Lung cancer is one of the leading causes of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for 84% of cases. Traditional treatments like surgery and chemotherapy have limited effectiveness and significant side effects. Despite combination chemotherapy being the preferred first-line therapy, the prognosis for advanced NSCLC remains poor, with a median survival of 8-11 months and a 1-year survival rate of 30%. There is a critical need for new treatments targeting the molecular mechanisms of NSCLC. Precision medicine, or targeted therapy, has emerged as a promising approach, focusing on genetic and epigenetic alterations. This method is more effective for advanced NSCLC. It involves drugs targeting specific genetic abnormalities such as ROS proto-oncogene 1 (ROS1), EGFR (Epidermal growth factor receptor), ALK (Anaplastic lymphoma kinase), BRAF (v-Raf murine sarcoma viral oncogene homolog B1, MET (Mesenchymal epithelial transcription factor), and RET (Rearranged during transfection) mutations, which are vital driver genes for lung cancer development and progression. With up to twenty treatments approved by the FDA, targeted medicines are still being developed, and targeted therapy and chemotherapy have dramatically improved patient outcomes. Despite progress, treating metastatic NSCLC remains challenging due to resistance to genetic changes. This narrative review provides a detailed description of the various classifications of molecular targeted therapeutic approaches employed in lung cancer management and its mechanisms of action in cancer prevention and its advantages and disadvantages.
One of the major hallmarks of Alzheimer’s disease (AD), deposition of amyloid plaques in the brain, arises from the proteolytic processing of the amyloid precursor protein (APP), a process in which the rate-limiting step is carried by β-secretase (BACE1). Due to this essential role in the development of AD, BACE1 has become a widely studied drug target for the development of new drugs aimed at blocking amyloid β peptide formation and aggregation through inhibition of BACE1 activity. The development of the first BACE1 inhibitors allowed the determination of its crystal structure and description of its active site, confirming the existence of eleven well-defined subsites able to accommodate a range of substrates, which enabled BACE1 to participate in a number of biological processes. For this reason, the study of BACE1 structure and determination of specific structural motifs responsible for the accommodation of known substrates could enable defining drugs with very specific targets, as well as provide insight into the mode of action of BACE1 itself. This review will focus on the overall structure of BACE1 and its active site, as well as on the effect of genetic polymorphisms and isoforms on its activity.
Ovarian cancer is one of the most common and deadliest tumors among women. Despite recent clinical advances, the combination of platinum-based chemotherapy and surgery remains the first-line therapeutic option. Due to frequent detection at an advanced stage and development of therapy resistance, the disease prognosis is often poor, and mortality rates remain high. Therefore, it is necessary to investigate new therapeutic approaches that would contribute to increased survival and higher life quality of ovarian cancer patients. One of these approaches is the use of the pro-oxidant effect of certain drugs that can disrupt the redox balance in tumor cells and lead to their death. Vitamin C (ascorbic acid or ascorbate) used in high concentrations suppresses cancer cell growth and metastasis. There are several mechanisms by which vitamin C exerts its antitumor function including pro-oxidant activity, epigenetic reprogramming and tumor environment oxygen sensing. The potential use of vitamin C in combinatorial therapies (as a support to standard therapies) should be reconsidered through more detailed mechanistic and clinical studies. Finding new therapeutic approaches would augment the available mechanisms in the fight against cancer leading to the increase in patient welfare and overall survival of cancer patients.
Aquaculture stands out as a highly promising practice within sustainable agriculture, especially when compared to other livestock production sectors. However, it faces significant challenges, including water pollution, fluctuations in dissolved oxygen levels, and the prevalence of both chronic and acute diseases. To address these issues, researchers in the aquaculture sector have been exploring and implementing innovative solutions. One of the most notable advancements is the use of nanobubble technology, which has already been applied in numerous aquaculture farms to mitigate these challenges. Nanobubbles (NBs) with a diameter of less than 200 nm have shown promising results in improving water quality in aquaculture systems, increasing dissolved oxygen availability, and improving the overall health of cultured organisms. This review will emphasize various practical applications of nanobubble technology in different areas of aquaculture, including their properties and characterization methods, and discuss the hotspots of current research to help shape the future of intensive aquaculture. It will also uncover the nanobubble technology application in water and wastewater treatment processes, such as disinfection, sterilization, and detoxification. Additionally, the review will discuss the application of nanobubble technology in improving the growth performance and health of aquatic organisms, including its roles in aeration, water quality management, nutrient, drug delivery, monitoring, algae control, and functional feeding strategies. However, extensive research and standardization to be optimized for the application of nanobubbles in culture systems to understand their chronic effects on growth and overall production of fishes.
Background and purpose: Clarias magur (Hamilton, 1822), the Asian or walking catfish, is a high-value fish species in India and Southeast Asia for its taste and nutritional value. The combined effect of ammonia and bacterial infection on C. magur has not been studied so far. Moreover, the mechanism of ammonia-induced toxicity and their adaptability in C. magur is poorly understood. Given this context, a systematic study was devised to examine the individual and combined exposure effect of unionized ammonia and Aeromonas caviae on haemato-biochemical and histopathological changes of different tissues of C. magur. Materials and methods: A 14-day experiment was conducted to expose the fish to sublethal doses of UIA, A. caviae, and a combination of both. Initially, we have determined the 96-hr LC50 value for UIA in C. magur. During the experimental period, various hematological parameters were tested, such as total erythrocyte count, hemoglobin, packed cell volume, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. Different biochemical parameters like blood glucose, serum, and tissue urea, serum glutamate pyruvate transaminase, and serum glutamate oxaloacetate transaminase levels and histopathological examination were performed. Results: The 96-hr LC50 value for UIA in C. magur was 7.21 mgL–1. The 14th day exposure of UIA (2.4 mgL–1), A. caviae (1.53 × 105 CFU mL–1), and their combination resulted in significant decreases in various hematological parameters such as total erythrocyte count, hemoglobin, packed cell volume, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. Additionally, there were notable increases in blood glucose, serum and tissue urea, serum glutamate pyruvate transaminase, and serum glutamate oxaloacetate transaminase levels in all treatment groups compared to the control. Histological examination revealed significant changes in gill, kidney, and liver tissues, including lamellar fusion, edema, nodular enlargement of lamellar tips, lamellar congestion and curling in gill tissues, cytoplasmic vacuolation, pyknosis, karyorrhexis, karyolysis, and degeneration of renal tubule cells in kidney tissues, and increased vacuolation in hepatocytes, disorganization of hepatic cords, and increased hemorrhage in liver tissues. Interestingly, the combined exposure to UIA and A. caviae resulted in fewer histological alterations than individual exposures. Furthermore, after the 14th day, the group exposed only to bacteria exhibited the lowest relative percent survival compared to those exposed to only UIA and the combination. Conclusions: This study signifies that there was a negative synergistic or antagonism effect in the fish after exposureto ammonia and bacteria in combination. This discrepancy indicates that elevated ammonia concentrations might haverestricted the survival of A. caviae or disrupted the infection process. The present study's findings open a new avenue for further understanding the mechanism of ammonia exposure in the direction of an alternative method to combat bacterial infections.
