Nanocarrier-Based Targeting of Pattern Recognition Receptors as an Innovative Strategy for Enhancing Sepsis Therapy.

Sepsis is a life-threatening condition caused by an abnormal immune response to infection, leading to multiple organ failure. Despite advances in understanding its pathophysiology, effective pharmacological interventions and nanomedicines to treat sepsis remain lacking. Pattern recognition receptors (PRRs), crucial in detecting microbial toxins and triggering inflammation, are promising therapeutic targets for bacterial sepsis and related organ injuries.

Oxidative stress markers and tissue iron overload after 12-months vitamin E supplementation for children with transfusion-dependent β-thalassemia on different iron chelators: A randomized placebo-controlled trial.

Background: Vitamin E is an anti-oxidant depleted in thalassemia as a result of iron overload.

Aim: We investigated the efficacy and safety of vitamin E as an adjuvant therapy to iron chelators in transfusion-dependent thalassemia patients in relation to tissue iron overload and examine its potential corrective value to oxidative stress markers including peroxiredoxin-2 (PRDX2).

Methods: This randomized prospective study included 180 pediatric patients with transfusion-dependent β-thalassemia who were equally divided into three groups to either receive desferrioxamine (DFO), deferiprone (DFP) or deferasirox (DFX).

Antimicrobial peptide-fucoidan nanoplexes: A novel multifunctional biomimetic nanocarrier for enhanced vancomycin delivery against bacterial infections and sepsis.

Sepsis, a critical medical emergency, continues to pose a substantial worldwide healthcare challenge that necessitates innovative approaches for enhanced treatment. Hence, this study aimed to develop multifunctional biomimetic vancomycin (VCM)-loaded nanoplexes (VCM-FU-PEP-NPs) utilizing a novel antimicrobial peptide (CC-19 peptide) and Fucoidan (FU) to target the Toll-like receptor (TLR) inflammatory pathway and augment the antibacterial efficacy against bacterial sepsis. The CC-19 peptide (CRPRKWIKIKFRCKSLKFC) was designed utilizing computer-aided drug design tools and subsequently synthesized.

Potential of nanocarrier-mediated delivery of vancomycin for MRSA infections.

Introduction: Methicillin-resistant (MRSA) threatens global health due to its resistance to vancomycin, which is the standard treatment despite limitations, including nephrotoxicity and low intracellular permeability. This necessitates the development of innovative strategies such as nanocarrier-mediated delivery to overcome such limitations. Nanocarriers serve as delivery systems for vancomycin and exhibit inherent antibacterial properties, potentially providing synergism and overcoming MRSA's resistance.

Multifunctional hyaluronic acid-based biomimetic/pH-responsive hybrid nanostructured lipid carriers for treating bacterial sepsis.

Introduction: The application of biomimetic and stimuli-responsive nanocarriers displays considerable promise in improving the management of bacterial sepsis and overcoming antimicrobial resistance. Therefore, the study aimed to synthesize a novel hyaluronic acid-lysine conjugate (HA-Lys) and to utilize the attributes of the synthesized HA-Lys with Tocopherol succinate (TS) and Oleylamine (OLA) in the formulation of multifunctional biomimetic pH-responsive HNLCs loaded with vancomycin (VCM-HNLCs), to combat bacterial sepsis.

Methods: A novel hyaluronic acid-lysine conjugate (HA-Lys) was synthesized and characterized using FTIR and H NMR spectroscopy.

Hyaluronic acid-silybin conjugate for the preparation of multifunctional, biomimetic, vancomycin-loaded self-assembled polymersomes against bacterial sepsis.

Sepsis, a life-threatening disruption, remains a significant global healthcare challenge that urgently needs novel strategies to improve management. This study aimed to develop multifunctional vancomycin-loaded polymersomes (VCM-HA-SIL-Ps) using a novel hyaluronic acid-silybin (HA-SIL) conjugate to target the TLR inflammatory pathway and enhance VCM's efficacy against bacterial sepsis. HA-SIL was synthesized and characterized by FT-IR, UV-Vis spectroscopy, and H NMR.

Multifunctional Dual Enzyme-Responsive Nanostructured Lipid Carriers for Targeting and Enhancing the Treatment of Bacterial Infections.

Bacterial infections pose an increasingly worrisome threat to the health of humankind, with antibiotic resistance contributing significantly to this burden. With current conventional antibiotics perpetuating the problem, and a paucity in developing antibiotics, drug delivery systems incorporating nanotechnology appear promising. As such, a dual enzyme-responsive multifunctional nanostructured lipid carrier (NLC) incorporating farnesol (FAN) and triglycerol monostearate (TGMS), was conceptualized for the codelivery of vancomycin (VCM) and antimicrobial peptide (AMP) to enhance the antibacterial activity of VCM.

Disease-Inspired Design of Biomimetic Tannic Acid-Based Hybrid Nanocarriers for Enhancing the Treatment of Bacterial-Induced Sepsis.

This study explored the development of novel biomimetic tannic acid-based hybrid nanocarriers (HNs) for targeted delivery of ciprofloxacin (CIP-loaded TAH-NPs) against bacterial-induced sepsis. The prepared CIP-loaded TAH-NPs exhibited appropriate physicochemical characteristics and demonstrated biocompatibility and nonhemolytic properties. Computational simulations and microscale thermophoresis studies validated the strong binding affinity of tannic acid (TA) and its nanoformulation to human Toll-like receptor 4, surpassing that of the natural substrate lipopolysaccharide (LPS), suggesting a potential competitive inhibition against LPS-induced inflammatory responses.

Novel peptide and hyaluronic acid coated biomimetic liposomes for targeting bacterial infections and sepsis.

Sepsis is a life-threatening syndrome resulting from an imbalanced immune response to severe infections. Despite advances in nanomedicines, effective treatments for sepsis are still lacking. Herein, vancomycin free base (VCM)-loaded dual functionalized biomimetic liposomes based on a novel TLR4-targeting peptide (P3) and hyaluronic acid (HA) (HA-P3-Lipo) were developed to enhance sepsis therapy.

Multi-functional pH-responsive and biomimetic chitosan-based nanoplexes for targeted delivery of ciprofloxacin against bacterial sepsis.

Bacterial sepsis is a mortal syndromic disease characterized by a complex pathophysiology that hinders effective targeted therapy. This study aimed to develop multifunctional, biomimetic and pH-responsive ciprofloxacin-loaded chitosan (CS)/sodium deoxycholic acid (SDC) nanoplexes (CS/SDC) nanoplexes with the ability to target and modulate the TLR4 pathway, activated during sepsis. The formulated nanoplexes were characterized in terms of physicochemical properties, in silico and in vitro potential biological activities.

Inflammation-responsive drug delivery nanosystems for treatment of bacterial-induced sepsis.

Sepsis, a complication of dysregulated host immune systemic response to an infection, is life threatening and causes multiple organ injuries. Sepsis is recognized by WHO as a big contributor to global morbidity and mortality. The heterogeneity in sepsis pathophysiology, antimicrobial resistance threat, the slowdown in the development of antimicrobials, and limitations of conventional dosage forms jeopardize the treatment of sepsis.

Stimuli-responsive and biomimetic delivery systems for sepsis and related complications.

Sepsis, a consequence of an imbalanced immune response to infection, is currently one of the leading causes of death globally. Despite advances in the discoveries of potential targets and nanotechnology, sepsis still lacks effective drug delivery systems for optimal treatment. Stimuli-responsive and biomimetic nano delivery systems, specifically, are emerging as advanced bio-inspired nanocarriers for enhancing the treatment of sepsis.

Prophylactic use of platelet-rich plasma for post-spinal low back pain following gynecological surgery: a randomized clinical trial.

Background: Post-spinal back pain is suggested to occur as a result of a localized inflammatory response that is often associated with some degree of muscle spasm. We aimed to evaluate the effect of platelet-rich plasma (PRP) in reducing the incidence of post-spinal back pain.

Methods: One hundred patients were randomly enrolled and scheduled for elective gynecological surgery under spinal anesthesia.

Estimate Stress-Strength Reliability Model Using Rayleigh and Half-Normal Distribution.

In the field of life testing, it is very important to study the reliability of any component under testing. One of the most important subjects is the "stress-strength reliability" term which always refers to the quantity  ( > ) in any statistical literature. It resamples a system with random strength () that is subjected to a random strength () such that a system fails in case the stress exceeds the strength.

Valuable Role of Neutrophil CD64 and Highly Sensitive CRP Biomarkers for Diagnostic, Monitoring, and Prognostic Evaluations of Sepsis Patients in Neonatal ICUs.

Background: Neonatal sepsis (NS) is a very critical medical situation associated with high morbidities and mortalities. There is an utmost need for a new tool helping in early diagnosis and proper management of sepsis neonates. Neutrophil CD64 (nCD64) shows a very promising value in this concerning issue.

Serum progranulin levels in paediatric patients with Gaucher disease; relation to disease severity and liver stiffness by transient elastography.

Background: Non-invasive screening for liver fibrosis using transient elastography (TE) could be of value in the management of Gaucher disease (GD). Progranulin (PGRN) is a novel disease modifier in GD and an independent marker of liver fibrosis.

Objectives: We determined PGRN levels in paediatric patients with GD and assessed its role as a potential marker for disease severity and relation to liver stiffness by TE.

Reticulocyte Hemoglobin Content (Ret He): A Simple Tool for Evaluation of Iron Status in Childhood Cancer.

Background: Cancer-related anemia is a common complication of cancer and its treatment that may be mediated by nutritional deficiency or inflammatory cytokines inhibiting erythropoiesis.

Aim: We evaluated the value of reticulocyte hemoglobin content (Ret He) as a marker of iron availability for erythropoiesis in childhood cancer and the impact of oral iron supplementation on hematologic parameters in patients with low Ret He.

Materials And Methods: This prospective study included 100 pediatric patients with cancer on chemotherapy who were screened for the presence of anemia.

Oxidative stress markers in neonatal respiratory distress syndrome: advanced oxidation protein products and 8-hydroxy-2-deoxyguanosine in relation to disease severity.

Objective: We assessed oxidant-antioxidant status and evaluated the role of lipid peroxidation, oxidative DNA damage, and protein oxidation in the development and severity of neonatal respiratory distress syndrome (RDS).

Methods: Forty preterm neonates with RDS were compared with another 40 preterm neonates without RDS enrolled as controls. Total antioxidant capacity (TAC), malondialdehyde (MDA), advanced oxidation protein products (AOPPs), 8-hydroxy-2-deoxyguanosine (8-OHdG), and trace elements (copper and zinc) were measured in cord blood (day 0) for all neonates and repeated on day 3 for the RDS group.

Angiopoietin-2 as a Marker of Retinopathy in Children and Adolescents With Sickle Cell Disease: Relation to Subclinical Atherosclerosis.

Objectives: Angiopoietin-2 (Ang-2) is a multifaceted cytokine that functions in both angiogenesis and inflammation. A proangiogenic state has been found in adults with sickle cell disease (SCD), mainly because of elevated Ang-2 levels. We determined Ang-2 level in 40 children and adolescents with SCD compared with 40 healthy controls and assessed its relation to retinopathy as well as carotid intimamedia thickness (CIMT).

Surfactant protein D as a marker for pulmonary complications in pediatric patients with sickle cell disease: Relation to lung function tests.

Background: Surfactant protein D (SP-D) is considered a candidate biomarker for lung integrity and for disease progression.

Aim: We determined the level of SP-D in children and adolescents with SCD and assessed its possible relation to pulmonary complications and lung function.

Methods: Serum SP-D levels were assessed in 50 SCD patients compared with 30 healthy controls.

Evaluation of continuous glucose monitoring system for detection of alterations in glucose homeostasis in pediatric patients with β-thalassemia major.

Background: Disturbances of glucose metabolism are common in β-thalassemia major (β-TM).

Aim: This study was conducted to assess the pattern of glucose homeostasis in pediatric β-TM patients comparing oral glucose tolerance test (OGTT) and continuous glucose monitoring system (CGMS).

Methods: Two-hundred β-TM patients were studied and those with random blood glucose (RBG) ≥7.

Auditory brainstem response in full-term neonates born to mothers with iron deficiency anemia: relation to disease severity.

Iron is crucial for fetal brain development; however, there are insufficient data regarding the effects of maternal iron deficiency anemia (IDA) on auditory neural maturation. We evaluated the effect of maternal IDA on auditory brainstem response (ABR) in full-term neonates. Out of 223 pregnant women, 50 were diagnosed as having IDA and 50 healthy mothers were enrolled as controls.

Comparison of intraperitoneal versus intravenous dexamethasone on postoperative nausea and vomiting after gynecological laparoscopy: a randomized clinical trial.

Background: Postoperative nausea and vomiting (PONV) is a common complication following laparascopic surgery. This study compared the effect of intraperitoneal versus intravenous dexamethasone for reducing PONV after gynecological laparoscopic surgeries.

Methods: Eighty adult female patients, American Society of Anesthesiologists physical status I-II, scheduled for gynecological laparoscopic surgery were randomized to receive 8 mg dexamethasone intravenously (IV) (n = 40) or intraperitoneally (IP) (n = 40).