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Mahmood Barani,1 Enrico Sangiovanni,2 Marco Angarano,2 Mohammad Amin Rajizadeh,3 Mehrnaz Mehrabani,4 Stefano Piazza,2 Hosahalli Veerabhadrappa Gangadharappa,5 Abbas Pardakhty,6 Mehrzad Mehrbani,7 Mario Dell’Agli,2 Mohammad Hadi Nematollahi8 1Medical Mycology and Bacteriology Research Center, Kerman University of Medical Sciences, Kerman, 76169-13555, Iran; 2Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, 20133, Italy; 3Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran; 4Physiology Research Center, Kerman University of Medical Sciences, Kerman, Iran; 5Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, India; 6Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran; 7Department of Traditional Medicine, Faculty of Traditional Medicine, Kerman University of Medical Sciences, Kerman, Iran; 8Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, IranCorrespondence: Mario Dell’AgliDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, Milan, 20133, ItalyEmail mario.dellagli@unimi.itMohammad Hadi NematollahiDepartment of Clinical Biochemistry, Kerman University of Medical Sciences, Kerman, IranEmail mh.nematollahi@yahoo.comAbstract: Nowadays, medicinal herbs and their phytochemicals have emerged as a great therapeutic option for many disorders. However, poor bioavailability and selectivity might limit their clinical application. Therefore, bioavailability is considered a notable challenge to improve bio-efficacy in transporting dietary phytochemicals. Different methods have been proposed for generating effective carrier systems to enhance the bioavailability of phytochemicals. Among them, nano-vesicles have been introduced as promising candidates for the delivery of insoluble phytochemicals. Due to the easy preparation of the bilayer vesicles and their adaptability, they have been widely used and approved by the scientific literature. The first part of the review is focused on introducing phytosome technology as well as its applications, with emphasis on principles of formulations and characterization. The second part provides a wide overview of biological activities of commercial and non-commercial phytosomes, divided by systems and related pathologies. These results confirm the greater effectiveness of phytosomes, both in terms of biological activity or reduced dosage, highlighting curcumin and silymarin as the most formulated compounds. Finally, we describe the promising clinical and experimental findings regarding the applications of phytosomes. The conclusion of this study encourages the researchers to transfer their knowledge from laboratories to market, for a further development of these products.Keywords: phytochemical, nanomedicine, phytosome, delivery, vesicle, disease

Lung Ischemia-reperfusion injury (LIRI) is a risk during lung transplantation that can cause acute lung injury and organ failure. In LIRI, the NF-E2-related factor 2(Nrf2)/ Kelch-like ECH-associated protein 1 (Keap1) signaling pathway and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway are two major pathways involved in regulating oxidative stress and inflammation, respectively. Myrtenol, a natural compound with anti-inflammatory and antioxidant properties, has potential protective effects against IRI. This study aimed to explore the impact of myrtenol encapsulated within niosomes on the prevention of LIRI and examine the role of the two pathways mentioned in this process. Wistar rats were segregated into four groups. Animals received the myrtenol (MN) (32 mg/kg) or vehicle through daily inhalation for a week before LIRI. Expression of IκB, p-IκB, Nrf2, Keap1, Heme Oxygenase-1(HO-1), NF-κB signaling proteins, reactive oxygen species (ROS) level, caspase-3 expression, arterial blood gases, lung edema, and histopathological indices were assessed. Niosomal myrtenol significantly reduced lung edema, ROS, Keap1, p-IκB, NF-kB, Caspase-3, PaCO2 (the carbon dioxide pressure in arterial blood), and histopathological indices. Additionally, the expression of IκB, Nrf2, HO-1, and PaO2 (the oxygen pressure in arterial blood) increased significantly in the pretreated group compared to the IR group. Overall, inhalation of the niosomal myrtenol protects against lung ischemia-reperfusion injury, presumably through the balance between Nrf2/Keap1 and NF-κB pathways. The findings suggest that the niosomal form of myrtenol may be a potential candidate for developing new drugs to prevent and treat LIR damage., Competing Interests: Declarations. Ethical approval: The experiments described in this work were conducted in accordance with the guidelines on ethical standards for investigation of animals. The protocol was reviewed and approved by the Ethic Committee of Kerman University of Medical Sciences, with the approval number: IR.KMU.REC.1400.056. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Previous studies have yielded controversial results regarding the effect of spirulina on blood pressure (BP), which need updating. So, this updated systematic review and meta-analysis of randomized controlled trials (RCTs) carry out a more accurate estimation of the effect of spirulina on BP in adults. This systematic searches (in PubMed/Medline, Scopus, and ISI Web of Science) until April 1, 2024, to identify related RCTs based on PICOS guidelines (population (individuals > 18 years old), the intervention (spirulina), the comparison (control or placebo group), the outcomes (systolic BP (SBP) and diastolic BP (DBP)), the study design (RCTs)), and PRISMA-checklist (Supporting Information, data S2). We evaluated the impact of spirulina on DBP and SBP. Conventional procedures were employed for analyzing publication bias, heterogeneity, and sensitivity. The GRADE criteria and the Cochrane assessment method were employed to evaluate the risk of bias (ROB) and certainty of evidence across the studies, respectively. The result shows spirulina consumption decreases SBP (WMD: -4.41 mmHg, 95% CI: -6.74 to -2.07, I 2  = 66.1%) and DBP (WMD: -2.84 mmHg, 95% CI: -4.65 to -1.03, I 2  = 62.3%). Subgroup analysis demonstrated SBP and DBP were still lower in individuals with ≥ 120 and ≥ 80 mmHg, hypertension (HTN) individuals, overweight individuals, age > 50 years, and > 8 weeks of intervention. Indeed, we do not observe publication bias, ROB, or interference studies in the overall results of BPs, and based on GRADE, our outcomes have moderate quality. Because of the low number of studies and participants, the dose-response and meta-regression are not significant. His study demonstrated spirulina intervention decreased SBP and DBP in HTN and overweight individuals, age > 50 years, and > 8 weeks of intervention. So, spirulina intake decreases BP and could be used in clinical practice. Furthermore, more and high-quality RCTs are needed to establish the clinical efficacy of the spirulina and determine cutoff spirulina interventions based on dose and duration. Trial Registration: PROSPERO: CRD42024534608., (© 2024 John Wiley & Sons Ltd.)

Background: Parkinson's disease (PD) is a multifaceted disease that is influenced by both genetic and environmental parameters. Non-coding RNAs have been shown to be ideal biomarkers for several diseases, including PD. This study was conducted to evaluate the expression levels of NEAT1, hsa-let-7a-5p, and miR-506-3p in individuals with PD to assess their efficacy for early-stage PD diagnosis., Methods: Twenty-four patients with PD and 29 healthy individuals participated in this study. The IntaRNA tool was used to predict potential base pairings between NEAT1 and let-7a-5p, and NEAT1 and miR-506-3p. RT-qPCR was employed to measure the relative expression of tyrosine hydroxylase (TH), as well as nuclear enriched abundant transcript 1 (NEAT1), hsa-let-7a-5p, and miR-506-3p levels in both groups. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the diagnostic value., Results: The PD group exhibited significantly elevated NEAT1 expression levels compared to the healthy control group. While the PD group exhibited an insignificant decreased TH expression level relative to the healthy group. Furthermore, the levels of hsa-let-7a-5p and miR-506-3p expression were seen to be decreased in patients with PD in comparison to the control group. Integration of NEAT1, hsa-let-7a-5p, and miR-506-3p levels significantly enhanced diagnostic capabilities and increased the AUC to 0.9501 (95% confidence interval: 0.8978-1.000, p < .0001)., Conclusions: The elevated NEAT1 expression and the decreased expression of hsalet- 7a-5p and miR-506-3p in PD patients indicate that these factors might contribute to the disease's pathogenesis. Combining the ROC curves of NEAT1 and hsa-let-7a-5p with miR-506-3p showed improved sensitivity and specificity, facilitating more accurate PD diagnosis. More importantly, they may contribute as promising non-invasive biomarkers for PD diagnosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Purpose: This study investigated modulating the G protein-coupled estrogen receptor (GPER) on the IRElα/TXNIP pathway and its role in drug resistance in MDA-MB231 cells., Experimental Approach: To determine the optimal concentrations of G 1 and 4-hydroxytamoxifen (TAM), GPER expression and ERK1/2 phosphorylation were analyzed using qRT-PCR and western blotting, respectively. Cells were treated with individual concentrations of G 1 (1000 nM), G 15 (1000 nM), and TAM (2000 nM), as well as combinations of these treatments (G 1 + G 15 , TAM + G 15 , and G 1 + TAM) for 24 and 48 h. The expression levels of GPER, IRE1α, miR-17-5p, TXNIP, ABCB1, and ABCC1 genes and TXNIP protein expression were evaluated. Finally, apoptosis and cell migration were examined using flow cytometry and the wound-healing assay, respectively., Findings/results: Activating GPER with its specific agonist G 1 and TAM significantly increased IRE1α levels in MDA-MB231 cells. IRE1α through splicing XBP1 led to unfolded protein response. In addition, decreased TXNIP gene and protein expression reduced apoptosis, increased migration, and upregulated the genes associated with drug resistance., Conclusion and Implication: Our investigation revealed that blocking the GPER/IRE1α/TXNIP pathway in MDA-MB231 cells could enhance treatment efficacy and improve chemotherapy responsiveness. The distinct unfolded protein response observed in MDA-MB231 cells may stem from the unique characteristics of these cells, which lack receptors for estrogen, progesterone, and HER2/neu hormones, possessing only the GPER receptor (ER - /PR - /HER2 - /GPER + ). This study introduced a new pathway in TNBC cells, indicating that targeting GPER could be crucial in comprehensive therapeutic strategies in TNBC cells., Competing Interests: The authors declared no conflicts of interest in this study., (Copyright: © 2024 Research in Pharmaceutical Sciences.)

Colorectal cancer (CRC) is the second greatest cause of cancer-related death in the world and chemotherapy, as an important part of CRC treatment, has some drawbacks, including systemic toxicity. Therefore, it is crucial to discover new and more effective CRC treatment plans. Rheum khorasanicum (R. khorasanicum) is a medicinal plant with high flavonoids, stilbenes, and anthraquinone contents, so it can be a potential source of antioxidants and can be used for therapeutic purposes and trigger apoptosis in cancer cells. In this study, we investigated the effects of hydroalcoholic root extract of R. khorasanicum treatment on inducing mitochondrial apoptosis of HT-29 and Caco-2 human colorectal adenocarcinoma cells. Firstly, the total phenolic and flavonoid content was determined. Then, the cytotoxic effects of R. khorasanicum on cells of three different types, including HT-29 and Caco-2 colon cancer cells as well as normal 3T3 cells were assessed using the MTT assay. To investigate the characteristics of cellular death, flow cytometry, and western blotting were performed. The results of this study indicated considerable phenolic (356.4±9.4 GAE/gDW) and flavonoid (934.55±17.1 QE/gDW) contents in R. khorasanicum. MTT assay's finding indicated that 100, 60, and 30μg/mL concentrations of R. khorasanicum reduce cell viability in HT-29 and Caco-2 cell lines significantly (P<0.05). It has been also revealed that R. khorasanicum extract induces apoptosis rather than necrosis in these cell lines. Moreover, Bcl-2 expression was significantly reduced in both HT-29 and Caco-2 cell lines, while Bax and cleaved caspase-3 expression soared considerably in the groups under R. khorasanicum treatment (P<0.05). In conclusion, our findings have suggested that high phenol and flavonoid contents of R. khorasanicum root extract possibly play an important role in cell cytotoxicity and apoptosis induction in HT-29 and Caco-2 colon cancer cells., (Copyright © 2024 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Background: Traditional Persian medicine has introduced effective remedies in opioid dependence care. One of the most widely used remedies is an herbal formulation containing Peganum harmala L. and Fraxinus excelsior L. (HF). This study investigated the effects of HF to attenuate the withdrawal signs and rewarding effects in morphine-dependent rats., Methods: Forty-nine male Wistar rats were randomly divided into seven groups. The control and vehicle groups received normal saline and sodium carboxymethyl cellulose, respectively. The morphine group received morphine for one week. The single and daily dose of HF groups received morphine similar to the morphine group, and HF (1.4 and 2.8 g/kg) once a day in the daily dose group and only on the last day of the experiment in the single dose of HF group. Finally, the withdrawal signs as well biochemical tests were evaluated. The behavioral parameters were assessed by conditioned place preference (CPP), elevated plus-maze and Y-maze tests. The antioxidant activity of HF was evaluated by measurement of serum contents of malondialdehyde, stable nitric oxide metabolites and total antioxidant capacity (TAC). Moreover, the protein expression of c-fos was assessed by western blotting., Results: Daily treatment with HF significantly reduced the score of CPP behavioral test, all of the withdrawal signs, TAC and the c-fos protein level., Conclusions: The results indicated that HF might be a promising complementary treatment in reducing morphine-induced physical and psychological dependence probably through modulation of c-fos protein expression.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Endoplasmic Reticulum (ER) stress and Unfolded Protein Response (UPR) play a key role in cancer progression. The aggregation of incorrectly folded proteins in the ER generates ER stress, which in turn activates the UPR as an adaptive mechanism to fix ER proteostasis. Inositol-requiring enzyme 1 (IRE1) is the most evolutionary conserved ER stress sensor, which plays a pro-tumoral role in various cancers. Targeting its' active sites is one of the most practical approaches for the treatment of cancers., Objective: In this study, we aimed to use the structure of 4μ8C as a template to produce newly designed compounds as IRE1 inhibitors., Methods: Various functional groups were added to the 4μ8C, and their binding affinity to the target sites was assessed by conducting a covalent molecular docking study. The potential of the designed compound for further in vitro and in vivo studies was evaluated using ADMET analysis., Results: Based on the obtained results, the addition of hydroxyl groups to 4μ8C enhanced the binding affinity of the designed compound to the target efficiently. Compound 17, which was constructed by the addition of one hydroxyl group to the structure of 4μ8C, can construct a strong covalent bond with Lys907. The outcomes of ADMET analysis indicated that compound 17 could be considered a drug-like molecule., Conclusion: Our results revealed that designed compound 17 could inhibit IRE1 activity. Therefore, this designed compound is a remarkable inhibitor of IRE1 and introduces a promising therapeutic strategy for cancer treatment., Competing Interests: The authors declare that the investigators in this study have no conflict of interest., (Thieme. All rights reserved.)

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 &lt; 0.001 vs. asthma group) and inflammatory cytokines (50 mg/kg; p &lt; 0.001 vs. asthma group) and increased antioxidant enzymes (50 mg/kg, p &lt; 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., (© 2023 S. Karger AG, Basel.)

Introduction: Ischemia-reperfusion injury (IRI) is directly related to forming reactive oxygen species, endothelial cell injury, increased vascular permeability, and the activation of neutrophils and cytokines. Niosomes are nanocarriers and an essential part of drug delivery systems. We aimed to investigate the effects of myrtenol's inhaled and intraperitoneal niosomal form, compared to its simple form, on lung ischemia reperfusion injury (LIRI)., Material and Method: Wistar rats were divided into ten groups. Simple and niosomal forms of myrtenol were inhaled or intraperitoneally injected daily for one week prior to LIRI. We evaluated oxidative stress, apoptotic, and inflammatory indices, nitric oxide, inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS) and histopathological indices., Results: Pretreatment with simple and niosomal forms of myrtenol significantly inhibited the indices of pulmonary edema, pro-inflammatory cytokines and proteins, oxidant agents, nitric oxide, iNOS, apoptotic proteins, congestion of capillaries, neutrophil infiltration, and bleeding in the alveoli. Furthermore, myrtenol increased anti-inflammatory cytokines, anti-oxidants agents, eNOS, anti-apoptotic proteins and the survival time of animals. The niosomal form of myrtenol showed a more ameliorative effect than its simple form., Conclusion: The results showed the superior protective effect of the inhalation of myrtenol niosomal form against LIRI compared to its simple form and systemic use., Competing Interests: Declaration of Competing Interest The authors declare there is no conflict of interest., (Copyright © 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Keratoconus (KC) is characterized by the predominant primary ectatic disease, affecting the cornea, necessitating corneal transplants in some cases. While some loci associated with KC risk have been identified, the understanding of the disease remains limited. Superoxide dismutase (SOD) enzymes play a crucial role in countering the reactive oxygen species and providing protection against oxidative stress (OS). Accordingly, the objective of this study was to investigate a potential association of a 50 nucleotide base pairs (bp) insertion/deletion (I/D) within the SOD1 promoter, and the located 1684 bp upstream of the SOD1 ATG, with KC in the Iranian population. Additionally, an assessment was conducted on SOD activity and the total antioxidant capacity (TAC), as determined by the ferric reducing-antioxidant power assay, along with malondialdehyde (MDA) levels. In this case-control study, genomic DNA was extracted from the blood cells of KC (n = 402) and healthy (n = 331) individuals. The genotype of this gene was determined using the PCR technique. Furthermore, the amount of SOD enzyme activity and the MDA and TAC levels were measured in the serum of the study groups. The (I/I) genotype was present in 84.23%, the (I/D) genotype in 15.06%, and the (D/D) genotype in 0.69% of both groups. A statistically significant relationship was seen between different genotypes and TAC, MDA, and SOD1 activity indices (P < 0.05). Individuals with the D/D genotype exhibited a decrease in total antioxidant capacity, an increase in the amount of MDA, and a decrease in SOD1 enzyme activity (P < 0.05). Moreover, the logistic regression analysis of KC development indicated that elevated levels of MDA increased the risk of KC incidence in the patient group compared to the healthy group, while a higher activity of SOD1 and greater values of TAC decreased the KC risk. The removal of the 50 bp fragment reduced SOD1 activity and elevated OS levels, thereby impacting the oxidant-antioxidant balance. This could potentially play a significant role in individuals afflicted by KC., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Coronary artery disease (CAD) and myocardial infarction (MI) are the most prevalent diseases globally. While several risk factors for MI are well assessed, the influence of trace elements on MI has not been thoroughly studied. This study aimed to evaluate lithium (Li) and zinc (Zn) levels in MI patients and healthy control and assess their relationship with oxidative stress (OS) parameters, such as nitric oxide (NO) and total antioxidant capacity (TAC)., Methods: This case-control study was performed on 182 patients with MI and 83 healthy subjects at Shafa Hospital in Kerman, Iran. MI patients were divided into two groups based on the angiography results: those with coronary artery block above 50 % (CAB >50 %, n = 92) and those with coronary artery block below 50 % (CAB <50 %, n = 90). A flame atomic absorption spectrometer was used to detect Li and Zn levels, and biochemical indices were measured by an autoanalyzer. Also, ferric reducing antioxidant power assay and the Griess method were used to measure the amounts of NO and TAC., Results: The levels of TAC and Li were significantly higher in the control group than in the patient groups (in both CAB >50 % and CAB <50 % groups). Furthermore, in the CAB <50 % group, TAC and Li levels were significantly higher than in the CAB >50 % group. In the Zn levels evaluation, higher concentration was seen in the CAB >50 % group compared to the CAB <50 % group (P < 0.05). Moreover, Zn and NO levels were significantly higher in both CAB groups compared to controls. In continue, Li levels had a positive association with TAC and ejection fraction percentage (EF%) as well as a negative association with NO levels and Zn levels had a significant positive association with NO and a negative association with TAC. In logistic regression analysis, Li, TAC, and high-density lipoprotein-cholesterol significantly decreased the odds ratio (OR) of MI, whereas Zn, NO, total cholesterol, triglyceride, low-density lipoprotein-cholesterol, and high-sensitivity C-reactive protein (hs-CRP) significantly increased the OR of MI. Furthermore, the area under the curve (AUC) analysis indicated that Li had the highest AUC for the diagnosis of CAB >50 % (Li < 167 ng/mL), and Zn ≥ 1810 μg/mL increased disease severity., Conclusion: Our investigation revealed that Li had a protective effect against CAD by decreasing OS and increasing EF%. However, Zn at concentrations higher than 1810 μg/mL was found to be cytotoxic and increased the risk of MI through increased OS. Taken togather, it could be concluded that Li supplementation may decrease the risk of CAD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

MXenes and graphene are two-dimensional materials that have gained increasing attention in neuroscience, particularly in sensing, theranostics, and biomedical engineering. Various composites of graphene and MXenes with fascinating thermal, optical, magnetic, mechanical, and electrical properties have been introduced to develop advanced nanosystems for diagnostic and therapeutic applications, as exemplified in the case of biosensors for neurotransmitter detection. These biosensors display high sensitivity, selectivity, and stability, making them promising tools for neuroscience research. MXenes have been employed to create high-resolution neural interfaces for neuroelectronic devices, develop neuro-receptor-mediated synapse devices, and stimulate the electrophysiological maturation of neural circuits. On the other hand, graphene/derivatives exhibit therapeutic applicability in neuroscience, as exemplified in the case of graphene oxide for targeted delivery of therapeutic agents to the brain. While MXenes and graphene have potential benefits in neuroscience, there are also challenges/limitations associated with their use, such as toxicity, environmental impacts, and limited understanding of their properties. In addition, large-scale production and commercialization as well as optimization of reaction/synthesis conditions and clinical translation studies are very important aspects. Thus, it is important to consider the use of these materials in neuroscience research and conduct further research to obtain an in-depth understanding of their properties and potential applications. By addressing issues related to biocompatibility, long-term stability, targeted delivery, electrical interfaces, scalability, and cost-effectiveness, MXenes and graphene have the potential to greatly advance the field of neuroscience and pave the way for innovative diagnostic and therapeutic approaches for neurological disorders. Herein, recent advances in therapeutic and diagnostic applications of graphene- and MXene-based materials in neuroscience are discussed, focusing on important challenges and future prospects.

Chalcones and their derivatives have been widely studied due to their versatile pharmacological and biological activities, such as anti-inflammatory, antibacterial, antiviral, and antitumor effects. These compounds have shown suitable antiviral effects through the selective targeting of a variety of viral enzymes, including lactate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), fumarate reductase, protein tyrosine phosphatase, topoisomerase-II, protein kinases, integrase/protease, and lactate/isocitrate dehydrogenase, among others. Chalcones and their derivatives have displayed excellent potential for combating pathogenic bacteria and fungi (especially, multidrug-resistant bacteria). However, relevant mechanisms should be further explored, focusing on inhibitory effects against DNA gyrase B, UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), and efflux pumps (e.g. , NorA), among others. In addition, the antifungal and antiparasitic activities of these compounds (e.g., antitrypanosomal and antileishmanial properties) have prompted additional explorations. Nonetheless, systematic analysis of the relevant mechanisms, biosafety issues, and pharmacological properties, as well as clinical translation studies, are vital for practical applications. Herein, recent advancements pertaining to the antibacterial, antiviral, antiparasitic, and antifungal activities of chalcones and their derivatives are deliberated, focusing on the relevant mechanisms of action, crucial challenges, and future prospects. Furthermore, due to the great importance of greener and more sustainable synthesis of these valuable compounds, especially on an industrial scale, the progress made in this field has been briefly discussed. Hopefully, this review can serve as a catalyst for researchers to delve deeper into the exploration and designing of novel chalcone compounds with medicinal properties, especially against pathogenic viruses and multidrug-resistant bacteria as major causes of concern for human health., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Aging causes substantial molecular to morphological changes in the brain. The brain cells are more susceptible towards oxidative damage due to impaired antioxidant defense system. Sirtuin1 (SIRT1) is a crucial cellular survival protein, which its gene has been identified as a direct target of microRNA 132 (miR-132). Trehalose contributes to preventing neuronal damage through several mechanisms. However, little is known about the interactive effects of aging and trehalose on the expression pattern of miR-132 and SIRT1 in the hippocampus. Male Wistar rats were divided into four groups. Two groups of aged (24 months) and young (4 months) rats were administered 2% trehalose solution for 30 days. Two other groups of aged and young rats received regular tap water. At the end of treatment, the levels of Sirt1 mRNA and its protein, malondialdehyde, protein carbonyl content, total antioxidant capacity, tumor necrosis factor α (TNF-α), as well as the expression of miR-132 were measured in the hippocampus. We found that trehalose treatment upregulated the expression of SIRT1 and miR-132. Moreover, administration of trehalose enhanced the level of total antioxidant activity whereas reduced the levels of lipid peroxidation, protein carbonyl content, and TNF-α. In conclusion, our data indicated that trehalose restored antioxidant status and alleviated inflammation in the hippocampus which was probably associated with the upregulation of SIRT1 and miR-132., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Photocatalysis can be considered as a green technology owing to its excellent potential for sustainability and fulfilling several principles of green chemistry. This process uses light radiation as the primary energy source, preventing or reducing the requirement for artificial light sources and exogenous catalytic entities. Photocatalysis has promising applications in biomedicine such as drug delivery, biosensing, tissue engineering, cancer therapeutics, etc. In targeted cancer therapeutics, photocatalysis can be employed in photodynamic therapy to form reactive oxygen species that damage cancerous cells' structure. Nanophotocatalysts can be used in targeted drug delivery, showing potential applications in nuclear-targeted drug delivery along with specific delivery of chemotherapeutics to cancer cells or tumor sites. On the other hand, in tissue engineering, nanophotocatalysts can be employed in designing scaffolds that promote cell growth and tissue regeneration. However, some important challenges pertaining to the performance of photocatalysis, large-scale production of nanophotocatalysts, optimization of reaction/synthesis conditions, long-term biosafety issues, stability, clinical translation, etc. still need further explorations. Herein, the most recent advancements pertaining to the biomedical applications of nanophotocatalysts are reflected, focusing on drug delivery, tissue engineering, biosensing, and cancer therapeutic potentials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Asthma is a common chronic allergic disease that affects a significant percentage of the world's population. Niosomes are nanoparticles consisting of non-ionic surfactants that can be used for drug delivery. This research was designed to investigate the impacts of inhalation of simple and niosomal forms of myrtenol against adverse consequences of asthma in rats. Asthma induction was performed via injection of ovalbumin, followed by its inhalation. Niosomes were created by a heating protocol, and their physicochemical features were evaluated. Forty-nine male Wistar rats were allotted into 7 groups (n=7 each): Control (CTL), vacant niosome (VN), Asthma, Asthma+VN, Asthma+SM (simple myrtenol), Asthma+NM (niosomal myrtenol), and Asthma+B (budesonide). Lung remodeling, serum immunoglobulin E (IgE), inflammatory  and cytokines, and antioxidant factors in the lung tissue and bronchoalveolar fluid (BALF), as well as), were evaluated. The results showed that myrtenol-loaded niosomes had appropriate encapsulation efficiency, kinetic release, size, and zeta potential. The thickness of the epithelial cell layer in the lungs, as well as cell infiltration, fibrosis, IgE, reactive oxygen species, interleukin (IL)-6, and tumor nuclear factor alpha (TNF-α) levels, decreased significantly. In contrast, superoxide dismutase and glutathione peroxide activity increased significantly in the serum and BALF of the treated groups. The niosomal form of myrtenol revealed a higher efficacy than simple myrtenol and was similar to budesonide in ameliorating asthma indices.  Inhalation of simple and niosomal forms of myrtenol improved the detrimental changes in the asthmatic lung. The niosomal form induced more prominent anti-asthmatic effects comparable to those of budesonide.

Today, a wide variety of bio- and nanomaterials have been deployed for cardiovascular tissue engineering (TE), including polymers, metal oxides, graphene/its derivatives, organometallic complexes/composites based on inorganic-organic components, among others. Despite several advantages of these materials with unique mechanical, biological, and electrical properties, some challenges still remain pertaining to their biocompatibility, cytocompatibility, and possible risk factors (e.g., teratogenicity or carcinogenicity), restricting their future clinical applications. Natural polysaccharide- and protein-based (nano)structures with the benefits of biocompatibility, sustainability, biodegradability, and versatility have been exploited in the field of cardiovascular TE focusing on targeted drug delivery, vascular grafts, engineered cardiac muscle, etc. The usage of these natural biomaterials and their residues offers several advantages in terms of environmental aspects such as alleviating emission of greenhouse gases as well as the production of energy as a biomass consumption output. In TE, the development of biodegradable and biocompatible scaffolds with potentially three-dimensional structures, high porosity, and suitable cellular attachment/adhesion still needs to be comprehensively studied. In this context, bacterial cellulose (BC) with high purity, porosity, crystallinity, unique mechanical properties, biocompatibility, high water retention, and excellent elasticity can be considered as promising candidate for cardiovascular TE. However, several challenges/limitations regarding the absence of antimicrobial factors and degradability along with the low yield of production and extensive cultivation times (in large-scale production) still need to be resolved using suitable hybridization/modification strategies and optimization of conditions. The biocompatibility and bioactivity of BC-based materials along with their thermal, mechanical, and chemical stability are crucial aspects in designing TE scaffolds. Herein, cardiovascular TE applications of BC-based materials are deliberated, with a focus on the most recent advancements, important challenges, and future perspectives. Other biomaterials with cardiovascular TE applications and important roles of green nanotechnology in this field of science are covered to better compare and comprehensively review the subject. The application of BC-based materials and the collective roles of such biomaterials in the assembly of sustainable and natural-based scaffolds for cardiovascular TE are discussed.

Carbon dots (CDs) with unique physicochemical features such as exceptional biocompatibility, low cost, eco-friendliness, abundant functional groups ( e.g. , amino, hydroxyl, and carboxyl), high stability, and electron mobility have been broadly investigated in nano- and biomedicine. In addition, the controlled architecture, tunable fluorescence emission/excitation, light-emitting potential, high photostability, high water solubility, low cytotoxicity, and biodegradability make these carbon-based nanomaterials suitable for tissue engineering and regenerative medicine (TE-RM) purposes. However, there are still limited pre- and clinical assessments, because of some important challenges such as the scaffold inconsistency and non-biodegradability in addition to the lack of non-invasive methods to monitor tissue regeneration after implantation. In addition, the eco-friendly synthesis of CDs exhibited some important advantages such as environmentally friendly properties, low cost, and simplicity compared to the conventional synthesis techniques. Several CD-based nanosystems have been designed with stable photoluminescence, high-resolution imaging of live cells, excellent biocompatibility, fluorescence properties, and low cytotoxicity, which make them promising candidates for TE-RM purposes. Combining attractive fluorescence properties, CDs have shown great potential for cell culture and other biomedical applications. Herein, recent advancements and new discoveries of CDs in TE-RM are considered, focusing on challenges and future perspectives., Competing Interests: The author(s) declare no competing interest., (This journal is © The Royal Society of Chemistry.)

Over recent years, much attention has been devoted to the field of screening natural products and/or their novel structures because of reversing cancer progression. The current research work was intended to explore the cytotoxic activity of ethanol and ethyl acetate extracts of dried fruit of Terminalia chebula Retz. (T. chebula) in MCF-7 cell line. High-performance thin-layer chromatographic (HPTLC) method and Folin-Ciocalteu colorimetric techniques were performed. Anti-proliferative activities of T. chebula fruit extracts on the MCF-7 cell line were evaluated using MTT assay. Effects of both extracts on the migration of MCF-7 cells and the size of MCF-7-derived spheroids were also evaluated. Moreover, antioxidant properties were measured by DPPH and FRAP methods. Western blotting was used to measure the HIF-1α and CXCR-4 protein levels. Chebulagic acid, gallic acid, chebulinic acid, and ellagic acid were found as major compounds in both extracts. The total phenolic contents based on gallic acid equivalent (GAE) in the ethanol and ethyl acetate extracts of T. chebula were found to be 453.68 ± 0.31 and 495.12 ± 0.43 mg GAE/g dry weight of the extract, respectively. Both extracts exerted a significant dose- and time-dependent cytotoxicity effect on MCF-7 cells. They also had a marked negative effect on the average size of MCF-7-derived spheroids and their migration rate. None of the extracts exhibited stronger antioxidant activities than vitamin C. Furthermore, both extracts at a concentration of 125 µg/ml could meaningfully decrease the expression levels of HIF-1α and CXCR-4 in MCF-7 cells. These data represent that T. chebula may be a valuable medicinal resource in the regulation of breast cancer proliferation, growth, and metastasis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The molecular mechanisms of opium action with regard to coronary artery disease (CAD) have not yet been determined. The aim of this study was to evaluate the effect of opium on the expression of scavenger receptors including CD36, CD68, and CD9 tetraspanin in monocytes and the plasma levels of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), malondialdehyde (MDA), and nitric oxide metabolites (NO x ) in CAD patients with and without opium addiction. This case-control study was conducted on three groups: (1) opium-addicted CAD patients (CAD + OA, n = 30); (2) CAD patients with no opium addiction (CAD, n = 30); and (3) individuals without CAD and opium addiction as the control group (Ctrl, n = 17). The protein and mRNA levels of CD9, CD36, and CD68 were evaluated by the flow cytometry and quantitative polymerase chain reaction (RT-qPCR) methods, respectively. The consumption of atorvastatin, aspirin, and glyceryl trinitrate was found be higher in the CAD groups compared with the control group. The plasma level of TNF-α was significantly higher in the CAD + OA group than in the CAD and Ctrl groups (p = 0.001 and p = 0.005, respectively). MDA levels significantly increased in CAD and CAD + OA patients in comparison with the Ctrl group (p = 0.010 and p = 0.002, respectively). No significant differences were found in CD9, CD36, CD68, IFN-γ, and NO x between the three groups. The findings demonstrated that opium did not have a significant effect on the expression of CD36, CD68, and CD9 at gene and protein levels, but it might be involved in the development of CAD by inducing inflammation through other mechanisms.

Cardiovascular diseases (CVDs) are known as the first causes of death throughout the world, and mainly myocardial infarction (MI), lead to 7.4 million deaths annually. Atherosclerosis is the major underlying cause of most CVDs. However, exposure to heavy metals, among other factors, deserves further attention as a risk factor for CVDs. This study was designed to evaluate the levels of arsenic (Ars) in myocardial infarction (MI) patients and healthy individuals as well as assess the association between the incidence of MI and Ars, total antioxidant capacity (TAC), and oxidative stress. This case-control study was conducted among patients with MI (n = 164) and normal individuals (n = 61) at Shafa Hospital in Kerman, Iran. Patients were classified into two groups, including coronary artery blocks above 50% (CAB > 50%, n = 83) and coronary artery blocks less than 50% (CAB < 50%, n = 83) based on their angiography findings. The demographic characteristics, clinical history, biochemical parameters, and serum Ars and TAC levels were evaluated. In the present study, both CAB groups had significantly reduced levels of TAC compared with the control. Furthermore, TAC was lower in the CAB > %50 group compared to the CAB < %50 group. Ars levels were significantly higher in both CAB groups compared with the control. There was a significant positive relationship between CAB and Ars, BG, HbA 1 c, urea, creatinine, TG, TC, and LDL-c, as well as a negative relationship between HDL-c and TAC. Moreover, TAC levels showed a significant inverse correlation with Ars, HbA 1 c, and creatinine, and a positive correlation with HDL-c. As risk factors, Ars, hs-CRP, TG, TC, and LDL-c enhance the severity of the disease, and HDL-c and TAC decrease the disease severity. Moreover, ROC curve analysis revealed that the highest AUC for the CAB > %50 (AUC = 78.29), and cytotoxic levels for both CAB groups (Ars ≥ 0.105 ppm), and no significant differences were found between the two groups. Our findings suggest that Ars at ≥ 0.105 ppm is able to increase the risk of MI through the increased OS and decreased TAC., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pulmonary fibrosis (PF) is the end stage of severe lung diseases, in which the lung parenchyma is replaced by fibrous scar tissue. The result is a remarkable reduction in pulmonary compliance, which may lead to respiratory failure and even death. Idiopathic pulmonary fibrosis (IPF) is the most prevalent form of PF, with no reasonable etiology. However, some factors are believed to be behind the etiology of PF, including prolonged administration of several medications (e.g., bleomycin and amiodarone), environmental contaminant exposure (e.g., gases, asbestos, and silica), and certain systemic diseases (e.g., systemic lupus erythematosus). Despite significant developments in the diagnostic approach to PF in the last few years, efforts to find more effective treatments remain challenging. With their immunomodulatory, anti-inflammatory, and anti-fibrotic properties, stem cells may provide a promising approach for treating a broad spectrum of fibrotic conditions. However, they may lose their biological functions after long-term in vitro culture or exposure to harsh in vivo situations. To overcome these limitations, numerous modification techniques, such as genetic modification, preconditioning, and optimization of cultivation methods for stem cell therapy, have been adopted. Herein, we summarize the previous investigations that have been designed to assess the effects of stem cell preconditioning or genetic modification on the regenerative capacity of stem cells in PF., Competing Interests: The authors declare no conflicts of interest.

The molecular mechanisms of opium with regard to coronary artery disease (CAD) have not yet been determined. The aim of the present study was to evaluate the effect of opium on the expression of scavenger receptors including CD36, CD68, and CD9 tetraspanin in monocytes and the plasma levels of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), malondialdehyde (MDA), and nitric oxide metabolites (NO x ) in patients with CAD with and without opium addiction. This case-control study was conducted in three groups: (1) opium-addicted patients with CAD (CAD+OA, n=30); (2) patients with CAD with no opium addiction (CAD, n=30); and (3) individuals without CAD and opium addiction as the control group (Ctrl, n=17). Protein and messenger RNA (mRNA) levels of CD9, CD36, and CD68 were evaluated by flow cytometry and reverse transcription-quantitative PCR methods, respectively. Consumption of atorvastatin, aspirin, and glyceryl trinitrate was found to be higher in the CAD groups compared with the control group. The plasma level of TNF-α was significantly higher in the CAD+OA group than in the CAD and Ctrl groups (p=0.001 and p=0.005, respectively). MDA levels significantly increased in the CAD and CAD+OA groups in comparison with the Ctrl group (p=0.010 and p=0.002, respectively). No significant differences were found in CD9, CD36, CD68, IFN-γ, and NO x between the three groups. The findings demonstrated that opium did not have a significant effect on the expression of CD36, CD68, and CD9 at the gene and protein levels, but it might be involved in the development of CAD by inducing inflammation through other mechanisms., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Iron is a trace element that is used to replicate the virus and has a role in the vital functions of the body and the host's innate immune system. The mechanism of iron in COVID-19 severity is still not well understood. The aim of this study was to evaluate the association of the iron with COVID-19 severity. A case-control study was performed on 147 patients with a positive PCR test result and 39 normal individuals admitted to the Persian Gulf Martyrs Hospital in Bushehr, Iran. The iron profiles and related tests were measured along with hematological analytes. Hemoglobin (Hb), Fe, and saturated transferrin decreased in all the groups compared to the controls, but ferritin increased in the patient groups. After adjusting for age and sex, we found that increased ferritin levels augmented the odds ratio (OR) of the disease in the moderate (OR = 2.95, P = 0.007), severe (OR = 6.1, P < 0.001), and critical groups (OR = 8.34, P < 0.001). The decreased levels of Fe reduced the OR of the disease in the mild (OR = 0.96, P < 0.001), moderate (OR = 0.96, P < 0.001), severe (OR = 0.95, P < 0.001), and critical (OR = 0.98, P = 0.001) groups. Fe (AUC = 85.95, cutoff < 75.5 µg/dL, P < 0.001) and ferritin (AUC = 84.45, cutoff > 157.5 ng/dL, P < 0.001) have higher AUC for disease prognosis, but only ferritin (AUC = 74.89, cutoff > 261.5 ng/dL, P < 0.001) has higher AUC for disease severity assays. It could be concluded that the use of iron chelators to reduce iron intake can be considered a therapeutic goal. In addition, measuring Fe and ferritin is beneficial for the diagnosis of the disease and determining its severity., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Tissue engineering of native vessels is an alternative approach for patients with vascular disease who lack sufficient saphenous vein or other suitable conduits for autologous vascular graft. Moreover, the harvest of vessels prolongs the surgical procedure and it may lead to the morbidity of donor site in elder patients: therefore, it seems that the use of tissue-engineered vessels would be an attractive and less invasive substitute for autologous vascular grafts. Apelin-13 plays a pivotal role in cell proliferation, survival, and attachment; therefore, covalent attachment of apelin-13 to the acellular scaffolds might be a favorable approach for improving recellularization efficacy., Methods: In the present study, the decellularization process was performed using various detergents. Afterward, the efficacy of decellularization procedure was evaluated using multiple approaches including assessment of DNA, hydroxyproline, and GAG content as well as Masson's trichrome and orcein staining used for collagen and elastin determination. Subsequently, the scaffold was bioconjugated with apelin-13 using the EDC-NHS linker and acellular scaffolds were recellularized using fibroblasts, endothelial cells, and smooth muscle cells. SEM images and characterization methods were also used to evaluate the effect of apelin-13 attachment to the acellular scaffold on tissue recellularization. We also developed a novel strategy to eliminate the remnant detergents from the scaffold and increase cell viability by incubating acellular scaffolds with Bio-Beads SM-2 resin. Testometric tensile testing machine was also used for the assessment of mechanical properties and uniaxial tensile strength of decellularized and recellularized vessels compared to that of native tissues., Results: Our results proposed 16-h perfusion of 0.25% sodium dodecyl sulfate (SDS) + 0.5% Triton X-100 combination to the vessel as an optimal decellularization protocol in terms of cell elimination as well as extracellular matrix preservation. Furthermore, the results demonstrated considerable elevation of cell adhesion and proliferation in scaffolds bioconjugated with apelin-13. The immunohistochemical (IHC) staining of CD31, α-SMA, and vimentin markers suggested placement of seeded cells in the suitable sites and considerable elevation of cell attachment within the scaffolds bioconjugated with apelin-13 compared to the non-bioconjugated, and decellularized groups. Moreover, the quantitative analysis of IHC staining of CD31, α-SMA, and vimentin markers suggested considerable elevation in the number of endothelial, smooth muscle, and fibroblast cells in the recellularized scaffolds bioconjugated with apelin-13 group (1.4% ± 0.02, 6.66% ± 0.23, and 9.87% ± 0.13%, respectively) compared to the non-bioconjugated scaffolds (0.03% ± 0.01, 0.28% ± 0.01, and 1.2% ± 0.09%, respectively) and decellularized groups (0.03% ± 0.007, 0.05% ± 0.01, and 0.13% ±0.005%, respectively). Although the maximum strain to the rupture was reduced in tissues decellularized using 0.5% SDS and CHAPS compared to that of native ones (116% ± 6.79, 139.1% ± 3.24, and 164% ± 8.54%, respectively), ultimate stress was decreased in all decellularized and recellularized groups. Besides, our results indicated that cell viability on the 1st, 3rd, and 7th day was 100.79% ± 0.7, 100.34% ± 0.08, and 111.24% ± 1.7% for the decellularized rat aorta conjugated with apelin-13, which was incubated for 48-h with Bio-Beads SM-2, and 73.37% ± 7.99, 47.6% ± 11.69, and 27.3% ± 7.89% for decellularized rat aorta scaffolds conjugated with apelin-13 and washed 48-h by PBS, respectively. These findings reveal that the incubation of the scaffold with Bio-Beads SM-2 is a novel and promising approach for increasing cell viability and growth within the scaffold., Conclusions: In conclusion, our results provide a platform in which xenograft vessels are decellularized properly in a short time, and the recellularization process is significantly improved after the bioconjugation of the acellular scaffold with apelin-13 in terms of cell adhesion and viability within the scaffold., (© 2022. The Author(s).)

Background: This study assessed the effects of single or combined administration of temozolomide (TMZ) and interferon-gamma (IFN-ᵞ) on anxiety-like behaviors, balance disorders, learning and memory, TNF-α, IL-10, some oxidant and antioxidants factors with investigating the toll-like receptor-4 (TLR4) and p-CREB signaling pathway in C6-induced glioblastoma of rats., Methods: 40 male Sprague-Dawley rats bearing intra-caudate nucleus (CN) culture medium or C6 inoculation were randomly divided into five groups as follows: Sham, Tumor, TMZ, IFN-ᵞ and a TMZ + IFN-ᵞ combination. The open-field test (OFT), elevated plus maze (EPM), rotarod, and passive avoidance test (PAT) were done on days 14-17. On day 17 after tumor implantation, brain tissues were extracted for histopathological evaluation. TNF-α, IL-10, SOD, GPX, TAC, MDA, the protein level of TLR4 and p-CREB was measured., Results: Combination therapy inhibited the growth of the tumor. Treatment groups alleviated tumor-induced anxiety-like behaviors and improved imbalance and memory impairment. SOD, GPX, and TAC decreased in the tumor group. The combination group augmented GPX and TAC. MDA decreased in treatment groups. TMZ, IFN-ᵞ reduced tumor-increased TNF-α and IL-10 level. The combination group declined TNF-α level in serum and IL-10 level in serum and brain. Glioblastoma induced significant upregulation of TLR4 and p-CREB in the brain which inhibited by IFN-ᵞ and TMZ+ IFN-ᵞ., Conclusion: The beneficial effects of TMZ, IFN-ᵞ, and TMZ+ IFN-ᵞ on neurocognitive functioning of rats with C6-induced glioblastoma may be mediated via modulating oxidative stress, reduced cytokines, and the downregulation of expression of TLR4 and p-CREB. Combination treatment appears to be more effective than single treatment., (Copyright © 2022. Published by Elsevier Inc.)

Organophosphate (OPPs) and organochlorine pesticides (OCPs) are the two predominant forms of pesticides extensively used all around the world and are being reconsidered as environmental pollutants. The current study sought to assess the role of socioeconomic factors on the level of pesticides residues and the oxidative effects of exposure to OPPs and OCPs among the farmworkers of southeast Iran. In this cross-sectional study, 192 farmworkers and 74 non-farmworkers (controls) were involved. Gas chromatography (GC) was performed to measure the serum levels of organochlorine chemicals (2,4-DDT, 4,4-DDT, 2,4-DDE, 4,4-DDE, α-HCH, β-HCH, and γ-HCH). Furthermore, acetylcholinesterase (AChE) activity, arylesterase activity of paraoxonase-1 (PON-1), and several oxidative stress (OS) markers were assessed. In addition, the impact of several parameters such as home to farm distance, education level, ventilation status, and personal protective equipment (PPE) on pesticide levels was analyzed. The levels of OCPs in the farmworkers were significantly higher than the control subjects. In addition, AChE activity, arylesterase activity of PON-1, and total antioxidant capacity in farmworkers were significantly less, and MDA levels were higher than the controls. Education level was associated with farmworkers' protective behavior. The current findings suggested that some phased out OCPs can still be measured in human samples in the southeast of Iran. Furthermore, the current study demonstrated that exposure to OCPs and OPPs was accompanied by adverse consequences regarding OS parameters and subsequent health problems. In addition, the findings of the present study suggest that improving farmworkers' education might be associated with reduced exposure to pesticides and less adverse health effects.

D614G is one of the most reported mutations in the spike protein of SARS-COV-2 that has altered some crucial characteristics of coronaviruses, such as rate of infection and binding affinities. The binding affinity of different antiviral drugs was evaluated using rigid molecular docking. The reliability of the docking results was evaluated with the induced-fit docking method, and a better understanding of the drug-protein interactions was performed using molecular dynamics simulation. The results show that the D614G variant could change the binding affinity of antiviral drugs and spike protein remarkably. Although Cytarabine showed an appropriate interaction with the wild spike protein, Ribavirin and PMEG diphosphate exhibited a significant binding affinity to the mutated spike protein. The parameters of the ADME/T analysis showed that these drugs are suitable for further in-vitro and in-vivo investigation. D614G alteration affected the binding affinity of the RBD and its receptor on the cell surface., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Drug development for cancer treatment is a complex process that requires special efforts. Targeting crucial proteins is the most essential purpose of drug design in cancers. Bcl-xl is an anti-apoptotic protein that binds to pro-apoptotic proteins and interrupts their signals. Pro-apoptotic Bcl-xl effectors are short BH3 sequences that form an alpha helix and bind to anti-apoptotic proteins to inhibit their activity. Computational systematic evolution of ligands by exponential enrichment (SELEX) is an exclusive approach for developing peptide aptamers as potential effectors. Here, the amino acids with a high tendency for constructing an alpha-helical structure were selected. Due to the enormous number of pentapeptides, Taguchi method was used to study a selected number of peptides. The binding affinity of the peptides to Bcl-xl was assessed using molecular docking, and after analysis of the obtained results, a final set of optimized peptides was arranged and constructed. For a better comparison, three chemical compounds with approved anti-Bcl-xl activity were selected for comparison with the top-ranked 5mer peptides. The optimized peptides showed considerable binding affinity to Bcl-xl. The molecular dynamics (MD) simulation indicated that the designed peptide (PO5) could create considerable interactions with the BH3 domain of Bcl-xl. The MM/GBSA calculations revealed that these interactions were even stronger than those created by chemical compounds. In silico SELEX is a novel approach to design and evaluate peptide-aptamers. The experimental design improves the SELEX process considerably. Finally, PO5 could be considered a potential inhibitor of Bcl-xl and a potential candidate for cancer treatment., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Oxidative stress has a major role in disease pathogenesis. However, limited studies have investigated the effect of various sample collection tubes on oxidative biomarkers. The present study aimed to evaluate the effect of different collection tubes on the variation of malondialdehyde (MDA), nitric oxide (NO), total thiol (t-SH), and ferric reducing ability of plasma (FRAP) levels. A total of 35 individuals participated in this study and each collected sample was separated into three different tubes: glass tubes (GTs), plain plastic tubes (PTs), and gel separator tubes (GSTs). The results of PTs and GSTs were compared to those of GTs as the reference tube. The comparison between the means of biomarkers in various tubes indicated that there was no significant difference in MDA results between tubes. In contrast, t-SH and NO content were significantly decreased in GSTs and PTs compared to GTs. However, the Bland-Altman analysis showed an acceptable concordance for the mentioned analytes and the statistically significant differences were not clinically significant for NO, MDA, and t-SH antioxidant parameters. Moreover, the FRAP level was considerably lower in GSTs compared to GTs. Nevertheless, the Bland-Altman analysis showed a high bias percentage for the FRAP assay when using PTs and GSTs. According to the present results, it can be concluded that switching to plastic blood collection tubes or serum separation tubes could influence the FRAP results. However, there was no interference for the interpretation of other antioxidant assays in different types of collection tubes. Hence, it is suggested to use GTs for total antioxidant capacity evaluations, especially the FRAP assay., Competing Interests: Authors state no conflict of interest.

Background: Medicinal plants have revealed much attention as an alternative or complementary treatment for opioid withdrawal syndrome. The current review collects all available literature to verify the efficiency of herbal remedies in the management of symptoms associated with opioid withdrawal., Methods: A systematic literature search was conducted from January 1990 to May 2021 on four bibliographic databases (Scopus, PubMed, Embase, and Web of Science) using the search terms "medicinal plant", "withdrawal syndrome", "opioid", and all their equivalents. All randomized controlled trials (RCTs), published in the English language were included for data synthesis. The search was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA). The Cochrane risk of bias tool was used to verify the quality of the included clinical trials., Findings: A total of 12 RCTs were collected and used for data synthesis. The results of these studies indicated that herbal medicines were effective in treating opioid withdrawal syndrome and could alleviate the withdrawal symptoms, such as abdominal constrictions, diarrhea, bone pain, perspiration, and insomnia, when compared to conventional medications such as buprenorphine, clonidine, and methadone. However, more than 30% of RCTs were found to be at high risk of bias in the areas of selection, performance, detection, attrition, and reporting., Conclusion: Although several RCTs have proven that herbal remedies are effective in reducing opioid withdrawal symptoms, the findings need to be viewed more carefully. Further RCTs with more participants, longer duration, and less risk of bias are needed in the claimed cases., (© 2022 Kerman University of Medical Sciences.)

Background: Pistachio is one of the main crops in Iran. Pistachio green hull, as a by-product of this fruit, is obtained in large quantities after the processing of pistachios. This novel work was designed to examine the possible anti-cancer impact of the pistachio hull extract in the liposomal form (PHEL) on HepG2 cells., Methods and Results: The thin-film hydration approach was used for preparing liposomes and the physicochemical features of the liposomes were subsequently characterized. Afterward, apoptosis and the expression of genes related to apoptosis were assessed using flow cytometry assay and quantitative real-time polymerase chain reaction (qPCR), respectively. According to the results, the size range of PHEL was between 198 and 201 nm with a negative surface charge of - 39.2 to - 42.9 mV. As revealed by the flow cytometry results, this liposomal extract exhibits good potential for the induction of apoptosis. Moreover, the qPCR results demonstrated the up-regulation of p53 and Bax expressions and the down-regulation of Bcl-2 expression with an associated Bax/Bcl-2 ratio up-regulation., Conclusion: The flow cytometry and real-time PCR results indicated the potential of this liposomal extract as an anti-cancer drug candidate for the treatment of liver cancer in the future, and the mitochondrial pathway involving the up-regulation of the Bax/Bcl-2 ratio can mediate its impact., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

The brain is one of the most challenging organs for drug delivery. It is preserved by the blood-brain barrier (BBB), which controls the transport of components into and out of the brain. Although various approaches have been utilized to cross the BBB, the drug delivery into the brain is still less successful than the other human body parts. Comprehensive knowledge about the mechanisms and functionalities of brain delivery for different components is required to overcome this complex barrier. In this review, we have discussed the BBB structure, its characteristics, and the BBB's mechanisms for transporting components between the brain and blood. Furthermore, the barriers in front of drug delivery systems, the strategies which should be employed for overcoming these barriers, and different pathways for brain targeting are discussed. Then, the drug delivery systems utilized for crossing the BBB, especially nanocarriers and novel approaches, are considered. Finally, the bioconjugated vesicles as versatile nanocarriers that combine the bioconjugation approach and vesicles are reviewed. This review focuses on the biomolecules used in nano vesicular systems for overcoming the BBB. Various biomolecules such as amino acids, peptides, proteins, antibodies, and carbohydrates could be used for bioconjugation. Bioconjugated vesicles like liposomes and niosomes utilize the related receptor or transporter to cross the BBB. These drug delivery systems have shown enhanced drug loading into the brain, which is discussed., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Glioblastoma is the most common and destructive brain tumor with increasing complexity. Flavonoids are versatile natural compounds with the approved anticancer activity, which could be considered as a potential treatment for glioblastoma. A quantitative structure-activity relationship (QSAR) can provide adequate data for understanding the role of flavonoids structure against glioblastoma. The IC 50 of various flavonoids for the U-87 cell line was used to prepare an adequate three-dimensional QSAR (3D-QSAR) model. The validation of the model was carried out using some statistical parameters such as R 2 and Q 2 . Based on the QSAR model, the activities of other marketed and newly designed flavonoids were predicted. Molecular docking study and molecular dynamics (MD) simulation were conducted for better recognition of the interactions between the most active compounds and Bcl-2 family proteins. Moreover, an AMDE/T analysis was performed for the most active flavonoids. A reliable 3D-QSAR was performed with R 2 and Q 2 of 0.91 and 0.82. The molecular docking study revealed that BCL-XL has a higher binding affinity with the most active compounds, and the MD simulation showed that some residues of the BH3 domain, such as Phe97, Tyr101, Arg102, and Phe105 create remarkable hydrophobic interactions with the ligands. ADME/T analysis also showed the potential of the active compounds for further investigation. 3D-QSAR study is a beneficial method to evaluate and design anticancer compounds. Considering the results of the molecular docking study, MD simulation, and ADME/T analysis, the designed compound 54 could be considered as a potential treatment for glioblastoma., (© 2021 Wiley Periodicals LLC.)

Pesticides are potentially hazardous chemicals that can cause injury to human health and the environment. The purpose of this study was to evaluate organophosphate pesticides (OPPs) and organochlorine pesticides (OCPs) exposure in farmworkers' children aged 6 to 11 years in Jiroft city in southeastern Iran. One hundred twenty farmworkers' children as case and 53 non-farmworkers' children aged 6 to 11 years as control were selected and the serum levels of OCPs were measured by using gas chromatography in all participants. In addition, erythrocyte acetylcholinesterase (AChE) and arylesterase activity of paraoxonase-1 (PON-1) were measured to evaluate OPPs effects. Catalase (CAT), superoxide dismutase3 (SOD3), glutathione peroxidase (GPx3) activities, and the levels of serum malondialdehyde (MDA), total antioxidant capacity (TAC), nitric oxide (NO), and protein carbonyl (PC) were measured to investigate OCPs and OPPs effects on oxidative stress (OS). The serum levels of beta-HCH, 4,4 DDE, and 4,4 DDT in the case group were significantly higher than the control group. In addition, in the case group, AChE, PON-1, CAT, SOD3, and GPx3 activities and the levels TAC were significantly lower, while MDA, PC, and NO levels were significantly higher than the control group. OCPs as illegal pesticides are present in southeast Iran and children are exposed to OCPs and OPPs in the studied area. In addition, higher serum levels of pesticides may be a major contributor in OS development, as a cause of many diseases., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Atorvastatin (AT), a competitive inhibitor of 3-hydroxymethyl-3-glutaryl-coenzyme-A reductase, is a cholesterol-lowering drug. AT has been shown to have neuroprotective, antioxidant, and anti-inflammatory properties. Previously, we have reported that AT could attenuate the behavioral, renal, and hepatic manifestations of aging. To clarify further the mechanisms involved, the present study was designed to evaluate the effect of AT on the expression of some aging-related genes in the brain of aging mice induced by D-galactose (DG)., Materials and Methods: For this purpose, AT (0.1 and 1 mg/kg/p.o.) was administrated daily in DG-received (500 mg/kg/p.o.) mice model of aging for six weeks. At the end of the experiment, mice were decapitated to remove the brains. Then, the expression profiles of sirtuin 1 (Sirt1), P53, P21, Bcl-2, Bax, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), interleukin 1 beta (IL1β), tumor necrosis factor-alpha (TNFα), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and brain-derived neurotrophic factor (BDNF) were assessed using the real-time PCR method., Results: The present study shows that DG decreases the expression of Sirt1, Bcl-2, CAT, GPx, and BDNF while increasing the expression of P53, P21, Bax, IL-1β, iNOS, COX-2, and TNF-α. According to the findings of the present study, AT (more potentially at the dose of 1 mg/kg) modulates the expression of these aging-related genes in the brain of aging mice., Conclusion: The results of the present study confirmed our previous reports on the anti-aging effects of AT at the gene level, the precise mechanisms and underlying pathways need further studies., Competing Interests: The authors declare that there are no conflicts of interest.

Objective: Gliomas are the most prevalent type of malignant primary brain tumors. Despite the availability of several treatment modalities, these tumors have poor prognostic features. Aberrant Hedgehog (Hh) signaling has been found to be implicated in the development of numerous malignancies including gliomas. Naringenin appears to have anti-proliferative and anti-cancer properties. However, there is no report describing its effects via the Hh signaling pathway on the C6 glioblastoma cell line. The current study was set to examine the anti-cancer effects of naringenin on C6 cells in order to determine the effect of this compound on the Hh signaling pathway., Methods: The anti-proliferative and apoptotic effects of naringenin against C6 and 3T3 fibroblast cells were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and annexin-V/PI dual staining assay, respectively. The effect of naringenin on the migration of C6 cells was evaluated by the migration scratch assay. To assess the anti-cancer effect of naringenin on the Hh signaling pathway, the expression of Gli-1, Smo, and Sufu at protein levels in C6 cells was analyzed using western blotting., Results: The obtained data indicated that naringenin exerted higher cytotoxicity against C6 cells (IC50 value of 114 ± 3.4 µg/mL) than normal 3T3 fibroblasts (IC50 value of 290 ± 7 µg/mL). Naringenin (114 µg/mL) also induced stronger apoptotic effects on C6 cells than 3T3 cells after 24 h of incubation. Furthermore, naringenin at a concentration of 114 µg/mL and a lower concentration of 60 µg/mL inhibited the migration of the C6 cell line. In addition, naringenin at a concentration of 114 µg/mL significantly decreased the expression of Gli-1 and Smo and elevated the expression of Sufu at the protein level in the C6 cell line., Conclusion: These data represent that naringenin may have a potential effect on the management of the proliferation and metastasis of malignant gliomas by inhibiting the Hh signaling pathway., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Xeroderma pigmentosum group D ( XPD ) is an essential component of the nucleotide excision repair (NER) pathway, which can play a major role in DNA repair processes. A deficiency in this pathway was suggested as a causative factor of autoimmune diseases. Therefore, the current study aimed to investigate the relationship between XPD Lys751Gln polymorphism (rs13181) as one of the most common XDP polymorphisms and the risk of two important auto-immune diseases,namely systemic lupus erythematosus (SLE) and multiple sclerosis (MS) in the Iranian population., Methods: 165 SLE patients and 165 age- and gender-matched healthy controls, and 150 MS patients and 150 age- and gender-matched healthy controls were genotyped for XPD rs13181 A/C polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method., Results: The results of the present study have indicated that both C allele frequency ( P = 0.012; odds ratio: 1.5; 95% confidence interval: 1.1-2.07) and CC genotype ( P = 0.007; odds ratio: 2.46; 95% confidence interval: 1.2-4.7) in SLE patient were significantly higher than those in control group. Furthermore, there were no significant differences between MS patients and normal subjects concerning the genotype and the allele frequencies., Conclusion: Our findings suggested that XPD rs13181 A/C polymorphism may be a crucial risk factor for the development of SLE but not MS in Iranian patients., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: Despite all the efforts to treat COVID-19, no particular cure has been found for this virus. Since developing antiviral drugs is a time-consuming process, the most effective approach is to evaluate the approved and under investigation drugs using in silico methods. Among the different targets within the virus structure, as a vital component in the life cycle of coronaviruses, RNA-dependent RNA polymerase (RdRP) can be a critical target for antiviral drugs. The impact of the existence of RNA in the enzyme structure on the binding affinity of anti-RdRP drugs has not been investigated so far., Methods: In this study, the potential anti-RdRP effects of a variety of drugs from two databases (Zinc database and DrugBank) were evaluated using molecular docking. For this purpose, the newly emerged model of COVID-19 (RdRP) post-translocated catalytic complex (PDB ID: 7BZF) that consists of RNA was chosen as the target., Results: The results indicated that idarubicin (IDR), a member of the anthracycline antibiotic family, and fenoterol (FNT), a known beta-2 adrenergic agonist drug, tightly bind to the target enzyme and could be used as potential anti-RdRP inhibitors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These outcomes revealed that due to the ligand-protein interactions, the presence of RNA in this structure could remarkably affect the binding affinity of inhibitor compounds., Conclusion: In silico approaches, such as molecular docking, could effectively address the problem of finding appropriate treatment for COVID-19. Our results showed that IDR and FNT have a significant affinity to the RdRP of SARS-CoV-2; therefore, these drugs are remarkable inhibitors of coronaviruses., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Malvidin is an anthocyanin which is involved in inhibiting inflammatory-related mediators in inflammatory diseases; however, its mechanism of action in THP-1 cells is not yet known. THP-1 is a human monocytic cell line that is derived from patients with acute monocytic leukemia. The present study aimed to investigate the effect of malvidin on inflammatory responses and oxidative stress in lipopolysaccharide (LPS)-induced THP-1 cells. THP-1 cells were stimulated with LPS (50 ng/ml) to induce inflammation in the presence or absence of malvidin. The anti/proinflammatory cytokines were evaluated by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Total protein levels/phosphorylation of c-Jun N-terminal kinase (JNK), P65-NF-κB, and IKKα/IKKβ were evaluated by western blot analysis. Malondialdehyde (MDA) and nitric oxide (NO) metabolite levels, ferric reducing antioxidant power (FRAP), total thiol (T-SH) content, and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity were measured to evaluate the antioxidant activity of malvidin in THP-1 cells. Treatment of LPS-stimulated THP-1 cells with malvidin (100 and 200 μM) led to the significant inhibition of interleukin-6 (IL-6), tumor necrosis factor-α, and IL-1β messenger RNA (mRNA) expression and protein levels as well as a significant increase in the IL-10 mRNA expression and protein secretion. Moreover, 200 μM malvidin treatment reduced the phosphorylation of JNK, IKKα/IKKβ, and P65-NF-κB. These findings showed that malvidin not only decreased the MDA and NO metabolite levels but also increased the FRAP and T-SH content as well as SOD and GPx activities. The findings of the present study demonstrated the potential role of malvidin in blocking inflammation and oxidative stress induced by LPS in THP-1 cell line, suggesting that malvidin is likely to be a therapeutic agent for inflammatory diseases., (© 2020 Wiley Periodicals LLC.)

Background and Purpose: Cancer is the primary cause of death in the world. Vanadium (IV) is a metal ion complex which has been proposed as a suitable candidate for cancer treatment. In this study, the interaction of the oxido-vanadium (IV) complex [VOL(bipy)] with salmon sperm DNA and Bovine Serum Albumin (BSA) was investigated through experimental and computational approaches. With the results of this experimental study, the mechanism and parameters related to the interaction of [VOL(bipy)] with DNA and BSA were determined., Materials and Methods: The kinetic interaction of DNA and BSA with [VOL(bipy)] was determined using absorption titration and fluorescence quenching, respectively. Moreover, the possible interactions were calculated by molecular docking prediction using the available software., Results: The binding constant (Kb) of the complex-DNA interaction was calculated to be 2.34×104 M-1, indicating a relatively strong interaction between the complex and DNA. It was found that the V(IV) complex interacted with DNA through the groove binding mode followed by partial intercalation into the DNA helix. The Kb values obtained for [VOL(bipy)]-BSA interaction were in the range of 1.07×103-5.82×104 M-1. The V(IV) complex was found to prefer the domain I binding pocket of BSA with the ΔGb value of -7.52 kcal/mol., Conclusion: Both experimental and computational analyses confirmed the interaction of the vanadium complex with DNA and BSA. The moderate affinity of [VOL(bipy)] for BSA indicates that this protein is a good candidate for transferring the complex., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Virosomes as membranous vesicles with viral fusion protein in their membrane are versatile vehicles for cargo delivery. The vesicular stomatitis virus glycoprotein (VSV-G) is a common fusogenic protein used in virosome preparation. This glycoprotein has been used in liposomal systems so far, but in this study, we have tried to use the niosomal form instead of liposome for. Niosomes are vesicular systems composed of non-ionic surfactants. Niosomes were constructed by the thin-film hydration method. VSV-G gene in pMD2.G plasmid was expressed in the HEK293T cell line and then was reconstituted in the niosome bilayer. The formation of niosomal virosomes was confirmed with different methods such as SDS-PAGE gel, western blotting, and transmission electron microscopy (TEM). The efficiency of niosomal virosome was investigated with the pmCherry reporter gene. SDS-PAGE and western blotting proved the expression and successful insertion of protein into the bilayer. The TEM images showed the spike projection of VSV-G on the surface of niosomes. The transfection results showed high efficiency of niosomal virosomes as a novel carrier. This report has verified that niosome could be used as an efficient bilayer instead of liposome to construct virosomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier Inc. All rights reserved.)

On a worldwide scale, the outbreak of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to extensive damage to the health system as well as the global economy. Hitherto, there has been no approved drug or vaccine for this disease. Therefore, the use of general antiviral drugs is at the first line of treatment, though complicated with limited effectiveness and systemic side effects. Given the pathophysiology of the disease, researchers have proposed various strategies not only to find a more specific therapeutic way but also to reduce the side effects. One strategy to accomplish these goals is to use CRISPR/Cas13 system. Recently, a group of scientists has used the CRISPR/Cas13 system, which is highly effective in eliminating the genome of RNA viruses. Due to the RNA nature of the coronavirus genome, it seems that this system can be effective against the disease. The main challenge regarding the application of this system is to deliver it to the target cells efficiently. To solve this challenge, it seems that using virosomes with protein S on their membrane surface can be helpful. Studies have shown that protein S interacts with its specific receptor in target cells named Angiotensin-Converting Enzyme 2 (ACE2). Here, we propose if CRISPR/Cas13 gene constructs reach the infected cells efficiently using a virosomal delivery system, the virus genome will be cleaved and inactivated. Considering the pathophysiology of the disease, an important step to implement this hypothesis is to embed protein S on the membrane surface of virosomes to facilitate the delivery of gene constructs to the target cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: The imbalance of Th17/Treg cells has been recently suggested as a new risk factors for recurrent implantation failure (RIF). Furthermore Th17/Treg cells are involved in immune regulation in peripheral blood and endometrial tissue of patients with RIF. In this research, we investigated the effects of Hydroxychloroquine (HCQ) on the level and function of Th17 and Treg cells in women with RIF. It may be possible to improve pregnancy outcomes by modulating high cytokine levels., Methods: Women with RIF received oral HCQ ( n  = 60) on day 4 of the menstrual cycle and continued until day 20 of the menstrual cycle and 2 days before embryo transfer and continued until the day of the pregnancy test, for a total of 16 days in another cycle. The serum levels of IL-17 and IL-10, the expression of transcription factors related to Th17 and Treg cells and the immune-reactivity of IL-17, IL-21 as Th17 related cytokines and IL-10, TGF- β as Treg related cytokines in endometrial tissues were evaluated by ELISA, real-time PCR, and fluorescent immunohistochemistry respectively., Results: Treatment with HCQ down-regulated Th17 related cytokines and function and up-regulated Treg related cytokines and function significantly ( p  < .001). RORγt, the Th17 transcription factor, expression was down-regulated and FOXP-3, the T-reg transcription factor, expression was up-regulated. The biochemical pregnancy rate was not significantly different in RIF patients before and after treatment., Conclusion: Our results demonstrated that the administration of HCQ in RIF women with immune cell disorders during pregnancy could affect the Th17/Treg ratio and enhance Treg and diminish Th17 responses which may be associated with successful pregnancy outcomes. However, significant difference in pregnancy outcomes was not observed in the present study.

An efficient gene delivery system has some critical factors that enhance the efficiency of nanocarrier. These factors are low production cost, high bioavailability, high encapsulation efficiency, controllable release, and targeting ability. Niosome (the nonionic surfactant vesicles) was considered as a promising gene delivery system. Niosome can increase stability and uptake of active agents. We used all mentioned factors in one optimized formulation entitled plasmid- loaded magnetic niosomes (PMN). To increase the bioavailability of niosomes, we used ergosterol (a natural lipid) instead of cholesterol in structure of niosome. Also, cetyl trimethyl ammonium bromide (CTAB) in different concentrations was used to improve encapsulation of plasmid and compared to niosomes that did not have CTAB (negative niosome). Afterward, magnetic nanoparticle (Fe 3 O 4 @SiO 2 ) was synthesized and loaded into niosome to obtain targeting ability. Prepared formulations were evaluated regarding size, zeta potential, morphology, encapsulation of magnetic nanoparticles and plasmid (Pm-cherry-N1), release rate, and transfection efficiency. Results demonstrated that optimum formulation (Nio/CTAB3%/Fe/P) has a nanometric size (118 ± 2.31 nm, positive zeta potential (+25 ± 0.67 mV), high loading of plasmid (72%), and good gene expression (35%). Interestingly, after applying a magnetic field below the cell plate, we obtained ac increased gene expression from 35% to 42%. These results showed that this new formulation would have a promising future and also can be used for delivering the other drugs and active agents.

Ceftriaxone (CTX) is a third-generation cephalosporin antibiotic that has broad-spectrum antimicrobial activity. This agent also has anti-inflammatory and antioxidant characteristics. In the current study, the effects of CTX against hepatorenal damages in a D-galactose (DGL) induced aging model were investigated. We used twenty-eight male mice which equally and randomly were separated into four groups as follows: Control, DGL group (treated with 500 mg/kg/day DGL orally for six weeks), DGL + CTX group (treated with 500 mg/kg/day DGL orally plus 200 mg/kg/day CTX intraperitoneally for six weeks), and CTX group (treated with 200 mg/kg/day CTX intraperitoneally for six weeks). The liver and kidney function indices such as serum creatinine, blood urine nitrogen, alanine aminotransferase, and aspartate aminotransferase were measured. Also, levels of malondialdehyde, catalase, and glutathione peroxidase in hepatic and renal tissues were evaluated. Moreover, the expression profiles of interleukin 1 beta and tumor necrosis factor alpha were assessed. The liver and kidney tissues were assessed for histopathological lesions. The results showed that aging induced by DGL leads to abnormalities in functional indices of the liver and kidneys. DGL also induced significant oxidative stress and inflammation, as well as histopathological lesions, in these organs. CTX improved functional indices, as well as the parameters of oxidative stress and inflammation, compared with the DGL-treated animals. These results were also confirmed by histological evaluations of the liver and kidneys. These data provide evidence for the therapeutic value of CTX in clinical practice for mitigating the hepatorenal damages of aging., Competing Interests: Declaration of competing interest Authors declare no conflict of interests related to this work., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Coronavirus disease 2019 (COVID-19), a new type and rapidly spread viral pneumonia, is now producing an outbreak of pandemic proportions. The clinical features and laboratory results of different age groups are different due to the general susceptibility of the disease. The laboratory findings of COVID-19 in pregnant women are also conflicting. Para-clinical investigations including laboratory tests and radiologic findings play an important role in early diagnosis and treatment monitoring of COVID-19. The majority of previous reports on the COVID-19 laboratory results were based on data from the general population and limited information is available based on age difference and pregnancy status. This review aimed to describe the COVID-19 laboratory findings in neonates, children, adults, elderly and pregnant women altogether for the first time. The most attracting and reliable markers of COVID-19 in patients were: normal C-reactive protein (CRP) and very different and conflicting laboratory results regardless of clinical symptoms in neonates, normal or temporary elevated CRP, conflicting WBC count results and procalcitonin elevation in children, lymphopenia and elevated lactate dehydrogenase (LDH) in adult patients, lymphopenia and elevated CRP and LDH in the elderly people, leukocytosis and elevated neutrophil ratio in pregnant women., (Copyright © 2020 IMSS. Published by Elsevier Inc. All rights reserved.)