Pesticides are among the most widely used synthetic chemicals worldwide to protect crops, but they pose several environmental and health issues. The present study evaluates toxic effects of acetamiprid (ACMP) in rat liver and kidney tissues. Rats were exposed to ACMP (21.7 mg/kg b.wt; 1/10^th LD₅₀) for 21 days. Oxidative stress generation, apoptotic progression, and structural changes were evaluated via biochemical assays, semi-quantitative PCR, western blotting, and histopathology. ACMP exposure significantly decreased body weight and altered relative organ weight in hepato-renal tissues. Significant oxidative stress was evident by increased oxidative injuries to lipids and proteins and alterations of endogenous anti-oxidative enzymes. The administration of ACMP upregulated mRNA expression of Bax and caspase-3, while downregulated the mRNA expression of Bcl-2 and released cytochrome c into the cytosol of the liver and kidney tissues. Likewise, exposure to ACMP caused severe degenerative changes in the histo-architecture of hepato-renal tissues. The results of the present study confirmed the toxicity of ACMP in rats’ liver and kidney tissues and emphasized the need for strict regulation and more mechanistic understanding to delineate the toxicity of ACMP in mammals.

A novel, sensitive, portable method for detecting DNA from various human samples is most desirable. This study aims to develop a microdevice for on-chip DNA extraction and detection by PCR from various forensic samples. A microchip constructed by sandwiching a fusion-5 filter disc between PMMA layers was characterized using SEM, FTIR, and XRD. DNA capture efficiency of the microchip from human samples was quantified by Real-Time PCR. PCR products were evaluated off-chip by DNA sequencing (STR Typing). On-site detection was performed by visualizing the DNA amplicons on Fusion-5 filter paper under UV light after EtBr staining. Among all concentrations, 5% by weight PMMA membrane was found most suitable for PMMA-Fusion-5 filter disc fluidic Microchip, the best smooth cross-section morphology by SEM, strong absorption vibrations at corresponding wavelengths by FTIR, increased amorphous phase by XRD were confirmed. Using this microdevice, DNA extraction from human whole blood was, without any leakage, fast (≤7 minutes), most efficient (highest, Ct=27.22) as evaluated by real-time PCR, needs just 2µl blood sample as shown by a typical, balanced STR profile. The microdevice designed for on-chip DNA extraction has excellent potential for rapid, on-site DNA detection from various samples.

URN:NBN:sciencein.cbl.2024.v11.665

Platinum-based chemotherapeutics inflict a spectrum of DNA damage, including DNA adducts, DNA-protein crosslinks (DPCs), and interstrand crosslinks (ICLs) to variable extents. These diverse lesions may contribute to the overall toxicity of these therapeutic agents. Nonetheless, a gap exists in comparative studies elucidating the specific DNA damage responsible for their toxicity. Therefore, we exposed MRC5SV cells to equitoxic doses (LD₁₀) of cisplatin (cisPt) and oxaliplatin (L-OHP) and systematically examined the induction of DPCs, ICL, and protein damage. Our findings suggest that DPCs emerge as the crucial cytotoxic DNA damage for both cisPt and L-OHP, highlighting their central role in the mechanism of action driving the cytotoxicity of platinum-based therapeutics. Both drugs show induction of ICLs as computed by the unique sensitivity of Fanconi anemia cells to the drugs. Additionally, both cisPt and L-OHP didn’t show protein damage as indicated by the absence of TRX1 oxidation post-treatment. Overall, our results underscore the critical involvement of DPCs in the toxicity of platinum-based drugs, emphasizing the importance of DPCs as potential cancer therapeutic targets.

URN:NBN:sciencein.cbl.2024.v11.663

Synthesis of 9-(4-bromophenyl)-6 aryl-[1,2,4]triazolo[4,3-a][1,8]naphthyridine-2-carbonitrile (4a-j) from 7-(2-(4bromobenzylidene)hydrazinyl)-6-aryl-1,8-naphthyridine-2-carbonitrile (3) oxidized with chloramines-T in methanol under microwave irradiation is a straight forward and very efficient process. Very high yields and excellent purities of the products were achieved. Elemental analysis, IR, ¹H NMR, ¹³C NMR and Mass spectroscopy are used to characterize the produced compounds. All synthesized compounds were tested for their antimicrobial efficacy and found moderately active against different types of bacterial and fungal strains in comparison with Streptomycin, Nystatin.

URN:NBN:sciencein.cbl.2024.v11.664

Antimicrobial resistance (AMR) poses a significant threat to global health. It makes treating bacterial infections increasingly difficult. AMR arises from various mechanisms of antibiotic resistance including enzymatic inactivation, target alteration, efflux pumps, and decreased permeability. The limited and often ineffective treatments relying on antibiotics and their combinations result in increased morbidity and mortality. Therefore, it is essential to explore alternative methods for combating the challenge of AMR. In recent years, there has been a notable shift towards precision medicine in the battle against AMR. Precision medicine, characterized by its focus on individualized treatment tailored to patients’ specific genetic makeup, offers a paradigm shift in addressing AMR challenges. By pinpointing molecular targets responsible for infection, precision medicine enables more targeted and effective therapies, minimizing the risk of antimicrobial resistance development. Precision medicine can provide an alternative option to combat AMR by focusing on targets responsible for the infection. Bacteriophages and antimicrobial peptides (AMPs) are groups of antimicrobials that can serve as novel alternatives to antibiotics for combating the global antibiotic resistance challenge. They have the potential to be used as targeted therapy. Despite challenges such as limited host range, which refers to the specific bacteria they can infect, and regulatory concerns related to their approval and usage, bacteriophages have proven effective against bacteria causing infections. Meanwhile, AMPs provide a potential treatment approach against antibiotic-resistant bacteria due to their low molecular weight and broad-spectrum antimicrobial activity. AMPs can serve as a first line of defense against microorganisms. When used alone or combined with other biomaterials to increase therapeutic action, they can serve as a first line of defense against microorganisms. This review article aims to provide a comprehensive overview of the current understanding and clinical potential of bacteriophages and AMPs as alternatives to conventional antibiotics in addressing the pressing challenge of AMR.

URN:NBN:sciencein.cbl.2024.v11.662