Synergistic antibacterial effect of the pistachio green hull extract-loaded porphysome decorated with 4-nitroimidazole against bacteria.

'Active targeting' refers to modifying a nanocarrier's surface with targeting ligands. This study introduced an efficient approach for immobilizing imidazole-based drugs onto the metallated-porphyrin complex within the porphysome nanocarrier. To enhance cellular and bacterial uptake, a Ni-porphyrin with a fatty acid tail was synthesized and placed in the bilayer center of DPPC, facilitating receptor-mediated endocytosis. The Ni-porphyrin in the head group of the Ni-porphyrin-tail was placed superficially in the polar region of the membrane. Spherical unilamellar vesicle formation (DPPC: Ni-porphyrin-tail 4:1 mole ratio), as metallo-porphysome, was achieved through supramolecular self-assembly in an aqueous buffer. These vesicles exhibited a diameter of 279 ± 7 nm and a zeta potential of -15.3 ± 2.5 mV, showcasing their unique cytocompatibility. Nitroimidazole was decorated on the surface of metallo-porphysomes and pistachio green hull extract (PGHE) was loaded into the carrier for synergistic activity against (E. coli) and (S. aureus) bacteria strains. The physicochemical properties of Nitroimidazole-porphysome-PGHE, including size, zeta potential, morphology, loading efficiency, and release profile under various pH and temperature conditions in simulated gastrointestinal fluids were characterized. This combination therapy prevented bacterial cell attachment and biofilm formation in Caco-2 cells, as colon epithelial cells. The remarkable benefit of this system is that it does not affect cell viability even at 0.5 mg/ml. This study demonstrates the potential of a new co-delivery system using biocompatible metallo-porphysomes to decrease bacterial infections.

Porphysome Engineered With Specific Protein Binding Sites as a Multimodal Theranostic Nanocarrier for Targeted Protein Delivery.

The immobilization of proteins on the surface of carriers is challenging due to the loss of protein structure and function in this process. Here, we report the development of the protein immobilization on the surface of the metallated-porphyrin complex in the porphysome nanocarrier. The conjugated Ni-porphyrin to fatty acid (as a tail) has been synthesized and independently placed at the depth of the bilayer center of Dipalmitoylphosphatidylcholine (DPPC) in which the Ni-porphyrin was at the polar region of the membrane and is thus superficial. This porphysome (DPPC: Ni-porphyrin, 4 : 1 mole ratio) was formed by supramolecular self-assembly with a diameter of 173±7 nm and zeta potential -8.5±3.4 mv, which exhibited no significant toxicity at the experimental concentrations and acceptable cellular uptake on MCF-7 cells. The physicochemical properties and specific protein binding sites of the firefly luciferase as a model protein into the porphysome (1 : 2 mole ratio) show the conjugation efficiency about 80 % and the conformation of protein was completely maintained. Furthermore, bioluminescence assay and SDS-PAGE confirmed the preservation of protein function. The stabilized platform of porphyrin-lipid structure can potentially improve the efficacy of protein functionality for a particular display, shifting porphysomes from a simple carrier to a therapeutic agent.

Hybrid Microfluidic Device for High Throughput Isolation of Cells Using Aptamer Functionalized Diatom Frustules.

Circulating tumor cells (CTCs), secreted from primary and metastatic malignancies, hold a wealth of essential diagnostic and prognostic data for multiple cancers. Significantly, the information contained within these cells may hold the key to understanding cancer metastasis, both individually and fundamentally. Accordingly, developing ways to identify, isolate and interrogate CTCs plays an essential role in modern cancer research. Unfortunately, CTCs are typically present in the blood in vanishingly low titers and mixed with other blood components, making their isolation and analysis extremely challenging. Herein, we report the design, fabrication and optimization of a microfluidic device capable of automatically isolating CTCs from whole blood. This is achieved in two steps, via the passive viscoelastic separation of CTCs and white blood cells (WBCs) from red blood cells (RBCs), and subsequent active magnetophoretic separation of CTCs from WBCs. We detail the specific geometries required to balance the elastic and inertial forces required for successful passive separation of RBCs, and the use of computational fluid dynamics (CFD) to optimize active magnetophoretic separation. We subsequently describe the use of magnetic biosilica frustules, extracted from Chaetoceros sp. diatoms, to fluorescently tag CTCs and facilitate magnetic isolation. Finally, we use our microfluidic platform to separate HepG2-derived CTCs from whole blood, demonstrating exceptional CTC recovery (94.6%) and purity (89.7%).

Mental Health and Prevention of Substance Use Programs in Iran: Component of the National Action Plan for Prevention and Control of Non-communicable Diseases.

Background: Mental disorders have a high prevalence and significant burden among all health conditions across the world and in Iran. Therefore, some targets in the field of mental health and substance and alcohol use prevention have been included in the National Action Plan for Prevention and Control of Non-communicable Diseases and Related Risk Factors. Methods: Keeping in mind the key priorities, important strategies have been considered for attaining the main targets in this field. These strategies fall under four categories of governance, prevention and reduction of risk factors, health care, and surveillance, and monitoring and evaluation strategies. Conclusion: The success of mental health and substance and alcohol use prevention programs in Iran can be partly related to the evidence-based approach adopted and also to the commitment of high-rank officials of the Ministry of Health and Medical Education to the principal strategy of increasing access to the general population to basic mental health services, among all other non-communicable diseases.

Imidazolium-based ionic liquid functionalized mesoporous silica nanoparticles as a promising nano-carrier: response surface strategy to investigate and optimize loading and release process for Lapatinib delivery.

Imidazolium-based ionic liquid functionalized PEGylated mesoporous silica nanoparticles MCM-41 (denoted as [ImIL-PEGylated@MCM-41] NPs) is synthesized and evaluated as an efficient and reliable pH-sensitive nano-carrier for controlled release of cationic Lapatinib (Lap) drug. This nano-DDS was fully characterized by dynamic light scattering, scanning electron microscopy, X-ray powder diffraction, Fourier transform infrared spectroscopy, N2 adsorption-desorption measurement, and differential scanning calorimeter. Furthermore, the drug loading content and in-vitro drug release profile were studied. The entrapment and loading efficiency of the optimized formulation for Lap were 91 ± 2.0% and 32.21 ± 2.70%, respectively. The results of cytotoxicity assay demonstrated that ImIL-PEG@MCM-41 has no significant toxicity on both cancerous and normal cell lines and the anticancer activity of Lap@ImIL-PEG@MCM-41 was comparable to free drug in case of human breast cells (SKBR3) and human embryonic kidney 293 cells (HEK-293). Meanwhile, three-dimensional (3D) cell culture was performed by multicellular tumor spheroids for understanding of cell response to drugs in physiologically 3D microenvironments. The results of Lap@ImIL-PEG@MCM-41 uptake during 48 hours showed a gradual release of the Lap through the multicellular tumor spheroids. This showed that the pH-responsive controlled release of Lapatinib leads to the satisfactory results in the in vitro breast cancer therapy.

Hemoglobin-incorporated iron quantum clusters as a novel fluorometric and colorimetric probe for sensing and cellular imaging of Zn(II) and cysteine.

The authors describe a novel water-soluble, stable, biocompatible, and highly fluorescent probe consisting of iron quantum clusters incorporated into human adult hemoglobin (Hb-FeQCs). The Hb-FeQCs were characterized by various spectroscopic techniques. The probe displays strong absorption and yellow fluorescence with a peak centered at 567 nm (photo-excited at 460 nm). The Hb-FeQCs show excellent photostability over a wide range of pH values (5-12), even in the presence of high electrolyte concentrations. A colorimetric and a fluorometric method were worked out for the quantitation Zn(II) and cysteine in aqueous solution. Zinc ions induce a visible color change from brown to yellow. The sensitivity of Hb-FeQCs towards other metal ions was negligible, with the exception of Co2+ and Cu2+, which caused a modest interference. The Hb-FeQCs were exploited in a sensitive and selective turn-on fluorescence assay for Zn2+. It is also found that cysteine quenches the fluorescence of the Hb-FeQCs/Zn(II) complex. Under the optimized conditions, the probe has a linear response in the 0.04 to 2.2 µM Zn(II) concentration range, with a 48 nM detection limit. Response to cysteine is linear in the 1-60 µM concentration range, with a 0.25 µM limit of detection. This fluorescent probe undergoes fluorescent emission intensity enhancement upon binding to zinc ions in living normal human fibroblast cells under visible lamp. The cellular imaging capability and very low cytotoxicity of this soluble iron quantum clusters can be potentially extended as an exciting sub-nanoplatform with promising biomaterial applications. Graphical abstract Schematic of yellow-emitting iron quantum clusters in hemoglobin matrix (Hb-FeQCs) were characterized and successfully applied for sensing zinc(II) and cysteine. The act as an on-off fluorescent probe and can be applied to image zinc ions in human fibroblast cells under visible light.

Oral Formulation of 5-Aminosalicylic Acid-Hemoglobin Bio-Adhesive Nanoparticles Enhance Therapeutic Efficiency in Ulcerative Colitis Mice: A Preclinical Evaluation.

The oral formulation design for colon-specific drug delivery brings some therapeutic benefits in the ulcerative colitis treatment. We recently reported the specific delivery of hemoglobin nanoparticles-conjugating 5-aminosalicylic acid (5-ASA-HbNPs) to the inflamed site. In the current study, the therapeutic effect of the 5-ASA-HbNPs formulation was confirmed in vivo. This evaluation of 5-ASA-HbNPs not only shows longer colonic retention time due to adhesive properties, also provides full support for it as compared with free 5-ASA. It was considered as a suitable bio-adhesive nanoparticle with mucoadhesive property to pass through the mucus layer and accumulate into the mucosa. In UC model mice, a two-fold decrease in the disease activity indexes and colon weight/length ratios was significantly observed in the group treated with 5-ASA-HbNPs. This group received one percent of the standard dosage of 5-ASA (50 µg/kg), while, a similar result was observed for a significant amount of free 5-ASA (5 mg/kg). Furthermore, microscopic images of histological sections of the extracted colons demonstrated that the 5-ASA-HbNPs and 5-ASA groups displayed instances of inflammatory damage within the colon. However, in comparison to the colitis group, the extent of this damage was relatively moderate, suggesting 5-ASA-HbNPs improved therapeutic efficacy with the lower dosage form.

Grafting of sinapic acid onto glucosamine nanoparticle as a potential therapeutic drug with enhanced anti-inflammatory activities in osteoarthritis treatment.

Glucosamine (Glu) is a cartilage and joint fluid matrix precursor that modulates osteoarthritic joint changes. To improve the enzymatic stability, glucosamine was developed into nanoglucosamine by the ionic gelation method through sodium tripolyphosphate (TPP) as cross-linking agent. The optimized mass ratio of Glu:TPP was (3:1) with the particle size 163 ± 25 nm and surface charge -5 mV. Then Sinapic acid (SA) as a natural phenolic acid with strong antioxidant and antimicrobial activities has been grafted onto glucosamine nanoparticles (GluNPs) with grafting efficiency (73 ± 6 %). The covalent insertion of SA was confirmed by UV-Vis, FTIR, 1HNMR, XRD, and FESEM analyses and the other physicochemical properties were also characterized. SA-g-GluNPs showed spherical shape with a mean diameter of 255 ± 20 nm and zeta potential +16 mV. The in vitro release profile of SA-g-GluNPs exhibited the sustained and pH-dependent drug release property. SA-g-GluNPs had a more pronounced effect on reducing the elevated levels of LPS-induced oxidative stress and pro-inflammatory cytokines than free SA in the human chondrocyte C28/I2 cell line. Furthermore, the antibacterial properties against E. coli and S. aureus were also improved by SA-g-GluNPs. This study demonstrated the potential of phenolic acid grafted GluNPs in therapeutic drug applications for chondroprotection and food industries.

Improvement of anti-biofilm activities via co-delivery of curcumin and gentamicin in lipid-polymer hybrid nanoparticle.

Pseudomonas aeruginosa is the most common pathogen that causes chronic lung infections and recurrence of the disease in cystic fibrosis patients by hiding inside cells and biofilm matrix. Herein, we developed gentamicin and curcumin-loaded lipid-polymer hybrid nanoparticle- (termed CG-HNPs) to evaluate in vitro activities against biofilm-embedded P. aeruginosa and compared with lipid nanoparticles containing the same drugs (CG-Lip). The nanoparticles were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), fluorescence spectroscopy, and ultraviolet-visible (UV-vis) spectroscopy, which demonstrated that HNPs with a diameter of approximately 340 nm were uniform. The optimal CG-HNPs formulation illustrated high encapsulation (∼70%) and controlled release characteristics (gradually released in 72 h). The antibacterial activities of generated nanoparticles are maintained against planktonic and biofilm bacteria and it is effective in damage established biofilms. Besides, HNPs were biocompatible and nontoxic to J774 and HFF cell lines and uptake by the macrophages (J774), which facilitated the killing of intracellular bacteria in macrophages. These results introduced CG-HNPs as a promising antibacterial agent for the treatment of chronic infections and intracellular bacteria due to excellent antibacterial activity.

Hemoglobin bio-adhesive nanoparticles as a colon-specific delivery system for sustained release of 5-aminosalicylic acid in the effective treatment of inflammatory bowel disease.

A colonic drug delivery system was developed to specifically deliver 5-aminosalicylic acid (5-ASA) to the inflamed site by conjugating with hemoglobin nanoparticles (HbNPs). The 5-ASA-HbNPs (eight 5-ASA molecules per Hb molecule) with the size of 220 nm and zeta potential of -14.6 mV is a tailored nanoparticle able to pass through the mucus layer. The 5-ASA-HbNPs do not undergo chemical and enzymatic hydrolysis in the simulated gastrointestinal fluids over 6 h. Significantly higher cellular uptakes and prolonged release was seen for the 5-ASA-HbNPs in Caco-2 cells, compared to free 5-ASA over 72 h. In addition, 5-ASA-HbNPs revealed similar therapeutic effectiveness with free 5-ASA against tumor necrosis factor and showed less inhibitory concentration (IC50) for myeloperoxidase enzyme activity. In vivo imaging of mouse demonstrated the localization of drug in the descending colon after oral administration and about 15% of the administered dose was recovered as 5-ASA from urine in 6 h. The use of these nanoparticles with the mucus adhesion properties and permeability to intestinal epithelial cells can be a good candidate with potential application in the colonic drug delivery field.

Fluorescence sensing and imaging with carbon-based quantum dots for early diagnosis of cancer: A review.

This review discusses recent advances and the reported strategies over the last ten years on the use of carbon-based quantum dots (QDs), including carbon dots (CDs), graphene quantum dots (GQDs), and polymer dots (PDs) in the design of fluorescence imaging and biosensing system for early diagnosis of cancers. Besides, this study comprehensively reports the latest developments in these years in the fluorescence imaging (FI) area with special attention to carbon-based QDs that take advantage of the excellent properties offered by these zero-dimensional (0D) nanomaterials as fluorescent tags. The most remarkable advantages of these carbon nanomaterials in the development of fluorescence sensing and imaging strategies compared to the conventional dyes arise from sharp emission spectra, long photostability, low-cost synthesis, reliability, reproducibility, high fluorescent intensity, and high surface functional groups such as carboxyl and amide, which impart better solubility in many solvents and aqueous media and facilitate their easy functionalization with biological species. The final section discusses the main challenges to be met to take full advantage of these properties in fluorescence bio-sensing and imaging as well as the possible future trends in this field based on the great advances that have occurred in recent years.

Mepolizumab as Possible Treatment for Allergic Bronchopulmonary Aspergillosis: A Review of Eight Cases.

Allergic bronchopulmonary aspergillosis (ABPA) is an eosinophilic pulmonary disorder caused by a hypersensitivity reaction to Aspergillus fumigatus that manifests with uncontrolled asthma, peripheral blood eosinophilia, and radiological findings, such as mucus plugging. Early diagnosis and proper treatment of ABPA are essential to prevent irreversible lung damage such as pulmonary fibrosis and bronchiectasis and improve the quality of life of patients. Beside inhaled medication for asthma, anti-inflammatory agents (i.e., systemic glucocorticoids) and antifungal agents are the mainstay treatment of ABPA. The goal of therapy using glucocorticoids and antifungal agents is to suppress the immune hyperreactivity to A. fumigatus and attenuate the fungal burden. Since the systemic glucocorticoid therapy may lead to serious adverse effects including osteoporosis, avascular necrosis, myopathy, cushingoid appearance, hypertension, insomnia, and increased risk of infection, a glucocorticoid-sparing agent could be considered. Mepolizumab is a humanized monoclonal antibody that binds to interleukin-5, which is the key mediator for eosinophil differentiation, activation, migration, and survival. We review eight cases of ABPA treated successfully with mepolizumab. Treatment with mepolizumab was not restricted to the total immunoglobulin E level, the limiting factor for omalizumab in ABPA. In addition, mepolizumab therapy improved forced expiratory volume in one second, radiological findings, and patient quality of life.

"Obscure" Appendiceal Orifice Polyps Can Be Challenging to Identify by Colonoscopy.

The primary purpose of screening colonoscopy is the detection and subsequent removal of precancerous polyps. However, effective recognition of appendiceal lesions with a standard endoscope is often challenging and is limited to the base of the cecum and appendiceal orifice. The majority of appendiceal polyps are found incidentally following an appendectomy, though rarely they may be discovered during a colonoscopy. Despite being visualized by colonoscopy, most of these polyps are generally referred for surgical resection. The risk of developing carcinoma in patients with appendiceal polyps is likely similar to that of other colonic polyps, so it is essential for the endoscopist to examine and visualize the appendiceal orifice thoroughly. Various techniques are available to the endoscopist that can increase the accuracy of colonoscopic evaluation. These include luminal inflation and deflation, looking behind and pressing haustral folds, and repetitive passage of the scope over poorly visualized areas. To our knowledge, only 3 cases have been reported in the literature describing the discovery of obscure appendiceal polyps using colonoscopic techniques. Here we describe three cases of appendiceal orifice polyps missed on initial visualization but subsequently protruded into the cecum following prolonged examination and gentle deflation in the cecum. The endoscopist should consider the possibility of an appendiceal neoplasm, especially if other colonic polyps have been found. Endoscopists should spend adequate time examining the cecum during a screening colonoscopy to expose and thoroughly examine the appendiceal region.

Portal Vein Thrombosis and Intra-Abdominal Hypertension Presenting as Complications of Hypertriglyceridemia-Induced Severe Acute Pancreatitis.

A 44-year-old male without any significant past medical history presented to the emergency department (ED) with the chief complaint of severe constant epigastric pain for three hours. On physical examination, the abdomen was distended and tender, particularly in the epigastric region. The lab work showed an elevation of the lipase (12,405 U/L) and triglycerides (5,837 mg/dL). An abdominal CT scan with contrast was ordered, which revealed non-necrotic pancreatitis. In addition, the liver ultrasound showed no evidence of gallstones. Subsequently, fluid infusion, meropenem, pain medication, and an insulin drip were started, and the patient was transferred to the intensive care unit (ICU). After six hours in the ICU, he complained of abdominal pain despite taking a high hydromorphone dose. On further physical examination, the abdomen was tender and distended but without rebound tenderness. The gastric distention on kidneys, ureter, and bladder (KUB) and a bladder pressure of 34 mmHg raised the suspicion for intra-abdominal hypertension (IAH), which led us to place a nasogastric tube (NGT) and consult the surgical team. The patient's symptoms and bladder pressure were closely followed and showed significant improvement. On day seven in the ICU, the patient responded well to medications; feeding through the Dobhoff tube was started, and his triglycerides decreased to approximately 1,000 mg/dL. Despite his general improvement and meropenem regimen, the patient spiked a fever of 38.5 °C. Due to the possibility of pancreatitis complications, a CT abdomen with contrast was ordered, which showed partial portal vein thrombosis (PVT). Subsequently, enoxaparin was started, and the patient was closely observed for gastrointestinal bleeding. Eventually, after 17 days in the ICU, the patient was transferred to the floor and then discharged from the hospital with normal lab tests and without evidence of portal thrombosis on abdominal CT. In this report, we illustrate and discuss a case of hypertriglyceridemia (HTG)-induced pancreatitis (HTGP), which progressed to PVT and IAH. Physicians should be aware that patients with HTG are inclined to have severe pancreatitis. In addition, the degree of triglyceride elevation is correlated with the severity of acute pancreatitis.

Encapsulation of an endostatin peptide in liposomes: Stability, release, and cytotoxicity study.

The endostatin protein is a potent inhibitor of angiogenesis and tumor growth. The anti-angiogenic and antitumor properties of full-length endostatin can be mimicked by its N-terminal segment, including residues 1-27. Therefore, our previous studies have shown that a mutant N-terminal peptide which the Zn-binding loop was replaced by a disulfide loop (referred to as the ES-SS peptide) has preserved antiangiogenic and antitumor properties compared to the native peptide. To increase stability and plasma half-life of the ES-SS peptide, the nano-sized liposomal formulations of the peptide with different ratio of phosphocholine (PC) were synthesized. The liposomal peptide formulations possessed an average size of around 100 nm with (-4 to -36 mv) in zeta potential. The encapsulation efficiency of the ES-SS peptide was in the range of 24-54% with different lipid: peptide molar ratios. In vitro release of the peptide from liposomes indicated a complete peptide release after 7 days. Cytotoxicity assay was evaluated using the human umbilical vein endothelial cells (HUVECs) for various concentrations of the liposomal peptide. The results depicted the gradual release of the peptide through liposomes. By comparing with the free peptide, the liposomal peptide formulations have indicated higher cell viability with IC50 value about 0.1 µM. The peptide-liposome interactions, as well as the peptide effect on the liposome structure, were also investigated through coarse-grained molecular dynamics (CG-MD) simulation. The results revealed that the peptides were assembled in the hydrophilic core of the liposome. The peptide behavior in liposome can stabilize the liposome structure and be a response to the observed low peptide release rate. The investigation is promising for designing a liposome-based anti-angiogenesis peptide delivery system.

Duodenal angiosarcoma can be misdiagnosed as a Dieulafoy's lesion.

Angiosarcomas are soft-tissue neoplasms that originate from the vascular epithelium. The most commonly involved sites include the skin and subcutaneous tissues. In the GI tract, generally, angiosarcomas involve the spleen and liver, although locations in the small intestine and colon have been very occasionally reported. In the present study we report the unusual case of a man with duodenal epithelioid angiosarcoma, presenting with anemia and recurrent upper gastrointestinal bleeding, which was initially misdiagnosed as a Dieulafoy's lesion. It is important to consider the diagnosis of gastrointestinal malignancy, including unusual neoplasms such as angiosarcomas, in the setting of anendoscopic appearance such as hemorrhagic nodule, purpuric mass and/or recurrent bleeding lesions that are persistent despite repeat interventions. In such cases, a biopsy should be considered to confirm the diagnosis.

Two unusual sites of metastases of esophageal adenocarcinoma.

The most common sites of metastasis for esophageal cancers include the liver, lungs, and bones. We report a rare case of esophageal adenocarcinoma with metastasis to the subcutaneous perianal region as well as to the small bowel. Physicians should consider the possibility of metastasis in a patient with esophageal adenocarcinoma even after the onset of remission. It is essential to examine these patients and maintain a high index of suspicion for possible metastases. Early recognition helps in the accurate staging of the disease and enables the initiation of life-prolonging therapy and achieving meaningful palliation.

A novel iron quantum cluster confined in hemoglobin as fluorescent sensor for rapid detection of Escherichia coli.

A new method based on fluorescent probe of iron quantum cluster has been proposed for rapid detection of Escherichia coli (E. coli). The iron quantum cluster was synthesized using hemoglobin as both a source of iron and a protective agent (Hb-FeQCs). The investigation of the sensitivity of Hb-FeQCs towards metal ions showed a highly selective turn off fluorescence for Cu2+. It suggests that Cu2+ can induce fluorescence quenching by binding to amino acids of Hb. The ability of E. coli bacteria to capture and reduce of Cu ions caused to efficient recovery of the fluorescence of Hb-FeQCs from Cu2+-caused quenching. This probe has a satisfactorily linear range of 0.35-35 µM for Cu2+ under the optimal iron quantum cluster concentration (500 µg/mL) with an 85 nM detection limit. Rapid and facile detection of E.coli bacteria with the limit of detection around 8.3 × 103 CFU/mL was successfully achieved in the artificially contaminated urine, tap water, and DMEM samples within 30 min. The fluorescence recovery was investigated by different types of bacteria and only E. coli revealed 56% recovery which related to its capability to Cu2+ reduction and the great potential of the fluorescent probe for rapid detection of pathogenic E. coli bacteria. Furthermore, the Hb-FeQCs can detect E. coli bacteria in an infected urine sample by retrieving up to 74% of its fluorescence which is helpful to accelerate the diagnosis and treatment of urinary tract infection (UTI).

Aggregation determines the selectivity of membrane-active anticancer and antimicrobial peptides: The case of killerFLIP.

Host defense peptides selectively kill bacterial and cancer cells (including those that are drug-resistant) by perturbing the permeability of their membranes, without being significantly toxic to the host. Coulombic interactions between these cationic and amphipathic peptides and the negatively charged membranes of pathogenic cells contribute to the selective toxicity. However, a positive charge is not sufficient for selectivity, which can be achieved only by a finely tuned balance of electrostatic and hydrophobic driving forces. A common property of amphipathic peptides is the formation of aggregated structures in solution, but the role of this phenomenon in peptide activity and selectivity has received limited attention. Our data on the anticancer peptide killerFLIP demonstrate that aggregation strongly increases peptide selectivity, by reducing the effective peptide hydrophobicity and thus the affinity towards membranes composed of neutral lipids (like the outer layer of healthy eukaryotic cell membranes). Aggregation is therefore a useful tool to modulate the selectivity of membrane active peptides and peptidomimetics.

PDMS Nano-Modified Scaffolds for Improvement of Stem Cells Proliferation and Differentiation in Microfluidic Platform.

Microfluidics cell-based assays require strong cell-substrate adhesion for cell viability, proliferation, and differentiation. The intrinsic properties of PDMS, a commonly used polymer in microfluidics systems, regarding cell-substrate interactions have limited its application for microfluidics cell-based assays. Various attempts by previous researchers, such as chemical modification, plasma-treatment, and protein-coating of PDMS revealed some improvements. These strategies are often reversible, time-consuming, short-lived with either cell aggregates formation, not cost-effective as well as not user- and eco-friendly too. To address these challenges, cell-surface interaction has been tuned by the modification of PDMS doped with different biocompatible nanomaterials. Gold nanowires (AuNWs), superparamagnetic iron oxide nanoparticles (SPIONs), graphene oxide sheets (GO), and graphene quantum dot (GQD) have already been coupled to PDMS as an alternative biomaterial enabling easy and straightforward integration during microfluidic fabrication. The synthesized nanoparticles were characterized by corresponding methods. Physical cues of the nanostructured substrates such as Young's modulus, surface roughness, and nanotopology have been carried out using atomic force microscopy (AFM). Initial biocompatibility assessment of the nanocomposites using human amniotic mesenchymal stem cells (hAMSCs) showed comparable cell viabilities among all nanostructured PDMS composites. Finally, osteogenic stem cell differentiation demonstrated an improved differentiation rate inside microfluidic devices. The results revealed that the presence of nanomaterials affected a 5- to 10-fold increase in surface roughness. In addition, the results showed enhancement of cell proliferation from 30% (pristine PDMS) to 85% (nano-modified scaffolds containing AuNWs and SPIONs), calcification from 60% (pristine PDMS) to 95% (PDMS/AuNWs), and cell surface marker expression from 40% in PDMS to 77% in SPION- and AuNWs-PDMS scaffolds at 14 day. Our results suggest that nanostructured composites have a very high potential for stem cell studies and future therapies.