Advancements in CRISPR-Cas Systems for Genome Editing towards Eradication of Human Microbial Pathogens.

CRISPR-Cas systems have been explored for targeted genome editing of several organisms. It is rapid, cost-effective, specific, and versatile technology. It requires expression of multidomain single Cas9 protein and single guide RNA (sgRNA) that targets desired nucleic acids in the presence of a protospacer adjacent motif (PAM).

Ubiquitin specific protease 7 deubiquitinates and regulates Aurora B-mediated cytokinesis.

Aurora B is a widely studied mitotic checkpoint kinase that forms a part of the chromosomal passenger complex. The entry to and exit from mitosis are exquisitely controlled by Aurora B proteins, which regulate mitotic phases including chromosomal condensation, segregation, and cytokinesis, ensuring faithful propagation of daughter cells. Abnormal regulation of Aurora B proteins during the cell cycle can cause increased chromosomal segregation errors and ultimately lead to cancer.

EGFR inhibitor suppresses tumor growth by blocking lipid uptake and cholesterol synthesis in non-small cell lung cancer.

Accelerated cholesterol and lipid metabolism are hallmarks of non-small cell lung cancer (NSCLC). Recently, epidermal growth factor receptor (EGFR) signaling has been shown to regulate de novo cholesterol synthesis and low-density lipoprotein receptor (LDLR) expression through SREBP-1-dependent pathways. This suggests that targeting EGFR signaling in cholesterol metabolism might provide a new therapeutic strategy for NSCLC.

Enhanced Production of Prodigiosin Utilizing Agro-industrial Yellow Mustard Cake Waste by a Novel Strain Serratia marcescens SBL03.

Prodigiosin is a red-hued bacterial pigment with promising anticancer, antimalarial, antiparasitic, and antibacterial therapeutic properties. However, the commercial exploitation of this secondary metabolite is hindered due to high production cost and poor yield. In this study, the prodigiosin-producing Serratia marcescens SBL03 strain was isolated and identified.

Targeting USP11 counteracts -associated interstitial lung disease in hiPSCs-derived alveolar organoids and in vivo models.

Interstitial lung disease (ILD) is a pulmonary disorder characterized by a combination of inflammation and fibrosis in the lung parenchyma, which initiates with the dysfunction of alveolar epithelial cells (AECs). The alveolar cells secrete surfactant proteins that lowers the surface tension of fluids in the lungs and maintains the stability of pulmonary tissue. Mutations on surfactant protein C (SFTPC), particularly I73T, are associated with a toxic gain of function that causes misfolding and the accumulation of immature SFTPC proteins, triggering pulmonary fibrosis (PF).

Loss of Ubiquitin-Specific Protease 11 Mitigates Pulmonary Fibrosis in Human Pluripotent Stem Cell-Derived Alveolar Organoids.

The etiology of chronic and lethal interstitial lung disease, termed idiopathic pulmonary fibrosis (IPF), remains unidentified. IPF induces pathological lung scarring that results in rigidity and impairs gas exchange, eventually resulting in premature mortality. Recent findings indicate that deubiquitinating enzymes play a key role in stabilizing fibrotic proteins and contribute to pulmonary fibrosis.

Multifunctional Polymeric Bioactive Coatings on Ti Implants through the Drug Delivery Approach: Corrosion Resistance, Biocompatibility, and Antibacterial Characteristics.

In the current study, we developed a controlled drug delivery system using a polymeric matrix composed of biopolymer poly(vinylidene fluoride) (PVDF) and ciprofloxacin (CPF)-loaded titanium (Ti) nanotubes (TNTs) on Ti substrates for biomedical applications. The TNT arrays over the Ti surface were obtained through an anodization route. The PVDF coatings were dip-coated on TNT-Ti loaded with CPF.

AXL kinase inhibitor exhibits antitumor activity by inducing apoptotic cell death in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer associated with a poor prognosis and decreased patient survival. It is intimately linked to AXL overexpression and AXL hyperactivation. Here, we explored the therapeutic potential of AX-0085, a small molecule AXL inhibitor.

Recent progress in CRISPR/Cas9 system for eye disorders.

Ocular disorders encompass a broad spectrum of phenotypic and clinical symptoms resulting from several genetic variants and environmental factors. The unique anatomy and physiology of the eye facilitate validation of cutting-edge gene editing treatments. Genome editing developments have allowed researchers to treat a variety of diseases, including ocular disorders.

Advances in applications of the CRISPR/Cas9 system for respiratory diseases.

Genetic and environmental factors can have an impact on lung and respiratory disorders which are associated with severe symptoms and have high mortality rates. Many respiratory diseases are significantly influenced by genetic or epigenetic factors. Gene therapy offers a powerful approach providing therapeutic treatment for lung diseases.

An Efficient Endothelial Cell Differentiation Protocol Using Bioactive Lipid O-Cyclic Phytosphingosine-1-Phosphate in Human Embryonic Stem Cells.

Bioactive lipids like sphingosine-1-phosphate (S1P) and lysophosphatidic acid have gained significant attention as signaling molecules with regulatory roles in stem cell proliferation and differentiation. The novel chemically synthesized sphingosine metabolite O-cyclic phytosphingosine-1-phosphate (cP1P) is derived from phytosphingosine-1-phosphate (P1P) and shares structural similarities with S1P. Previously, the role of cP1P in regulating ALK3/BMPR signaling during cardiomyocyte differentiation from human embryonic stem cells (hESCs) was demonstrated.

The Role of Deubiquitinating Enzymes in Primary Bone Cancer.

Bone is a living, intricate, and dynamic tissue providing locomotion and protection of the body. It also performs hematopoiesis and mineral homeostasis. Osteosarcoma (OS), Ewing sarcoma (ES), and chondrosarcoma (CS) are primary bone cancers.

Usp7 Regulates Glial Lineage Cell-Specific Transcription Factors by Modulating Histone H2B Monoubiquitination.

Histone H2B monoubiquitination (H2Bub1) is a dynamic posttranslational modification which are linked to DNA damage and plays a key role in a wide variety of regulatory transcriptional programs. Cancer cells exhibit a variety of epigenetic changes, particularly any aberrant H2Bub1 has frequently been associated with the development of tumors. Nevertheless, our understanding of the mechanisms governing the histone H2B deubiquitination and their associated functions during stem cell differentiation remain only partially understood.

Current progress in high-throughput screening for drug repurposing.

High-throughput screening (HTS) is a simple, rapid and cost-effective solution to determine active candidates from large library of compounds. HTS is gaining attention from Pharmaceuticals and Biotechnology companies for accelerating their drug discovery programs. Conventional drug discovery program is time consuming and expensive.

USP28 promotes tumorigenesis and cisplatin resistance by deubiquitinating MAST1 protein in cancer cells.

Cisplatin is a chemotherapy drug that causes a plethora of DNA lesions and inhibits DNA transcription and replication, resulting in the induction of apoptosis in cancer cells. However, over time, patients develop resistance to cisplatin due to repeated treatment and thus the treatment efficacy is limited. Therefore, identifying an alternative therapeutic strategy combining cisplatin treatment along with targeting factors that drive cisplatin resistance is needed.

βTrCP1 promotes SLC35F2 protein ubiquitination and inhibits cancer progression in HeLa cells.

The solute carrier family 35 F2 (SLC35F2) belongs to membrane-bound carrier proteins that are associated with multiple cancers. The main factor that determines cancer progression is the expression level of SLC35F2. Thus, identifying the E3 ligase that controls SLC35F2 protein abundance in cancer cells is critical.

E3 ubiquitin ligase APC/C regulates SLC35F2 protein turnover and inhibits cancer progression in HeLa cells.

Background: The solute carrier family 35 F2 (SLC35F2), belongs to membrane-bound carrier proteins that control various physiological functions and are activated in several cancers. However, the molecular mechanism regulating SLC35F2 protein turnover and its implication in cancer progression remains unexplored. Therefore, screening for E3 ligases that promote SLC35F2 protein degradation is essential during cancer progression.

USP19 Negatively Regulates p53 and Promotes Cervical Cancer Progression.

p53 is a tumor suppressor gene activated in response to cellular stressors that inhibits cell cycle progression and induces pro-apoptotic signaling. The protein level of p53 is well balanced by the action of several E3 ligases and deubiquitinating enzymes (DUBs). Several DUBs have been reported to negatively regulate and promote p53 degradation in tumors.

CRISPR-dCas9 system for epigenetic editing towards therapeutic applications.

In the past few decades, epigenetics has emerged as an important area of study to enable a better understanding of gene expression and its regulation. Due to epigenetics, stable phenotypic changes have been possible without alterations in DNA sequences. Epigenetic changes may occur due to DNA methylation, acetylation, phosphorylation and other such mechanisms which alter the level of gene expression without making any difference to DNA sequences.

CRISPR/Cas9-based genome-wide screening of the deubiquitinase subfamily identifies USP3 as a protein stabilizer of REST blocking neuronal differentiation and promotes neuroblastoma tumorigenesis.

Background: The repressor element-1 silencing transcription factor (REST), a master transcriptional repressor, is essential for maintenance, self-renewal, and differentiation in neuroblastoma. An elevated expression of REST is associated with impaired neuronal differentiation, which results in aggressive neuroblastoma formation. E3 ligases are known to regulate REST protein abundance through the 26 S proteasomal degradation pathway in neuroblastoma.

Phage engineering and phage-assisted CRISPR-Cas delivery to combat multidrug-resistant pathogens.

Antibiotic resistance ranks among the top threats to humanity. Due to the frequent use of antibiotics, society is facing a high prevalence of multidrug resistant pathogens, which have managed to evolve mechanisms that help them evade the last line of therapeutics. An alternative to antibiotics could involve the use of bacteriophages (phages), which are the natural predators of bacterial cells.

Amyloid precursor protein in Alzheimer's disease.

Amyloid precursor protein (APP) is a membrane protein expressed in several tissues. The occurrence of APP is predominant in synapses of nerve cells. It acts as a cell surface receptor and plays a vital role as a regulator of synapse formation, iron export and neural plasticity.

Rewiring of metabolic pathways in yeasts for sustainable production of biofuels.

The ever-increasing global energy demand has led world towards negative repercussions such as depletion of fossil fuels, pollution, global warming and climate change. Designing microbial cell factories for the sustainable production of biofuels is therefore an active area of research. Different yeast cells have been successfully engineered using synthetic biology and metabolic engineering approaches for the production of various biofuels.

Low density lipoprotein receptor endocytosis in cardiovascular disease and the factors affecting LDL levels.

Cardiovascular disease (CVD) is the one of major global health issues with approximately 30% of the mortality reported in the mid-income population. Low-density lipoprotein (LDL) plays a crucial role in development of CVD. High LDL along with others forms a plaque and blocks arteries, resulting in CVD.