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Background: Breast cancer is characterized by uncontrolled cell growth in the breast tissue and is a leading cause of death globally. Cytotoxic effects and reduced efficacy of currently used therapeutics insist to look for new chemo-preventive strategies against breast cancer. LKB1 gene has recently been categorized as a tumor suppressor gene where its inactivation can cause sporadic carcinomas in various tissues. Mutations in the highly conserved LKB1 catalytic domain lead to the loss of function and subsequently elevated expression of pluripotency factors in breast cancer. Objectives: The utilization of drug-likeness filters and molecular simulation has helped evaluate the pharmacological activity and binding abilities of selected drug candidates to the target proteins in many cancer studies. Methods: The current in silico study provides a pharmacoinformatic approach to decipher the potential of novel honokiol derivatives as therapeutic agents against breast cancer. AutoDock Vina was used for molecular docking of the molecules. A 100 nano second (ns) molecular dynamics simulation of the lowest energy posture of 3'-formylhonokiol- LKB1, resulting from docking studies, was carried out using the AMBER 18. Results: Among the three honokiol derivatives, ligand-protein binding energy of 3' formylhonokiol with LKB1 protein was found to be the highest via molecular docking. Moreover, the stability and compactness inferred for 3'- formylhonokiol with LKB1 are suggestive of 3' formylhonokiol being an effective activator of LKB1 via simulation studies. Conclusion: It was further established that 3'- formylhonokiol displays an excellent profile of distribution, metabolism, and absorption, indicating it is an anticipated future drug candidate.

Over the past decade, three-dimensional printing (3DP) has gained popularity among the public and the scientific community in a variety of disciplines, including engineering, medicine, manufacturing arts, and, more recently, education. The advantage of this technology is that it is capable of designing and printing almost any object shape using various materials such as ceramics, polymers, metals and bio.inks. This has further favored the use of this technology for biomedical applications in both clinical and research settings. In biomedicine, there has been a remarkable development of a variety of biomaterials, which in turn has accelerated the significant role of this technology as synthetic scaffolds in various forms such as scaffolds, constructs or matrices. In this chapter, we would like to review the trailblazing literature on the application of 3DP technology in biomedical engineering. This chapter focuses on various 3DP techniques and biomaterials for tissue engineering applications (TE). 3DP technology has a variety of applications in biomedicine and TE (B- TE). Customized structures for B- TE applications using 3DP have several advantages, e.g., they are easy to fabricate and are inexpensive. On the other hand, conventional technologies, which are costly, time-consuming, and labor intensive, are generally not compatible with 3DP. Therefore, the capabilities of 3DP, which is a novel fabrication technology, need to be explored for many other potential applications. Here, we provide a comprehensive overview of the different types of 3DP technologies and how they can potentially be used.

The zinc finger-containing transcription factor Gli3 is a key mediator of Hedgehog (Hh) signaling pathway. In vertebrates, Gli3 has widespread expression pattern during early embryonic development. Along the anteroposterior axes of the central nervous system (CNS), dorsoventral neural pattern elaboration is achieved through Hh mediated spatio-temporal deployment of Gli3 transcripts. Previously, we and others uncovered a set of enhancers that mediate many of the known aspects of Gli3 expression during neurogenesis. However, the potential role of Gli3 associated enhancers in trait evolution has not yet received any significant attention. Here, we investigate the evolutionary patterns of Gli3 associated CNS-specific enhancers that have been reported so far. A subset of these enhancers has undergone an accelerated rate of molecular evolution in the human lineage in comparison to other primates/mammals. These fast-evolving enhancers have acquired human-specific changes in transcription factor binding sites (TFBSs). These human-unique changes within subset of Gli3 associated CNS-specific enhancers were further validated as single nucleotide polymorphisms through 1000 Genome Project Phase 3 data. This work not only infers the molecular evolutionary patterns of Gli3 associated enhancers but also provides clues for putative genetic basis of the population-specificity of gene expression regulation.

Breast cancer is characterized by an uncontrolled cell growth in the breast tissue and is a leading cause of death globally. Cytotoxic effects and reduced efficacy of currently used therapeutics insist to look for new chemo-preventive strategies against breast cancer. LKB1 gene has recently been categorized as a tumor suppressor gene where it’s inactivation can cause sporadic carcinomas in various tissues, including the breast. Mutations in the highly conserved LKB1 catalytic domain leads to the loss of function and subsequently elevated expression of pluripotency factors in breast cancer. The utilization of drug-likeness filters and molecular simulation has helped evaluate the pharmacological activity and binding abilities of selected drug candidates against the target proteins in many cancer studies. The current in silico study provides a pharmacoinformatic approach to decipher the potential of novel honokiol derivatives as therapeutic agents against breast cancer through binding of target LKB1 protein. Among the three honokiol derivatives, ligand-protein binding energy of 3' formylhonokiol with LKB1 protein was found to be the highest via molecular docking. Moreover, stability and compactness inferred for 3' formylhonokiol with LKB1 is suggestive of 3' formylhonokiol being an effective activator of LKB1 via simulation studies. It was further established that 3' formylhonokiol displays an excellent profile of distribution, metabolism, and absorption, indicating it as an anticipated future drug candidate.

Helicobacter cinaedi is a Gram-negative bacterium from the family Helicobacteraceae and genus Helicobacter. The pathogen is a causative agent of gastroenteritis, cellulitis, and bacteremia. The increasing antibiotic resistance pattern of the pathogen prompts the efforts to develop a vaccine to prevent dissemination of the bacteria and stop the spread of antibiotic resistance (AR) determinants. Herein, a pan-genome analysis of the pathogen strains was performed to shed light on its core genome and its exploration for potential vaccine targets. In total, four vaccine candidates (TonB dependent receptor, flagellar hook protein FlgE, Hcp family type VI secretion system effector, flagellar motor protein MotB) were identified as promising vaccine candidates and subsequently subjected to an epitopes’ mapping phase. These vaccine candidates are part of the pathogen core genome: they are essential, localized at the pathogen surface, and are antigenic. Immunoinformatics was further applied on the selected vaccine proteins to predict potential antigenic, non-allergic, non-toxic, virulent, and DRB*0101 epitopes. The selected epitopes were then fused using linkers to structure a multi-epitopes’ vaccine construct. Molecular docking simulations were conducted to determine a designed vaccine binding stability with TLR5 innate immune receptor. Further, binding free energy by MMGB/PBSA and WaterSwap was employed to examine atomic level interaction energies. The designed vaccine also stimulated strong humoral and cellular immune responses as well as interferon and cytokines’ production. In a nutshell, the designed vaccine is promising in terms of immune responses’ stimulation and could be an ideal candidate for experimental analysis due to favorable physicochemical properties.

The death toll and the total number of infected individuals due to the ongoing pandemic of SARS-CoV-2 infection have exceeded that of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) as the disease has raged around the world. So far the global efforts to tackle COVID-19 include the launch of Sputnik V vaccine by Russia, 42 vaccines presently undergoing clinical trials on humans and around 92 vaccines under preclinical active investigation in animals. Majority of the SARS-CoV-2 infected individuals have been reported to show mild symptoms whereas a considerable number show no symptoms at all. SARS-CoV-2 is believed to spread from infected individuals who are asymptomatic in addition to the symptomatic individuals. In this review we discussed how the mildly infected and asymptomatic individuals raise serious concerns and complicate the processes of screening, detection, quarantine, tracking and treatmentthatareinpracticetopreventthetransmissionofthe COVID-19.

The National Genomics Data Center (NGDC) provides a suite of database resources to support worldwide research activities in both academia and industry. With the rapid advancements in higher-throughput and lower-cost sequencing technologies and accordingly the huge volume of multi-omics data generated at exponential scales and rates, NGDC is continually expanding, updating and enriching its core database resources through big data integration and value-added curation. In the past year, efforts for update have been mainly devoted to BioProject, BioSample, GSA, GWH, GVM, NONCODE, LncBook, EWAS Atlas and IC4R. Newly released resources include three human genome databases (PGG.SNV, PGG.Han and CGVD), eLMSG, EWAS Data Hub, GWAS Atlas, iSheep and PADS Arsenal. In addition, four web services, namely, eGPS Cloud, BIG Search, BIG Submission and BIG SSO, have been significantly improved and enhanced. All of these resources along with their services are publicly accessible at https://bigd.big.ac.cn.

In recent years, the number of human long noncoding RNAs (lncRNAs) that have been identified has increased exponentially. However, these lncRNAs are poorly annotated compared to protein-coding genes, posing great challenges for a better understanding of their functional significance and elucidating their complex functioning molecular mechanisms. Here we employ both community and expert curation to yield a comprehensive collection of human lncRNAs and their annotations. Specifically, LncRNAWiki (http://lncrna.big.ac.cn/index.php/Main_Page) uses a wiki-based community curation model, thus showing great promise in dealing with the flood of biological knowledge, while LncBook (http://bigd.big.ac.cn/lncbook) is an expert curation-based database that provides a complement to LncRNAWiki. LncBook features a comprehensive collection of human lncRNAs and a systematic curation of lncRNAs by multi-omics data integration, functional annotation, and disease association. These protocols provide step-by-step instructions on how to browse and search a specific lncRNA and how to obtain a range of related information including expression, methylation, variation, function, and disease association. © 2019 by John Wiley & Sons, Inc.

The human nose has a diversified morphology among different geographical distributions and serves as a natural conditioning system for the inhaled air. Several studies have put forth statistically sound observations of the presence of large-bulbous noses in hot and humid Africa and narrower-aquiline noses in cold and dry Europe. These diverse nasal shapes have been termed as local adaptations to a region's climate. Over the past couple of decades, several GWA studies have linked potential loci with several diseases and morphological traits including the human nasal forms. In this study, highly significant SNPs associated with eight nasal morphological traits from previously reported GWA studies were collected. SNP data was obtained from the 1000 Genomes Project Phase III. By employing tests such as extended haplotype homozygosity (EHH), haplotype bifurcation diagrams and Fst measure, a subset of 6 nasal-associated SNPs were found to be significantly differentiated among the human sub-populations indicating that positive selection has acted on human nasal-associated loci.

SARS-CoV2 has affected millions of people around the globe with hundreds of mortalities. The emergence of SARS-COV2 is very recent, and there is no potential drug or vaccine available. In this review, we have compiled the most frequently used computational methods in drug discovery, target proteins of SARS-CoV2 as well as implementation of computational methods. Most recent literature on SARS-CoV2 has been compiled from various journal search engines including Google Scholar, Academia, PubMed, Scopus, Research Gate, and the Web of Science. The keywords chosen for the searches were COVID-19, Corona Virus, SARS-CoV2, drug development and future directions. This review has far reaching implications to both the public health and pharmaceutical industries for potential novel drug development against SARS-CoV2.