Beneficial Effects Research Articles

One-Carbon Metabolism Nutrients, Genetic Variation, and Diabetes Mellitus.

Diabetes mellitus (DM) affects about 9.3% of the population globally. Hyperhomocysteinemia (HHcy) has been implicated in the pathogenesis of DM, owing to its promotion of oxidative stress, β-cell dysfunction, and insulin resistance. HHcy can result from low status of one-carbon metabolism (OCM) nutrients (e.g., folate, choline, betaine, vitamin B6, B12), which work together to degrade homocysteine by methylation. The etiology of HHcy may also involve genetic variation encoding key enzymes in OCM. This review aimed to provide an overview of the existing literature assessing the link between OCM nutrients status, related genetic factors, and incident DM. We also discussed possible mechanisms underlying the role of OCM in DM development and provided recommendations for future research and practice. Even though the available evidence remains inconsistent, some studies support the potential beneficial effects of intakes or blood levels of OCM nutrients on DM development. Moreover, certain variants in OCM-related genes may influence metabolic handling of methyl-donors and presumably incidental DM. Future studies are warranted to establish the causal inference between OCM and DM and examine the interaction of OCM nutrients and genetic factors with DM development, which will inform the personalized recommendations for OCM nutrients intakes on DM prevention.

Ameliorative effect of Ononis natrix against chronic lead poisoning in mice: neurobehavioral, biochemical, and histological study.

Lead (Pb) is one of the most common heavy metals with toxicological effects on many tissues in humans as well as animals. In order to counteract the toxic effects of this metal, the administration of synthetic or natural antioxidants is thus required. The aim of this study was to examine the beneficial effect of the aqueous extract of Ononis natrix (AEON) against lead acetate-induced damage from a behavioral, biochemical, and histological point of view. Forty-eight male mice were divided into four equal groups: Ctr (control); Pb (lead acetate 1g/l); Pb + On 100 mg/kg (lead acetate 1 g/l + AEON 100 mg/kg); Pb + On 500 mg/kg (lead acetate 1 g/l + AEON 500 mg/kg). AEON was administered orally from day 21 after the start of lead exposure up to the end of the experiment. The results revealed that lead induced behavioral disorders, increased serum levels of liver markers (AST, ALT, and bilirubin), as well as kidney markers (urea and creatinine). At the same time, levels of thiobarbituric acid reactive substances (TBARS) and glutathione peroxidase (GPx) increased significantly. Moreover, Pb caused structural changes in the liver and kidneys of Pb-exposed mice. However, AEON administration significantly improved all lead-induced brain, liver, and kidney dysfunctions. Our results suggest that AEON could be a source of molecules with therapeutic potential against brain, liver, and kidney abnormalities caused by lead exposure.

Saffron the “Red Gold” and Its CNS Activity: A Challenge for Future Applications in Nutraceuticals

Saffron, indicated as “the red gold,” is an extraordinary spice with a unique aroma and organoleptic properties that is largely diffused in food preparation as well as a traditional medicine in many countries of the world. In the last years, several studies have considered this spice for CNS-based disorders showing its potential usefulness. In this review, we considered the role of saffron as a nutraceutical for the management of the most diffused CNS diseases considering the important role of oxidative stress on the pathogenesis of such diseases. In fact, recent findings support a crucial role of oxidative stress in different CNS diseases suggesting an important role of antioxidants. Preclinical and clinical evidence of its efficacy in different physiopathological pathways involved in several CNS diseases were discussed showing evidence of pharmacological activities and beneficial effects in pathological models or in small trials. Due to low toxicity and significant activities on oxidative stress and inflammation as well as the ability to modulate mitochondrial function, the saffron extracts and their constituents appear to be promising nutraceutical active compounds in this area. Further investigations are in progress to assess the efficacy and safety of preventive agents as nutraceuticals or as adjuvant compounds to be used in combinations with other therapeutic approaches. Saffron nutraceuticals with significant antioxidant activity can be useful in improving the quality of life of patients suffering from several different pathological conditions related to CNS. In this review, we summarized the more recent studies showing that standardized saffron products can be a valuable instrument of well-being due to their effects on multiple targets that support the health of the brain and related tissues.

Polr3b heterozygosity in mice induces both beneficial and deleterious effects on health during ageing with no effect on lifespan.

The genetic pathways that modulate ageing in multicellular organisms are typically highly conserved across wide evolutionary distances. Recently RNA polymerase III (Pol III) was shown to promote ageing in yeast, C. elegans and D. melanogaster. In this study we investigated the role of Pol III in mammalian ageing using C57BL/6N mice heterozygous for Pol III (Polr3b+/-). We identified sexually dimorphic, organ-specific beneficial as well as detrimental effects of the Polr3b+/- mutation on health. Female Polr3b+/- mice displayed improved bone health during ageing, but their ability to maintain an effective gut barrier function was compromised and they were susceptible to idiopathic dermatitis (ID). In contrast, male Polr3b+/- mice were lighter than wild-type (WT) males and had a significantly improved gut barrier function in old age. Several metabolic parameters were affected by both age and sex, but no genotype differences were detected. Neither male nor female Polr3b+/- mice were long-lived compared to WT controls. Overall, we find no evidence that a reduced Pol III activity extends mouse lifespan but we do find some potential organ- and sex-specific benefits for old-age health.

Clinical outcomes with metformin use in diabetic patients with compensated cirrhosis: a systematic review and meta-analysis.

Previous studies have demonstrated a beneficial effect of metformin in patients with cirrhosis, but no improvement in liver histology. To investigate the impact of metformin on mortality and hepatic decompensation in people with diabetes with compensated cirrhosis. Medline, Embase and Cochrane databases were searched from inception to February 2023 for studies reporting results regarding the impact of metformin on all-cause mortality and hepatic decompensation in people with diabetes with compensated cirrhosis. The risk of bias was assessed by ROBINS-I Cochrane tool. R software 4.3.1 was used for all analyses. Six observational studies were included in the final analysis. Metformin use was associated with reduced all-cause mortality or liver transplantation [hazard ratio (HR): 0.55; 95% confidence interval (CI) 0.37-0.82], while no benefit was shown in the prevention of hepatic decompensation (HR: 0.97; 95% CI: 0.77-1.22). In the subgroup analysis, metformin use was associated with reduced all-cause mortality or liver transplantation (HR: 0.50; 95% CI 0.38-0.65) in patients with metabolic-associated steatohepatitis cirrhosis, while two studies reported no survival benefit in patients with cirrhosis due to hepatitis C (HR: 0.39; 95% CI 0.12-1.20). Metformin use is associated with reduced all-cause mortality, but not with the prevention of hepatic decompensation in people with diabetes with compensated cirrhosis. The mortality benefit is most likely driven by better diabetes and cardiovascular health control.

The beneficial role of combinatorial spondias mombin and metformin treatments in Streptozotocin (STZ)-induced Pancreatic damage

There is increasing folkloric evidence of the use of the Spondias mombin plant in the management of various illnesses including diabetes. This could be attributed to its anti-hyperglycemic activity. In the same manner, combinatorial therapy has been reported to give a better achievement of glycemic control. On this note, we examined the role of Spondias mombin or Metformin and their combined administrations following streptozotocin-induced hyperglycemia and pancreatic damage in Wistar rats.For this study, 10 groups of rats (80–150 g) were utilized (A-J, n = 10). 1 mL/kg of citrate buffer (i.p.) was administered to the experimental control, while Groups B through F & I received Streptozotocin (STZ 60 mg/kg, i.p.), Spondias mombin (600 mg/kg p.o.), (400 mg/kg p.o), (200 mg/kg p.o), metformin (12.5 mg/kg p.o), and Spondias mombin + metformin (12.5 mg/kg) respectively; group B (untreated) while others were treated following hyperglycemia induction. Spondias mombin (400 mg/kg) only and metformin (12.5 mg/kg) only were administered to groups G and H, while J (not-induced) received Spondias mombin + metformin (12.5 mg/kg). Treatment lasted four weeks. The pancreatic tissues were evaluated for histoarchitectural damage with the Hematoxylin and Eosin, Masson Trichome, and Periodic acid Schiff's stains. The Bcl-2 antibody was used to label the Bcl-2 protein for apoptotic changes. Data were analyzed using one-way ANOVA and mean comparisons were done with the Duncan Multiple Range post hoc test. Significant differences were set at p < 0.05.Pancreatic induction with STZ resulted in pancreatic histoarchitectural alterations while Spondias mombin treatment only and combined Spondias mombin treatments with metformin ameliorated these abnormalities. Serum insulin was significantly decreased (p < 0.05), Peritoneal fluid α-Amylase, was significantly increased (p < 0.05), and serum caspase-3 levels were significantly increased (p < 0.05) in the STZ-only treated group compared to the control. Spondias mombin, metformin only, and the Spondias mombin+metformin administered groups (C-F, and I) restored these alterations. Bcl-2 Immunoreactivity was in a dose-dependent fashion. The Combined administrations of Spondias mombin and metformin exerted beneficial effects in Streptozotocin-induced pancreatic damage.

Perceptions, Experiences, and Patterns of Cannabis Use in Individuals with Mood and Anxiety Disorders in the Context of Cannabis Legalization and Medical Cannabis Program in Canada - A Qualitative Study.

Perceptions of cannabis as a potential medical treatment for mood and anxiety disorders have been increasing in the context of legalizations, availability, and medical cannabis programs, though current evidence predominately indicates risks and negative effects of cannabis use (CU) on mental health outcomes. This study aims to understand motivations, perceptions, effects, and patterns of CU in individuals with mood and anxiety disorders. Thirty-six adult patients diagnosed with mood or anxiety disorders, obsessive-compulsive disorder, or posttraumatic stress disorder who were currently using cannabis completed an in-depth qualitative interview on individual motivations, perceptions, experiences, effects, and patterns of their CU. The thematic analysis focused on phases of CU and sources of cannabis products and information. Reported motivations for initiation of CU included curiosity, peer pressure, and dissatisfaction with conventional treatments. Factors such as psychotropic effects and coping with mental health symptoms and insomnia contributed to the continuation of CU. More negative effects, including cognitive dysfunction, worsening of mood, and anxiety symptoms, were acknowledged with ongoing CU. Concerning findings included common initiation of CU before age 18, combined medical and recreational CU, rare consultation of medical professionals on CU, and potential effects and harms. Findings indicate individual complexity of motivations, perceptions, and patterns of CU in the study population. The reported potential beneficial effects of specific cannabis products should be further investigated. Findings emphasize patient-provider dialogue on both CU and conventional treatments. Information from this study can contribute to and inform the development of education, prevention, and intervention strategies.

Beneficial Effects of Fibroblast Growth Factor-1 on Retinal Pigment Epithelial Cells Exposed to High Glucose-Induced Damage: Alleviation of Oxidative Stress, Endoplasmic Reticulum Stress, and Enhancement of Autophagy.

Diabetic retinopathy (DR) severely affects vision in individuals with diabetes. High glucose (HG) induces oxidative stress in retinal cells, a key contributor to DR development. Previous studies suggest that fibroblast growth factor-1 (FGF-1) can mitigate hyperglycemia and protect tissues from HG-induced damage. However, the specific effects and mechanisms of FGF-1 on DR remain unclear. In our study, FGF-1-pretreated adult retinal pigment epithelial (ARPE)-19 cells were employed to investigate. Results indicate that FGF-1 significantly attenuated HG-induced oxidative stress, including reactive oxygen species, DNA damage, protein carbonyl content, and lipid peroxidation. FGF-1 also modulated the expression of oxidative and antioxidative enzymes. Mechanistic investigations showed that HG induced high endoplasmic reticulum (ER) stress and upregulated specific proteins associated with apoptosis. FGF-1 effectively alleviated ER stress, reduced apoptosis, and restored autophagy through the adenosine monophosphate-activated protein kinase/mammalian target of the rapamycin signaling pathway. We observed that the changes induced by HG were dose-dependently reversed by FGF-1. Higher concentrations of FGF-1 (5 and 10 ng/mL) exhibited increased effectiveness in mitigating HG-induced damage, reaching statistical significance (p < 0.05). In conclusion, our study underscores the promising potential of FGF-1 as a safeguard against DR. FGF-1 emerges as a formidable intervention, attenuating oxidative stress, ER stress, and apoptosis, while concurrently promoting autophagy. This multifaceted impact positions FGF-1 as a compelling candidate for alleviating retinal cell damage in the complex pathogenesis of DR.

Perspectives About Ascorbic Acid to Treat Inflammatory Bowel Diseases.

It is known that reactive oxygen species cause abnormal immune responses in the gut during inflammatory bowel diseases (IBD). Therefore, oxidative stress has been theorized as an agent of IBD development and antioxidant compounds such as vitamin C (L-ascorbic acid) have been studied as a new tool to treat IBD. Therefore, the potential of vitamin C to treat IBD was reviewed here as a critical discussion about this field and guide future research. Indeed, some preclinical studies have shown the beneficial effects of vitamin C in models of ulcerative colitis in mice and clinical and experimental findings have shown that deficiency in this vitamin is associated with the development of IBD and its worsening. The main mechanisms that may be involved in the activity of ascorbic acid in IBD include its well-established role as an antioxidant, but also others diversified actions. However, some experimental studies employed high doses of vitamin C and most of them did not perform dose-response curves and neither determined the minimum effective dose nor the ED50. Allometric extrapolations were also not made. Also, clinical studies on the subject are still in their infancy. Therefore, it is suggested that the research agenda in this matter covers experimental studies that assess the effective, safe, and translational doses, as well as the appropriate administration route and its action mechanism. After that, robust clinical trials to increase knowledge about the role of ascorbic acid deficiency in IBD patients and the effects of their supplementation in these patients can be encouraged.

Sodium-glucose cotransporter 2 inhibitors influence skeletal muscle pathology in patients with heart failure and reduced ejection fraction.

Patients with heart failure and reduced ejection fraction (HFrEF) exhibit skeletal muscle pathology, which contributes to symptoms and decreased quality of life. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve clinical outcomes in HFrEF but their mechanism of action remains poorly understood. We aimed, therefore, to determine whether SGLT2i influence skeletal muscle pathology in patients with HFrEF. Muscle biopsies from 28 male patients with HFrEF (New York Heart association class I-III) treated with SGLT2i (>12 months) or without SGLT2i were compared. Comprehensive analyses of muscle structure (immunohistochemistry), transcriptome (RNA sequencing), and metabolome (liquid chromatography-mass spectrometry) were performed, and serum inflammatory profiling (ELISA). Experiments in mice (n = 16) treated with SGLT2i were also performed. Myofiber atrophy was ~20% less in patients taking SGLT2i (p = 0.07). Transcriptomics and follow-up measures identified a unique signature in patients taking SGLT2i related to beneficial effects on atrophy, metabolism, and inflammation. Metabolomics identified influenced tryptophan metabolism in patients taking SGLT2i: kynurenic acid was 24% higher and kynurenine was 32% lower (p < 0.001). Serum profiling identified that SGLT2i treatment was associated with lower (p < 0.05) pro-inflammatory cytokines by 26-64% alongside downstream muscle interleukin (IL)-6-JAK/STAT3 signalling (p = 008 and 0.09). Serum IL-6 and muscle kynurenine were correlated (R = 0.65; p < 0.05). Muscle pathology was lower in mice treated with SGLT2i indicative of a conserved mammalian response to treatment. Treatment with SGLT2i influenced skeletal muscle pathology in patients with HFrEF and was associated with anti-atrophic, anti-inflammatory, and pro-metabolic effects. These changes may be regulated via IL-6-kynurenine signalling. Together, clinical improvements following SGLT2i treatment in patients with HFrEF may be partly explained by their positive effects on skeletal muscle pathology.

Earlier spring greening in Northern Hemisphere terrestrial biomes enhanced net ecosystem productivity in summer

The northern terrestrial biomes are being remarkably altered by climate change. Higher springtime temperature induces the earlier greening of vegetation, which may further influence ecosystem functions during the subsequent season. However, the response of summer net ecosystem productivity to spring vegetation greenness and phenology changes has not yet been quantified. To understand the impact of such phenological changes on terrestrial carbon sink of the following season, here we integrate remotely-sensed vegetation data and model simulations of carbon flux with an explainable machine learning approach. We find that the lagged effects of widespread earlier spring greening are increasing the summer ecosystem carbon sink across the northern vegetated areas (30° to 90°N) from 1982 to 2015. In particular, response disparities exist in non-agricultural biomes, and the vegetation with moderate tree coverage is more sensitive to earlier spring greening. Furthermore, modest tree restoration can strengthen the beneficial effects of earlier spring greening. This study improves our understanding of interseasonal vegetation-climate-carbon coupling that drives the key ecological feedback within climate change projections.

Fishing for the evidence on community water fluoridation: a commentary on the CATFISH study.

Goodwin M, Emsley R, Kelly M P et al. Evaluation of water fluoridation scheme in Cumbria: the CATFISH prospective longitudinal cohort study. Southampton: National Institute for Health and Care Research, 2022. This longitudinal, prospective cohort study, recruited two populations - a birth cohort and older school cohort - assessing the effects of community water fluoridation (CWF) over a five-year period. The control group received non-fluoridated drinking water in the East of Cumbria, while the intervention group received fluoridated drinking water in the West of Cumbria. The primary outcome measures were the presence or absence of decay into dentine in primary and permanent teeth. Cost effectiveness was assessed by quality-adjusted life-years. Birth Cohort: Modest beneficial effect (17.4% with decay, 21.4% in control). Adjusted Odd Ratios (AOR): 0.74 (95% CI: 0.56 to 0.98). Older Cohort: Insufficient evidence of difference (19.1% with decay and 21.9% in control). AOR: 0.80 (95% CI: 0.58 to 1.09). The authors concluded that CWF was effective in the birth cohort and that the modest absolute reduction in caries should be considered in the context of other preventive measures. A longer follow-up period was recommended to fully understand the benefits and risks of CWF in contemporary low-prevalence populations.

BMSCs-derived exosomes inhibit macrophage/microglia pyroptosis by increasing autophagy through the miR-21a-5p/PELI1 axis in spinal cord injury.

Spinal cord injury (SCI) results in a diverse range of disabilities and lacks effective treatment options. In recent years, exosomes derived from bone mesenchymal stem cells (BMSCs) have emerged as a promising cell-free therapeutic approach for treating ischemic brain injury and other inflammatory conditions. Macrophage/microglial pyroptosis has been identified as a contributing factor to neuroinflammation following SCI. The therapeutic potential of BMSC-derived exosomes in macrophage/microglia pyroptosis-induced neuroinflammation, however, has to be determined. Our findings demonstrate that exosomes derived from BMSCs can enhance motor function recovery and mitigate neuroinflammation subsequent to SCI by upregulating the expression of autophagy-related proteins and inhibiting the activation of NLRP3 inflammasomes in macrophage/microglia. Moreover, miR-21a-5p is markedly increased in BMSCs-derived exosomes, and knocking down miR-21a-5p in BMSCs-derived exosomes eliminates the beneficial effects of administration; upregulation of miR-21a-5p in BMSCs-derived exosomes enhances the beneficial effects of administration. Mechanistically, miR-21a-5p positively regulates the autophagy of macrophage/microglia by reducing PELI1 expression, which in turn inhibits their pyroptosis. This research provides novel evidence that exosomes derived from BMSCs can effectively suppress macrophage/microglia pyroptosis through the miR-21a-5p/PELI1 axis-mediated autophagy pathway, ultimately facilitating functional restoration following SCI. In particular, our constructed miR-21a-5p overexpression exosomes greatly improved the efficacy of BMSCs-derived exosomes in treating spinal cord injury. These results establish a foundation for the prospective utilization of exosomes derived from BMSCs as a novel biological intervention for spinal cord injury.

The effectiveness of exercise interventions targeting sleep in older adults with cognitive impairment or Alzheimer's disease and related dementias (AD/ADRD): A systematic review and meta-analysis.

Sleep loss is associated with reduced health and quality of life, and increased risk of Alzheimer's disease and related dementias. Up to 66% of persons with Alzheimer's disease and related dementias experience poor sleep, which can predict or accelerate the progression of cognitive decline. Exercise is a widely accessible intervention for poor sleep that can protect against functional and cognitive decline. No previous systematic reviews have investigated the effectiveness of exercise for sleep in older adults with mild cognitive impairment or Alzheimer's disease and related dementias. We systematically reviewed controlled interventional studies of exercise targeting subjectively or objectively (polysomnography/actigraphy) assessed sleep in persons with mild cognitive impairment or Alzheimer's disease and related dementias. We conducted searches in PubMed, Embase, Scopus and Cochrane-Library (n = 6745). Nineteen randomised and one non-randomised controlled interventional trials were included, representing the experiences of 3278 persons with mild cognitive impairment or Alzheimer's disease and related dementias. Ten had low-risk, nine moderate-risk, and one high-risk of bias. Six studies with subjective and eight with objective sleep outcomes were meta-analysed (random-effects model). We found moderate- to high-quality evidence for the beneficial effects of exercise on self-reported and objectively-measured sleep outcomes in persons with mild cognitive impairment or Alzheimer's disease and related dementias. However, no studies examined key potential moderators of these effects, such as sex, napping or medication use. Our results have important implications for clinical practice. Sleep may be one of the most important modifiable risk factors for a range of health conditions, including cognitive decline and the progression of Alzheimer's disease and related dementias. Given our findings, clinicians may consider adding exercise as an effective intervention or adjuvant strategy for improving sleep in older persons with mild cognitive impairment or Alzheimer's disease and related dementias.

Age-dependent development trends (models) of intestinal significant microbiota species and Eimeria oocysts in coccidia-challenged broiler chickens as affected by dietary encapsulated organic acids and anticoccidial drugs

ABSTRACT The study was conducted to investigate the effect of dietary encapsulated organic acids (EOAs) and anticoccidials on the age-dependent development trend of intestinal Lactobacillus, E. coli, coliforms, and Eimeria in Eimeria spp.-infected broiler chickens from reused litter. In total, 525 mixed-sex 1-day-old broiler chickens were used in an uninfected/un-supplemented control plus a 2 (no EOA or 0.1% EOA) × 3 (no anticoccidial, 0.05% maduramicin, and 0.02% diclazuril) factorial arrangement of treatments as a completely randomized design with five replicates of 15 chickens. Results indicated that the cubic model is the best model for explaining the development trends of the intestinal microbial population in uninfected and infected chickens (affected by the EOAs and anticoccidials). Based on the cubic models, the microbial populations had development trends with a decreasing slope from 1-day-old until the early or middle finisher period. EOAs and anticoccidials, especially their simultaneous usage, improved (P < 0.05) the linear and cubic models’ slope (affected negatively by Eimeria infection). A polynomial model (order = 6) was determined as the best model for explaining the EOAs and anticoccidial effects on the trend of intestinal Eimeria oocysts in infected chickens. The infection peak (which happened at 25 days) was reduced by EOAs and anticoccidials, especially their simultaneous usage. In conclusion, cubic and polynomial (order = 6) regressions are the best models fitted for explaining the microbiota and Eimeria oocysts trends, respectively. EOAs and anticoccidials, especially their simultaneous usage, had beneficial effects on the microbiota and Eimeria development trends and gastrointestinal health in coccidia-infected broiler chickens.‏ RESEARCH HIGHLIGHTS Cubic regression is the best model for explaining intestinal microbiota development. Polynomial regression is the best model for intestinal Eimeria oocysts development. Age-development trends are affected by dietary encapsulated organic acids and anticoccidials.

Gene-edited cells: novel allogeneic gene/cell therapy for epidermolysis bullosa.

Epidermolysis bullosa (EB) is a group of rare genetic skin fragility disorders, which are hereditary. These disorders are associated with mutations in at least 16 genes that encode components of the epidermal adhesion complex. Currently, there are no effective treatments for this disorder. All current treatment approaches focus on topical treatments to prevent complications and infections. In recent years, significant progress has been achieved in the treatment of the severe genetic skin blistering condition known as EB through preclinical and clinical advancements. Promising developments have emerged in the areas of protein and cell therapies, such as allogeneic stem cell transplantation; in addition, RNA-based therapies and gene therapy approaches have also become a reality. Stem cells obtained from embryonic or adult tissues, including the skin, are undifferentiated cells with the ability to generate, maintain, and replace fully developed cells and tissues. Recent advancements in preclinical and clinical research have significantly enhanced stem cell therapy, presenting a promising treatment option for various diseases that are not effectively addressed by current medical treatments. Different types of stem cells such as primarily hematopoietic and mesenchymal, obtained from the patient or from a donor, have been utilized to treat severe forms of diseases, each with some beneficial effects. In addition, extensive research has shown that gene transfer methods targeting allogeneic and autologous epidermal stem cells to replace or correct the defective gene are promising. These methods can regenerate and restore the adhesion of primary keratinocytes in EB patients. The long-term treatment of skin lesions in a small number of patients has shown promising results through the transplantation of skin grafts produced from gene-corrected autologous epidermal stem cells. This article attempts to summarize the current situation, potential development prospects, and some of the challenges related to the cell therapy approach for EB treatment.

Sports Activities in Children with Cerebral Palsy: A Narrative Review.

Physical exercise is known to have beneficial effects on psychosocial well-being and cognitive performance. Children with cerebral palsy (CP) showed lower levels of physical activity (PA) than healthy children; this fact, in addition to the basic clinical condition, increased the sedentary habit with a psychological impact and motor impairment of these children. Furthermore, children and adolescents with CP are less committed to sports activities than typically developing children of the same age. The aim of the present narrative review was to increase the amount of knowledge regarding the effectiveness and importance of specific and individualized sports in children with CP. A comprehensive search of MED-LINE and EMBASE databases was performed, including specific search terms such as "cerebral palsy" combined with "sport", "physical activity", and the names of different sports. No publication date limits were set. We included studies with an age range of 0-18 years. The main results pointed out that most of the sports improved motor function, quality of life, and coordination in children and adolescents with CP. Physicians, therapists, and parents should become aware of the benefits of sports activities for this population of patients. Specific sports activities could be included as a usual indication in clinical practice in addition to rehabilitation treatment.

Protective effects of docosahexaenoic acid supplementation on cognitive dysfunction and hippocampal synaptic plasticity impairment induced by early postnatal PM2.5 exposure in young rats.

PM2.5 exposure is a challenging environmental issue that is closely related to cognitive development impairment; however, currently, relevant means for prevention and treatment remain lacking. Herein, we determined the preventive effect of docosahexaenoic acid (DHA) supplementation on the neurodevelopmental toxicity induced by PM2.5 exposure. Neonatal rats were divided randomly into three groups: control, PM2.5, and DHA + PM2.5 groups. DHA could ameliorate PM2.5-induced learning and memory dysfunction, as well as reverse the impairment of hippocampal synaptic plasticity, evidenced by enhanced long-term potentiation, recovered synaptic ultrastructure, and increased expression of synaptic proteins. Moreover, DHA increased CREB phosphorylation and BDNF levels and attenuated neuroinflammation and oxidative stress, reflected by lower levels of IBA-1, IL-1β, and IL-6 and increased levels of SOD1 and Nrf2. In summary, our findings demonstrated that supplementation of DHA effectively mitigated the cognitive dysfunction and synaptic plasticity impairment induced by early postnatal exposure to PM2.5. These beneficial effects may be attributed to the upregulation of the CREB/BDNF signaling pathway, as well as the reduction of neuroinflammation and oxidative stress.

Effect of Vermicompost and Nitrogen Fertilizer on the Growth and Production of Aloe Vera

Purpose: The effect of vermicompost and nitrogen fertilizers on the growth and production of Aloe vera were conducted using factorial based on Randomized Complete Block Design (RCBD).&#x0D; Background: Vermicompost can be used in sustainable agriculture to support growing populations by increasing water holding capacity, nutrient supply, high porosity, adequate ventilation and drainage, and production of plant hormones that have beneficial effects on seed germination.&#x0D; Methods: According to the RCBD method, treatments were included: four levels of vermicompost (V0: Control, V1: 75, V2: 150 and V3: 200 g per pot) and four levels of nitrogen fertilizer (N0: control, N1: 500, N2: 1000, and N3: 1500 mg per pot) using urea.&#x0D; Results: The results showed that application of 150 g of vermicompost and 1000 mg of nitrogen had the highest effect on growth traits, and application of 200 g of vermicompost and 1500 mg of nitrogen had the greatest effect on sucker characteristics, so that the highest number of suckers was obtained by using 200 g of vermicompost and 1000 and 1500 mg of nitrogen. However, simultaneous application of 150 g of vermicompost and 1000 mg of nitrogen had the greatest effect on plant height, number of leaves, and leaf diameter, and treatment with 200 g of vermicompost and 1500 mg of nitrogen had the greatest effect on the number of suckers, stem weight, number of leaves, sucker height, total biomass and Aloin content.&#x0D; Conclusions: Therefore, simultaneous use of vermicompost and nitrogen fertilizer in Aloe vera cultivation plays an important role in the production and enhancement of sucker and plant yield.

Evaluating Strategies to Enhance Li Transference in Salt-in-Ionic Liquid Electrolytes: Mixed Anions, Coordinating Cations, and High Salt Concentration.

The increased safety of salt-in-ionic liquid electrolytes compared with established carbonate-based systems has promoted intense research in this field, but low conductivities, slow lithium transport, and unfavorable lithium anion correlations still prevent a mass market application. In particular, strong Li-anion correlations lead to dominant vehicular Li transport with the same drift direction for anions and lithium in the electric field. Here, three different strategies and their mutual interplay are evaluated, which could reduce Li-anion coordination, i.e., high salt concentration, a mixed-anion composition, as well as an ether functionalization of the organic cation. To this end, two series of highly concentrated IL-based electrolytes, based on either ethylmethylimidazolium (EMIM) or the ether-functionalized 1-methoxyethyl-1-methylpyrrolidinium (Pyr12O1) organic cation, and employing mixed bis(fluorosulfonyl)imide/bis(trifluoromethylsulfonyl)imide (FSI/TFSI) anions are investigated. Measurements of conductivities, diffusion coefficients, and electrophoretic mobilities reveal no beneficial effect due to the increased heterogeneity of the FSI/TFSI-based electrolyte matrix, generally showing improved transport properties with increasing FSI share. However, a combination of both the ether-functionalized cation and high FSI content is proven successful, as lithium mobilities are positive, and vehicular transport is overcome by structural Li transport. Our study demonstrates the decisive role of synergy of the different approaches: While the single effect of a high salt concentration, weakly lithium-coordinating anions, or organic cations with lithium-affine functional groups is too weak to prevent vehicular transport, their joint effect can overcome vehicular Li transport, leading to improved Li conduction in ionic liquids.