Cadmium (Cd) remediation in Pseudomonas aeruginosa is achieved through the function of two vital genes, cadA and cadR, that code for P-type ATPase (CadA) and transcription regulatory protein (CadR), respectively. Although numerous studies are available on these metal-sensing and regulatory proteins, the promoter of these genes, metal sensing and binding ability, are poorly understood. The present work is aimed at the characterization of the CadR protein, identification of the P _cadR promoter and protein–promoter–metal binding affinity using bioinformatics and to validate the results by cloning the P _cadR promoter in Escherichia coli DH5α. The promoter regions and its curvature were identified and analysed using PePPER software (University of Groningen, The Netherland) and the Bendit program (Version: v.1.0), respectively. Using Phyre, the three-dimensional structure of CadR was modelled, and the structure was validated by Ramachandran plots. The DNA-binding domain was present in the N-terminal region of CadR. A dimeric interface was observed in helix-turn-helix and metal ion-binding sites at the C-terminal. Docking studies showed higher affinity of Cd to both CadR (Atomic contact energy = −15.04 kcal/Mol) and P _cadR (Atomic contact energy = −40.18 kcal/Mol) when compared to other metal ions. CadR with P _cadR showed the highest binding affinity (Atomic contact energy= −250.40 kcal/Mol) when compared with P _cadA. In vitro studies using green fluorescent protein tagged with P _cadR ( gfp-P _cadR) cloned in E. coli-expressed gfp protein in a concentration-dependent manner upon Cd exposure. Based on our in silico studies and in vitro molecular cloning analysis, we conclude that P _cadR and CadR are active only in the presence of Cd. The CadR protein has the highest binding affinity with P _cadR. As it became apparent that the cadR gene regulates the P _cadR activity in the presence of Cd with high specificity, and the cadR and P _cadR can be used as a biological tool for development of a microbial biosensor.

Experimental induction of hyperoxaluria by ethylene glycol (EG) administration is disapproved as it causes metabolic acidosis while the oral administration of chemically synthesized potassium oxalate (KOx) diet does not mimic our natural system. Since existing models comprise limitations, this study is aimed to develop an improved model for the induction of dietary hyperoxaluria, and nephrocalcinosis in experimental rats by administration of naturally available oxalate rich diet. Male albino Wistar rats were divided into five groups. Group I, control; group II rats received 0.75% EG, group III rats fed with 5% KOx diet and group IV and V rats were administered with spinach extract of 250 and 500 mg soluble oxalate/day respectively, for 28 d. Urine and serum biochemistry were analyzed. After the experimental period, rats were sacrificed, liver and kidney tissue homogenates were used for antioxidant and lipid peroxidation assay. Relative change in expression of kidney injury molecule-1 (KIM-1) and crystal modulators genes in kidney tissues were evaluated. Tissue damage was assessed by histology studies of liver and kidney. Experimental group rats developed hyperoxaluria and crystalluria. Urine parameters, serum biochemistry, antioxidant profile, lipid peroxidation levels and gene expression analysis of experimental group II and III rats reflected acute kidney damage compared to group V rats. Histopathology results showed moderate hyperplasia in liver and severe interstitial inflammation in kidneys of group II and III than group V rats. Ingestion of naturally available oxalate enriched spinach extract successfully induced dietary hyperoxaluria and nephrocalcinosis in rats with minimal kidney damage.

The mitigation of cadmium (Cd) pollution, a significant ecological threat, is of paramount importance. Pseudomonas aeruginosa harbors 2 Cd resistance genes, namely, cadR and cadA. Presently, our focus is on the identification and characterization of the cation-transporting P-type ATPase (cadA) in Pseudomonas aeruginosa BC15 through in silico methods. The CadA protein and its binding capacities remain poorly understood, with no available structural elucidation. The presence of the cadA gene in P aeruginosa was confirmed, showing a striking 99% sequence similarity with both P aeruginosa and P putida. Phylogenetic analysis unveiled the evolutionary relationship between CadA protein sequences from various Pseudomonas species. Physicochemical analysis demonstrated the stability of CadA, revealing a composition of 690 amino acids, a molecular weight of 73 352.85, and a predicted isoelectric point (PI) of 5.39. Swiss-Model homology modelling unveiled a 33.73% sequence homology with CopA (3J09), and the projected structure indicated that 89.3% of amino acid residues were situated favourably within the Ramachandran plot, signifying energetic stability. Notably, the study identified metal-binding sites in CadA, namely, H3, C30, C32, C35, H48, C89, and C106. Docking studies revealed a higher efficiency of Cd binding with CadA compared to other heavy metals. This underscores the crucial role of N-terminal cysteine residues in Cd removal. It is evident that CadA of P aeruginosa BC15 plays a crucial role in Cd tolerance, rendering it a potential microorganism for Cd toxicity bioremediation. The structural and functional elucidation of CadA, facilitated by this study, holds promise for advancing cost-effective strategies in the remediation of cadmium-contaminated environments.

The increasing global incidence of colorectal cancer (CRC) necessitates the development of innovative and targeted therapeutic interventions. Marine-derived bioactive compounds have gained prominence due to their structural diversity, intrinsic bioactivity, and potential to modulate oncogenic and tumor-suppressive microRNAs (miRNAs). Simultaneously, miRNAs have gained attention as critical regulators of gene expression in CRC, influencing key processes such as proliferation, metastasis, apoptosis, and chemoresistance. Nanotechnology has further transformed this field by enhancing drug solubility, stability, and tumor-specific delivery, thereby enabling combinatorial approaches such as the co-delivery of miRNA-targeted nano-formulations with conventional chemotherapeutics. Notably, co-delivery systems combining miRNA-targeted nano-marine drugs with conventional chemotherapy have shown synergistic effects in overcoming drug resistance and enhancing therapeutic efficacy. Despite encouraging preclinical outcomes, clinical translation remains constrained by challenges related to pharmacokinetics, scalability, immunogenicity, and regulatory compliance. This review critically evaluates the mechanistic interplay between marine compounds and miRNAs in CRC, advances in nanoformulation strategies, and translational barriers, providing insights into future directions for clinical application.

In Allium cepa (L.) cultivation, salinity stress is the most important environmental factor worldwide that affects plant growth, protection as well as yield stability. The present study was carried out to examine the alterations in soil dynamics, antioxidants, biochemical and secondary metabolic profile of A. cepa under alkaline stress. Various parameters of A. cepa were studied under salinity stress by exposing them to different concentrations of sodium carbonate (SC) and sodium bicarbonate (SBC) salts (0, 10 and 100mM). Treatment of both SC and SBC in A. cepa increases superoxide dismutase, glutathione peroxidase and catalase concentrations. These were attributed to increase in peroxide, lipid peroxides as well as carbonyl groups. The salinity stress was driven by the alterations in the soil dynamics. Of note, the salt stress induces secondary metabolites changes in A. cepa. The compounds like phenol 2 4-bis (1 1-dimethylethyl), hexadecane, 7,9-di-tert-butyl-1-oxaspiro (4,5) deca-6,9-diene-2,8-dione, 1,2-benzenedicarboxylic acid, butyl octyl ester, 1,2-benzenedicarboxylic acid, diisooctyl ester are elevated. In addition, the level of total proteins is reduced in all the groups except 10mM and Proline amino acid in the shoot is elevated. Reversing all the parameters tested to achieve control levels in A. cepa indicates that significant cellular mechanism appeared in stress condition that brings back the altered parameters to normal levels. The biochemical and secondary metabolite profile analysis of the petroleum ether extracts of A. cepa under various alkaline stress conditions reveals that the composition of secondary metabolites and their concentration in A. cepa varies depending on the extent of alkaline stress.