Raghavendra Sashi Krishna Nagampalli

Protein tyrosine kinases (PTKs) are key enzymes of cellular signaling, regulating key processes such as proliferation, differentiation, migration, metabolism, and apoptosis. Tyrosine kinases (TKs) modulate protein functions in normal and disease states by phosphorylation of tyrosine residues on target proteins. In this critical role, dysregulation of TKs is directly linked with disease progression, particularly in cancer, therefore making TKs an attractive target for therapeutic intervention. The PTK family is broadly classified into receptor TKs (RTKs) and non-receptor TKs (NRTKs), having variation at both structural and functional levels. RTKs are membrane-bound kinases that initiate intracellular signaling when they react with extracellular ligands, whereas NRTKs within the cytoplasm or nucleus convey intracellular signaling upon receptor activation. This paper aims to review the organization, mechanistic activity, and therapeutic potential of PTKs, with a particular focus on epidermal growth factor receptor and proto-oncogene tyrosine-protein kinase (Src) as representatives of RTK and NRTK, respectively. In addition, this review also focuses on addressing emerging strategies to enhance tyrosine kinase inhibitor efficacy and overcome acquired resistance in cancer therapy.

Background: Multi-antibiotic resistance has become an alarming issue in treating bacterial infections in both community and medical environments. Globally, the scientific community has been exploring multi-antibiotic techniques to find new ways to address this challenge. To address this critical challenge and explore alternative antibiotic treatments, we investigated the potential of Solanum trilobatum, an edible and medicinally important herb plant in Ayurvedic medicine. Methods: Our research focused on a 60 kDa serine protease isolated and purified from the leaves of S. trilobatum, which showed evidence of possessing hydrolase activity. In this study, we examined the capability of the purified enzyme to eradicate preformed biofilms of S. aureus in combination with ampicillin. Additionally, we assessed the stability of the enzyme in the presence of metal ions and detergents. Results: Enzyme kinetics revealed a Vmax of 48.63 µM/min and a Km of 14.08 µM, indicating efficient enzymatic activity. Furthermore, the enzyme exhibited maximum activity at physiological pH, suggesting its potential effectiveness under physiological conditions. Conclusions: Our preliminary findings highlight the promising role of this enzyme as a potential agent to combat S. aureus biofilms, especially when used in conjunction with ampicillin, as an alternative antibiotic approach.

Protein tyrosine kinases (PTKs) are key enzymes of cellular signaling, regulating key processes such as proliferation, differentiation, migration, metabolism, and apoptosis. TKs modulate protein functions in normal and disease states by phosphorylation of tyrosine residues on target proteins. On this critical role, dysregulation of TKs is directly linked with disease progression, particularly in cancer, therefore making TKs an attractive target for therapeutic intervention. The PTK family is broadly classified into receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (NRTKs), having variation at both structural and functional levels. RTKs are membrane-bound kinases that initiate intracellular signaling when they react with extracellular ligands, whereas NRTKs within the cytoplasm or nucleus convey intracellular signaling upon receptor activation. This review aims at the organization, mechanistic activity, and therapeutic potential of PTKs, with a particular focus on epidermal growth factor receptor (EGFR) and Src kinase as representative of RTK and NRTK, respectively. Additionally, this review also focuses on addressing emerging strategies to enhance TKI efficacy and overcome acquired resistance in cancer therapy.

Objectives. Biofilm infections caused by S. aureus present a significant threat to human health, leading to nosocomial infections on a global scale. To address this critical challenge and explore alternative antibiotic treatments, we investigated the potential of Solanum trilobatum (S. trilobatum), an edible and medicinally important herb plant in Ayurvedic medicine.

The ATP-binding cassette (ABC) transporter superfamily, one of the largest membrane protein families, plays a crucial role in multidrug resistance (MDR) in cancer by mediating the efflux of various chemotherapeutic agents, thereby lowering their intracellular concentrations and diminishing therapeutic effectiveness. Beyond drug efflux, these transporters are also involved in vital biological processes, such as signal transduction in cancer. Over the past few decades, extensive structural and functional research has provided valuable insights into ABC transporters’ broad substrate specificity and transport mechanisms, leading to promising strategies for overcoming MDR. This review will provide a structural understanding of the interactions between ABC transporters and inhibitors to develop novel cancer therapeutics. Additionally, we focus on methods such as irradiation-based immune therapies, thermal therapies, nanomedicine, CRISPR-Cas, and natural therapies that can genetically modify ABC transporters to reduce their expression or reverse the drug efflux ability. Knowledge gained from these approaches can then be translated into the development of new cancer therapeutics that can combat chemotherapy resistance.

Cancer treatment is evolving with the advent of nanotechnology, shifting from conventional therapies to precision medicine. Nanoparticles (1–100 nm) which encapsulate drugs and direct them to tumor sites offer unique advantages in cancer therapy, including enhanced drug delivery, reduced toxicity, and improved specificity. This editorial examines various types of nanoparticles, with focus on those that have progressed to clinical trials, while addresses the challenges in translating these innovations from the laboratory to clinical practice. Despite the growing body of researNanoparticlesch, the number of approved nanodrugs remains limited. Hence a deeper understanding of nano formulations and their targeting mechanisms will be crucial to advancing cancer treatment in the future.

The ATP-binding cassette (ABC) transporter superfamily, one of the largest membrane protein families, plays a crucial role in multidrug resistance (MDR) in cancer by mediating the efflux of various chemotherapeutic agents, thereby lowering their intracellular concentrations and diminishing therapeutic effectiveness. Beyond drug efflux, these transporters are also involved in vital biological processes, such as signal transduction in cancer. Over the past few decades, extensive structural and functional research has provided valuable insights into the broad substrate specificity and transport mechanisms of ABC transporters, leading to promising strategies for overcoming MDR. This review will provide a structural understanding of the interactions between ABC transporters and inhibitors to develop novel cancer therapeutics. Additionally, we focus on methods such as irradiation-based immune therapies, thermal therapies, nanomedicine, CRISPR-CAS, and natural therapies that can genetically modify ABC transporters to reduce their expression or reverse the drug efflux ability. Knowledge gained from these approaches can then be translated into the development of new cancer therapeutics that can combat chemotherapy resistance.