Adhesion Formation Research Articles

Dialysis treatment, in vitro, and anticoagulation activity of polysulfone-polyacrylamide based-blend membranes: an experimental study.

The majority of treatments are performed with polysulfone (PSf) membranes. The main issue of the PSf membrane is its lack of endothelial function, leading to various processes like platelet adhesion, protein adsorption, and thrombus formation when comes in contact with blood. The crucial aspect in the development of hemodialysis (HD) membrane materials is a biocompatibility factor. This study aims to improve the performance and biocompatibility of PSf membranes by utilizing polyethylene glycol (PEG) as a pore-forming agent and polyacrylamide (PAA) as a multifunctional modifying additive owing to its non-toxic, and biocompatible nature. The formulated HD membranes were characterized using Fourier Transform Infrared (FTIR) spectroscopy, Scanning Electron Microscopy (SEM), and Water Contact Angle (WCA) measurements. The biocompatibility results showed that PSf-PAA membranes reduced the adsorption of bovine serum albumin (BSA) protein, hemolysis process, thrombus formation, and platelets adhesion with improved in vitro cytotoxicity results as well as anticoagulation performance. The protein separation results showed that PSf-PAA membranes were able to reject 90.1% and 92.8% of BSA protein. The membranes also showed better uremic waste clearance for urea (76.56% and 78.24%) and creatinine (73.71% and 79.13%) solutes, respectively. It is conceivable that these modern-age membranes may surpass conventional HD membranes regarding both efficiency and effectiveness.

The role of endospore appendages in spore-spore interactions in the pathogenic Bacillus cereus group.

Species within the Bacillus cereus sensu lato group, known for their spore-forming ability, are recognized for their significant role in food spoilage and food poisoning. The spores of B. cereus are adorned with numerous pilus-like appendages, referred to as S-ENAs and L-ENAs. These appendages are thought to play vital roles in self-aggregation, adhesion, and biofilm formation. Our study investigates the role of S-ENAs and L-ENAs, as well as the impact of various environmental factors on spore-to-spore contacts and the interaction between spores and vegetative cells, using both bulk and single-cell approaches. Our findings indicate that ENAs, especially their tip fibrillae, play a crucial role in spore self-aggregation, but not in the adhesion of spores to vegetative cells. The absence of L-BclA, which forms the L-ENA tip fibrillum, reduced spore aggregation mediated by both S-ENAs and L-ENAs, highlighting the interconnected roles of S-ENAs and L-ENAs. We also found that increased salt concentrations in the liquid environment significantly reduced spore aggregation, suggesting a charge dependency of spore-spore interactions. By shedding light on these complex interactions, our study offers valuable insights into spore dynamics. This knowledge can inform future studies on spore behaviour in environmental settings and assist in developing strategies to manage bacterial aggregation for beneficial purposes, such as controlling biofilms in food production equipment.

Laparoscopic salpingostomy for two types of hydrosalpinx: a step-by-step video tutorial

This study aims to illustrate our laparoscopic salpingostomy approach for two types of hydrosalpinx, emphasizing various reproductive surgical techniques. A step-by-step demonstration of the technique is provided alongside narrated video footage. University hospital. Infertile patients with hydrosalpinx seeking natural conception. Laparoscopic salpingostomy for clubbed hydrosalpinx is demonstrated with video and includes the following steps: 1) creating an opening into the tube at the terminal end for hydrosalpingeal fluid drainage; 2) dissecting and removing peritubal and periovarian adhesions; 3) excising redundant fimbrial tissues to restore fimbrial mobility; 4) evert the mucosa using an intussusception method until endothelial folds are visible; 5) confirming tubal patency with a dye test; 6) heating the serosal surface of the tube to evert the edges; 7) suturing the edges using 6-0 vicryl to the proximal serosa of the tube circumferentially with an inverting suture technique; 8) thoroughly irrigating with Ringer's solution to remove blood clots and debris; and 9) applying auto-crosslinked hyaluronan gel to the exposed raw surface. Salpingostomy for the cystic type differs, notably in carefully shaving the adhesive tubal end from the ovary until the tubo-ovarian ligament is completely exposed. The primary aim of salpingostomy is to reduce the likelihood of distal tube re-obstruction. If hydrosalpinx recurs after salpingostomy, there remains a possibility of requiring additional surgery, such as salpingectomy, prior to IVF. (s): Extensive adhesions were meticulously dissected and removed from the peritoneal cavity. Fimbrial mobility was restored to establish a patent fallopian tube capable of ovum pickup. Electrocoagulation and suturing techniques were employed to evert the tube edges, effectively reducing the risk of re-obstruction. The utilization of an inverting suture technique aided in inwardly turning the cut edges, minimizing the risk of adhesion formation. Laparoscopic salpingostomy, when performed by surgeons proficient in reproductive surgical techniques, provides a significant option for patients with hydrosalpinx seeking natural conception. The decision to preform salpingostomy or salpingectomy is usually made intraoperatively on the basis of the severity of tubal disease. Clinical history is also an important factor in decision to perform salpingostomy.

Establishment of a postoperative bowel adhesion model in Rats

Postoperative adhesive bowel obstruction is a frequent cause of hospital admission in a surgical department. Emergency surgery is needed in a majority of patients with bowel ischemia or peritonitis; most adhesive bowel obstruction can be managed non-operatively. Many studies have investigated benefits of using oral water-soluble contrast to manage adhesive bowel obstruction. Treatment recommendations are still controversial. Intestinal adhesions commonly occur in patients after abdominal surgery, often between intestines, between intestines and the abdominal wall, or within the peritoneum. Adhesions can lead to symptoms such as abdominal pain, constipation, and bloating, and may result in serious complications such as intestinal obstruction, bowel necrosis, acute peritonitis, and sepsis, which can be life-threatening. Therefore, reducing the occurrence of intestinal adhesions is crucial for abdominal surgery. To minimize adhesions, endoscopic techniques can be employed to reduce the abdominal opening area and thus decrease the probability of adhesion formation. However, this approach requires specialized equipment and surgical skills, making it somewhat challenging. Alternatively, anti-adhesion products can be used to lower the risk of adhesion formation. In this study, a murine cecal abrasion adhesion model was established and will be simulated common adhesion scenarios observed in patients after abdominal surgery. The efficacy of anti-adhesion gel materials will be then evaluated to assess their anti-adhesion properties. The record of gross adhesion severity assessment was performed. The adhesion status between the cecum and abdominal wall was observed on postoperative days 3 and 14. The results was shown that three days post-surgery operation, the group exhibited more severe adhesions upon gross examination. By day 14 post-surgery operation (at animal sacrifice), the histopathological analysis revealed that the group exhibited thicker fibrous tissue thickness, increased neovascularization, and higher collagen accumulation in the peritoneum. Therefore, based on the results of this experiment, a postoperative bowel adhesion rat is reliable and can be safely used to test the efficacy of novel anti-adhesive formulations to prevent intra-abdominal adhesions by using this model.

Myeloid Cells and Sensory Nerves Mediate Peritendinous Adhesion Formation via Prostaglandin E2.

Peritendinous adhesion that forms after tendon injury substantially limits daily life. The pathology of adhesion involves inflammation and the associated proliferation. However, the current studies on this condition are lacking, previous studies reveal that cyclooxygenase-2 (COX2) gene inhibitors have anti-adhesion effects through reducing prostaglandin E2 (PGE2) and the proliferation of fibroblasts, are contrary to the failure in anti-adhesion through deletion of EP4 (prostaglandin E receptor 4) gene in fibroblasts in mice of another study. In this study, single-cell RNA sequencing analysis of human and mouse specimens are combined with eight types of conditional knockout mice and further reveal that deletion of COX2 in myeloid cells and deletion of EP4 gene in sensory nerves decrease adhesion and impair the biomechanical properties of repaired tendons. Furthermore, the COX2 inhibitor parecoxib reduces PGE2 but impairs the biomechanical properties of repaired tendons. Interestingly, PGE2 local treatment improves the biomechanical properties of the repaired tendons. These findings clarify the complex role of PGE2 in peritendinous adhesion formation (PAF) and tendon repair.

Evaluation of sodium hyaluronate-based composite hydrogels for prevention of nasal adhesions.

During the healing process after intra-nasal surgery, the growth and repair of damaged tissues can result in the development of postoperative adhesions. Various techniques have been devised to minimize the occurrence of postoperative adhesions which include insertion of stents in the middle meatus, application of removable nasal packing, and utilizing biodegradable materials with antiadhesive properties. This study assesses the efficacy of two sodium hyaluronate (SH)-based freeze-dried hydrogel composites in preventing postoperative nasal adhesions, comparing them with commonly used biodegradable materials in nasal surgery. The freeze-dried hydrogels, sodium hyaluronate and collagen 1(SH-COL1) and sodium hyaluronate, carboxymethyl cellulose, and collagen 1 (SH-CMC-COL1), were evaluated for their ability to reduce bleeding time, promote wound healing, and minimize fibrous tissue formation. Results showed that SH-CMC-COL1 significantly reduced bleeding time compared to both biodegradable polyurethane foam and SH-COL1. Both SH-COL1 and SH-CMC-COL1 exhibited enhanced wound healing effects, as indicated by significantly greater wound size reduction after two weeks compared to the control. Histological analyses revealed significant differences in re-epithelialization and blood vessel count among all tested materials, suggesting variable initial wound tissue response. Although all treatment groups had more epithelial growth, with X-SCC having higher blood vessel count at 7 d post treatment, all treatment groups did not differ in all histomorphometric parameters by day 14. However, the long-term application of SH-COL1 demonstrated a notable advantage in reducing nasal adhesion formation compared to all other tested materials. This indicates the potential of SH-based hydrogels, particularly SH-COL1, in mitigating postoperative complications associated with nasal surgery. These findings underscore the versatility and efficacy of SH-based freeze-dried hydrogel composites for the management of short-term and long-term nasal bleeding with an anti-adhesion effect. Further research is warranted to optimize their clinical use, particularly in understanding the inflammatory factors influencing tissue adhesions and assessing material performance under conditions mimicking clinical settings. Such insights will be crucial for refining therapeutic approaches and optimizing biomaterial design, ultimately improving patient outcomes in nasal surgery.

The Therapeutic Potential of Ganoderma lucidum Karst and Ziziphus jujuba Mill for Postsurgical Adhesion Band Formation

Background: Intra-abdominal adhesions are a commonly occurring postoperative complication following abdominopelvic surgery. Peritoneal adhesion formation can lead to infertility, chronic pelvic pain, and intestinal obstruction. The anti-inflammatory and anti-oxidant activities of Ganoderma lucidum Karst (G. lucidum) and Ziziphus jujuba Mill (Z. jujuba) have been reported. Here, we have explored the therapeutic potential of Ganoderma lucidum Karst (G. lucidum) and Z. jujuba against postsurgical adhesion band formation. The NC3Rs ARRIVE guidelines were followed during experimental studies. Methods: G. lucidum powder (800 mg/kg) and Z. jujuba powder (400 mg/kg) were administered using oral gavage to different groups of male albino Wistar rats. After ten days of treatment, macroscopic evidence for peritoneal adhesions and adhesion band score were determined. Furthermore, the anti-inflammatory and antifibrosis effects of G. lucidum and Z. jujuba were assessed using histopathology, ELISA, and real-time polymerase chain reaction methods. Also, alterations in some oxidative stress parameters were evaluated. Results: G. lucidum and Z. jujuba significantly decreased adhesion bands and were associated with a reduction in inflammatory cell infiltration into damaged tissues and the mRNA and protein expression of inflammatory cytokines via modulation of TNF-α, IL-6, IL-1β, and TGF-β. Moreover, both agents inhibited fibrotic adhesion band formation by decreasing collagen deposition and reducing profibrotic marker expression, Col1A1, at the peritoneum adhesion tissues. G. lucidum and Z. jujuba improved some antioxidant factors in rats’ adhesion tissues. The result of LC-MS showed that Ganoderma lucidum Karst and Ziziphus jujuba Mill consist of components with antioxidant activity, including ganoderic acid, lucidenic acid, quercetin, linoleic acid, malic acid, and benzoic acid. Conclusion: The results have demonstrated the therapeutic potential of G. lucidum and Z. jujuba in reducing peritoneal adhesion through anti-inflammatory and anti-fibrotic properties, indicating their promising value as a new therapeutic approach in preventing postsurgical adhesion.

ADHESIVE DISEASE OF THE ABDOMINAL CAVITY: ETIOMORPHOPATHOGENESIS, CLINIC, DIAGNOSIS, TREATMENT AND PREVENTION AT THE PRESENT STAGE

In surgery of the gastrointestinal tract, peritoneal adhesions are detected in 80-90% of cases, including open surgical interventions, abdominal adhesions occur in 70-90% of patients, with laparoscopic – in 24-35% of patients. The number of deaths in adhesive disease ranges from 14 to 52%, and in patients with concomitant pathology, whose age exceeds sixty years, reaches 68%. The main etiological factors of the formation of adhesions are mechanical, chemical, physical and infectious effects. The pathogenesis of the formation of adhesions includes three processes: inhibition of fibrinolytic and extracellular matrix degradation systems; inflammatory reaction with cytokine production, mainly TGF-β1; tissue hypoxia as a result of interruption of blood supply to mesothelial cells and submesothelial fibroblasts. The clinical picture of SBBP, as a rule, is characterized by dyspeptic disorders in the early stages, and is accompanied by symptoms of intestinal obstruction in the advanced ones. The "gold standard". Treatment of adhesive disease can be carried out using conservative therapy or surgical intervention. To date, prevention is the most preferred method to prevent the consequences of the development of adhesive disease. Despite the improvement of surgical techniques, the development of new approaches to treatment and diagnosis, adhesions remain an inevitable consequence of intra-abdominal operations. Understanding the pathogenesis of the formation of the adhesive process and adhesion, the possibility of their transformation, especially at the cellular and molecular level, can help in the further development of more effective methods of treatment and prevention of SBP.

Construction of a Curcumin‐Loaded PLLA/PCL Micro‐Nano Conjugated Fibrous Membrane to Synergistically Prevent Postoperative Adhesion From Multiple Perspectives

AbstractPostoperative adhesion (POA) has emerged as a prevalent clinical challenge in soft tissue repair, emphasizing the critical need for preventive measures. However, the complex POA development process makes POA prevention from a single aspect insufficient. Hence, a curcumin‐loaded poly‐L‐lactic acid‐poly (caprolactone) micro‐nano conjugated fibrous membrane (PAPC MCFM (cur)) is engineered to synergistically prevent POA from multiple perspectives, in which poly (caprolactone) (PCL) nanofibers (118 ± 12 nm) with low orientation traverse the oriented poly‐L‐lactic acid (PLLA) microfibers (2.0 ± 0.3 µm). The PAPC MCFM not only significantly improves the mechanical properties of the anisotropic fibrous membrane (AIFM) that the modulus of elasticity and the tensile strength in the direction vertical to microfiber orientation increase by 4.5 and 13.0 times, respectively, but also can further enhance the “contact guidance effect” of AIFM, i.e., hindering fibroblast adhesion, proliferation, and differentiation to myofibroblast through inhibiting integrin β1 activation, vinculin expression and focal adhesion (FA) formation, and the nuclear localization activation of yes‐associated protein (YAP). Except for these effects, PAPC MCFM loading with 2.5 mg mL−1 curcumin can further prevent POA by delivering anti‐inflammatory, antioxidant, and antibacterial properties, and by suppressing fibrosis through decreased transforming growth factor‐β1(TGF‐β1) expression, showing effective POA prevention in rat abdominal cavity and rabbit dura mater models.

The Therapeutic Potential of Targeting the Connexin43 as a New Approach to Reducing Post-Surgical Adhesion.

Post-surgical peritoneal adhesions are a serious problem causing complications, such as bowel obstruction, infertility, and pain. There are currently no effective ways of preventing post-surgical adhesions. Excess secretion of proinflammatory cytokines and profibrotic molecules by immune cells and adherent fibroblasts is the main mechanism thatpromotes post-operative fibrotic scars. Although many studies have been conducted on the pathological causes of this disorder, there are still many unknown facts in this matter, so assessment of the role of different molecules in causing inflammation and adhesion can lead to the creation of new treatment methods. Connexins are a group of proteins related to gap junctions that have a role in cell communication and transmitted signaling between adjacent cells. Between different types of connexin protein isoforms, connexin43 is known to be involved in pathological conditions related to inflammation and fibrosis. Recent studies have reported that inhibition of connexin43 has the potential to reduce inflammation and fibrosis by reducing the expression of molecules like α-SMA and plasminogen activator inhibitor (PAI) that are involved in the early stages of adhesion formation. Further, inhibition of connexin43 may have therapeutic potential as a target to prevent post-surgical peritoneal adhesions.

Interleukin-33 promotes intrauterine adhesion formation in mice through the mitogen-activated protein kinase signaling pathway

IL-33 belongs to the inflammatory factor family and is closely associated with the inflammatory response. However, its role in the development of intrauterine adhesions (IUAs) remains unclear. In this study, the role of IL-33 in the formation of IUAs after endometrial injury was identified via RNA sequencing after mouse endometrial organoids were transplanted into an IUA mouse model. Major pathological changes in the mouse uterus, consistent with the expression of fibrotic markers, such as TGF-β, were observed in response to treatment with IL-33. This finding may be attributed to activation of the phosphorylation of downstream MAPK signaling pathway components, which are activated by the release of IL-33 in macrophages. Our study provides a novel mechanism for elucidating IUA formation, suggesting a new therapeutic strategy for the prevention and clinical treatment of IUAs.

Mdm2 requires Sprouty4 to regulate focal adhesion formation and metastasis independent of p53

Although the E3 ligase Mdm2 and its homologue and binding partner MdmX are the major regulators of the p53 tumor suppressor protein, it is now evident that Mdm2 and MdmX have multiple functions that do not involve p53. As one example, it is known that Mdm2 can regulate cell migration, although mechanistic insight into this function is still lacking. Here we show in cells lacking p53 expression that knockdown of Mdm2 or MdmX, as well as pharmacological inhibition of the Mdm2/MdmX complex, not only reduces cell migration and invasion, but also impairs cell spreading and focal adhesion formation. In addition, Mdm2 knockdown decreases metastasis in vivo. Interestingly, Mdm2 downregulates the expression of Sprouty4, which is required for the Mdm2 mediated effects on cell migration, focal adhesion formation and metastasis. Further, our findings indicate that Mdm2 dampening of Sprouty4 is a prerequisite for maintaining RhoA levels in the cancer cells that we have studied. Taken together we describe a molecular mechanism whereby the Mdm2/MdmX complex through Sprouty4 regulates cellular processes leading to increase metastatic capability independently of p53.

Measuring Integrin Force Loading Rates Using a Two-Step DNA Tension Sensor.

Cells apply forces to extracellular matrix (ECM) ligands through transmembrane integrin receptors: an interaction which is intimately involved in cell motility, wound healing, cancer invasion and metastasis. These small (piconewton) integrin-ECM forces have been studied by molecular tension fluorescence microscopy (MTFM), which utilizes a force-induced conformational change of a probe to detect mechanical events. MTFM has revealed the force magnitude for integrin receptors in a variety of cell models including primary cells. However, force dynamics and specifically the force loading rate (LR) have important implications in receptor signaling and adhesion formation and remain poorly characterized. Here, we develop an LR probe composed of an engineered DNA structure that undergoes two mechanical transitions at distinct force thresholds: a low force threshold at 4.7 pN (hairpin unfolding) and a high force threshold at 47 pN (duplex shearing). These transitions yield distinct fluorescence signatures observed through single-molecule fluorescence microscopy in live cells. Automated analysis of tens of thousands of events from eight cells showed that the bond lifetime of integrins that engage their ligands and transmit a force >4.7 pN decays exponentially with a τ of 45.6 s. A subset of these events mature in magnitude to >47 pN with a median loading rate of 1.1 pN s-1 and primarily localize at the periphery of the cell-substrate junction. The LR probe design is modular and can be adapted to measure force ramp rates for a broad range of mechanoreceptors and cell models, thus aiding in the study of molecular mechanotransduction in living systems.

Correlation analysis of functional relationships between morphological indicators of small intestine mersis during the supply process

аdhesion disease has become a widespread disease, which for years has maintained a tendency to constant growth, and remains one of the most complex and unsolved topical problems of the functional state of the abdominal cavity. At the moment, most changes in the functioning of the gastrointestinal tract are associated with a violation of the tissue barrier during the penetration of pathogenic types of microorganisms and absorption of toxic substances, which is one of the effects of biological factors on the intestine. Understanding the structure of the body, its morphological and functional features, the ability to understand the patterns of vital and pathological processes in various organs, tissues and the whole body. At the moment, the functional connections between the immune, nervous and endocrine links in the functioning of the tissues of the peritoneum and its components during the progressive adhesion process remain incompletely investigated. At the same time, it is also important to pay attention to the behavioral characteristics of the organism. Purpose of our investigation was to investigate the correlational relationships between the morphological indicators of the mesentery of the small intestine during the experimental adhesion process. The analysis of the relationship between the body weight and BMI of the animals of the experimental group with the morphological parameters of the adhesion formations (quantity and thickness) showed a high level of correlation, and confirms the influence of intensive processes of fibrin formation on the morphometric indicators of the experimental animals. Correlation analysis between the number of detected milk spots, the thickness of detected adhesions and the total number of lymphocytes, as well as PNA+-immunologically immature and SBA+B-lymphocytes at each observation period in the animals of the experimental group during the adhesion process showed the dependence of the thickness of fibrin formations and the number of immunocompetent cells, which can be characterized as a local immune response that determines the intensity of collagen formation by the serous membranes and affects the degree of adhesion formation. The revealed correlations between antigen-presenting cells, the area of ​​collagen fibers of the 1st and 3rd types, and the total number of lymphocytes, as well as PNA+-immunologically immature and SBA+-B-lymphocytes at each observation period in the animals of the experimental group during the adhesion process, indicate the morphogenetic function of lymphocytes against the background of the growth of the protein-synthesizing function of fibroblasts, which leads to an increase in the synthesis of collagen and other components of the connective tissue matrix. On the 14th and 21st days of the study, correlations were established between the number of antigen-presenting cells and the area of ​​collagen fibers of the 1st and 3rd types at each observation period in the animals of the experimental group during the adhesion process. The presence of these correlations indicates that the morpho-functional state of the SALC lymphoid tissue associated with the serous membranes of the peritoneum is determined by the activation of one or another link of immunity. After an antigenic impact on the body, there are shifts in the direction of activation of the population of B1-lymphocytes of the mesentery of the small intestine and B2-lymphocytes, which changes the structure of the tissue barrier of the peritoneum and affects the general state of the body.

Genomic Analysis of Cronobacter condimenti s37: Identification of Resistance and Virulence Genes and Comparison with Other Cronobacter and Closely Related Species.

Cronobacter condimenti are environmental commensals that have not been associated with any clinical infections. To date, they are the least understood and described Cronobacter species within the genus. The objective of this study was to use a draft genome sequence (DGS) of the Cronobacter condimenti strain s37 to screen for genes encoding for antibiotic resistance, virulence, response to environmental stress, and biofilm formation. The strain was isolated in Poland from commercial small radish sprouts. This is the second genome of this species available in the GenBank database. The comparative genome analysis (cgMLST) of C. condimenti s37 with other Cronobacter spp. including the pathogenic species C. sakazakii and the plant-associated closely related genera Franconibacter and Siccibacter was also performed. The assembled and annotated genome of the C. condimenti s37 genome was 4,590,991 bp in length, with a total gene number of 4384, and a GC content of 55.7%. The s 37 genome encoded for genes associated with resistance to stressful environmental conditions (metal resistance genes: zinc, copper, osmotic regulation, and desiccation stress), 17 antimicrobial resistance genes encoding resistance to various classes of antibiotics and 50 genes encoding for the virulence factors. The latter were mainly genes associated with adhesion, chemotaxis, hemolysis, and biofilm formation. Cg-MLST analysis (3991 genes) revealed a greater similarity of C. condimenti s37 to S. turicensis, F. pulveris, and C. dublinensis than to other species of the genus Cronobacter. Studies on the diversity, pathogenicity, and virulence of Cronobacter species isolated from different sources are still insufficient and should certainly be continued. Especially the analysis of rare strains such as s37 is very important because it provides new information on the evolution of these bacteria. Comparative cgMLST analysis of s37 with other Cronobacter species, as well as closely related genera Franconibacter and Siccibacter, complements the knowledge on their adaptability to specific environments such as desiccation.

Structural insights of an LCP protein-LytR-from Streptococcus dysgalactiae subs. dysgalactiae through biophysical and in silico methods.

The rise of antibiotic-resistant bacterial strains has become a critical health concern. According to the World Health Organization, the market introduction of new antibiotics is alarmingly sparse, underscoring the need for novel therapeutic targets. The LytR-CpsA-Psr (LCP) family of proteins, which facilitate the insertion of cell wall glycopolymers (CWGPs) like teichoic acids into peptidoglycan, has emerged as a promising target for antibiotic development. LCP proteins are crucial in bacterial adhesion and biofilm formation, making them attractive for disrupting these processes. This study investigated the structural and functional characteristics of the LCP domain of LytR from Streptococcus dysgalactiae subsp. dysgalactiae. The protein structure was solved by X-ray Crystallography at 2.80Å resolution. Small-angle X-ray scattering (SAXS) data were collected to examine potential conformational differences between the free and ligand-bound forms of the LytR LCP domain. Additionally, docking and molecular dynamics (MD) simulations were used to predict the interactions and conversion of ATP to ADP and AMP. Experimental validation of these predictions was performed using malachite green activity assays. The determined structure of the LCP domain revealed a fold highly similar to those of homologous proteins while SAXS data indicated potential conformational differences between the ligand-free and ligand-bound forms, suggesting a more compact conformation during catalysis, upon ligand binding. Docking and MD simulations predicted that the LytR LCP domain could interact with ADP and ATP and catalyze their conversion to AMP. These predictions were experimentally validated by malachite green activity assays, confirming the protein's functional versatility. The study provides significant insights into the structural features and functional capabilities of the LCP domain of LytR from S. dysgalactiae subsp. dysgalactiae. These findings pave the way for designing targeted therapies against antibiotic-resistant bacteria and offer strategies to disrupt bacterial biofilm formation.

Muticomponent Melt‐Electrowritten Vascular Graft to Mimic and Guide Regeneration of Small Diameter Blood Vessels

AbstractCardiovascular disease is a leading cause of morbidity. Current treatments include vessel substitution using autologous/synthetic vascular grafts, but these commonly fail in small diameter applications, largely due to compliance mismatch and clot formation. In this study, a multicomponent vascular graft, that takes inspiration from native vessel architecture, is developed to overcome these limitations. Melt electrowriting (MEW) is used to produce tubular scaffolds with vascular‐mimetic fiber architecture and mechanics, which is combined with a lyophilized fibrinogen matrix with tailored degradation kinetics to generate a hybrid graft. The MEW framework not only contributes to graft mechanics, but also provides contact guidance to direct cell/neotissue orientation and mimic the native tunica media. This construct is further functionalized with heparin, which in combination with the smooth extracellular matrix (ECM) surface, reduced platelet adhesion and clot formation providing a substrate for endothelization, thereby mimicking the function of the intima. Lastly, an outer electrospun layer representing the adventitia is added to improve elasticity and reduce permeability. This graft satisfies ISO implantability requirements, matches the compliance of native vessels, and reestablishes physiological flow with minimal clot formation in a preclinical model. Therefore, this graft represents an innovative off‐the‐shelf alternative to address the unmet clinical need for small‐diameter vascular grafts.

Endometriosis: A Comprehensive Exploration of Inflammatory Mechanisms and Fertility Implications.

Endometriosis is a prevalent gynecological disorder characterized by the ectopic growth of endometrial-like tissue outside the uterus. This condition poses significant challenges due to its chronic nature, debilitating symptoms such as pelvic pain and infertility, and substantial impact on quality of life. Central to the pathogenesis of endometriosis are inflammatory mechanisms that perpetuate tissue proliferation, adhesion formation, and immune dysregulation within the pelvic cavity. Inflammation plays a pivotal role in the development and progression of endometriosis, influencing the severity of symptoms and complications associated with the disease. Dysregulated immune responses contribute to the persistence of ectopic endometrial implants, exacerbating pelvic pain and other symptoms experienced by affected individuals. Moreover, the inflammatory milieu created by endometriotic lesions disrupts normal ovarian function, impairs follicular development, and compromises reproductive outcomes, thereby posing challenges to fertility. This review comprehensively explores the inflammatory mechanisms underlying endometriosis and their implications for fertility. Synthesizing current research and clinical insights elucidates the intricate interplay between inflammation, disease progression, and reproductive health outcomes. Understanding these complex interactions is essential for developing targeted diagnostic strategies and optimizing therapeutic approaches tailored to alleviate symptoms and improve fertility outcomes in individuals with endometriosis. Ultimately, this review aims to enhance the understanding of endometriosis pathophysiology, inform clinical practice, and stimulate further research to advance personalized care and management strategies for this challenging condition.

The results of preventing postoperative achilles tendon adhesion using cross-linked and non-cross-linked hyaluronic acid, a study with rat model

BackgroundThere are many adhesion barrier materials, cross-linked or non-cross-linked hyaluronic acid (HA), used during surgeries.PurposeThis study investigates the efficacy of cross-linked and non-cross-linked HA in preventing Achilles tendon adhesions. We hypothesized that non-cross-linked HA may be more effective than cross-linked HA in preventing Achilles tendon adhesions following injury and repair.MethodsTwenty male Sprague Dawley rats, totaling 40 legs, underwent Achilles tendon transection and repair. Following the surgery, they were treated simultaneously with cross-linked and non-cross-linked HA formulations. The rats were divided into four groups: a positive control group, a group treated with BMC non-cross-linked HA gel, a group treated with DEFEHERE cross-linked HA gel, and a group treated with ANIKA cross-linked HA gel. Four weeks after surgery, macroscopic evaluation of peritendinous adhesion and histological analysis were conducted to assess the effectiveness of the treatments.ResultsNon-cross-linked BMC HA demonstrated superior efficacy in preventing tendon adhesions compared to cross-linked HA and control groups. Histological analysis confirmed reduced adhesion severity in the non-cross-linked HA group (P < 0.05). The findings support the potential of non-cross-linked HA as a treatment to inhibit tendon adhesions. Further research, including clinical trials, is warranted to validate these results in human subjects.ConclusionsNon-cross-linked BMC HA had significantly lower tendon adhesions parameters and better healing scores in histological analysis than cross-linked HA and control group did. Non-cross-linked HA holds promise as a potential treatment to inhibit the formation of such adhesions.

Cationic homopolypeptides: A versatile tool to design multifunctional antimicrobial nanocoatings

Postoperative infections are the most common complications faced by surgeons after implant surgery. To address this issue, an emerging and promising approach is to develop antimicrobial coatings using antibiotic substitutes. We investigated the use of polycationic homopolypeptides in a layer-by-layer coating combined with hyaluronic acid (HA) to produce an effective antimicrobial shield. The three peptide-based polycations used to make the coatings, poly(l-arginine) (PAR), poly(l-lysine), and poly(l-ornithine), provided an efficient antibacterial barrier by a contact-killing mechanism against Gram-positive, Gram-negative, and antibiotic-resistant bacteria. Moreover, this activity was higher for homopolypeptides containing 30 amino-acid residues per polycation chain, emphasizing the impact of the polycation chain length and its mobility in the coatings to deploy its contact-killing antimicrobial properties. However, the PAR-containing coating emerged as the best candidate among the three selected polycations, as it promoted cell adhesion and epithelial monolayer formation. It also stimulated nitric oxide production in endothelial cells, thereby facilitating angiogenesis and subsequent tissue regeneration. More interestingly, bacteria did not develop a resistance to PAR and (PAR/HA) also inhibited the proliferation of eukaryotic pathogens, such as yeasts. Furthermore, in vivo investigations on a (PAR/HA)-coated hernia mesh implanted on a rabbit model confirmed that the coating had antibacterial properties without causing chronic inflammation. These impressive synergistic activities highlight the strong potential of PAR/HA coatings as a key tool in combating bacteria, including those resistant to conventional antibiotics and associated to medical devices.