Biology and Life Sciences

Abstract: Endophytic fungi are microorganisms that reside asymptomatically within healthy plant tissues and establish complex symbiotic relationships with their host plants. In recent years, these microorganisms have gained increasing attention due to their remarkable ability to produce diverse secondary metabolites with significant biological and pharmacological activities. Numerous studies have demonstrated that endophytic fungi isolated from medicinal plants can synthesize bioactive compounds exhibiting antioxidant, antimicrobial, antiviral, anti-inflammatory, antidiabetic, and anticancer properties. Interestingly, some endophytes are capable of producing metabolites structurally similar or identical to those found in their host plants, including taxol, camptothecin, and various phenolic compounds. Compared with conventional plant extraction, endophytic fungi offer several advantages such as rapid growth, sustainable production, reduced environmental impact, and the potential for large-scale fermentation. These characteristics make endophytes promising alternative sources of natural products for pharmaceutical, cosmetic, agricultural, and industrial applications. This review summarizes the biological characteristics of endophytic fungi, methods for isolation and identification, and the major classes of bioactive compounds derived from fungal endophytes, with emphasis on their pharmacological significance and future biotechnological potential.

Abstract: Climate change is placing global agriculture under growing pressure, as plants must withstand extreme environmental conditions such as drought and high salinity, both inducing osmotic and oxidative stress. As part of their survival strategies, plants accumulate protective molecules (osmolytes), including the amino acid proline. For decades, plant biology has largely assumed that high proline accumulation under stress signals strong stress tolerance. However, this review challenges that “proline-centric” perspective. Analyses across a wide range of plant species reveal a more complex picture. Stress-induced proline accumulation is not universal: in some species, proline levels remain relatively unchanged, with other metabolites acting as functional osmolytes, or increase only in response to artificially applied severe stress conditions. Even when proline increases, its absolute concentrations may be too low to contribute significantly to osmotic adjustment. Nevertheless, proline may still be involved in stress tolerance mechanisms through its additional roles, detoxifying reactive oxygen species (ROS), directly stabilising proteins or acting as a stress signalling molecule. Comparative analyses of genetically related taxa with varying degrees of stress tolerance sometimes show negative correlations between proline accumulation and tolerance, with higher proline concentrations measured in the most sensitive genotypes. Overall, the evidence indicates that proline’s role in plant survival is highly context-dependent and strongly influenced by genetic background and must therefore be evaluated on a case-by-case basis. Distinguishing whether proline acts as an adaptive defence or merely as a biochemical marker of physiological strain is essential for accurately assessing plant stress tolerance.

Abstract: Neuroinflammation, driven by microglial activation and oxidative stress, is a key pathological feature of various neurodegenerative diseases. Dendropanax morbifera Léveille (DM) is a medicinal plant known for its diverse pharmacological activities; how-ever, the influence of leaf developmental stage on its neuroprotective potential remains poorly understood. In this study, we compared the phytochemical profiles of young DM (YDM) and mature DM leaves and evaluated their effects on neuronal metabolism and microglia-mediated neuroinflammation. HPLC analysis revealed that YDM contained approximately 2.4-fold higher levels of chlorogenic acid than DM, while DM exhibited higher quercetin content. In differentiated N2A neuronal cells, YDM treatment significantly upregulated the expression of key metabolic and mitochondrial regulators, including PGC-1α, PPARγ, and CPT2, suggesting an enhanced capacity for mitochondrial biogenesis and fatty acid β-oxidation. Under inflammatory conditions, YDM more potently suppressed the secretion of pro-inflammatory cytokines (IL-6 and TNF-α) in LPS-stimulated BV2 microglia compared to DM. Further-more, in N2A cells treated with a BV2–conditioned medium, both extracts effectively mitigated reactive oxygen species production and restored brain-derived neurotrophic factor expression. These findings demonstrate that leaf age is a critical determinant of the phytochemical composition and biological activity of DM. Our results suggest that chlorogenic acid-rich YDM preparations may offer superior therapeutic advantages in targeting neuroinflammatory and metabolic dysregulation in the central nervous system.

Abstract: Coastal lagoons are key wintering habitats for waders, yet long-term changes in their community structure remain poorly understood in Mediterranean systems. We analysed a 30-year dataset (1993–2022, excluding 2021) of wintering waders in the Venice Lagoon to assess trends in abundance, community structure, thermal composition and spatial patterns. Total abundance increased significantly (+3.5% yr⁻¹), while species richness ranged between 12–21 species per winter. Community structure changed markedly, with increasing dominance of a few species, particularly Dunlin, leading to reduced evenness. Species-level analyses showed a prevalence of increasing trends: nine of the 19 species analysed increased significantly, one declined, one was stable and eight showed uncer-tain trends. The Community Temperature Index (CTI) increased significantly (p = 0.001), suggesting a shift towards species with higher thermal affinities, but this pattern was not robust to the exclusion of Dunlin C. alpina, indicating dominance-driven dynamics. Spatial analyses revealed a strong increase in the open lagoon (p < 0.001) and a decline in fish farms (p = 0.008), indicating a shift towards natural tidal habitats. Overall, the assemblage is increasing but structurally simplified, highlighting the need to integrate species- and community-level approaches when interpreting ecological indicators.

Abstract: Old murine bone marrow-derived monocytes and macrophages (BMMs) display enhanced CD38 protein, a nicotinamide adenine dinucleotide (NAD⁺) glycohydrolase, and reduced NAD⁺ level after infection with oral pathogens compared with young controls. We aimed to determine whether treatment with a CD38-specific inhibitor (78c) in mice with experimental periodontitis could alleviate alveolar bone loss and enhance NAD⁺ levels in tissues compared with vehicle treatment. Twenty young (2-month-old) and twenty old (18-month-old) C57BL/6J mice with experimental periodontitis were treated with either vehicle or 78c twice daily via intraperitoneal injection for 4 weeks. The liver, spleen, and right maxillary tissues were harvested to analyze NAD⁺ levels. The left maxillary tissues were scanned by micro-CT, processed for tissue sectioning, and stained with hematoxylin and eosin (H&E) and tartrate-resistant acid phosphatase (TRAP). Treatment with 78c significantly enhanced NAD⁺ levels in the liver and spleen of both young and old mice, and significantly increased NAD⁺ in the right maxilla of old mice compared with vehicle treatment. Additionally, treatment with 78c alleviated alveolar bone loss in both young and old mice. Our results support the notion that 78c is a promising therapeutic strategy for treating periodontal disease associated with aging.

Abstract: The sterility of injection pharmaceutical preparation is the most crucial requirement to achieve, as it is injected directly to human body, either intravenously, intramuscularly, or other injection routes and once drug is injected, it moves to other parts of the body through blood flow follows the rules of drug distribution and will have direct contact to all tissues and organ [1]. Theoretically, in order to prevent contamination of microbial by inhibiting the proliferation process, especially in multiple dose of injection drugs, in the final formulation of the drug may need special addition of suitable preservative agent in the preparation [2]. The first step to perform this experimental study was by preparing the sterile pharmaceutical preparation, Diphenhydramine Hydrochloride injection at Sterile Pharmaceutical Preparation Laboratory, of Universitas Muhammadiyah Malang, Indonesia. Once the injection drug was ready, the second step conducted sterility test. The most common method used for sterility test in injection drugs is named direct inoculation. It was conducted by preparing sample from diluted solution of the injection drug, and the concentration was divided into five groups of sample 1:1, 1:2, 1:3, 1:4, 1:5, and undiluted sample (with three times replications) has determined certain level of inactivation of benzyl alcohol as its preservative agent, that was undiluted sample in Thioglycolate medium and 1:1 in Casamino medium. The indicator of bacterial growth in the study was Bacillus subtilis for Thioglycolate medium on range of temperature 30°-35 °C, and Candida albicans as an indicator of fungal growth in Casamino medium on range of temperature 20°-25 °C, both of Thioglycolate and Casamino medium were observed for 14 days. Inactivation of preservative agent and sterility test were performed under LAFC condition and it required some controls of LAFC environment to ensure that experiment was conducted under optimum condition and to avoid false positive result. According to those results of our study, the sterility test has indicated that our Diphenhydramine Hydrochloride injection was sterile after over a period of 14 days of observation.

Abstract: Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide and remains therapeutically challenging owing to its marked inter- and intratumoral heterogeneity, diverse etiologies, and high rates of drug resistance. This review aims to summarize the current knowledge on the complexity of HCC and to evaluate emerging therapeutic strategies, with a particular focus on targeting the RNA-binding protein HuR as a novel approach to overcome treatment limitations. Methods: A narrative review was conducted of peer-reviewed publications focusing on HCC pathogenesis, tumor heterogeneity, resistance mechanisms, and therapeutic developments. Emphasis was placed on studies investigating the molecular drivers of HCC, tumor microenvironment interactions, and novel treatment strategies. Results: HCC progression is driven by complex interactions between genetic, epigenetic, and environmental factors, resulting in significant variability in treatment response. Tumor heterogeneity, cancer stem cell populations, and an immunosuppressive tumor microenvironment contribute to resistance to conventional therapies, including multikinase inhibitors and immune checkpoint inhibitors. Emerging strategies targeting these mechanisms, such as combination immunotherapies, metabolic targeting, and epigenetic modulation, show promise, but remain limited by incomplete efficacy. HuR is a central post-transcriptional regulator that stabilizes mRNAs encoding oncogenic and pro-survival factors. Preclinical studies have demonstrated that the pharmacological inhibition of HuR disrupts tumor-promoting pathways and enhances therapeutic sensitivity. Conclusions: The complexity of HCC necessitates multifaceted precision-based therapeutic approaches. Targeting HuR is a promising strategy for addressing tumor heterogeneity and drug resistance. Continued integration of molecular profiling, advanced technologies, and rational combination therapies is critical for translating these advances into improved clinical outcomes.

Abstract: Enzyme replacement therapy (ERT) for central nervous system symptoms and newborn screening (NBS) are available in Japan for patients with mucopolysaccharidosis type II (MPS II). The participants were individuals referred to our facility through NBS who were suspected of having neuronopathic MPS II. We reviewed the clinical course of patients who received intracerebroventricular (ICV)-ERT, idursulfase beta (Hunterase®), followed by hematopoietic stem cell transplantation (HSCT) using umbilical cord blood. Longitudinal measurements of heparan sulfate (HS) in the cerebrospinal fluid (CSF) were performed as a therapeutic biomarker, and developmental age was evaluated. Three patients diagnosed and treated with ICV-ERT received cord blood transplantation (CBT). All patients achieved successful engraftment with no severe complications except for one patient with sinusoidal obstruction syndrome. The HS in the CSF showed a temporary increase during the ERT discontinuation period owing to CBT and a subsequent reduction after the resumption of ICV-ERT. The patients exhibited age-appropriate development. The pattern of change in HS suggests the importance of continuing ICV-ERT even after HSCT. The combination of ICV-ERT and CBT may yield promising outcomes in patients with neuronopathic MPS II and underscores the importance of early intervention through NBS.

Abstract: Production of a biodegradable, environmentally friendly polymer film material, composed of potato starch (PS), xanthan gum (XG), and plasticizers: glycerin, sorbitol, and citric acid, was carried out. The effect of these components on the structural and biopolymer composite mechanical properties, including elasticity and tensile strength, was investigated. The addition of XG significantly reduces the hardness for the film forming materials, thereby lowering the difficulty of gelatinization. It was demonstrated that increasing the plasticizers mass during composite blend preparation improved elasticity but reduced the mechanical strength of the films. It is assumed that these additives in the biopolymer disrupted hydrogen bonds and other intermolecular contacts between starch and gum macro chains. Glycerol influences the elasticity of the bioplastic, while sorbitol influences its strength. Taking various factors into account, the optimal combined concentration of glycerol, sorbitol and citric acid was determined in composite during film preparation. Based on the results of the new polymeric films’ flexibility study, it was concluded that they could be used as a replacement for traditional, non-biodegradable polymeric materials. At the optimal concentration of components, the strength of polymer films is 1.6 MPa, and the relative elongation is 45%.

Abstract: Anaerobic bacteria are the dominant group in the animal intestinal microbiota, and most strains cannot grow or proliferate normally upon exposure to air. Blautia sp. AUH-JLD56 (KF374935) is a strictly anaerobic strain previously isolated by our research group from human feces. Under anaerobic conditions, this strain converts arctigenin to 3′-demethylarctigenin (3′-DMAG), reaching a maximum conversion concentration of 3.6 mM. To improve the oxygen tolerance of this wild-type strain, we performed long-term oxygen tolerance domestication and successfully obtained an oxygen-tolerant mutant. Phenotypic analysis showed that the growth of the oxygen-tolerant mutant under aerobic conditions (OD_{600 nm} = 2.37) was slightly lower than that of the wild-type under strictly anaerobic conditions (OD_{600 nm} = 2.82). Compared with the wild-type, the mutant exhibited an accelerated aerobic growth rate and enabled stable conversion of arctigenin. Notably, under aerobic conditions, the mutant achieved a maximum conversion concentration of 8.2 mM, which is significantly higher than the 3.6 mM obtained with the wild-type under anaerobic conditions. This study realizes, for the first time, efficient aerobic bioconversion of arctigenin to 3′-DMAG using an oxygen-tolerant derivative of a strict anaerobe, thereby overcoming the oxygen-dependent limitation of such strains. Our approach provides a new strategy and technical reference for the oxygen tolerance domestication and industrial application of other intestinal strict anaerobes with specific enzymatic functions.

Abstract:

Disordered eating in young adults is shaped by sociocultural pressures and may be modulated by genetic variation. We examined sex differences in eating-pathology, psychosocial correlates, at two candidate loci Hypocretin and Neuropeptide S (HCRTR1 rs10914456; NPSR1 rs324981). A total of 550 individuals visiting various nutrition clinics were initially approached for participation in the study. Of these, 460 consented to take part ,after exclusions, 360 completed SCOFF; 200 scoring >2 proceeded to EAT-26 and comprised the analytic sample (100 males, 100 females). Psychosocial factors (media influence, academic pressure, peer pressure, isolation/loneliness, and K-pop self-comparison) were assessed by a structured questionnaire. EAT-26 total and subscales were compared by sex (t-tests). Genotypes were contrasted by sex using χ² tests; allele frequencies were derived from genotype counts and ORs with CI were computed. Females showed higher EAT-26 total scores than males (29.7±1.9 vs 23.2±1.3; t(198)=2.82, p<0.005); 68% of females and 76% of males scored ≥20. Anorexia subscale scores were greater in females (t(198)=3.713, p<0.0003), as well as binge-eating scores (t(198)=1.722, p<0.05); bulimia indices did not differ by sex (p>0.05). Body dissatisfaction was common (87%) without sex difference (p>0.05).Significant sex associations were observed for media influence (χ²=67.94, p<0.05), academic pressure (χ²=45.6, p<0.0001), K-pop self-comparison (χ²=112.12, p<0.0001), peer pressure (χ²=46.37, p<0.05),and isolation/loneliness (χ²=28.72, p<0.0001).Genotyping data revealed marked sex-dependent associations at both loci. For HCRTR1 rs10914456, female cases showed a significantly higher frequency of the risk (TT) genotype, conferring 4.86-fold greater odds of carrying T-allele relative to males (OR = 4.86, 95% CI: 1.46–16.17, p = 0.001). In contrast, for NPSR1 rs324981, males exhibited a pronounced T-allele–driven risk pattern, being T-carriers (AT+TT) relative to females (OR = 4.11, 95% CI 1.23–13.68, p = 0.022).Within females specifically, the AA genotype was significantly overrepresented compared with T-carrying genotypes (AA vs AT+TT: OR = 3.25, 95% CI: 1.59–6.66, p = 0.0013).Collectively, these results highlight a female-specific recessive risk pattern at HCRTR1 and a male-specific dominant T-allele effect at NPSR1, underscoring robust sex-differentiated genetic susceptibility to disordered eating. Overall females exhibited severe eating-pathology and heightened psychosocial sensitivity than males, while genetic risk showed locus-specific sex patterns. Integrating psychosocial screening with genetic profiling may lead to early intervention.

Abstract: Microbiology laboratories generate extensive experimental outputs that are often in-sufficiently translated into applied innovation and technology development. This study presents a Routine-to-Research-to-Innovation (R2R) framework integrating routine labor-atory workflows with bioactivity validation, formulation development, and intellectual property (IP) mapping. Lactic acid bacteria isolated from Thai fermented foods demon-strated strong bacteriocin activity and storage stability, while secondary metabolites de-rived from Streptomyces and Brevibacillus exhibited antibacterial, antioxidant, and an-ti-inflammatory activities with prototype formulation potential. Red palm oil-based sys-tems enriched with microbial bioactives also showed favorable physicochemical stability under accelerated conditions. Patent landscape analysis (Thailand, 2020–2025) demon-strated translational alignment between laboratory outputs and existing innovation do-mains, supporting the potential application of the R2R framework in translational micro-biology, technology transfer, and early-stage innovation development.

Abstract: The embryological basis for the lamination of the retroperitoneal fascia has long remained an anatomical paradox. Classical peritoneal fusion theories cannot account for either the highly organized multilaminar architecture of the mature fascia or the striking temporal lag between early visceral fixation (gestational weeks 9–18) and the abrupt, synchronized emergence of definitive fascial laminae around week 20. Integrating recent advances in fetal biomechanics, we propose that this developmental lag reflects a system-level mechanical transition driven by the geometric constraints of scaling and the evolutionary demands of obligate bipedalism.

Abstract: Abiotic stresses, including drought, salinity, alkalinity, temperature extremes, flooding, heavy metals, and emerging pollutants, challenge plant growth and productivity by disturbing water relations, ion balance, redox homeostasis, membrane stability, energy metabolism, and developmental progression. Although substantial progress has been made in identifying stress-responsive hormones, second messengers, kinases, transcription factors, transporters, and metabolic regulators, plant stress adaptation cannot be fully explained by linear signaling cascades or single tolerance genes. A major unresolved question is how early molecular events are reorganized into coordinated physiological and developmental outputs that support survival, recovery, and productivity. In this review, we propose an intermolecular interaction–driven adaptive remodeling framework for plant abiotic stress responses. This framework emphasizes that stress tolerance emerges from dynamic changes in receptor–ligand recognition, protein–protein interactions, calcium decoding, redox-sensitive modification, phosphorylation networks, transcriptional regulation, chromatin-associated control, and metabolite-mediated feedback. We discuss how these interaction networks converge on core signaling hubs, including abscisic acid, reactive oxygen species, Ca²⁺, and kinase/phosphatase systems, and how they remodel stomatal behavior, root architecture, ion and pH homeostasis, redox buffering, metabolism, development, and reproductive resilience. We further highlight how natural variation, multi-omics, genome editing, high-throughput phenotyping, and field validation can translate interaction-centered stress biology into crop resilience. This perspective provides a conceptual bridge between molecular stress perception, network behavior, physiological adaptation, and climate-resilient agriculture.

Abstract: Since its emergence in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected a wide range of animal species, including wildlife. Although SARS-CoV-2 infection has been widely reported in wildlife, particularly in white-tailed deer (WTD; Odocoileus virginianus) across the United States, data on viral circulation in New England wildlife remain limited. Here, we evaluated SARS-CoV-2 infection and serological evidence of previous exposure in free-ranging wildlife from the northeastern United States. We examined samples from 1,646 animals representing 28 wildlife species, collected through wildlife rehabilitation centers, clinics, and hunter harvests in New England and Virginia between 2022 and 2025. SARS-CoV-2 RNA was detected in three WTD from Massachusetts and Vermont. Phylogeographic analysis of Vermont WTD sequences indicated a human SARS-CoV-2 lineage as the most likely source, consistent with a single human-to-deer spillover event followed by subsequent circulation within deer. Serological screening using ELISA detected SARS-CoV-2 antibodies in 12 individ-uals from three species, including Eastern cottontail (Sylvilagus floridanus), Eastern coyote (Canis latrans), and raccoon (Procyon lotor), although neutralizing antibodies were found in only one Eastern cottontail. Overall, these findings reveal ongoing but limited SARS-CoV-2 circulation in northeastern wildlife and highlight the importance of continued surveillance to detect spillover events, monitor viral evolution, and evaluate potential risks posed by wildlife.

Abstract: Fibroblast growth factor (FGF) signaling plays a pivotal role in the development, maintenance, and regeneration of musculoskeletal tissues. While its transcriptional regulation has been extensively characterized, accumulating evidence indicates that FGF activity is also modulated by a diverse array of post-transcriptional mechanisms. In this review, microRNAs, long non-coding RNAs, alternative splicing, and RNA modifications are examined as key regulators of FGF ligands and receptors across bone, cartilage, muscle, and tooth. Enhancer RNAs and RNA-binding proteins are also discussed as potential modulators of FGF transcript stability and translation. By integrating both established and emerging layers of RNA-level regulation, this review outlines a complex, tissue-specific architecture that fine-tunes FGF signaling in development and repair. To highlight this layered regulatory dimension, the concept of a pathway-specific RNA regulome is introduced, referring to the network of RNA-based mechanisms that modulate signaling cascades, such as FGF, across distinct biological processes. The therapeutic implications of targeting post-transcriptional nodes, particularly through non-coding RNAs and epitranscriptomic marks, are highlighted as promising avenues for future musculoskeletal interventions.

Abstract: DNA/cell mass homeostasis is a pervasive feature of living organisms. As the cell grows in response to nutrient availability, it must duplicate each chromosome once and only once each division cycle. Across the eukaryote Tree of Life, cells differ in their sizes in a manner that depends directly on the amount of DNA they harbor, what has been termed the “nucleotypic effect”: cell size expands or contracts as DNA content increases or decreases. In eukaryotes, any deviation from DNA/mass homeostasis results in the deregulation of the developmental program and the initiation of carcinogenesis and other genetic pathologies. In bacteria, deviation from, or perturbation of, DNA/mass homeostasis alters important physiological features such as the cell cycle timing of DNA replication initiation and the co-ordination of initiation with replication termination and cell division. In prokaryotes, the timing of initiation occurs at a relatively constant and growth rate invariant mass, termed the initiation mass (Mi), and depends strictly on DNA replication fork rates and membrane biogenesis. Complex “machines”, frequently referred to as hyperstructures or factories, mediate the phase transitions that define the different periods of the bacterial cell cycle. The following will examine how the cell size and DNA/mass homeostasis maintains a balance between replication initiation and elongation, that gate the phase transitions that organize the cell cycle in time and space.

Abstract: The establishment of a reference population for genomic selection in Korean beef cattle is an ongoing process. There is a high likelihood of sex-specific differences in the composition of the reference and test populations. This study evaluates the accuracy of Genomic Estimated Breeding Values (GEBVs) for carcass traits in Hanwoo cattle, specifically investigating the efficacy of cow-based reference populations. The effectiveness of genomic selection (GS) is heavily dependent on the composition and size of the reference population. Utilizing genotype data from a Hanwoo 50k SNP chip and phenotypic data from 19,168 steers and 6,233 cows, the study estimated GEBV accuracies for carcass weight (CWT), eye muscle area (EMA), backfat thickness (BF), and marbling score (MS) using the GBLUP method. Results demonstrate that steer-based reference populations achieved the highest accuracy (0.64–0.88), averaging 0.78, likely due to standardized management and higher trait heritability (0.39–0.51) compared to cows. In contrast, cow-based reference populations exhibited prediction accuracies (0.55–0.75) in four traits using adjusted residual phenotype, averaging 0.64, but remained highly practical alternatives. While growth traits (CWT and EMA) showed significant bias in cross-sex predictions, fat deposition traits (BF and MS) remained stable across sexes. The study concludes that although steer-based populations provide optimal accuracy, incorporating cows into the reference population is strategically vital in Hanwoo.

Abstract: This study aimed to characterize metabolomic changes in the eye lens of senescence-accelerated OXYS rats in comparison with control Wistar rats, and to identify biochemical shifts associated with genotype, age, and cataract progression. Cataract severity was clinically graded. Rats' lenses were analyzed using quantitative ¹H NMR spectroscopy at 3.6 and approximately 4.5 months of age. A total of 43 metabolites were quantified. We found that at 3.6 months of age, OXYS lenses exhibited a significant accumulation of 17 metabolites, primarily amino acids, compared to Wistar rats, suggesting an imbalance between amino acid uptake and crystallin biosynthesis. However, by 4.5 months, OXYS lenses exhibited rapid metabolic changes characterized by significant decreases in amino acid, glucose, and key energy/antioxidant markers, including NAD, adenylate energy charge, and hypotaurine. Clinical cataract grade (Grade 2 vs. 3) had a negligible impact on the overall metabolomic profile. Our results indicate that profound metabolic reorganization, including an initial amino acid excess followed by energy and antioxidant depletion, precedes the morphological manifestation of cataracts in OXYS rats. We suggest that a biochemical "point of no return" occurs early in cataractogenesis, while subsequent increase in lens opacification is a secondary consequence of preexisting metabolic disturbances.

Abstract:

Leukocyte recruitment from blood into tissues involves sequential adhesive steps, including rolling and integrin-dependent arrest. The integrin VLA-4 is known to mediate firm adhesion, but can also support rolling. CD44–hyaluronan interactions have also been implicated in leukocyte rolling. Here, we used parallel-plate flow chamber assays to compare the contributions of CD44 and VLA-4 to monocyte rolling on different cellular monolayers. Monocytoid WEHI 78/24 cells rolled and adhered through CD44 on hyaluronan-presenting ECV304 monolayers, whereas VLA-4 dominated adhesion on endothelial monolayers expressing functional VCAM-1. Primary human monocytes showed similar CD44-dependent rolling on ECV304 monolayers. Blocking CD44, adding soluble hyaluronan, or removing surface hyaluronan with hyaluronidase reduced rolling and adhesion. These results show that CD44 can support monocyte rolling when VLA-4/VCAM-1 adhesion is not the dominant interaction. This cell-based flow model distinguishes CD44/hyaluronan-mediated rolling from VLA-4/VCAM-1-rolling and may help analyze monocyte rolling on hyaluronan, including tumor-derived monolayers.