Current Chemical Biology - Current Issue

Scientific and non-scientific groups have contributed to raising awareness in recent years about animal welfare. The results of such efforts include the creation of legal frameworks concerning animal abuse (or mistreatment) and the growing number of technical requirements for the commercial exploitation of animal-derived products (such as beef, milk, and eggs). Nonetheless, thermal stress is poorly explored in animal welfare research despite its life-threatening consequences.

In this study, we discuss the biochemical and physiological effects of thermal stress in cattle, broilers, dogs and cats.

This review was conducted using data published in Portuguese and English, retrieved from Lilacs, Scielo, and PubMed databases, using the keywords “stress, cold, heat, canines, felines, broilers, poultry, milk cattle, and beef cattle”. Papers were considered if they were published from 2013 to 2025.

Thermal stress refers to a series of biochemical and physiological changes that occur due to short-, moderate-, or long-term exposure to excessively high or low temperatures, where adaptive mechanisms fail to restore normal body temperature. Defining ideal body temperatures for animals can be challenging, as they are influenced by factors such as sex, general health status, body mass, species, and breed. In the species studied, heat typically increases levels of Reactive Oxygen Species (ROS), cortisol, transaminases, creatine kinase, and lactic acid, while decreasing levels of Superoxide Dismutase (SOD) and ATP. Cold exposure increases T4 production, proinflammatory cytokines, such as TNF-α and IL-4, and decreases SOD and lipid content in various tissues.

Studies on thermal stress are necessary to provide evidence on what actions are needed to control and adjust environmental conditions for proper husbandry of production and companion animals.

Dysregulated metabolism, including lipid peroxidation, contributes to the various stages of breast cancer, including initiation and progression. However, 4-HNE mimetic as a new class of drugs of epigenetic enzymes is not explored.

The objective of this study was to explore the relevance of lipid peroxidation products in breast cancer and the design of mimetic 4-HNE as an inhibitor of SIRT2.

The metabolite profiling of 4-HNE was collected from the urine of breast cancer patients and healthy subjects by employing an in-house developed vertical tube gel electrophoresis (VTGE) tool and LC-HRMS. The determination of lipid peroxidation products MDA was estimated by thiobarbituric acid-reactive substance (TBARS) assay. Mimetic 4-HNE (4-HNEM) was designed and evaluated for their inhibitory binding affinity upon a potential target SIRT2 using molecular docking and molecular dynamics (MD) simulations.

Metabolic profiling of 4-HNE indicated detectable levels in the urine of breast cancer patients over non-detectable levels in healthy subjects. Also, the level of TBARS MDA appeared to be reduced in the urine of breast cancer patients over healthy control. Computational tool-assisted molecular docking-based screening data predicted that 4-HNE has a good inhibitory binding affinity (-7.0 kcal/mol) upon SIRT2. Furthermore, the designed mimetic 4-HNEM projected an improved inhibitory binding affinity (-8.7 kcal/mol) against SIRT2. Furthermore, mimetic 4-HNEM exhibited equivalent strong binding affinity and specific interacting amino acid residues (ARG97, PHE119, ALA186, PHE234, PHE235) similar to a known SIRT2 inhibitor 8NO. ADMET profiles of 4-HNEM, including drug-induced liver injury and cytotoxicity, were found to be slightly better than a known SIRT2 inhibitor 8NO.

This study emphasizes the relevance of 4-HNE and MDA as biomarkers in breast cancer. A mimetic 4-HNEM is projected to be a novel small-molecule inhibitor of SIRT2 that could be explored as a potential combinatorial anticancer agent.

The global rise in antibiotic resistance among pathogenic bacteria poses a critical threat to public health. Pseudomonas aeruginosa, a Gram-negative opportunistic pathogen, displays both intrinsic and acquired resistance mechanisms. Emerging evidence implicates post-transcriptional tRNA modifications in antibiotic resistance, positioning tRNA-modifying enzymes like trmA as potential therapeutic targets.

This study aims to identify potential inhibitors of trmA to disrupt essential cellular pro- cesses and counter antibiotic resistance.

We employed a structure-based virtual screening strategy to identify compounds structurally analogous to S-adenosylmethionine, a universal methyl group donor and known trmA binder. Top-ranked compounds were further evaluated through molecular dynamics (MD) simulations to examine binding-induced conformational dynamics and stability.

Compound 24762163 emerged as a lead candidate with favorable binding affinity and structural compatibility, as confirmed through docking and MD simulations. The compound formed stable interactions with the active site of trmA, indicating its inhibitory potential.

The computational findings suggest that compound 24762163 may effectively disrupt trmA function, thereby impairing tRNA methylation and hindering protein synthesis in P. aeruginosa. Given the essential role of tRNA modifications in bacterial survival and resistance, targeting trmA represents a promising strategy for novel antimicrobial development.

This study identifies compound 24762163 as a promising trmA inhibitor and a potential therapeutic agent to counter antibiotic resistance in Pseudomonas aeruginosa. Targeting tRNA-modifying methyltransferases may offer a novel approach in the fight against drug-resistant pathogens.

Eryngium triquetrum (Apiaceae) is a medicinal plant traditionally used for its diuretic and anti-inflammatory properties. Despite its ethnopharmacological relevance, the anti-inflammatory, antidiabetic, and hemolytic activities of its essential oil and falcarinol-rich fraction (FRF) remain poorly explored. This study aimed to characterize the chemical constituents of the essential oil extracted from the aerial parts of E. triquetrum and to evaluate its anti-inflammatory, antidiabetic, and hemolytic properties, along with those of its falcarinol-rich fraction (FRF). Synergistic interactions with standard reference drugs were also assessed.

The essential oil and FRF were analyzed by gas chromatography–mass spectrometry (GC/MS). Anti-inflammatory activity was determined using the albumin denaturation assay, antidiabetic potential via α-amylase inhibition, and hemolytic activity using human erythrocytes. Combinations with diclofenac and acarbose were also tested.

Falcarinol was the major component in the essential oil (28.9%) and FRF (89.3%). FRF exhibited stronger anti-inflammatory (IC50 = 48.1 µg/mL) and antidiabetic (IC50 = 23.37 µg/mL) activities than the essential oil. Synergistic combinations with diclofenac and acarbose significantly improved efficacy (IC50 = 17.1 and 16.7 µg/mL, respectively). Hemolytic effects were minimal at active doses.

The pronounced bioactivities are mainly attributed to falcarinol. Its synergistic action with reference drugs reinforces its therapeutic interest.

E. triquetrum essential oil and its FRF represent promising natural agents for managing inflammation and type 2 diabetes. Further in vivo and clinical investigations are required to support their medical application.

The study investigates the quantification of sinensetin, a bioactive compound with antioxidant, anti-obesity, and anti-cancer properties, in cat's whiskers (Orthosiphon aristatus). The primary aim is to evaluate the effect of different extraction methods on sinensetin yield and to validate an high-performance liquid chromatography (HPLC) method for accurate quantification.

The research employed two extraction techniques: reflux and maceration. The HPLC method was validated for accuracy, precision, linearity, and specificity using a reverse-phase C18 column maintained at 25°C. The mobile phase consisted of acetonitrile (60:40) and 0.1% formic acid, with an isocratic elution. A 20 µl injection volume and a flow rate of 1 ml/min were used for analysis.

Validation results indicated a recovery rate of 98.37 ± 3.44% and a precision relative standard deviation (RSD) of 1.12%. The linearity correlation value was found to be 0.999. Sinensetin concentrations were quantified at 0.42 ± 0.006% for the macerated extract and 0.30 ± 0.006% for the reflux extract.

The findings demonstrate that the HPLC method is both accurate and precise for determining sinensetin levels, with maceration yielding higher concentrations than reflux. These results contribute to the understanding of extraction efficiency and the potential therapeutic applications of sinensetin.

This study confirms that accurate quantification of sinensetin in cat's whiskers is achievable using validated HPLC methods, highlighting the importance of extraction techniques in maximising bioactive compound yields.