High‐density lipoproteins (HDLs) are deeply implicated in atherosclerosis. HDL, myeloperoxidase (MPO), and paraoxonase‐1 (PON1) form a functional ternary complex where PON1 partially inhibits the MPO activity, and MPO in turn partially inactivates PON1. The activity of MPO is dependent on the concentration of hydrogen peroxide, but the extremely low concentrations of hydrogen peroxide in serums severely constrain MPO activity. PON1 has the activities of organophosphatase, arylesterase, and thiolactonase, but these hydrolase activities are extraneous to antioxidative stress. Thus, we proposed that MPO and PON1 may be involved in atherosclerosis by acting as proteins, rather than enzyme activities. Cholesterol efflux assay, ATP‐binding cassette transporter A1 (ABCA1)–dependent cholesterol efflux, and LCAT activity assay were performed. The effect of MPO, PON1, and serums from the individuals with ASCVD and healthy individuals on cholesterol efflux of human acute monocytic leukemia cell line (THP‐1 cells) was compared. Noncatalytic functions of MPO and PON1 were analyzed using recombinant proteins and neutralizing antibodies. Wound healing assay and tube formation assay were used to analyze noncatalytic functions of MPO and PON1 in modulating the involvement of human umbilical vein endothelial cells (HUVECs). We found that MPO protein decreased the cholesterol efflux; by contrast, PON1 protein increased the cholesterol efflux of THP‐1 cells. Importantly, MPO antibody partially restored cholesterol efflux, but PON1 antibody partially reduced cholesterol efflux of THP‐1 cells. Moreover, ABCA1 was necessary for controlling the involvement of MPO and PON1 in modulating cholesterol efflux of THP‐1 cells. There existed the confrontations between the noncatalytic functions of PON1 and MPO in migration of endothelial cells. Instead, MPO protein enhanced the expression of intercellular adhesion molecule‐1 (ICAM‐1) and E‐selectin of HUVECs; nonetheless, PON1 protein reduced the expression of these adhesion molecules. Of note, PON1 protein was unable to balance out the induction of MPO protein for these adhesion molecules in that the expression of these adhesion molecules generated by the combination of MPO protein and PON1 protein was similar to that of MPO. The activation of THP‐1 cells induced by MPO protein directly impaired in vitro microvascular structure via increasing the expression of IL‐6 and TNFα regulated by NF‐κB p65 of THP‐1 cells. Together, the noncatalytic functions entail MPO and PON in modulating the involvement of monocytes and endothelial cells in atherosclerosis.

IntroductionCompensated cirrhosis carries a significant risk of progression to decompensation, which substantially worsens prognosis. Accurate prediction of decompensation events is critical for guiding surveillance, optimizing intervention timing, and improving patient outcomes. Although many prognostic biomarkers have been studied, findings remain heterogeneous. This umbrella review synthesizes evidence from systematic reviews and meta‐analyses to identify and appraise biomarkers predicting decompensation in alcoholic and nonalcoholic compensated cirrhosis.MethodsPubMed, Scopus, and Web of Science were searched to August 15, 2025, for English‐language systematic reviews and meta‐analyses. From the included meta‐analyses, prognostic performance, heterogeneity, and publication bias were recorded.ResultsFour systematic reviews were included, two with meta‐analyses. Strong predictors across reviews were serum albumin, INR, bilirubin, platelet count, and liver stiffness measurement. HVPG remained a robust invasive predictor, while emerging biomarkers—interleukin‐6, keratin‐18, and extracellular vesicles—were associated with an increased risk of decompensation, although the certainty of evidence was limited by heterogeneity and methodological constraints. Composite scores enhanced predictive accuracy. AMSTAR 2 ratings ranged from high to low, with common reporting limitations. Overlap analysis indicated moderate redundancy among primary studies.ConclusionsBoth established and emerging biomarkers predict decompensation in compensated cirrhosis. Integrated multidomain models combining clinical, biochemical, and imaging‐derived measures may provide the greatest predictive value for guiding clinical decision‐making.

Whey, a by‐product of the cheese manufacturing industry, represents one of the most abundant and polluting effluents in the global food industry. Despite traditionally being underutilized and often discarded, its rich nutrient profile, particularly protein and lactose, has increasingly sparked an interest in its value within biotechnological processes. This review analyses the potential of whey as a sustainable substrate for the microbial production of value‐added bioproducts, focussing on L‐threonine production as a strategic case study, while addressing the environmental impact of inadequate disposal and current utilization strategies. A comparative analysis with other agroindustrial waste demonstrates whey’s competitive advantages in terms of composition, cost‐effectiveness and sustainability metrics. Furthermore, L‐threonine biological and industrial importance, and the most relevant advances in metabolic engineering, optimized fermentation and emerging tools such as optogenetics and machine learning are discussed, as they facilitate enhanced L‐threonine yields through the creation of robust, high‐producing strains. Technoeconomic analysis at pilot scale (33.8 tons/year) indicates that whey‐based production offers a comparative cost advantage of 7.4% over glucose‐based processes (20.55 USD/kg vs. 22.20 USD/kg). While absolute costs at pilot scale exceed current industrial market prices (1.31–1.66 USD/kg)—reflecting typical scale effects—the demonstrated comparative advantage and substantial environmental benefits (waste valorization, elimination of disposal costs and circular economy alignment) position whey‐based L‐threonine production as a strategic biorefinery opportunity with significant potential for industrial‐scale implementation. This cost benefit is primarily driven by the lower market price of whey compared to commercial glucose substrates, which compensates for the slightly higher downstream processing costs (5.90 vs. 5.40 USD/kg) required for complex matrices. Downstream processing considerations, including recovery, purity requirements and economic viability, are comprehensively addressed. This review concludes that whey, far from being merely a pollutant, has the characteristics required to become an asset for biotechnology. Utilizing whey as a culture medium for L‐threonine production by E. coli in bioreactors not only offers a solution to mitigate a significant environmental issue but also opens a path for the cost‐effective, sustainable production of a globally high‐demand amino acid. Whey represents a strategic biorefinery platform with potential for industrial‐scale implementation. Continued research and development in this area are fundamental to fully realizing this potential.

Glioblastoma is one of the most aggressive and widely recognized types of brain tumors, characterized by significant cellular and molecular diversity and an inherently aggressive nature. The treatment remains highly challenging, with limited effectiveness and persistently low survival rates. For this reason, researchers are continuously expanding the chemical space of anticancer agents by exploring complex sources such as animal venoms and incorporating in silico tools to accelerate discovery. Indeed, venoms serve as libraries of proteins and peptides, providing a rich source of novel chemical structures for glioblastoma therapy. Some review articles have examined the mechanisms by which venom‐derived peptides target glioblastoma cell lines; nevertheless, key structural insights and computational analyses remain underexplored. In this era of artificial intelligence (AI) and advancements in in silico approaches, our review documented the antiglioblastoma properties of venom peptides and underscores the value of computational methods in peptide‐based drug development. To this end, a comprehensive search was conducted in PubMed, Elsevier, Springer, Lilacs, Google Scholar, and SciELO databases. Furthermore, in silico analyses were conducted to evaluate the anticancer potential, hemolytic activity, toxicity, and blood–brain barrier (BBB) penetrating properties of venom‐derived peptides. In total, 26 unique sequences were identified, with their structural properties and mechanisms of cell death comprehensively characterized. The development of peptide‐based anticancer drugs remains in its early stages, with minimal advancement toward preclinical evaluation using in vivo models. The advancement of AI models offers opportunities to accelerate peptide discovery. However, our case study revealed divergences among AI‐based predictions, as well as discrepancies between computational and experimental findings, underscoring the need for further model refinement and validation through experimental data integration. In summary, venoms remain promising peptide libraries that offer valuable natural molecular templates. These peptides require chemical optimization to enhance their stability and BBB permeability. Such advances could enable selective targeting within the glioblastoma niche and support the development of more effective therapies.

Type 2 diabetes mellitus (T2DM) is a state where the body's glucose metabolism is compromised. AMP-activated protein kinase, or AMPK, has an important part to play in glucose metabolism, and the liver kinase B1 (LKB1) protein functions as a major upstream kinase for AMPK activation, thereby making it appealing therapeutic targets for treating and preventing T2DM. Drug resistance cases for biguanides like metformin is a serious concern and pose great threat to treatment success for diabetic patients. Thus, the hunt for biguanide-like small molecules with enhanced insulin sensitizing potentials is necessary. In the present study, interaction between LKB1 and biguanides such as phenformin, metformin, and buformin has been thoroughly assessed using computational tools. Ligand-based pharmacophore mapping of 29,000 phytochemicals collected from NPASS database was carried out. The screening was conducted to hunt novel antidiabetic compounds targeting LKB1 pathway to improve insulin sensitivity in T2DM. Molecular docking of 31 phytochemicals with good pharmacophore fit scores was then carried out to identify hit compounds. ADMET analysis was also utilized to screen down compounds. dragmacidin D, dioncopeltine A, saussureamine C, and agelastatin D have good binding affinities and acceptable ADMET parameters. Molecular dynamics simulation was carried out to confer the stability of ligand-protein complex under simulated human body conditions. After 100 nanoseconds molecular dynamics simulation, the LKB1 protein complexed with compounds (saussureamine C and agelastatin D) was found to be stable. The results of the current study can be useful in developing antidiabetic medications with enhanced insulin sensitization activates superior to those available in market.

Malaria remains a significant and worldwide health threat with increasing resistance to current treatments, stimulating the demand for innovative approaches in pursuing drug discovery. This systematic review integrates the progress made from 2014 through 2024 regarding molecular methods like gene expression profiling, molecular docking and machine learning to understand the biology of Plasmodium and identify new drug targets and compounds, focusing on herbal remedies and computational methods. Several studies were found using a PRISMA-guided search of PubMed, Scopus and Web of Science (64 studies found). The data extracted were gene expression outcomes, docking affinities, ML models and experimental validations (in vitro/in vivo). Molecular docking emerged as the dominant technique (32.37%), followed by in vitro antiplasmodial assays (14.39%), ADMET profiling (10.79%) and gene expression studies (3.60%). RNA-seq analysis revealed key host and parasite genes modulated by herbal treatments, including those involved in apoptosis and inflammation. Notably, compounds like isorhamnetin and myricetin 3-O-glucoside showed exceptionally high binding affinities to Plasmepsin II and Plasmodium falciparum lactate dehydrogenase (PfLDH) (ΔG < -13 kcal/mol). ML models like random forest and support vector machine (SVM) exhibited high predictive results (AUC value up to 0.87) for bioactivity and resistance patterns that showed flavonoids (quercetin) and terpenoids (eugenol) as good candidates. Pathways that are often attacked are haemoglobin degradation, glycolysis, pyrimidine metabolism and protein synthesis. Multiomics, docking and ML integration improve the target identification and prioritise the compounds. This review illustrates the great potential of molecular techniques for the development of drugs against antimalarial helicases that are not resistant to drug therapy. However, in vivo data holes and methodology inconsistency limit clinical translation. Future work should include standardisation of protocols and studies of synergistic combinations of phytochemicals.

During tumorigenesis and metastasis, cancer cells initiate antioxidant defense mechanisms to prevent irreversible damage, thereby sustaining tumor growth. The functionality of reactive oxygen species (ROS)-scavenging proteins is dependent on nicotinamide adenine dinucleotide phosphate (NADPH), which is regulated by specific metabolic enzymes, which are described as potential biomarkers of cancer aggressiveness. Immunohistochemistry (IHC) is one of the most accessible and widely utilized techniques to augment the pathological diagnosis of cancer. Hence, this review addresses the protein expression of NADPH-related enzymes, as assessed by IHC, and their associations with human cancer progression factors (overall survival, tumor staging, metastasis, and recurrence). Studies indicate that glucose-6-phosphate dehydrogenase (G6PD), along with malic enzymes and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), represents the most pertinent enzymes examined through IHC concerning cancer aggressiveness. The immunolabeling method produced consistent results for this group of enzymes, which might lead to successful application in predicting tumor prognosis. Other NADPH-related enzymes, such as glutamate dehydrogenase (GDH), aldehyde dehydrogenase 1 (ALDH1), and dihydrofolate reductase (DHFR), deserve more extensive investigation to elucidate their potential as cancer biomarkers via IHC.

Juvenile dermatomyositis (JDM) is a rare autoimmune disease primarily affecting children, characterized by muscle weakness and skin lesions. This study identifies 145 genes significantly associated with JDM through differential gene expression analysis, weighted gene coexpression network analysis (WGCNA), protein-protein interaction network analysis, and miRNA and transcription factor (TF) prediction, using blood and muscle microarray sequencing datasets. Functional enrichment analysis indicates that these genes are involved in crucial biological processes, including cytokine-mediated signaling, extracellular matrix organization, and immune response. Further analysis reveals key TFs (e.g., STAT1 and NFKB1) and miRNAs (e.g., hsa-miR-127-3p and hsa-miR-17-5p) that may regulate the expression of these critical genes in JDM. The findings provide new insights into the molecular mechanisms of JDM and offer potential targets for future diagnostic and therapeutic strategies.

Bromelain is one of the protease enzymes found in all parts of pineapple (Ananas comosus (L.) Merr.), including the crown and peel. This enzyme has been widely used in various fields of life, including the food industry, health, pharmaceuticals, and cosmetics. However, pineapple processing often focuses on the flesh of the fruit, leaving behind substantial agricultural waste, such as crown and peel waste. The waste is often collected and stored before being used, causing the bromelain enzyme to decrease or even dissipate. Therefore, this study aims to determine the effect of time and the condition of storage of pineapple crown and peel waste on total protein content and protease activity. The extracted bromelain was precipitated with ethanol and then dried, and total protein content and protease activity were determined. The results showed that pineapple crown and peel waste can be stored for 7 days at 29 ± 1°C and humidity of 70 ± 2% and 20 days at 4 ± 0.5°C and humidity of 40 ± 2%, respectively. The total protein content and protease activity were 169.94 ± 2.68 μg/mL and 46.35 ± 0.69 IU/mg for crown bromelain, while those for peel bromelain were 229.75 ± 15.61 μg/mL and 29.10 ± 1.98 IU/mg, respectively. In conclusion, pineapple crown waste has the potential to be developed as a source of bromelain.

Chronic kidney disease (CKD) is a major health issue associated with oxidative stress and inflammation that leads to progressive renal damage. Natural antioxidants, gallic acid (GA) and alpha‐tocopherol (AT), have gained attention for their strong free radical‐scavenging, inflammation‐reducing, and tissue‐repairing properties, and their individual or combined administration may offer therapeutic potential in CKD management. This experiment was designed to explore the potential ameliorative effects of GA and AT against CKD induced by adenine in male rats. Adult rats weighing 180–220 g (n = 48) were distributed among eight experimental groups. Except for Group I (control), all groups received a standard rat diet supplemented with 0.75% (w/w) adenine for 4 weeks to induce CKD. During the same period, the experimental groups received oral treatments of GA and AT at doses of 100 and 400 mg/kg body weight, respectively, as well as their combinations (GA–AT) at the same doses. The treatments were administered simultaneously for 4 weeks to evaluate their effects on adenine‐induced CKD. The results indicated that both GA and the combination of GA–AT were significantly more effective than AT alone in improving renal function markers such as uric acid, creatinine, albumin, and urea. Additionally, these treatments led to better outcomes for serum concentrations of these markers and oxidative stress biomarkers. Histopathological analysis confirmed the beneficial effects on kidney tissue compared to the diseased group. Moreover, both GA and the GA–AT combination treatments showed superior results in the relative expression of mRNA markers related to kidney function, including Igfbp7, Vcam1, and Timp2. Molecular docking studies demonstrated notable binding affinities and interactions between key kidney markers and selected GA and AT compounds. These findings suggest that GA, particularly in combination with AT, effectively restores kidney function in adenine‐induced CKD, supporting further research to optimize their clinical applications in CKD management.