Search Results (116)

Background and Objectives: Infection, trauma, skin cancer, foreign substance injections and lymphedema are among the most frequent causes of penile skin defects. Scrotal flaps are a promising reconstructive option for penile resurfacing, offering improved functional and aesthetic outcomes; however, there is no clear consensus on their superiority. Materials and Methods: A review of the literature was performed in PubMed Central and Scopus, and multiple keywords were employed. The initial search retrieved 9181 articles; 32 articles were finally selected, of which 13 were case reports and 19 were case series. Results: A total of 368 patients were included, the majority (71%) consulting for sclerosing lipogranuloma. Seven types of scrotal flaps were used: unilateral scrotal flap (n = 1), bilateral anterior scrotal flaps (n = 149), two-stage scrotal flap (n = 57), bipedicled bilateral anterior scrotal flaps (n = 140), apron-style scrotal flap (n = 1), scrotal pull-up (n = 13), and island dartos musculocutaneous flap (n = 7). Patient satisfaction was high in all studies. Outcome evaluation was typically conducted using subjective questionnaires with 2 or 5 items or visual analog scales. Few studies employed validated sexual function questionnaires, as the IIEF-5 or the EHS. Conclusions: Scrotal flaps provide good quality tissue for penile resurfacing, having the closest resemblance to normal penis skin. For a better understanding of the outcomes of different scrotal flaps, a thorough evaluation of postoperative complications should be made. The LOS and revision surgery rates may serve as surrogates for the financial burden of the procedure. Erectile function should be thoroughly evaluated with a 10-item Likert scale, IIEF-5, EHS, and POSAS. Full article

The metabolism of drugs and foreign substances in humans typically involves multiple enzymatic steps, particularly in phase-1 biotransformation in the liver, where various cytochrome P450 monooxygenases (CYPs) play crucial roles. This complexity can lead to a wide range of metabolites. Understanding the contributions of individual CYPs and their interactions within these intricate enzyme cascades can be challenging. We recently developed an in vitro biotransformation platform employing various Chinese Hamster Ovarian (CHO) cell clones. These clones express human cytochrome P450 oxidoreductase (CPR), and each is defined by a specific human CYP enzyme expression, thus exhibiting no detectable endogenous CYP enzyme activity (mono-CYP CHO platform). In this study, we investigated whether the mono-CYP CHO platform is a suitable tool for modeling complex drug metabolization reactions in vitro. Tamoxifen (TAM) was selected as a model substance due to its role as a prodrug widely used in breast cancer therapy, where its main active metabolite, endoxifen, arises from a two-step metabolism primarily involving the CYP system. Specifically, the combined activity of CYP3A4 and CYP2D6 is believed to be essential for efficient endoxifen production. However, the physiological metabolization pathway of TAM is more complex and interconnected, and the reasons for TAM’s therapeutic success and variability among patients are not yet fully understood. Analogous to our recently introduced mono-CYP3A4 CHO cells, we generated a CHO cell line expressing human CPR and CYP2D6, including analysis of CYP2D6 expression and specific activity. Comparative studies on the metabolization of TAM were performed with both mono-CYP CHO models individually and in co-culture with intact cells as well as with isolated microsomes. Supernatants were analyzed by HPLC to calculate individual CYP activity for each metabolite. All the picked mono-CYP2D6 clones expressed similar CYP2D6 protein amounts but showed different enzyme activities. Mono-CYP2D6 clone 18 was selected as the most suitable for TAM metabolization based on microsomal activity assays. TAM conversion with mono-CYP2D6 and -3A4 clones, as well as the combination of both, resulted in the formation of the expected main metabolites. Mono-CYP2D6 cells and microsomes produced the highest detected amounts of 4-hydroxytamoxifen and endoxifen, along with N-desmethyltamoxifen and small amounts of N,N-didesmethyltamoxifen. N-desmethyltamoxifen was the only TAM metabolite detected in notable quantities in mono-CYP3A4, while 4-hydroxytamoxifen and endoxifen were present only in trace amounts. In CYP2D6/3A4 co-culture and equal mixtures of both CYP microsomes, all metabolites were detected at concentrations around 50% of those in individual clones, indicating no significant synergistic effects. In conclusion, our mono-CYP CHO model confirmed the essential role of CYP2D6 in synthesizing the active TAM metabolite endoxifen and indicated that CYP2D6 is also involved in producing the by-metabolite N,N-didesmethyltamoxifen. The differences in metabolite spectra between the two mono-CYP models highlight the CYP specificity and sensitivity of our in vitro system. Full article

It is now known that diet or food is one of the environmental factors that can induce or contribute to autoimmunity. In a healthy person with a normal functioning immune system, food substances encounter no resistance and are allowed passage through the immune barriers without triggering immune reactivity. However, clinicians are becoming increasingly aware that modern food-processing methods can increase or decrease the immune reactivity of foods, including allergic reactions. Immune reactions to undigested food antigens could result in the production of IgE antibodies, which are involved in immediate immune reactivity, and in IgG and IgA antibodies, which are involved in delayed immune reactivity. Currently, measurements of these antibodies are generally only performed against antigens derived from raw foods. However, testing for food reactivity based only on raw food consumption is inaccurate because people eat both raw and cooked foods. Even home-cooked foods undergo different kinds of preparation or processing. Food processing can change the structure of raw food materials into secondary, tertiary, and quaternary structures that can have different reactive properties. This can affect the body’s normal oral tolerance of food, causing the immune system to mistakenly identify food as a harmful foreign substance and react to it immunologically, leading to food immune reactivity. This abnormal reaction to food molecules can lead to the production of antibodies against not just target food antigens but also the body’s own tissues, which can have significant implications in autoimmunity induction due to cross-reactivity and the other mechanisms discussed here. We hope that this present review will stimulate further research on the role of modified food antigens in the induction of autoimmunity based on some or all of the key points discussed in this review. Full article

Purpose: Pharmaceutical parenteral drug products (PDPs) and orally inhaled nasal drug products (OINDPs) are critical medications for patient care, for which the route of administration is intravenous or oral/nasal inhalation, and the drug products directly infuse into the bloodstream or lungs, but they are categorized as high-risk for leachables. Method: These external foreign chemical substances (leachables) may adversely affect and alter patient safety. Results: These primary container closure systems and manufacturing process equipment mainly comprise rubber elastomers, polypropylene, resin, ink, adhesives, glass, or plastic material. To establish the ID of detected compounds and their quantity in the finished parenteral drug formulation and then to assess the formulation for toxicological safety, broad-scope non-specific analytical screening methods are required that are capable of screening out and quantifying the predicted/unpredicted leachable compounds at the levels that pose anticipated toxicological concerns for human patients. Before the selection of the final primary packaging system for the parenteral drug product, their extractable screening profile/knowledge is required to minimize leachable compounds in the finished drug product formulation and to develop and manufacture a safe product for human patients. The adverse effect or toxicity of leachables proportionally increases with an increase in the dose of the drug product or the duration of therapy because the volume of the drug product administered to a patient in a larger quantity is directly proportional to the concentration of the detected leachable. Conclusion: This document outlines the detailed process/scientific approach for conducting an organic leachable screening profile for parenteral drug products with respect to the chemical nature of leachables, i.e., polarity, propensity, volatility, and techniques. Full article

Background/Objectives: The skin is an important barrier that protects against invasion by foreign substances and retains water in the body. Several skin diseases involve dry skin due to a disrupted skin barrier, and most skin diseases that appear on dry skin are accompanied by itch. Dry skin-induced itch and mechanical alloknesis reduce quality of life. Sulfated hemicellulose (i.e., pentosan polysulfate sodium), similar to heparin, is a compound belonging to the sulfated polysaccharide family; however, in contrast to heparin, it is derived from plant materials. We herein investigate the effects of the topical application of OJI-204, a sulfated hemicellulose made by purifying and chemically synthesizing hemicellulose, on dry skin in a mouse model. Methods: The mouse model of dry skin was generated using a mixture of acetone and ether with water. Either OJI-204 (3% or 10%) or 0.3% heparinoid, PBS (control), was applied twice a day to the acetone and diethyl ether/water (AEW)-treated area. The degree of skin dryness was evaluated by measuring transepidermal water loss and stratum corneum hydration. Scratching behavior was recorded the day before AEW treatment and the day after the final day, and an alloknesis assay was performed on the day after the final day. Results: We found that 3% or 10% OJI-204 attenuated dry skin conditions (erythema/hemorrhage, scarring/dryness, edema, and excoriation/erosion) and itchiness more effectively than 0.3% heparinoid. Furthermore, the degree of dryness improved to the same degree as that with heparinoid. OJI-204 also significantly reduced dry skin-induced spontaneous itch and mechanical alloknesis. Conclusions: These results suggest the potential of OJI-204 as a therapeutic or preventive agent for dry skin. Full article

Many polyunsaturated fatty acids within cells exhibit diverse physiological functions. Particularly, arachidonic acid is the precursor of highly bioactive prostaglandins and leukotrienes, which are pro-inflammatory mediators. However, polyunsaturated fatty acids, such as arachidonic, docosahexaenoic, and eicosapentaenoic acids, can be metabolized into specialized proresolving mediators (SPMs), which have anti-inflammatory properties. Given that pro-inflammatory mediators and SPMs are produced via similar enzymatic pathways, SPMs can play a crucial role in mitigating excessive tissue damage induced by inflammation. Mast cells are immune cells that are widely distributed and strategically positioned at interfaces with the external environment, such as the skin and mucosa. As immune system sentinels, they respond to harmful pathogens and foreign substances. Upon activation, mast cells release various pro-inflammatory mediators, initiating an inflammatory response. Furthermore, these cells secrete factors that promote tissue repair and inhibit inflammation. This dual function positions mast cells as central regulators, balancing between the body’s defense mechanisms and the need to minimize tissue injury. This review investigates the production of SPMs by mast cells and their subsequent effects on these cells. By elucidating the intricate relationship between mast cells and SPMs, this review aims to provide a comprehensive understanding of the mechanism by which these cells regulate the delicate balance between tissue damage and repair at inflammatory sites, ultimately contributing to the resolution of inflammatory responses. Full article

Non-clinical enterococci are relatively poorly studied by means of acquired antibiotic resistance to tetracycline and by the distribution, functionality and role of their CRISPR systems. Background: In our study, 72 enterococcal strains, isolated from various non-clinical origins, were investigated for their phenotypic and genotypic (tet(M), tet(O), tet(S), tet(L), tet(K), tet(T) and tet(W)) tetracycline resistance. Methods: The genetic determinants for HGT (MGEs (Int-Tn and prgW), inducible pheromones (cpd, cop and cff), aggregation substances (agg, asa1, prgB and asa373) and CRISPR–Cas systems were characterized by PCR and whole-genome sequencing. Results: Four tet genes (tetM, tetO, tetS and tetT) were detected in 39% (n = 28) of our enterococcal population, with tetM (31%) being dominant. The gene location was linked to the Tn6009 transposon. All strains that contained tet genes also had genes for HGT. No tet genes were found in E. casseliflavus and E. gilvus. In our study, 79% of all tet-positive strains correlated with non-functional CRISPR systems. The strain E. faecalis BM15 was the only one containing a combination of a functional CRISPR system (cas1, cas2, csn2 and csn1/cas9) and tet genes. The CRISPR subtype repeats II-A, III-B, IV-A2 and VI-B1 were identified among E. faecalis strains (CM4-II-A, III-B and VI-B1; BM5-IV-A2, II-A and III-B; BM12 and BM15-II-A). The subtype II-A was the most present. These repeats enclosed a great number of spacers (1–10 spacers) with lengths of 31 to 36 bp. One CRISPR locus was identified in plasmid (p.Firmicutes1 in strain E. faecalis BM5). We described the presence of CRISPR loci in the species E. pseudoavium, E. pallens and E. devriesei and their lack in E. gilvus, E. malodoratus and E. mundtii. Conclusions: Our findings generally describe the acquisition of foreign DNA as a consequence of CRISPR inactivation, and self-targeting spacers as the main cause. Full article

Background: Hydrogen gas (H₂) has been shown to be effective in the treatment of various clinical conditions, from acute illnesses to chronic illnesses. However, its clinical indications and the corresponding appropriate hydrogen delivery methods have yet to be determined. This is due to the fact that the pharmacokinetics and pharmacodynamics of hydrogen in each delivery method have not been experimentally proven. Here, we verified the pharmacokinetics of hydrogen after the infusion of hydrogen-saturated saline. Methods: Hydrogen-saturated saline was prepared and checked for sterility and component specifications. Hydrogen-saturated saline was administered intravenously (125 mL/h) through the left internal jugular vein of pigs, and the blood hydrogen concentration was measured over time. Results: It was confirmed that hydrogen can be safely mixed under pressure into intravenous solutions (pharmaceutical products) without the contamination of foreign substances by using a needle-less vial access cannula. No change in the PH or composition of the solution was observed due to hydrogen filling. The hydrogen concentrations of blood samples collected from the left internal jugular vein 3 cm to the heart from the tip of the infusion line were 6.4 (30 min), 4.7 (60 min), 4.9 (90 min), and 5.3 (120 min) ppb w/w, respectively. The hydrogen concentrations of blood samples collected from the right atrium were 0.7 (30 min), 0.5 (60 min), 0.7 (90 min), and 0.7 (120 min) ppb, respectively. The hydrogen concentration of blood samples collected from the right internal carotid artery were 0.1 (pre), 0.2 (30 min), 0.3 (60 min), 0.0 (90 min), and 0.0 (120 min) ppb w/w, respectively. Conclusions: We confirmed that hydrogen could be safely pressurized and filled into intravenous (pharmaceutical) solution without contamination by foreign objects using a needle-free vial access cannula. When saturated hydrogen saline was dripped intravenously, almost all of the hydrogen was expelled during its passage through the lungs and could not be supplied to the arterial side. Full article

Hemolymph enables communication between organs in insects and ensures necessary coordination and homeostasis. Its composition can provide important information about the physiological state of an insect and can have diagnostic significance, which might be particularly important in the case of harmful insects subjected to biological control. Galleria mellonella Linnaeus 1758 (Lepidoptera: Pyralidae) is a global pest to honey bee colonies. The hemolymph of its larvae was examined after infection with the soil fungus Conidiobolus coronatus (Constantin) Batko 1964 (Entomophthorales). It was found that after one hour of contact with the fungus, the volume of the hemolymph increased while its total protein content decreased. In larvae with a high pathogen load, just before death, hemolymph volume decreased to nearly initial levels, while total protein content and synthesis (incorporation of ³⁵S-labeled methionine) increased. The hemolymph polypeptide profile (SDS-PAGE followed by autoradiography) of infected insects was significantly different from that of healthy larvae. Hemocytes of infected larvae did not surround the fungal hyphae, although they encapsulated small foreign bodies (phase contrast microscopy). Infection had a negative effect on hemocytes, causing oenocyte and spherulocyte deformation, granulocyte degranulation, plasmatocyte vacuolization, and hemocyte disintegration. GC-MS analysis revealed the presence of 21 compounds in the hemolymph of control insects. C. coronatus infection caused the appearance of 5 fatty acids absent in healthy larvae (heptanoic, decanoic, adipic, suberic, tridecanoic), the disappearance of 4 compounds (monopalmitoylglycerol, monooleoylglycerol, monostearin, and cholesterol), and changes in the concentrations of 8 compounds. It remains an open question whether substances appearing in the hemolymph of infected insects are a product of the fungus or if they are released from the insect tissues damaged by the growing hyphae. Full article

Active infrared thermography (IRT) in non-destructive testing is an attractive technique used to detect wide areas in real-time on site. Most of the objects inspected on site generally have rough surfaces and foreign substances, which significantly affects their detectability. To solve this problem, in this study, line scanning (LS)-based induction thermography was used to acquire thermal image data of a specimen containing foreign substances. The heat distribution caused by foreign substances was removed using the Gaussian filtering-based Fast Fourier Transform (FFT) algorithm. After that, the data augmentation was performed by analyzing the correlation, and crack detection for the images was performed using you only look once (YOLO) deep learning. This study presents a method for removing non-uniform heat sources using the FFT algorithm, securing virtual data augmentation, and a detection mechanism for moving inspection objects using AI deep learning. Full article

The blood–brain barrier (BBB) serves as a highly selective barrier between the blood and the central nervous system (CNS), and its main function is to protect the brain from foreign substances. This physiological property plays a crucial role in maintaining CNS homeostasis, but at the same time greatly limits the delivery of drug molecules to the CNS, thus posing a major challenge for the treatment of neurological diseases. Given that the high incidence and low cure rate of neurological diseases have become a global public health problem, the development of effective BBB penetration technologies is important for enhancing the efficiency of CNS drug delivery, reducing systemic toxicity, and improving the therapeutic outcomes of neurological diseases. This review describes the physiological and pathological properties of the BBB, as well as the current challenges of trans-BBB drug delivery, detailing the structural basis of the BBB and its role in CNS protection. Secondly, this paper reviews the drug delivery strategies for the BBB in recent years, including physical, biological and chemical approaches, as well as nanoparticle-based delivery technologies, and provides a comprehensive assessment of the effectiveness, advantages and limitations of these delivery strategies. It is hoped that the review in this paper will provide valuable references and inspiration for future researchers in therapeutic studies of neurological diseases. Full article

In recent years, there has been a growing recognition of microplastics (MPs) as significant emerging pollutants. Soil contamination by MPs, comprising plastic particles smaller than 5 mm, originates from diverse sources. The introduction of foreign substances such as MPs can instantly modify the physical properties of soil or influence soil processes, depending upon the characteristics of the plastic. The limited available studies provide evidence that insufficient attention is being paid to the impact of plastic input on soil evaporation processes. The objective of this study was to assess the impact of contamination of three types of soil (Chernozem, Umbrisol, and Luvisol) with different MPs (high-density polyethylene, polyvinyl chloride, and polystyrene) at a concentration of 5% (w/w) on the evaporative mass loss. The presence of polyvinyl chloride (PVC), high-density polyethylene (HDPE), and polystyrene (PS) significantly altered evaporative soil loss, dry bulk density, and saturated water content in different soil types. Evaporative mass loss significantly increased in Luvisol and Umbrisol soils contaminated with HDPE and in Umbrisol contaminated with PVC. In Chernozem, contamination with all examined MPs significantly reduced dry bulk density. A similar decrease in dry bulk density was observed in Luvisol and Umbrisol with PVC and HDPE. Significant reductions in saturated water content were recorded in Chernozem contaminated with HDPE, Luvisol with PS, and Umbrisol with both HDPE and PS. Full article

Drug delivery, tissue engineering, and cell promotion in biomedical fields heavily rely on the use of nanomaterials (NMs). When they penetrate cells, NPs undergo degradation and initiate the generation of reactive oxygen species (ROS) by causing changes in the structures of organelles linked to mitochondria. Inside the cell, the excess production of ROS can initiate a chain reaction, along with the autophagy process that helps maintain ROS balance by discarding unnecessary materials. At present, there is no effective treatment for Alzheimer’s disease (AD), a progressive neurodegenerative disease. The use of NMs for siRNA delivery could become a promising treatment for AD and other CNS disorders. Recent research demonstrates that the use of combined NPs can induce autophagy in cells. This article emphasizes the importance of the shape of siRNA-encapsulated NMs in determining their efficiency in delivering and suppressing gene activity in the central nervous system. Because of its strict selectivity against foreign substances, the blood–brain barrier (BBB) significantly hinders the delivery of therapeutic agents to the brain. Conventional chemotherapeutic drugs are significantly less effective against brain cancers due to this limitation. As a result, NMs have become a promising approach for targeted drug delivery, as they can be modified to carry specific ligands that direct them to their intended targets. This review thoroughly examines the latest breakthroughs in using NMs to deliver bioactive compounds across the BBB, focusing on their use in cancer treatments. The review starts by examining the structure and functions of the BBB and BBTB, and then emphasizes the benefits that NMs offer. Full article

ATP-binding cassette transporter subfamily G member 2 (ABCG2) is responsible for the excretion of foreign substances, such as uric acid (UA) and indoxyl sulfate (IS), from the body. Given the importance of increased ABCG2 expression in UA excretion, we investigated the enhancement of intestinal ABCG2 expression using Lactiplantibacillus plantarum 06CC2 (LP06CC2). Mice were reared on a potassium oxonate-induced high-purine model at doses of 0.02% or 0.1% LP06CC2 for three weeks. Results showed that LP06CC2 feeding resulted in increased ABCG2 expression in the small intestine. The expression level of large intestinal ABCG2 also showed a tendency to increase, suggesting upregulation of the intestinal excretion transporter ABCG2 by LP06CC2. Overall, LP06CC2 treatment increased fecal UA excretion and showed a trend towards increased fecal excretion of IS, suggesting that LP06CC2 treatment enhanced the expression of intestinal ABCG2, thereby promoting the excretion of UA and other substances from the intestinal tract. Full article

Many therapies require the transport of therapeutic compounds or substances encapsulated in carriers that reduce or, if possible, eliminate their direct contact with healthy tissue and components of the immune system, which may react to them as something foreign and dangerous to the patient’s body. To date, inorganic nanoparticles, solid lipids, micelles and micellar aggregates, liposomes, polymeric micelles, and other polymer assemblies were tested as drug carriers. Specifically, using polymers creates a variety of options to prepare nanocarriers tailored to the chosen needs. Among polymers, aliphatic polyesters are a particularly important group. The review discusses controlled synthesis of poly(β-butyrolactone)s, polylactides, polyglycolide, poly(ε-caprolactone), and copolymers containing polymacrolactone units with double bonds suitable for preparation of functionalized nanoparticles. Discussed are syntheses of aliphatic polymers with controlled molar masses ranging from a few thousand to 10⁶ and, in the case of polyesters with chiral centers in the chains, with controlled microstructure. The review presents also a collection of methods useful for the preparation of the drug-loaded nanocarriers: classical, developed and mastered more recently (e.g., nanoprecipitation), and forgotten but still with great potential (by the direct synthesis of the drug-loaded nanoparticles in the process comprising monomer and drug). The article describes also in-vitro and model in-vivo studies for the brain-targeted drugs based on polyester-containing nanocarriers and presents a brief update on the clinical studies and the polyester nanocarrier formulation approved for application in the clinics in South Korea for the treatment of breast, lung, and ovarian cancers. Full article