ill patients with COVID-19.

What has single-cell transcriptomics taught us about long non-coding RNAs in the ventricular-subventricular zone?

Long non-coding RNA (lncRNA) function is mediated by the process of transcription or through transcript-dependent associations with proteins or nucleic acids to control gene regulatory networks. Many lncRNAs are transcribed in the ventricular-subventricular zone (V-SVZ), a postnatal neural stem cell niche. lncRNAs in the V-SVZ are implicated in neurodevelopmental disorders, cancer, and brain disease, but their functions are poorly understood. V-SVZ neurogenesis capacity declines with age due to stem cell depletion and resistance to neural stem cell activation. Here we analyzed V-SVZ transcriptomics by pooling current single-cell RNA-seq data. They showed consistent lncRNA expression during stem cell activation, lineage progression, and aging. In conjunction with epigenetic and genetic data, we predicted V-SVZ lncRNAs that regulate stem cell activation and differentiation. Some of the lncRNAs validate known epigenetic mechanisms, but most remain uninvestigated. Our analysis points to several lncRNAs that likely participate in key aspects of V-SVZ stem cell activation and neurogenesis in health and disease.

Recruiting Immunity for the Fight against Colorectal Cancer: Current Status and Challenges.

Cancer immunotherapies have changed the landscape of cancer management and improved the standard treatment protocols used in multiple tumors. This has led to significant improvements in progression-free survival and overall survival rates. In this review article, we provide an insight into the major immunotherapeutic methods that are currently under investigation for colorectal cancer (CRC) and their clinical implementations. We emphasize therapies that are based on monoclonal antibodies (mAbs) and adoptive cell therapy, their mechanisms of action, their advantages, and their potential in combination therapy. We also highlight the clinical trials that have demonstrated both the therapeutic efficacy and the toxicities associated with each method. In addition, we summarize emerging targets that are now being evaluated as potential interventions for CRC. Finally, we discuss current challenges and future direction for the cancer immunotherapy field.

Preparing the Bone Tissue Regeneration Ground by Exosomes: From Diagnosis to Therapy.

Bone tissue engineering employs acellular scaffolds or scaffolds, along with cells and growth factors, to provide the mechanical support needed, as well as serve as a delivery vehicle for bioactive molecules to the injury sites. As tissue engineering continues to evolve, it has integrated two emerging fields: stem cells and nanotechnology. A paracrine factor that is found to be responsible for the major regenerative effect in stem cell transplantation is an extracellular vesicle called an 'exosome'. Recent advances in nanotechnology have allowed the 'exosome' to be distinguished from other extracellular vesicles and be polymerized into a well-defined concept. Scientists are now investigating exosome uses in clinical applications. For bone-related diseases, exosomes are being explored as biomarkers for different bone pathologies. They are also being explored as a therapeutic agent where progenitor cell-derived exosomes are used to regenerate damaged bone tissue. In addition, exosomes are being tested as immune modulators for bone tissue inflammation, and finally as a delivery vehicle for therapeutic agents. This review discusses recently published literature on the clinical utilization of exosomes in bone-related applications and the correlated advantages. A particular focus will be placed on the potential utilization of regenerative cell-derived exosomes as a natural biomaterial for tissue regeneration.

The long non-coding RNA Paupar promotes KAP1-dependent chromatin changes and regulates olfactory bulb neurogenesis.

Many long non-coding RNAs (lncRNAs) are expressed during central nervous system (CNS) development, yet their in vivo roles and mechanisms of action remain poorly understood. Paupar, a CNS-expressed lncRNA, controls neuroblastoma cell growth by binding and modulating the activity of transcriptional regulatory elements in a genome-wide manner. We show here that the Paupar lncRNA directly binds KAP1, an essential epigenetic regulatory protein, and thereby regulates the expression of shared target genes important for proliferation and neuronal differentiation. Paupar promotes KAP1 chromatin occupancy and H3K9me3 deposition at a subset of distal targets, through the formation of a ribonucleoprotein complex containing Paupar, KAP1 and the PAX6 transcription factor. Paupar-KAP1 genome-wide co-occupancy reveals a fourfold enrichment of overlap between Paupar and KAP1 bound sequences, the majority of which also appear to associate with PAX6. Furthermore, both Paupar and Kap1 loss-of-function in vivo disrupt olfactory bulb neurogenesis. These observations provide important conceptual insights into the trans-acting modes of lncRNA-mediated epigenetic regulation and the mechanisms of KAP1 genomic recruitment, and identify Paupar and Kap1 as regulators of neurogenesis in vivo.