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Background: The objective of the present study was to assess potential immunotoxic effects of aspartame in BALB/c mice., Methods: Aspartame was administered orally at 400 and 2000 mg/kg for two weeks (five days per week). Specific parameters of humoral and cellular immune responses including hemagglutinating antibody (HA) titer, cytokine production (IFN-γ and IL-4 levels), delayed type hypersensitivity (DTH) response to SRBCs, histopathological examination of spleen and bone marrow, and T-lymphocyte proliferation in response to phytohemagglutinin-A (PHA) were evaluated., Results and Conclusion: Aspartame at 400 and 2000 mg/kg did not significantly change hematological and histopathological parameters, HA titer, IFN-γ and IL-4 levels, DTH, and lymphoproliferation responses (p > 0.05). Aspartame at 400 and 2000 mg/kg did not induce any noticeable effects in immune system parameters of mice after a 14-day feeding. Aspartame was found to be safe to BALB/c mice immune system., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing financial interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Aging is an unavoidable process in the body that is accompanied by impaired tissue homeostasis and various changes. Carvacrol has attracted considerable attention for its wide range of pharmacological activities. Therefore, this study attempted to explore the protective effect of carvacrol in aged rats. Materiel and methods: The aged rats were given carvacrol (15 or 30 mg/kg/day) for 4 weeks. Morris water maze and passive avoidance tests were used to determine the learning and memory abilities of the rats. The hippocampus and cortex samples were taken for biochemical analysis. Results: In comparison to young control rats, aged control rats showed learning and memory deficits. There was improvement in the Morris water navigation test and passive avoidance test performance in the treatment groups versus the aged control group. An increment in malondialdehyde (MDA) and a decrease in total thiol groups in the hippocampus and cortex samples of aged control rats in comparison to the young control group were observed. Carvacrol decreased MDA levels and increased total thiol groups in the hippocampus and cortex samples of aged rats. Conclusion: Carvacrol improved learning and memory in aged rats, probably through its anti-oxidation effects.

Current treatments for rheumatoid arthritis produce untoward effects; thus, considerable effort has been made to recognize effective herbal medicines against the condition. In the present study, the therapeutic effect of Diospyros kaki fruit hydroalcoholic extract (DFHE) on complete Freund's adjuvant (CFA)-induced arthritis in rats was investigated. The extract was characterized using liquid chromatography-electrospray mass spectrometry (LC-ESIMS). Male Wistar rats were grouped as follows (eight rats in each): control, CFA, CFA + indomethacin (5 mg/kg), CFA + DFHE (50 mg/kg), and CFA + DFHE (100 mg/kg). Paw volume, mechanical allodynia, thermal hyperalgesia, and arthritis score were evaluated. Serum levels of malondialdehyde (MDA), thiol groups, tumor necrosis factor-alpha (TNF-α), as well as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were evaluated. Carotenoids were found to be the major components of DFHE. Administration of DFHE (100 mg/kg) significantly decreased arthritis score, paw volume, and thermal hyperalgesia, and improved mechanical allodynia. MDA and TNF-α levels were decreased while thiol levels and SOD and GPx activities were increased in DFHE-treated groups compared to the CFA group. These results suggest that D. kaki extract caused an improvement in clinical signs of rheumatoid arthritis symptoms possibly through suppression of oxidative stress and inflammation., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Food Science & Nutrition published by Wiley Periodicals LLC.)

Background: Aging affects cellular functions and impairs tissue homeostasis. Carvacrol, a polyphenolic compound, has been shown to exert a wide range of pharmacological effects, such as antioxidant, anti-inflammatory, and anticancer characteristics., Methods: This investigation aimed to evaluate the effect of carvacrol in elderly male rats. Carvacrol at a dose of 15 or 30 mg/kg was administrated daily per os for 60 days to aged rats. The liver, heart, and kidney samples were taken for the analysis of oxidative stress markers. Serum samples were used to evaluate liver enzymes (alanine transaminase (ALT) and aspartate aminotransferase (AST))., Results: The levels of malondialdehyde (MDA) in the liver, heart, and kidney tissues of aged rats were higher. Conversely, the level of thiol was lower in the mentioned tissues than in the young control group. The levels of MDA in the liver, heart, and kidney tissues of aged rats were significantly reduced by carvacrol, which was accompanied by increased levels of total thiol. ALT and AST levels were higher in the serum of aged rats than in the young control ones. Carvacrol decreased ALT and AST levels in the serum of aged rats versus aged control rats., Conclusion: Carvacrol can be effective in protecting susceptible aged tissues and organs by increasing antioxidant defenses and decreasing liver enzymes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: A somatosensory nerve lesion or disease causes neuropathic pain. Presently, prescribed treatments are unsatisfactory or ineffective. The kernel oil of the apricot tree ( Prunus armeniaca L) is known for its anti-inflammatory and antioxidant effects. This study investigated the effect of apricot kernel oil in chronic constriction injury (CCI)- induced neuropathic pain in rats., Materials/methods: Liquid chromatography-electrospray mass spectrometry (LC-ESIMS) analysis was carried out to gain a deeper understanding of the apricot kernel oil's main compounds. Rats were treated daily with apricot kernel oil (2 and 4 ml/kg) or gabapentin (100 mg/kg) for 14 days after CCI induction. Hot plate, acetone drop, and Von Frey hair tests were performed to evaluate thermal and mechanical activity. Spinal cord malondialdehyde (MDA), total thiol, interleukin (IL)-1β, and tumor necrosis factor α (TNF-α) levels were assessed to measure biochemical changes., Results: The most detected compounds in apricot kernel oil were lipids and fatty acids. CCI produced a significant increase in thermal hyperalgesia, mechanical allodynia, and cold allodynia. Moreover, CCI increased the inflammation and oxidative stress markers in spinal cord samples. Oral administration of apricot kernel oil and gabapentin significantly decreased the CCI-induced nociceptive pain threshold. Besides, spinal cord biochemical changes were attenuated., Conclusions: Our findings suggest that apricot kernel oil could attenuate neuropathic pain, possibly through anti-inflammatory and antioxidant properties., 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., (© 2024 The Authors.)

Epidermolysis bullosa (EB) is a rare genetic dermatosis characterized by skin fragility and blister formation. With a wide phenotypic spectrum and potential extracutaneous manifestations, EB poses significant morbidity and mortality risks. Currently classified into four main subtypes based on the level of skin cleavage, EB is caused by genetic mutations affecting proteins crucial for maintaining skin integrity. The management of EB primarily focuses on preventing complications and treating symptoms through wound care, pain management, and other supportive measures. However, recent advancements in the fields of stem cell therapy, tissue engineering, and gene therapy have shown promise as potential treatments for EB. Stem cells capable of differentiating into skin cells, have demonstrated positive outcomes in preclinical and early clinical trials by promoting wound healing and reducing inflammation. Gene therapy, on the other hand, aims to correct the underlying genetic defects responsible for EB by introducing functional copies of mutated genes or modifying existing genes to restore protein function. Particularly for severe subtypes like Recessive Dystrophic Epidermolysis Bullosa (RDEB), gene therapy holds significant potential. This review aims to evaluate the role of new therapeutic approaches in the treatment of EB. The review includes findings from studies conducted on humans. While early studies and clinical trials have shown promising results, further research and trials are necessary to establish the safety and efficacy of these innovative approaches for EB treatment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Stroke is a highly prevalent and devastating condition affecting millions worldwide. The Devil's Claw (DCW) plant is a native African plant whose anti-inflammatory, antioxidant, and neuroprotective properties have been investigated. We postulated that DCW could protect the brain injury caused by cerebral ischemia., Materials and Methods: The rats were randomly divided into four groups. The sham and control (Ctrl) groups received pretreatment with a distilled water vehicle. Doses of 200 and 400 mg/kg were selected for pretreatment with DCW. The filament or intravascular occlusion method was used for middle cerebral artery occlusion (MCAO). The Triphenyl tetrazolium chloride (TTC) staining method was used to investigate the infarct zone and penumbra volume. The neuroprotective effect of DCW was measured by hematoxylin staining. Movement performance was evaluated from neurological deficit score, rotarod performance, and open field tests., Results: TTC staining showed that the DCW/400 group could maintain the penumbra's structure and reduce the infarct volume compared to the Ctrl group (p<0.001). Histological studies confirmed the neuroprotective properties of DCW at doses of 200 and 400 mg/kg compared to the Ctrl group (p<0.01 and p<0.0001, respectively). The results of behavioral tests showed an improvement in behavioral performance in pretreatment 400 mg/kg doses compare to Ctrl group (p<0.0001)., Conclusion: The study showed that pretreatment with DCW with its neuron protection potential reduces the infarct area and restores motor function after MCAO., Competing Interests: The authors have declared that there is no conflict of interest.

Aberrant cell proliferation is one of the main characteristics of tumor cells that can be affected by many cellular processes and signaling pathways. Kinesin superfamily proteins (KIFs) are motor proteins that are involved in cytoplasmic transportations and chromosomal segregation during cell proliferation. Therefore, regulation of the KIF functions as vital factors in chromosomal stability is necessary to maintain normal cellular homeostasis and proliferation. KIF deregulations have been reported in various cancers. MicroRNAs (miRNAs) and signaling pathways are important regulators of KIF proteins. MiRNAs have key roles in regulation of the cell proliferation, migration, and apoptosis. In the present review, we discussed the role of miRNAs in tumor biology through the regulation of KIF proteins. It has been shown that miRNAs have mainly a tumor suppressor function via the KIF targeting. This review can be an effective step to introduce the miRNAs/KIFs axis as a probable therapeutic target in tumor cells., 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 © 2024 Elsevier B.V. All rights reserved.)

Hypercholesterolemia is a critical risk factor for atherosclerosis, mostly attributed to lifestyle behavior such as diet. Recent advances have emphasized the critical effects of gastrointestinal bacteria in the pathology of hypercholesterolemia and atherosclerosis, suggesting that the gastrointestinal microbiome can therefore provide efficient therapeutic targets for preventing and treating atherosclerosis. Thus, interventions, such as probiotic therapy, aimed at altering the bacterial composition introduce a promising therapeutic procedure. In the current review, we will provide an overview of anti-atherogenic probiotics contributing to lipid-lowering, inhibiting atherosclerotic inflammation, and suppressing bacterial atherogenic metabolites., Competing Interests: Declaration of competing interest The authors declare there are no financial and/or non-financial competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse effect of cisplatin. The current study aimed to determine whether PEGylated nanoliposomal cisplatin can limit CIPN in an animal model., Methods: Cisplatin-loaded PEGylated liposome nanoparticles (Cis-PL) were produced as a combination of lecithin, cholesterol, and DSPE-mPEG2000 in a molar ratio of 50:45:5 and were characterized by polydispersity index (PDI), zeta potential, Field emission scanning electron microscopy (FESEM) analysis, as well as encapsulation efficiency (EE). Fifteen male rats were provided and randomly divided into 3 groups including Cis-PL group, cisplatin group, and control group. Behavioural tests (hot-plate test and acetone drop test) were used for evaluating CIPN. Moreover, oxidative stress markers and histopathological analysis were applied. Treatment-related toxicity was assessed by haematological analysis as well as liver and renal function tests., Results: Cis-PL had an average particle size of 125.4, PDI of 0.127, and zeta potential of -40.9 mV. Moreover, the Cis-PL exhibited a high EE as well as low levels of leakage rate at 25 °C. In a hot-plate test, paw withdrawal latency was longer in Cis-PL group in comparison to rats treated with cisplatin. A lower number of withdrawal responses was detected during acetone drop test in Cis-PL group than in cisplatin-treated rats. Assessment of oxidative stress markers showed that Cis-PL could improve oxidative stress. Additionally, histopathological assessment demonstrated that the number of satellite cells was significantly reduced in the dorsal root ganglion (DRG) of Cis-PL-treated rats compared with those treated with cisplatin. The cisplatin group had elevated white blood cells counts, reduced platelet counts, and higher levels of bilirubin, ALT (alanine aminotransferase, and AST (aspartate aminotransferase), and creatinine compared with the control group, which was ameliorated in Cis-PL group., Conclusions: Data from the current study support the previous hypothesis that Cisplatin-loaded PEGylated liposome could be a promising solution for CIPN in the future by modulating oxidative stress and preventing glial cell activation in DRG, suggesting further clinical studies to investigate the efficacy of this agent and its potential application in clinical practice., 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 © 2024 Elsevier B.V. All rights reserved.)

The lymphatic system, crucial for tissue fluid balance and immune surveillance, can be severely impacted by disorders that hinder its activities. Lymphatic malformations (LMs) are caused by fluid accumulation in tissues owing to defects in lymphatic channel formation, the obstruction of lymphatic vessels or injury to lymphatic tissues. Somatic mutations, varying in symptoms based on lesions' location and size, provide insights into their molecular pathogenesis by identifying LMs' genetic causes. In this review, we collected the most recent findings about the role of genetic and inflammatory biomarkers in LMs that control the formation of these malformations. A thorough evaluation of the literature from 2000 to the present was conducted using the PubMed and Google Scholar databases. Although it is obvious that the vascular endothelial growth factor receptor 3 mutation accounts for a significant proportion of LM patients, several mutations in other genes thought to be linked to LM have also been discovered. Also, inflammatory mediators like interleukin-6, interleukin-8, tumor necrosis factor-alpha and mammalian target of rapamycin are the most commonly associated biomarkers with LM. Understanding the mutations and genes expression responsible for the abnormalities in lymphatic endothelial cells could lead to novel therapeutic strategies based on molecular pathways., (© 2024 John Wiley & Sons Ltd.)

Ischemic stroke is a leading cause of disability and death in patients. Despite considerable recent advances in the treatment of ischemic stroke, only a limited number of effective neuroprotective agents are available for stroke. Green tea (Camellia sinensis) is a popular herbal plant, and numerous studies have indicated its health benefits for several diseases. Green tea is of interest due to its high content of catechin derivatives, including epicatechin, gallocatechin, epicatechin gallate, epigallocatechin, and epigallocatechin-3-gallate. This review tried to develop a feasible background for the potential effects of green tea and its bioactive derivatives concerning protection against ischemic stroke. Green tea's antioxidants, anti-inflammatory, anti-apoptotic, and neuroprotective effects are believed to be efficacious in stroke treatment. Evidence supports the idea that green tea can be used to assist in treating ischemic stroke., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Tarragon, with the scientific name of Artemisia dracunculus , is a perennial herbaceous plant with a wide spectrum of pharmacologic properties. In the current investigation, BALB/c mice were used to examine the immunomodulatory effects of hydroalcoholic extract of tarragon (HET)., Methods: Mice were treated with hydroalcoholic extract of Artimisia dracunculus (HET) at two doses (250 and 500 mg/kg) for 14 days. The host hematological parameters, spleen cellularity histopathology, hemagglutination titer assay (HA), delayed-type hypersensitivity (DTH) responses, IFN-γ and IL-4 levels produced by spelenocytes, and the proliferation of lymphocytes were assayed., Results: HET at a high dose significantly could increase the number of white blood cells and lymphocytes compared to the control group. The lymphocyte proliferation in exposure to PHA significantly increased in the HET group at both doses compared to the control group, whilst this index in the presence of LPS increased significantly for the 500 mg/kg-HET group only. Moreover, in the HA and DTH tests, HET significantly increased the proliferation of lymphocytes as compared with the control group. Furthermore, HET significantly increased the amount of IFN-γ parallel to a decrease in the level of IL-4 in compared to the control group., Conclusion: Based on our findings, HET has potent immunostimulant characteristics. More investigation into tarragon's potential to be used in the treatment of disorders caused by a weakened immune response should be conducted., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The biochemical integrity of the brain is critical in maintaining normal central nervous system (CNS) functions. One of the factors that plays an important role in causing biochemical impairment of the brain is known as oxidative stress. Oxidative stress is generally defined as the excessive formation of free radicals relative to antioxidant defenses. The brain is particularly susceptible to oxidative stress because of its high oxygen consumption and lipid-rich content. Therefore, oxidative stress damage is associated with abnormal CNS function. Psychiatric disorders are debilitating diseases. The underlying pathophysiology of psychiatric disorders is poorly defined and may involve the interplay of numerous clinical factors and mechanistic mechanisms. Considerable evidence suggests that oxidative stress plays a complex role in several neuropsychiatric disorders, including anxiety, bipolar disorder, depression, obsessivecompulsive disorder, panic disorder, and schizophrenia. To address these issues, we reviewed the literature and considered the role of oxidative stress as one of the first pathological changes in the course of neuropsychiatric disorders, which should receive more attention in future research., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ischemic stroke is one of the major causes of global mortality, which puts great demands on health systems and social welfare. Ischemic stroke is a complex pathological process involving a series of mechanisms such as ROS accumulation, Ca 2 + overload, inflammation, and apoptosis. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients has led scientists to find new treatments. The use of herbal medicine, as an alternative or complementary therapy, is increasing worldwide. For centuries, our ancestors had known the remedial nature of Nigella sativa (Family Ranunculaceae) and used it in various ways, either as medicine or as food. Nowadays, N. sativa is generally utilized as a therapeutic plant all over the world. Most of the therapeutic properties of this plant are attributed to the presence of thymoquinone which is the major biological component of the essential oil. The present review describes the pharmacotherapeutic potential of N. sativa in ischemic stroke that has been carried out by various researchers. Existing literature highlights the protective effects of N. sativa as well as thymoquinone in ischemia stroke via different mechanisms including anti-oxidative stress, anti-inflammation, anti-apoptosis, neuroprotective, and vascular protective effects. These properties make N. sativa and thymoquinone promising candidates for developing potential agents for the prevention and treatment of ischemic stroke., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Astrocytes are a multifunctional subset of glial cells that are important in maintaining the health and function of the central nervous system (CNS). Reactive astrocytes may release inflammatory mediators, chemokines, and cytokines, as well as neurotrophic factors. There may be neuroprotective (e.g., cytokines, like IL-6 and TGF-b) and neurotoxic effects (e.g., IL-1β and TNF-a) associated with these molecules. In response to CNS pathologies, astrocytes go to a state called astrogliosis which produces diverse and heterogenic functions specific to the pathology. Astrogliosis has been linked to the progression of many neurodegenerative disorders. Phytochemicals are a large group of compounds derived from natural herbs with health benefits. This review will summarize how several phytochemicals affect neurodegenerative diseases (e.g., Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, and Parkinson's disease) in basic medical and clinical studies and how they might affect astrogliosis in the process., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Neuropathic pain is a disabling condition caused by various diseases and can profoundly impact the quality of life. Unfortunately, current treatments often do not produce complete amelioration and can be associated with potential side effects. Recently, herbal drugs have garnered more attention as an alternative or a complementary treatment. In this article, we summarized the results of randomized clinical trials to evaluate the effects of various phytomedicines on neuropathic pain. In addition, we discussed their main bioactive components and potential mechanisms of action to provide a better view of the application of herbal drugs for treating neuropathic pain., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Insomnia leads to the development of mental problems and missing of accuracy in affected persons. Various investigations have previously revealed which medicinal plants play a role in the improvement of insomnia. In this study, we evaluated the effect of hydro-alcoholic extract of Datura stramonium on insomnia in mice., Methods: The extracts and fractions at different concentrations were injected intraperitoneally (i.p.) to mice 30 min before the sodium pentobarbital (30 mg/kg, i.p.). Additionally, the blood was collected from cardiac and serum separated to measure brain-derived neurotrophic factor (BDNF). The LC-MS was done to identify the active components. Flumazenil or naloxone were also applied to study the possible mechanism of extract. The PC12 cells were then exposed to different doses of extract and fractions, in order to evaluate cytotoxicity by MTT assay and the measured LD 50 ., Results: The hydro-alcoholic extracts of calyx, seed and petal elevated sleep duration and decreased sleep latency. In addition, water, ethyl acetate and n -butanol fractions of hydro-alcoholic extract of petal increased sleep duration. Of note, Naloxone significantly reversed the hypnotic effect of the extract. The extract increased the level of BDNF in serums. As well, the toxicity assessment revealed that the extracts had not toxic on PC12 cells. The LD 50 value was obtained as 4.8 g/kg., Conclusion: This research demonstrated that D. stramonium (including seed, petal and calyx) increased the hypnotic effect without neurotoxicity on PC12 cells. Sleep induction may be related to its active ingredients as well as the effect on opioid receptors.

Objective: Almost all diseases of the nervous system are related to neuroinflammation, oxidative stress, neuronal death, glia activation, and increased pro-inflammatory cytokines. Cognitive disorders are one of the common complications of nervous system diseases. The role of some plant compounds in reducing or preventing cognitive disorders has been determined. Silibinin is a plant bioflavonoid and exhibits various effects on cognitive functions. This article discusses the different mechanisms of the effect of silibinin on cognitive disorders in experimental studies., Materials and Methods: Databases, including ISI, , Google Scholar, Scopus, Medline and PubMed, were investigated from 2000 to 2021, using related keywords to find required articles ., Results: Silibinin can improve cognitive disorders by different pathways such as reducing neuroinflammation and oxidative stress, activation of reactive oxygen species- Brain-derived neurotrophic factor- Tropomyosin receptor kinase B (ROS-BDNF-TrkB) pathway in the hippocampus, an increase of dendritic spines in the brain, inhibition of hyperphosphorylation of tau protein and increasing the expression of insulin receptor (IR) and insulin-like growth factor receptor 1 (IGF-1R), inhibiting inflammatory responses and oxidative stress in the hippocampus and amygdala, and decrease of Homovanillic acid/Dopamine (HVA/DA) ratio and 3,4-Dihydroxyphenylacetic acid + Homovanillic acid/Dopamine (DOPAC+ HVA/DA) ratio in the prefrontal cortex and 5-hydroxyindoleacetic acid/5-hydroxytryptamine (5-HIAA/5-HT) ratio in the hippocampus., Conclusion: These results suggest that silibinin can be considered a therapeutic agent for the symptom reduction of cognitive disorders, and it acts by affecting various mechanisms such as inflammation, programmed cell death, and oxidative stress., Competing Interests: The authors have declared that there is no conflict of interest.

Mammalian target of rapamycin (mTOR) is a central regulator of cellular growth and homeostasis. Changes in mTOR activity are often observed in many neurological diseases, such as stroke. Intracerebral hemorrhage (ICH) is associated with high mortality and morbidity. However, there are currently no treatments that have been shown to enhance outcomes following ICH, so new treatments are urgently required. In this study, a selective mTOR inhibitor, everolimus, was applied to investigate the outcome after ICH and the possible underlying mechanism. The ICH model was established by autologous blood injection. Everolimus (50 and 100 µg/kg) was administered intraperitoneally for 14 consecutive days' post-operation. The neurological functions were examined at 3, 7, and 14 days' post-ICH. Samples of brain tissue were collected to perform histopathological and immunohistochemical (NF-k-positive cell) examinations. Besides, the striatum was used to evaluate parameters related to oxidative stress (superoxide dismutase (SOD) activity, malondialdehyde (MDA), and total thiol levels) and inflammation markers (TNF-α and NO). Everolimus ameliorated ICH-induced neurological deficits. In addition, treatment with everolimus reduced infarct volume and NF-k-β positive cells as compared to the ICH group. Furthermore, everolimus significantly increased total thiol content and SOD activity while significantly reducing MDA, NO, and TNF- levels as compared to the ICH group. Collectively, our investigation showed that everolimus improves ICH outcome and modulates oxidative stress and inflammation after ICH. Treatment with rapamycin reduced neurological deficient, oxidative stress, and inflammation in a rat model of intracerebral hemorrhage., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pain can become a chronic and deliberating experience with a significant burden. In preclinical and clinical studies, Saffron (Crocus sativus L.) has shown analgesic activities. Considering the unsatisfactory results of current therapeutic management for chronic pain conditions, we aimed to review saffron's analgesic activity and underlying mechanisms. Saffron showed antinociceptive activities in formalin-, carrageenan-, and capsaicin-induced experimental pain models. Saffron analgesic activities affected several targets, including ion channels of nociceptors; the adrenergic system and central histaminic system; inhibition of inflammatory pathways, apoptotic pathways, and oxidative stress; regulation of NO pathway, and the endocannabinoid system. Clinical studies showed analgesia of Saffron in rheumatoid arthritis, after-pain following childbirth, dysmenorrhea, and fibromyalgia. Our literature review showed that saffron can be beneficial as an adjunct therapy to commonly used analgesics in practice, particularly in chronic pain conditions., (© 2023 John Wiley & Sons, Ltd.)

The Nastaran plant, with the scientific name of Rosa canina , has been used since ancient times as a plant with medicinal properties. In the present study, human umbilical vein endothelial cells (HUVECs) were used to examine the protective effects of R. canina fruit extract (RCFE) and its flavonoid ingredient (quercetin) against H 2 O 2 -induced cell injury. RCFE (1.25-20 μg/mL) and quercetin (1.25-20 μM) were exposed to H 2 O 2 -oxidizing agent (1 and 2 mM) and the protective effect was examined on HUVEC cells by Alamar Blue test. The amount of intracellular reactive oxygen species (ROS) was measured by using DCFDA reagent by fluorimetric method. The effects of RCFE and quercetin on cell apoptosis were studied by staining with hypotonic PI solution and flow cytometry. The amount of PARP and survivin involved in the apoptotic process was measured using the western blot analysis. The results of the Alamar Blue test showed that RCFE and quercetin could reduce the toxicity of H 2 O 2 . RCFE and quercetin were able to significantly increase cell viability against H 2 O 2 . Also, it was found that RCFE and quercetin reduced the production of ROS by H 2 O 2 . It was found that RCFE and quercetin reduced the apoptosis and sub-G1 peak area in flow histogram after exposure of cells to H 2 O 2 . Based on western blot results, pretreatment with RCFE and quercetin could significantly increase survivin protein after exposure of cells to H 2 O 2 . Also, RCFE and quercetin could significantly reduce the amount of cleaved PARP after exposure of cells to H 2 O 2 . RCFE and its ingredient (quercetin) can be considered a promising source of phytochemicals in the prevention of cardiovascular diseases., Competing Interests: None., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Neuropathic pain is a chronic condition that causes long-term burning sensations. Despite significant efforts, current treatments for neuropathic pain are ineffective in curing the condition, which means new therapeutic options must be developed. One such option is the use of stem cell therapy in combination with anti-inflammatory herbal components, which has shown promise in treating neuropathic pain. The study aimed to investigate the effects of bone marrow mesenchymal stem cells (BM-MSCs) with luteolin on sensory deficits and pathological changes in a neuropathic model. The results showed that luteolin, either alone or in combination with BM-MSCs, effectively reduced sensory deficits related to mechanical and thermal hypersensitivity. In addition, luteolin alone and combined with BM-MSCs reduced oxidative stress in neuropathic rats and inhibited cellular responses, particularly reactive astrocytes. The study concluded that combining luteolin and BM-MSCs may offer an effective therapeutic strategy for patients with neuropathic pain, although further research is needed., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The significance of angiogenesis in tumour progression has been widely documented. Hence, the identification of anti-angiogenic agents with fewer common side effects would be valuable in cancer therapy. In this study, we evaluated the anti-angiogenic and anti-proliferative effects of a hydro-alcoholic extract of fenugreek seed (HAEF) on human umbilical vein endothelial cells (HUVECs). Human umbilical vein endothelial cells were treated with various concentrations of HAEF and the half-maximal inhibitory concentration (IC 50 ) value was estimated by using the MTT assay. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and matrix metalloproteinase enzyme (MMP-2 and MMP-9) gene expression profiles were evaluated by using quantitative RT-PCR (qRT-PCR). Moreover, MMP activities and PI3K, Akt and cyclin D1 protein expression levels were evaluated by gel zymography and Western blotting, respectively. HAEF reduced HUVEC viability, with an IC 50 value of 200 μg/ml. The qRT-PCR results demonstrated that treatment with HAEF markedly reduced MMP-2/MMP-9, VEGF and bFGF gene expression, as compared to the control group. We also found that MMP-2/MMP-9 enzyme activity and PI3K/Akt/cyclin D1 protein expression were notably decreased in cells treated with HAEF. Our results suggest that HAEF can potentially inhibit angiogenesis, and also affect cellular proliferation by targeting the PI3K/Akt/cyclin D1 pathway. Thus, fenugreek seed extract merits further investigation as a source of compounds with anti-cancer properties.

In metazoan cells, DNA replication initiates from thousands of genomic loci scattered throughout the genome called DNA replication origins. Origins are strongly associated with euchromatin, particularly open genomic regions such as promoters and enhancers. However, over a third of transcriptionally silent genes are associated with DNA replication initiation. Most of these genes are bound and repressed by the Polycomb repressive complex-2 (PRC2) through the repressive H3K27me3 mark. This is the strongest overlap observed for a chromatin regulator with replication origin activity. Here, we asked whether Polycomb-mediated gene repression is functionally involved in recruiting DNA replication origins to transcriptionally silent genes. We show that the absence of EZH2, the catalytic subunit of PRC2, results in increased DNA replication initiation, specifically in the vicinity of EZH2 binding sites. The increase in DNA replication initiation does not correlate with transcriptional de-repression or the acquisition of activating histone marks but does correlate with loss of H3K27me3 from bivalent promoters., Competing Interests: Declaration of interests I.A. is a partner at mireX Genomics., (Copyright © 2023. Published by Elsevier Inc.)

Background: Neuropathic pain is a subtype of chronic pain characterized by a primary lesion or dysfunction of the peripheral or central nervous system. The current pain management of neuropathic pain is inadequate and needs new medications., Aim: We studied the effects of 14 days of intraperitoneal ellagic acid (EA) and gabapentin administration in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the right sciatic nerve., Methods: Rats were divided into six groups: (1) control, (2) CCI, (3) CCI + EA (50 mg/kg), 4) CCI + EA (100 mg/kg), 5) CCI + gabapentin (100 mg/kg), and 6) CCI + EA (100 mg/kg) + gabapentin (100 mg/kg). Behavioral tests, including mechanical allodynia, cold allodynia, and thermal hyperalgesia, were conducted on days - 1(pre-operation), 7, and 14 post-CCI. In addition, at day 14 post-CCI, spinal cord segments were collected to measure the expression of inflammatory markers, including tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), and oxidative stress markers, including malondialdehyde (MDA) and thiol., Results: CCI increased mechanical allodynia, cold allodynia, and thermal hyperalgesia in rats which were reduced by treatment with EA (50 or 100 mg/kg), gabapentin, or their combination. CCI increased TNF-α, NO, and MDA levels and decreased thiol content in the spinal cord, which all were reverted by administration of EA (50 or 100 mg/kg), gabapentin, or their combination., Conclusion: This is the first report on ellagic acid's ameliorative effect in rats' CCI-induced neuropathic pain. This effect can be attributed to its anti-oxidative and anti-inflammatory, thus making it potentially useful as an adjuvant to conventional treatment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The ongoing coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a large global outbreak. The reports of domestic animals' infection with SARS-CoV-2 raise concerns about the virus's longer-lasting spread, the establishment of a new host reservoir, or even the evolution of a new virus, as seen with COVID-19. In this review, we focus on the susceptibility of domestic animals, especially companion animals, towards SARS-CoV-2 in light of existing studies of natural infection, experimental infection, and serological surveys. Susceptibility of domestic and companion animals to SARS-CoV-2 infection., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Information on the pattern of acute poisonings in hospitals of Birjand city, Iran, is limited. This study aimed to address this knowledge gap by examining the admissions in a major poisoning center in eastern Iran. This cross-sectional study included patients admitted to the Imam Reza Hospital in Birjand over 12 months. Medical records of the poisoned patients were reviewed, and the study variables were used for data analysis. During the study period, 534 cases of acute poisonings were evaluated. The patient's ages ranged from 12 to 84 years, with a high rate of poisonings between 15 and 35 years. The female predominance in poisoning cases was 52.1%. Most cases of poisonings occurred in spring, and the common route of exposure was oral (93.1%). The incidence of poisoning in married couples, uneducated patients, and residents of urban areas was 56.5%, 90.1%, and 74.6%, respectively. Patients with a previous medical history experienced addiction and psychiatric disorders. Intentional poisoning accounted for 23.4% of acute poisoning cases referred to the hospital in the current study. The main groups of toxicants were pharmaceutical products (48.1%), narcotics (25.8%), chemical products (10.1%), envenomation (7.1%), and alcohol (1.7%). The mean hospital stay was 2.5 ± 3.0 days, and the final treatment outcome was complete recovery, except for one patient intoxicated by warfarin and alprazolam. Our results indicate that the high toxicity cases were related to pharmaceutical product and opioids abuse, especially methadone (8.4%), alprazolam (7.9%), clonazepam (7.5%), and acetaminophen (9.9%) taken orally and more commonly happened at home. Due to the high rate of deliberate poisonings, especially among young adults and students, monitoring drug distribution and exceptional attention to mental health should be seriously considered by national health authorities to prevent suicide attempts., (© 2023. The Author(s).)

Sleep plays an important function in neuro-immuno-endocrine homeostasis. Sleep disorders have been associated with an increased risk of metabolic and cognitive impairments. Among different factors that have an effect on sleep metabolism, a growing body of literature has investigated growth factors in the course of sleep quality and disorders. A good example of growth factors is fibroblast growth factors (FGFs), which are a large family of polypeptide growth factors. Evidence has shown that FGFs are involved in the modulation of sleep-wake behavior by their receptor subtypes and ligands, e.g., FFG1 plays an important role in the quality of sleep through somnogenic effects, while the high level of FGF23 is associated with secondary disorders in shift workers. Therefore, a controversial effect of FGFs can be seen in the course of sleep in physiologic and pathologic conditions. Further investigation on this topic would help us to understand the role of FGFs in sleep disorders as a therapeutic option and biomarker., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Neuropathic pain originating from a dysfunction in the nervous system is often intractable and chronic. Recently, several studies using nanoparticles suggested a new way to control neuropathic pain. This study intended to explore the potential neuroprotective effect of Cerium Oxide Nanoparticles (CNPs) synthesized by pullulan in neuropathic pain in rats., Methods: On the right common sciatic nerve of male Wistar rats, the chronic constriction injury (CCI) procedure was used to establish a neuropathic pain model. CNPs were injected into the caudal vein of the rat. Behavioral methods were used to detect mechanical allodynia, cold allodynia, and thermal hyperalgesia in rats. Besides, inflammation factors, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, nitric oxide (NO), and markers of oxidative stress, including Malondialdehyde (MDA) and total thiol, were measured in the spinal cord segment of rats., Results: In rats with CCI, mechanical allodynia, cold allodynia, and thermal hyperalgesia developed, which improved when the rats were administered CNPs. Spinal cord specimens of CCI rats had elevated inflammation and oxidative stress status (↑IL-1β, ↑TNF-α, ↑NO, ↑MDA) and decreased antioxidative levels (↓total thiol). As a result of CNPs treatment, these changes were reversed in the spinal cord specimens., Conclusion: CNPs alleviate neuropathic pain by exhibiting antioxidative and anti-inflammatory activities., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The pathological accumulation of quinolinic acid (QA) is often associated with neuritis and neuronal cell death in several neurodegenerative diseases, through the overproduction of free radicals. Urolithin B and auraptene have been reported to exert potent antioxidant effects - however, little is known about the protective effects of these compounds against QA-induced neurotoxicity. Therefore, this study aimed to explore the in vitro protective effects of urolithin B and auraptene against QA-induced neurotoxicity in the SH-SY5Y neuroblastoma cell line. The MTT assay was used to evaluate cell viability, and flow cytometry was carried out to evaluate effects on the cell cycle and apoptosis. The intracellular levels of reactive oxygen species (ROS) were also determined. Our findings showed that auraptene at non-toxic concentrations had no protective effect on QA-induced toxicity. However, urolithin B at concentrations of 0.6 μM and 2.5 μM enhanced the viability of cells treated with QA. Moreover, while the percentage of apoptotic cells (i.e. in the sub-G1 phase) was shown to significantly increase after QA treatment, pre-treatment with urolithin B reduced the number of these apoptotic cells. Furthermore, urolithin B, as an antioxidant, also significantly reduced QA-induced ROS production. Our findings suggest that urolithin B may possess potent antioxidant and neuroprotective effects against QA-induced neurotoxicity that merit further investigation.

Background: Alzheimer's disease (AD) is a major neurodegenerative disorder with multiple manifestations, including oxidative stress, brain-derived neurotrophic factor (BDNF) depletion, and cholinergic dysfunction. Capparis spinosa (C. spinosa) is identified as a potential source of nutrition for alleviating various ailments. The current study assessed the ameliorating properties of C. spinosa hydroethanolic extract on memory dysfunction and the possible roles of oxidative stress and BDNF in the scopolamine (Scop)-treated rats., Methods: Forty male Wistar rats were divided into the following four groups: Control, Scop (2 mg/kg, intraperitoneal injection (i.p.)), Scop + C. spinosa 150, and Scop + C. spinosa 300 groups. The rats were given C. spinosa extract (150 or 300 mg/kg, oral) for 3 weeks. During the third week, Passive Avoidance (PA) and Morris Water Maze (MWM) tests were done to assess memory and learning performance. Finally, oxidative stress markers and BDNF in the brain tissue were evaluated., Results: Scop injection was associated with a significant increase in the time latency and travelled distance to reach the platform during the learning phase of MWM In the probe test, the Scoptreated rats showed a lower time and distance in the target area. Furthermore, Scop injection significantly decreased the latency to enter the dark while increasing the dark time and the frequency of entries to the dark zone of the PA task. C. spinosa extract effectively reversed the behavioural changes induced by Scop. Treatment with the extract also significantly increased the levels of superoxide dismutase, catalase, thiols, and BDNF, while decreasing malondialdehyde production in the brains of the Scop-injured rats., Conclusion: C. spinosa hydroethanolic extract successfully ameliorated Scop-induced memory impairment by modifying BDNF and oxidative stress markers in the brain of amnesic rats., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The purpose of the present study was to study the potential anti-arthritic and antioxidant effects of trehalose in an experimental model of complete Freund's adjuvant (CFA)-induced arthritis., Methods: Arthritis was induced via subcutaneous injection of CFA (0.1) into the right footpad of each rat. Trehalose (10 mg/kg per day) and indomethacin (5 mg/kg) as a reference drug were intraperitoneally injected into CFA-induced arthritic rats from days 0 to 21. Changes in paw volume, pain responses, arthritic score, and oxidative/antioxidative parameters were determined., Results: Trehalose administration could significantly decrease arthritis scores (p <0.01) and paw edema (p <0.001), and significantly increase the nociceptive threshold (p <0.05) in CFA-induced arthritic rats. Trehalose also significantly reduced the pro-oxidant-antioxidant balance values when compared to CFA treatment alone. In addition, no significant difference was found between the trehalose group and indomethacin as a positive control group., Conclusion: The current study suggests that trehalose has a protective effect against arthritis, which may be mediated by antioxidative effects of this disaccharide., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A great number of research has been focused on plants as a source of medicine against many diseases to overcome the many side effects of chemical drugs. Safranal, one of the main constituents of saffron [Crocus sativus], has a broad spectrum of pharmacological effects, including anti-inflammatory, antioxidant, and antiapoptotic effects. The present review elaborates on the current understanding of the neuroprotective effects of safranal. According to data published so far, safranal has the potential to exert neuroprotective effects in neurological disorders such as epilepsy, stroke, multiple sclerosis, Parkinson, and Alzheimer's disease. Safranal could be considered a promising therapeutic agent in the future, although there is a great need for clinical trial studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Increased quinolinic acid (QA) accumulation has been found in many neurodegenerative diseases. Artemisia absinthium (A. absinthium) has been reported to have neuroprotective and antioxidant activities. This study was designed to evaluate the effect of A. absinthium in QAinduced neurotoxicity in OLN-93 Cells., Methods: OLN-93 cells were cultured in a DMEM medium containing 10% (v/v) fetal bovine serum, 100 units/ml penicillin, and 100 μg/ml streptomycin. The cells were pretreated with concentrations of A. absinthium extract for two h and then exposed to QA for 24 h. After 24 h cell viability, the level of malondialdehyde (MDA), reactive oxygen species (ROS), and apoptotic cells were quantitated in OLN-93 Cells., Results: Pretreatment with A. absinthium extract prevented the loss of cell viability in OLN-93 cells. ROS generation, lipid peroxidation, and apoptosis in QA-injured OLN-93 cells were reduced following A. absinthium extract pretreatment., Conclusion: A. absinthium extract exerts its neuroprotective effect against QA-induced neurotoxicity via oxidative stress and apoptosis modulation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Neuropathic pain, a chronic pain condition, puts a considerable burden on its patients. However, different pathophysiological characteristics of neuropathic pain make the current treatment medications insufficient in controlling pain. Identifying treatment effects with Capparis Spinosa hydro-alcoholic extract in an animal model of neuropathic pain. Liquid chromatography-mass spectrometry (LC-MS) was used to identify the components of C. Spinosa hydro-alcoholic extract. To establish a neuropathic pain model, adult male Wistar rats underwent chronic constriction injury (CCI) surgery in their left sciatic nerve. Male wistar rats were divided into four groups: CCI, Sham, CCI with C. Spinosa (100 mg/kg), and CCI with C. Spinosa (200 mg/kg). Rats were treated with a hydro-alcoholic extract from aerial parts of the C. Spinosa (orally, daily) starting from CCI induction until 14 days after. Behavioral tests (mechanical allodynia, cold allodynia, and thermal hyperalgesia) and biochemical tests (IL-1β, TNF-α, MDA, and total thiol) were taken from animals. The LC-MS analysis identified 22 compounds in C. Spinosa extract with the predominance of flavonoids. CCI produced a significant (P < 0.001) increase allodynia (mechanical and cold) and thermal hyperalgesia in comparison with sham group. Oral administration of C. Spinosa significantly (P < 0.05) ameliorated CCI-induced nociceptive pain compared with CCI group. Spinal cord specimens of CCI rats had significant (P < 0.05) elevated inflammation status (↑IL-1β, ↑TNF-α), and significant (P < 0.05) decreased antioxidative status (↑MDA, ↓total thiol) in comparison with the sham group. These changes were reversed following C. Spinosa treatment. C. Spinosa alleviates neuropathic pain by exhibiting antioxidative and anti-inflammatory effects. The responsible components for these effects are possibly the flavonoid compounds in C. Spinosa extract., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: COVID-19, an epidemic of coronavirus infection, has become a major global threat. The coronavirus mainly targets the human respiratory system, followed by cytokine storm, and altered immune responses associated with disease progression and adverse outcomes. Sumac and pomegranate juice are rich in bioactive compounds, which potentially have antiviral activities. This study is aimed at investigating the effect of a diet based on the use of sumac and pomegranate juice on the treatment of outpatients with COVID-19., Methods: In this study, 182 outpatients with COVID-19 were randomly divided into two groups receiving a diet containing pomegranate juice and sumac along with standard treatment and the control group (group 2) receiving standard treatment., Results: Consumption of a diet containing pomegranate juice and sumac in outpatients with COVID-19, who were receiving standard-of-care treatment, led to a significant decrease in fever, chills, cough, weakness, smell and taste disorders, shortness of breath, diarrhea, nausea and vomiting, and abdominal pain compared with outpatients with COVID-19 who received only standard treatment., Conclusion: Clinical trials of outpatients have limitations such as patients' resilience to post-COVID-19 follow-up. However, the use of pomegranate juice and sumac can be efficacious in reducing COVID-19 symptoms. This trial is registered with IRCT20190406043175N3., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Fatemeh Forouzanfar et al.)

Background: Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates cell growth and metabolism and integrates various signals under physiological and pathological conditions. Altered signaling of mTOR has been shown to play pathogenic roles in ischemic stroke. In the present study, the protective effect of everolimus, the selective mTOR inhibitor, in the middle cerebral artery occlusion (MCAO) model of ischemic stroke was evaluated., Methods: Wistar rats were exposed to MCAO (30 min) followed by reperfusion for 24 h. Everolimus (100, and 500 µg/kg) was administered at the time of reperfusion, intraperitoneally. 24 h post operation, the neurological function, infarct volume, histopathological alterations and the markers of oxidative stress including superoxide dismutase (SOD) activity, malondialdehyde (MDA), and total thiol levels were analyzed in the peri-infarct region., Results: In the rats subjected to MCAO, everolimus ameliorated neurological deficits, neuronal cell loss, and infarct volume, as compared to the stroke group. Also, everolimus significantly increased SOD activity and total thiol content, while markedly decreased the MDA level, as compared to MCAO group., Conclusion: Single-dose administration of everolimus significantly improved neurological deficits and inhibited cortical cell loss by enhancing redox status, subsequently protected cerebral ischemia-reperfusion injury in rats., Competing Interests: Declaration of Competing Interest None, (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: The clinical use of tacrolimus is limited due to its side effects. This research investigated the protective activities of pomegranate seed oil (PSO) against TAC toxicity., Materials and Methods: The groups are included normal (1 ml of corn oil), TAC (2 mg/kg), and co-treatment of PSO (0.4 and 0.8 ml/kg) and TAC. All administrations were carried out intraperitoneally for 14 days. After the last injection, blood was collected from the heart., Results: TAC increased creatinine and urea. Increased malondialdehyde, reduced thiol content and superoxide dismutase. The elevation of lactate dehydrogenase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine kinase-MB and creatinine phosphokinase that confirmed cardiac toxicity. PSO reduced TAC toxicity. PSO decreased TAC-induced pathology injury., Conclusion: PSO reduced TAC toxicity in renal and heart via scavenging free radicals., Competing Interests: The authors have declared that there is no conflict of interest.

Pharmacological studies revealed that cedrol, a natural sesquiterpene, has antioxidant, anti-inflammatory, and analgesic properties. This study is aimed at evaluating the potential antiarthritic activity of cedrol in a rat experimental model of arthritis induced by using complete Freund's adjuvant (CFA). Arthritis was induced in Wistar rats by CFA (0.1 ml) injection. Cedrol (10 and 20 mg/kg) and indomethacin (5 mg/kg) were orally administered from day one and continued for 21 days. The antiarthritic activity was assessed through mechanical allodynia and thermal hyperalgesia responses, paw edema assessment, and arthritis scores. Serum TNF- α and IL-1 β levels were measured for the evaluation of inflammation. Furthermore, serum oxidative stress markers, including malondialdehyde (MDA) and thiol levels, as well as superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, were also assessed. Oral administration of cedrol and indomethacin significantly decreased paw edema and arthritis score. Besides, cedrol and indomethacin significantly decreased pain responses. In the serum of the CFA group, TNF- α , IL-1 β , and MDA were higher, while thiol and SOD and GPx were lower than the control group. Treatment by cedrol and indomethacin corrected the biochemical parameters in the serum. In this study, cedrol offers potential antiarthritic properties through its anti-inflammatory and antioxidant effects., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Fatemeh Forouzanfar et al.)

Background: Garcinia mangostana, commonly also called mangosteen, is an evergreen tropical tree, and its pericarps have been used in traditional herbal medicine for different diseases. The anticancer efficacy of the ethanolic extract from the pericarps of Garcinia mangostana was investigated in human prostate cancer cells (PC3), melanoma cells (B16F10), breast cancer cells (MCF7), and glioblastoma (U87) cell lines., Methods: 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay was used to measure cell viability. Propidium iodide (PI) staining and analysis on a flow cytometer were used to identify apoptosis. Action on cell migration was evaluated by scratch assay and gelatin zymography. Furthermore, the level of intracellular reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) activity was measured. Moreover, we investigated the synergistic efficacy with several combinations of Garcinia mangostana extract (GME) with doxorubicin., Results: GME reduced cell viability in malignant cell dose time-dependently. GME-induced sub- G1 peak in flow cytometry histogram of treated cells control representing apoptotic cell death is involved in GME toxicity. Furthermore, GME exhibited inhibitory effects on the migration ability of U87 cells, which was accompanied by inhibition in the activity and expression of MMP2 (matrix metalloproteinase-2). Besides, GSH level and SOD activity were significantly reduced while there was an increase in ROS and MDA concentration following 24 hr of GME treatment. Moreover, a combination of GME (1.5-25 μg/mL) with Dox (6 μg/mL) displayed synergistic efficacy and cell growth inhibition., Conclusion: In conclusion, GME could cause cell death in PC3, MCF7, U87, and B16F10 cell lines, in which apoptosis plays an imperative role. Plant extract decreased the migration ability of the cells by inhibiting the activity and expression of Matrix metalloproteinases (MMPs). G. mangostana could be a promising therapeutic strategy to treat cancer in the future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Heat Shock Proteins (HSPs) are important molecular chaperones that facilitate many functions of the cells. They also play a pivotal role in cell survival, especially in the presence of stressors, including nutritional deprivation, lack of oxygen, fever, alcohol, inflammation, oxidative stress, heavy metals, as well as conditions that cause injury and necrosis. In the face of a painful stimulus encounter, many factors could be associated with pain that may include nitric oxide, excitatory amino acids, reactive oxygen species (ROS) formation, prostaglandins, and inflammatory cytokines. One influential factor affecting pain reduction is the expression of HSPs that act as a ROS scavenger, regulate the inflammatory cytokines, and reduce pain responses subsequently. Hence, we assembled information on the painkilling attributes of HSPs. In this field of research, new painkillers could be developed by targetting HSPs to alleviate pain and widen our grasp of pain in pathological conditions and neurological diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Oral infections and dental caries are considered serious health problems. Therefore, searching for new agents with antimicrobial properties seems to be crucial. This study aimed to evaluate the antimicrobial activity of the recombinant Thrombocidin-1 [TC-1] peptide on some oral pathogens. Also, the cytotoxicity of this peptide on human gingival fibroblast cells was investigated., Methods: In this study, Pichia pastoris was used for the expression of recombinant TC-1. The microbroth dilution method was used to determine the minimum inhibitory concentration [MIC] and minimum bacterial concentration [MBC]. It tested against four main oral pathogens; Streptococcus mutans, Streptococcus salivarius, Streptococcus oralis, and Enterococcus faecalis. Moreover, the cytotoxicity analysis was done on gingival fibroblast cells by the MTT method. The data were analyzed using a two-way analysis of variance [ANOVA] and Tukey's HSD tests., Results: The most bactericidal effect of TC-1 was against S. salivarius, the highest bacteriostatic effect was against S. salivarius, and S. oralis had the lowest MIC value of 1.512 μg/ml. The Thrombocidin- 1 peptide showed lower antibacterial properties against E. faecalis compared with CHX, unlike the stronger antimicrobial effect on examined streptococci. According to cytotoxicity examination, no concentration of TC-1 presented over 50% growth inhibition [IC50] of the fibroblasts cells., Conclusion: Based on antimicrobial tests and cytotoxicity results, the Thrombocidin-1 peptide may be useful as a safe antibacterial agent against some oral pathogens in dental materials., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Degeneration and apoptotic death of the photoreceptor cell-layer of retina are a major cause of irreversible blindness in the development era. The stem cell replacement therapy is one of the strategies for the retinal repairing. In addition, exogenous signals critically contribute to the direction of lineage decisions that causes the fate-restricted photoreceptor progenitors from stem cell progeny in culture. It has been found that epidermal growth factor (EGF), taurine, and retinoic acid (RA) initially act in the instructive as well as lineage-restricted way in the progenitor lineage for producing neuroretinal cells or photoreceptor like cells from stem cell. The study aims to investigate the effect of RA and taurine in differentiation of the human bone marrow stem cell into cone photoreceptors cells and retinal ganglion cells. Mesenchymal stem cell was derived from human bone marrow of the term delivery. Therefore, the cultured cells have been treated with Dulbecco's modified Eagle's medium (DMEM)/high glucose (H + ). After the four-cell passage, basal medium was replaced with DMEM/F12 complemented with 50 μmol/L taurine, RA (1 µM) and EGF (1 µg/ml). Subsequently cellular change morphology was detected following 7 and 14 days. Then, gene expression of neuroretinal and photoreceptor cell biomarkers (CRX, OTX2, PKC-α, recoverin, and Rho) were examined by quantitative polymerase chain reaction (Q-PCR). Also, cells were cultured, fixed, and then immunocytochemical analyzed. Primary antibodies included CRX and Rho. Cellular morphology demonstrated spindle elongated morphology. Taurine alone and combination of RA upregulate neuroretinal and photoreceptor cell biomarkers in messenger RNA and protein levels but along with EGF have not significant effect. Our data showed that taurine combination with RA can differentiate bone marrow mesenchymal stem cells into neuroretinal or photoreceptor like cells in vitro that can offer an attractive treatment ground for transplantation in the cell-replacement therapy for some forms of the retinal degeneration., (© 2021 Wiley Periodicals LLC.)

Ischemic stroke is a devastating central nervous disease. Despite extensive research in to this area, few innovative neuroprotective treatments have been presented. 7-methoxycoumarin, also known as herniarin, is a common natural coumarin in several plant species. This project examined the effects of the herniarin in rats subjected to the middle cerebral artery occlusion (MCAO). Herniarin at doses of 10 and 20 mg/kg was administered through intraperitoneal injection for 7 days before MCAO induction. Rats were subjected to a 30 min MCAO and a subsequent 24 h' reperfusion. 24 h after the termination of MCAO, neurologic outcome, volume of brain infarction, level of interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α), as inflammatory markers, and oxidative stress markers including levels of total thiol, malondialdehyde (MDA), and superoxide dismutase (SOD) activity were estimated. Herniarin administration decreased the MCAO-induced infarct volume and neurological deficits. Moreover, pretreatment with herniarin significantly decreased the levels of MDA while simultaneously increasing the level of total thiol and SOD activity in the brain tissues of MCAO rats. Moreover, herniarin pretreatment decreased the levels of IL-1β and TNF-α in the brain tissues of MCAO rats. These results suggest that herniarin presents beneficial effects against ischemic stroke, partly through the inhibition of oxidative stress and inflammation., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The weight of evidence suggests that sleep is essential for the processes of memory consolidation and sleep deprivation (SD) impairs the retention of long-term memory in both humans and experimental animals, which is associated with oxidative stress damage within the brain. Green tea polyphenols have revealed carcinogenic, antioxidant, anti-, and anti-mutagenic properties. We aimed to investigate the possible protective effect of green tea extract (GTE) and its main active catechin, epigallocatechin-3-gallate (EGCG), on post-training total sleep deprivation (TSD) -induced spatial memory deficits and oxidative stress profile in the hippocampus of the rat., Methods: Male rats were treated with saline, GTE (100 and 200 mg/kg/day), and EGCG (50 mg/kg/day) intraperitoneally for 21 days and then trained in Morris water maze (MWM) in a single day protocol. Immediately after the end of MWM training, animals were sleep deprived for 6 h by the gentle handling method, and then evaluated for spatial memory. Hippocampal levels of malondialdehyde, (MDA), and thiol was assessed as oxidant and antioxidant markers., Results: Spatial memory was impaired in the TSD group and GTE at the dose of 200 mg/kg/day as well as EGCG at the dose of 50 mg/kg/day could reverse the impairment to the saline-treated levels. Despite the unchanged MDA levels, hippocampal total thiol was significantly decreased after TSD and EGCG increased it to the basal levels., Conclusion: In conclusion, green tea and its main catechin, EGCG, could prevent memory impairments during 6 h of TSD; probably through normalizing the antioxidant thiol defense system which was impaired during TSD., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

COVID-19 is the cause of a pandemic associated with substantial morbidity and mortality. As yet, there is no available approved drug to eradicate the virus. In this review article, we present an alternative study area that may contribute to the development of therapeutic targets for COVID-19. Growing evidence is revealing further pathophysiological mechanisms of COVID-19 related to the disregulation of inflammation pathways that seem to play a critical role toward COVID-19 complications. The NF-kB and JAK/STAT signaling pathways are highly activated in acute inflammation, and the excessive activity of these pathways in COVID-19 patients likely exacerbates the inflammatory responses of the host. A group of non-coding RNAs (miRNAs) manage certain features of the inflammatory process. In this study, we discuss recent advances in our understanding of miRNAs and their connection to inflammatory responses. Additionally, we consider the link between perturbations in miRNA levels and the onset of COVID-19 disease. Furthermore, previous studies published in the online databases, namely web of science, MEDLINE (PubMed), and Scopus, were reviewed for the potential role of miRNAs in the inflammatory manifestations of COVID-19. Moreover, we disclosed the interactions of inflammatory genes using STRING DB and designed interactions between miRNAs and target genes using Cityscape software. Several miRNAs, particularly miR-9, miR-98, miR-223, and miR-214, play crucial roles in the regulation of NF-kB and JAK-STAT signaling pathways as inflammatory regulators. Therefore, this group of miRNAs that mitigate inflammatory pathways can be further regarded as potential targets for far-reaching-therapeutic strategies in COVID-19 diseases., (Copyright © 2021. Published by Elsevier B.V.)