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The Juice clarification is an important operation in the fruit processing industry. Sour Orange is a source of vitamin C that is cultivated in the north of Iran. Since turbidity of this fruit after juice extraction affects on quality, shelf-life and concentration of juice; clarification and removing of turbidity-causing factors is important. In this study, the effect of membrane parameters including pressure (1.2-2.2 bar) and temperature (25-35 °C) on the quality characteristics of sour orange during membrane clarification was investigated. The response surface methodology (RSM) by Design-Expert Software was used to optimize the clarification conditions. Results of the experiments showed that the Browning index was raised by increasing of temperature, but vitamin C content, Total antioxidant activity value and clarity was decreased in this condition. The Browning index was decreased by increasing of pressure; however, no significant effect was observed on the other quality characteristics. Results of process optimization indicated that the best condition to maximize of vitamin C content, total antioxidant and clarity and to minimize of Browning index achieved at 25 °C and 1.7 bar. In this condition the vitamin C content, Browning index, Total antioxidant activity and clarity was 24.9 (mg/100 cc juice), 0.106, 87.97% and 97.1%, respectively. [ABSTRACT FROM AUTHOR]

PURPOSE, The relationship between refractory errors and intelligence and the importance of genetic, regional and environmental factors in such associations, were investigated in a group of school children. SUBJECTS AND METHODS, One hundred and thirty-seven students (34.3% boys and 65.7% girls) from two primary schools were enrolled in the study. Cycloplegic refraction was performed and a spherical equivalent (SE) ≥ 0.5D were determined as hyperopia; <-0.5D myopia and <1 cyl D astigmatism. Demographic factors, parent's education level, teacher based assessment of school performance and average score were also evaluated. RESULTS, Seventy-eight (56.9%) of subjects showed a form of refractory error; 27%, 3% and 2.9% were myope, hyperope or astigmat, respectively, whereas 12.4% of them had both myopia and astigmatism and 10.2% showed hyperopia and astigmatism; 43.1% were normal. CONCLUSIONS, Although our data revealed no distinction of average score between normal group and myopia, hyperopia, astigmatism or hyperopia-astigmatism, there is a statistically significant difference between normal group and those who had both myopia and astigmatism in which the later had a lower mediocre. Our results is somehow in contrast with other parallel studies demonstrating that positive connection between school performance and myopia can be explained by the geographical or racial discrepancies as well as subjects involved in the study and divergent set of cut off limits. [ABSTRACT FROM AUTHOR]

Abstract: Previous studies have generated controversy about the extent of co-localization between substance P- and catecholamine-containing neurons that project to the spinal cord. In earlier studies, estimates using immunofluorescence after colchicine have ranged from almost all, to almost none. We sought to resolve this issue by combining in situ hybridization and immunofluorescence. Catecholamine (A1 to A7, C1 to C3; tyrosine hydroxylase immunoreactive) neurons in the rat brainstem were examined to determine their content of mRNA for the preprotachykinin-A gene. In the A1 to A7 and the C1 to C3 cell groups, preprotachykinin-A mRNA was found only in substantial amounts in the C1–C3 cell groups. On average 20.9±0.9% (234/1120, n=3) of rostral C1 neurons contained preprotachykinin-A mRNA. Co-localization was also observed in C2 and C3 neurons to a similar extent. Retrograde tract-tracing with cholera toxin B subunit was used to identify bulbospinal neurons and 17.9±2.7% (96/529 cells) of the bulbospinal tyrosine hydroxylase-containing neurons of the rostral C1 cell group were found to contain preprotachykinin-A mRNA. In addition a new population of non-catecholaminergic bulbospinal preprotachykinin-A neurons is described in an area corresponding to the recently described caudal pressor area. To confirm that the preprotachykinin-A mRNA observed in cells in the medulla was converted to protein, dual immunofluorescence for fiber labeling at the confocal level was carried out. This confirmed colocalization of substance P and tyrosine hydroxylase in the intermediolateral cell column, but nowhere else, in a small number of cases. The results provide evidence for a much larger population of substance P/neurokinin A containing neurons in the brainstem than was previously suspected. Furthermore, many of these neurons are catecholaminergic and spinally projecting. The specific sympathetic outflow that these neurons influence remains to be determined. [Copyright &y& Elsevier]

GPCRs are inherently flexible molecules existing in an equilibrium of multiple conformations. Binding of GPCR agonists shifts this equilibrium. Certain agonists can increase the fraction of active-like conformations that predispose the receptor to coupling to a particular signal transducer or a select group of transducers. Such agonists are called biased, in contrast to balanced agonists that facilitate signaling via all transducers the receptor couples to. These biased agonists preferentially channel the signaling of a GPCR to particular G proteins, GRKs, or arrestins. Preferential activation of particular G protein or arrestin subtypes can be beneficial, as it would reduce unwanted on-target side effects, widening the therapeutic window. However, biasing GPCRs has two important limitations: a) complete bias is impossible due to inherent flexibility of GPCRs; b) receptor-independent functions of signal transducer proteins cannot be directly affected by GPCR ligands or differential receptor barcoding by GRK phosphorylation. This article is part of the Special Issue on "Ligand Bias"., Competing Interests: Declaration of competing interest The authors declare no conflicts of interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Paraquat (PQ), a widely used non-selective herbicide, induces severe lung toxicity by promoting cell death and tissue necrosis through the generation of reactive oxygen species (ROS) and free radicals. This study aimed to develop and evaluate novel niosomal nanoparticles (NPs) encapsulating curcumin and piperine to mitigate PQ-induced acute pulmonary toxicity in Balb/c mice., Methods: The NPs were prepared using non-ionic surfactants and cholesterol via the thin film hydration method., Results: Characterization revealed high encapsulation efficiency (>85%), proper particle sizes (264-286 nm), narrow polydispersity index (PDI) (0.19 ± 0.04 to 0.23 ± 0.02), and good stability over 90 days. Thermal analysis confirmed successful encapsulation of curcumin and piperine within the niosomal NPs. In vivo studies showed that PQ exposure significantly elevated ROS, lipid peroxidation (LPO), and protein carbonylation (PC) levels, while reducing glutathione (GSH) levels and impairing mitochondrial function (P < 0.001). However, co-treatment with curcumin- and piperine-loaded niosomal NPs effectively reversed these effects (P < 0.001), improving mitochondrial function., Conclusion: The combined formulation of curcumin and piperine in niosomal NPs offers a promising therapeutic strategy for treating PQ-induced pulmonary toxicity, likely due to enhanced bioavailability and potent antioxidant activity., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Gastric ulcers are a common gastrointestinal disorder associated with significant morbidity and mortality. It can also increase the risk of gastric cancer. This study aimed to investigate the effect of benfotiamine on experimentally-induced gastric ulcers in male rats. In this study, 30 Wistar male rats were divided randomly into six groups: control (normal), indomethacin, omeprazole, and treatment groups, including 50, 100, and 200 mg/kg of benfotiamine. Gastric ulcer was induced by indomethacin gavage. Omeprazole and different therapeutic doses of benfotiamine were administered for three days. Twenty-four hours after the last treatment, the rats were euthanized, and samples were collected.The results demonstrated that 100 and 200 mg/kg of benfotiamine treatment significantly improved indomethacin-induced gastric tissue damage. Moreover, benfotiamine at 100 and 200 mg/kg effectively attenuated the levels of pro-inflammatory cytokines IL-6 and TNF-α and oxidative stress markers MDA and ROS while increasing the antioxidant GSH. These findings suggest that benfotiamine's gastroprotective effects are mediated through its antioxidant and anti-inflammatory properties, which help mitigate the tissue damage and inflammatory response associated with indomethacin-induced gastric ulcers.However, further research is needed to elucidate the precise molecular mechanisms underlying these beneficial effects and to evaluate the potential therapeutic application of benfotiamine in clinical settings., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

To overcome the challenges associated with the co-delivery of AuNPs (gold nanoparticles) and miRNA as an anti-breast cancer combination therapy, niosomal systems were developed using Span 60, cholesterol, and a cationic lipid (CTAB), and the formulations were optimized using Box-Behnken experimental design. The niosomal formulations with the smallest size were selected for further optimization of size, surface charge, entrapment efficiency, and stability. To achieve this, AuNPs and DSPE-PEG2000 (2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000)were added to the formulation. The optimized niosomal formulation could effectively encapsulate AuNPs with an entrapment efficiency of 34.49% ± 0.84 and a spherical particle size of 153.6 ± 4.62 nm. The incorporation of PEG and CTAB led to notable enhancements in the overall characteristics of the delivery system. To evaluate the effectiveness of the combination therapy, various assessments such as cytotoxicity, apoptosis, and gene expression properties were conducted. The results demonstrated that the combination delivery using the new C-PEG-Nio-AuNPs (cationic pegylated niosomal gold nanoparticles) system and miRNA had the lowest IC50, the highest apoptosis rate, and the most significant upregulation of miRNA and BAX/BCL2 expression in MCF-7 cell growth. In conclusion, this innovative co-delivery approach represents a promising breakthrough in the development of therapeutic agents for breast cancer treatment. By combining multiple therapeutic agents within a single delivery system, this method has the potential to enhance treatment efficacy, reduce side effects, and improve patient outcomes., (© 2024. The Author(s).)

This study reports on the synthesis of Mn 1 - x Zn x Fe 2 O 4 (Mn, Zn ferrite) magnetic nanoparticles (MNPs) as drug delivery carriers for effective therapeutic outcomes. The MNPs were prepared using the coprecipitation method, and their magnetic properties were investigated based on their composition. Among the compositions tested, Mn 0.8 Zn 0.2 Fe 2 O 4 MNPs exhibited superparamagnetic properties with a saturation magnetization moment of 34.6 emu/g at room temperature (25°C). To enhance the water solubility of curcumin (Cur), known for its hydrophobic nature, it was successfully loaded onto alginate (Alg)/chitosan (Chit)@Mn 0.8 Zn 0.2 Fe 2 O 4 nanoparticles (NPs). The nanocomposite was characterized by field emission scanning electron microscopy (FE-SEM) which revealed a particle size of approximately 20 nm. The crystalline structure of the NPs was analyzed using X-ray diffraction, while Fourier-transform infrared (FTIR), energy-dispersive X-ray, and map analysis techniques were employed for further characterization. In terms of drug release, there was an initial burst release of Cur (around 18%) within the first hour, followed by a slower release (approximately 61%) over the next 36 h. The anti-tumor properties of the Cur-loaded NPs were evaluated using the Methyl Thiazol Tetrazolium (MTT) assay and quantitative real-time polymerase chain reaction. The MTT assay confirmed a higher cytotoxic effect of Cur-loaded Alg/Chit@Mn 0.8 Zn 0.2 Fe 2 O 4 NPs on the MCF-7 breast cancer cell line compared to free Cur, highlighting the significance of incorporating Cur into nano-sized carrier systems., (© 2023. The Author(s).)

Bioethanol's importance as a renewable energy carrier led to the development of new devices for the high-throughput screening (HTS) of ethanol-producing microorganisms, monitoring ethanol production, and process optimization. This study developed two devices based on measuring CO 2 evolution (an equimolar byproduct of microbial ethanol fermentation) to allow for a fast and robust HTS of ethanol-producing microorganisms for industrial purposes. First, a pH-based system for identifying ethanol producers (Ethanol-HTS) was established in a 96-well plate format where CO 2 emission is captured by a 3D-printed silicone lid and transferred from the fermentation well to a reagent containing bromothymol blue as a pH indicator. Second, a self-made CO 2 flow meter (CFM) was developed as a lab-scale tool for real-time quantification of ethanol production. This CFM contains four chambers to simultaneously apply different fermentation treatments while LCD and serial ports allow fast and easy data transfer. Applying ethanol-HTS with various yeast concentrations and yeast strains displayed different colors, from dark blue to dark and light green, based on the amount of carbonic acid formed. The results of the CFM device revealed a fermentation profile. The curve of CO 2 production flow among six replications showed the same pattern in all batches. The comparison of final ethanol concentrations calculated based on CO 2 flow by the CFM device with the GC analysis showed 3% difference which is not significant. Data validation of both devices demonstrated their applicability for screening novel bioethanol-producer strains, determining carbohydrate fermentation profiles, and monitoring ethanol production in real time., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We are constantly encountering with low doses of chemicals in everyday life rather than toxic doses at a time. So, ongoing low-dose exposures of environmental chemicals commonly encountered are very likely to cause an adverse health effects. Perfluorooctanoic acid (PFOA) is frequently used for production of an array of consumer products and industrial processes. The present study evaluated the underlying mechanisms of PFOA-induced liver damage and also potential protection by taurine. Male Wistar rats were exposed to PFOA alone and in combination with taurine (25, 50, and 100 mg/kg/day) by gavage for 4 weeks. Liver function tests as well as histopathological examinations were studied. Also, oxidative stress markers, mitochondrial function, and nitric oxide (NO) production in liver tissues were measured. In addition, the expression of apoptosis-related genes (caspase-3, Bax, and Bcl-2), inflammation-associated genes (TNF-α, IL-6, NF-B), and c-Jun-N-terminal kinase (JNK) were evaluated. Taurine significantly reversed serum biochemical and histopathological alterations in the liver tissue following exposure to PFOA (10 mg/kg/day). Similarly, taurine alleviated mitochondrial oxidative damage-induced by PFOA in the liver tissue. An increased Bcl2: Bax ratio with decrees in the expression level of caspase-3, and decreased expression of inflammatory markers (TNF-α and IL-6), NF-B, and JNK were also observed following the administration of taurine. These findings suggest a protective role of taurine against PFOA-induced hepatotoxicity via the inhibition of oxidative stress, inflammation, and apoptosis., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: Perfluorooctanoic acid (PFOA) is a persistent organic pollutant (POP), broadly present in the environment. Due to long biological half-life, it is accumulated in the body, especially the liver, causing hepatocellular damage. This study was designed to assess the effects of rutin on PFOA-induced liver damage in rats., Materials and Methods: Male Wistar rats were exposed to PFOA (10 mg/kg/day) alone, or in combination with different doses of rutin (25, 50, and 100 mg/kg/day) by oral gavage for 4 weeks., Results: PFOA altered the levels of liver enzymes, induced a notable change in the tissue structure of the liver, caused some levels of mitochondrial dysfunction, and increased the expression of pro-apoptotic and pro-inflammatory genes. Co-treatment with rutin mitigated the PFOA-induced elevation of liver enzymes, histopathological defects, oxidative damage, and mitochondrial dysfunction. In addition, rutin declined the stimulatory effects of PFOA on the Bax: Bcl2 ratio and reduced the PFOA-induced gene expression of TNF-α, IL-6, NF-ƙB, and JNK., Conclusion: These findings suggest rutin as a protective agent for PFOA-induced liver injury, albeit the protection was partial. Possible mechanisms are inhibition of oxidative stress, mitochondrial dysfunction, and inflammatory response., Competing Interests: The authors declare that they have no conflicts of interest.

Depression is a very common mental disorder and mechanism that is associated with mitochondrial dysfunction. In the present study, we examined the mechanisms of action of isolated brain mitochondria in rats with depression for the first time. This will help identify the mitochondrial protective pathways of the two drugs and shed light on new therapeutic goals for developing antidepressants. Forced swimming, tail suspension, and sucrose preference tests were used to assess depressive-like behaviors and the oxidative stress factors of brain tissue, and measure the gene expression of apoptotic and anti-apoptotic, neuroplasticity, and neuroinflammatory factors by RT-PCR and acetylcholinesterase (AChE) activity in brain tissue (hippocampus and prefrontal) and the serum levels of corticosterone and fasting blood sugar. The results showed that the separation of neonatal rats from their mothers induced depressive-like behaviors, weight loss, mitochondrial dysfunction, increased expression of genes involved in neuroinflammation, apoptosis, genes involved in the depressive process, and decreased expression of genes involved in mood in both the hippocampus and prefrontal cortex. Maternal separation increased serum corticosterone levels, caused dysfunction of the cholinergic system, and also increased AChE activity. Treatment with different concentrations of minocycline and edaravone (1, 20, and 50 mg/kg), 5MTHF, and citalopram for 14 days showed that these drugs improved depression-like behaviors and mitochondrial function. It also reduced the expression of genes involved in neuroinflammation, apoptosis, and depression and increased the expression of genes involved in mood. In conclusion, minocycline and edaravone have neuroprotective, mitochondrial protective, antioxidant, anti-inflammatory, and anti-apoptotic effects against depressive-like behaviors caused by chronic stress., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The β-adrenoceptor blockers may have anti-oxidant properties or induce β-arrestin recruitment beyond classical desensitization of receptor/G protein coupling, offering potential therapeutic benefits. Here, we investigated the effects of carvedilol, metoprolol and propranolol in an animal model of cisplatin-induced nephrotoxicity. Rats received the β-blockers (3 or 12 mg/kg/day) with or without cisplatin, and kidney function was investigated using renal scintigraphy, histopathology, and serum variables. Metoprolol and propranolol as well as low-dose carvedilol did not alter kidney function, per se. Meanwhile, high-dose carvedilol reduced renal accumulation of Technetium-99m (99mTc)-labeled dimercaptosuccinic acid (99mTc-DMSA) without significant effect on other variables. Furthermore, low-dose carvedilol prevented cisplatin-induced reduction of tracer uptake, but high-dose of this drug aggravated the situation. In this regard, both low and high -doses of carvedilol significantly inhibited cisplatin effects on kidney histology, BUN and creatinine levels. Also, high-dose propranolol inhibited cisplatin adverse effects on radiotracer uptake, histological manifestations, BUN and creatinine levels, while metoprolol failed to cause a notable effect. Taken together, carvedilol and high-dose propranolol may offer potential benefits in cisplatin nephrotoxicity.

Three classes of G-protein-coupled receptor (GPCR) partners - G proteins, GPCR kinases, and arrestins - preferentially bind active GPCRs. Our analysis suggests that the structures of GPCRs bound to these interaction partners available today do not reveal a clear conformational basis for signaling bias, which would have enabled the rational design of biased GRCR ligands. In view of this, three possibilities are conceivable: (i) there are no generalizable GPCR conformations conducive to binding a particular type of partner; (ii) subtle differences in the orientation of individual residues and/or their interactions not easily detectable in the receptor-transducer structures determine partner preference; or (iii) the dynamics of GPCR binding to different types of partners rather than the structures of the final complexes might underlie transducer bias., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The goal of this experimentation was to increase the cutaneous absorption of venlafaxine HCl (VFX) encapsulated in a niosome (venlasosme) produced by an ultrasonic approach. The impact of the cholesterol:surfactant (Chol:Surf) proportion was examined to modify the venlasosme properties. Photon correlation spectroscopy, powder X-ray diffraction (PXRD), SEM, DSC, and ATR-FTIR spectroscopy were utilized to investigate the solid-state and morphology of VFX in the venlasosme. The studies revealed that increasing the level of Chol in the venlasosme increased the size of the particles. Alterations in the Chol to surfactant ratios (when Chol decreased from 2.5 to 0%) caused the zeta potential enhancement from 7.37 ± 0.67 to 15.53 ± 1.47 mV. The venlasosme with the highest cholesterol concentration (2.5%) had the highest encapsulation efficiency (approximately 63%). PXRD results revealed that VFX in venlasosme was in the amorphous form. The levels of VFX in the cutaneous layers and the receiver compartment were higher for the venlasosme gel than for VFX simple gel in the cutaneous permeability study and showed no cutaneous irritancy in rats. Furthermore, the venlasosme gel demonstrated significant antinociceptive and anti-inflammatory responses when compared to the control groups (VFX simple gel and diclofenac gel). The topical administration of the venlasosme gel also considerably increased the tail-flick and hot-plate response time when compared to the VFX simple gel, control groups, and diclofenac gel (p < 0.05). These findings suggest that niosomes can improve VFX efficacy as an antinociceptive and anti-inflammatory substance by improving the medicaments delivery to the specified site., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Aging inhibits male reproductive function and can have an impact on fertility. This study elucidated the accelerating role of sodium arsenite (As 3+ ) on D-galactose-induced reproductive aging in male rats. The rats in the study are divided into nine groups. Group I is young control. Group II is naturally aged 24-month-old rats, other animal groups received As 3+ (0.5, 1, and 2 mg/kg/day, i.p.) and/or D-galactose (DG) (50 mg/kg/day, i.p.) for 8 weeks. Then, sperm parameters, histopathological manifestations, oxidative stress markers, and gene expression of inflammatory factors (TNF-α, IL-6, and NF-ƙB), apoptosis-related genes (Bcl-2 and Bax), and C-Jun N-terminal kinase (JNK) were evaluated in testis tissue. As 3+ (1 and 2 mg/kg) induced significant changes in evaluated factors compared to control group. Co-treatment with DG and As 3+ caused morphological changes as well as a significant decrease in sperm motility and count. In DG + As 3+ group, histopathological changes were also more obvious. Moreover, as compared to the DG group, co-treated animals exhibited a significant increase in oxidant markers and a decrease in antioxidant levels. Accordingly, DG co-exposure with As 3+ markedly enhances the expressions of TNF-α, IL-6, and NF-ƙB compared to DG alone. Likewise, in the testis of rats treated with As3 + plus DG compared to DG alone, there was up-regulation of Bax (pro-apoptotic), down-regulation of Bcl-2 (anti-apoptotic), and elevation of JNK expression. These findings suggest sodium arsenite as an accelerating cause for D-galactose-induced aging process in testis tissue., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The present study aimed to formulate atorvastatin niosome (Atrosome) through an ultrasonic technique and to determine its contribution to the extent of wound healing in an animal model. The optimized Atrosome formulation (Atrosome-2) was stable at 4 °C for 3 months. Differential scanning calorimetry (DSC), ATR-Fourier transform infrared spectroscopy (ATR-FTIR), and powder X-ray diffraction (PXRD) analysis revealed that atorvastatin (ATR) was well encapsulated within the niosomes either in a stabilized amorphous form or a molecularly dispersed state. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscope (AFM) confirmed the spherical nature of the Atrosomes. The optimized formulation showed polydispersity index, particle size, drug encapsulation efficiency (EE%), and zeta potential of 0.457 ± 0.05, 196.33 ± 6.45 nm, 86.15 ± 0.58 %, and - 20.73 ± 0.98 mV, respectively. ATR release from the Atrosome gel followed the first-order kinetic model and showed no cytotoxicity in the in vitro cytotoxicity test. Cell viability (human foreskin fibroblast cell line) was nearly 99%. An excision wound model was also applied in male Wistar rats to examine the in vivo efficacy of the optimized formulation, followed by investigating malondialdehyde (MDA, an end-product of lipid peroxidation), superoxide dismutase (SOD, an endogenous antioxidant), hydroxyproline levels, and glutathione peroxidase (GPx) in skin tissue samples. MDA significantly decreased in the Atrosome gel group after 21 days, while GPx, SOD, and hydroxyproline levels demonstrated an increase. According to histological results, rats receiving Atrosomes were treated effectively faster when compared to the other formulation used., (© 2022. The Author(s).)

Background: Cognitive impairment is an unpleasant and progressive mental disorder characterized by learning and memory disabilities. Stress and alcohol are two known environmental factors that increase cognitive impairment. This study was designed to evaluate the relative role of cyclooxygenase 2 in alcohol or stress-induced cognitive impairment., Materials and Methods: Male Wistar rats were randomly divided into groups with six rats in each. The groups included sham, control, alcohol (15% ethanol in drinking water), and restraint stress (restraint 6 h per day). Three separated groups received celecoxib at a dose of 20 mg/kg in addition to those listed above. The treatments continued daily for 28 days. The object recognition task (ORT) and Morris water maze (MWM) are used to evaluate the learning and memory., Results: Alcohol or restrain stress significantly increased the time and distance needed to find the hidden platform in MWM. Furthermore, they decreased the recognition index in ORT compared to the control group. Administration of celecoxib significantly decreased the required time and traveled distance to reach the platform in alcohol-treated animals but not in the stress-exposed rats. Celecoxib also significantly increased the recognition index both in alcohol- or restraint stress-exposed animals., Conclusion: We found that either alcohol or restraint stress impairs memory in rats. In MWM, celecoxib improved the alcohol-induced memory impairment but could not show a reduction in memory deterioration due to restraint stress. In ORT, celecoxib reversed memory impairment due to both alcohol and restraint stress., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Advanced Biomedical Research.)

Tramadol (TR) is a centrally acting analgesic drug that is used to relieve pain. The therapeutic (0.1-0.8 mg/l), toxic (1-2 mg/l) and lethal (>2 mg/l) ranges were reported for TR. The present study was designed to evaluate which doses of TR can induce liver mitochondrial toxicity. Mitochondria were isolated from the five rats' liver and were incubated with therapeutic to lethal concentrations (1.7-600 μM) of TR. Biomarkers of oxidative stress including: reactive oxygen species (ROS), lipid peroxidation (LPO), protein carbonyl content, glutathione (GSH) content, mitochondrial function, mitochondrial membrane potential (MMP) and mitochondrial swelling were assessed. Our results showed that ROS and LPO at 100 μM and protein carbonylation at 600 μM concentrations of TR were significantly increased. GSH was decreased specifically at 600 μM concentration. Mitochondrial function, MMP and mitochondrial swelling decreased in isolated rat liver mitochondria after exposure to 100 and 300 μM, respectively. This study suggested that TR at therapeutic and toxic levels by single exposure could not induce mitochondrial toxicity. But, in lethal concentration (≥100 μM), TR induced oxidative damage and mitochondria dysfunction. This study suggested that ROS overproduction by increasing of TR concentration induced mitochondrial dysfunction and caused mitochondrial damage via Complex II and membrane permeability transition pores disorders, MMP collapse and mitochondria swelling., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Arrestins are a small family of four proteins in most vertebrates that bind hundreds of different G protein-coupled receptors (GPCRs). Arrestin binding to a GPCR has at least three functions: precluding further receptor coupling to G proteins, facilitating receptor internalization, and initiating distinct arrestin-mediated signaling. The molecular mechanism of arrestin-GPCR interactions has been extensively studied and discussed from the "arrestin perspective", focusing on the roles of arrestin elements in receptor binding. Here, we discuss this phenomenon from the "receptor perspective", focusing on the receptor elements involved in arrestin binding and emphasizing existing gaps in our knowledge that need to be filled. It is vitally important to understand the role of receptor elements in arrestin activation and how the interaction of each of these elements with arrestin contributes to the latter's transition to the high-affinity binding state. A more precise knowledge of the molecular mechanisms of arrestin activation is needed to enable the construction of arrestin mutants with desired functional characteristics.

Background: Recruitment of β-arrestin to G protein-coupled receptors (GPCRs), initially described to cause receptor desensitization, has recently been shown to take active roles in cell signaling. We investigated the effects of TRV027, an angiotensin AT 1 receptor β-arrestin-biased ligand, as well as losartan and valsartan on cisplatin-induced kidney injury., Method: Male Sprague-Dawley rats were treated with angiotensin receptor ligands (1 or 10 mg/kg/day) with or without cisplatin, and kidney variables were monitored using animal SPECT, histopathology, and serum parameters., Results: TRV027, losartan, and valsartan did not alter renal dimercaptosuccinic acid (DMSA) uptake, histopathological manifestations of kidney injury, blood urea nitrogen (BUN), and creatinine or Na + and K + levels, per se. However, when rats co-treated with cisplatin and either of the AT 1 receptor blockers at higher doses, we observed aggravation of cisplatin-induced reduction of radiotracer uptake but improvement of cisplatin-induced hypokalemia, and insignificant effect on histological findings. Furthermore, we noted an additional increase in cisplatin-induced augmentation of BUN and creatinine levels in cisplatin plus valsartan group. TRV027 (1 mg/kg/day) inhibited cisplatin adverse effects on radiotracer uptake, kidney histology, BUN, and creatinine as well as electrolyte levels, but it failed to produce protective effects at higher dose (10 mg/kg/day)., Conclusion: Low-dose TRV027 may offer potential benefits in kidney injury due to cisplatin.

G protein coupled receptors (GPCRs) convey signals across membranes via interaction with G proteins. Originally, an individual GPCR was thought to signal through one G protein family, comprising cognate G proteins that mediate canonical receptor signaling. However, several deviations from canonical signaling pathways for GPCRs have been described. It is now clear that GPCRs can engage with multiple G proteins and the line between cognate and non-cognate signaling is increasingly blurred. Furthermore, GPCRs couple to non-G protein transducers, including β-arrestins or other scaffold proteins, to initiate additional signaling cascades. Receptor/transducer selectivity is dictated by agonist-induced receptor conformations as well as by collateral factors. In particular, ligands stabilize distinct receptor conformations to preferentially activate certain pathways, designated 'biased signaling'. In this regard, receptor sequence alignment and mutagenesis have helped to identify key receptor domains for receptor/transducer specificity. Furthermore, molecular structures of GPCRs bound to different ligands or transducers have provided detailed insights into mechanisms of coupling selectivity. However, receptor dimerization, compartmentalization, and trafficking, receptor-transducer-effector stoichiometry, and ligand residence and exposure times can each affect GPCR coupling. Extrinsic factors including cell type or assay conditions can also influence receptor signaling. Understanding these factors may lead to the development of improved biased ligands with the potential to enhance therapeutic benefit, while minimizing adverse effects. In this review, evidence for ligand-specific GPCR signaling toward different transducers or pathways is elaborated. Furthermore, molecular determinants of biased signaling toward these pathways and relevant examples of the potential clinical benefits and pitfalls of biased ligands are discussed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Nanosuspensions, liquid dispersions with nanometer size distribution, are becoming trendy in pharmaceutical practice to formulate poorly water-soluble drugs and to enhance their bioavailability. Generally, nanosuspensions are produced in two main approaches; top-down or bottom-up. The former is based on size-reduction of large particles via milling or high pressure homogenization. The latter is focused on the mechanisms of nucleation and particle growth., Methods: In this review, the critical factors influencing the kinetics or dynamics of nucleation and growth are discussed. Subsequently, the mechanisms of nanosuspension instability as well as strategies for stabilization are elaborated. Furthermore, the effects of stabilizers on key parameters of instability as well as the process of choosing an appropriate stabilizer is discussed., Results: Steric and electrostatic stabilizations or combination of them is essential for nanosuspensions formulation to prevent coagulation. Accordingly, some characteristics of stabilizers play critical role on stability and optimization of nanosuspensions; i.e., HLB and concentration. Nevertheless, after reviewing various articles, it is ascertained that each formulation requires individual selection of surfactants according to the parameters of the particle surface and the medium., Conclusions: Based on the results, application of excipients such as stabilizers requires proper optimization of type and concentration. This implies that each formulation requires its own optimization process. Graphical Abstract ᅟ.

Background: Marine sponges are associated with numerically vast and phylogenetically diverse microbial communities at different geographical locations. However, little is known about the archaeal diversity of sponges in the Persian Gulf. The present study was aimed to identify the symbiotic archaea with a sponge species gathered from the Persian Gulf, Iran., Methods: Sponge sample was collected from a depth of 3 m offshore Bushehr, Persian Gulf, Iran. Metagenomic DNA was extracted using a hexadecyl trimethyl ammonium bromide (CTAB) method. The COI mtDNA marker was used for molecular taxonomy identification of sponge sample. Also, symbiotic archaea were identified using the culture-independent analysis of the 16S rRNA gene and PCR- cloning., Results: In this study, analysis of multilocus DNA marker and morphological characteristics revealed that the sponge species belonged to Chondrilla australiensis isolate PG&#95;BU4. PCR cloning and sequencing showed that all of the sequences of archaeal 16S rRNA gene libraries clustered into the uncultured archaeal group., Conclusion: The present study is the first report of the presence of the genus of Chondrilla in the Persian Gulf. Traditional taxonomy methods, when used along with molecular techniques, could play a significant role in the accurate taxonomy of sponges. Also, the uncultured archaea may promise a potential source for bioactive compounds. Further functional studies are needed to explore the role of the sponge-associated uncultured archaea as a part of the marine symbiosis.

Background: Echinococcus granulosus is one the most important zoonotic disease which is endemic in worldwide. Molecular method has allowed discrimination of different genotypes (G1-G10), providing new approach in development of prevention and control program of hydatid cyst. This study was conducted to identify the genotypes of E. granulosus from domestic animals in nine districts of North Khorasan Province using the mitochondrial cox1 gene sequence., Methods: Overall, 122 hydatid cyst were collected during 2016-2017 from sheep (n=43) and cattle (n=79). DNA was extracted from protoscoleces and germinal layers and amplified by PCR. Phylogenetic analysis was also performed by analyzing the complete nucleotide sequences of mitochondrial cytochrome C oxidase subunit 1 (cox1) of E. granulosus genotypes from various locations., Results: Sequencing of the amplified products revealed the presence of G1 as dominant genotype, G3 and Echinococcus canadenesis in one isolate each. Altogether, 9 haplotypes were detected based on cox1 gene. Haplotype 3 was the common variant that found in 58 including 42 cattle and 16 sheep., Conclusion: This study provided knowledge on the identity of E. granulosus cysts collected from sheep and cattle in North Khorasan Province. Furthermore, these results showed the potentials of sheep as a main source of infection to humans, contributing the transmission and maintain of hydatid cyst in this region., Competing Interests: Conflict of interest The authors declare that there is no conflict of interests.

Occurrence and frequency of six most prescribed antibiotics (tetracycline, norfloxacin, azithromycin, anhydro erythromycin, cephalexin, and amoxicillin) were assessed in three wastewater treatment plants (WWTPs), and in water and sediments of the Persian Gulf at Bushehr coastline, Iran. The antibiotics concentration in the influent and effluent of septic tank (the hospital WWTP), activated sludge (the hospital WWTP), and stabilization pond (municipal WWTP) ranged between 7.89 and 149.63, 13.49-198.47, 6.55-16.37 ng/L, respectively. Conventional treatment resulted in incomplete removal of most of the studied antibiotics. Furthermore, the activated sludge was more effective in terms of antibiotic elimination compared to the stabilization pond or septic tank. The mean concentration of antibiotics ranged 1.21-51.50 ng/L in seawater and 1.40-25.32 ng/g in sediments during summer and winter. Norfloxacin was the dominant detected antibiotic in seawater, sediments, and influent of two hospital WWTPs. Seasonal comparisons showed significant differences for erythromycin and amoxicillin concentrations in seawater. Spatial variation indicated the role of physicochemical properties on distribution of antibiotics in seawater and sediments. The results emphasize the need to pay attention to antibiotic contamination in water and sediments of the Persian Gulf., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Autonomic imbalance plays a pivotal role in the pathophysiology of inflammatory bowel diseases (IBD). The central nervous system (CNS) cooperates dynamically with the immune system to regulate inflammation through humoral and neural pathways. In particular, acetylcholine (Ach), the main neurotransmitter in the vagus nerve, decreases the production of pro-inflammatory cytokines through a mechanism dependent on the α7 nicotinic Ach receptors (α7nAChRs). Areas covered: Here, we review the evidence for involvement of the cholinergic anti-inflammatory pathway (CAP) in IBD. We also elaborate the role of α7nAChRs and subsequent cellular pathways in CAP. Finally, we review potential therapeutic implications of modulators of these receptors. Expert opinion: Alpha7nAChR modulators possess both cognitive improving and anti-inflammatory properties. Although, these agents demonstrated therapeutic benefits in experimental models, their efficacy has not always been translated in clinical trials. Thus, development of more specific α7nAChR ligands as well as more experimental studies and better controlled trials, especially in the field of IBD, are encouraged for a progress in this field.

Biochemical and histological assays are currently used for the diagnosis and characterization of kidney injury. The purpose of this study was to compare technetium-99m-labeled dimercaptosuccinic acid ( 99m Tc-DMSA) renal scintigraphy, as a non-invasive method, with common biochemical and histopathological methods in two animal models of acute kidney injury. Nephrotoxicity was induced either by gentamicin (100 mg/kg/day for one week) or unilateral ureteral ligation (UUO). Renal scintigraphy was performed 1 h after intravenous injection of 99mTc-DMSA (3 mCi). Furthermore, plasma levels of blood urea nitrogen (BUN), creatinine, sodium, and potassium were determined using an autoanalyzer. At the end of experiments, kidneys were excised for the measurement of activity uptake (mCi/gr) using a dose calibrator as well as histopathological examinations with hematoxylin and eosin (H&E) staining. There was a significant decrease in 99mTc-DMSA uptake in both gentamicin (P value = 0.049) and UUO (P value = 0.034) groups, and it was more significant in the former. The levels of BUN and creatinine increased in both gentamicin and UUO groups, while the levels of sodium and potassium remained unchanged. Furthermore, a strong correlation was found between DMSA uptake and histopathological findings. Scintigraphy with 99mTc-DMSA is capable of detection of kidney injury in both gentamicin and UUO groups. Moreover, a significant correlation was found between scintigraphy parameters and histopathological findings. This suggests 99mTc-DMSA as a non-invasive method for the evaluation of kidney injury induced by drugs or anatomical disorders.