Plant-derived bioactive compounds for the inhibition of biofilm formation: a comprehensive review.

Biofilm formation is a widespread phenomenon that impacts different fields, including the food industry, agriculture, health care and the environment. Accordingly, there is a serious need for new methods of managing the problem of biofilm formation. Natural products have historically been a rich source of varied compounds with a wide variety of biological functions, including antibiofilm agents. In this review, we critically highlight and discuss the recent progress in understanding the antibiofilm effects of several bioactive compounds isolated from different plants, and in elucidating the underlying mechanisms of action and the factors influencing their adhesion. The literature shows that bioactive compounds have promising antibiofilm potential against both Gram-negative and Gram-positive bacterial and fungal strains, via several mechanisms of action, such as suppressing the formation of the polymer matrix, limiting O2 consumption, inhibiting microbial DNA replication, decreasing hydrophobicity of cell surfaces and blocking the quorum sensing network. This antibiofilm activity is influenced by several environmental factors, such as nutritional cues, pH values, O2 availability and temperature. This review demonstrates that several bioactive compounds could mitigate the problem of biofilm production. However, toxicological assessment and pharmacokinetic investigations of these molecules are strongly required to validate their safety.

Petroselinum crispum L., essential oil as promising source of bioactive compounds, antioxidant, antimicrobial activities: In vitro and in silico predictions.

This exploratory study aims to identify the volatile compounds in PC-Eo (Petroselinum crispum L. essential oil) and evaluate its antioxidant and antimicrobial properties in vitro. Molecular docking, drug-likeness prediction, and pharmacokinetics (absorption, distribution, metabolism, excretion, and toxicity-ADMET) were among the in silico simulations that were used to explain the biological properties observed in vitro. For PC-Eo's chemical screening, gas chromatography-mass spectrophotometry (GC-MS) was employed. The antioxidant activity of PC-Eo was evaluated using five in vitro complementary techniques, including 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) radical scavenging activity, ß-Carotene bleaching test (BCBT), reducing power (RP), and phosphomolybdenum assay (TAC). GC-MS analysis revealed that the primary components of PC-Eo are apiol (49.05 %), Myristicin (21.01 %), and 1-allyl-2,3,4,5-tetramethoxybenzene (13.14 %). The results of the in vitro antioxidant assays indicate that PC-Eo exhibits a superior antioxidant profile. The in vitro antimicrobial activity of PC-Eo was assessed against five strains, including 2 g-positive bacteria, 2 g-negative bacteria, and one fungal strain (Candida albicans). The disc-diffusion assay revealed significant antibacterial and antifungal activities against all strains, with zones of inhibition exceeding 15 mm. The microdilution test highlighted the lowest MIC and MBC values with gram-positive bacteria, ranging from 0.25 to 0.5 % v/v for MIC and 0.5-1.0 % v/v for MBC. For the fungal strain, MIC was recorded at 1.25 % and MFC at 2.5 % v/v. PC-Eo demonstrates bactericidal and fungicidal activity based on the MBC/MIC and MFC/MIC ratios. According to the ADMET study, the primary PC-Eo compounds have advantageous pharmacokinetic characteristics. These findings provide empirical support for the traditional uses of this plant and indicate its possible use as a natural remedy.

The Anti-urolithiatic effect of the roots of Saussurea costus (falc) Lipsch agonist ethylene glycol and magnesium oxide induced urolithiasis in rats.

Phytotherapy, which involves the use of plant extracts and natural compounds for medicinal purposes, is indeed a promising alternative for managing urinary lithiasis. Many plants have been studied for their potential to prevent and treat kidney stones, and they may offer a more natural and potentially less harmful approach compared to conventional treatments. Additionally, phytotherapy may be more cost-effective. The aim of the present study was to investigate the antilithic potential of extracts and essential oils of Saussurea costus (Falc) Lipsch in two in vivo models, one on ethylene glycol-induced calcium oxalate crystal formation and the other to assess the effects of these extracts on magnesium oxide-induced struvite crystal formation. The experiment involved the administration of different doses of aqueous and ethanolic extracts of S. costus (200 and 400 mg/kg) and essential oils (25 and 50 mg/kg) to male Wistar rats, followed by the evaluation of various physiological, biochemical and histopathological parameters. The results demonstrated that the administration of S. costus essential oils and extracts had significant effects on the rats, influencing body weight, urine volume, crystal deposition, cytobacteriological examination of urine, and serum biochemical parameters. Histopathological examinations revealed varying impacts on the kidneys and livers of the treated rats. The findings suggest that S. costus extracts and essential oils may hold promise in inhibiting calcium oxalate crystal formation in vivo and influencing various physiological and biochemical parameters in rats. Overall, the 200 mg/kg ethanolic extract of S. costus demonstrated antilithiatic efficacy, did not exhibit signs of toxicity and reduced the number of crystals in the kidneys. Furthermore, the study did not find a significant effect on reducing struvite crystals.

Second-year results from CINEMA: A novel, patient-centered, team-based intervention for patients with Type 2 diabetes or prediabetes at high cardiovascular risk.

Background: The care for patients with type 2 diabetes mellitus (T2DM) necessitates a multidisciplinary team approach to reduce cardiovascular (CV) risk but implementation of effective integrated strategies has been limited. Methods and Results: We report 2-year results from a patient-centered, team-based intervention called CINEMA at University Hospitals Cleveland Medical Center. Patients with T2DM or prediabetes at high-risk for CV events, including those with established atherosclerotic CVD, elevated coronary artery calcium score ≥100, chronic heart failure with reduced ejection fraction, chronic kidney disease (CKD) stages 2-4, and/or prevalent metabolic syndrome were included. From May 2020 through September 2022, 426 patients were enrolled in the CINEMA program. A total of 227 (54%) completed ≥1 follow-up visit after an initial baseline visit with median (IQR) follow-up time 4 [3], [4], [5], [6], [7] months with maximum follow-up time 19 months. Mean age was 60 years, 47 % were women, and 37 % were Black and 85% had prevalent T2DM, 48 % had established ASCVD, 29% had chronic HF, 27% had CKD and mean baseline 10-year ASCVD risk estimate was 25.1 %; baseline use of a SGLT2i or GLP-1RA was 21 % and 18 %, respectively. Patients had significant reductions from baseline in body weight (-5.5 lbs), body mass index (-0.9 kg/m2), systolic (-3.6 mmHg) and diastolic (-1.2 mmHg) blood pressure, Hb A1c (-0.5 %), total (-10.7 mg/dL) and low-density lipoprotein (-9.0 mg/dL) cholesterol, and triglycerides (-13.5 mg/dL) (p<0.05 for all). Absolute 10-year predicted ASCVD risk decreased by ∼2.4 % (p<0.001) with the intervention. In addition, rates of guideline-directed cardiometabolic medication prescriptions significantly increased during follow-up with the most substantive changes seen in rates of SGLT2i and GLP-1RA use which approximately tripled from baseline (21 % to 57 % for SGLT2i and 18 % to 65 % for GLP-1RA, p<0.001 for both). Conclusions: The CINEMA program, an integrated, patient-centered, team-based intervention for patients with T2DM or prediabetes at high risk for cardiovascular disease has continued to demonstrate effectiveness with significant improvements in ASCVD risk factors and improved use of evidence-based therapies. Successful implementation and dissemination of this care delivery paradigm remains a key priority.

Crohn's disease proteolytic microbiota enhances inflammation through PAR2 pathway in gnotobiotic mice.

Emerging evidence implicates microbial proteolytic activity in ulcerative colitis (UC), but whether it also plays a role in Crohn's disease (CD) remains unclear. We investigated the effects of colonizing adult and neonatal germ-free C57BL/6 mice with CD microbiota, selected based on high (CD-HPA) or low fecal proteolytic activity (CD-LPA), or microbiota from healthy controls with LPA (HC-LPA) or HPA (HC-HPA). We then investigated colitogenic mechanisms in gnotobiotic C57BL/6, and in mice with impaired Nucleotide-binding Oligomerization Domain-2 (NOD2) and Protease-Activated Receptor 2 (PAR2) cleavage resistant mice (Nod2-/-; R38E-PAR2 respectively). At sacrifice, total fecal proteolytic, elastolytic, and mucolytic activity were analyzed. Microbial community and predicted function were assessed by 16S rRNA gene sequencing and PICRUSt2. Immune function and colonic injury were investigated by inflammatory gene expression (NanoString) and histology. Colonization with HC-LPA or CD-LPA lowered baseline fecal proteolytic activity in germ-free mice, which was paralleled by lower acute inflammatory cell infiltrate. CD-HPA further increased proteolytic activity compared with germ-free mice. CD-HPA mice had lower alpha diversity, distinct microbial profiles and higher fecal proteolytic activity compared with CD-LPA. C57BL/6 and Nod2-/- mice, but not R38E-PAR2, colonized with CD-HPA had higher colitis severity than those colonized with CD-LPA. Our results indicate that CD proteolytic microbiota is proinflammatory, increasing colitis severity through a PAR2 pathway.

Lessons Learned From a Patient-Centered, Team-Based Intervention for Patients With Type 2 Diabetes at High Cardiovascular Risk: Year 1 Results From the CINEMA Program.

Background The care for patients with type 2 diabetes necessitates a multidisciplinary team approach to reduce cardiovascular risk, but implementation of effective integrated strategies has been limited. Methods and Results We conceptualized and initiated a patient-centered, team-based intervention called Center for Integrated and Novel Approaches in Vascular-Metabolic Disease (CINEMA) at University Hospitals Cleveland Medical Center. Patients with type 2 diabetes at high risk for cardiovascular events, including those with established atherosclerotic cardiovascular disease, elevated coronary artery calcium score >100, chronic heart failure with reduced ejection fraction, and/or chronic kidney disease stages 2 to 4 were included. Herein, we present the year 1 results for the program. From May 2020 through August 2021, there were 417 referrals. Among 206 eligible patients, 113 (55%) completed a baseline and ≥1 follow-up visit through December 2021, with mean (SD) time of 105 (34) days between baseline and first follow-up visits. Mean age was 59 years, with 49% women and 37% Black patients. Patients had significant reductions from baseline in glycosylated hemoglobin (-10.8%), total cholesterol (-7.9%), low-density lipoprotein cholesterol (-13.5%), systolic blood pressure (-4.0%), and body mass index (-2.7%) (P≤0.001 for all). In addition, among the 129 (63%) eligible patients not on sodium-glucose cotransporter 2 inhibitor or glucagon-like peptide-1 receptor agonist at baseline, 81% were prescribed evidence-based therapy with sodium-glucose cotransporter 2 inhibitor (n=66 [51%]) and/or glucagon-like peptide-1 receptor agonist (n=67 [52%]) to reduce the risk of cardiovascular disease in the initial 3-month follow-up period. Conclusions A team-based, patient-centered approach to high-risk disease management appears to be a promising paradigm for care delivery associated with greater use of evidence-based therapies and improved control of multiple cardiovascular risk factors.

Antibiotic-Impregnated Liquid-Infused Coatings Suppress the Formation of Methicillin-Resistant Staphylococcus aureus Biofilms.

Medical device-associated infections are an ongoing problem. Once an implant is infected, bacteria create a complex community on the surface known as a biofilm, protecting the bacterial cells against antibiotics and the immune system. To prevent biofilm formation, several coatings have been engineered to hinder bacterial adhesion or viability. In recent years, liquid-infused surfaces (LISs) have been shown to be effective in repelling bacteria due to the presence of a tethered liquid interface. However, local lubricant loss or temporary local displacement can lead to bacteria penetrating the lubrication layer, which can then attach to the surface, proliferate, and form a biofilm. Biofilm formation on biomedical devices can subsequently disrupt the chemistry tethering the slippery liquid interface, causing the LIS coating to fail completely. To address this concern, we developed a "fail-proof" multifunctional coating through the combination of a LIS with tethered antibiotics. The coatings were tested on a medical-grade stainless steel using contact angle, sliding angle, and Fourier transform infrared spectroscopy. The results confirm the presence of antibiotics while maintaining a stable and slippery liquid interface. The antibiotic liquid-infused surface significantly reduced biofilm formation (97% reduction compared to the control) and was tested against two strains of Staphylococcus aureus, including a methicillin-resistant strain. We also demonstrated that antibiotics remain active and reduce bacteria proliferation after subsequent coating modifications. This multifunctional approach can be applied to other biomaterials and provide not only a fail-safe but a fail-proof strategy for preventing bacteria-associated infections.

Polysiloxane Nanofilaments Infused with Silicone Oil Prevent Bacterial Adhesion and Suppress Thrombosis on Intranasal Splints.

Like all biofluid-contacting medical devices, intranasal splints are highly prone to bacterial adhesion and clot formation. Despite their widespread use and the numerous complications associated with infected splints, limited success has been achieved in advancing their safety and surface biocompatibility, and, to date, no surface-coating strategy has been proposed to simultaneously enhance the antithrombogenicity and bacterial repellency of intranasal splints. Herein, we report an efficient, highly stable lubricant-infused coating for intranasal splints to render their surfaces antithrombogenic and repellent toward bacterial cells. Lubricant-infused intranasal splints were prepared by creating superhydrophobic polysiloxane nanofilament (PSnF) coatings using surface-initiated polymerization of n-propyltrichlorosilane (n-PTCS) and further infiltrating them with a silicone oil lubricant. Compared with commercially available intranasal splints, lubricant-infused, PSnF-coated splints significantly attenuated plasma and blood clot formation and prevented bacterial adhesion and biofilm formation for up to 7 days, the typical duration for which intranasal splints are kept. We further demonstrated that the performance of our engineered biointerface is independent of the underlying substrate and could be used to enhance the hemocompatibility and repellency properties of other medical implants such as medical-grade catheters.

Intestinal organoids: A new paradigm for engineering intestinal epithelium in vitro.

In recent years, the advent of intestinal organoid culture systems has revolutionized in vitro studies of the small intestine epithelium. Intestinal organoids are derived from self-organizing and self-renewing intestinal stem cells and closely recapitulate the native intestinal epithelium. They therefore represent a more physiologically-relevant in vitro model than conventional cell cultures for studying intestinal development, biology and pathophysiology. Moreover, they represent a promising and unprecedented new tool in the realm of regenerative and personalized medicine. In this review, we outline the current approaches to develop intestinal organoids and describe the strategies used to induce complexity, multicellularity and modularity in organoid culture systems; this knowledge will contribute to improved biomimicry of the organoid culture system. We focus on co-culture systems and explore the convergence of organoid technology and engineering principals. Finally, we describe applications of intestinal organoids in various fields.

Probing the interaction of silver nanoparticles with tau protein and neuroblastoma cell line as nervous system models.

Interestingly pharmaceutical sciences are using nanoparticles (NPs) to design and develop nanomaterials-based drugs. However, up to recently, it has not been well realized that NPs themselves may impose risks to the biological systems. In this study, the interaction of silver nanoparticles (AgNPs) with tau protein and SH-SY5Y neuroblastoma cell line, as potential nervous system models, was examined with a range of techniques including intrinsic fluorescence spectroscopy, circular dichroism (CD) spectroscopy, 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and acridine orange/ethidium bromide (AO/EB) dual staining method. Fluorescence study showed that AgNPs with a diameter of around 10-20 nm spontaneously form a static complex with tau protein via hydrogen bonds and van der Waals interactions. CD experiment revealed that AgNPs did not change the random coil structure of tau protein. Moreover, AgNPs showed to induce SH-SY5Y neuroblastoma cell mortality through fragmentation of DNA which is a key feature of apoptosis. In conclusion, AgNPs may induce slight changes on the tau protein structure. Also, the concentration of AgNPs is the main factor which influences their cytotoxicity. Since, all adverse effects of NPs are not well detected, so probably additional more specific testing would be needed.

Increasing angulation decreases measured aortic stent graft pullout forces.

OBJECTIVE: Experimentally measured pullout forces for stent grafts (SGs) are used in clinical discussions and as reference values in bench studies and computer simulations. Previous values of these forces are available from studies in which the SG was pulled out in the straight caudal direction. However, clinical and numerical studies have suggested that displacement forces acting on SGs are directed more anteriorly. The objective of this study was to measure pullout forces as a function of angulation and to test the hypothesis that pullout forces decrease with increasing angulation. METHODS: Six different SGs (Bolton Treovance, Cook Zenith Flex, Cook Zenith LP, Medtronic Endurant, Medtronic Talent, and Vascutek Anaconda) were deployed in fresh bovine aortas, then pulled out by an electronic motor at 1 mm/s, while tension force was measured continuously with a digital load cell. The SG off-axis angulation was changed from 0 to 90 degrees in increments of 10 degrees. The test system was submerged in a custom-built temperature-controlled saline bath at 37°C. At least three tests were performed for each device at each angle (with the exception of the Cook Zenith Flex, which experienced plastic deformation of its barbs after a single test per device). Each aortic specimen was used only once and then discarded. Hand-sutured graft anastomoses were also tested at 0 degrees to provide a reference value. RESULTS: A total of 374 pullout tests were performed for the SGs and anastomoses. Sixty-four tests were excluded because of failure of the aorta or apparatus before device pullout. The remaining 310 tests showed pullout forces that demonstrated a decrease in the average pullout force for all six devices from 0 to 90 degrees (Bolton Treovance from 39.3 N to 23.9 N; Cook Zenith Flex from 59.8 N to 48.9 N; Cook Zenith LP from 50.3 N to 41.8 N; Medtronic Endurant from 29.9 N to 25.8 N; Medtronic Talent from 6.0 N to 5.5 N; and Vascutek Anaconda from 37.0 N to 30.3 N). For reference, the mean pullout force for the hand-sutured anastomoses was 63 N. CONCLUSIONS: This study reports for the first time the change in pullout force with angulation, showing a general pullout force decrease with increasing angle. With a larger number of samples than in previous studies, our results provide updated benchmark data that can be used for clinical discussions, computational and experimental studies, and future device design.