ATP releasing channels and the ameliorative effects of high intensity interval training on diabetic heart: a multifaceted analysis.

Type 2 diabetes (T2D) can cause severe cardiac complications at functional, histologic and molecular levels. These pathological complications could be mediated by ATP-releasing channels such as Panx1 and ATP receptors, in particular P2X7. The aim of our study was to investigate the effect of high-intensity interval training (HIIT) on T2D-induced cardiac complications at the functional, histopathological and molecular levels, with a particular focus on ATP-releasing channels. 48 male Wistar rats at the age of 8 weeks were randomly allocated into four groups: control (Con), Diabetes (T2D), Training (TR), and Diabetes + Training (T2D + TR). T2D was induced by a high-fat diet plus a low dose (35 mg/kg) of STZ administration. Rats in the TR and T2D + TR groups underwent an 8-weeks training program involving intervals ranging from 80 to 100% of their maximum running speed (Vmax), with 4-10 intervals per session. Protein expression of Interleukin 1ß (IL1ß), Interleukin 10 (IL-10), Pannexin 1 (Panx1), P2X7R (purinergic P2X receptor 7), NLRP1 (NLR Family Pyrin Domain Containing 1), BAX, and Bcl2 were measured in the heart tissue. Additionally, we assessed heart function, histopathological changes, as well as insulin resistance using the homeostasis model assessment of insulin resistance (HOMA-IR). In contrast to the T2D group, HIIT led to increased protein expression of Bcl2 and IL-10 in the heart. It also resulted in improvements in systolic and diastolic blood pressures, heart rate, ± dp/dt (maximum and minimum changes in left ventricular pressure), while reducing protein expression of IL-1ß, Panx1, P2X7R, NLRP1, and BAX levels in the heart. Furthermore, left ventricular diastolic pressure (LVDP) was reduced (P ≤ 0.05). Moreover, heart lesion scores increased with T2D but decreased with HIIT, along with a reduction in fibrosis percentage (P ≤ 0.05). The results of this study suggest that the cardioprotective effects of HIIT on the diabetic heart may be mediated by the modulation of ATP-releasing channels. This modulation may lead to a reduction in inflammation and apoptosis, improve cardiac function, and attenuate cardiac injury and fibrosis.

Genipin-Cross-Linked Silk Fibroin/Alginate Dialdehyde Hydrogel with Tunable Gelation Kinetics, Degradability, and Mechanical Properties: A Potential Candidate for Tissue Regeneration.

Genipin-cross-linked silk fibroin (SF) hydrogel is considered to be biocompatible and mechanically robust. However, its use remains a challenge for in situ forming applications due to its prolonged gelation process. In our attempt to facilitate the in situ fabrication of a genipin-mediated SF hydrogel, alginate dialdehyde (ADA) was utilized as a reinforcement template. Here, SF/ADA-based hydrogels with different compositions were synthesized covalently and ionically. Incorporating ADA into the SF hydrogel increased pore size (44.66-174.66 µm), porosity (61.59-80.40%), and the equilibrium swelling degree (7.60-30.17). Moreover, a wide range of storage modulus and compressive modulus were obtained by adjusting the proportions of SF and ADA networks within the hydrogel. The in vitro cell analysis using preosteoblast cells (MC3T3-E1) demonstrated the cytocompatibility of all hydrogels. Overall, the covalently and ionically cross-linked SF/ADA hydrogel represents a promising solution for in situ forming hydrogels for applications in tissue regeneration.

Caffeine attenuates spermatogenic disorders in mice with induced chronic scrotal hyperthermia.

OBJECTIVE: Chronic scrotal hyperthermia (SHT) can lead to serious disorders of the male reproductive system, with oxidative stress playing a key role in the onset of these dysfunctions. Thus, we evaluated the impact of caffeine, a potent antioxidant, on cellular and tissue disorders in mice with chronic SHT. METHODS: In this experimental study, 56 adult male NMRI mice were allocated into seven equal groups. Apart from the non-treated control group, all were exposed to heat stress. Two groups, termed "preventive" and "curative," were orally administered caffeine. The preventive mice began receiving caffeine immediately prior to heat exposure, while for the curative group, a caffeine regimen was initiated 15 consecutive days following cessation of heat exposure. Each treated group was subdivided based on pairing with a positive control (Pre/curative [Cur]+PC) or a vehicle (Pre/Cur+vehicle). Upon conclusion of the study, we assessed sperm characteristics, testosterone levels, stereological parameters, apoptosis, antioxidant and oxidant levels, and molecular markers. RESULTS: Sperm parameters, testosterone levels, stereological parameters, biochemical factors (excluding malondialdehyde [MDA]), and c-kit gene expression were significantly elevated in the preventive and curative groups, especially the former, relative to the other groups. Conversely, expression levels of the heat shock protein 72 (HSP72) and nuclear factor kappa beta (NF-κß) genes, MDA levels, and apoptotic cell density were markedly lower in both caffeine-treated groups relative to the other groups, with more pronounced differences observed in the preventive group. CONCLUSION: Overall, caffeine attenuated cellular and molecular abnormalities induced by heat stress in the testis, particularly in the mice treated under the preventive condition.

High-intensity intermittent training ameliorates methotrexate-induced acute lung injury.

Inflammation and oxidative stress are recognized as two primary causes of lung damage induced by methotrexate, a drug used in the treatment of cancer and immunological diseases. This drug triggers the generation of oxidants, leading to lung injury. Given the antioxidant and anti-inflammatory effects of high-intensity intermittent training (HIIT), our aim was to evaluate the therapeutic potential of HIIT in mitigating methotrexate-induced lung damage in rats. Seventy male Wistar rats were randomly divided into five groups: CTL (Control), HIIT (High-intensity intermittent training), ALI (Acute Lung Injury), HIIT+ALI (pretreated with HIIT), and ALI + HIIT (treated with HIIT).HIIT sessions were conducted for 8 weeks. At the end of the study, assessments were made on malondialdehyde, total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (Gpx), myeloperoxidase (MPO), interleukin 10 (IL-10), tumor necrosis factor-alpha (TNF-α), gene expression of T-bet, GATA3, FOXP3, lung wet/dry weight ratio, pulmonary capillary permeability, apoptosis (Caspase-3), and histopathological indices.Methotrexate administration resulted in increased levels of TNF-α, MPO, GATA3, caspase-3, and pulmonary edema indices, while reducing the levels of TAC, SOD, Gpx, IL-10, T-bet, and FOXP3. Pretreatment and treatment with HIIT reduced the levels of oxidant and inflammatory factors, pulmonary edema, and other histopathological indicators. Concurrently, HIIT increased the levels of antioxidant and anti-inflammatory factors.

Kdr genotyping and the first report of V410L and V1016I kdr mutations in voltage-gated sodium channel gene in Aedes aegypti (Diptera: Culicidae) from Iran.

BACKGROUND: Aedes aegypti is the main vector of arboviral diseases worldwide. The species invaded and became established in southern Iran in 2020. Insecticide-based interventions are primarily used for its control. With insecticide resistance widespread, knowledge of resistance mechanisms is vital for informed deployment of insecticidal interventions, but information from Iranian Ae. aegypti is lacking. METHODS: Fifty-six Ae. aegypti specimens were collected from the port city of Bandar Lengeh in Hormozgan Province in the South of Iran in 2020 and screened for kdr mutations. The most common kdr mutations in Latin America and Asia (V410L, S989P, V1016G/I and F1534C), especially when present in combinations, are highly predictive of DDT and pyrethroid resistance were detected. Phylogenetic analyses based on the diversity of S989P and V1016G/I mutations were undertaken to assess the phylogeography of these kdr mutations. RESULTS: Genotyping all four kdr positions of V410L, S989P, V1016G/I and F1534C revealed that only 16 out of the 56 (28.57%) specimens were homozygous wild type for all kdr mutation sites. Six haplotypes including VSVF (0.537), VSVC (0.107), LSVF (0.016), LSIF (0.071), VPGC (0.257) and LPGC (0.011) were detected in this study. For the first time, 11 specimens harbouring the V410L mutation, and 8 samples with V1016I mutation were found. V410L and V1016I were coincided in 8 specimens. Also, six specimens contained 1016G/I double mutation which was not reported before. CONCLUSIONS: The relatively high frequency of these kdr mutations in Iranian Ae. aegypti indicates a population exhibiting substantial resistance to pyrethroid insecticides, which are used widely in control operations and household formulations. The detection of the 410L/1016I kdr mutant haplotype in Iranian Ae. aegypti suggests possible convergence of invasive populations from West Africa or Latin America. However, as Iran has very limited maritime/air connections with those African countries, a Latin American origin for the invasive Ae. aegypti in Iran is more plausible.

Novel nucleotide variations in the thrombomodulin (THBD) gene involved in coagulation pathways can increase the risk of recurrent pregnancy loss (RPL).

Recurrent pregnancy loss (RPL) is a common but complex complication in fertility conditions, affecting about 15-20% of couples. Although several causes have been proposed for RPL, it occurs in about 35-60% of cases without a known explanation. A strong assumption is that genetic factors play a role in the etiology and pathophysiology of PRL. Therefore, several genes are proposed as candidates in the pathogenesis of RPL. The current study aimed to investigate the effects of nucleotide changes in the THBD (thrombomodulin) gene as an RPL-related candidate gene. This gene encodes a cell receptor for thrombin and is involved in reproductive loss in RPL cases. Its involvement in the natural anticoagulant system has been extensively studied. By genetic screening of the entire coding and noncoding regions of the THBD gene, we found twenty-seven heterozygous and homozygous nucleotide changes. Ten of them led to amino acid substitutions, seven variants were identified in the promoter region, and eight of them occurred in 3'UTR. Potentially, the pathogenicity effects of these variations on THBD protein were evaluated by several prediction tools. The numerous genomic variations prompted noticeable modifications of the protein's structural and functional properties. Furthermore, in-silico scores were consistent with deleterious effects for these mutations. The results of this study provide genetic information that will be useful in the future for clinicians, scientists, and students to understand the unknown causes of RPL better. It may also pave the way for developing diagnostic/prognostic approaches to help treat PRL patients.

Inhalation of Spray-Dried Extract of Salvia rosmarinus Spenn Alleviates Lung Inflammatory, Oxidative, and Remodeling Changes in Asthmatic Rats.

INTRODUCTION: For centuries, Salvia rosmarinus Spenn has been applied as folk medicine to cure different diseases due to its anti-inflammatory, antibacterial, antioxidant, antifungal, and antitumor effects. To find bioactive medicinal herbs exerting a protective effect on airway inflammation and remodeling, we assessed the anti-oxidative and anti-inflammatory effects of an aqueous spray-dried extract of Salvia rosmarinus Spenn. (rosemary) in an ovalbumin-induced asthmatic rat model. METHODS: Rats were randomly divided into normal control (control), asthma, asthma+rosemary extract (RE) (13 mg/kg), asthma+RE (50 mg/kg), and asthma+budesonide groups. After 50 days, animals were anesthetized, and then blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected for subsequent serological and pathological studies. Histopathology of lung tissues was evaluated by H&E staining. The oxidative stress parameters and airway inflammation factors in BALF and lung tissue were explored. RESULTS: Using thin layer chromatography, the presence of rosmarinic acid was confirmed in aqueous extract of rosemary. Furthermore, RE markedly decreased immunoglobulin E levels (50 mg/kg; p < 0.001 vs. asthma group) and inflammatory cytokines (50 mg/kg; p < 0.001 vs. asthma group) and increased antioxidant enzymes (50 mg/kg, p < 0.001 vs. asthma group). Furthermore, RE at a concentration of 50 mg/kg obviously reduced the number of inflammatory cells, goblet cells, and pathological changes compared to the asthma group. CONCLUSION: The results showed that RE administration might prevent or alleviate allergic asthma-related pathological change, probably via antioxidant and anti-inflammatory mechanisms.

Ameliorating effects of Acacia arabica and Ocimum basilicum on acetic acid-induced ulcerative colitis model through mitigation of inflammation and oxidative stress.

Introduction: Ulcerative colitis (UC) is a chronic recurrent inflammatory disease of the large intestine and rectum. The disease is characterized by oxidative stress and severe inflammation. Research has shown the anti-oxidative and anti-inflammatory effects induced by consuming the Acacia arabia and Ocimum basilicum. The present study aimed to evaluate the effect of treatment with O. basilicum together with A. arabica on healing, inflammation, and oxidative stress in the course of experimental colitis in rats. Methods: A total number of 50 male rats were selected and randomly assigned to five groups of 10 rats each. Colitis was induced in rats by enemas with a 4 % acetic acid solution. Four days after the colitis induction, the rats were orally treated for the next 4 days with saline or a combination of A. arabica and O. basilicum (1000 mg/kg) or sulfasalazine (100 mg/kg). Results: Acetic acid-induced colitis increased the colon's macroscopic and histopathological damage scores; increased colon levels of MDA (Malondialdehyde), MPO (Myeloperoxidase), TNF-α (Tissue necrosis factor α), IL6 (Interleukin 6), and IL17 (Interleukin 17); and decreased SOD (Superoxide Dismutase), GPx (Glutathione Peroxidase), and IL10 (Interleukin 10) levels in the treated rats compared with the control group (P < 0.001). Overall, a combination of A. arabica and O. basilicum reduced macroscopic and histopathological damage scores (P < 0.01) of the colon, and MDA, MPO, TNF-α, IL6 (P < 0.001), and IL17 (P < 0.01) levels of the colon. Furthermore, it increased SOD, GPx, and IL10 levels compared to the colitis group (P < 0.01). Conclusion: A. arabica and O. basilicum have improving effects on UC by reducing inflammation and oxidative stress.

Evaluation of Laboratory Findings of Patients with Coronavirus Disease 2019 in Kerman, Iran.

Background & Objective: Since December 2019 in Wuhan, China there is a new form of pneumonia and after expansion in other countries, World Health Organization (WHO) called it Coronavirus Disease 2019 (COVID-19). Since the clinical laboratory findings have played an important role in the progression of the disease, this study aimed to evaluate the laboratory findings in COVID-19 patients (before vaccination). Methods: In this case-control study that was conducted from February to August 2020; the laboratory test status in 101 positive COVID-19 patients was evaluated and compared with 101 healthy individuals. Results: The results of our study showed that 21% of patients had low WBC, 24.75% low RBC, 37.62%, low Hb, 18.81% with low HCT, 29.7%, low Plt, 41.58% had High PT, 71.29% high CRP, 17.82% high urea, 11.88% high CR, 15.84% high LDH, 10.89% low sodium, 14.75% low potassium (K). The quantitative examination of blood factors showed that lymph%, mixed%, PLT, HCT, Hb, and RBC were higher in the control group than in the case group. While Neu%, WBC, PTT, CRP, UREA, LDH, K in the patient group were higher than in the control group. Conclusion: According to the results of the study, it can be concluded that in the clinical treatment of COVID-19 patients, much attention should be paid to the laboratory indicators to identify and intervene early in critically ill patients.

The effect of electronic error-reporting forms on nurse's stress and the rate of error-reporting.

OBJECTIVES: The patient safety culture includes a systematic approach that promotes safe care for patients and the leadership that supports it. Medical errors threaten patient safety. A significant portion of medical errors is committed by nurses. Although error-reporting provides valuable information to prevent errors, most nurses do not report their errors due to their high level of stress. This study was to investigate the effect of electronic error-reporting forms on nurses' stress and the rate of error-reporting. METHODS: The nurses' level of stress was compared when using paper error-reporting and 6 months after using electronic forms. A revised version of the Coudron questionnaire was completed by 186 nurses. Data were analyzed by SPSS 23 using Wilcoxon test. The number of reported errors in paper and electronic media was compared over the same period. RESULTS: Implementation of the electronic error-reporting form reduced the job stress of nurses by 22.22 points (p=.00) and increased the error-reporting rate by 12.86% (p<.05). CONCLUSIONS: Although nurse's stress significantly decreases after implementing electronic error-reporting forms, their level of stress is still high and they are still at risk for physical and mental problems. Using methods like modifying the error-reporting form will increase the error-reporting rate.

The Diabetic Lung Can Be Ameliorated by Citrullus colocynthis by Reducing Inflammation and Oxidative Stress in Rats with Type 1 Diabetes.

Background: Diabetes impacts various organs in the body and some reports showed that the lung is also affected by diabetes, and an imbalance of inflammation and oxidative stress may participate to diabetic lung impairments. The present study is conducted to assess the impacts of Citrullus colocynthis (CC) on some aspects of these impairments. Methods: Frothy two male Wistar rats (3-4 months old and weighing 200-250 g) were used in the present research. Animals were divided into 3 groups of control, Diabetes, and Diabetes + Drug. CC was administered to diabetic rats orally. The lung tissue and BALF oxidative stress and inflammatory indices including the MDA, TAC, SOD, Gpx, TNFα, IL-6, IL-17, and IL-10 were evaluated by the ELISA method. Results: Our observations disclosed the ameliorative impacts of CC administration against oxidative stress and inflammation imbalance. Also, it was found that CC improved body weight and fasting blood sugar in rats with diabetes. Conclusion: We can conclude that the administration of CC can be effective in improving diabetic lungs in rats.

Comparison of preventive and therapeutic effects of continuous exercise on acute lung injury induced with methotrexate.

Methotrexate (Mtx) is used to treat various diseases, including cancer, arthritis and other rheumatic diseases. However, it induces oxidative stress and pulmonary inflammation by stimulating production of reactive oxygen species and cytokines. Considering the positive effects of physical activity, our goal was to investigate the preventive and therapeutic role of continuous training (CT) on Mtx-induced lung injury in rats. The rats were divided into five groups of 14 animals: a control group (C); a continuous exercise training group (CT; healthy rats that experienced CT); an acute lung injury with Mtx group (ALI); a pretreatment group with CT (the rats experienced CT before ALI induction), and a post-treatment group with CT (the rats experienced CT after ALI induction). One dose of 20 mg/kg Mtx intraperitoneal was administered in the Mtx and training groups. Forty-eight hours after the last exercise session all rats were sacrificed. According to our results, the levels of tumour necrosis factor-α (TNF-α), malondialdehyde (MDA), myeloperoxidase (MPO), GATA binding protein 3 (GATA3) and caspase-3 in the ALI group significantly increased compared to the control group, and the levels of superoxide dismutase (SOD), glutathione peroxidase (GPX), total antioxidant capacity (TAC), interleukin-10 (IL-10), forkhead box protein 3 (FOXP3), and T-bet decreased. In contrast, compared to the acute lung injury group, pretreatment and treatment with CT reduced TNF-α, MDA, MPO, GATA3 and caspase-3 and increased SOD, GPX, TAC, IL-10, FOXP3 and T-bet levels. The effects of CT pretreatment were more significant than the effects of CT post-treatment. Continuous exercise training effectively reduced oxidative stress and inflammatory cytokines and ameliorated Mtx-induced injury, and the effects of CT pretreatment were more significant than the effects of CT post-treatment. NEW FINDINGS: What is the central question of this study? Considering the high prevalence of lung injury in society, does exercise as a non-pharmacological intervention have ameliorating effects on lung injury? What is the main finding and its importance? Exercise can have healing effects on the lung after pulmonary injury through reducing inflammation, oxidative stress and apoptosis. Considering the lower side effects of exercise compared to drug treatments, the results of this study may be useful in the future.

Investigation of osteogenesis and angiogenesis in perfusion bioreactors using improved multi-layer PCL-nHA-nZnO electrospun scaffolds.

PURPOSE: Bone tissue engineering aims to create a three-dimensional, matured, angiogenic scaffold with a suitable thickness that resembles a natural bone matrix. On the other hand, electrospun fibers, which researchers have considered due to their good biomimetic properties, are considered 2D structures. Due to the highly interwoven network and small pore size, achieving the desired thickness for bone lesions has always been challenging. In bone tissue engineering, bioreactors are crucial for achieving initial tissue maturity and introducing certain signals as flow parameters for differentiation. METHODS: In the present study, Human bone marrow mesenchymal stem cells (hBMSCs) and human umbilical vein endothelial cells (HUVECs) were co-cultured in a perfusion bioreactor on treated (improved pore size by gelatin sacrification and subsequent ultrasonication) 5-layer polycaprolactone-nano hydroxyapatite-nano zinc oxide (T-PHZ) scaffolds to investigate osteogenesis and angiogenesis simultaneously. The flow parameters and stresses on the cells were studied using two patterns of parallel and vertical scaffolds relative to the flow of the culture medium. In dynamic vertical flow (DVF), the culture medium flows perpendicular to the scaffolds, and in dynamic parallel flow (DPF), the culture medium flows parallel to the scaffolds. In all evaluations, static samples (S) served as the control group. RESULTS: Live/dead, and MTT assays demonstrated the biocompatibility of the 5-layer scaffolds and the suitability of the bioreactor's functional conditions. ALP activity, EDAX analysis, and calcium content measurements exhibited greater osteogenesis for T-PHZ scaffolds in DVF conditions. Calcium content increased by a factor of 2.2, 1.8, and 1.6 during days 7 to 14 of culture under DVF, DPF and S conditions, respectively. After 21 days of co-culturing, an immunohistochemistry (IHC) test was performed to investigate angiogenesis and osteogenesis. Five antibodies were investigated in DVF, CD31, VEGFA, and VEGFR2 for angiogenesis, osteocalcin, and RUNX2 for osteogenesis. Compressive stress applied in DVF mode has increased osteogenic activity compared to DPF. CONCLUSION: The results indicated the development of ideal systems for osteogenesis and angiogenesis on the treated multilayer electrospun scaffolds in the perfusion bioreactor.

Selective preparation of crystalline or fibrous nano-cellulose carboxylate to fabricate an anti-bacterial hydrogel in co-operation with ZnO and recycled gelatin.

Bio-polymeric based nano-composites and hydrogels are newsworthy nano-biomaterials. Herein, crystalline or fibrous nano-cellulose carboxylate (NCCC and NCCF) were selectively prepared via the controllable direct oxidative-hydrolysis of MC in alkaline NaClO2 at 1:2 mol ratio, 90 °C, and 24 h for NCCC and at 1:1 mol ratio, 70 °C, and 20 h for NCCF. Characterization of NCCC and NCCF were performed by comparative Fourier transform infrared (FT-IR) spectroscopy, field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), thermal gravimetric analysis (TGA), and energy dispersive X-ray spectroscopy (EDS). Then, NCCC was cross-linked to the recycled gelatin (Gel) from the medicine capsules and the as-prepared nano-ZnO by maleic anhydride (MA) to give the novel hydrogel Gel/MA/NCCC/nano-ZnO. Nano-ZnO plays multi-roles in this hydrogel preparation, as either catalyst for the esterification of cellulose hydroxyls and amidation of gelatin amino groups or as the anti-bacterial part of hydrogel. The in vitro anti-bacterial activity results against the three gram-negative and gram-positive bacteria by well diffusion method confirmed Gel/MA/NCCC/nano-ZnO as an antibacterial agent with the activity order of P. aeruginosa > S. aureus > E. coli. The top anti-bacterial activity of this hydrogel against the gram-negative resistant bacteria of P. aeruginosa suggests its potential for biomedical applications.

Copper and Magnetic Activated Carbon Nanocomposites: Application as Recoverable Catalyst for C-S Coupling Reaction.

In this study, activated carbon (AC) was prepared from pistachio nut shell precursor as agricultural by-product. The prepared AC was used to synthesize an efficient nanocomposite via loading of the copper metal and magnetic nanoparticles (Cu-MAC@C4H8SO3H NCs) onto its structure. The structure of the nanocatalyst was characterized by different methods such as FT-IR, TEM, EDS, XRD, VSM, and TGA analysis. The catalytic activity of the prepared composite was tested in a special C-S coupling, namely with the reaction of 2-mercapto-3-phenylquinazolin-4(3H)-one with iodobenzene or bromobenzene. The products of the aryl thioquinazoline derivatives were obtained in good yields and in short reaction times and the products were characterized with 1H, 13C NMR and CHNS analysis. On the other hand, with easy and high recovery of Cu-MAC@C4H8SO3H NCs through magnetic separation, a simple and green method to enhance the efficiency of the nanocatalyst has been provided. The nanocatalyst was reused in the next reaction in up to five cycles without obvious activity decrease.

Modification of Extracellular Vesicle Surfaces: An Approach for Targeted Drug Delivery.

Extracellular vesicles (EVs) are a promising drug delivery vehicle candidate because of their natural origin and intrinsic function of transporting various molecules between different cells. Several advantages of the EV delivery platform include enhanced permeability and retention effect, efficient interaction with recipient cells, the ability to traverse biological barriers, high biocompatibility, high biodegradability, and low immunogenicity. Furthermore, EV membranes share approximately similar structures and contents to the cell membrane, which allows surface modification of EVs, an approach to enable specific targeting. Enhanced drug accumulation in intended sites and reduced adverse effects of chemotherapeutic drugs are the most prominent effects of targeted drug delivery. In order to improve the targeting ability of EVs, chemical modification and genetic engineering are the most adopted methods to date. Diverse chemical methods are employed to decorate EV surfaces with various ligands such as aptamers, carbohydrates, peptides, vitamins, and antibodies. In this review, we introduce the biogenesis, content, and cellular pathway of natural EVs and further discuss the genetic modification of EVs, and its challenges. Furthermore, we provide a comprehensive deliberation on the various chemical modification methods for improved drug delivery, which are directly related to increasing the therapeutic index.

Comparing maternal and neonatal prooxidant-antioxidant balance during delivery

Objective: Oxidative stress (OS) is due to a disturbance in the balance between the production of free radicals and antioxidant defense, resulting in a predominance of free radicals over endogenous anti-oxidant defenses. OS may have many causes. Pregnancy, and especially delivery, are associated with increased OS. The relationship between maternal and infant prooxidant-antioxidant balance (PAB) is unclear. Therefore, the aim of the present study was to compare PAB in mother and baby pairs. Material and Methods: This cross-sectional study was conducted in 104 mothers and normal term infants during 2017-2020. PAB was measured in healthy mothers before delivery and in umbilical cord samples after delivery. Data on the infant characteristics including age, gestational age, birth weight, Apgar score, and maternal history including the duration of mother's education, weight of the last month, and gravidity were collected using a researcher-made questionnaire. The cord and maternal PAB were compared by statistical methods. Results: In this study, the mean PAB of the neonates and mothers was 30.76 and 214.87 HK, respectively. The results revealed a moderate association between the PAB neonate and maternal PAB before delivery but it was not significant. Conclusion: Overall, the level of oxidants and antioxidants reduced during pregnancy and before delivery, and it was found that the relative incidence of neonatal PAB increases by increasing maternal PAB.

Preparation of gum tragacanth/poly (vinyl alcohol)/halloysite hydrogel using electron beam irradiation with potential for bone tissue engineering.

Nanocomposite hydrogels based on tyramine conjugated gum tragacanth, poly (vinyl alcohol) (PVA), and halloysite nanotubes (HNTs) were prepared by electron beam irradiation and characterized. The FTIR, 1H NMR, and TGA results confirmed the chemical incorporation of HNTs into gum tragacanth. Gel content and swelling of hydrogels decreased with HNTs loading up to 20 % wt. The mechanical strength of hydrogels increased by increasing HNTs content up to 10 % with 371 kPa fracture stress at 0.95 fracture strain, compared to 312 kPa stress at 0.79 strain for gum tragacanth/PVA hydrogel. Hydrogel's biocompatibility and osteogenic activity were tested by seeding rabbit bone marrow mesenchymal stem cells. The cell viability was >85 % after 7 days of culture. In vitro secretion of ALP and calcium deposition on hydrogels in alizarin red assay after 21 days of culture indicated hydrogel potential for bone tissue engineering.

Comparison of new biomarkers in the diagnosis of perinatal asphyxia.

Objectives: Precise and early diagnosis of neonatal asphyxia may improve outcomes. Recent studies aim to identify diagnostic biomarkers in neonates at risk for brain damage. The current study was designed to evaluate the diagnostic value of new biomarkers for neonatal asphyxia. Materials & Methods: This prospective study was conducted with an available sampling of infants upper 35 weeks of gestational age, including neonates with asphyxia (case group) and healthy controls, 2014-2022, in Ghaem Hospital, Mashhad, Iran. Data collection was performed utilizing a researcher-made questionnaire, including maternal and neonatal characteristics, as well as clinical and laboratory evaluation. Serum umbilical cord levels of interleukin-6 (IL6), interleukin-1-beta (IL- 1ß), pro-oxidant-antioxidant balance (PAB), and heat shock protein-70 (HSP70), as well as nucleated red blood cells count (NRBC), were determined. Data were analyzed by t-test, Chi-square, receiver operating characteristic (ROC), and regression models. Results: The differences in variables IL6, IL1ß, PAB, NRBC/100WBC, and HSP70 were statistically significant between the two groups (in all cases, P<0.0001). In the diagnosis of asphyxia, the most sensitive marker (89%) was IL1ß more than 2.39 pg/ml and HSP 70 upper than 0.23 ng/ml, while IL6 was higher than 9pg/ml, determined as the most specific marker (85%). Furthermore, a combination of HSP + PAB and IL6 + lL1b + PAB + NRBC/100WBC possesses the prediction power of 93.2% and 87.3%, respectively, for diagnosing asphyxia. Conclusion: According to data analysis, the combination of new biochemical markers (NRBC count, IL6, IL1ß, PAB, and HSP 70) could be a reliable marker for diagnosing infants with asphyxia.

Perillyl alcohol (PA) mitigates inflammatory, oxidative, and histopathological consequences of allergic asthma in rats.

Allergic asthma is an inflammatory and chronic condition, which is the most common asthma phenotype. It is usually defined by sensitivity to environmental allergens and leads to the narrowing of the airways. Around 300 million individuals are suffering from asthma worldwide. The purpose of the current research was to evaluate the effect of perillyl alcohol (PA) on oxidative stress and inflammation parameters in rats with allergic asthma. Experimental asthma was induced by ovalbumin (OVA) sensitization and inhalation in five groups of rats including control, asthma, asthma + vehicle, asthma + PA, and asthma + dexamethasone (Dexa). PA (50 mg/kg) or Dexa (2.5 mg/kg) were administered intraperitoneally for seven consecutive days following asthma induction. Histopathological evaluation was performed via hematoxylin and eosin (H&E) and Masson's trichrome staining. The enzyme-linked immunosorbent assay (ELISA) was used for the evaluation of the cytokine levels, including tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-17, and IL-10, as well as oxidative stress biomarkers including reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), total antioxidant capacity (TAC), and glutathione peroxidase (GPx) in the lung tissue and bronchoalveolar lavage fluid (BALF). Real-time polymerase chain reaction (PCR) was utilized for assessing the mRNA expression of FOXP3 and GATA3 and western blot analysis was used for the measurement of nuclear factor kappa B (NF-κB) protein expression. PA and Dexa decreased the pathological alterations and the expression levels of inflammatory factors (cytokines, GATA3, and NF-κB) in the lung tissue and BALF of asthmatic rats. PA restored GPx, SOD, and TAC levels and reduced ROS, MDA, nitrite, and total protein in the lung and BALF. Overall, our findings demonstrated that PA can be used as a therapeutic agent in asthma patients, but it is essential to monitor its effects in future clinical studies.