Alpinia calcarata (A. calcarata) Roscoe (Family: Zingiberaceae) is a rhizomatous perennial herb used in traditional medicine to treat inflammatory conditions. This study aimed to develop a topical emulgel dosage form by incorporating the essential oil of A. calcarata rhizome and to investigate it’s in vitro anti-inflammatory activity. A thin-layer chromatographic fingerprint of the essential oil of A. calcarata rhizome was developed. Then, an emulsion base containing plant oil was formulated and incorporated within a Carbopol gel base. The physical characteristics of this formulation were evaluated subsequently. The anti-inflammatory mechanism of the emulgel was determined by in vitro blood cell membrane stabilization assay and thrombolytic activity assay. The results were statistically analyzed by one-way analysis of variance. The thin-layer chromatographic fingerprint of the test oil demonstrated several bands with unique retention factor values. The formulated herbal emulgel was white, viscous, and homogeneous in appearance. The spreadability was 118 g·cm/M, and the pH of the emulgel was 6.30 at 25°C. The A. calcarata emulgel significantly (p < 0.05) inhibited heat-induced in vitro hemolysis, with the highest activity at a 50 µg/mL dose (87.68 ± 0.35%) compared to the placebo. Furthermore, this activity was found to be dependent on the essential oil concentration (r2 = 0.99) of the emulgel. Therefore, it was concluded that the essential oil of A. calcarata rhizome is an effective active ingredient to be used in a topical emulgel formulation, whereas the diverse phytochemicals present in the essential oil would be the underlying source of its anti-inflammatory activity.

Guaiac fecal occult blood test (gFOBT) is often used to evaluate evidence of food protein-induced allergic proctocolitis (FPIAP) in children in primary care and gastroenterology settings; however, it has not been validated for this diagnosis, and little is known about the positivity rates in early infancy. In this study, we used samples from healthy asymptomatic infants aged two weeks to two months to evaluate the gFOBT positivity rate compared to those diagnosed with FPIAP.

This was a nested case-control study. Frozen stool samples from infants aged two days to five months enrolled in the Gastrointestinal Microbiome and Allergic Proctocolitis study were evaluated using gFOBT (n = 123). The results were interpreted by three blinded staff members, including a trained clinical research coordinator, a pediatric gastroenterologist, and an experienced medical assistant. Additionally, the samples were analyzed using a quantitative fecal immunochemical test (FIT) for hemoglobin to compare with gFOBT results.

Eight percent of samples from the 100 healthy asymptomatic infants were gFOBT positive (11% when including positive and equivocal results). Seventy-four percent of samples from infants diagnosed with FPIAP were gFOBT positive. The interrater reliability of gFOBT interpretation was 81%. Of the healthy samples that yielded a positive gFOBT result, 50% also yielded a positive FIT result. Of the 23 FPIAP samples that yielded a positive gFOBT result, 29% yielded a positive FIT result.

Healthy asymptomatic infants in early infancy were gFOBT positive up to 11% of the time. Caution should be used when interpreting gFOBT results in young infants in a diagnostic setting.

Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome characterized by systemic inflammation and immune dysregulation, in which macrophages play a key role in organ injury. This study aimed to investigate the role and mechanism of pyruvate dehydrogenase kinase 4 (PDK4) in ACLF to identify therapeutic targets that modulate macrophage function and mitigate ACLF progression.

Single-cell RNA sequencing data from healthy and ACLF liver tissues were analyzed from the Sequence Read Archive database. Transcriptomic data of peripheral blood mononuclear cells from ACLF patients (GSE168048) were also examined. In vitro experiments assessed PDK4 expression and macrophage polarization, and conditioned-medium studies evaluated effects on LO2 hepatocytes. In vivo validation was performed in ACLF mouse models treated with a PDK4 inhibitor.

Single-cell analysis revealed a predominance of M1-polarized hepatic macrophages in ACLF with marked upregulation of PDK4. Peripheral blood mononuclear cell transcriptomics showed that higher PDK4 expression correlated with 28-day mortality. In vitro, PDK4 expression increased in M1 macrophages; PDK4 inhibition attenuated M1 polarization and reduced cytotoxic effects on LO2 cells. In vivo, pharmacologic inhibition of PDK4 suppressed M1 polarization in macrophages, alleviated liver inflammation, and reduced tissue injury. Mechanistically, PDK4 promoted M1 polarization via activation of signal transducer and activator of transcription 1 signaling.

PDK4 is a key pro-inflammatory regulator in ACLF by promoting M1 macrophage polarization. Targeting PDK4 may be a promising strategy to attenuate inflammation and improve clinical outcomes in ACLF.

Harlequin ichthyosis, one of the rarest and most severe skin disorders, is mainly characterized by extreme hyperkeratosis, severely impairing the natural barrier function of the skin. This congenital disease results from a mutation in the ABCA12 gene responsible for lipid transport, whereby healthy skin development is assured. Harlequin ichthyosis is an autosomal recessive condition that requires parents to carry a defective gene copy for the disorder to manifest in their offspring. Babies born with Harlequin ichthyosis have thick skin plates that crack and flake off; they easily become dehydrated, infected, and may suffer from respiratory complications. With new improvements in neonatal care and systemic therapy, notably retinoid therapy, infants’ survival rates have improved. This review provides an inclusive overview of the pathophysiology, clinical features, diagnostic methods, management, and potential future therapies for Harlequin ichthyosis. In addition, a discussion on genetic counseling and its importance in managing family risk factors is also included, as well as a look into cutting-edge research focused on gene therapy and potential curative treatments.

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.

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.

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.

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.