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Neurodegeneration is a pathological process characterized by progressive neuronal impairment, dysfunction, and loss due to mitochondrial dysfunction, oxidative stress, inflammation, and apoptosis. Many studies have shown that lithium protects against neurodegeneration. Herein, we summarize recent clinical and laboratory studies on the neuroprotective effects of lithium against neurodegeneration and its potential to modulate mitochondrial dysfunction, oxidative stress, inflammation, and apoptosis. Recent findings indicate that lithium regulates critical intracellular pathways such as phosphatidylinositol-3 (PI3)/protein kinase B (Akt)/glycogen synthase kinase-3 (GSK3β) and PI3/Akt/response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF). We queried PubMed, Web of Science, Scopus, Elsevier, and other related databases using search terms related to lithium and its neuroprotective effect in various neurodegenerative diseases and events from January 2000 to May 2022. We reviewed the major findings and mechanisms proposed for the effects of lithium. Lithium's neuroprotective potential against neural cell degeneration is mediated by inducing anti-inflammatory factors, antioxidant enzymes, and free radical scavengers to prevent mitochondrial dysfunction. Lithium effects are regulated by two essential pathways: PI3/Akt/GSK3β and PI3/Akt/CREB/BDNF. Lithium acts as a neuroprotective agent against neurodegeneration by preventing inflammation, oxidative stress, apoptosis, and mitochondrial dysfunction using PI3/Akt/GSK3β and PI3/Akt/CREB/BDNF signaling pathways.

Severe Acute Respiratory Syndrome Coronavirus-2 (COVID-19) is a respiratory disease that causes dysfunction in respiration. Since late 2019, this virus has infected and killed millions of people around the world and imposed many medical and therapeutic problems in the form of a pandemic. According to recent data, COVID-19 disease can increase the risk of stroke, which can be deadly or cause many neurological disorders after the disease. During the last two years, many efforts have been made to introduce new therapies for management of COVID-19-related complications, including stroke. To achieve this goal, several conventional drugs have been investigated for their possible therapeutic roles. Minocycline, a broad-spectrum, long-acting antibiotic with anti-inflammatory and antioxidant properties, is one such conventional drug that should be considered for treating COVID-19-related stroke, as indirect evidence indicates that it exerts neuroprotective effects, can modulate stroke occurrence, and can play an effective and strategic role in management of the molecular signals caused by stroke and its destructive consequences. The matrix metalloprotease (MMP) signaling pathway is one of the main signaling pathways involved in the occurrence and exacerbation of stroke; however, its role in COVID-19-induced stroke and the possible role of minocycline in the management of this signaling pathway in patients with COVID-19 is unclear and requires further investigation. Based on this concept, we hypothesize that minocycline might act via MMP signaling as a neuroprotective agent against COVID-19-induced neurological dysfunction, particularly stroke.

Background Tramadol (TRA) is a pain killer, which its abuse is widely increased during recent years, but clear mechanism for induction of neurotoxicity remains unclear. The present study aims to investigate involvement of apoptosis and autophagy signaling pathways and also mitochondrial system on TRA induced neurotoxicity. Materials and Methods Sixthy adult male rats were randomly divided into five groups that received standard saline and TRA in doses of 25, 50, 75, 100 and 150 mg/kg as intraperitoneal administration for 21 days, respectively. In 22th day, Open Field Test (OFT), as standard test for hippocampal cell damages was used. Also hippocampal level of JNK, Bcl-2, Beclin1 and Bax proteins as well as mitochondrial quadruple complex enzymes was measured Results TRA at doses 75,100 and 150 mg/kg causes dysfunction in OFT behavioral and also in mentioned high doses could increases level of both activated (total) and non-activated from of JNK and also increased Beclin-1 and Bax. TRA at doses of 75,100 and 150 mg/kg increased phosphorylated form of Bcl-2 level while decreased un-phosphorylated (total form) form of Bcl-2. Conclusion According to obtained data, TRA causes activation of apoptosis and or autophagy processes via modulation of TNF-α or IL-1β/JNK/Bcl-2/Beclin1 and Bcl-2/Bax signaling pathway and causes dysfunction of mitochondrial respiratory chain enzymes.

High risk of acute morbidities and even mortality from expanding the antibiotics resistant infectious wounds force indefinite efforts for development of high performance wound-healing materials. Herein, we design a procedure to fabricate a hyaluronic acid (HA)-based hydrogel to conjugate curcumin (Gel-H.P.Cur). The highlight of this work is to provide a favorite condition for capturing curcumin with protecting its structure and intensify its activities because of the synchronization with HA. Accordingly, HA as a major component of dermis with critical role in establishing skin health, could fortify the wound healing property as well as antibacterial activity of the hydrogel. Gel-H.P.Cur showed antibacterial properties against Pseudomonas aeruginosa (P. aeruginosa), which were examined by bactericidal efficiency, disk diffusion, anti-biofilm, and pyocyanin production assays. The effects of Gel-H.P.Cur on the inhibition of quorum sensing (QS) regulatory genes that contribute to expanding bacteria in the injured place was also significant. In addition, Gel-H.P.Cur showed high potential to heal the cutaneous wounds on the mouse excisional wound model with repairing histopathological damages rapidly and without scar. Taken together, the results strongly support Gel-H.P.Cur as a multipotent biomaterial for medical applications regarding the treatment of chronic, infected, and dehiscent wounds.

Introduction: The neuroprotective impact of curcumin and the role of CREB (Cyclic AMP Response Element Binding protein)-BDNF (Brain-Derived Neurotrophic Factor) signaling pathway was evaluated in Methamphetamine (METH)-induced neurodegeneration in rats. Methods: Sixty adult male rats were randomly divided into 6 groups. While normal saline and 10 mg/kg METH were administered intraperitoneally in groups 1 and 2, groups 3, 4, 5, and 6 received METH (10 mg/kg) and curcumin (10, 20, 40, and 80 mg/kg, respectively) simultaneously. Morris water maze test was administered, and oxidative hippocampal, antioxidant, inflammatory, apoptotic, and CREB and BDNF were assessed. Results: We found that METH disturbs learning and memory. Concurrent curcumin therapy (40 and 80 mg/kg) decreased cognitive disturbance caused by METH. Multiple parameters, such as lipid peroxidation, the oxidized form of glutathione, interleukin 1 beta, tumor necrosis factor-alpha, and Bax were increased by METH therapy, while the reduced type of glutathione, Bcl-2, P-CREB, and BDNF concentrations in the hippocampus were decreased. Conclusion: Different doses of curcumin adversely attenuated METH-induced apoptosis, oxidative stress, and inflammation but enhanced the concentrations of P-CREB and BDNF. The neuroprotection caused by curcumin against METH-induced neurodegeneration is mediated through P-CREB-BDNF signaling pathway activation.

Background and Objectives: Considering rising antibiotic resistance in various strains of Streptococcus pneumoniae, there is a need to find new immunogenic candidates for developing pneumococcal vaccines. Immunoglobulin A1 (IgA1) protease is one of the virulence factors playing an important role in the pathogenesis of S. pneumoniae infections. In the present study, we aimed to evaluate the titer of antibody against pneumococcal recombinant IgA1 protease in the serum of healthy humans. Materials and Methods: A part of the IgA1 protease gene (705 bp) from S. pneumonia ATCC 49619 was amplified by PCR and then digested using restriction enzymes and ligated by the pET28a expression vector. The recombinant protein was expressed in E. coli BL21 strain. Affinity chromatography was used to purify the protein. The titer of antibody against the recombinant protease was determined in healthy individuals in three age groups of 40 years using indirect Enzyme-Linked Immunosorbent Assay (ELISA). Results: The expression and purification of the IgA1 recombinant protease were successful. The concentration of the purified protein was determined as 1.013 mg/ml using the NanoDrop method. The titer of anti-recombinant IgA1 protease antibody (20, 40, 80 and 160) showed a significant correlation with age (p-value Conclusion: In the present study, desirable antibody titers against the pneumococcal recombinant IgA1 protease were seen in the three groups’ serum of healthy individuals. However, a significant correlation was not totally observed among groups.

Background The inhibition of quorum sensing (QS) is considered as a novel strategy for development of antipathogenic agents and management of nosocomial infections caused by Pseudomonas aeruginosa. The present study aimed to investigate the anti-quorum sensing activity of sub-MIC concentrations of quercetin (Q), imipenem (IPM) and ciprofloxacin (CIP) alone and in combination against P. aeruginosa. Methods We determined the MIC and synergistic activity of Q, IPM and CIP against P. aeruginosa PAO1. The effect of sub-MIC (1/4 and 1/16 MIC) concentrations of Q, IPM and CIP alone and in combination on QS related virulence factors and expression of lasI and lasR genes was also determined. Results The addition of Q decreased the MIC of IPM and CIP and there was additive effect from these combinations. Quercetin did not show significant effects on cell growth at concentrations of 1/4 and 1/16 MIC. However, sub-MIC concentrations (1/4 and 1/16 MIC) of Q in combination with IPM or CIP showed the significant reduction in QS dependent phenotypes (P lasI compared with untreated control (P P. aeruginosa.

During the recent years, viral epidemic due to coronaviruses, such as SARS (Severe Acute Respiratory Syndrome), Middle East Respiratory Coronavirus Syndrome (MERS), and COVID-19 (coronavirus disese-19), has become a global problem. In addition to causing cardiovascular and respiratory lethal dysfunction, these viruses can cause neurodegeneration leading to neurological disorders. Review of the current scientific literature reveals the multiple neuropathies and neuronal dysfunction associated with these viruses. Here, we review the major findings of these studies and discuss the main neurological sequels and outcomes of coronavirus infections with SARS, MERS, and COVID-19. This article analyzes and discusses the main mechanisms of coronavirus-induced neurodegeneration according to the current experimental and clinical studies. Coronaviruses can damage the nerves directly through endovascular dysfunctions thereby affecting nerve structures and synaptic connections. Coronaviruses can also induce neural cell degeneration indirectly via mitochondrial dysfunction inducing oxidative stress, inflammation, and apoptosis. Thus, coronaviruses can cause neurological disorders by inducing neurovascular dysfunction affecting nerve structures and synaptic connections, and by inducing inflammation, oxidative stress, and apoptosis. While some of these mechanisms are similar to other RNA viruses, the neurotoxic mechanisms of COVID-19, MERS, and SARS-CoV viruses are unknown and need detailed clinical and experimental studies.

Neurodegeneration is a gradual mechanism of neuronal loss arising from numerous cellular and molecular events such as mitochondrial dysfunction, oxidative stress, inflammation, and apoptosis, and the consequence of these processes is neuroplasticity impairment, cognitive diseases, mood-related diseases, and normal cellular activity. Over the last year, major advances have been made in the field of the introduction of herbal compounds with neuroprotective efficacy, one of which is curcumin. Curcumin (diferuloylmethane) is the most abundant turmeric component extracted from the Curcuma longa plant rhizomes. Accumulating evidence indicates that curcumin may induce mitochondrial biogenesis and can function as an antioxidant, anti-inflammatory, and anti-apoptotic agent, which may be used effectively to treat chronic neurodegenerative diseases and any situation in which the neurodegeneration process takes place. Curcumin has been shown to play a critical role in activating two essential signaling pathways phosphatidylinositol-3(PI3)/ protein kinase B(Akt)/ glycogen synthase kinase-3 (GSK3) and PI3/Akt/cAMP response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) and preventing the incidence of neurodegeneration via these two pathways. Curcumin's protective functions against neural cell degeneration due to mitochondrial dysfunction and consequent events such as oxidative stress, inflammation, and apoptosis in neural cells have been documented and clinical data have increased to suggest that curcumin may be a standard candidate as a neuroprotective agent. Therefore, in this review, we summarized the clinical and experimental studies and interpreted the key contributory mechanisms of neuroprotective properties of curcumin in neurodegenerative diseases and disorders. We also tried to understand the function of PI3/Akt/GSK3 and PI3/Akt/CREB/BDNF signaling pathways in the neuroprotective properties of curcumin and tried to evaluate their association with antioxidant, anti-inflammatory, anti-apoptosis and biogenesis effects of mitochondria.

Neurodegenerative disorders are characterized by mitochondrial dysfunction and subsequently oxidative stress, inflammation, and apoptosis that contribute to neuronal cytotoxicity and degeneration. Recent studies reported that crocin, a carotenoid chemical compound common in crocus and gardenia flowers, has protective effects in neurodegenerative disorders due to its anti-oxidative, anti-inflammatory, and anti-apoptotic properties in the nervous system. This article reviews the new experimental, clinical, and pharmacological studies on the neuroprotective properties of crocin and its potential mechanisms to modulate metabolic oxidative stress and inflammation in neurodegenerative disorders.

The use of metal complexes to reduce or inhibit virulence factors of Pseudomonas aeruginosa is a promising strategy for the management and control of infections caused by this multidrug-resistant pathogen. The present study aimed to investigate the anti-quorum sensing activity of sub-minimum inhibitory concentrations (sub-MIC) of copper(II) sulfate pentahydrate-curcumin complex (Cu-CUR), iron(III) nitrate nonahydrate -curcumin complex (Fe-CUR), zinc(II) chloride-curcumin complex (Zn-CUR) and free curcumin (free-CUR) against P. aeruginosa PAO1. Metal-CUR complexes were synthesized and characterized by spectroscopic methods. The effect of sub-MIC (1/4 and 1/16 MIC) concentrations of metal-CUR complexes and free-CUR on cell growth, biofilm formation, motility, alginate and pyocyanin production, H2O2 susceptibility and expression of lasI and lasR genes in PAO1 was determined. MIC of metal-CUR complexes and free-CUR was determined as 62.5 and 125 µg/ml, respectively. Metal-CUR complexes at concentration of 62.5 µg/ml significantly reduced the cell growth to 1.5%–3.3%. Although we did not measure the anti-QS activity of metal-CUR complexes directly against PAO1, they indicated anti-QS activity in C. violaceum CV026. Copper-CUR complex at the concentration of 1/4 MIC showed the greatest inhibitory effect on swarming and twitching motilities, biofilm formation, alginate and pyocyanin production, sensitivity to H2O2 and reduction in the expression levels of lasI and lasR genes (P P. aeruginosa.

The article's abstract is no available.

Quorum sensing (QS) inhibition by metal-antibiotic complexes is a promising strategy for the management and control of multidrug resistant Pseudomonas aeruginosa infections. We investigated the anti-quorum sensing activity of sub-minimum inhibitory concentration (sub-MIC) of copper(II) sulfate pentahydrate-ciprofloxacin (Cu-CIP) complex and free ciprofloxacin (free-CIP) against P. aeruginosa PAO1. Copper-CIP complex was synthesized and its characterization was assessed using spectroscopic methods and single crystal X-ray analysis. The effect of sub-MIC (1/4 and 1/16 MIC) concentrations of Cu-CIP and free-CIP on cell growth, biofilm formation, motility, alginate and pyocyanin production, H2O2 susceptibility and expression of QS circuit genes lasI and lasR in PAO1 was determined. Minimum inhibitory concentration of Cu-CIP complex and free-CIP was determined as 0.125 µg/ml. Copper-CIP complex did not show significant effect on the cell growth at concentrations of 1/4 and 1/16 MIC. However, sub-MIC concentrations (1/4 and 1/16 MIC) of Cu-CIP showed the significant reduction in violacein production, motility, biofilm formation, alginate and pyocyanin production and sensitivity to H2O2 in a concentration dependent manner (P lasI and lasR transcriptional expression (89.5% and 96.2% respectively). Considering the biological effects of Cu-CIP complex and its inhibitory activity on QS related virulence traits at low concentrations (0.03 and 0.007 µg/ml), it may be used as an effective approach in the management of infections caused by P. aeruginosa.

Background Alcohol abuse causes severe damage to the brain neurons. Studies have reported the neuroprotective effects of curcumin against alcohol-induced neurodegeneration. However, the precise mechanism of action remains unclear. Methods Seventy rats were equally divided into 7 groups (10 rats per group). Group 1 received normal saline (0.7 ml/rat) and group 2 received alcohol (2 g/kg/day) for 21 days. Groups 3, 4, 5 and 6 concurrently received alcohol (2 g/kg/day) and curcumin (10, 20, 40 and 60 mg/kg, respectively) for 21 days. Animals in group 7 self- administered alcohol for 21 days. Group 8 treated with curcumin (60 mg/kg, i.p.) alone for 21 days. Open Field Test (OFT) was used to investigate motor activity in rats. Hippocampal oxidative, antioxidative and inflammatory factors were evaluated. Furthermore, brain cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and brain derived neurotrophic factor (BDNF) levels were studied at gene level by reverse transcriptase polymerase chain reaction (RT-PCR). In addition, protein expression for BDNF, CREB, phosphorylated CREB (CREB-P), Bax and Bcl-2 was determined by western blotting. Result Voluntary and involuntary administration of alcohol altered motor activity in OFT, and curcumin treatment inhibited this alcohol-induced motor disturbance. Also, alcohol administration augmented lipid peroxidation, mitochondrial oxidized glutathione (GSSG), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and Bax levels in isolated hippocampal tissues. Furthermore, alcohol-induced significant reduction were observed in reduced form of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities and CREB, BDNF and Bcl-2 levels. Also curcumin alone did not change the behavior and biochemical and molecular parameters. Conclusion Curcumin can act as a neuroprotective agent against neurodegenerative effects of alcohol abuse, probably via activation of CREB-BDNF signaling pathway.

Context: The major aim of tissue engineering is inducing of the body’s mechanisms to regenerate damaged tissues to original condition and task. Scaffolds are 3D porous constructs which provide a cellular microenvironment needed for tissue engineering. Choosing a biomaterial with proper biological, physical, and mechanical properties is of great importance in tooth tissue engineering. Thus, the current study reviews the properties of different polymers and ceramics for use as scaffolds in tooth dental regeneration. Evidence Acquisition: The current study searched databases such as Elsevier, Wiley, Google Scholar, and PubMed in English from 1972 to 2018. After going through the required process, 29 articles were eventually confirmed and enrolled in this review paper. Conclusions: The results of this work confirmed that thanks to having the ability to provide suitable amounts of interconnected porosities, high ratio of surface area to volume, proper mechanical strength, and different geometries required for tissue engineering, polymers are a good option for regeneration of tooth tissues. Although bioceramics such as calcium phosphate and glasses have good biocompatibility and bioactivity, their poor mechanical properties and low degradation rate limit their extensive use in tooth tissue regeneration.

Context: Balance control results from multiple interactions between different systems: input from the visual, the somatosensory, and the vestibular systems are integrated and regulated by the central nervous system to ensure standing balance. One of the effective interventions is using ankle taping. The purpose of this review was to assess the effectiveness of ankle taping on balance in central nervous system diseases. Evidence Acquisition: This study is a systematic review and databases PubMed, Cochrane Library, Google Scholar, Science Direct, Ovid, Scopus, and Web of Science were searched for original scientific articles that were published between January 1990 to July 2018. Studies investigating the effect of therapeutic ankle taping on balance in central nervous system diseases were included. The PEDro quality scale was used to investigate the studies included; it investigates taping, balance, central nervous system disease. Results: Seven articles were included from 256 relevant articles. There were differences among the studies in terms of methodology, design, outcomes, sample size, procedure, etc. The results showed that using lower leg taping can be effective in balance improvement. Conclusions: Using lower leg taping can be effective in balance improvement in central nervous system diseases.

Manganese oxyhydroxide (MnOOH) nanoparticles were synthesized by the reaction of [Mn(Hsal)2] complex and NaOH in the presence of ultrasound irradiation. In this study, the effect of different reaction parameters such as type of solvent, sonication time and type of surfactant on the morphology and the particle size of product were studied. The as-synthesized nanoparticles, with an average size of 10–15 nm, were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectra (FT-IR) and energy dispersive spectrometry (EDS). To the best of author’s knowledge, it is the first time that [Mn(Hsal)2] complex is used as manganese source for the synthesis of MnOOH nanoparticles.

Background : The neuroprotective effects of duloxetine and neurodegenerative effects of methamphetamine have been shown in previous studies, but their exact mechanism remain unclear. In the current study it involved molecular mechanisms of neuroprotective effects of duloxetine against methamphetamine induced neurodegeneration were clarified. Methods : About 40 adult male rats randomly were divided to 5 groups. Group 1 and 2, as control and methamphetamine treated, received normal saline and methamphetamine (10 mg/kg) respectively. Groups 3, 4 and 5 concurrently treated with methamphetamine and duloxetine at doses of 10, 20 and 30 mg/kg respectively. All treatments were undertaken for 21 days. On day 22 Open Field Test (OFT) were used to examine the level of motor activity disturbance and anxiety in animals. After that hippocampus was isolated from each rat and oxidative, antioxidant, inflammatory factors and also level or expression of total and phosphorylated forms of CREB and P‑CREB and BDNF proteins were measured. Results : Duloxetine in all mentioned doses could inhibit the effects of methamphetamine induced motor activity disturbance in MWM. Chronic abuse of methamphetamine could increase malondialdehyde (MDA), tumor necrosis factor‑Alpha (TNF‑ α ) and interleukine‑1beta (IL‑1 β ) while caused decreases in superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities and decreased CREB (both forms) and BDNF proteins, while duloxetine could prevent these malicious effects of methamphetamine. Conclusions : We conclude that P‑CREB/ BDNF signaling pathways might have critical role in duloxetine neuroprotective effects against methamphetamine induced neurodegeneration. Keyword : Duloxetine, methamphetamine, motor activity, neurodegeneration, P‑CREB/BDNF pathway

A novel and simple one-step solid state reaction in the presence of a suitable surfactant, sodium dodecyl sulfate (SDS), and a novel precursor, [bis(acetylacetonato)zinc(II)]; [Zn(acac)2]; has been developed to synthesize uniform zinc oxide microflakes with an average thickness of 0.3–2.4 μm. In the absence of SDS the product samples contained microrods. The formation of zinc oxide microflakes depends on the molar ratio of Zn(II)/SDS and the experimental procedure. The products were characterized by X-ray diffraction, photoluminescence spectroscopy, FT-IR spectroscopy, surface area, scanning electron microscopy and transmission electron microscopy to depict the phase and morphology. The synthesized ZnO microflakes have a hexagonal zincite structure.

Evidence has shown that liver disease caused by hepatitis viruses can be more aggressive and severe in HIV infected subjects. Therefore, the present cross-sectional study aimed to evaluate the seroprevalence of HDV infection among HIV/HBV co-infected clients in Shiraz, southwest Iran. In this study, 178 patients co-infected with HBV and HIV individuals were enrolled. The diagnosis of HIV infection was documented based on serological assays. The demographic and complementary data were collected by a questionnaire. HBsAg and HDV Ab were detected by commercial quantitative enzyme linked immunosorbent assay kits according to the manufacturer’s instructions. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also measured. The mean age of the participants was 37.4±7.4 years (range 22-63). 175 (98.4 %) patients were male and 3 (1.6 %) were female. Among 178 patients co-infected with HIV/HBV, 35 cases (19.7%, 95% CI: 14%-25%) were anti-HDV‏ positive and 143 (80.3%) were negative for anti-HDV. HDV exposure in HIV/HBV co-infected patients was associated with blood transfusion (P=0.002, OR: 14.3) and prison history (P=0.01, OR: 2.31) but not with age, marital status, unsafe sex contact, and injection drug abuse. Our data showed a relatively high prevalence of HDV infection in HIV infected population in Shiraz, Iran. The high frequency of HDV Ab in patients with blood transfusion and prison history reveals that HDV transmission occurs more frequently in the parental route than sexual contacts; therefore, blood screening for HDV diagnosis in the high-risk group is recommended.