Sevoflurane causes cognitive impairment by inducing iron deficiency and inhibiting the proliferation of neural precursor cells in infant mice.

AIMS: Numerous studies on animals have shown that exposure to general anesthetics in infant stage may cause neurocognitive impairment. However, the exact mechanism is not clear. The dysfunction of iron metabolism can cause neurodevelopmental disorders. Therefore, we investigated the effect of iron metabolism disorder induced by sevoflurane (Sev) on cognitive function and the proliferation of neural precursor cells (NPCs) and neural stem cells (NSCs) in infant mice. METHODS: C57BL/6 mice of postnatal day 14 and neural stem cells NE4C were treated with 2% Sev for 6 h. We used the Morris water maze (MWM) to test the cognitive function of infant mice. The proliferation of NPCs was measured using bromodeoxyuridine (BrdU) label and their markers Ki67 and Pax6 in infant brain tissues 12 h after anesthesia. Meanwhile, we used immunohistochemical stain, immunofluorescence assay, western blot, and flow cytometer to evaluate the myelinogenesis, iron levels, and cell proliferation in cortex and hippocampus or in NE4C cells. RESULTS: The results showed that Sev significantly caused cognitive deficiency in infant mice. Further, we found that Sev inhibited oligodendrocytes proliferation and myelinogenesis by decreasing MBP and CC-1 expression and iron levels. Meanwhile, Sev also induced the iron deficiency in neurons and NSCs by downregulating FtH and FtL expression and upregulating the TfR1 expression in the cortex and hippocampus, which dramatically suppressed the proliferation of NSCs and NPCs as indicated by decreasing the colocalization of Pax6+ and BrdU+ cells, and caused the decrease in the number of neurons. Interestingly, iron supplementation before anesthesia significantly improved iron deficiency in cortex and hippocampus and cognitive deficiency induced by Sev in infant mice. Iron therapy inhibited the decrease of MBP expression, iron levels in neurons and oligodendrocytes, and DNA synthesis of Pax6+ cells in hippocampus induced by Sev. Meanwhile, the number of neurons was partially recovered in hippocampus. CONCLUSION: The results from the present study demonstrated that Sev-induced iron deficiency might be a new mechanism of cognitive impairment caused by inhaled anesthetics in infant mice. Iron supplementation before anesthesia is an effective strategy to prevent cognitive impairment caused by Sev in infants.

The Use of Metallic Nanoparticles in Wound Healing: New Perspectives.

Chronic wounds represent a challenge for the health area, as they directly impact patients' quality of life and represent a threat to public health and the global economy due to their high cost of treatment. Alternative strategies must be developed for cost-effective and targeted treatment. In this scenario, the emerging field of nanobiotechnology may provide an alternative platform to develop new therapeutic agents for the chronic wound healing process. This manuscript aims to demonstrate that the application of metallic nanoparticles (gold, silver, copper, and zinc oxide) opened a new chapter in the treatment of wounds, as they have different properties such as drug delivery, antimicrobial activity, and healing acceleration. Furthermore, metallic nanoparticles (NPs) produced through green synthesis ensure less toxicity in biological tissues, and greater safety of applicability, other than adding the effects of NPs with those of extracts.

Photobiomodulation associated with lipid nanoparticles and hyaluronic acid accelerate the healing of excisional wounds.

Objectives: This article aimed to investigate the effects of the association between photobiomodulation and hyaluronic acid incorporated in lipid nanoparticles in an epithelial lesion model in inflammatory parameters and oxidative stress. Methods: Eighty Wistar rats were randomly assigned to the following groups: epithelial lesion group (EL); EL+PBM; EL+HA; EL+SLNs; EL+SLNs-HA; EL+PBM+HA; EL+PBM+SLNs; EL+PBM+SLNs-HA. The animals were anesthetized with 4% isofluorane after shaving and induced to an epithelial lesion. Topical treatment with a gel containing HA (0.9%) and/or SLNs (10 mg/mL) and with laser irradiation occurred daily for 1 week. Results: The results showed an increase in wound contraction on the seventh day in the LE + LBM + AH-NPL group, a reduction in pro-inflammatory cytokines (IL-6, IL-1ß, and TNF-α), an increase in anti-inflammatory cytokines (IL- 4 and IL-10) and TGF-ß. The levels of pro-inflammatory cytokine IL-4 and TGF-ß also showed an increase in the LE + NPL-AH, LE + FBM + AH, LE + FBM + NPL and LE + FBM + NPL-AH groups. Regarding oxidative stress parameters, the levels of DCF and nitrite decreased in the combined therapy group when compared to the control group, as well as oxidative damage (carbonyl and sulfhydryl). In the antioxidant defense, there was an increase in GSH and SOD in the combination therapy group. Histological analysis showed a reduction in inflammatory infiltrate in the combination therapy group. The number of fibroblasts and the compaction of collagen fibers did not obtain significant responses. Conclusions: Results analyzed together showed that the combined therapy favored the repair process, and that studies can be carried out to enhance the histological analysis therapy favored the tissue repair process and that studies can be carried out to enhance the histological analysis.

Solanum pubescens Wild Fruits Essential Oil - A Golden Casket for its Antimicrobial and Anti-inflammatory Mediated Wound Healing Efficacy in Vertebrate Model Mus musculus.

BACKGROUND: Solanum pubescens Willd, growing wild in the hills of Rayadurg jurisdiction of Southwestern Andhra Pradesh, has gained significant attention among researchers for its diverse folkloric applications, existence of novel phytochemicals and leaf extracts which hold great medicinal promises. To date, the S. pubescens fruit's essential oil (SPO) has never been investigated. METHODS: The current research has been focused to evaluate the chemical composition of S. pubescens fruit essential oil through Gas Chromatography-Mass Spectrometry (GC-MS), followed by the investigation of antibacterial, antifungal, anti-inflammatory, analgesic and wound healing activities in appropriate models to uncover its biological potentials. Extraction of (Solanopuboil/SPO) from the fresh unripe fruits of Solanum pubescens was carried out in Buchner funnel and Whatman no.10 filter paper and concentrated at 40°C using a rotary evaporator. The metabolic profiling of SPO was analysed by GC-MS technique. The MIC, MBC, activity index, and total antimicrobial activity of SPO were evaluated using standard procedures. Anti-inflammatory activity of SPO was screened using Carrageenan induced paw oedema and Cotton pellet-induced granuloma. Tail immersion test, Acetic acid writhing response and Formalin paw lick test was performed in rats in order to examine the analgesic activity of SPO. Wound healing activity of SPO was investigated by performing the incision wound model, Excision wound model and Dead space wound model in rats. RESULTS: The SPO displayed a constant degree of antimicrobial activity against B. cereus, B. subtilis, E. coli, A. niger, A. fumigatus and C. albicans with significant anti-inflammatory and analgesic activities. Also, a prominent wound healing potential of it was observed in excision, incision and dead space wound models with considerable elevation in granulation tissue hydroxyproline, hexuronic acid and hexosamine content in association with remarkable regulation of anti-inflammatory and antioxidant markers i.e., Lipid peroxidase (LPO), Nitric Oxide (NO), Superoxide dismutase (SOD), Glutathione (GSH), Catalase (CAT), Glutathione Peroxidase (GPx). CONCLUSION: These findings strongly validate the therapeutic potential of S. pubescens fruit essential oil in antimicrobial and anti-inflammatory mediated wound healing and suggests its promising application as valuable and novel indigenous leads in the food and pharmaceutical industries. To the best of our knowledge, this is the first-ever investigatory report on the systematic phytochemical and therapeutic examination of S. pubescens fruit essential oil.

The Dose Response of Taurine on Aerobic and Strength Exercises: A Systematic Review.

Taurine is a naturally occurring amino acid involved in various functions, including regulating ion channels, cell volume, and membrane stabilization. However, how this molecule orchestrates such functions is unknown, particularly the dose response in exercised muscles. Therefore, this review aimed to systematically review the dose response of taurine on both aerobic and strength exercise performance. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, relevant articles were sought on PubMed, Medline, Web of Science, and Google Scholar using related terms, including taurine, exercise performance, exercise, muscle, physical training, running, strength, endurance exercise, resistance exercise, aerobic exercise, and swimming. Ten articles were retrieved, reviewed, and subjected to systematic analysis. The following parameters were used to assess exercise performance in the selected studies: creatine kinase (CK), lactic acid dehydrogenase, carbohydrate, fat, glycerol, malondialdehyde, enzymatic antioxidants, blood pH, taurine level, and muscular strength. From the selected literature, we observed that taurine supplementation (2 g three times daily) with exercise can decrease DNA damage. Furthermore, 1 g of acute taurine administration before or after exercise can decrease lactate levels. However, acute administration of taurine (6 g) at a high dose before the start of exercise had no effect on reducing lactate level, but increased glycerol levels, suggesting that taurine could be an effective agent for prolonged activities, particularly at higher intensities. However, further studies are warranted to establish the role of taurine in fat metabolism during exercise. Finally, we observed that a low dose of taurine (0.05 g) before performing strength enhancing exercises can decrease muscular fatigue and increase enzymatic antioxidants. Systematic Review Registration:http://www.crd.york.ac.uk/PROSPERO, PROSPERO (CRD42021225243).

Taurine Reverses Oxidative Damages and Restores the Muscle Function in Overuse of Exercised Muscle.

Exercise-induced oxidative stress is linked with the expression level of endogenous antioxidants, but these antioxidants cannot overcome all oxidative stress-related damages in the cells, particularly when cells are under physiological stress. Sometimes, compounds are needed for cellular function, which are produced/activated within the cells, and these compounds can be synthesized by performing exercise, especially high-performance exercise. Taurine is a sulfur-containing amino acid used for various physiological functions. However, its synthesis and accumulation under the oxidative environment may be compromised. Recently, we have shown that taurine level is increased during exercise performance with a decrease in oxidative damage in overused muscles. Other studies have also shown that short-term supplementation with taurine increased physiological performance during severe work intensities, suggesting the role of taurine in improving muscle performance during exercise. However, its precursor cysteine is used in the synthesis of other compounds like GSH and Coenzyme A, which are important for regulating the redox system and energy homeostasis. It is, therefore, important to understand whether taurine synthesis within the cells can blunt the activity of other compounds that are beneficial in preventing oxidative damage during intense exercise. Furthermore, it is important to understand whether taurine supplementation can prevent the conditions observed in the physiological stress of muscles. This review discusses how taurine synthesis could alter exercise-induced ROS generation and the relationship between the physiological stress of muscle and subsequent improvements in exercise performance.

Current Evidence on Traditional Chinese Exercise for Cancers: A Systematic Review of Randomized Controlled Trials.

Traditional Chinese exercise (TCE) has gradually become one of the widespread complementary therapies for treatment and recovery of cancers. However, evidence based on the systematic evaluation of its efficacy is lacking, and there appears to be no conclusion regarding the setting of TCE interventions. The purpose of this systematic review is to summarize the current randomized controlled trials (RCTs) that outline the effects of TCE on cancer patients. Relevant studies were searched by GOOGLE SCHOLAR, SCIENCEDIRECT, and WEB OF SCIENCE using "traditional Chinese exercise" and "cancer." Only RCTs published in peer-reviewed English journals were included. A total of 27 studies covering 1616 cancer patients satisfied the eligibility criteria for this review. Despite the methodological limitation and relatively high risk of bias possessed by some included studies, positive evidence was still detected on the effects of TCE on these cancer-related health outcomes in physical, psychological, and physiological parameters. The 60-min or 90-min course of TCE intervention for two to three times per week for 10 to 12 weeks was found to be the most common setting in these studies and has effectively benefited cancer patients. These findings add scientific support to encourage cancer patients to practice TCE during or after conventional medical treatment. Nevertheless, future well-designed RCTs with improved methodology and larger sample size on this field are much warranted for further verification.

Sevoflurane anesthesia during pregnancy in mice induces cognitive impairment in the offspring by causing iron deficiency and inhibiting myelinogenesis.

Maternal anesthetic exposure during pregnancy is associated with an increased risk of cognitive impairment in offspring. The balance of cerebral iron metabolism is essential for the development of brain tissue. Iron deficiency affects the myelinogenesis and nerve tissue development, especially in fetus or infant, which has a key role in cognitive function. We aimed to investigate whether maternal sevoflurane (Sev) exposure caused cognitive impairment in offspring through inducing iron deficiency and inhibiting myelinogenesis. Pregnant mice (gestation stage day 14) were treated with 2% Sev for 6 h. Cognitive function of offspring mice was determined by the Morris water maze and Context fear conditioning test. Iron levels were assayed by Perl's iron staining and synchrotron imaging. Hippocampus and cortex tissues or cerebral microvascular endothelial cells of offspring mice (postnatal day 35) were harvested and subjected to Western blot and/or immunhistochemistry to assess ferritin, transferrin receptor 1(TfR1), Ferroportin-1 (FpN1), myelin basic protein (MBP), tight junction protein ZO-1, occludin, and claudin-5 levels. Beginning with postnatal day 30, the offspring were treated with iron therapy for 30 days, and the indicators above were tested. Our results showed Sev dramatically decreased the iron levels of brain and impaired cognitive function in offspring mice. Sev decreased the expression of heavy chain ferritin (FtH), light chain ferritin (FtL), MBP, ZO-1, occludin, claudin-5, and FpN1, and increased TfR1 in hippocampus and cortex or cerebral microvascular endothelial cells of offspring mice, indicating that Sev caused the iron deficiency and impaired the myelinogenesis in the brain of offspring. Interestingly, iron therapy prompted the myelinogenesis and improved impaired cognitive function at postnatal day 60. Our research uncovered a new mechanism which showed that iron deficiency induced by Sev and myelin formation disorder due to decreased iron of brain may be an important risk factor for cognitive impairment in offspring. It was necessary for offspring to be supplied iron supplement whose mother suffered exposure to sevoflurane during pregnancy.

Modulatory effects of taurine on metabolic and oxidative stress parameters in a mice model of muscle overuse.

OBJECTIVE: The aim of this study was to investigate the regulatory effects of taurine on the biochemical parameters of muscle injury by overuse. METHODS: Male Swiss mice were divided into four groups: control (Ctrl), overuse (Ov), taurine (Tau), and overuse plus taurine (OvTau). High-intensity exercise sessions were administered for 21 d with concomitant subcutaneous injections of taurine (150 mg/kg). The mice were then sacrificed. The quadriceps muscles were surgically removed for subsequent histologic analysis and evaluation of mitochondrial function, oxidative stress parameters, tissue repair, and DNA damage markers. RESULTS: The Ov group showed significant differences compared with the Ctrl group (all P <0.05). The fiber area decreased by 49.34%, whereas the centralized nuclei contents (Ctrl = 1.33%; Ov = 28.67%), membrane potential (Ctrlsuc = 179.05 arbitrary fluorescence units (AFUs), Ctrlsuc+ADP = 198.11 AFUs; Ovsuc = 482.95 AFUs, Ovsuc+ADP = 461.6 AFUs), complex I activity (Ctrl = 20.45 nmol ⋅ min ⋅ mg protein, Ov = 45.25 nmol ⋅ min ⋅ mg protein), hydrogen peroxide (Ctrlsuc = 1.08 relative fluorescence unit (RFU) ⋅ sec ⋅ mg protein, Ctrlsuc+ADP = 0.23 RFU ⋅ sec ⋅ mg protein; Ovsuc = 5.02 RFU ⋅ sec ⋅ mg protein, Ovsuc+ADP = 0.26 RFU ⋅ sec ⋅ mg protein) and malondialdehyde (Ctrl = 0.03 nmol ⋅ mg ⋅ protein, Ov = 0.06 nmol ⋅ mg ⋅ protein) levels, and DNA damage (Ctrlfreq = 7.17%, Ovfreq = 31.17%; Ctrlindex = 4.17, Ovindex = 72.5) were increased. Taurine administration reduced the number of centralized nuclei (OvTau = 5%), hydrogen peroxide levels (OvTausuc = 2.81 RFU ⋅ sec ⋅ mg protein, OvTaussuc+ADP = 1.54 RFU ⋅ sec ⋅ mg protein), membrane potential (OvTausuc = 220.18 AFUs, OvTaussuc+ADP = 235.28 AFUs), lipid peroxidation (OvTau = 0.02 nmol/mg protein), and DNA damage (OvTaufreq = 21.33%, OvTauindex = 47.83) and increased the fiber area by 54% (all P <0.05). CONCLUSION: Taken together, these data suggest that taurine supplementation modulates various cellular remodeling parameters after overuse-induced muscle damage, and that these positive effects may be related to its antioxidant capacity.

Effects of reactive oxygen species and interplay of antioxidants during physical exercise in skeletal muscles.

A large number of researches have led to a substantial growth of knowledge about exercise and oxidative stress. Initial investigations reported that physical exercise generates free radical-mediated damages to cells; however, in recent years, studies have shown that regular exercise can upregulate endogenous antioxidants and reduce oxidative damage. Yet, strenuous exercise perturbs the antioxidant system by increasing the reactive oxygen species (ROS) content. These alterations in the cellular environment seem to occur in an exercise type-dependent manner. The source of ROS generation during exercise is debatable, but now it is well established that both contracting and relaxing skeletal muscles generate reactive oxygen species and reactive nitrogen species. In particular, exercises of higher intensity and longer duration can cause oxidative damage to lipids, proteins, and nucleotides in myocytes. In this review, we summarize the ROS effects and interplay of antioxidants in skeletal muscle during physical exercise. Additionally, we discuss how ROS-mediated signaling influences physical exercise in antioxidant system.

Regulation of ROS defense system by Hybanthus enneaspermus in CCl4 induce cardiac damage.

The purpose of this study is to regulate the ROS (Reactive oxygen species) defense system in cardiac damage induced by CCl4(Carbon tetra chloride) in rats using Hybanthus enneaspermus. Administration of CCl4induces damage in the heart of rats as proved by estimation of antioxidant enzymes such as, SOD (Superoxide dismutase), CAT (catalase), GPx (Glutathione Peroxdiase), GR (Glutathione Reductase), GST (Glutathione-S-Transferaes). However, treatment with HEE in CCl4intoxicated rats was found to be protected the heart, as indicated by the enzyme level in serum. A significant increment of serum enzymes level such as SOD, CAT, GPx, GR and GST were observed following HEE treatment during CCl4intoxication whereas MDA (Malondialdehyde) level in HEE treated rats were decreased. The results of our experiment suggest that the treatment of HEE may be the critical remedy for the adverse effect of CCl4in heart function.