In Silico Analysis Predicts Mutational Consequences of CITED2, NUDT4, and Ar18B in Patients with Bipolar Disorder.

Bipolar disorder is a mood-related disorder, which can be portrayed as extreme shifts in energy, mood, and activity levels which can also be characterized by manic highs and depressive lows that can be often misdiagnosed as unipolar disorder due to primitive diagnostics techniques based on clinical assessments as well as diagnostic complexities arising due to its heterogeneous nature and overlapping symptoms with conditions like schizophrenia. leading to delays in treatment Strong evidence in support of genetic and epigenetic aspects of bipolar disorder, including mechanisms such as compromised hypothalamic-pituitary-adrenal axis, immune-inflammatory imbalances, oxidative stress, and mitochondrial dysfunction are found. Moreover, some previous research has already stated the role of genes like CITED2, NUDT4, and Arl8B in these processes. The primary goal of this study is to investigate the involvement of the genes in exploring and validating their potential as biomarkers for bipolar disorder. In silico tools like MutationTaster, PolyPhen2, SIFT, GTEx, PhenoScanner, and RegulomeDB were used to perform mutational and gene expression analyses. Results revealed potentially dangerous mutations caused in CITED2, NUDT4, and Arl8B, those which can have diverse outcomes. RegulomeDB, GTEx, and PhenoScanner reveal the involvement of these genes in various brain regions highlighting their relevance to bipolar disorder. This analysis suggests the potential utility of CITED2, NUDT4, and Arl8B as diagnostic markers hence shedding light on their roles to elaborate the molecular range of bipolar disorder. The study also contributes to providing valuable insights into the genetic and molecular basis of bipolar disorders.

Chitosan nanoplatform for the co-delivery of palbociclib and ultra-small magnesium nanoclusters: dual receptor targeting, therapy and imaging.

Theranostic nanoparticles have gained significant attention in cancer diagnosis and therapy. In this study, estrone (ES) and folic acid (FA) functionalized single and dual receptor targeted theranostic chitosan nanoparticles were developed for breast cancer imaging and therapy. These nanoparticles (NPs) were loaded with palbociclib (PB) and ultra-small magnesium nanoclusters (UMN). The developed nontargeted theranostic NPs (PB-UMN-CS-NPs), estrogen receptor targeted theranostic NPs (PB-UMN-CS-ES-NPs), folate receptor targeted theranostic NPs (PB-UMN-CS-FA-NPs), and dual targeted theranostic NPs (PB-UMN-CS-ES-FA-NPs) have particle sizes of 178.4 ± 1.21 nm, 181.6± 1.35 nm, 185.1± 1.33 nm, and 198.2± 1.43 nm with surface charges of +19.02± 0.382 mV, +13.89±0.410 mV, +16.72±0.527 mV and +15.23±0.377 mV, respectively. Cytotoxicity studies on estrogen receptor (ER) and folate receptor (FR) expressing breast cancer cells revealed that dual-targeted theranostic NPs (PB-UMN-CS-FA-ES-NPs) were more effective, inhibiting cell growth by 54.17 and 42.23 times in MCF-7 and T-47D cells compared to free PB, respectively. Additionally, developed NPs were capable of inhibiting the cell cycle progression of MCF-7 cells from the G1 phase to the S phase more efficiently compared to free PB. Ultrasound and photoacoustic (USG/PA) imaging demonstrated that dual targeted theranostic NPs were capable of effectively reducing hypoxic tumor volume and significantly suppressing tumor vascularity compared to free PB, nontargeted, FR targeted and ER targeted NPs. Moreover, in vivo optical imaging demonstrated tumor specific accumulation of the dual-targeted theranostic NPs. Furthermore, in vitro hemocompatibility and histopathological studies confirmed the biocompatibility of developed nanoformulations.

Molecular docking approaches and its significance in assessing the antioxidant properties in different compounds.

In the last few years, the significance of antioxidant compounds and their properties has attracted great interest from the scientific community. The role of an antioxidant in managing & regulating oxidative stress and also in the protection of the human body from severe adverse effects due to excess release of free radicles or reactive oxygen species (ROS) is remarkable. From aiding protection & combating severe illnesses such as cancer, neurodegeneration, aging, and diabetes to being a vital part of the treatment of SARs-CoV-19 is of great importance. Therefore, the study of anti-oxidants is of great importance in human sustenance. Additionally, molecular docking techniques and their various mathematical features help in understanding the molecular interactions of anti-oxidants based on their lowest binding energy. The evaluation of the binding score between two constituent molecules will provide insight as to the binding process and also suggest possible novel therapeutic targets for the treatment of diseases. In this chapter, we will discuss the significance of molecular docking techniques in the study of antioxidant compounds.

White light-emitting, biocompatible, water-soluble metallic magnesium nanoclusters for bioimaging applications.

Ultra-small (1.6 nm), water-soluble, white light-emitting (WLE), highly stable (∼8 months) BSA templated metallic (Mg0) nanoclusters (fluorescent magnesium nanoclusters = FMNCs) is developed using the green and facile route. Synthesis was facilitated by the reduction of magnesium salt, where template bovine serum albumin is utilized as a reducing agent and ascorbic acid act as a capping agent to impart stability in water, thereby obtaining stabilized Mg0nanoclusters In solution, stabilized Mg0nanoclusters produce white light (450-620 nm with FWHM ∼120 nm) upon 366 nm light excitation. This white light emission was found to have a CIE coordinate of 0.30, 0.33 [pure white light CIE (0.33, 0.33)]. Taking advantage of WLE and ultrasmall size, FMNCs were used forin vitrofluorescence imaging of HaCaT cell lines, yielding blue (τ= 2.94 ns, with a relative of QY = 1.2 % w.r.t QS), green (τ= 3.07 ns; relative quantum yield of 4.6% w.r.t R6G) and red (τ= 0.3 ns) images. Further, incubation of FMNCs with HEK293 (Human embryonic kidney cell) and cancerous MDA-MB-231 (Breast cancer cell line) human cell lines yielded 100 % cell viability. Current work is envisioned to contribute significantly in the area of science, engineering, and nanomedicine.

Establishment of resveratrol and its derivatives as neuroprotectant against monocrotophos-induced alteration in NIPBL and POU4F1 protein through molecular docking studies.

Monocrotophos (MCP) is a broad spectrum organophosphorus insecticide, which is widely used as foliar spray to the different important crops. MCP may reach the soil and the aquatic environment directly or indirectly during and after the application, which leads to the different environmental issues. MCP is found to be associated with neurotoxicity and its toxic effects have been monitored during different stages of neuronal development. Identification of gene expression in MCP-induced neurotoxicity during neuronal developmental stage is a major area of genomic research interest. In accordance with this identification, screening of potential neuroprotective, natural resources are also required as a preventive aspects by targeting the impaired genes. In this current course of work, microarray experiment has been used to identify genes that were expressed in monocrotophos (MCP)-induced mesenchymal stem cells (MSC) and also the neuroprotectant activity of RV on MCP-exposed MSCs. Microarray experiment data have been deposited in NCBI's Gene Expression Omnibus database and are accessible through GEO Series accession number GSE121261. In this paper, we have discussed two important genes NIPBL (nipped-B-like protein) and POU4F1 (POU domain, class 4, transcription factor 1). These genes were found to be significantly expressed in MCP-exposed MSC and show minimum expression in presence of RV. Homology modelling and docking study was done to identify the interaction and binding affinity of resveratrol and its derivatives with NIPBL and POU4F1 protein. Docking analysis shows that RV and its derivatives have strong interaction with NIPBL and POU4F1 protein hence proves the significance of resveratrol as potential neuroprotectant. This paper highlights the hazardous impact of MCP on neuronal development disorders and repairing potentiality of RV and its derivatives on altered genes involved in neuronal diseases. Graphical Abstract.

Clustering, Pathway Enrichment, and Protein-Protein Interaction Analysis of Gene Expression in Neurodevelopmental Disorders.

Neuronal developmental disorder is a class of diseases in which there is impairment of the central nervous system and brain function. The brain in its developmental phase undergoes tremendous changes depending upon the stage and environmental factors. Neurodevelopmental disorders include abnormalities associated with cognitive, speech, reading, writing, linguistic, communication, and growth disorders with lifetime effects. Computational methods provide great potential for betterment of research and insight into the molecular mechanism of diseases. In this study, we have used four samples of microarray neuronal developmental data: control, RV (resveratrol), NGF (nerve growth factor), and RV + NGF. By using computational methods, we have identified genes that are expressed in the early stage of neuronal development and also involved in neuronal diseases. We have used MeV application to cluster the raw data using distance metric Pearson correlation coefficient. Finally, 60 genes were selected on the basis of coexpression analysis. Further pathway analysis was done using the Metascape tool, and the biological process was studied using gene ontology database. A total of 13 genes AKT1, BAD, BAX, BCL2, BDNF, CASP3, CASP8, CASP9, MYC, PIK3CD, MAPK1, MAPK10, and CYCS were identified that are common in all clusters. These genes are involved in neuronal developmental disorders and cancers like colorectal cancer, apoptosis, tuberculosis, amyotrophic lateral sclerosis (ALS), neuron death, and prostate cancer pathway. A protein-protein interaction study was done to identify proteins that belong to the same pathway. These genes can be used to design potential inhibitors against neurological disorders at the early stage of neuronal development. The microarray samples discussed in this publication are part of the data deposited in NCBI's Gene Expression Omnibus (Yadav et al., 2018) and are accessible through GEO Series (accession number GSE121261).

In Silico Mining of Conserved miRNAs of Indian Catfish Clarias batrachus (Linnaeus, 1758) from the Contigs, ESTs, and BAC End Sequences.

MicroRNAs are small non-coding RNAs which play significant role in RNA interference. The present work deals with mining of the conserved miRNA and their target genes from the contigs, ESTs, and BAC end sequences of commercially important catfish, Clarias batrachus, from India. A total of 138, 1 and 1 conserved pre-miRNA sequences, were mined from the contigs, ESTs, and BAC end sequences, respectively. The analysis of families of the conserved pre-miRNA revealed conservation of the fish-specific family mir-430 and other important families, such as mir-455, let-7, mir-133, and mir-137. The mir-455 is involved in hypoxia signaling, let-7 family represents potential anti-tumor molecules involved in human cancer therapy, whereas mir-133 and mir-137 have high therapeutic potentials. Using an alternate computational in silico approach, mining of mature miRNAs resulted in identification of 210 mature miRNAs from contigs, 1 from EST, and 2 each from forward as well as reverse BAC end sequences. Target prediction of these putative miRNAs resulted in the identification of 66,758 and 18,747 target genes in C. batrachus and Danio rerio, respectively. Functional annotation of these miRNAs indicated their involvement in diverse biological functions. The findings of the present study can serve as a valuable resource for further functional genomics studies in C. batrachus.

A New Insight of Herbal Promises Against Ocular Disorders: An Occuloinformatics Approach.

Ocular biology is a prominent area of research and advancement, as eyes are the most precious for us to see this beautiful world. Though we have overcome many ocular problems, but still challenges, no doubt exist in the path of the journey. Many ocular disorders still either have surgery or symptomatic drugs as a treatment. If we could get a better preventive way or single drug with many and more potential effects, will definitely be a boon for our society. Keeping the way we tried to focus on the impending effects of phytochemicals on some important ocular disorders. Our study promised with virtual screening based on important insilico protocols that can be a landmark for better futuristic approach towards novel drug development. As a selection Eales' Disease, Diabetic Retinopathy, Uveitis, Age related Macular Disorder, CRVO were taken. Causative Protein identification is the basic of study and further advance Insilico approaches were based on this target in respective disorders. Retinol Binding protein-3 and Retinal S antigen protein in case of Eales, Erythropoietin in the case of Diabetic Retinopathy, Nucleotide-binding oligomerization domain-containing protein-2 in case of Uveitis, Hemicentin-1 in case of Age related Macular Disorder, Coagulation Factor-V in case of CRVO were identified. Insilico characterization, Secondary and Tertiary structure prediction makes the study more prominent towards virtual screening. Virtual Screening was based on the parameters of docking, which reflects the potentiality of Ginkgolide, D-pinitol, Gugglesterones, Berberine and Curcumin herbal molecules against above mentioned ocular disorders respectively. Study signifies about the spectacular vision of herbal uses just to limit the vast side effects of synthetic chemicals used as ocular drugs.