Exploring the multimodal health-promoting properties of resveratrol: A comprehensive review.

Resveratrol, a natural polyphenol in various plants, has gained significant attention for its potential health-promoting properties. It has been demonstrated, after reviewing various clinical and in vitro studies, that resveratrol possesses potent antioxidant potential. Resveratrol demonstrates cellular component protection by directly neutralizing free radicals (FRs) and enhancing the expression of natural antioxidant enzymes, thereby mitigating oxidative damage to proteins, lipids, and nucleic acids. Clinical trials have shown promising results, indicating that resveratrol supplementation can enhance antioxidant defenses and reduce oxidative damage markers in various populations. In addition to its antioxidant effects, resveratrol exhibits potent anti-inflammatory properties. It can modulate key inflammatory pathways, such as nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs), thereby suppressing the production of pro-inflammatory cytokines and chemokines. Furthermore, resveratrol's multimodal effects extend beyond its antioxidant and anti-inflammatory properties. It has been discovered to exert regulatory effects on various cellular processes, including apoptosis, cell cycle progression, angiogenesis, and immunological responses. The primary aim of this review paper is to provide a thorough overview of the current knowledge on resveratrol, including its chemical composition, bioaccessibility, clinical effectiveness, and utilization in nanotechnology to enhance its bioavailability. From future perspectives, revising the administration methods for certain contexts and understanding the underlying systems responsible for resveratrol's effects will require further inquiry. For the highest potential health results, advanced trial-based research is necessary for combinational nano-delivery of resveratrol.

The interplay between diabetes and non-alcoholic fatty liver disease: a cross-sectional study from Pakistan.

Background and objectives: Non-alcoholic fatty liver disease (NAFLD) is characterized by ectopic deposition of fat in the liver, in the absence of other secondary causes of fat buildup. The relationship between NAFLD, including alanine aminotransferase (ALT), and glycated haemoglobin (HbA1c), is important for predicting the severity of disease and prognosis. This study aims to investigate the association of HbA1c in type 2 diabetes mellitus (T2DM) patients with NAFLD via measuring the ALT levels. Materials and methods: This retrospective cross-sectional study enroled 130 patients with T2DM and NAFLD. The association between levels of HbA1c and ALT in patients of NAFLD with controlled and uncontrolled T2DM, respectively, was investigated. Stratification was done based on gender and diabetic control, using HbA1c levels as a marker of glycemic control. Serum ALT levels were also compared in both groups. Results: The mean age of the participants was 50.2±5.7 years. The total participants were 130, of which 77 (59.3%) were females and 53 (40.7%) were males. The numbers of patients having uncontrolled T2DM (HbA1c>7%), and controlled T2DM (HbA1c <7%) were 78 (60%) and 52 (40%), respectively. Moreover, 46 (35.3%) females and 32 (24.7%) males had uncontrolled T2DM, and 31 (23.8%) females and 21 (16.2%) males had controlled T2DM. The mean ALT level for uncontrolled and controlled T2DM in female patients was found to be 24.6±3.4 and 13.5±2.4, respectively, (P <0.05). For male patients, it was found to be 54.0±4.9 and 29.1±5.4, respectively (P=0.008). Conclusion: There is a positive association between elevated HbA1c and ALT levels in T2DM patients with NAFLD.

Effect of stress urinary incontinence on vaginal microbial communities.

BACKGROUND: Postpartum women often experience stress urinary incontinence (SUI) and vaginal microbial dysbiosis, which seriously affect women's physical and mental health. Understanding the relationship between SUI and vaginal microbiota composition may help to prevent vaginal diseases, but research on the potential association between these conditions is limited. RESULTS: This study employed 16S rRNA gene sequencing to explore the association between SUI and vaginal dysbiosis. In terms of the vaginal microbiota, both species richness and evenness were significantly higher in the SUI group. Additionally, the results of NMDS and species composition indicated that there were differences in the composition of the vaginal microbiota between the two groups. Specifically, compared to postpartum women without SUI (Non-SUI), the relative abundance of bacteria associated with bacterial dysbiosis, such as Streptococcus, Prevotella, Dialister, and Veillonella, showed an increase, while the relative abundance of Lactobacillus decreased in SUI patients. Furthermore, the vaginal microbial co-occurrence network of SUI patients displayed higher connectivity, complexity, and clustering. CONCLUSION: The study highlights the role of Lactobacillus in maintaining vaginal microbial homeostasis. It found a correlation between SUI and vaginal microbiota, indicating an increased risk of vaginal dysbiosis. The findings could enhance our understanding of the relationship between SUI and vaginal dysbiosis in postpartum women, providing valuable insights for preventing bacterial vaginal diseases and improving women's health.

Recent advancements in polyurethane-based membranes for gas separation.

Gas separation membranes are critical in a variety of environmental research and industrial applications. These membranes are designed to selectively allow some gases to flow while blocking others, allowing for the separation and purification of gases for a variety of applications. Therefore, the demand for fast and energy-efficient gas separation techniques is of central interest for many chemical and energy production diligences due to the intensified levels of greenhouse and industrial gases. This encourages the researchers to innovate techniques for capturing and separating these gases, including membrane separation techniques. Polymeric membranes play a significant role in gas separations by capturing gases from the fuel combustion process, purifying chemical raw material used for plastic production, and isolating pure and noncombustible gases. Polyurethane-based membrane technology offers an excellent knack for gas separation applications and has also been considered more energy-efficient than conventional phase change separation methodologies. This review article reveals a thorough delineation of the current developments and efforts made for PU membranes. It further explains its uses for the separation of valuable gases such as carbon dioxide (CO2), hydrogen (H2), nitrogen (N2), methane (CH4), or a mixture of gases from a variety of gas spillages. Polyurethane (PU) is an excellent choice of material and a leading candidate for producing gas-separating membranes because of its outstanding chemical chemistry, good mechanical abilities, higher permeability, and variable microstructure. The presence of PU improves several characteristics of gas-separating membranes. Selectivity and separation efficiency of PU-centered membranes are enhanced through modifications such as blending with other polymers, use of nanoparticles (silica, metal oxides, alumina, zeolite), and interpenetrating polymer networks (IPNs) formation. This manuscript critically analyzes the various gas transport methods and selection criteria for the fabrication of PU membranes. It also covers the challenges facing the development of PU-membrane-based separation procedures.

Biopsychosocial determinant of quality of life of older adults in Pakistan and Canada.

Background: The rapidly rising average age of the older adults has brought various global healthcare challenges. A core challenge is how to enhance their quality of life (QoL). Objective: The objective of the current study was to test the significance of biopsychosocial determinants of quality of life of older adults in Pakistan and Canada. Methodology: A cross-sectional survey was carried out on a conveniently approached purposive sample of 1,005 older adults (Pakistani = 557 and Canadian = 448) of age range between 60 years and 80 years. The data were collected via demographic datasheet, World Health Organization Quality of Life Brief Scale, Health and Lifestyle Questionnaire, General Self-Efficacy Scale, Rosenberg Self-Esteem Scale, and Berlin Social Support Scale. Results: The results of hierarchical regression analysis showed that biopsychosocial factors (viz., health and lifestyle, chronic illness, self-efficacy, self-esteem, and social support) significantly predicted (R 2 = .27, and.68) quality of life of older adults in Pakistan and Canada, respectively, after controlling the demographic variables. Significant differences were found between Pakistani and Canadian older adults on biopsychosocial factors: Canadian older adults scored significantly higher on health and lifestyle, self-efficacy, and quality of life, and older adults in Pakistan scored significantly higher on self-esteem and social support. Conclusion: A significant amount of better QoL of older adults can be achieved through enhancing the biopsychosocial correlates of their QoL, both in Pakistan and Canada.

Exploring the serotonin-probiotics-gut health axis: A review of current evidence and potential mechanisms.

Modulatory effects of serotonin (5-Hydroxytryptamine [5-HT]) have been seen in hepatic, neurological/psychiatric, and gastrointestinal (GI) disorders. Probiotics are live microorganisms that confer health benefits to their host. Recent research has suggested that probiotics can promote serotonin signaling, a crucial pathway in the regulation of mood, cognition, and other physiological processes. Reviewing the literature, we find that peripheral serotonin increases nutrient uptake and storage, regulates the composition of the gut microbiota, and is involved in mediating neuronal disorders. This review explores the mechanisms underlying the probiotic-mediated increase in serotonin signaling, highlighting the role of gut microbiota in the regulation of serotonin production and the modulation of neurotransmitter receptors. Additionally, this review discusses the potential clinical implications of probiotics as a therapeutic strategy for disorders associated with altered serotonin signaling, such as GI and neurological disorders. Overall, this review demonstrates the potential of probiotics as a promising avenue for the treatment of serotonin-related disorders and signaling of serotonin.

Tailoring Bi2Se3 Topological Insulator for Visible-NIR Photodetectors with Schottky Contacts Using Liquid Phase Exfoliation.

Layered semiconductors of the V-VI group have attracted considerable attention in optoelectronic applications owing to their atomically thin structures. They offer thickness-dependent optical and electronic properties, promising ultrafast response time, and high sensitivity. Compared to the bulk, 2D bismuth selenide (Bi2Se3) is recently considered a highly promising material. In this study, 2D nanosheets are synthesized by prolonged sonication in two different solvents, such as N-methyl-2-pyrrolidone (NMP) and chitosan-acetic acid solution (CS-HAc), using the liquid-phase exfoliation (LPE) method. X-ray diffraction confirms the amorphous nature of exfoliated 2D nanosheets with maximum peak intensity at the same position (015) crystal plane as that obtained in its bulk counterpart. SEM confirms the thin 2D nanosheet-like morphology. Successful exfoliation of Bi2Se3 nanosheets up to five layers is achieved using CS-HAc solvent. The as-synthesized 2D nanosheets in different solvents are employed to fabricate the photodetector. At minimum selected power density, the photodetector fabricated using exfoliated ultrathin 2D nanosheets exhibits the highest range of responsivity, varying from 15 to 2.5 mA/W, and detectivity ranging from 2.83 × 109 to 6.37 × 107. Ultrathin 2D Bi2Se3 nanosheets have fast rise and fall times, ranging from 0.01 to 0.12 and 0.01 to 0.06 s, respectively, at different wavelengths. Ultrathin Bi2Se3 nanosheets have improved photodetection parameters as compared to multilayered nanosheets due to the high surface to volume ratio, reduced recombination and trapping of charge carrier, improved carrier confinement, and faster carrier transport due to the thin layer.

Assessment of articular cartilage degradation in response to an impact injury using µMRI.

PURPOSE: Degradation of articular cartilage (AC) due to injury to the knee joint may initiate post-traumatic osteoarthritis (PTOA). Failure to diagnose the onset of the disease at an early stage makes the cure ineffective for PTOA. This study investigated the consequences of a mechanical injury to the knee in a rabbit model using microscopic magnetic resonance imaging (µMRI) at high resolution. MATERIALS AND METHODS: A mechanical injury was induced to the knee joints of 12 rabbits. Cartilage blocks were extracted from the non-impacted and impacted knee joints after 2 and 14 weeks post-impact. The specimens were studied using µMRI T2 relaxation and inductively coupled plasma analysis to determine the early degradation of the articular cartilage. RESULTS: The data established a connection between T2 relaxation time and the early progression of knee PTOA after an impact injury. T2 values were found to be higher in the impacted cartilage at both 2 and 14 weeks, in particular, T2-55° values in the impacted samples displayed a significant rise of 6.93% after 2 weeks and 20.02% after 14 weeks. Lower glycosaminoglycan measurement and higher water content in the impacted cartilage confirmed the µMRI results. CONCLUSIONS: This µMRI T2 study was able to detect cartilage damage in the impacted knees. In addition, greater degradation in the affected knees at 14 weeks than at 2 weeks indicated the progressive nature of cartilage deterioration over time. The µMRI results were in accord with the biochemical analysis, indicating the detection of early structural damage in the cartilage.

Depth-Dependent Strain Model (1D) for Anisotropic Fibrils in Articular Cartilage.

The mechanical response of articular cartilage (AC) under compression is anisotropic and depth-dependent. AC is osmotically active, and its intrinsic osmotic swelling pressure is balanced by its collagen fibril network. This mechanism requires the collagen fibers to be under a state of tensile pre-strain. A simple mathematical model is used to explain the depth-dependent strain calculations observed in articular cartilage under 1D axial compression (perpendicular to the articular surface). The collagen fibers are under pre-strain, influenced by proteoglycan concentration (fixed charged density, FCD) and collagen stiffness against swelling stress. The stiffness is introduced in our model as an anisotropic modulus that varies with fibril orientation through tissue depth. The collagen fibers are stiffer to stretching parallel to their length than perpendicular to it; when combined with depth-varying FCD, the model successfully predicts how tissue strains decrease with depth during compression. In summary, this model highlights that the mechanical properties of cartilage depend not only on proteoglycan concentration but also on the intrinsic properties of the pre-strained collagen network. These properties are essential for the proper functioning of articular cartilage.

Rigorous Comparison of Extracellular Vesicle Processing to Enhance Downstream Analysis for Glioblastoma Characterization.

Extracellular vesicles (EVs) are highly sought after as a source of biomarkers for disease detection and monitoring. Tumor EV isolation, processing, and evaluation from biofluids is convoluted by EV heterogeneity and biological contaminants and is limited by technical processing efficacy. This study rigorously compares common bulk EV isolation workflows (size exclusion chromatography, SEC; membrane affinity, MA) alongside downstream RNA extraction protocols to investigate molecular analyte recovery. EV integrity and recovery is evaluated using a variety of technologies to quantify total intact EVs, total and surface proteins, and RNA purity and recovery. A comprehensive evaluation of each analyte is performed, with a specific emphasis on maintaining user (n = 2), biological (n = 3), and technical replicates (n≥3) under in vitro conditions. Subsequent study of tumor EV spike-in into healthy donor plasma samples is performed to further validate biofluid-derived EV purity and isolation for clinical application. Results show that EV surface integrity is considerably preserved in eluates from SEC-derived EVs, but RNA recovery and purity, as well as bulk protein isolation, is significantly improved in MA-isolated EVs. This study concludes that EV isolation and RNA extraction pipelines govern recovered analyte integrity, necessitating careful selection of processing modality to enhance recovery of the analyte of interest.

Comparison and effect of plain and calcium fortified yogurt on glycemic responses, anthropometrics and metabolic biomarkers.

Metabolic syndromes including obesity and diabetes are the most common health issues due to insulin resistance, disturbance in glucose homeostasis, lack of exercise, and improper diet. The current study was planned to evaluate the potential effects of regular diet with fortified yogurt on blood glycemia and anthropometric responses. Plain yogurt was procured from the local market, and then it was fortified with calcium. Furthermore, the subsequent effect of fortified yogurt on blood glucose, insulin, and anthropometric measurements was assessed at different time intervals. A total of 40 healthy females and males aged about 20 years with a normal BMI range (20-24.9 kg/m2) were recruited within the Government College University Faisalabad. Participants filled out the habits Performa, stress factors questionnaire, and activity questionnaire. Blood glucose (BG) and visual analogous scale (VAS) performs were also taken in the fasting stage and then assigned treatment was given. After 15, 30, 45, 60, 90, and 120 min intervals VAS and BG estimation was carried out. The results shows that fortified yogurt contained a higher amount of calcium. Likewise, a similar trend was observed for the desire to eat, a feeling of fullness, palatability, physical comfort, and overall acceptability. The results obtained from various analyses were statistically evaluated.

Aortoiliac Occlusion in a Rare Instance of Leriche Syndrome Type I in a 65-Year-Old Woman With Chronic Leg Discomfort Refractory to Pregabalin.

Aortoiliac occlusive disease (AIOD), also known as Leriche syndrome, is a form of peripheral artery disease (PAD) that involves narrowing, and in severe cases, complete occlusion, of infrarenal abdominal aorta and/or iliac and femoropopliteal arteries. It classically presents as a triad of symptoms, i.e., leg pain, erectile dysfunction, and abnormally weak or absent femoral pulses. If untreated, it can progress to ischemia and gangrene of the affected regions of pelvis and lower extremities. Like any other PAD, AIOD is most commonly caused by atherosclerosis and usually occurs in strong association with severe cardiovascular diseases. Due to the rarity of this disease, its incidence and prevalence are still unknown making it harder to diagnose especially in patients without the classic risk factors and typical presentation. We report a case of AIOD in a 65-year-old woman who presented with atypical symptoms. She was diagnosed with AIOD type I upon further investigation, which was managed successfully.

Synthesis and characterization of mesoporous bioactive glass nanoparticles loaded with peganum harmala for bone tissue engineering.

Globally, there is an increase in a number of bone disorders including osteoarthritis (OA), osteomyelitis, bone cancer, and etc., which has led to a demand for bone tissue regeneration. In order to take use of the osteogenic potential of natural herbs, mesoporous bioactive glass nanoparticles (MBGNs) have the ability to deliver therapeutically active chemicals locally. MBGNs influence bioactivity and osteointegration of materials making them suitable for bone tissue engineering (BTE). In the present study, we developed Peganum Harmala (P. harmala) loaded MBGNs (PH-MBGNs) synthesized via modified Stöber process. The MBGNs were analyzed in terms of surface morphology, chemical make-up, amorphous nature, chemical interaction, pore size, and surface area before and after loading with P. harmala. A burst release of drug from PH-MBGNs was observed within 8 h immersion in phosphate buffer saline (PBS). PH-MBGNs effectively prevented Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) from spreading. Furthermore, PH-MBGNs developed a hydroxyapatite (HA) layer in the presence of simulated body fluid (SBF) after 21 days, which confirmed the in-vitro bioactivity of MBGNs. In conclusion, PH-MBGNs synthesized in this work are potential candidate for scaffolding or a constituent in the coatings for BTE applications.

Ixodes scapularis nymph saliva protein blocks host inflammation and complement-mediated killing of Lyme disease agent, Borrelia burgdorferi.

Tick serine protease inhibitors (serpins) play crucial roles in tick feeding and pathogen transmission. We demonstrate that Ixodes scapularis (Ixs) nymph tick saliva serpin (S) 41 (IxsS41), secreted by Borrelia burgdorferi (Bb)-infected ticks at high abundance, is involved in regulating tick evasion of host innate immunity and promoting host colonization by Bb. Recombinant (r) proteins were expressed in Pichia pastoris, and substrate hydrolysis assays were used to determine. Ex vivo (complement and hemostasis function related) and in vivo (paw edema and effect on Bb colonization of C3H/HeN mice organs) assays were conducted to validate function. We demonstrate that rIxsS41 inhibits chymase and cathepsin G, pro-inflammatory proteases that are released by mast cells and neutrophils, the first immune cells at the tick feeding site. Importantly, stoichiometry of inhibition analysis revealed that 2.2 and 2.8 molecules of rIxsS41 are needed to 100% inhibit 1 molecule of chymase and cathepsin G, respectively, suggesting that findings here are likely events at the tick feeding site. Furthermore, chymase-mediated paw edema, induced by the mast cell degranulator, compound 48/80 (C48/80), was blocked by rIxsS41. Likewise, rIxsS41 reduced membrane attack complex (MAC) deposition via the alternative and lectin complement activation pathways and dose-dependently protected Bb from complement killing. Additionally, co-inoculating C3H/HeN mice with Bb together with rIxsS41 or with a mixture (rIxsS41 and C48/80). Findings in this study suggest that IxsS41 markedly contributes to tick feeding and host colonization by Bb. Therefore, we conclude that IxsS41 is a potential candidate for an anti-tick vaccine to prevent transmission of the Lyme disease agent.

Biodegradable Packaging Based on Poly(vinyl Alcohol) and Carboxymethyl Cellulose Films Incorporated with Ascorbic Acid for Food Packaging Applications.

Petroleum-based plastics are used as packaging materials because of their low cost and high availability; however, continuous use of these nondegradable materials especially in the food industry has led to environmental pollution. The present study aimed to synthesize antibacterial and biodegradable films based on natural biopolymers carboxymethyl cellulose (CMC), poly(vinyl alcohol) (PVA), and ascorbic acid (AA) cross-linked in the presence of glutaraldehyde (GA). The films were synthesized in two different concentrations, 60PVA:40CMC:AA and 70PVA:30CMC:AA with a fixed amount of AA. Films with smooth texture and overall uniform thickness were obtained. Fourier transform infrared spectroscopy (FTIR) confirmed the cross-linking between the aldehyde group of GA and hydroxyl of PVA through detection of acetal and ether bridges. The synthesized films were thermally stable in the temperature range of 180-300 °C; however, 70PVA:30CMC:AA showed higher weight loss in this range as compared to the 60PVA:40CMC:AA film. Soil burial test demonstrated that the 60PVA:40CMC:AA film was more degradable (71% at day 15) as compared to the 70PVA:30CMC:AA film (65% at day 15). The films exhibited excellent antimicrobial activity against Gram-positive staphylococcus aureus(inhibition zone of 21 mm) and Gram-negative Escherichia coli (inhibition zone of 15 mm). In comparison, the 60PVA:40CMC:AA film showed better results in terms of high mechanical strength, uniform morphology, higher soil burial degradation, and lower water vapor transmission rate. Therefore, the prepared film could be used as a promising candidate in the food packaging industry.

Effects of fasciatherapy versus fascial manipulation on pain, range of motion and function in patients with chronic neck pain.

BACKGROUND: Neck pain is among the common musculoskeletal problem that hinders a person's daily activities. Fascial tightness is a familiar cause of chronic neck pain that is often neglected and can further cause neck disability and a limited range of motion. OBJECTIVE: The purpose was to compare the effects of fascia therapy and fascial manipulation on pain, range of motion and function in patients with chronic neck pain. METHODS: A randomized clinical trial was conducted from February to August 2022 in the Riphah Rehabilitation Centre, Lahore, Pakistan. Fifty-two participants of both genders, aged 18-40 years with chronic neck pain of at least 3-6 months were included. Group A (n = 26) received fascia therapy along with a conventional physical therapy protocol of hot pack, strengthening and stretching, while group B (n = 26) received the fascial manipulation treatment with conventional physical therapy. All the participants were assessed at baseline and after 3 weeks (3 sessions per week). Numeric Pain Rating Scale (NPRS), Neck Disability Index (NDI) and Goniometer (range of motions) were the outcome measures. SPSS 25 was used for the data analysis and normality of the data through the Shaphiro-Wilk test (p > 0.05), and parametric tests were applied. RESULTS: The mean age of group A was 24.82 ± 2.64 years, and group B was 24.17 ± 2.20 years. The independent t-test result showed no significant difference (p ≥ 0.05) in all parameters except in cervical extension and right-side bending (p < 0.05). At the same time, the pair-wise comparison showed significant results (p < 0.05) for all outcome measures in both groups. CONCLUSION: DBM fascia therapy improved cervical extension and side bending (right) more than the fascial manipulation group.It is concluded that DBM fascia therapy shows more improvement as compared to other group. TRIAL REGISTRATION NUMBER: This study was registered at ClinicalTrials.gov ID: NCT05272111 on 09/03/2022.

A Recurrent Nonsense Mutation in NECTIN4 Underlying Ectodermal Dysplasia-Syndactyly Syndrome with a Novel Phenotype in a Consanguineous Kashmiri Family.

EDSS1, a syndrome characterized by ectodermal dysplasia-syndactyly, is inherited in an autosomal recessive manner due to mutations in the NECTIN4/PVRL4 gene. Clinical manifestations of the syndrome include defective nail plate, sparse to absent scalp and body hair, spaced teeth with enamel hypoplasia, and bilateral cutaneous syndactyly in the fingers and toes. Here, we report a consanguineous family of Kashmiri origin presenting features of EDSS1. Using whole exome sequencing, we found a recurrent nonsense mutation (NM_030916: c.181C > T, p.(Gln61 ∗)) in the NECTIN4 gene. The variant segregated perfectly with the disorder within the family. The candidate variant was absent in 50 in-house exomes pertaining to other disorders from the same population. In addition to the previously reported clinical phenotype, an upper lip cleft was found in one of the affected members as a novel phenotype that is not reported by previous studies in EDSS1 patients. Therefore, the study presented here, which was conducted on the Kashmiri population, is the first to document a NECTIN4 mutation associated with the upper lip cleft as a novel phenotype. This finding broadens the molecular and phenotypic spectrum of EDSS1.

Corrosion, surface, and tribological behavior of electrophoretically deposited polyether ether ketone coatings on 316L stainless steel for orthopedic applications.

Electrophoretic deposition (EPD) of polyether ether ketone (PEEK) coatings on metallic implants has recently attracted a great deal of interest; however, further investigation into their corrosion, surface, and tribological properties is required for their clinical application. Using Potentiodynamic polarization and Mott-Schottky analysis of PEEK coatings, we analyzed the electrochemical corrosion behavior of electrophoretically deposited PEEK coatings on 316L stainless steel (SS) substrates. In addition, the tribological behavior of the coatings was determined through pin-on-disc and scratch testing. Initially, the EPD parameters were optimized using a Taguchi Design of Experiment (DoE) approach. The coatings exhibited irregular shaped grains along with ∼66 µm of thickness. Fourier transform infrared spectroscopy confirmed the presence of functional groups ascribed with PEEK. The coatings were moderately hydrophobic and had an average roughness of ∼2 µm. The corrosion studies demonstrated promising features of current density and corrosion potential, indicating that corrosion resistance significantly improves with PEEK coating. Electrochemical impedance spectroscopy also confirmed the corrosion resistance of PEEK coating. The coatings exhibited a slightly lower wear resistance than SS samples, but still possessed adequate wear and scratch resistance for biomedical applications. The current study confirmed that the PEEK coatings on metallic implants is effective for orthopedic applications where corrosion and tribology are major concerns.

3D Printing Assisted Fabrication of Copper-Silver Mesoporous Bioactive Glass Nanoparticles Reinforced Sodium Alginate/Poly(vinyl alcohol) Based Composite Scaffolds: Designed for Skin Tissue Engineering.

Additive manufacturing (also known as 3D printing) is a promising method for producing patient-specific implants. In the present study, sodium alginate (Na-ALG)/poly(vinyl alcohol) (PVA) polymer blends of varying ratios (1:0, 3:1, 1:1, and 1:3) were used to produce tailored-designed skin scaffolds using a 3D bioprinter. Samples of skin scaffolds were printed at 20 layers with a layer height of 0.15 mm using a needle with an inner diameter of 330 µm while maintaining the extrusion speed, extrusion width, and fill density at 10 mm/s, 0.2 mm, and 85%, respectively. The Na-ALG/PVA blend with a 3:1 ratio showed the best printability due to its good viscosity and minimal nozzle leakage, allowing for the fabrication of skin scaffolds with high fidelity and the desired morphological characteristics. Then, copper-silver doped mesoporous bioactive glass nanoparticles (Cu-Ag MBGNs) were incorporated into the Na-ALG/PVA blend (which had already been prepared by using a Na-ALG:PVA ratio of 3:1) in order to obtain therapeutic (angiogenic and antibacterial) effects. The fabricated Na-ALG/PVA/Cu-Ag MBGNs biocomposite scaffolds with dimensions of 20 mm× 20 × 3 mm3 and pore size of 400 ± 60 µm exhibited a promising fidelity. The presence of chemical bonds attributed to Na-ALG, PVA, and Cu-Ag MBGNs and the uniform distribution of Na, C, and O elements within the microstructure of the scaffolds were confirmed by EDX, SEM, and FTIR analyses. The scaffolds were hydrophilic and exhibited proper swelling and degradation behavior for skin tissue engineering. According to the inhibition halo test, the scaffolds exhibited strong antibacterial activity against Staphylococcus aureus and Escherichia coli. The cytocompatibility to human-derived fibroblast cells was confirmed by the WST-8 assay and in vivo Chorioallantoic Membrane Assay. In addition, Na-ALG/PVA/Cu-Ag MBGNs showed angiogenic potential, exhibiting favorable wound healing properties.

Longitudinal analysis of serum-derived extracellular vesicle RNA to monitor dacomitinib treatment response in EGFR-amplified recurrent glioblastoma patients.

Background: Glioblastoma (GBM) is a highly aggressive and invasive brain tumor associated with high patient mortality. A large fraction of GBM tumors have been identified as epidermal growth factor receptor (EGFR) amplified and ~50% also are EGFRvIII mutant positive. In a previously reported multicenter phase II study, we have described the response of recurrent GBM (rGBM) patients to dacomitinib, an EGFR tyrosine kinase inhibitor (TKI). As a continuation of that report, we leverage the tumor cargo-encapsulating extracellular vesicles (EVs) and explore their genetic composition as carriers of tumor biomarker. Methods: Serum samples were longitudinally collected from EGFR-amplified rGBM patients who clinically benefitted from dacomitinib therapy (responders) and those who did not (nonresponders), as well as from a healthy cohort of individuals. The serum EV transcriptome was evaluated to map the RNA biotype distribution and distinguish GBM disease. Results: Using long RNA sequencing, we show enriched detection of over 10 000 coding RNAs from serum EVs. The EV transcriptome yielded a unique signature that facilitates differentiation of GBM patients from healthy donors. Further analysis revealed genetic enrichment that enables stratification of responders from nonresponders prior to dacomitinib treatment as well as following administration. Conclusion: This study demonstrates that genetic composition analysis of serum EVs may aid in therapeutic stratification to identify patients with dacomitinib-responsive GBM.