Wall Permeability Research Articles

Metabolic Profile of Gut Microbiota and Levels of Trefoil Factors in Adults with Different Metabolic Phenotypes of Obesity

Obesity is associated with changes in the gut microbiota, as well as increased permeability of the intestinal wall. In 130 non-obese volunteers, 57 patients with metabolically healthy obesity (MHO), and 76 patients with metabolically unhealthy obesity (MUHO), bacterial DNA was isolated from stool samples, and the 16S rRNA gene was sequenced. The metabolic profile of the microbiota predicted by PICRUSt2 (https://huttenhower.sph.harvard.edu/picrust/) was more altered in patients with MUHO than MHO. Obesity, especially MUHO, was accompanied by an increase in the ability of the gut microbiota to degrade energy substrates, produce energy through oxidative phosphorylation, synthesize water-soluble vitamins (B1, B6, B7), nucleotides, heme, aromatic amino acids, and protective structural components of cells. Such changes may be a consequence of the microbiota adaptation to the MUHO-specific conditions. Thus, a vicious circle is formed, when MUHO promotes the depletion of gut microbiome, and further degeneration of the latter contributes to the pathogenesis of metabolic disorders. The concentration of the trefoil factor family (TFF) in the serum of the participants was also determined. In MHO and MUHO patients, TFF2 and TFF3 levels were increased, but we did not find significant associations of these changes with the metabolic profile of the gut microbiota.

Applications of Metal Nanoparticles in Healthcare and Food Safety

The increased world population has led to a rise in pollution, raising the risk of food contamination and foodborne illness. It is often said that illness enters by the mouth. Food spoilage has always been a great hazard to human health. Therefore, ensuring the safety of food is essential in the pursuit of good health. The advent of nanotechnology has sparked potential in the food industry. Nanotechnology has also shown its ability to reduce cases of foodborne diseases, thereby improving global food security from the root. With the introduction of nanoparticles (NPs), particularly metal NPs like gold and silver, food processing and delivery methods have been further refined. These NPs have demonstrated effective resistance against pathogens. Their antimicrobial abilities play a vital role in nano materials for food packaging. The main mechanism of metal NPs involves their interaction with bacterial cell walls, which enhances cell wall permeability and achieves cell wall damage. At the same time, toxic radicals are released from the NPs and can be dissolved to be absorbed by bacteria. These results in the leakage of cellular contents, inhibiting cell replication, and ultimately, cell death. The application of metal-based NPs significantly contributes to food safety. Therefore, in this work, the applications of various nanomaterials in food safety and healthcare are discussed in detail. This work will contribute to promoting the deep application of nanomaterials in food safety and healthcare.

Synergistic antibacterial activity of baicalin in combination with oxacillin sodium against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) poses a challenge for clinical treatment and combining antibiotics with other agents might be a promising strategy to overcome this challenge. This study explored the synergistic antibacterial activity of baicalin (traditional Chinese medicine extract) and the narrow-spectrum beta-lactam antibiotic oxacillin sodium, both of which are poorly active against MRSA in vitro. The combination of baicalin and oxacillin sodium showed a synergistic effect with a fractional inhibitory concentration index of 0.5. Mechanistically, the supplementation of baicalin increased the permeability of bacterial cell walls and cell membranes, enhancing oxacillin sodium entry and bactericidal action. The combination of baicalin and oxacillin sodium also significantly inhibited MRSA USA300 biofilm formation by further reducing polysaccharide intercellular adhesion production. Therefore, the combination of baicalin and oxacillin sodium offers a new therapeutic option for addressing clinical MRSA resistance. Further studies, including clinical trials, will be required to validate the observed in vitro results.

Comparative growth inhibition of 6PPD and 6PPD-Q on microalgae Selenastrum capricornutum, with insights into 6PPD-induced phototoxicity and oxidative stress

Widespread environmental detection of tire additive N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and its toxic metabolite 6PPD-Q has raised great concerns for their potential impact on aquatic biota. This study investigated the effects of 6PPD and 6PPD-Q on the model green microalgae (Selenastrum capricornutum). Results showed that 6PPD at the concentrations of 1–5 mg·L−1 stimulated S. capricornutum growth, while higher concentrations (10–50 mg·L−1) inhibited growth with an IC50(96 h) of 8.78 mg·L−1. However, at concentrations up to 10 mg·L−1, no toxicity was observed for S. capricornutum exposed to 6PPD-Q. Under the stress of 6PPD, S. capricornutum exhibited increased cellular membrane permeability and cell wall rupture, indicating structural damage to the algae cell. Microalgal oxidative stress was induced through the accumulation of reactive oxygen species (ROS), reaching levels of 1.65–5.29 times higher than the non-exposure cells, which altered enzymatic activities including superoxide dismutase (SOD) and catalase. Exposure to 6PPD at concentrations of 10–50 mg·L−1 resulted in photosynthetic toxicity as evidenced by decreased Chlorophyll a (Chl a) content and adverse effects on chlorophyll fluorescence parameters, such as maximum photochemical quantum yield (Fv/fm), PSII (photosystem II) effective quantum yield [Y(II)], and photosynthetic electron transfer rate (ETR). While the concentrations employed may be higher than those typically found in the environment, this study uncovers a significant finding that 6PPD may demonstrate even greater toxicity to microalgae than its derivative, 6PPD-Q. This underscores the need for further investigation into the ecological risks of 6PPD, particularly in the context of primary producers like microalgae.

Mathematical model of solute transport in channels with variable geometry and permeable walls

This paper investigates solute transport dynamics within a steady, viscous, Newtonian fluid flow through channels of varying geometry (convergent–divergent boundaries) and permeable walls. The significant impact of osmotic pressure on solute concentration is particularly highlighted by modeling osmotic pressure as a cubic function of solute concentration. Approximate solutions to the Navier–Stokes equations and solute transport equations, along with the corresponding boundary conditions, have been derived. The effects of varying geometry and various emerging parameters on hydrostatic and osmotic pressures, solute concentration, and solute clearance are illustrated through graphs. Results indicate a linear decline in hydrostatic pressure and a nonlinear rise in osmotic pressure along the channel length, with divergent channels producing higher solute and wall concentrations than uniform or convergent channels. Increased ultrafiltration and absence of osmotic pressure yield greater wall concentrations. Solute clearance rates increase with the wall slope, transmittance coefficient, permeability, and ultrafiltration parameters, underscoring intricate parameter relationships within filtration. A dataset is used to visually present and analyze the influence of different physiological factors on solute concentration, with graphs corresponding to real physiological conditions. For channels with the uniform width, the findings closely align with previous results, demonstrating its applicability to solute exchange in glomerular capillaries as well as to other blood vessels or capillaries.

Mechanism of Tanyu Tongzhi Formula in treatment of atherosclerosis by maintaining vascular homeostasis based on TGF-β signaling pathway

This study aimed to investigate the potential mechanism and the compatibility significance of Tanyu Tongzhi Formula in treating atherosclerosis(AS) in mice based on the transforming growth factor-β(TGF-β)/Smad2/3 signaling pathway. Eight C57BL/6J mice were as assigned to a normal control group and fed a regular diet, while 35 ApoE~(-/-) mice of the same strain were fed a high-fat diet for 8 weeks to establish an AS model. The model mice were randomly divided into a model group, a Tanyu Tongzhi group(18.2 mg·kg~(-1)), a Huatan(phlegm-resolving) group(10.4 mg·kg~(-1)), and a Quyu(blood stasis-resolving) group(7.8 mg·kg~(-1)), with 8 mice in each group. Except for the normal group, all other groups continued to be fed a high-fat diet for 8 weeks to maintain the AS model, and then the mice were treated by gavage for 8 weeks. Plasma levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), interleukin-1β(IL-1β), and interleukin-18(IL-18) were measured using enzyme-linked immunosorbent assay(ELISA). Hematoxylin and eosin(HE) staining, oil red O staining, and Russell-Movat pentachrome staining were performed to observe the pathological changes in the aortic tissue. The proportions of aortic plaque area, lipid-stained area, collagen fibers, and elastic fibers were calculated. Immunofluorescence was used to detect the protein expression levels of matrix metalloproteinase 2(MMP2) and tissue inhibitor of metalloproteinases 2(TIMP2). Western blot was used to detect the protein expression levels of TGF-β1, TGF-β2, Smad2/3, and Smad7 in aortic tissue. Real-time fluorescence quantitative PCR(RT-qPCR) was used to measure the mRNA expression levels of TGF-β receptor(TGF-βR), TGF-β1, Smad2/3, Smad7, intercellular adhesion molecule-1(ICAM-1), and vascular cell adhesion molecule-1(VCAM-1) in aortic tissue. The results showed that compared with the normal control group, the model group had increased plasma TC and LDL-C, significantly decreased HDL-C, and significantly elevated plasma IL-1β and IL-18 levels. The model group also exhibited an increased proportion of aortic plaque area, lipid-stained area, and collagen fiber area, along with significantly upregulated MMP2 and downregulated TIMP2 expression in the aortic arch. Additionally, the expression levels of TGF-βR, TGF-β1, and p-Smad2/3 proteins and mRNA in the aortic tissue were significantly elevated, while Smad7 expression was decreased. Compared with the model group, the Tanyu Tongzhi group showed significantly reduced plasma TC and LDL-C levels, significantly increased HDL-C levels, and significantly decreased plasma IL-1β and IL-18 levels. The Tanyu Tongzhi group also exhibited a significant reduction in aortic plaque size and severity, a significant downregulation of MMP2 expression in the aortic arch, and significantly decreased ICAM-1 and VCAM-1 mRNA expression levels. Moreover, the Tanyu Tongzhi group demonstrated significantly reduced expression levels of TGF-β1 and p-Smad2/3 proteins and mRNA in the aortic tissue, and an increased expression level of Smad7 protein to varying degrees. Compared with the Tanyu Tongzhi group, the Quyu group had significantly higher LDL-C levels and elevated plasma IL-1β and IL-18 levels. The Huatan group showed upregulated MMP2 expression and downregulated TIMP2 expression in the aortic arch. In conclusion, Tanyu Tongzhi Formula, which is composed based on the pathogenesis of phlegm and blood stasis, maintains vascular homeostasis by primarily regulating lipid metabolism and controlling inflammatory factors through the Huatan group, and maintaining vascular wall permeability, inhibiting plaque development, and stabilizing plaques through the Quyu group. The mechanism of action may involve inhibiting TGF-β1 expression in the aorta, reducing Smad2/3 phosphorylation, and simultaneously increasing Smad7 expression.

Anti-Bacterial and Anti-Biofilm Activities of Essential Oil from Citrus reticulata Blanco cv. Tankan Peel Against Listeria monocytogenes.

In recent years, plant essential oils have been confirmed as natural inhibitors of foodborne pathogens. Citrus reticulata Blanco cv. Tankan peel essential oil (CPEO) showed anti-Listeria monocytogenes (LM) activities, and this study investigated the associated mechanisms by using high-resolution electron microscope, fluorescence spectrometer, flow cytometer, potentiometer, and transcriptome sequencing. The results showed that CPEO restrained LM growth at a minimum inhibitory concentration of 2% (v/v). The anti-LM abilities of CPEO were achieved by disrupting the permeability of the cell wall, damaging the permeability, fluidity, and integrity of the cell membrane, disturbing the membrane hydrophobic core, and destroying the membrane protein conformation. Moreover, CPEO could significantly inhibit the LM aggregation from forming biofilm by reducing the extracellular polymeric substances' (protein, polysaccharide, and eDNA) production and bacterial surface charge numbers. The RNA sequencing data indicated that LM genes involved in cell wall and membrane biosynthesis, DNA replication and repair, quorum sensing and two-component systems were expressed differently after CPEO treatment. These results suggested that CPEO could be used as a novel anti-LM agent and green preservative in the food sector. Further studies are needed to verify the anti-LM activities of CPEO in real food.

THE EFFECT OF THE INFLAMMATORY RESPONSE ON THE DEVELOPMENT OF PREGNANCY COMPLICATED BY PREECLAMPSIA

Preeclampsia remains one of the main causes of obstetric and perinatal complications. The frequency of preeclampsia in the structure of pregnancy complications varies from 6 % to 12 % in healthy pregnant women and from 20 % to 40 % in pregnant women with extragenital pathology. There is growing interest in investigating the exact pathophysiological mechanism of the preeclampsia process as this may identify new potential screening biomarkers. There is evidence that inflammatory mechanisms are a key link between placental ischemia and endothelial dysfunction. It has been hypothesized that impaired regulatory systems are unable to regulate the resolution of inflammatory pathways, contributing to an exaggerated immune response. It is appropriate to call pregnancy a unique immune state that is modulated, but not suppressed. Modulation of the immune system leads to differentiated reactions depending on the stage of pregnancy. Each stage of pregnancy is characterized by a unique inflammatory state. The first and third trimesters are pro-inflammatory, while the second trimester is an anti-inflammatory phase. Proinflammatory mediators, such as IL-6, directly and indirectly through TNF-α, bradykinin, thrombin cause degradation of the endothelial glycocalyx, which leads to an increase in the permeability of the vascular wall with the progression of capillary leakage into the interstitial space. Inflammatory damage to the glycocalyx that occurs during preeclampsia increases intercellular permeability associated with leakage of fluid and albumin into the interstitial space. As a result of damage to the endothelium, there is an increase in the volume of extracellular fluid, which is manifested in women with severe preeclampsia in the form of edema with pathological fluid retention. Further studies are needed to clarify the role of inflammatory mediators in predicting the risk of developing preeclampsia. Further study of the problem will reveal potential targets for treatment, primarily related to inhibition of inflammatory processes and prevention of damage to the endothelial glycocalyx.

GATNM: Graph with Attention Neural Network Model for Mycobacterial Cell Wall Permeability of Drugs and Drug-like Compounds

Mycobacterium tuberculosis cell wall has complexity and unusual organization. These conditions make the nutrients and antibiotics difficult to penetrate this wall which affects the low activity of several antimycobacterial drugs in mycobacteria cells. Based on this information, the cell wall permeability prediction in some compounds becomes important and would help develop novel antitubercular drugs. Recently, there have been many predictions helped by computational technology using the Simplified Molecular Input Line Entry System (SMILES) input drug compounds. In this study, we applied computational technology to predict the permeability of cell walls to some compounds or drugs. We evaluated several common machine learning models for their ability to predict cell wall permeability. However, none of these models achieved satisfactory performance. We investigated a Graph with Attention Neural Network (GATNN) model to address this challenge. In the case of permeability detection, to the best of our knowledge, the GATNN model is considered a new approach to improve the prediction performance of the penetration ability of some compounds to the cell wall of the mycobacterial. Additionally, we optimized the accuracy value to get the best hyperparameter and the best model by Optuna. After getting the optimal model, by using the benchmark dataset, this model has slightly increased the performance over the previous model in accuracy and specificity to 78.9% and 81.5%. As a complementary, we also provided an ensemble model and generated the interpretability of the model. The code and materials of all experiments in this paper can be accessed freely at this link: https://github.com/asw1982/MTbPrediction.

Collagenous enteritis as a rare cause of exudative enteropathy in a child. Case report

Exudative enteropathy (EE) syndrome can be associated with various diseases of the gastrointestinal tract (GIT) and is manifested by edematous syndrome, hypoproteinemia, hypoalbuminemia, lymphocytopenia, hypogammaglobulinemia, and an increase in the level of α-1-antitrypsin in the feces. More than 60 medical conditions are associated with loss of protein through the gastrointestinal tract, including erosive-ulcerative diseases of the gastrointestinal tract, non-erosive lesions of the mucous membrane causing an increase in the permeability of the intestinal wall, as well as disorders with an increase in pressure in the lymphatic system. Correct diagnosis and timely replacement and pathogenetic therapy are essential for the rapid cessation of pathological losses, the recovery of the proteinogram, and the prevention of life-threatening complications. Collagenous enteritis is one of the rare diseases of the small intestine associated with EE syndrome. The article presents a clinical case of a young child with EE and collagenous enteritis. The stages of the diagnostic workup in detecting EE syndrome in the child are discussed, and the pathogenetic factors that determined the development of this disorder are considered.

A review of intracranial aneurysm imaging modalities, from CT to state-of-the-art MR.

Traditional guidance for intracranial aneurysm (IA) management is dichotomized by rupture status. Fundamental to ruptured aneurysm management is the detection and treatment of subarachnoid hemorrhage, along with securing the aneurysm by the safest technique. On the other hand, unruptured aneurysms first require a careful assessment of natural history versus treatment risk, including an imaging assessment of aneurysm size, location, and morphology, along with additional evidence-based risk factors such as smoking, hypertension, and family history. Unfortunately, a large proportion of ruptured aneurysms are in the lower risk size category (<7mm), putting a premium on discovering a more refined non-invasive biomarker to detect and stratify aneurysm instability prior to rupture. In this review of aneurysm work-up, we cover the gamut of established imaging modalities (e.g., CT, CTA, DSA, FLAIR, 3D-TOF-MRA, CE-MRA) as well as more novel MR techniques (MR-VWI, DCE-MRI, CFD). Additionally, we evaluate the current landscape of AI software and their integration into diagnostic and risk stratification pipelines for IAs. These advanced MR techniques, increasingly complemented with AI models, offer a paradigm shift by evaluating factors beyond size and morphology, including vessel wall inflammation, permeability, and hemodynamics. Additionally, we provide our institution's scan parameters for many of these modalities as reference. Ultimately, this review provides an organized, up-to-date summary on the array of available modalities/sequences for IA imaging to help build protocols focused on IA characterization.ABBREVIATIONS: IA = intracranial aneurysm; LP = lumbar puncture; UIA = unruptured intracranial aneurysm; VWI = vessel wall imaging; 3DRA = 3D Rotational Angiography.

Zonulin’s Impact on Intestinal Permeability and the Development of Infant Colic: Mechanisms of Interrelation

Objective. To identify the mechanisms of the relationship between the effect of zonulin protein on the intestinal wall and the occurrence of infantile colic based on the study of scientific sources. Materials and Methods. Scientific articles were searched in PubMed, Scopus, Web of Science, and F1000Research databases. Ninety-six sources published between 1991 and 2023 were selected. Results. The history of the discovery of the zonulin protein is presented, together with a modern view of the structure of the dense intercellular junctions of the intestinal epithelium, and the processes by which the effect of zonulin on altering the permeability of the intestinal barrier is realised are described. The data of several studies in which increased levels of zonulin were found in groups of children with colic and with GI dysfunction are presented. There is a review of works in which the connection of zonulin with extraintestinal pathology - psychiatric disorders, endocrine, autoimmune, cardiopulmonary, allergic, infectious diseases - has been noted. Zonulin is a promising pharmacological target - to date, there is a specific zonulin inhibitor molecule showing efficacy in the treatment of celiac disease and multisystemic inflammatory syndrome in children. Conclusion. The analysis of publications shows the undoubted relevance of the study of zonulin as a factor affecting the permeability of the intestinal wall and a number of other processes. Its role in the formation of intestinal colic requires more detailed study, as discoveries in this area can be actively integrated into clinical practice.

Processing Solid Hydrogels into Hollow Structures by Infrared Laser Light for Highly-Efficient Drug Loading and Controlled Release.

Hollow hydrogels, characterized by their three-dimensional networks akin to biological tissues, are extensively utilized in artificial blood vessels, drug delivery, and nerve conduits due to their superior biocompatibility and fluid-transportation capacity. Nonetheless, the fabrication of hollow hydrogels presents significant challenges, including intricate steps, costly equipment, and structural instability. Consequently, refining the preparation techniques for hollow hydrogels remains paramount to surmounting the limitations of conventional methods. This research introduces an innovative approach that markedly diverges from traditional techniques, offering notable convenience and efficiency in the creation of hollow hydrogel structures. The central novelty of this method lies in employing laser light to induce an in situ photothermal effect, leading to the formation of hollow configurations. This laser-driven transformation of solid hydrogels into hollow structures addresses numerous shortcomings associated with traditional methods. For instance, conventional chemical approaches often necessitate several days to yield hollow hydrogels, and the resultant structures tend to be fragile and susceptible to damage under external pressure. In contrast, the laser-assisted technique facilitates the formation of hollow structures within 240 s, significantly outpacing traditional methods. To achieve controlled drug release, silk fibroin was integrated into the wall of the hollow hydrogels, enabling modulation of wall permeability and directing the drug release process.

Improvement of 9α-hydroxyandrost-4-ene-3,17-dione production in Mycolicibacterium neoaurum by regulation of cell wall formation and transcriptional regulator PadR

The biotransformation of phytosterol into high value steroid intermediates such as 9α-hydroxyandrost-4-ene-3,17-dione (9-OHAD) in Mycolicibacterium is the cornerstone of the steroid pharmaceuticals. However, the limited permeability of the dense mycobacterial cell wall severely hinders the efficient transportation of phytosterol and their bioconversion to 9-OHAD. In this study, we disrupted the genetic pathways involved in trehalose biosynthesis, trehalose recycle and by-product formation, leading to alterations in cell wall formation, cell permeability and 9-OHAD productivity. This manipulation led to an increase of 63.7% in the yield of 9-OHAD, reaching 10.8 g/L at a phytosterol concentration of 20 g/L in shake flask. The enhancement of cell permeability and 9-OHAD production were achieved through the deletion of genes TreS, TreY, OtsA, LpqY, and SugC, as well as the inactivation of regulator PadR. Notably, it was found that the increase in TMM content of cell wall components via TLC analysis directly affected the distribution of 9-OHAD within and outside the cell, ultimately leading to an increase in extracellular production of 9-OHAD from 12% to 32.1%. Therefore, this study provides with an effective strategy for enhancing 9-OHAD production by increasing cell permeability while minimizing by-product 4-AD formation.

Perfusion computer tomography of the kidneys. Research technique. Perfusion indicators in the norm: case-control

INTRODUCTION: Perfusion computed tomography (PCT) is a contrast research technique that allows one to assess blood flow in the cortical and medulla layers of the renal parenchyma at the level of the microcirculatory bed, the influence of additional renal vessels and stenoses of the renal arteries on hemodynamics in the renal parenchyma.OBJECTIVE: To optimize the technique of perfusion computed tomography of the kidneys. Determine the most informative indicators of perfusion in the renal parenchyma in the norm. Assess the relationship between perfusion parameters and the number of renal vessels, the presence of renal artery stenosis.MATERIALS AND METHODS: PCT was performed in 46 patients with no anamnestic and clinical laboratory data on kidney disease who were undergoing examination for other pathological conditions, including 35 patients aged from 20 to 90 years (average age — 63.1 years) without hemodynamically significant stenosis and 11 patients aged from 64 to 94 years (mean age 80.3 years) with renal artery stenosis of 50% or higher. Perfusion indices were calculated using maximum slope and deconvolution algorithms, kinetic curves were plotted on a time-density graph, and color parametric maps.RESULTS: A quantitative assessment of perfusion parameters in the cortical and medulla of the kidneys, a qualitative analysis of the state of its parenchyma on color parametric maps, and the shapes of kinetic curves on the time-density graph were analyzed. Changes in perfusion parameters were established depending on the age, number and condition of the renal vessels.DISCUSSION: In the renal cortical layer, there was a predominance of indicators of blood flow velocity (BF), blood flow volume (BV), the rate of increase in the density of the contrast agent (CM) in the tissue (MSI), capillary wall permeability (PS) and lower values of the average transit time of the contrast agent (MTT) and the time to reach the maximum contrast agent density in the tissue (TTP) in comparison with the medulla. On the color parametric maps BF, BV, MSI, the cortical layer was characterized by intense red coloring, the medulla — yellow-green, on the TTP map green and blue coloring of the layers was determined, respectively. In elderly patients, there was a decrease in BF, BV with a concomitant lengthening of TTP in the cortical layer without changes in coloring on color parametric maps. On the density-time graph, the kinetic curve of the cortical layer was characterized by the appearance of a peak 10 seconds after the onset of the peak value in the abdominal aorta with further continuation of the curve in the form of a plateau; the kinetic curve of the medulla was characterized by a gradual moderate rise in the curve from 15 seconds after the start of scanning without the formation of peaks values.CONCLUSION: PCT is an informative method for quantitative and qualitative assessment of perfusion in the renal parenchyma.

Simulation of plaque formation in a realistic geometry of a human aorta: effects of endothelial layer properties, heart rate, and hypertension.

Nowadays, cardiovascular diseases are the most common cause of death worldwide. Besides, atherosclerosis is a cardiovascular disease that occurs with persistent narrowing of arteries, especially medium and large-sized arteries. Atherosclerosis begins with a local elevation in the permeability of the arterial wall as a result of endothelial inflammation. Subsequently, excess LDL permeates into the arterial wall. Then, through several chemical responses and reactions, foam cells are produced. These foam cells serve as a crucial indicator for assessing the development of atherosclerosis within the arteries. In this study, the effect of endothelial layer modeling, heart rate (HR) and hypertension on the foam cell accumulation is numerically investigated in a patient-specific geometry of the human thoracic aorta. Navier-Stokes, Darcy, and mass transfer equations are used to obtain the velocity and concentration field within the domain. Regarding the dependence of endothelial cell properties on time-averaged wall shear stress, it is observed that foam cells are mainly concentrated in the outer curvature of the aortic arch, downstream of the left subclavian artery. However, considering oscillatory-shear-rate as the determinant of endothelial cell properties leads to the accumulation of foam cells in the inner curvature of the descending aorta. Regarding the HR, with the increase of HR, the volume average concentration of the foam cell decreases. However, there is no substantial difference between the cases of different HRs. Moreover, foam cell concentration significantly increases in the hypertension case. This result implies that a slight increase in the blood pressure may induce irreparable problems in the circulatory system.

Antibacterial activity and mechanism of Stevia extract against antibiotic-resistant Escherichia coli by interfering with the permeability of the cell wall and the membrane.

Natural plant-derived compounds with broad-spectrum antimicrobial activity have become an effective strategy against multidrug-resistant bacteria. The present study was designed to compare the antibacterial activity of six chlorogenic acid (CA) isomers extracted from stevia and investigated the underlying antibacterial mechanisms involved. The results indicated that isochlorogenic acid C (ICAC) exhibited the strongest antibacterial activity against the tested bacteria, especially E. coli, at a 2 mg/mL minimum inhibitory concentration (MIC) and 8 mg/mL minimum bactericidal concentration (MBC). At the MBC, ICAC inhibited 72.66% of the clinical multidrug-resistant strains. Scanning electron microscopy (SEM) revealed that ICAC induced considerable morphological alterations in E. coli ATCC25922 and C4E2. The significant increase in the activity of extracellular alkaline phosphatase (AKP) indicated that ICAC damages the permeability of the bacterial cell wall. Additionally, the intracellular membrane (IM) permeability and the content of lipopolysaccharide (LPS), a main component of the outer membrane (OM), were determined. The significant decrease in LPS content and increased leakage of intracellular proteins and K+ from E. coli indicated that ICAC could induce the exfoliation of OM and disrupt IM permeability, resulting in the loss of barrier function. The uptake of propidium iodide (PI), a compromised cell membrane nucleic acid stain, and confocal laser scanning microscopy (CLSM) further demonstrated that ICAC disrupted IM integrity. Moreover, the bactericidal effect and damage to bacterial microstructural function occurred in a dose-dependent manner. These data demonstrate that ICAC has excellent antibacterial activity and is a promising approach for overcoming the antibiotic resistance of pathogenic bacteria.

Claudin is a promising biomarker of intestinal wall permeability

To date, sufficient information is available on changes in the levels of tight contact proteins (TCPs) in various diseases. Of greatest interest is the study of claudin due to numerous studies confirming the important role of this protein in the development of pathologies. Deafness, behavioural changes, and nerve conduction disorders occur due to insufficient claudin production. Claudin is involved in the maintenance of cell polarity due to its apical location in the cell. When pathological processes occur, claudin may undergo phosphorylation, leading to changes in cell polarity and impaired regulation of APC levels. Irritable bowel syndrome is one of the possible causes of impaired regulation of claudin levels. In this pathology there is adecrease in claudin-1 expression. In addition, claudins play different roles in different tumour tissues, and the same protein may be differentially expressed in different forms of cancer. Claudin-4 expression is upregulated as disease progresses in colorectal cancer (CRC), oesophageal squamous cell carcinoma, and its upregulation is associated with decreased invasiveness and metastatic potential, which is positively correlated with improved prognosis. In contrast, overexpression of CLDN 4 in breast cancer (BC) and pancreatic cancer (PC) is positively correlated with invasion, metastasis, angiogenesis and poor prognosis. Aim: systematisation of available data on the biological role and clinical significance of claudin. Materials: review of Russian and foreign literature from 2013-2023.

Effects of Microbial Proteins on Qingzhuan Tea Sensory Quality during Pile Fermentation.

To determine the effects of microbial proteins on Qingzhuan tea sensory quality during tea pile fermentation, tea leaf metabolomic and microorganism proteomic analyses were performed. In total, 1835 differential metabolites and 443 differentially expressed proteins of the microorganisms were identified. Correlation analysis between metabolomics and proteomics data revealed that the levels of microbial proteins EG II and CBH I cellulase may play important roles in cell wall construction and permeability, which were crucial for the interaction between tea leaves and microorganisms. Microbial proteins heat shock proteins (HSP), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and CuAO related to detoxification and stress responses showed a positive correlation with tea theanine, glutamine, γ-aminobutyric acid, glutamic acid, catechin, (-)-gallocatechin gallate, and (-)-catechin gallate, suggesting their effects on tea characteristic compound accumulation, thus affecting Qingzhuan tea sensory quality.

Free convective heat transfer flow in a glass bead porous medium varying permeability and sinusoidal wall temperature

Free convective heat transfer flow in a glass bead porous medium varying permeability and sinusoidal wall temperature