Ultrahigh-Loading Manganese-Based Electrodes for Aqueous Batteries via Polymorph Tuning.

Manganese-based aqueous batteries utilizing Mn2+ /MnO2 redox reactions are promising choices for grid-scale energy storage due to their high theoretical specific capacity, high power capability, low-cost, and intrinsic safety with water-based electrolytes. However, the application of such systems is hindered by the insulating nature of deposited MnO2 , resulting in low normalized areal loading (0.005-0.05 mAh cm-2 ) during the charge/discharge cycle. In this work, the electrochemical performance of various MnO2 polymorphs in Mn2+ /MnO2 redox reactions is investigated, and ɛ-MnO2 with low conductivity is determined to be the primary electrochemically deposited phase in normal acidic aqueous electrolyte. It is found that increasing the temperature can change the deposited phase from ɛ-MnO2 with low conductivity to γ-MnO2 with two order of magnitude increase in conductivity. It is demonstrated that the highly conductive γ-MnO2 can be effectively exploited for ultrahigh areal loading electrode, and a normalized areal loading of 33 mAh cm-2 is achieved. At a mild temperature of 50 °C, cells are cycled with an ultrahigh areal loading of 20 mAh cm-2 (1-2 orders of magnitude higher than previous studies) for over 200 cycles with only 13% capacity loss.

The Effects of Transcranial Focused Ultrasound Stimulation of Nucleus Accumbens on Neuronal Gene Expression and Brain Tissue in High Alcohol-Preferring Rats.

We investigated the effect of low-intensity focused ultrasound (LIFU) on gene expression related to alcohol dependence and histological effects on brain tissue. We also aimed at determining the miRNA-mRNA relationship and their pathways in alcohol dependence-induced expression changes after focused ultrasound therapy. We designed a case-control study for 100 days of observation to investigate differences in gene expression in the short-term stimulation group (STS) and long-term stimulation group (LTS) compared with the control sham group (SG). The study was performed in our Experimental Research Laboratory. 24 male high alcohol-preferring rats 63 to 79 days old, weighing 270 to 300 g, were included in the experiment. LTS received 50-day LIFU and STS received 10-day LIFU and 40-day sham stimulation, while the SG received 50-day sham stimulation. In miRNA expression analysis, it was found that LIFU caused gene expression differences in NAc. Significant differences were found between the groups for gene expression. Compared to the SG, the expression of 454 genes in the NAc region was changed in the STS while the expression of 382 genes was changed in the LTS. In the LTS, the expression of 32 genes was changed in total compared to STS. Our data suggest that LIFU targeted on NAc may assist in the treatment of alcohol dependence, especially in the long term possibly through altering gene expression. Our immunohistochemical studies verified that LIFU does not cause any tissue damage. These findings may lead to new studies in investigating the efficacy of LIFU for the treatment of alcohol dependence and also for other psychiatric disorders.

Fabrication of magnetic helical microribbons made of nickel thin films sandwiched between silicon nitride layers for microswimming applications.

Helical swimming is adopted by microswimming robots since it is an efficient mechanism and commonly observed among microorganisms swimming at low Reynolds numbers. However, manufacturing of micro-helices made of sub-micron magnetic thin layers is neither straightforward nor well-established, advanced materials and methods are necessary to obtain such structures as reported in the literature. In this paper, a topological patterning method utilizing basic microfabrication methods is presented for the self-assembly of magnetic micro-helices made of a sandwiched nickel thin film (50-150 nm) between two silicon nitride layers. Strain mismatch between the thin films and the geometric anisotropy introduced by the slanted patterns on the top nitride layer result in self-rolled-up helical microribbons. Moreover, inspired by the actual release process during the wet-etching of the microribbon from the substrate, moving boundary conditions are incorporated in a numerical model to simulate the self-rolling of trilayer ribbons. The simulation results are compared and validated by experimental data within 7% error for all cases, including the geometries that do not result in a helical shape. The swimming performance of the magnetized micro-helix is demonstrated inside a capillary glass tube experimentally and cross-validated with a numerical model.

Template-free preparation of iron oxide loaded hollow silica spheres and their anticancer proliferation capabilities.

Hollow silica spheres (HSS) exhibited high-specific surface area, low toxicity, low density, and good biocompatibility. The effectivity of HSS material can be improved further by loading nanoparticles for smart biological applications. In this work, magnetic nanoparticle (iron oxide; Fe3O4)-loaded pure HSS (c-HSS-Fe) were synthesized successfully using a template-free chemical route and investigated for their anticancer cell proliferation capabilities against cancerous cell lines: human colorectal carcinoma cells (HCT-116). The structure, morphology, chemical bonding, and thermal stability of the prepared HSS derivatives were studied using spectroscopic and microscopic techniques. Our analyses confirmed the successful preparation of Fe3O4 loaded HSS material (sphere diameter ∼515 nm). The elemental analysis revealed the existence of Fe along with Si and O in the Fe3O4 loaded HSS material, thus reaffirming the production of the c-HSS-Fe product. The effects of silica spheres on HCT-116 cells were examined microscopically and by MTT assays. It was observed that the c-HSS-Fe demonstrated dose-dependent behavior and significantly reduced the cancer cell proliferation at higher doses. Our results showed that c-HSS-Fe was more effective and profound in reducing the cancer cells' activities as compared to unloaded HSS material where the cancer cells have undergone nuclear disintegration and fragmentation. It is concluded that c-HSS-Fe is a powerful bio-active material against cancerous cells.

Tofacitinib enhances remyelination and improves myelin integrity in cuprizone-induced mice.

AIM: Demyelination and subsequent remyelination are well-known mechanisms in multiple sclerosis (MS) pathology. Current research mainly focused on preventing demyelination or regulating the peripheral immune system to protect further damage to the central nervous system. However, information about another essential mechanism, remyelination, and its balance of the immune response within the central nervous system's boundaries is still limited. MATERIALS AND METHODS: In this study, we tried to demonstrate the effect of the recently introduced Janus kinase (JAK)-signal transducer and activator of transcription (STAT) inhibitor, tofacitinib, on remyelination.Demyelination was induced by 6-week cuprizone administration, followed by 2-week tofacitinib (10, 30, and 100 mg/kg) treatment. RESULTS: At the functional level, tofacitinib improved cuprizone-induced decline in motor coordination and muscle strength, which were assessed by rotarod and hanging wire tests. Tofacitinib also showed anti-inflammatory effect by alleviating the cuprizone-induced increase in the central levels of interferon-γ (IFN-γ), interleukin (IL)-6, IL-1ß, and tumor necrosis alpha (TNF-α). Furthermore, tofacitinib also suppressed the cuprizone-induced increase in matrix metalloproteinases (MMP)-9 and MMP-2 levels. Additionally, cuprizone-induced loss of myelin integrity and myelin basic protein expression was inhibited by tofacitinib. At the molecular level, we also assessed phosphorylation of STAT-3 and STAT-5, and our data indicates tofacitinib suppressed cuprizone-induced phosphorylation in those proteins. CONCLUSION: Our study highlights JAK/STAT inhibition provides beneficial effects on remyelination via inhibition of inflammatory cascade.

Vertical cavity capacitive transducer.

The capacitive micromachined ultrasonic transducer (CMUT) has inherent advantages, such as larger bandwidth and monolithic integration capability with electronics, when compared to the piezoelectric transducer. The most significant shortcoming of the device is the trade-off between input and output sensitivities. Adequate receive sensitivity requires an electric field intensity on the order of 105 V/m, which can be achieved by sub-micron gap heights. However, a small gap limits the device stroke and, consequently, the maximum output pressure. This paper addresses this problem by proposing a CMUT with a vertical cavity. The membrane of the device has a piston part that is surrounded by the sidewalls of a vertical cylinder formed in the substrate. The fringing electric field pulls the piston in the vertical direction; hence, the gap height remains fixed, which alleviates the hard limit on device stroke. The performance of the proposed device is compared to that of the conventional CMUT by theoretical and analytical methods, and a micro-fabrication method is devised. Additionally, a millimeter-scale device has been manufactured and tested as a proof of concept.

Highly Flexible and Tailorable Cobalt-Doped Cross-Linked Polyacrylamide-Based Electrolytes for Use in High-Performance Supercapacitors.

A novel hydrogel polymer electrolyte was prepared by incorporation of 1,4-butanediol diglycidyl ether (BG) to cross-linked polyacrylamide (PAM). The electrolyte (PAMBG) was modified with cobalt (II) sulfate with various doping ratios (PAMBGCoX) to increase the capacitance by increasing faradaic reactions. The supercapacitor device assembly was performed by using active carbon (AC) electrodes and hydrogel polymer electrolytes. The specific capacitance of the PAMBGCo5 device indicated 130 F g-1 , which is at least a seven-fold improvement due to the insertion of Co as a redox component. The electrolyte device, PAMBGCo5, displays superior performance having an energy density of 38 Wh kg-1 at a power density of 500 W kg-1 . Additionally, with the same hydrogel, the device performed 10,000 galvanostatic charge-discharge cycles via retaining 91% of the initial capacitance. A cost-effective electrolyte, PAMBGCo5, was tested in a carbon-based supercapacitor under bent and twisted conditions at various angles, confirming the robustness of the device.

Vorinostat-loaded titanium oxide nanoparticles (anatase) induce G2/M cell cycle arrest in breast cancer cells via PALB2 upregulation.

Breast cancer is a group of diseases in which cells divide out of controlled, typically resulting in a mass. Erlotinib is targeted cancer drug which functions as an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase. It is used mainly to treat of non-small cell lung cancer patients and has an action against pancreatic cancer. Vorinostat (aka suberanilohydroxamic acid) is an inhibitor of histone deacetylases (HDAC), which has an epigenetic modulation activity. It is used to treat cutaneous T cell lymphoma. In the present study, the erlotinib (ERL) and vorinostat (SAHA) loaded TiO2 nanoparticles (NPs) were used for the treatment of the breast cancer cells (MDA-MB-231 and MCF-7) and human cancerous amniotic cells (WISH). Cell count and viability were negatively affected in all treatments compared to normal cells and bare TiO2 NPs. Apoptosis results indicated a significant increase in the total apoptosis in all treatments compared with control cells. ERL- and SAHA-loaded TiO2 NPs treatments arrested breast cancer cells at G2/M phase, which indicate the cytotoxic effect of these treatment. Partner and localizer of BRCA2 (PALB2) gene expression was assessed using qPCR. The results indicate that PLAB2 was upregulated in ERL- and SAHA-loaded TiO2 NPs compared with control cells and can be used as nanocarrier for chemotherapy drugs. However, this conclusion necessitates further confirmative investigation.

Coronavirus diseases 2019: Current biological situation and potential therapeutic perspective.

Coronavirus Disease 2019 (COVID-19) caused by a Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was first reported in Wuhan, China at the end of December 2019. SARS-CoV-2 is a highly pathogenic zoonotic virus and closely related to the Severe Acute Respiratory Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The COVID-19 was declared as a global pandemic due to its high infectiousness, and worldwide morbidities and mortalities. The Chinese scientists at the start of the outbreak reported genome sequences, which made the characterization of glycoproteins and other structural proteins possible. Moreover, researchers across the world have widely focused on understanding basic biology, developing vaccines, and therapeutic drugs against the COVID-19. However, until now, no promising treatment options, as well as vaccines, are available. In this review, we have described SARS-CoV-2's genome, transmission, and pathogenicity. We also discussed novel potential therapeutic agents that can help to treat the COVID-19 patients.

Neuroprotective action of agmatine in rotenone-induced model of Parkinson's disease: Role of BDNF/cREB and ERK pathway.

Numerous studies have investigated the role of agmatine in the central nervous system and indicated neuroprotective properties. In addition to its potent antioxidant effects, agmatine is an endogenous neuromodulator and has wide spectrum molecular actions on different receptor subtypes (NMDA, Imidazoline 1-2, alpha-2 adrenoreceptor, 5-HT2a, 5-HT3) and cellular signaling pathways (MAPK, PKA, NO, BDNF). Although the neuroprotective effects of agmatine demonstrated in experimental Parkinson's disease model, the effects of agmatine with the aspect of neuroplasticity and possible signaling mechanisms behind agmatine actions have not been investigated. Herein, in this study, we investigated the role of the of agmatine on rotenone-induced Parkinson's disease model. Agmatine at the dose of 100 mg/kg i.p., was mitigated oxidative damage and alleviated motor impairments which were the results of the rotenone insult. Additionally, agmatine decreased neuronal loss, tyrosine hydroxylase immunoreactivity and increased cREB, BDNF and ERK1/2 expression in the striatum, which are crucial neuroplasticity elements of striatal integrity. Taken together, the present study expands the knowledge of molecular mechanisms behind neuroprotective actions of agmatine in Parkinson's disease, and as far as we have known, this is the first study to delineate agmatine treated activation of cellular pathways which are important elements in neuronal cell survival.

Design of Crosslinked Hydrogels Comprising Poly(Vinylphosphonic Acid) and Bis[2-(Methacryloyloxy)Ethyl] Phosphate as an Efficient Adsorbent for Wastewater Dye Removal.

The development of adsorbents with high adsorption capacity and fast separation is of utmost importance for the environmental management of dye-bearing wastewaters. Within this scope, crosslinked hydrogels including poly(vinylphosphonic acid) (PVPA) and bis[2-(methacryloyloxy)ethyl] phosphate (BMEP) were designed with varying mole ratios of BMEP (5-40%). The Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Brunauer-Emmett-Teller (BET) results revealed that the fabrication of crosslinked PVPA-BMEP hydrogels enhanced: (i) functionalities of PA groups in the structure of hydrogels, (ii) thermal stabilities up to 250 °C, and (iii) interaction between methylene blue (MB) molecules and hydrogels. The pseudo second-order kinetic model best described the experimental adsorption data. The behaviors of the isotherms were more appropriate for Langmuir than Freundlich isotherm for the experimental data. PVPA-BMEP (40%) hydrogel indicated a fast and an outstanding MB adsorption capacity of 2841 mg g-1, which has not been reported yet for polymer hydrogels, to the best of our knowledge. The thermodynamic studies concluded that MB adsorption process was spontaneous and exothermic in nature. The overall results suggest that the designed and fabricated PVPA-BMEP hydrogels have great potential for the efficient removal of coloring materials from wastewaters.

PMMA-Based Wafer-Bonded Capacitive Micromachined Ultrasonic Transducer for Underwater Applications.

This article presents a new wafer-bonding fabrication technique for Capacitive Micromachined Ultrasonic Transducers (CMUTs) using polymethyl methacrylate (PMMA). The PMMA-based single-mask and single-dry-etch step-bonding device is much simpler, and reduces process steps and cost as compared to other wafer-bonding methods and sacrificial-layer processes. A low-temperature (< 180 ∘ C ) bonding process was carried out in a purpose-built bonding tool to minimize the involvement of expensive laboratory equipment. A single-element CMUT comprising 16 cells of 2.5 mm radius and 800 nm cavity was fabricated. The center frequency of the device was set to 200 kHz for underwater communication purposes. Characterization of the device was carried out in immersion, and results were subsequently validated with data from Finite Element Analysis (FEA). Results show the feasibility of the fabricated CMUTs as receivers for underwater applications.

Delivery of Conjugated Silicon Dioxide Nanoparticles Show Strong Anti-Proliferative Activities.

Conjugation of different molecules is a promising approach to enhance the drug delivery and treatment. In the present study, here, we have synthesized silica oxide (SiO2) nanoparticles conjugated with (3-Glycidyloxypropyl) trimethoxysilane (3GPS) and further reacted with 1,2,4-triazole (Tri), 3-aminotriazole (ATri), 5-aminetetrazole (Atet), imidazole (Imi). The structure, size, and morphology of nanocomposite materials were characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) methods. These nanocomposite materials were tested on human colorectal carcinoma cells (HCT-116) to examine their anti-cancer capabilities by using MTT assay and morphometric analysis. Our results revealed that nanocomposite materials decreased cancer cell viability and cell proliferation and caused cell death in a concentration-dependent manner. Our findings demonstrate that SiO2-conjugated nanocomposite materials possess strong anti-cancer capabilities and hold a great potential for the colon cancer treatments.

Effects of agomelatine in rotenone-induced Parkinson's disease in rats.

The effects of melatonin and melatonin analogs in experimental Parkinson's disease (PD) models remain controversial. Agomelatine, a novel analog of melatonin, is both agonists for melatonin-1 and melatonin-2 receptors and antagonist of 5-HT2C receptors. While agomelatine has been commonly used as an anti-depressant and sleep drug, information about effects of agomelatine in PD are still lacking. Male Sprague-Dawley rats (220-260 g) were injected with rotenone (0.5 µg, n = 16) or vehicle (1 µl DMSO, n = 8) into the left substantia nigra (SN) and ventral tegmental area under stereotaxic surgery. After ten days, the rats were assessed for the confirmation of PD by the rotational test following apomorphine injection (2 mg/kg, i.p.). The confirmed rats were divided into two groups which received daily p.o. agomelatine (40 mg/kg, n = 8) or saline (2 ml/rat, n = 8) for consecutively 18 days. Twenty-four hours after the last drug administration, the rotational test was repeated and motor coordination was assesed just before the decapitation. Brain tissues were taken for biochemical, molecular and histopathological evaluations. Agomelatine treated animals showed augmented apomorphine-induced rotation response and impaired motor coordination compared to the rotenone group. Furthermore, agomelatine treatment significantly induced apoptosis with an increase in caspase-3 expression independent from PARP-1 activation. Agomelatine treatment caused increased protein oxidation levels, in addition to a decrease in neuron number in the striatum. Although we investigated the effects of the agomelatine in the manner of ameliorating the rotenone toxicity in animals, agomelatine exacerbates rotenone-induced toxicity which mimics Parkinson's disease pathology.

Synthesis and Characterization of Novel Azole Functionalized Poly(glycidyl methacrylate)s for Antibacterial and Anticandidal Activity.

BACKGROUND: Presently, rise in the infectious diseases and subsequent development of drug resistance, is a global threat to human health. However, much efforts are being made by scientists, to develop novel antimicrobials, and also to improve the efficacy of available drugs, in order to combat the lifethreatening infections. OBJECTIVE: Synthesis and characterization of azole functional polymer systems for antimicrobial applications. MATERIALS AND METHODS: Poly(glycidyl methacrylate) (PGMA), was produced by free radical polymerization of the monomer, glycidyl methacrylate (GMA). Different azole functional PGMAs were produced, through chemical modification with imidazole (Im), 1H-1,2,4-triazole (Tri) and 3-amino-1,2,4-triazole (ATri), to get PGMA-Imi, PGMA-Tri and PGMA-ATri, respectively. The structure was confirmed by Fourier transform infrared spectroscopy (FT-IR), thermal properties were investigated by Thermogravimetric Analysis (TGA), and surface morphology was studied by scanning electron microscopy (SEM). Newly synthesized derivatives were further explored, for their antibacterial and anticandidal activities. RESULTS: All the three synthesized and characterized derivatives, displayed a significant activity against the tested microorganisms. The minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC), recorded against Staphylococcus aureus (S. aureus), was 0.5 &1mg/ml for PGMA-Imi, followed by PGMA-ATri & PGMA-Tri, respectively, followed by E. coli with, 1 & 2 mg/ml, 4 & 8 mg/ml, 4& 8 mg/ml, respectively, whereas the maximum MIC & MFC was recorded against C. albicans i.e., 8 & 16 mg/ml, 4 & 8 mg/ml ,4 & 8 mg/ml for PGMA-ATri, PGMA-Tri, PGMA-Imi, respectively. CONCLUSION: In the present work, we report on the state-of-the-art, azole functional polymer systems for antimicrobial applications. These findings suggest that the synthesized azole functional polymer films have antimicrobial properties, which could be potential candidates for coating applications in the biomedical and wastewater treatment field.

Silicone-based composite materials simulate breast tissue to be used as ultrasonography training phantoms.

A silicone-based composite breast phantom is fabricated to be used as an education model in ultrasonography training. A matrix of silicone formulations is tracked to mimic the ultrasonography and tactile response of human breast tissue. The performance of two different additives: (i) silicone oil and (ii) vinyl-terminated poly (dimethylsiloxane) (PDMS) are monitored by a home-made acoustic setup. Through the use of 75 wt% vinyl-terminated PDMS in two-component silicone elastomer mixture, a sound velocity of 1.29 ±â€¯0.09 × 103 m/s and an attenuation coefficient of 12.99 ±â€¯0.08 dB/cm-values those match closely to the human breast tissue-are measured with 5 MHz probe. This model can also be used for needle biopsy as well as for self-exam trainings. Herein, we highlight the fabrication of a realistic, durable, accessible, and cost-effective training platform that contains skin layer, inner breast tissue, and tumor masses.

Synthesis of chitosan nanoparticles, chitosan-bulk, chitosan nanoparticles conjugated with glutaraldehyde with strong anti-cancer proliferative capabilities.

In recent years, natural and synthetic polymers have attracted much attention due to their great potentials in medical science. In the present study, we have investigated the effect of chitosan-bulk (Ch-bulk), chitosan nanoparticles (ChNP), chitosan nanoparticles conjugated with glutaraldehyde (ChNP-GA) with an average size of 300-400 nm on human colorectal carcinoma cells (HCT-116) to examine their cytotoxic and anti-cancer abilities. We have evaluated the effects of Ch-bulk, ChNP, ChNP-GA on cancer cells by morphometric and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays respectively. Our results revealed that the Ch-bulk, ChNP, ChNP-GA decreased cell viability, cell proliferation and caused cell death in a concentration-dependent manner. Both morphometric and quantitative analyses confirmed that (Ch-bulk) and Chitosan nanoparticles (ChNP and ChNP-GA) induced concentration-dependent effects on the cancer cells. Among these three, ChNP-GA produced a more profound effect on the survivability with compared to each-bulk and Ch-NP treated groups. A dose of 2 mg/mL did not produced much effect on the cancer cell death, however, a dose of 4 mg/mL-6 mg/mL produced significant morphological changes like nuclear condensation and augmentation. Interestingly, a dose of 8 mg/mL produced significant cell death 48 hours post-treatment. In addition, during our morphometric analysis, we found that (Ch-bulk) and Chitosan nanoparticles (ChNP and ChNP-GA) treated cells underwent nuclear disintegration and fragmentation which lead to programmed cell death. Our studies demonstrate that the Ch-bulk, ChNP and ChNP-GA holds a great potential in the treatment of colon cancer.

Opioid Receptors Contribute to Antinociceptive Effect of Tianeptine on Colorectal Distension-Induced Visceral Pain in Rats.

Tianeptine is a clinically effective atypical antidepressant with distinct neurochemical properties. In this study, we aimed to investigate the contribution of opioid receptors in the antinociceptive effect of tianeptine on visceral pain in awake rats and to differentiate the subtype and the localization (central and/or peripheral) of these opioid receptors involved in this antinociception. Visceromotor response to noxious colorectal distension (CRD) was quantified with electromyographic recordings, obtained from previously implanted electrodes into the external oblique musculature of rats under anesthesia, before and after tianeptine administration. The opioid receptor antagonist naloxone hydrochloride (NLX) and peripherally restricted opioid receptor antagonist naloxone methiodide (NLXM) were administered intravenously 10 min before tianeptine (10 mg/kg, i.v.). The antinociceptive effect of tianeptine was abolished by NLX (1 and 2 mg/kg, i.v.), but was partially reduced by NLXM (1 and 2 mg/kg, i.v.). A µ-opioid receptor-selective dose (0.03 mg/kg, i.v.) of NLX, but not NLXM, significantly inhibited the antinociceptive effect of tianeptine. Our results suggest that antinociceptive effect of tianeptine on CRD-induced visceral nociception in rats involves the activation of both central and peripheral opioid receptors.

Protective effects of dietary omega-3 fatty acid supplementation on organophosphate poisoning.

In this study, we aimed to study the possible preventive effect of docosahexaenoic acid (DHA), a dietary omega-3 fatty acid, on toxicity caused by chlorpyrifos (CPF). Six groups of Sprague Dawley rats (200-250 g) consisting of equal numbers of males and females (n = 8) were assigned to study. The rats were orally given for 5 days. The control group was administered pure olive oil, which was the vehicle for CPF. The CPF challenge groups were administered oral physiological saline, pure olive oil, or DHA (50, 100 and 400 mg/kg dosages) for 5 days. The animals were weighed on the sixth day and then administered CPF (279 mg/kg, subcutaneously). The rats were weighed again 24 h following CPF administration. The body temperatures and locomotor activities of the rats were also measured. Blood samples, brain and liver tissues were collected for biochemical, histopathological and immunohistochemical examinations. A comparison with the control group demonstrated that CPF administration increased malondialdehyde (MDA) levels in blood, brain and liver, while it reduced catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) concentrations ( p < 0.05-0.001). Advanced oxidation protein products (AOPPs) increased only in the brain ( p < 0.001). DHA reduced these changes in MDA and AOPP values ( p < 0.05-0.001), while it increased CAT, SOD and GPx concentrations ( p < 0.05-0.001). Similarly, DHA prevented the decreases in body weight, body temperature and locomotor activities caused by CPF at 100 mg/kg and 400 mg/kg dosages ( p < 0.05-0.001). Similar to the physiological and biochemical changes, the histopathological damage scores, which increased with CPF ( p < 0.05-0.01), decreased at all three dosages of DHA ( p < 0.05-0.01). Our findings suggest that DHA, by supporting the antioxidant mechanism, reduces toxicity caused by CPF.

Some Novel Mannich Bases of 5-(3,4-Dichlorophenyl)-1,3,4-oxadiazole-2(3H)-one and Their Anti-Inflammatory Activity.

Non-steroidal anti-inflammatory drugs (NSAIDs), which are widely used for the treatment of rheumatic arthritis, pain, and many different types of inflammatory disorders, cause serious gastrointestinal (GI) side effects. The free carboxylic acid group existing on their chemical structure is correlated with GI toxicity related with all routine NSAIDs. Replacing this functional group with the 1,3,4-oxadiazole bioisostere is a generally used strategy to obtain an anti-inflammatory agent devoid of GI side effects. In the present work, a novel group of 5-(3,4-dichlorophenyl)-1,3,4-oxadiazole-2(3H)-one Mannich bases were synthesized and characterized on the basis of IR, 1 H NMR, and elemental analysis results. The target compounds were first tested for cytotoxicity to determine a non-toxic concentration for anti-inflammatory screening. Anti-inflammatory effects of the compounds were evaluated by in vitro lipopolysaccharide (LPS)-induced NO production and in vivo carrageenan footpad edema with ulcerogenic profile. In LPS-induced RAW 264.7 macrophages, most of the compounds showed inhibitory activity on nitrite production while compounds 5a, 5h, and 5j exhibited the best profiles by suppressing the NO production. To evaluate the in vivo anti-inflammatory potency of the compounds, the inflammatory response was quantified by increment in paw size in the carrageenan footpad edema assay. The anti-inflammatory data scoring showed that compounds 5a-d, 5g, and 5j, at the dose of 100 mg/kg, exhibited anti-inflammatory activity, which for compound 5g was comparable to that of the reference drug indomethacin with 53.9% and 55.5% inhibition in 60 and 120 min, respectively.