Anti-adhesive Effect Research Articles

Hybrid Bio-Based Silicone Coatings with Anti-adhesive Properties.

Hybrid polysiloxanes and polysilsesquioxanes grafted with naturally occurring bioactive phytochemicals: eugenol and linalool, were synthesized and investigated with regard to their structure and properties. The two series of materials, differing in the type of inorganic structure and the content of active groups, were coated onto the surface of glass plates, and their antibiofilm activities against bacteria Aeromonas hydrophila were assessed by luminometry and fluorescence microscopy. Bioactivity was correlated with specific properties of the hybrid coatings (chemical structure, surface free energy and adhesiveness). The functionalized polysilsesquioxanes exhibited the most favorable anti-adhesive effects. Cell adhesion after 6 days of incubation, expressed as RLU/cm2, was significantly reduced (44 and 67 for, respectively, Z-E-100 and Z-L-100, compared to 517 for the control glass carrier). The surface stickiness of polysiloxane films deteriorated their anti-adhesion properties, despite the presence of a large amount of bioactive species.

Polypropylene composite hernia mesh with anti-adhesion layer composed of PVA hydrogel and liposomes drug delivery system

Polypropylene (PP) mesh has been widely used in hernia repair as prosthesis material owing to its excellent balanced biocompatibility and mechanical properties. However, abdominal adhesion between the visceral and PP mesh is still a major problem. Therefore, anti-adhesive PP mesh was designed with poly(vinyl alcohol) (PVA) hydrogel and liposomes drug delivery system. First, PVA hydrogel coating was formed on the surface of PP mesh with freezing-thawing processing cycles (FTP). Subsequently, the lyophilized PVA10-c-PP was immersed in rapamycin (RPM)-loaded liposome solution until swelling equilibrated to obtain the anti-adhesion mesh RPM@LPS/PVA10-c-PP. It was demonstrated that the hydrogel coating can stably fix on the surface of PP mesh even after immersed in PBS solution at 37 °C or 40 °C for up to 30 days. In vitro cell tests revealed the excellent cytocompatibility and the potential to inhibit cell adhesion of the modified PP mesh. Moreover, the anti-adhesive effects of the RPM@LPS/PVA10-c-PP mesh was evaluated through in vivo experiments. The RPM@LPS/PVA10-c-PP mesh exhibited less adhesion than original PP mesh throughout the duration of implantation. At 30 days, the adhesion score of RPM@LPS/PVA10-c-PP mesh was 1.37 ± 0.75, however the original PP was 3 ± 0.71. Furthermore, the results of H&E and Masson trichrome staining proved that the RPM@LPS/PVA10-c-PP mesh showed slighter inflammation response and significant looser fibrous tissue surrounded the PP filaments as compared to the native PP. The current findings manifested that this type of RPM@LPS/PVA10-c-PP might be a potential candidate for anti-adhesion treatment. Data availabilityData will be made available on request.

Preparation of 2D ZIF-L and Its Antibacterial and Antifouling Properties

The excessively leached metal ions from traditional metallic antimicrobial nanoparticles are harmful to biological and human tissues. Metal-organic frameworks (MOFs) coordinating bioactive metal ions to organic bridging ligands can potentially address this issue, avoiding the excessive leaching of metal ions and simultaneously exhibiting high effective antibacterial activities. Here, we report the preparation of a 2-dimensional leaves-like zeolitic imidazolate framework (ZIF-L) for potential antibacterial and anti-algae applications. The ZIF-L nanosheet exhibits complete inactivation of Escherichia coli (phosphate buffer saline: 4 h) and Bacillus subtilis (seawater: 0.5 h). The ZIF-L/epoxy composite has excellent antibacterial effect, poisoning effect and anti-adhesion effect on a variety of marine algae. It is worth noting that the removal rate (Escherichia coli) for ZIF/epoxy composite can be reached to 90.20% by only adding ZIF-L (0.25 wt%). This work will inspire researchers to develop more metal-organic frameworks materials for applications in the antibacterial and anti-algae fields.

Combined Verapamil-Polydopamine Nanoformulation Inhibits Adhesion Formation in Achilles Tendon Injury Using Rat Model

Topical verapamil has been demonstrated to reduce the fibroproliferative scar. Therefore, it was hypothesized that topical verapamil could reduce adhesion formation after tendon repair. The current study aimed to examine the effects of verapamil-loaded polydopamine nanoparticles (VP-PDA NPs) on the adhesion formation of Achilles tendon laceration and repair in a rat model. We randomly assigned 72 male Sprague-Dawley rats to the control, the PDA NPs, and the VP-PDA NPs groups (n = 24 per group). The quality of tendon healing was evaluated by the maximal tensile strength four and six weeks after surgery. The degree of tendon adhesion was scored on days 4, 15, 29, and 43 after surgery. The expressions of transforming growth factor-beta 1 (TGF-β1), vimentin, α-smooth muscle actin (α-SMA), and collagens type I and III were detected through Western blotting or immunohistochemistry at four weeks after surgery. In vitro release tests revealed that 61.3% of verapamil was released from VP-PDA NPs in four weeks. There was a significant increase in average failure to load in the VP-PDA NPs group (89.27 ± 5.09 N) compared with the PDA NPs group (65.52 ± 2.04 N) (p = 0.003) and the control group (74.52 ± 4.24 N) (p = 0.029). Adhesion scores were significantly reduced in the VP-PDA NPs group at six weeks (3.175 ± 0.08) and four weeks (3.35 ± 0.25) compared with the other groups. Moreover, VP-PDA NPs significantly reduced the expression of vimentin, α-SMA, TGF-β1, and collagens type I and III. These data suggest that VP-PDA NPs reduced adhesion formation and enhanced tendon healing during rat tendon injury. Since topical verapamil has been used in clinics without side effects, VP-PDA NPs would have direct translation implications. However, its anti-adhesive effects on intrasynovial tendon injury must be examined.

The Anti-Adhesion Effect of Nisin as a Robust Lantibiotic on the Colorectal Cancer Cells.

Bacteriocins are a type of antimicrobial peptide that are produced by probiotics. They have been studied as possible therapeutic drugs and have been used to suppress bacterial development in foods. Nisin is a potent bacteriocin having the anti-microbial and anti-cancer characteristics produced by Lactococcus lactis. The aim of the present paper is to evaluate the influence of Nisin on cell adhesion and its two related genes, mmp-2 and mmp-9, in the colorectal cancer cell line. For this purpose, HT-29 cells were treated with various concentrations of Nisin and the cell cytotoxicity, cell adhesion, and gene expression were evaluated using the MTT assay, cell adhesion assay, and real-time PCR. Our findings showed that 32 to 1024 μg/ml of Nisin resulted in a significant reduction in cell viability (P < 0.05). Furthermore, 128 and 256 μg/ml of Nisin significantly reduced the cell adhesion, and mmp-2 and mmp-9 gene expressions (P < 0.05). Our findings suggested that Nisin could prevent metastasis and cancer progression.

Клинико-патогенетические аспекты лечения и профилактики пиелонефрита у детей

Treatment of pyelonephritis in children should be combined, long-term and individual-based. The success of the therapy in children largely depends on the prompt appointment and the correct choice of antimicrobial therapy.To evaluate the efficiency of the dietary supplement "Cystenium II" in a group of children aged 7 to 14 years with a diagnosis of acute and chronic recurrent pyelonephritis in the acute phase.A total of 60 children aged 7 to 14 years with a diagnosis of acute or chronic recurrent pyelonephritis in the acute stage were included in the study. The clinical group consisted of 30 patients (mean age 12.1+/-1.8 years), while the control group included 30 patients of mean age 11.2+/-1.7 years. In the control group patients received only standard antibiotic therapy, while in the clinical group it was combined with a dietary supplement "Cystenium II" 1 tablet 2 times a day with meals for 14 days. After the course of antibacterial treatment, the children in the clinical group continued to take the studied dietary supplement for another 14 days in order to prevent the recurrence of pyelonephritis. The results of treatment (patient's condition, presence of pain, dysuria, fever) were assessed on the 3rd, 7th, 14th day, 1 and 6 months after the start of treatment. A urinalysis was performed at the baseline, on the 7th and 14th days, as well as after 1 and 6 months. Urine culture was performed before and after antibiotic therapy at the baseline, on the 14th day, 1 and 6 months after the start of treatment.The main indicators of urinalysis (leukocytes, red blood cells, protein) returned to normal values in 26 (86.7%) patients of the clinical group and in 23 (76.7%) patients of the control group on the 7th day after the start of treatment. At the completion of the basic therapy (after 14 days) normal clinical parameters (absence of leukocyturia, microhematuria, proteinuria) were observed in all patients of the clinical group and in 28 (93.3%) patients of the control group. After a month of follow-up, the disturbances in urinalysis (leukocytes, red blood cells, protein) in the control group were again seen in 3 (10%) patients, as well as after 6 months. However, in the clinical group all patients had normal urinalysis (absence of leukocyturia, microhematuria, proteinuria) after 1 month and only in 1 (3.3%) case leukocyturia, as well as an increase in the number of red blood cells and protein was detected by 6 months.According to our results, the use of dietary supplements "Cystenium II" (manufactured by Akvion, Russia), due to the constituents of D-mannose (450 mg), cranberry fruit extract with a standardized activity of 500 mg (36 mg of proanthocyanidins) and vitamin C (60 mg), may cause anti-inflammatory and anti-adhesive effects (resolving of leukocyturia and bacteriuria). This allows to use the dietary supplement Cystenium II in children from 7 years of age in the combination therapy of acute pyelonephritis, as well as exacerbation of chronic pyelonephritis. The obtained results showed a high overall therapeutic efficacy of combination therapy using Cystenium II after 6 months from the start of treatment (relapse in 1 patient), in contrast to the control group (relapse in 6 patients).the use of dietary supplement "Cystenium II" allowed to reduce the number of repeated courses of antibiotic therapy in children during 6 months of follow-up and, most likely, reduced the frequency of development of chronic pyelonephritis after an acute inflammation. Therefore, the wide clinical use of dietary supplements "Cystenium II" for the combined treatment of acute and exacerbation of chronic pyelonephritis in children older than 7 years seems to be very reasonable.

Antiadhesion effect of the chitosan-based film incorporated with essential oils against foodborne bacteria

In the food sector, bacterial adhesion on surfaces followed by biofilm development is responsible for food contamination and spoilage, and foodborne illness , leading to considerable economic losses. Therefore, this present study aimed to elaborate a biodegradable material that inhibits bacterial adhesion and thus biofilm formation. For this purpose, chitosan-based films (CH-films) containing four different essential oils (EOs) were elaborated. The impact of these EOs on the physicochemical properties as well as the antiadhesion activity of the CH-films was evaluated. The contact angle results showed that the addition of EOs has modified significantly the physicochemical properties of the CH-film. The electron donor (γ - ) and Lifshitz-Van der Waals component (γ LW ) values increased, whereas the qualitative hydrophobicity ( θ w) and electron acceptor (γ + ) values decreased. The analysis of bacterial adhesion using environmental scanning electron microscopy (ESEM) revealed that the CH-film containing C. zeylanicum EO exhibits the strongest antiadhesion activity against E. coli , E. hirae , and S. aureus compared to the other CH-films, with coverage rate values equal to 5.16 ± 1.13%, 2.8 ± 0.38%, and 1.52 ± 0.53%, respectively. Moreover, ESEM analysis showed that the antiadhesion effect of C. zeylanicum EO on P. aeruginosa strain was accompanied by a rupture of bacterial cells. From these findings, the CH-films incorporated with EOs could potentially be applied in the food industry to prevent microbial adhesion to surfaces and eventual biofilm formation. • The elaboration of a biodegradable film with antiadhesion activity using chitosan and essential oils. • The chemical constituents of pelargonium, thyme, cinnamon, and clove essential oils were identified. • The physicochemical properties of the chitosan-based film were affected by the incorporation of essential oils. • The chitosan-based film containing cinnamon essential oil showed strong antiadhesion activity against the tested strains. • The cell structure of P. aeruginosa was destabilized after contact with the film containing cinnamon essential oil.

Efficacy of Qingre Huashi decoction on infection of : inhibiting adhesion, antioxidant, and anti-inflammation.

To investigate the phytochemical profile of Qingre Huashi decoction (, QHD) and evaluate the mechanisms rationalizing the use of QHD against ()-associated gastritis. QHD is composed of 11 herbs, which was prepared by a fixed Pharmacy and concentrated into clear paste. High-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (HPLC-QTOF/MS) was used to detect the phytochemical profile of QHD. The toxicity of QHD against and human gastric epithelial cells was evaluated by the toxicology test and cell counting kit-8 assay. The adhesion model was constructed by incubating and gastric mucosal epithelial cells for 2 h. The urease assay was used to examine the anti-adhesion effects of QHD, and gene expression of adhesins was evaluated by quantitative polymerase chain reaction. The antioxidant activity was assessed by DCFH-DA labeling. To evaluate the anti-inflammatory effect, the levels of pro-inflammatory cytokines in the culture supernatant were detected by enzyme-linked immunosorbent assay. HPLC-QTOF/MS profiling indicated the presence of primary compounds 1-20 in QHD. Drug concentration was determined as 1, 2, and 5 mg/mL by the toxic concentration of QHD against and human gastric epithelial cells. QHD prevented adhesion to the human gastric epithelial cells and reduced levels of reactive oxygen species. QHD also reduced the level of interleukin-8 and other pro-inflammatory cytokines that were upregulated by infection. QHD could inhibit adhesion, and exert antioxidant and anti-inflammatory effects .

Anti-adhesion and antibiofilm activities of Lavandula mairei humbert essential oil against Acinetobacter baumannii isolated from hospital intensive care units

This study aimed to assess, for the first time, the anti-adhesion and antibiofilm effects of Lavandula mairei Humbert essential oil against multidrug resistant Acinetobacter baumannii. Scanning electron microscope was used for visualizing its antibiofilm activity and the effect of this oil on surface physicochemical parameters was examined as a possible anti-adhesive target. Chemical analysis of Lavandulaa mairei essential oil showed a high content of carvacrol composition (79.12%). The oil tested exhibited antibacterial efficacy with inhibition diameters of 33 to 37.33 mm and minimum inhibitory and bactericidal concentrations of 1.56 µl ml−1. The oil inhibited adhesion by 83.66%, detach 73.30% of adherent cells and eliminated 64.02% of the biofilm compared to the untreated control. Lavandula mairei essential oil has proven its possible application as a preventive strategy by intervening in the initial adhesion of Acinetobacter baumannii to polystyrene.

Evaluation of the optimal dose for maximizing the anti-adhesion performance of a self-degradable dextran-based material

LYDEX, which is a hydrogel composed of aldehyde-functionalized dextran and succinic anhydride-treated ε-poly-L-lysine, was previously developed by our group as a self-degradable adhesive with an excellent functionality. As a result, this hydrogel has been investigated for a wide range of medical applications, including hemostatic agents, sealants, wound dressings for endoscopes, and anti-adhesion materials. Previously, the unique potential of LYDEX to control the in vivo degradation rate depending on its composition was verified for use in anti-adhesion applications. Although the gel thickness also plays a significant role in determining the degradation rate, this issue was not sufficiently investigated in previous studies. Thus, in the current study, the optimal LYDEX dose (film thickness) for maximizing the anti-adhesion material performance was verified using a rabbit colon model and it was confirmed that the gel film thickness affects the degradation period and anti-adhesion effect. The obtained results suggest the potential for designing LYDEX materials suitable for application at a wider range of in vivo treatment sites, which could be extremely valuable for the development and use of novel anti-adhesion materials with adequate hemostatic and sealant performances.

Superhydrophobic PDMS/SiNPs/T-ZnOw coating with reduced adhesion of Streptococcus mutans for dental caries prevention

The prevention of dental caries is based mainly on killing the cariogenic bacteria Streptococcus mutans. Prevention of S. mutans adhesion through the development of physical structures is rarely utilized. In this study, a superhydrophobic PDMS/SiNPs/T-ZnOw (PST) coating was prepared for use on a bovine tooth by mixing polydimethylsiloxane (PDMS), silicon dioxide nanoparticles (SiNPs), and tetrapod-like zinc oxide whiskers (T-ZnOw) using one-pot solution and spray methods. The results showed that the superhydrophobicity and roughness of the coating, affected by the PDMS content, were positively correlated with the anti-adhesive effect on S. mutans. The PST coating with PDMS, SiNPs, and T-ZnOw at a ratio of 2.5:1:1 exhibited the highest water contact angle (161°) and the best anti-adhesion effect (97.2% at 4 h and 98.1% at 12 h). The anti-adhesion property towards S. mutans was attributed to its needle-like structure, and the biofilm live-dead staining test showed that the coating had no bactericidal effect. In addition, the coating exhibited favorable durability and biocompatibility, providing a solid foundation for application in the human oral cavity. Thus, this study provides an effective method for caries prevention.

Streptococcus salivarius 24SMBc Genome Analysis Reveals New Biosynthetic Gene Clusters Involved in Antimicrobial Effects on Streptococcus pneumoniae and Streptococcus pyogenes

Streptococcus salivarius 24SMBc is an oral probiotic with antimicrobial activity against the otopathogens Streptococcus pyogenes and Streptococcus pneumoniae. Clinical studies have reinforced its role in reducing the recurrence of upper respiratory tract infections (URTIs) and rebalancing the nasal microbiota. In this study, for the first time, we characterized 24SMBc by whole genome sequencing and annotation; likewise, its antagonistic activity vs. Streptococcus pneumoniae and Streptococcus pyogenes was evaluated by in vitro co-aggregation and competitive adherence tests. The genome of 24SMBc comprises 2,131,204 bps with 1933 coding sequences (CDS), 44 tRNA, and six rRNA genes and it is categorized in 319 metabolic subsystems. Genome mining by BAGEL and antiSMASH tools predicted three novel biosynthetic gene clusters (BGCs): (i) a Blp class-IIc bacteriocin biosynthetic cluster, identifying two bacteriocins blpU and blpK; (ii) an ABC-type bacteriocin transporter; and (iii) a Type 3PKS (Polyketide synthase) involved in the mevalonate pathway for the isoprenoid biosynthetic process. Further analyses detected two additional genes for class-IIb bacteriocins and 24 putative adhesins and aggregation factors. Finally, in vitro assays of 24SMBc showed significant anti-adhesion and co-aggregation effects against Streptococcus pneumoniae strains, whereas it did not act as strongly against Streptococcus pyogenes. In conclusion, we identified a novel blpU-K bacteriocin-encoding BGC and two class-IIb bacteriocins involved in the activity against Streptococcus pneumoniae and Streptococcus pyogenes; likewise the type 3PKS pathway could have beneficial effects for the host including antimicrobial activity. Furthermore, the presence of adhesins and aggregation factors might be involved in the marked in vitro activity of co-aggregation with pathogens and competitive adherence, showing an additional antibacterial activity not solely related to metabolite production. These findings corroborate the antimicrobial activity of 24SMBc, especially against Streptococcus pneumoniae belonging to different serotypes, and further consolidate the use of this strain in URTIs in clinical settings.

Vathasura Kudineer, an Andrographis based polyherbal formulation exhibits immunomodulation and inhibits chikungunya virus (CHIKV) under invitro conditions

Ethnopharmacological relevanceChikungunya disease (CHIKD) is caused by the alphavirus, chikungunya virus (CHIKV) and is characterized by acute fever and joint inflammation; the inflammation continues even after clearance of the virus from the system, persisting for several months to years. Currently, there are no modern medicines/vaccines available for its treatment and use of over-the-counter anti-inflammatory generic medicines to relieve symptoms is generally practiced. In India, Indian traditional medicines hold a lot of promise to treat this infection and are routinely used during outbreaks. Aim of the studyIn the present study, we characterized the phytochemical and physicochemical properties of aqueous and ethanol extracts of the Vathasura Kudineer (VSK), a Andrographis based Siddha polyherbal formulation. Additionally, we evaluated its immunomodulatory and antiviral potential using an in vitro system. Materials and methodsAqueous and ethanolic extracts of VSK were prepared and their physico and phytochemical properties were obtained by biochemical and biophysical assays, HPTLC and FTIR. The aqueous extracts of VSK and several of its ingredients were evaluated for their cytotoxicity in Vero cells and using the maximum non-toxic concentration (MNTC), were processed further for evaluating their ability to inhibit CHIKV infection in Vero cells. We performed the co-treatment assay with ethanol extract of VSK and several of its ingredients to assess the antiviral activity against chikungunya virus on Vero cells and through pre-treatment assay (anti-adhesive effect), co-incubation assay (virucidal effect) and post-treatment assay (post-entry effect) were evaluated. Further, we tested the aqueous extract of VSK along with some of its ingredients for their immunomodulatory properties. We performed antioxidant and anti-inflammatory assays using LPS-simulated RAW 264.7 cells. For antioxidant capacity of extracts, we performed extra-cellular ABTS radical scavenging activity and intra-cellular effects on ROS generation and SOD activity. We assessed the effect on most important inflammatory mediators like Nitric oxide (NO) and Prostaglandin E2 (PGE2) and pro-inflammatory cytokines like interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNFα). ResultsWe provided the fingerprint of the phytochemicals of both ethanol and aqueous extracts of VSK that can be used for identification. We observed that ethanol extract was able to inhibit CHIKV infection at MNTC with 48 h of treatment on Vero cells. Its ingredient VSKI-As (Anethum sowa) found to be most effective to show virucidal effect while VSKI-Cs (Clerodendrum serratum) and VSKI-Pn (Pipper nigrum) found to be effective in post-entry effect. VSK was able to show ABTS radical scavenging activity, reduce ROS generation, inhibit the inflammatory mediators (NO and PGE2) and pro-inflammatory cytokines (IL-1β and TNFα) production in LPS-stimulated RAW 264.7 cells. ConclusionsWe provided the evidence that VSK has both immunomodulatory as well as antiviral potential. It shows virucidal as well as post-entry effects on chikungunya virus. VSK can inhibit pro-inflammatory cytokines, IL-1β and TNFα production by suppressing the inflammatory mediators, NO and PGE2.

In vitro physicochemical and biological properties of titanium alloy, zirconia, polyetheretherketone, and carbon fiber-reinforced polyetheretherketone

Implant repair is a common means to restore the normal function of the hard tissues (bone or teeth). At present, the commonly and potentially used implant materials include titanium alloy (Ti), zirconia (Zr), polyetheretherketone (PEEK), and 30% carbon fiber reinforced PEEK (CFR-PEEK). This study compares their physicochemical and biological properties, including surface morphology, contact angle, nano hardness, elastic modulus, and the impact on the proliferation and osteogenic differentiation of bone marrow mesenchyml stem cell. Additionally, the differences in bacteria adhesion rates among materials were compared. CFR-PEEK had the highest contact angle, followed by PEEK, Zr, and Ti. Zr had the highest nano hardness and modulus of elasticity, followed by Ti, CRF-PEEK, and PEEK. There was no statistically significant difference in cytotoxicity among materials based on the liquid extract test. However, the relative cell proliferation rate on the surface of CFR-PEEK was slightly lower than that of Ti and Zr. Moreover, alkaline phosphatase activity, extracellular matrix mineralization, and osteogenic gene expression with the Ti and Zr materials were higher than with the PEEK and CFR-PEEK materials at Day 7, and Zr showed the highest osteogenic gene expression level among materials at Day 14. Ti had the greatest number of bacterial colonies that adhered to it, followed by Zr, CFR-PEEK, and PEEK. While the mechanical properties of PEEK and CFR-PEEK were closer to bone tissue and their anti-adhesion effect against bacteria was better than those of Ti and Zr, modification methods are needed to improve the osteogenic properties of these biopolymers.

Paraoxonase 1 gene polymorphisms in lipid oxidation and atherosclerosis development.

Paraoxonase 1 (PON1) is calcium-dependent aryldialkylphosphatase, thought to possess; anti-oxidant, anti-adhesion, anti-inflammatory, anti-thrombosis and anti-apoptosis effects, as well as lipid-modifying properties. Numerous clinical studies have shown associations between different PON1 polymorphisms and different cardiovascular pathologies. The rs622 (c.575A > G) and the rs854560 (c.163A > T) are the most studied PON1 SNPs in the coding region, with rs705381 (− 162A/G), rs854572 (− 909G/C) and rs705379 (− 108C/T) being the most studied SNPs in the regulatory PON1 gene region. The three major PON1 activities are aryldialkylphosphatase, arylesterase and lactonase activity. The different SNPs affect PON1 serum concentrations and enzyme activity, thus leading to pro-/anti-atherogenic effects. In that setting, it is very difficult to establish as to whether the genotype or phenotype of PON1 is primarily associated with cardiovascular risk. Given the current scientific evidence, PON1 genotyping might be reasonable in patients with high and very high cardiovascular risk.

Attenuation of Pseudomonas aeruginosa Quorum Sensing Virulence of Biofilm and Pyocyanin by mBTL-Loaded Calcium Alginate Nanoparticles.

Pseudomonas aeruginosa contributes to many chronic infections and has been found to be resistant to multiple antibiotics. Pseudomonas use a quorum sensing system (QS) to control biofilm establishment and virulence factors, and, thus, quorum sensing inhibitors (QSIs), such as meta-bromo-thiolactone (mBTL), are promising anti-infective agents. Accordingly, this study intended to investigate the antibacterial and anti-virulence activity of mBTL-loaded calcium alginate nanoparticles (CANPs) against Pseudomonas aeruginosa and different QS mutants. The results show that the mBTL-CANPs had higher antibacterial activity, which was made evident by decreases in all tested strains except the ∆lasR/∆rhlR double mutant, with MIC50 (0.5 mg/mL) of mBTL-CANPs compared with free mBTL at MIC50 (˃1 mg/mL). The biofilm formation of P. aeruginosa and some QS-deficient mutants were reduced in response to 0.5–0.125 mg/mL of mBTL-encapsulating CANPs. The pyocyanin production of the tested strains except ∆lasA and ∆rhlR decreased when challenged with 0.5 mg/mL of mBTL-loaded NPs. The subsequent characterization of the cytotoxic effect of these NPs on human lung epithelial cells (A549) and cystic fibrosis fibroblast cells (LL 29) demonstrated that synthesized NPs were cytocompatible at MIC50 in both cell lines and markedly reduced the cytotoxic effect observed with mBTL alone on these cells. The resulting formulation reduced the P. aeruginosa strains’ adhesion to A549 comparably with mBTL, suggesting their potential anti-adhesive effect. Given the virulence suppressing action, cytocompatibility, and enhanced anti-biofilm effect of mBTL-CANPs, and the advantage of alginate-based NPs as an antimicrobial delivery system these nanoparticles have great potential in the prophylaxis and treatment of infection caused by Pseudomonas aeruginosa.

D-mannose for preventing and treating urinary tract infections.

Urinary tract infections (UTIs) are very common, affecting more than 7 million people worldwide. Whilst many people may only experience a single episode in their lifetime and are generally responsive to standard antibiotics, a significant proportion of adults and children (approximately 15% to 25%) are chronic symptomatic UTI sufferers. Certain population groups are at greater risk than others, such as immunosuppressed and people with chronic kidney disease. D-mannose is a sugar part of normal human metabolism found within most diets. The mechanism of action is to prevent bacterial adherence to the uroepithelial cells. The D-mannose-based inhibitors can block uropathogenic Escherichia coli adhesion and invasion of the uroepithelial cells. The bacteria are then understood to essentially be eliminated by urination. Early pilot studies on animals and humans have trialled concentrated forms of D-mannose (tablets or sachets) in doses ranging from 200 mg up to 2 to 3 g and found possible efficacy in reducing UTI symptoms or recurrence. Although the anti-adhesive effects of D-mannose have been well-established, only recently have we seen a small number of pilot studies and small clinical trials conducted. To assess the benefits and harms of D-mannose for preventing and treating UTIs in adults and children. We searched the Cochrane Kidney and Transplant Register of Studies up to 22 February 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We included RCTs measuring and reporting the effect of D-mannose, in any combination and any formulation, to prevent or treat UTIs in adults and children, females and males, in any setting (including perioperative). Authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria. Data extraction was independently carried out by two authors using a standard data extraction form. Methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another author. The certainty of the evidence was assessed using the GRADE approach. We included seven RCTs (719 participants) in adult females and males who had either acute cystitis or a history of recurrent (at least two episodes in six months or three episodes in 12 months) UTIs (symptomatic or asymptomatic). Two were prevention studies, four were prevention and treatment studies (two perioperative and one in people with multiple sclerosis), and one was a treatment study. Time periods ranged from 15 days to six months. No two studies were comparable (by dose or treatments), and we could not undertake meta-analyses. Individual studies reported no clear evidence to determine whether D-mannose is more or less effective in preventing or treating UTIs. D-mannose (2 g) had uncertain effects on symptomatic and bacteriuria-confirmed UTIs when compared to no treatment (1 study, 205 participants; very low certainty evidence) and antibiotics (nitrofurantoin 50 mg) (1 study, 206 participants; very low certainty evidence). D-mannose, in combination with herbal supplements, had uncertain effects on symptomatic and bacteria-confirmed UTI and pain when compared to no treatment (1 study, 40 participants; very low certainty evidence). D-mannose 500 mg plus supplements (N-acetylcysteine and Morinda citrifolia fruit extract) had uncertain effects on symptomatic and bacteriuria-confirmed UTIs when compared to an antibiotic (prulifloxacin 400 mg) (1 study, 75 participants; very low certainty evidence). Adverse events were very few and poorly reported; none were serious (mostly diarrhoea and vaginal burning). Overall, the quality of the evidence is poor. Most studies were judged to have unclear or high risk of bias across most domains. Data was sparse and addressed very few outcomes. The GRADE evaluation was rated as very low certainty evidence due to very serious limitations in the study design or execution (high risk of bias across all studies) and sparse data (single study data and small sample sizes). There is currently little to no evidence to support or refute the use of D-mannose to prevent or treat UTIs in all populations. This review highlights the severe lack of high-quality RCTs testing the efficacy of D-mannose for UTIs in any population. Despite UTIs being one of the most common adult infections (affecting 50% of women at least once in their lifetime) and the growing global antimicrobial resistance, we found very few studies that adequately test this alternative treatment. Future research in this field requires, in the first instance, a single adequately powered RCT comparing D-mannose with placebo.

Collagen Type-I Agent Reduced Postoperative Bowel Adhesions Following Laparoscopic and Robot-Assisted Radical Prostatectomy: A Prospective, Single-Blind Randomized Clinical Trial.

This study aimed to compare the anti-adhesive effect of collagen type-I (COL) agent and hyaluronic acid-carboxymethylcellulose (HA/CMC) following laparoscopic and robotic radical prostatectomies. This study was a randomized, controlled, single-blind, multicenter study using COL and HA/CMC in patients who underwent laparoscopic and robotic radical prostatectomies. All patients were randomly assigned to either the COL (n = 66) or HA/CMC (n = 65) group. Viscera slide ultrasound sonography was recorded on the day of surgery (V2) and 12 weeks later (V4). The primary end point was the difference in the excursion distance in the viscera slide ultrasonography between V2 and V4. A total of 131 patients participated in this study. The viscera slide distance in the test and control groups was 1.89 ± 0.49 cm and 1.80 ± 0.45 cm, respectively, at V2 (p = 0.275). The average distance of the viscera slide in the test and control group was 1.59 ± 0.49 cm and 1.64 ± 0.45 cm, respectively at V4 (p = 0.614). None of the patients showed significant adverse effects. This randomized study showed that the efficacy and stability of the gel-type COL anti-adhesion agent are not inferior to those of HA/CMC, of which the properties are established.

Combined treatment of xyloglucan derivative hydrogel and anti-C5a receptor antibody in preventing peritoneal adhesion

Postoperative peritoneal adhesion is a common complication after surgery with high morbidity. In addition to improving surgical operations, medical therapy and physical barriers are the two main ways to prevent postoperative peritoneal adhesion. Satisfactory efficacy is not often obtained by the single antiadhesion method, and the combination of barrier therapy and antiadhesion drugs has attracted more attention. In this study, we first demonstrated that aberrant complement activation was associated with peritoneal injury and inflammatory responses. Correspondingly, blocking the C5a-C5aR axis reaction effectively reduced inflammatory reactions. Therefore, we creatively developed an integrated treatment of xyloglucan derivative (mXG) hydrogel and intravenous anti-C5a receptor antibody (anti-C5aRab) aimed at peritoneal adhesion, and then systematically evaluated the therapeutic efficacy using a sidewall defect-cecum abrasion model in mice. In vitro and in vivo experiments showed that the mXG hydrogel had good biocompatibility and degradability and could serve as a safe anti-adhesion barrier. The results showed that anti-C5aRab treatment could significantly inhibit peritoneal adhesions by reducing neutrophil infiltration and the expression of phosphorylated Smad2. Taken together, the mXG hydrogel integrated with anti-C5aRab showed superior antiadhesion performance and holds promising clinical applications in preventing peritoneal adhesion. STATEMENT OF SIGNIFICANCE: Postoperative peritoneal adhesion is an urgent problem to be solved after surgery. Previously, a biodegradable and thermoreversible xyloglucan derivative (mXG) hydrogel was developed that effectively prevented postoperative peritoneal adhesions, but obvious inflammatory responses and proliferation could still be observed. In addition, aberrant complement activation is associated with a variety of inflammatory diseases. We demonstrated that aberrant complement activation is involved in peritoneal adhesion. In this work, mXG hydrogel and intravenous anti-C5a receptor antibody (anti-C5aRab) were integrated to address peritoneal adhesions. The anti-C5aRab reduced the inflammatory responses. In addition, the mXG hydrogel was easy to use and effectively isolated the wound surface at the local injury site. Overall, this integrated treatment significantly improved the antiadhesion effect.

Antioxidant and Antimicrobial Properties of Helichrysum italicum (Roth) G. Don Hydrosol.

(1) Background: According to the emergence and spread of antibiotic resistance, there is an urge for new promising substances. The purpose of the study was to test the antioxidant, cytotoxic and antimicrobial properties of the Helichrysum italicum (Roth) G. Don essential oil (EO) and hydrosol. (2) Methods: The antioxidant potential was determined using the DPPH (2,2-diphenyl-1-picrylhydrazyl) method. The cytotoxicity for human skin and intestinal cells was tested using primary and immortalized cell line models. The minimum inhibitory concentration (MIC) of hydrosol was then determined for six bacterial strains covering four commonly reported food pathogens. Further on, the hydrosol at a concentration of 1/8 MIC was used to test the antiadhesive effect by the crystal violet (CV) staining method. (3) Results: the EO showed a 100-times higher antioxidant and 180- to 25.000-times higher cytotoxic activity, when compared to hydrosol. Nevertheless, all bacterial strains, with the exception of Staphylococcus aureus, were sensitive to hydrosol in the range of 12.5% (V/V) for Campylobacter jejuni, to MIC values of 100% (V/V) for Escherichia coli and Pseudomonas aeruginosa. The antiadhesive potential of hydrosol was also shown. (4) Conclusions: Even though hydrosols are a by-product of the EO distillation process, they possess valuable biological activities.