Amaranth is conventionally consumed as a significant source of nutrients and bioactive compounds and is a potential alternate crop. The present study aimed to validate the folklore and ethnomedicinal claims regarding the utilization of foliar tissues of the pseudocereal Amaranthus hypochondriacus L. for their pharmacological propensities, primarily focusing on bioactive polyphenolic compounds and associated anti-degenerative properties, in view of the scarce evidence available on the same.

Reverse-phase high-performance liquid chromatography coupled with a photodiode array assay of nineteen significant bioactive polyphenolic compounds, along with their in vitro antioxidant-based pharmacological properties (superoxide and hydroxyl radical scavenging properties, metal-chelating and reducing properties, radical scavenging properties, anti-lipid peroxidation and protein coagulation properties, and α-glucosidase and α-amylase inhibitory activities), were assessed and compared for foliar extracts of ten promising experimental accessions of Amaranthus hypochondriacus, grown in two different seasons (summer and winter).

The results exhibited germplasm-specific variations in the pharmacological potential of foliar tissues of the experimental amaranths, which can be substantiated by data showing a close correlation between the abundance of bioactive polyphenolic compounds (naringin, myricetin, naringenin, apigenin, rutin, catechin, quercetin) and in vitro antioxidant (2,2-diphenyl-1-picrylhydrazyl, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assay, hydroxyl radical scavenging, reducing, and metal-chelating) properties, as well as anti-diabetic (inhibition of α-glucosidase and α-amylase activities) and anti-inflammatory (anti-lipid peroxidation) attributes. Accessions IC107144 and IC47434 stood out as the most promising medicinal crops based on overall in vitro anti-degenerative properties and the bioavailability of polyphenolic compounds.

Overall, the results validated the traditional ethnomedicinal claim regarding the utilization of foliar tissues of the underutilized pseudocereal Amaranthus hypochondriacus L., and identified lead germplasms (IC107144 and IC47434) as low-cost natural sources of bioactive compounds, potentially promoting their pharmacological utilization.

Empirical and theoretical studies can be distinguished among the areas of investigation of the renin-angiotensin-aldosterone system (RAAS) and its relationship with the development of cardiovascular diseases. Theoretical work is based mainly on the bioinformatic analysis of key elements of RAAS (genes, proteins, metabolites), on calculations and predictions of protein interactions, and on mechanisms of RAAS gene expression regulation. An associative gene network based on big data analysis allows us to reveal relationships among the proteins, regulatory pathways, and biological processes acting in RAAS, as well as to identify new diagnostic markers, therapeutic targets, putative molecular mechanisms of the development of RAAS-associated diseases, drug interactions, and drug toxicity.

The reconstruction and analysis of associative gene networks were performed using ANDSystem. The regulation of RAAS-associated gene expression was analyzed by transcription factor (TF) binding sites (TFBSs) prediction in the proximal promoters of these genes and by studying interactions between TFs themselves using the Ensembl Biomart web service and AnimalTFDB 4.0. The recognition of potential TFBSs in RAAS gene promoters was performed using MoLoTool.

According to the centrality criteria of the RAAS associative gene network, the following proteins were identified as exerting a significant influence on information interplay between network components: IL6, EDN1, TNFA, MK01, LEP, and JUN. Analysis of the ten identified TFs and their TFBSs among the genes in the RAAS network under study revealed clusters of three to 26 genes regulated by them.

Components with the highest values of centrality and vertex degrees were identified in the reconstructed associative gene network of the RAAS, and ten TFs supposed to regulate 26 RAAS genes were determined.

Microsatellite-stable colorectal cancer, which accounts for roughly 80–85% of cases, remains largely refractory to immune checkpoint inhibitors compared with microsatellite instability-high tumors. This review synthesizes current evidence on tumor-intrinsic and microenvironmental mechanisms underlying immune checkpoint inhibitor resistance in microsatellite-stable colorectal cancer—including low neoantigen burden and impaired antigen presentation, activation of Wnt/β-catenin and MAPK signaling that exclude T cells, an immunosuppressive cellular milieu (regulatory T cells, myeloid-derived suppressor cells, M2-like tumor-associated macrophages, cancer-associated fibroblasts), metabolic reprogramming, and gut microbiome dysbiosis—and evaluates translational strategies aimed at overcoming these barriers. Preclinical and early-phase clinical data indicate that rational, mechanism-guided combinations (vascular normalization, myeloid reprogramming, metabolic inhibitors, antigen-priming approaches, and microbiome modulation) can enhance immune infiltration and produce benefits in biomarker-defined subgroups. Moving the field forward will require biomarker-driven, adaptive clinical trials with embedded translational endpoints to optimize patient selection and manage toxicity.

Traumatic brain injury (TBI)-associated cognitive impairment is highly prevalent, severely impacting patients’ daily life and social functioning, with its mechanisms incompletely understood. Globally, TBI affects over 69 million people annually, and post-TBI cognitive impairment may last for years, or even a lifetime, imposing heavy burdens on patients’ families. The brain-lymphatic axis (glymphatic + peripheral lymphatic systems, especially meningeal vessels) has gained attention: glymphatic dysfunction (dependent on astrocyte endfeet Aquaporin-4 polarization, key for clearing β-amyloid and other wastes) causes metabolic waste accumulation and neuroinflammation, while peripheral lymphatic stasis worsens cognitive decline. This review aims to summarize their roles, dissect mechanisms, and outline therapies. The review found that most current studies explore the glymphatic system and the peripheral lymphatic system in isolation, lacking understanding of their dynamic interplay (e.g., bidirectional inflammatory factor transmission, immune cell migration, synergistic dysfunction); longitudinal studies that track axis changes across TBI stages (acute, subacute, chronic) are scarce; diagnostic tools are insufficient (non-invasive biomarkers lack large-scale clinical validation, and imaging has limited clinical use); and existing therapeutic strategies mostly target single subsystems, with few combined interventions for the whole axis. In conclusion, this review highlights critical gaps in current knowledge and proposes integrated, axis-targeted approaches as a promising direction for future research and therapeutic development.

The association between chronic inflammation and cancer has reshaped our understanding of tumorigenesis and cancer therapy. Inflammatory responses can both promote and suppress cancer, depending on the context and timing. Key molecular players, such as nuclear factor kappa-light-chain-enhancer of activated B cells, interleukin-6, signal transducer and activator of transcription 3, and a variety of immune cell types, including tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, orchestrate an environment conducive to tumor survival, angiogenesis, metastasis, and immune evasion. In recent years, immunotherapy, particularly immune checkpoint inhibitors, has revolutionized cancer treatment. However, its success varies across tumor types and patients, underscoring the need to understand the tumor microenvironment and inflammatory context. This review examines the mechanistic underpinnings of inflammation-driven cancer, discusses translational research efforts targeting inflammatory pathways, and explores clinical applications, including the integration of immunotherapy with anti-inflammatory agents and biomarkers for personalized treatment. Future directions in the field include the application of artificial intelligence, microbiome research, single-cell technologies, and gene editing tools to further tailor therapies and overcome resistance mechanisms.

Chaperone-like proteins are involved in the pathogenesis of coronavirus infection through regulation of the viral life cycle, immune response, and antigen presentation. A recently discovered class of chaperones, called heat-resistant obscure proteins (Hero proteins), performs functions similar to other molecular chaperones. This study aimed to investigate the association between the gene encoding the Hero protein SERF2 (Hero7) and the risk of severe COVID-19.

This case-control study was conducted according to the STROBE protocol. A total of 1,373 unrelated Russians (178 patients with severe COVID-19 and 1,195 controls) were recruited. Genotyping of rs4644832 in the SERF2 gene was performed using a probe-based polymerase chain reaction approach. The effects of the single nucleotide polymorphisms (SNPs) were analyzed using bioinformatics tools, including GTExPortal, eQTLGen, HaploReg, atSNP, Gene Ontology, Lung Disease and Common Metabolic Diseases Knowledge Portals, and the STRING database.

SNP rs4644832 in the SERF2 gene (effect allele G) was associated with a decreased risk of severe COVID-19 in the total sample (odds ratio (OR) = 0.56, 95% confidence interval (CI) 0.39–0.81, P = 0.001), females (OR = 0.51, 95% CI 0.31–0.87, P = 0.006), non-smokers (OR = 0.46, 95% CI 0.29–0.74, P = 0.0004), individuals with body mass index ≥ 25 (OR = 0.42, 95% CI 0.25–0.7, P = 0.0004), individuals with low fruit and vegetable intake (OR = 0.38, 95% CI 0.22–0.67, P = 0.0004), and individuals with low physical activity (OR = 0.41, 95% CI 0.23–0.75, P = 0.002).

The G allele of rs4644832 in the SERF2 gene appears to have a protective effect against severe COVID-19. Functional annotation of rs4644832 suggests that it may influence COVID-19 pathogenesis through regulation of proteostasis, ubiquitination, inflammation-induced protein aggregation, the viral life cycle, and cytoskeletal functions.

For individuals with decompensated advanced chronic liver disease (dACLD), the onset of refractory ascites (RA) represents a dramatic event. In this setting, a relevant proportion of RA patients develop kidney dysfunction, as well as hepatorenal syndrome-acute kidney injury, with limited therapeutic and survival chances. An 81-year-old woman with dACLD-RA was admitted with severe ascites and stage IV chronic kidney dysfunction. On the second day, hepatorenal syndrome-acute kidney injury occurred, requiring standard medical therapy. Intravenous human albumin (HA) and terlipressin administration were compromised by poor venous access and severe respiratory dysfunction. After excluding transjugular intrahepatic portosystemic shunt and transplantation due to age and comorbidities, peritoneal dialysis (PD) was initiated, leading to renal recovery and ascites resolution. Two weeks later, she was readmitted due to the unfeasibility of accessing peripheral veins for the intravenous administration of HA, which was essential to support circulatory function, preserve oncotic balance, and properly manage both RA and chronic kidney dysfunction. A novel PD+HA protocol was therefore started, with intraperitoneal infusion of HA-enriched dialysate to allow a positive albumin gradient from dialysate to blood. Over 12 months, serum albumin levels increased, and clinical stability and improved nutritional status were observed, with no additional hospitalizations or complications. This is the first case describing the application of HA-enriched PD in managing a dACLD patient with RA and kidney dysfunction. HA-enriched PD may represent a promising strategy in complex dACLD care by guaranteeing frequent and small-volume paracentesis and preservation of oncotic pressure without dialytic albumin loss.

Hepatic iron deposition (HID) in the reticuloendothelial system (RES) is associated with histological severity in metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to assess the interaction between the transferrin (TF)-rs1049296 C>T variant and HID patterns on the risk of significant liver fibrosis in MASLD.

We analyzed 406 adults with liver biopsy-confirmed MASLD. HID was categorized as hepatocellular, RES, or mixed, based on Perl's iron staining. The association between iron-related genetic variants and significant liver fibrosis (fibrosis stage ≥ F2) was analyzed, focusing on the interactions between single-nucleotide polymorphism genotypes and iron deposition patterns. Multivariable logistic regression analysis was used to adjust for potential confounders.

HID was detected in 271 (66.7%) patients, with hepatocellular, RES, and mixed patterns accounting for 11.1%, 18.0%, and 37.7%, respectively. A significant interaction was observed between HID and the TF-rs1049296 genotype (Pinteraction = 0.035). In multivariable analysis, male sex, hypertension, severe lobular inflammation, and mixed hepatocellular/RES iron deposition were independent predictors of significant liver fibrosis. RES deposition markedly increased the risk of significant liver fibrosis (adjusted odds ratio: 6.65; 95% confidence interval: 1.84–23.97, p < 0.05), particularly in men with isolated RES iron deposition (adjusted odds ratio: 5.26; 95% confidence interval: 1.21–22.81, p < 0.05).

The TF-rs1049296 T allele interacts with RES iron deposition to identify a MASLD subpopulation at elevated risk of progressive liver disease, providing opportunities for refined risk stratification and personalized management.

PVT is a harmful event in cirrhosis, and the prevention and treatment of PVT are important in the management of cirrhosis and portal hypertension. The study aimed to observe the efficacy of Danggui Buxue Decoction (DBD) on portal vein thrombosis (PVT) in cirrhosis and to elucidate the related mechanism using a modified animal model.

A model of PVT in cirrhosis was established by partial portal vein ligation and intraperitoneal injection of CCl4 in rats, which showed obvious PVT with intra- and extravenous thrombosis as well as liver cirrhosis. Rats were randomly assigned into four groups and received intragastric administration of DBD (12 g/kg/day) or rivaroxaban (20 mg/kg/day) for 6 weeks.

DBD attenuated collagen deposition and reduced thrombus formation in model livers, increased portal vein blood flow, expanded the portal vein diameter, and reduced prothrombin time and international normalized ratio in the model rats. In addition, DBD reduced hepatic von Willebrand factor and plasminogen activator inhibitor-1 expression and increased hepatic fibrin degradation product content in the liver tissues of model rats.

We modified a model of cirrhotic PVT in rats and found that DBD had a good effect on PVT and liver fibrosis, with the mechanisms related to the enhancement of portal vein blood flow and the protection against endothelial cell injury.

The prognostic nutritional index (PNI), calculated from serum albumin and lymphocyte count, reflects a patient’s immune-nutritional status and has been proposed as a prognostic marker in hepatocellular carcinoma (HCC). However, its role in advanced HCC patients treated with atezolizumab plus bevacizumab (Ate/Bev) remains unclear. In this study, we aimed to evaluate the prognostic value of PNI in patients receiving first-line Ate/Bev therapy.

We retrospectively analyzed 362 patients with unresectable HCC who received Ate/Bev between November 2020 and June 2023 across two centers. Based on prior literature, a cutoff of 45 was used to classify patients into low-PNI (<45) and high-PNI (≥45) groups. Propensity score matching was performed to balance baseline characteristics.

After propensity score matching, 130 patients (65 per group) were included in the analysis. The high-PNI group showed a significantly lower incidence of grade ≥ 3 treatment-related adverse events (10.8% vs. 24.6%, p = 0.039), a higher objective response rate (38.4% vs. 20.0%, p = 0.037), and significantly longer overall survival (16.7 vs. 7.9 months, p = 0.009). Although progression-free survival was longer in the high-PNI group (4.8 vs. 3.0 months), the difference was not statistically significant (p = 0.597). Multivariate analysis confirmed that PNI was an independent predictor of overall survival (hazard ratio: 0.574, 95% confidence interval: 0.353–0.933, p = 0.025), after adjusting for vascular invasion, alpha-fetoprotein levels, concurrent therapy, and post-treatment interventions.

PNI is an independent prognostic factor for overall survival in advanced HCC patients treated with Ate/Bev in real-world clinical practice. Incorporating PNI into routine assessments may enhance risk stratification and guide therapeutic decision-making.