In Situ Synthesis and Self-Assembly of Peptide-PEG Conjugates: A Facile Method for the Construction of Fibrous Hydrogels.

Peptide-based hydrogels have gained considerable attention as a compelling platform for various biomedical applications in recent years. Their attractiveness stems from their ability to seamlessly integrate diverse properties, such as biocompatibility, biodegradability, easily adjustable hydrophilicity/hydrophobicity, and other functionalities. However, a significant drawback is that most of the functional self-assembling peptides cannot form robust hydrogels suitable for biological applications. In this study, we present the synthesis of novel peptide-PEG conjugates and explore their comprehensive hydrogel properties. The hydrogel comprises double networks, with the first network formed through the self-assembly of peptides to create a ß-sheet secondary structure. The second network is established through covalent bond formation via N-hydroxysuccinimide chemistry between peptides and a 4-arm PEG to form a covalently linked network. Importantly, our findings reveal that this hydrogel formation method can be applied to other peptides containing lysine-rich sequences. Upon encapsulation of the hydrogel with antimicrobial peptides, the hydrogel retained high bacterial killing efficiency while showing minimum cytotoxicity toward mammalian cells. We hope that this method opens new avenues for the development of a novel class of peptide-polymer hydrogel materials with enhanced performance in biomedical contexts, particularly in reducing the potential for infection in applications of tissue regeneration and drug delivery.

Multi-Modality Imaging in Vasculitis.

Systemic vasculitides are a rare and complex group of diseases that can affect multiple organ systems. Clinically, presentation may be vague and non-specific and as such, diagnosis and subsequent management are challenging. These entities are typically classified by the size of vessel involved, including large-vessel vasculitis (giant cell arteritis, Takayasu's arteritis, and clinically isolated aortitis), medium-vessel vasculitis (including polyarteritis nodosa and Kawasaki disease), and small-vessel vasculitis (granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis). There are also other systemic vasculitides that do not fit in to these categories, such as Behcet's disease, Cogan syndrome, and IgG4-related disease. Advances in medical imaging modalities have revolutionized the approach to diagnosis of these diseases. Specifically, color Doppler ultrasound, computed tomography and angiography, magnetic resonance imaging, positron emission tomography, or invasive catheterization as indicated have become fundamental in the work up of any patient with suspected systemic or localized vasculitis. This review presents the key diagnostic imaging modalities and their clinical utility in the evaluation of systemic vasculitis.

How Artificial Intelligence Can Enhance the Diagnosis of Cardiac Amyloidosis: A Review of Recent Advances and Challenges.

Cardiac amyloidosis (CA) is an underdiagnosed form of infiltrative cardiomyopathy caused by abnormal amyloid fibrils deposited extracellularly in the myocardium and cardiac structures. There can be high variability in its clinical manifestations, and diagnosing CA requires expertise and often thorough evaluation; as such, the diagnosis of CA can be challenging and is often delayed. The application of artificial intelligence (AI) to different diagnostic modalities is rapidly expanding and transforming cardiovascular medicine. Advanced AI methods such as deep-learning convolutional neural networks (CNNs) may enhance the diagnostic process for CA by identifying patients at higher risk and potentially expediting the diagnosis of CA. In this review, we summarize the current state of AI applications to different diagnostic modalities used for the evaluation of CA, including their diagnostic and prognostic potential, and current challenges and limitations.

Reference intervals of complete blood count parameters in the adult western Sudanese population.

BACKGROUND: A complete blood count (CBC) analysis is one of the most common conventional blood tests that physicians frequently prescribe. THE OBJECTIVE: of this study was to determine the reference intervals (RIs) of CBC parameters in the population of healthy adults living in the western Sudan region. METHODS: A cross-sectional study of healthy people residing in the western area of Sudan was carried out. We assessed the CBC RIs in samples taken from 153 individuals using an automated haematology analyser (Sysmex KX-21) and a modified Box-Cox transformation procedure to transform the data into a Gaussian distribution after eliminating outliers using the Dixon method. IBM SPSS Statistics version 25 was used to analyse the data, and t tests were employed to examine variations in the mean CBC parameters according to sex and age. P was considered significant at ≤ 0.05. RESULTS: Beyond all the other measured values, the only CBC parameters that significantly differed between the sexes were haemoglobin (HGB) and white blood cell (WBC) counts. Women were found to experience more WBC counts than men did. However, they have less HGB RIs.The male participants in our study exhibited lower WBC count RIs, a significantly lower limit, and a greater upper limit of platelet RIs than did the individuals from other nations. CONCLUSIONS: Compared with males, females had higher platelet and WBC counts and lower HGB.

SiONx Coating Regulates Mesenchymal Stem Cell Antioxidant Capacity via Nuclear Erythroid Factor 2 Activity under Toxic Oxidative Stress Conditions.

Healing in compromised and complicated bone defects is often prolonged and delayed due to the lack of bioactivity of the fixation device, secondary infections, and associated oxidative stress. Here, we propose amorphous silicon oxynitride (SiONx) as a coating for the fixation devices to improve both bioactivity and bacteriostatic activity and reduce oxidative stress. We aimed to study the effect of increasing the N/O ratio in the SiONx to fine-tune the cellular activity and the antioxidant effect via the NRF2 pathway under oxidative stress conditions. The in vitro studies involved using human mesenchymal stem cells (MSCs) to examine the effect of SiONx coatings on osteogenesis with and without toxic oxidative stress. Additionally, bacterial growth on SiONx surfaces was studied using methicillin-resistant Staphylococcus aureus (MRSA) colonies. NRF2 siRNA transfection was performed on the hMSCs (NRF2-KD) to study the antioxidant response to silicon ions. The SiONx implant surfaces showed a >4-fold decrease in bacterial growth vs. bare titanium as a control. Increasing the N/O ratio in the SiONx implants increased the alkaline phosphatase activity >1.5 times, and the other osteogenic markers (osteocalcin, RUNX2, and Osterix) were increased >2-fold under normal conditions. Increasing the N/O ratio in SiONx enhanced the protective effects and improved cell viability against toxic oxidative stress conditions. There was a significant increase in osteocalcin activity compared to the uncoated group, along with increased antioxidant activity under oxidative stress conditions. In NRF2-KD cells, there was a stunted effect on the upregulation of antioxidant markers by silicon ions, indicating a role for NRF2. In conclusion, the SiONx coatings studied here displayed bacteriostatic properties. These materials promoted osteogenic markers under toxic oxidative stress conditions while also enhancing antioxidant NRF2 activity. These results indicate the potential of SiONx coatings to induce in vivo bone regeneration in a challenging oxidative stress environment.

Association between electronic nicotine delivery systems use and risk of stroke: a meta-analysis of 1,024,401 participants.

Introduction: To evaluate the relationship between electronic nicotine delivery systems (ENDS) use and the risk of stroke when compared to non-smokers. Methods: A comprehensive search was conducted until June 15, 2023. We included observational studies that assessed association of current or former usage of ENDS with risk of stroke compared with non-smokers, reported the risk estimate as odds ratio (OR) or hazard ratio (HR) and were adjusted for possible confounders. Results: 6 studies with 1,024,401 participants were included in our analysis. ENDS use was associated with a significant increased risk of stroke (OR = 1.52; 95% CI: 1.17-1.97) compared with non-users. A non-significant association was found between former ENDS use and risk of stroke (OR = 1.03; 95% CI: 0.87-1.21). Conclusions: The ENDS usage appears to be associated with a higher risk of stroke compared to non-use, whereas there was no association between former ENDS use and the risk of stroke.

Revolutionizing bone regeneration: advanced biomaterials for healing compromised bone defects.

In this review, we explore the application of novel biomaterial-based therapies specifically targeted towards craniofacial bone defects. The repair and regeneration of critical sized bone defects in the craniofacial region requires the use of bioactive materials to stabilize and expedite the healing process. However, the existing clinical approaches face challenges in effectively treating complex craniofacial bone defects, including issues such as oxidative stress, inflammation, and soft tissue loss. Given that a significant portion of individuals affected by traumatic bone defects in the craniofacial area belong to the aging population, there is an urgent need for innovative biomaterials to address the declining rate of new bone formation associated with age-related changes in the skeletal system. This article emphasizes the importance of semiconductor industry-derived materials as a potential solution to combat oxidative stress and address the challenges associated with aging bone. Furthermore, we discuss various material and autologous treatment approaches, as well as in vitro and in vivo models used to investigate new therapeutic strategies in the context of craniofacial bone repair. By focusing on these aspects, we aim to shed light on the potential of advanced biomaterials to overcome the limitations of current treatments and pave the way for more effective and efficient therapeutic interventions for craniofacial bone defects.

Advanced Methodology for Rapid Isolation of Single Myofibers from Flexor Digitorum Brevis Muscle.

Isolated individual myofibers are valuable experimental models that can be used in various conditions to understand skeletal muscle physiology and pathophysiology at the tissue and cellular level. This report details a time- and cost-effective method for isolation of single myofibers from the flexor digitorum brevis (FDB) muscle in both young and aged mice. The FDB muscle was chosen for its documented history in single myofiber experiments. By modifying published methods for FDB myofiber isolation, we have optimized the protocol by first separating FDB muscle into individual bundles before the digestion, followed by optimizing the subsequent digestion medium conditions to ensure reproducibility. Morphological and functional assessments demonstrate a high yield of isolated FDB myofibers with sarcolemma integrity achieved in a shorter time frame than previous published procedures. This method could be also adapted to other types of skeletal muscle. Additionally, this highly reproducible method can greatly reduce the number of animals needed to yield adequate numbers of myofibers for experiments. Thus, this advanced method for myofiber isolation has the potential to accelerate research in skeletal muscle physiology and screening potential therapeutics "ex vivo" for muscle diseases and regeneration.

Mass Spectrometry Approaches for Detection and Determination of Prostaglandins from Biological Samples.

Accurate determination of prostaglandins (PGs) from biological samples is critical for understanding their biological functions and interactions during physiological and pathological processes. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a highly sensitive, accurate, and high-throughput approach for simultaneous detection of ultra-trace PGs from a single biological sample. Here we describe LC-MS/MS techniques and related sample pretreatment methods including both off-line and on-line SPE for the determination of PGs in biological samples.

Effect of the Renin-Angiotensin System Inhibitors on Inflammatory Markers: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To synthesize more conclusive evidence on the anti-inflammatory effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). METHODS: PubMed, Scopus, and Embase were searched from inception until March 1, 2021. We included randomized controlled trials (RCTs) that assessed the effect of ACEIs or ARBs, compared with placebo, on any of the following markers: C-reactive protein (CRP), interleukin 6 (IL-6), or tumor necrosis factor α (TNF-α). Mean changes in the levels of these markers were pooled as a weighted mean difference (WMD) with a 95% CI. RESULTS: Thirty-two RCTs (n=3489 patients) were included in the final analysis. Overall pooled analysis suggested that ACEIs significantly reduced plasma levels of CRP (WMD, -0.54 [95% CI, -0.88 to -0.21]; P=.002; I2=96%), IL-6 (WMD, -0.84 [95% CI, -1.03 to -0.64]; P<.001; I2=0%), and TNF-α (WMD, -12.75 [95% CI, -17.20 to -8.29]; P<.001; I2=99%). Moreover, ARBs showed a significant reduction only in IL-6 (WMD, -1.34 [95% CI, -2.65 to -0.04]; P=.04; I2=85%) and did not significantly affect CRP (P=.15) or TNF-α (P=.97) levels. The lowering effect of ACEIs on CRP levels remained significant with enalapril (P=.006) and perindopril (P=.01) as well as with a treatment duration of less than 24 weeks (WMD, -0.67 [95% CI, -1.07 to -0.27]; P=.001; I2=94%) and in patients with coronary artery disease (WMD, -0.75 [95% CI, -1.17 to -0.33]; P<.001; I2=96%). CONCLUSION: Based on this meta-analysis, ACEIs showed a beneficial lowering effect on CRP, IL-6, and TNF-α, whereas ARBs were effective as a class in reduction of IL-6 only.

Coenzyme Q10 Reduces Infarct Size in Animal Models of Myocardial Ischemia-Reperfusion Injury: A Meta-Analysis and Summary of Underlying Mechanisms.

Objective: Effective interventions that might limit myocardial ischemia-reperfusion (I/R) injury are still lacking. Coenzyme Q10 (CoQ10) may exert cardioprotective actions that reduce myocardial I/R injury. We conducted this meta-analysis to assess the potential cardioprotective effect of CoQ10 in animal models of myocardial I/R injury. Methods: We searched PubMed and Embase databases from inception to February 2022 to identify animal studies that compared the effect of CoQ10 with vehicle treatment or no treatment on myocardial infarct size in models of myocardial I/R injury. Means and standard deviations of the infarct size measurements were pooled as the weighted mean difference with 95% confidence interval (CI) using the random-effects model. Subgroup analyses were also conducted according to animals' species, models' type, and reperfusion time. Results: Six animal studies (4 in vivo and 2 ex vivo) with 116 animals were included. Pooled analysis suggested that CoQ10 significantly reduced myocardial infarct size by -11.36% (95% CI: -16.82, -5.90, p < 0.0001, I2 = 94%) compared with the control group. The significance of the pooled effect estimate was maintained in rats, Hartley guinea pigs, and Yorkshire pigs. However, it became insignificant in the subgroup of rabbits -5.29% (95% CI: -27.83, 17.26; I2 = 87%). Furthermore, CoQ10 significantly reduced the myocardial infarct size regardless of model type (either in vivo or ex vivo) and reperfusion time (either ≤ 4 h or >4 h). Conclusion: Coenzyme Q10 significantly decreased myocardial infarct size by 11.36% compared with the control group in animal models of myocardial I/R injury. This beneficial action was retained regardless of model type and reperfusion time.

Surface Characteristics and In-Vitro Studies of TiO2 Coatings by Plasma Electrolytic Oxidation in Potassium-Phosphate Electrolyte.

Plasma electrolytic oxidation (PEO) was used to produce titanium oxide (TiO2) coatings on Ti surface in potassium - phosphate electrolyte. The morphology, wettability, phase, and chemical compositions were studied as a function of processing parameters. The bioactivity of the coating was assessed by the ability to form biomimetic apatite in-vitro using cell culture medium. In-vitro studies using human mesenchymal stem cells were also conducted to evaluate cells' proliferation and viability of the treated Ti. The results revealed that the produced TiO2 coatings comprised pore features with the pore size increasing with applied current density and treatment duration due to high energy discharge channels at higher potential. The PEO treated Ti exhibited superhydrophilic characteristics with a contact angle <1°. The findings indicated that the large actual surface area produced by the PEO treatment and the presence of negatively charge P O 4 3 - are the key factors for the superhydrophilic behavior. The in-vitro studies revealed that the PEO treated groups had higher amount of biomimetic apatite formation compared to the as-polished Ti. The PEO treatment significantly enhanced the cells' adhesion and growth after 24 and 72 hrs compared to the untreated Ti. A significant difference in the bioactivity was not observed between anatase and rutile.

Interfacial adhesion and surface bioactivity of anodized titanium modified with SiON and SiONP surface coatings.

Titanium (Ti) surface modification via coating technologies (plasma spraying, electron-beam deposition) has been used to enhance bone-implant bonding by increasing the rate of hydroxyapatite (HA) formation, a property known as bioactivity. Regardless the enhancement in the surface activity, the high fabrication-temperature (> 600 °C) reduces coating-implant adhesion due to thermal expansion mismatch and reduces bioactivity due to increased crystallinity in the coating. Thus, amorphous surface coatings with strong Ti-substrate adhesion that can be fabricated at relatively low temperatures are crucially needed for enhanced osseointegration. Therefore, this study aimed to enhance the Ti surface bioactivity via strongly adherent bioactive thin film coatings deposited by low temperature (< 400 °C) plasma enhanced chemical vapor deposition technique on nanopore anodized-Ti (A-Ti) surface. Two groups of coating (silicon oxynitride (SiON) and silicon oxynitrophosphide (SiONP)) were deposited on anodized Ti and tested for interfacial adhesion and surface bioactivity. TEM and XPS were used to investigate the interfacial composition while interfacial adhesion was tested using nano-indentation tests which indicated a strong interfacial adhesion between the coatings and the A-Ti substrate. Surface bioactivity of the modified Ti was tested by comprehensive surface characterization (i.e., chemical composition, surface energy, morphology, and mechanical properties) and apatite formation on each surface. SiONP coating significantly enhanced the Ti surface bioactivity that presented the highest surface coverage of carbonated hydroxyapatite (HCA, ~ 40%) with a Ca/P ratio (~ 1.65) close to the stoichiometric hydroxyapatite (~ 1.67) found in bone biomineral. The HCA structure and morphology were confirmed by HR-TEM/SAED, XRD, FT-IR, and HR-SEM/EDX. MSCs in-vitro studies indicated preferable cells adhesion and proliferation on the modified surfaces without any cytotoxic effects. This study concluded that the improved surface bioactivity of Ti-SiON and Ti-SiONP coatings suggests their potential use as strongly adherent bioactive surface coatings for Ti implants.

Wettability and in-vitro study of titanium surface profiling prepared by electrolytic plasma processing.

Electrolytic plasma processing (EPP) was used to create hydrophilic surface profiles on titanium. The wettability, surface morphology characteristics and chemical composition of the treated samples were studied as a function of EPP processing parameters. The EPP profiled surfaces comprised of a characteristic "hills and valleys" morphology because of continuous surface melting and freezing cycles. A bimodal surface profile was produced with 2-3 µm height hills and valleys with nano-roughness (≤200 nm). The produced profile resulted in a significant contact angle decrease (from 38.7° to 5.4°). Ratios of actual surface area to projection area (r) and fraction of solid surface remaining dry (φ) were obtained from profilometry. The surface characteristics and large r values produced by EPP were able to induce hemi-wicking. Hence, EPP produced superhydrophilic surfaces on Ti. The bioactivity of EPP treated Ti was evaluated using cell free and MC3T3 cells in-vitro studies. The treated Ti surface significantly increased the bioactivity and formed stoichiometric hydroxyapatite after immersion in a bone cell culture medium for 21 days. Cells' attachment and proliferation studies indicated that EPP treated surface significantly enhances the cells' adhesion and growth after 24 and 48 h compared to the untreated surface. The results show that Ti surface profiling by EPP constitutes a promising method to potentially improve bone implant bonding.

Mini review: Biomaterials in repair and regeneration of nerve in a volumetric muscle loss.

Volumetric muscle loss (VML) following a severe trauma or injury is beyond the intrinsic regenerative capacity of muscle tissues, and hence interventional therapy is required. Extensive muscle loss concomitant with damage to neuromuscular components overwhelms the muscles' remarkable regenerative capacity. The loss of nervous and vascular tissue leads to further damage and atrophy, so a combined treatment for neuromuscular junction (NMJ) along with the volumetric muscle regeneration is important. There have been immense advances in the field of tissue engineering for skeletal muscle tissue and peripheral nerve regeneration, but very few address the interdependence of the tissues and the need for combined therapies to repair and regenerate fully functional muscle tissue. This review addresses the problem and presents an overview of the biomaterials that have been studied for tissue engineering of neuromuscular tissues associated with skeletal muscles.

Association of statin use in older people primary prevention group with risk of cardiovascular events and mortality: a systematic review and meta-analysis of observational studies.

BACKGROUND: Current evidence from randomized controlled trials on statins for primary prevention of cardiovascular disease (CVD) in older people, especially those aged > 75 years, is still lacking. We conducted a systematic review and meta-analysis of observational studies to extend the current evidence about the association of statin use in older people primary prevention group with risk of CVD and mortality. METHODS: PubMed, Scopus, and Embase were searched from inception until March 18, 2021. We included observational studies (cohort or nested case-control) that compared statin use vs non-use for primary prevention of CVD in older people aged ≥ 65 years; provided that each of them reported the risk estimate on at least one of the following primary outcomes: all cause-mortality, CVD death, myocardial infarction (MI), and stroke. Risk estimates of each relevant outcome were pooled as a hazard ratio (HR) with a 95% confidence interval (CI) using the random-effects meta-analysis model. The quality of the evidence was rated using the GRADE approach. RESULTS: Ten observational studies (9 cohorts and one case-control study; n = 815,667) fulfilled our criteria. The overall combined estimate suggested that statin therapy was associated with a significantly lower risk of all-cause mortality (HR: 0.86 [95% CI 0.79 to 0.93]), CVD death (HR: 0.80 [95% CI 0.78 to 0.81]), and stroke (HR: 0.85 [95% CI 0.76 to 0.94]) and a non-significant association with risk of MI (HR 0.74 [95% CI 0.53 to 1.02]). The beneficial association of statins with the risk of all-cause mortality remained significant even at higher ages (> 75 years old; HR 0.88 [95% CI 0.81 to 0.96]) and in both men (HR: 0.75 [95% CI: 0.74 to 0.76]) and women (HR 0.85 [95% CI 0.72 to 0.99]). However, this association with the risk of all-cause mortality remained significant only in those with diabetes mellitus (DM) (HR 0.82 [95% CI 0.68 to 0.98]) but not in those without DM. The level of evidence of all the primary outcomes was rated as "very low." CONCLUSIONS: Statin therapy in older people (aged ≥ 65 years) without CVD was associated with a 14%, 20%, and 15% lower risk of all-cause mortality, CVD death, and stroke, respectively. The beneficial association with the risk of all-cause mortality remained significant even at higher ages (> 75 years old), in both men and women, and in individuals with DM, but not in those without DM. These observational findings support the need for trials to test the benefits of statins in those above 75 years of age.

Silicon Oxynitrophosphide Nanoscale Coating Enhances Antioxidant Marker-Induced Angiogenesis During in vivo Cranial Bone-Defect Healing.

Critical-sized bone defects are challenging to heal because of the sudden and large volume of lost bone. Fixative plates are often used to stabilize defects, yet oxidative stress and delayed angiogenesis are contributing factors to poor biocompatibility and delayed bone healing. This study tests the angiogenic and antioxidant properties of amorphous silicon oxynitrophosphide (SiONPx) nanoscale-coating material on endothelial cells to regenerate vascular tissue in vitro and in bone defects. in vitro studies evaluate the effect of silicon oxynitride (SiONx) and two different SiONPx compositions on human endothelial cells exposed to ROS (eg, hydrogen peroxide) that simulates oxidative stress conditions. in vivo studies using adult male Sprague Dawley rats (approximately 450 g) were performed to compare a bare plate, a SiONPx-coated implant plate, and a sham control group using a rat standard-sized calvarial defect. Results from this study showed that plates coated with SiONPx significantly reduced cell death, and enhanced vascular tubule formation and matrix deposition by upregulating angiogenic and antioxidant expression (eg, vascular endothelial growth factor A, angiopoetin-1, superoxide dismutase 1, nuclear factor erythroid 2-related factor 2, and catalase 1). Moreover, endothelial cell markers (CD31) showed a significant tubular structure in the SiONPx coating group compared with an empty and uncoated plate group. This reveals that atomic doping of phosphate into the nanoscale coating of SiONx produced markedly elevated levels of antioxidant and angiogenic markers that enhance vascular tissue regeneration. This study found that SiONPx or SiONx nanoscale-coated materials enhance antioxidant expression, angiogenic marker expression, and reduce ROS levels needed for accelerating vascular tissue regeneration. These results further suggest that SiONPx nanoscale coating could be a promising candidate for titanium plate for rapid and enhanced cranial bone-defect healing. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.