Preparation of graphene oxide nanoparticles and their derivatives: Evaluation of their antimicrobial and anti-proliferative activity against 3T3 cell line

Antibacterial applications of graphene derivatives have been very highlighted during the last decade. In this study, graphene-based materials, i.e., graphene oxide (GO), reduced graphene oxide (RGO), and carboxylated graphene oxide (GO-COOH), were synthesized and characterized by UV-vis spectrophotometry, energy dispersive X-ray spectroscopy (EDX), and TEM. The main difference in these nanomaterials is the content of their oxygen-containing functional groups. According to EDX elemental analysis, GO-COOH has the highest ratio of carbon to oxygen and the highest oxygen-containing functional groups. Cytotoxicity of GO, RGO, and GO-COOH in eight concentrations at two times (24 and 48 h) on 3T3 cell lines showed concentration-dependence cytotoxicity for these three nanomaterials. The antimicrobial and antibiofilm properties of these three materials against gram-negative (Pseudomonas aeruginosa) and gram-positive (Staphylococcus aureus) bacteria, as well as a fungus (Candida albicans), were evaluated by MIC, MBC, anti-biofilm, and Time-Kill tests. Our data demonstrated that the GO-COOH has the highest antimicrobial properties, which can result from increasing the oxygen-containing functional groups. To the best of our knowledge, comparing all cytotoxic, antibacterial, antifungal, and anti-biofilm properties of these three graphene derivatives in one study has not been reported yet

Investigating the Mechanisms Involved in Scopolamine-induced Memory Degradation

In the present study, the mechanisms involved in scopolamine-induced memory impairment have been investigated. The molecular events that take place during memory mostly include mechanisms that are seen in the acquisition phase. Results showed that one of the mechanisms of memory destruction caused by scopolamine, in addition to weakening the cholinergic system, is the indirect effect of scopolamine on other neurotransmitter systems, including the glutamatergic system. Scopolamine injection increases dopamine by inhibiting M2/4 muscarinic autoreceptors. These autoreceptors are located on dopaminergic presynaptic neurons, and their activation reduces the release of dopamine. Therefore, blocking these autoreceptors by scopolamine can increase the release of dopamine. Both D1 and D2 receptors are involved in learning and memory processes. In general, stimulation of dopamine D1 receptors follows an inverted U-shaped dose-response curve, meaning that both insufficient and excessive amounts of dopamine cause memory impairment. Therefore, an indirect effect on the dopaminergic system can be one of the scopolamine-induced memory impairment mechanisms. Effects on cell membrane potential and neuron plasticity, and interaction with acetylcholine are among other mechanisms. Serotonin plays a complex role in memory and learning. Serotonin receptors (5-HT2A) also play a role in memory function by affecting calcium transport. This action is similar to dopamine and other G-protein-coupled receptors, which activate phospholipase C, enter calcium into the cell, and activate calcineurin. Activation of 5-HT2A and 5-HT4 receptors by specific agonists of these receptors enhances long-term potentiation (LTP), which plays a significant role in memory. On the other hand, specific 5-HT3 receptor antagonist improves LTP. The 5-HT6 receptor antagonist can improve memory function. Therefore, different serotonin receptors have different roles in memory function, and the interaction between scopolamine and these receptors needs further study. It has been shown that histamine increases the secretion of acetylcholine in the hippocampus, and postsynaptic H1 and presynaptic H3 receptors play a major role in memory and learning; however, whether scopolamine can cause memory impairment through interaction with histamine receptors has been not reviewed

Clinical and preclinical advances in PSMA-Directed Antibody-Drug conjugates (ADCs): Current status and hope for the future

Prostate-specific membrane antigen (PSMA) is a type II membrane glycoprotein overexpressed in a variety of tumors, especially in nearly all prostate cancers, which makes it a potentially attractive antigen for targeted cancer therapies. More importantly, PSMA, due to no shedding into circulation and efficient internalization after antibody binding, becomes a potential target for antibody-drug conjugates (ADCs), a valid and emerging paradigm of cancer treatment. Four and eight PSMA-directed ADCs have been or are currently being investigated in clinical trials (three of which failed to confirm the promising results while one is currently being evaluated in an ongoing clinical study) and preclinical studies, respectively, for the treatment of PSMA-positive solid tumors, especially prostate cancer. The present study aims to completely review clinical- and preclinical-stage PSMA-directed ADCs

Helicobacter pylori seropositivity in Iranian patients with vitiligo: a case-control study

Background: Vitiligo is an autoimmune disease of the skin that affects both sexes and people of any age. The genetic and environmental factors are involved in the vitiligo etiology. Helicobacter pylori (H. pylori) has an important role in vitiligo progression. Therefore, the present study evaluated H. pylori seropositivity in vitiligo patients compared to healthy individuals. Method: H. pylori infection was investigated in 210 vitiligo patients and 127 sex-and age-matched healthy controls using Enzyme-Linked Immunosorbent Assay (ELISA) test. The data was analyzed using SPSS software version 20.0, and the groups were compared using T-test and ANOVA tests. P < 0.05 was considered statistically significant. Resul t s: Vi t i l i go pat i ent s had hi gher medi an l evel s of I gG (29.68 ± 28.28 RU/mL) than (19.08 ± 20.12 RU/mL) in healthy controls (P < 0.000). Moreover, there was no significant difference between groups based on the level of IgM (P < 0.207). In the vitiligo group, IgG or IgM means were different compared to age (P < 0.33)/ (P < 0.017) and early symptoms (P < 0.00) (P < 0.02), respectively. Unlike IgG, there was a significant difference between the mean level of IgM, the onset age of vitiligo (P < 0.022), and the duration of the disease (P < 0.05). Moreover, males and females with vitiligo had a higher seropositivity to H. pylori antibodies than the control group. Conclusion: Vitiligo was found to be significantly associated with H. pylori in Iranian patients. Therefore, it seemed probable that H. pylori had an important role in the initiation or progression of disease activity in vitiligo

Oral supplementation with crocin (a constituent of saffron) in subjects with cigarette smoking: a clinical trial

Smoking is one of the main causes of death in the world. Cigarette use is related with various components of metabolic syndrome (e.g., insulin resistance, raised blood pressure, dyslipidemia, oxidative stress, inflammation state) and psychiatric disorders. This study was conducted to determine the effect of crocin (Cro) supplementation on nicotine dependence, anxiety, depression, and metabolic indices in smokers. A total of 50 smokers were selected and randomly categorized into two groups (crocin and placebo). The intervention group received crocin (30 mg per day; n = 25) and placebo (containing Avicel; n = 25) once a day. The primary (nicotine dependence, depression, and anxiety inventory) and secondary (metabolic indices) outcomes were assessed at the start of the intervention and after the 3 months. Multiple linear regression models were used to assess the treatment effects on the outcomes adjusting for confounding variables. The primary outcome results such as nicotine dependence, depression, and anxiety inventory did not have a significant difference among the intervention groups (P > 0.05). Also in the secondary outcomes, fasting plasma glucose (FPG), insulin, and homeostasis model of assessment-insulin resistance (HOMA-IR) levels did indicate a significant difference by Cro intervention (β − 3.27 mg/dL; 95% CI, − 5.23, − 1.31; P = 0.002; β − 0.76 μIU/mL; 95% CI, − 1.38, − 0.15; P = 0.01; β − 0.18; 95% CI, − 0.29, − 0.07; P = 0.002), respectively. There were also significant reductions in serum levels of high-sensitivity C-reactive protein (hs-CRP) (β − 0.72 mg/L; 95% CI, − 1.37, − 0.07; P = 0.03), compared with the placebo. Cro intake may have favorable effects on the level of FPG, insulin, HOMA-IR, and hs-CRP in smokers. However, due to the small sample size and limited scientific reports on smokers, further studies are necessary. ClinicalTrial.gov Identifier: IRCT20170420033551N1

Vaccine enhancement and improved immunogenicity using erythrocytes as carriers

Achieving optimal immunogenicity and efficacy in vaccination presents significant challenges, including the need for multiple doses and the limited immunogenicity observed with certain vaccine formulations. To overcome these obstacles, researchers are exploring supplementary components and innovative delivery strategies. The development of an effective vaccine delivery technology is crucial for achieving sufficient protective immunity and disease prevention. This article focuses on the potential of erythrocytes as vaccine carriers to enhance vaccine effectiveness, particularly in the context of whole particle vaccines. The extended lifespan of erythrocytes enables sustained antigen exposure, resulting in continuous antigen presentation to immune cells. Moreover, erythrocytes exhibit biocompatibility, a well-established safety profile, and the capacity to modulate immune responses through interactions with complement receptors. These characteristics position erythrocytes as an appealing platform for targeted vaccine delivery. The hypothesis suggests utilizing bispecific monoclonal antibodies to complement receptor 1 and specific pathogen proteins to hitchhike inactivated pathogens onto erythrocytes. These modified erythrocytes can then serve as carriers to deliver the whole particle vaccine to antigen-presenting cells (APCs) or function as APCs themselves in the spleen. This article puts forward treatment protocols aimed at improving accessibility of vaccinations at the appropriate location, reducing the frequency of vaccine doses, and stimulating sufficient protective immunit

The Effect of Psychological Intervention Based on Mobile Application on Self-Efficacy and Self-Concept of Patients Undergoing Laparoscopic Cholecystectomy: Original Article

Background: Self-efficacy and self-concept are psychological factors that affect the results of surgery and the recovery of patients. The study aimed to investigate the effectiveness of psychological intervention based on mobile applications in improving the self-efficacy and self-concept of laparoscopic cholecystectomy candidates. Methods: In this semi-experimental study, 60 candidates for laparoscopic cholecystectomy in Shahrekord in 2022 were divided into two groups using permutation blocks. The intervention group used a psychological intervention based on a mobile application for two months, and the control group received only the usual hospital care. Data were collected using two questionnaires, the general self-efficacy of Sherer and the self-concept of Rogers in three stages, before, immediately, and two months after the intervention, and analyzed with descriptive statistics parameters and inferential statistics tests. Findings: Before the intervention, the average self-efficacy score in the intervention and control groups was 62.70 ± 9.30 and 59.50 ± 7.22, respectively, and the average self-concept score in the intervention and control groups was 10.69 ± 3.45 and 10.63 ± 3.19, respectively, that no was statistically significant difference between the groups in terms of self-efficacy (P = 0.14) and self-concept (P = 0.13). But, immediately after the intervention, the average score of self-efficacy (P = 0.04) and self-concept (P = 0.04) had a statistically significant difference between the two groups. Also, two months after the intervention, the difference in the two groups' mean self-efficacy scores (P = 0.01) and self-concept (P = 0.01) was significant. Conclusion: Psychological intervention based on mobile application can be used as an effective intervention to improve the self-efficacy and self-concept of laparoscopic cholecystectomy candidates

Advances in skin gene therapy: utilizing innovative dressing scaffolds for wound healing, a comprehensive review

The skin, serving as the body's outermost layer, boasts a vast area and intricate structure, functioning as the primary barrier against external threats. Disruptions in the composition and functionality of the skin can lead to a diverse array of skin conditions, such as wounds, burns, and diabetic ulcers, along with inflammatory disorders, infections, and various types of skin cancer. These disorders not only exacerbate concerns regarding skin health and beauty but also have a significant impact on mental well-being. Due to the complexity of these disorders, conventional treatments often prove insufficient, necessitating the exploration of new therapeutic approaches. Researchers develop new therapies by deciphering these intricacies and gaining a thorough understanding of the protein networks and molecular processes in skin. A new window of opportunity has opened up for improving wound healing processes because of recent advancements in skin gene therapy. To enhance skin regeneration and healing, this extensive review investigates the use of novel dressing scaffolds in conjunction with gene therapy approaches. Scaffolds that do double duty as wound protectors and vectors for therapeutic gene delivery are being developed using innovative biomaterials. To improve cellular responses and speed healing, these state-of-the-art scaffolds allow for the targeted delivery and sustained release of genetic material. The most recent developments in gene therapy techniques include RNA interference, CRISPR-based gene editing, and the utilization of viral and non-viral vectors in conjunction with scaffolds, which were reviewed here to overcome skin disorders and wound complications. In the future, there will be rare chances to develop custom methods for skin health care thanks to the combination of modern technology and collaboration among discipline

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions. Funding: Bill & Melinda Gates Foundation

Therapeutic Potential of Ocimum basilicum L. Extract in Alleviating Autistic‐Like Behaviors Induced by Maternal Separation Stress in Mice: Role of Neuroinflammation and Oxidative Stress

A confluence of genetic, environmental, and epigenetic factors shapes autism spectrum disorder (ASD). Early-life stressors like MS play a contributing role in this multifaceted neurodevelopmental disorder. This research was to explore the efficacy of Ocimum basilicum L. (O.B.) extract in mitigating behaviors reminiscent of autism prompted by maternal separation (MS) stress in male mice, focusing on its impact on neuroinflammation and oxidative stress. MS mice were treated with O.B. extract at varying dosages (20, 40, and 60 mg/kg) from postnatal days (PND) 51–53 to PND 58–60. Behavioral experiments, including the Morris water maze, three-chamber test, shuttle box, and resident-intruder test, were conducted post-treatment. The method of maternal separation involved separating the pups from their mothers for 3 h daily, from PND 2 to PND 14. Molecular analysis of hippocampal tissue was performed to assess gene expression of Toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). Hippocampal and serum malondialdehyde (MDA) levels and total antioxidant capacity (TAC) were measured. O.B. extract administration resulted in the amelioration of autistic-like behaviors in MS mice, as evidenced by improved spatial and passive avoidance memories and social interactions, as well as reduced aggression in behavioral tests. O.B. extract attenuated oxidative stress and neuroinflammation, as indicated by decreased MDA and increased TAC levels, as well as downregulation of TLR4, TNF-α, and IL-1β expression in the hippocampus. O.B. extract may offer a novel therapeutic avenue for ASD, potentially mediated through its anti-inflammatory and antioxidant propertie