Transdermal application of diacerin loaded-terpene enriched invasomes: an approach to augment anti-edema and nociception inhibition activity.

This study aimed to formulate diacerein loaded terpene-enriched invasomes (DCN-TINV) to fulfill a fruitful management of osteoarthritis. A 23 factorial design was adopted, including A: cholesterol concentration (%w/v), B: ethanol volume (mL) and C: phosphatidylcholine: drug ratio as the studied factors. Invasomes were constructed using the thin film hydration technique. Herein, percent entrapment efficiency (EE%), particle size (PS), poly-dispersity index (PDI) and zeta potential (ZP) were statistically analyzed using Design-Expert® software to select the optimum formula. The selected criteria for detecting the optimum formula were restricting PS (<350 nm), dismissing PDI, magnifying ZP (as absolute value) and EE%. The selected formula was further scrutinized through multiple in-vitro studies, including Fourier-transform infrared spectroscopy, differential scanning calorimetry, pH measurement, stability study, release profile and transmission electron microscopy. Furthermore, the ex-vivo performance was evaluated through ex-vivo skin permeation and deposition. Finally, it was subjected to an array of in-vivo tests, namely Draize test, histopathology, In-vivo skin penetration, edema size, and nociception inhibition measurements. The optimum formula with desirability (0.913) demonstrated EE% (89.21% ± 2.12%), PS (319.75 ± 10.11 nm), ZP (-55 ± 3.96 mV) and a prolonged release profile. Intriguingly, revamped skin permeation (1143 ± 32.11 µg/cm2), nociception inhibition (77%) and In-vivo skin penetration (144 µm) compared to DCN suspension (285 ± 21.25 µg/cm2, 26% and 48 µm, respectively) were displayed. The optimum DCN-TINV exhibited plausible safety and stability profiles consolidated with auspicious efficacy for better management of osteoarthritis.

Capped flexosomes for prominent anti-inflammatory activity: development, optimization, and ex vivo and in vivo assessments.

This study aimed to formulate diacerein (DCN)-loaded flexosomes for enhanced efficacy against osteoarthritis. A 23 D-optimal design was employed, investigating the impact of surfactant type (A), surfactant concentration (%w/v) (B), and oleylamine amount (mg) (C). Flexosomes were formulated using a rotary evaporator, and Design-Expert® software was utilized to statistically analyze entrapment efficiency (EE%), zeta potential (ZP), poly-dispersity index (PDI), and particle size (PS) to determine the optimum formula. The selection criteria prioritized increased ZP (as absolute value) and EE%, coupled with decreased PDI and PS. Rigorous physicochemical, in vivo, and ex vivo tests were conducted to validate the safety, stability, and activity of the optimal formula. Physicochemical assessments encompassed pH measurement, transmission electron microscopy, differential scanning calorimetry, release profiles, storage effects, and Fourier transform infrared spectroscopy. In vivo tests included permeation studies, histopathology, anti-inflammatory activity, and skin irritancy, while ex vivo tests focused on permeation parameters and skin deposition. The optimum formula demonstrated high desirability (0.931), along with favorable EE% (90.93%), ZP (- 40.4 mV), particle size (188.55 nm), and sustained behavior. Notably, improved in vivo permeation (132 µm), skin deposition (193.43 µg/cm2), and antinociceptive activity (66%) compared to DCN suspension (48 µm, 66.31 µg/cm2, and 26%, respectively) were observed. The optimal formula also exhibited excellent safety and storage characteristics. In conclusion, DCN-loaded flexosomes exhibit significant potential for effectively managing osteoarthritis.

Radiometric characteristics of some metallic ores and nonmetallic deposits: an example, Wadi Al-Allaqi, South Eastern Desert, Egypt.

Hydrothermal alteration processes are connected to many mineral formations, particularly auriferous deposits. In this study, airborne gamma-ray spectrometry (GRS) data and the analysis of radioactive materials (eU, eTh, and K) are applied to search for regions with hydrothermal alteration activity. An example is presented from Wadi Al-Allaqi, South Eastern Desert, Egypt. GRS was used to analyse various radiometric data to address potential mineral deposit areas, to map regions potentially showing metallic ore mineralisation, and to point out new geological mineral resources. The Kd (potassium deviation), "F" parameter and Th-normalisation of the K and eU anomalies were calculated, and locating new exploratory targets in the study area that exhibit high F-parameter, Kd, and K/eTh values was recommended. Additionally, the research region has a few isolated enriched spots of (K). Therefore, GRS data was used to characterise and estimate potential metallic ores, nonmetallic deposits, and gold ore zones associated with the alteration zones. Results show that most of the known mineral deposits and gold occurrences in the area, according to the metallogenic map of Egypt, are located in zones with a ratio value of (0.25-0.30) (K%/(U or Th ppm)) maps which may suggest a moderate degree of alteration. Also, most mineral deposits and gold occurrences are found in intermediate altered zones, or K-enriched sites, with a Kd% of (0.2. The work represents an attempt to map hydrothermal alteration zones associated with mineral deposits in the Wadi Al-Allaqi area. Generally, natural radiation characteristics and attributes suggest criteria that can be used globally for regional mineral exploration.

Neuroprotective effect of curcumin against experimental autoimmune encephalomyelitis-induced cognitive and physical impairments in mice: an insight into the role of the AMPK/SIRT1 pathway.

Multiple sclerosis (MS) is an incurable chronic neurodegenerative disease where autoimmunity, oxidative stress, and neuroinflammation collaboration predispose myelin sheath destruction. Interestingly, curcumin, a natural polyphenol, showed a neuroprotective effect in numerous neurodegenerative diseases, including MS. Nevertheless, the influence of curcumin against MS-induced cognitive impairment is still vague. Hence, we induced experimental autoimmune encephalomyelitis (EAE) in mice using spinal cord homogenate (SCH) and complete Freund's adjuvant, which eventually mimic MS. This study aimed not only to evaluate curcumin efficacy against EAE-induced cognitive and motor dysfunction, but also to explore a novel mechanism of action, by which curcumin exerts its beneficial effects in MS. Curcumin (200 mg/kg/day) efficacy was evaluated by behavioral tests, histopathological examination, and biochemical tests. Concisely, curcumin amended EAE-induced cognitive and motor impairments, as demonstrated by the behavioral tests and histopathological examination of the hippocampus. Interestingly, curcumin activated the adenosine monophosphate (AMP)-activated protein kinase/silent mating type information regulation 2 homolog 1 (AMPK/SIRT1) axis, which triggered cyclic AMP response element-binding protein/brain-derived neurotrophic factor/myelin basic protein (CREB/BDNF/MBP) pathway, hindering demyelination of the corpus callosum. Furthermore, AMPK/SIRT1 activation augmented nuclear factor erythroid 2-related factor 2 (Nrf2), a powerful antioxidant, amending EAE-induced oxidative stress. Additionally, curcumin abolished EAE-induced neuroinflammation by inhibiting Janus kinase 2 /signal transducers and activators of transcription 3 (JAK2/STAT3) axis, by various pathways, including AMPK/SIRT1 activation. JAK2/STAT3 inhibition halts inflammatory cytokines synthesis. In conclusion, curcumin's neuroprotective effect in EAE is controlled, at least in part, by AMPK/SIRT1 activation, which ultimately minimizes EAE-induced neuronal demyelination, oxidative stress, and neuroinflammation.

Synthesis of 1,2,4-triazole and 1,3,4-oxadiazole derivatives as inhibitors for STAT3 enzymes of breast cancer.

Disubstituted five-membered heterocycles (1,2,4-triazole and 1,3,4 oxadiazole) were synthesized and investigated as inhibitors for signal transducer and activator of transcription 3 (STAT3) enzyme of breast cancer. 3-(Benzylthio)-5-(4-chlorobenzyl)-4H-1,2,4-triazol-4-amine (12d) was found to be the most active among the synthesized compounds with a half-maximal inhibitory concentration (IC50 ) value of 1.5 µM on MCF7 cells and was found to show a great inhibitory effect on the STAT3 enzyme. Compounds 9a,b,d,e,f, 11, and 12a,b,f,e show IC50 values in the range of 3-12 µM for the MCF7 cell line. Molecular modeling was used to investigate the biological results of the synthesized compounds.

Experimental and DFT study of photocatalytic activity of reduced graphene oxide/copper sulfide composite for removal of organic dyes from water.

In this work, successful nanocomposites composed of different ratios of reduced graphene oxide and copper sulphide (xCuS-rGO) were fabricated to aid in treating water contaminated with organic dyes. XRD, TEM, SEM, XPS, IR, EDX and BET were applied for the characterization of (CuS-rGO). The photocatalytic strength of the prepared nanocomposites was evaluated using artificial sunlight irradiation. The nanocomposites were tested for their ability to degrade both anionic and cationic organic dyes, including amaranth and rhodamine B (RhB). The excellent photocatalytic strength of our composites, relative to pristine CuS and rGO, was interpreted as rGO sheets being very porous. In addition, the charge moved efficiently from rGO to CuS. The combined properties enhanced the efficiency of photodegradation of CuS-rGO composite across the dyes under the illumination of simulated sunlight. The electron transportation from rGO sheets to the CuS conduction band enhances the charge separation and transportation. The role of superoxide radicals in photocatalytic degradation was unveiled and the interactions between the studied dyes and our catalysts were investigated by density functional theory study and scavenging investigation. This work gives new ideas about the preparation and properties of (CuS-rGO) composites and their broad application in solving environmental problems.

Clinical, radiological profile and prognostic role of transcranial color-coded duplex in cerebral venous thrombosis: a case-control study.

BACKGROUND: Cerebral venous thrombosis is a rare type of stroke, occurring more among young individuals. The presentation is highly variable, and this can delay diagnosis and management, thereby affecting outcome. The aim is to study the clinical, radiological profile, risk factors for cerebral venous thrombosis (CVT) and the role of transcranial color-coded duplex (TCCD) in CVT prognosis among Egyptian patients. METHODS: Eighty CVT patients and 80 normal healthy individuals were included. Magnetic resonance imaging, magnetic resonance venography, and genetic thrombophilia tests were done for patients. Deep cerebral venous system was evaluated using B-mode transcranial color-coded duplex (TCCD) for both groups. RESULTS: Showed female predominance with gender specific risk factors being the most common etiology. The most common hereditary thrombophilia was homozygous factor V Leiden mutation and anti-thrombin III (AT III). Headache was the most common presentation. Forty-three patients had transverse sinus thrombosis. Regarding TCCD, there was an increase in mean blood flow velocities, peak flow velocities and end diastolic flow velocities in deep middle cerebral vein and basal veins in CVT group compared to control group. There was a positive correlation not reaching statistical significance between flow velocities in the deep venous system and modified Rankin Scale. CONCLUSION: Clinical presentation is extremely variable. In our population, homozygous factor V Leiden mutation and AT III deficiency were the most common. Increased deep cerebral venous system flow velocities using TCCD in patients with CVT reflect their venous hemodynamic state.

Cerebrovascular reactivity after functional activation of the Brain using Photic Stimulation in Migraine and Tension Type Headache: a transcranial doppler Ultrasonography Study.

BACKGROUND: Previous studies in headache patients measured the cerebrovascular reactivity (CVR) in response to photic stimulation but they have yielded contradictory results. The purpose of study was to measure CVR of both migraine and chronic tension headache (TTH) patients in response to photic stimulation. METHODS: The study included 37 migraineurs and 24 chronic TTH patients compared with 50 age- and sex-matched healthy volunteers. Peak systolic, end diastolic, mean flow velocities and CVR (PSV, EDV, MFV, and CVR) were measured using TCD ultrasonography of the middle, anterior, posterior cerebral and vertebral arteries (MCA, ACA, PCA, and VA) before and after 100 s of 14 Hz photic stimulation. RESULTS: A three-way repeated measures ANOVA interaction with main factors of Vessels (MCA, ACA, PCA, VA), Time (pre-post photic) and Groups (migraine, TTH, and control group) revealed significant 3-way interactions for measures of PSV (P = 0.012) and MFV (P = 0.043). In the migraine patients there was significantly higher PSV, EDV, and MFV in the MCA, ACA, and PCA after photic stimulation compared with baseline. The CVR of the MCA was also significantly higher in migraineurs than controls. In the TTH group, there was significantly higher PSV, EDV, and MFV (P = 0.003, 0.012, 0.002 respectively) in the VA after photic stimulation than at baseline. The CVR was significantly higher in the VA of TTH patients than controls. CONCLUSION: Compared with controls after photic stimulation, the higher CVR of the MCA in migraineurs and of the VA in TTH patients could be used as diagnostic tool to differentiate between the two types of headaches.

Semaglutide, a novel glucagon-like peptide-1 agonist, amends experimental autoimmune encephalomyelitis-induced multiple sclerosis in mice: Involvement of the PI3K/Akt/GSK-3ß pathway.

Multiple sclerosis (MS) is a disabling neurodegenerative disease that causes demyelination and axonal degeneration of the central nervous system. Current treatments are partially effective in managing MS relapses and have a negligible impact on treating MS cognitive deficits and cannot enhance neuronal remyelination, imposing a need for a new MS remedy. Semaglutide, a novel glucagon-like peptide-1 agonist, has recently displayed a neuroprotective effect on several neurodegenerative diseases, suggesting that it may have a protective effect in MS. Therefore, this study was conducted to investigate the influence of semaglutide on experimental autoimmune encephalomyelitis (EAE)-induced MS in mice. Here, EAE was induced in mice using spinal cord homogenate, which eventually altered the mice's cognitive and motor functions, similar to what is observed in MS. Interestingly, intraperitoneally administered semaglutide (25 nmol/kg/day) amended EAE-induced cognitive and motor deficits observed in novel object recognition, open field, rotarod, and grip strength tests. Moreover, histological examination revealed that semaglutide treatment attenuated hippocampal damage and corpus callosum demyelination caused by EAE. Additionally, biochemical testing revealed that semaglutide activates the PI3K/Akt axis, which eventually hampers GSK-3ß activity. GSK-3ß activity inhibition attenuates demyelination and triggers remyelination through CREB/BDNF; furthermore, it boosts Nrf2 and SOD levels, protecting the mice from EAE-induced oxidative stress. Additionally, GSK-3ß inhibition minimizes neuroinflammation, as reflected by decreased NF-kß and TNF-α levels. In conclusion, semaglutide has a neuroprotective effect in EAE-induced MS in mice, which is mediated by activating the ramified PI3K/Akt/GSK-3ß pathway.

Using of airborne gamma-ray spectrometric data to the exposure of potassic alteration -recognition of alteration relates to gold mineralization.

It is well known that many mineral deposits are related to hydrothermal processes, especially auriferous deposits. In this research paper, we show how to distinguish areas that have experienced hydrothermal activity, by construing airborne gamma-ray spectrometry data, especially potassium. An indirect application of aerial gamma-ray spectrometry technique is used to detect possible minerals deposits. In this region, an airborne gamma ray survey (K, eU and eTh) was carried out, based on irregular K, "F" parameter -, and Th-normalized of the K and eU anomalies. This work exhibits the mapping of hydrothermal regions possibly showing gold mineralization and the pointing out of new geological portions for this sequence, establishing prospective criteria for regional mineral exploration. We can suggest a new exploratory target, the area that is located next to Jabal Al-Ardiya (white colour on ternary map), which is characterized by high values of F-parameter, KD%, and K/eTh. Besides, enriched areas are found scattered in the north-eastern side of the study area. As result, the airborne gamma ray spectromertic data, might be used for estimation of prospective Gold Ore zones associated with the potassium alteration."

Cerebrovascular function in tension-type headache and migraine with or without aura: Transcranial Doppler study.

The aim of the current study was to determine whether tension-type headache (TTH) and migraine with or without aura have altered anterior and posterior circulation compared with normal volunteers as assessed by Transcranial Doppler (TCD) ultrasonography. The study included 24 patients with chronic TTH and 37 patients with migraine (16 with aura and 21 without aura) classified according to the diagnostic criteria of the International Headache Society 2018. They were compared with a control group of 50 age- and sex-matched healthy volunteers. Each participant was examined with TCD ultrasonography of the middle, anterior and posterior cerebral and vertebral arteries (MCA, ACA, PCA, and VA) at rest. Patients in the TTH group had a significantly lower peak systolic velocity (PSV) and mean flow velocity (MFV) in the MCA compared with controls, whereas EDV and MFV in the ACA were significantly higher in the migraine without aura group than controls. Within the 3 groups of patients, the TTH group had significantly lower PSV in the MCA and PCA than the group of migraine with aura. In addition, the TTH group had significantly lower PSV and MFV in the MCA and a lower EDV in the VA than migraine patients without aura. In conclusion, the possibility of cerebrovascular changes is confirmed in the present study in both TTH and migraine without aura. The former has a low MFV in the MCA whereas the latter has a high MFV in the ACA.

Antifungal Activities of Sulfur and Copper Nanoparticles against Cucumber Postharvest Diseases Caused by Botrytis cinerea and Sclerotinia sclerotiorum.

Nanoparticles (NPs) have attracted great interest in various fields owing to their antimicrobial activity; however, the use of NPs as fungicides on plants has not been sufficiently investigated. In this study, the antifungal activities of sulfur nanoparticles (S-NPs) and copper nanoparticles (Cu-NPs) prepared by a green method were evaluated against Botrytis cinerea and Sclerotinia sclerotiorum. The formation of NPs was confirmed by transmission electron microscopy (TEM) and X-ray diffraction analysis (XRD). The antifungal activities of NPs (5-100 µg/mL), CuSO4 (4000 µg/mL), and micro sulfur (MS) were compared to those of the recommended chemical fungicide Topsin-M 70 WP at a dose of 1000 µg/mL. They were evaluated in vitro and then in vivo at different temperatures (10 and 20 °C) on cucumber (Cucumis sativus) fruits. The total phenolic content (TPC) and total soluble solids (TSS) were determined to study the effects of various treatments on the shelf life of cucumber fruits, compared to untreated cucumber as a positive control. The diameters of S-NPs and Cu-NPs ranged from 10 to 50 nm, and 2 to 12 nm, respectively. The results revealed that S-NPs exhibited the highest antifungal activity, followed by Cu-NPs. However, CuSO4 showed the lowest antifungal activity among all treatments. The antifungal activity of the prepared NPs increased with the increase in NP concentration, while the fungal growth was less at low temperature. The cytotoxicity of the prepared NPs was evaluated against the WI-38 and Vero cell lines in order to assess their applicability and sustainability. S-NPs caused less cytotoxicity than Cu-NPs.

New Bioactive Fused Triazolothiadiazoles as Bcl-2-Targeted Anticancer Agents.

A series of 3-(6-substituted phenyl-[1,2,4]-triazolo[3,4-b]-[1,3,4]-thiadiazol-3-yl)-1H-indoles (5a-l) were designed, synthesized and evaluated for anti-apoptotic Bcl-2-inhibitory activity. Synthesis of the target compounds was readily accomplished through a reaction of acyl hydrazide (1) with carbon disulfide in the presence of alcoholic potassium hydroxide to afford the corresponding intermediate potassium thiocarbamate salt (2), which underwent cyclization reaction in the presence of excess hydrazine hydrate to the corresponding triazole thiol (3). Further cyclisation reaction with substituted benzoyl chloride derivatives in the presence of phosphorous oxychloride afforded the final 6-phenyl-indol-3-yl [1,2,4]-triazolo[3,4-b]-[1,3,4]-thiadiazole compounds (5a-l). The novel series showed selective sub-micromolar IC50 growth-inhibitory activity against Bcl-2-expressing human cancer cell lines. The most potent 6-(2,4-dimethoxyphenyl) substituted analogue (5k) showed selective IC50 values of 0.31-0.7 µM against Bcl-2-expressing cell lines without inhibiting the Bcl-2-negative cell line (Jurkat). ELISA binding affinity assay (interruption of Bcl-2-Bim interaction) showed potent binding affinity for (5k) with an IC50 value of 0.32 µM. Moreover, it fulfils drug likeness criteria as a promising drug candidate.

Quinazoline-tethered hydrazone: A versatile scaffold toward dual anti-TB and EGFR inhibition activities in NSCLC.

Globally, lung cancer and tuberculosis are considered to be very serious and complex diseases. Evidence suggests that chronic infection with tuberculosis (TB) can often lead to lung tumors; therefore, developing drugs that target both diseases is of great clinical significance. In our study, we designed and synthesized a suite of 14 new quinazolinones (5a-n) and performed biological investigations of these compounds in Mycobacterium tuberculosis (MTB) and cancer cell lines. In addition, we conducted a molecular modeling study to determine the mechanism of action of these compounds at the molecular level. Compounds that showed anticancer activity in the preliminary screening were further evaluated in three cancer cell lines (A549, Calu-3, and BT-474 cells) and characterized in an epidermal growth factor receptor (EGFR) binding assay. Cytotoxicity in noncancerous lung fibroblast cells was also evaluated to obtain safety data. Our theoretical and experimental studies indicated that our compounds showed a mechanism of action similar to that of erlotinib by inhibiting the EGFR tyrosine kinase. In turn, the antituberculosis activity of these compounds would be produced by the inhibition of enoyl-ACP-reductase. From our findings, we were able to identify two potential lead compounds (5i and 5l) with dual activity and elevated safety toward noncancerous lung fibroblast cells. In addition, our data identified three compounds with excellent anti-TB activities (compounds 5i, 5l, and 5n).

Quinazolinone dimers as a potential new class of safer Kv1 inhibitors: Overcoming hERG, sodium and calcium channel affinities.

The discovery of more selective and safer voltage-gated potassium channel blockers is an extremely demanding approach. Designing selective Kv1.5 inhibitors is very challenging as only limited data is available on this target due to a lacking crystal structure for this ion channel receptor. Herein, we synthesized a series of 21 novel quinazolinone dimers 3a-i, 5a-i and 10a-c. We tried to avoid structural features responsible for non-selectivity and for most potassium channel blockers' side effects in our design. In contrast to other works, which lack investigation over wide ranges of potassium and sodium channels, we screened the inhibitory activity of our synthesized compounds over multiple voltage-gated potassium channels, including six different human Kv1 channel subtypes Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv1.5 and Kv1.6 channels as well as Kv2.1, Kv3.1, Kv4.3, Kv7.2, Kv7.3, Kv10.1, hERG, and Shaker IR. Moreover, these compounds' selectivity was investigated on sodium channels Nav1.2, Nav1.4 and Nav1.5 and calcium channels Cav3.1-Cav3.3. The results revealed two compounds (3a and 3e) with low micromolar Kv1.5 inhibition activity with EC50 values of 5.1 ± 0.9 µM and 12.5 ± 1.1 µM, respectively. However, at higher concentrations, they also showed inhibitory activity on Kv1.3 and Kv1.1 channels. This might be due to structural similarities between these three Kv1 channel isoforms. Compound 3a shows a slight preference for Kv1.5. Interestingly, they lack any activity on other potassium channels (including hERG), sodium channels, and calcium channels. Our findings recommend quinazolinone dimers with ethylene linker as a potential new class of safer Kv1 inhibitors and a good start for designing more selective and potent Kv1.5 inhibitors.

One pot synthesis of new cross-linked chitosan-Schiff' base: Characterization, and anti-proliferative activities.

Four novel chitosan hydrogels were successfully synthesized through the cross-linking reaction of chitosan with different concentrations of ethyl 5-(3,5-dihydroxy-1,4-dioxan-2-yl)-2-methylfuran-3-carboxylate. Their structures were confirmed by Fourier transform infrared spectroscopy (FT-IR), 13C Cross polarization magic angle spinning nuclear magnetic resonance spectroscopy (CP/MAS 13C NMR), ultraviolet-visible spectroscopy, thermogravimetric analysis (TGA, DTA), and X-ray diffraction (XRD). Cytotoxicity on hepatocellular carcinoma (HepG-2) cell line and a normal African green monkey kidney (Vero) cell line were studied using the MTT assay. The resultant hydrogels showed a good inhibitory effect comparing to the un-modified parent; the hydrogels with the lowest degree cross-linking (0.125 and 0.25 mol cross-linker per one chitosan residue) showed potent anticancer activity in the HepG2 cells with IC50 of 57.9 and 80.9 µg/ml, respectively. These results show that the newly synthesized cross-linked chitosan derivatives demonstrated more selectivity to the HepG2 than the Vero cells, indicating its potential for Investigation in the cure of hepatocellular carcinoma.

Diffusion tensor imaging of corpus callosum in adolescent females with borderline personality disorder.

OBJECTIVES: The aim of this study was to assess the structural alteration of corpus callosum (CC) in adolescent females with Borderline Personality Disorder (BPD) and detect the relationship between these changes and BPD symptoms. METHODS: A comparative case control study was conducted on 50 adolescent females that were divided into 2 groups; 25 outpatients suffering from BPD (according to DSM-IV-TR diagnostic criteria) compared to 25 healthy adolescents. All subjects were assessed by Borderline Personality Questionnaire, Barratt impulsivity scale-11, Brief Non-Suicidal Self-Injury Assessment tool, Beck Scale for Suicidal Ideation, and Diffusion tensor imaging. RESULTS: Relative to control subjects, BPD patients had significantly lower fractional anisotropy (FA) values in the genu and lower mean diffusivity (MD) values in the body of CC. There was a negative correlation between FA values in the genu and body of CC and impulsivity. MD in the body of CC was positively correlated with motor impulsiveness and negatively correlated with suicidality. CONCLUSION: Adolescent females with BPD show structural alterations in the CC that are related to symptoms of emotional dysregulation and impulsivity.

In vitro biological activities and in vivo hepatoprotective role of brown algae-isolated fucoidans.

Brown seaweeds are rich in polysaccharides, such as fucoidan (FUC) which has shown beneficial effects in several medical conditions. The aim of the present study was to assess the antioxidant, anti-inflammatory, and hepatoprotective properties of Colpomenia sinuosa- and Sargassum prismaticum-isolated FUC in vitro and in vivo. The hot acid extraction method was used to isolate FUC from C. sinuosa (FCS) and S. prismaticum (FSP) species. The antioxidant, anticancer, as well as the effect on neurotransmitter-degrading enzyme and disaccharidase activities were measured using standard protocols. Moreover, the hepatoprotective effect of two FCS doses (100 and 200 mg/kg) on paracetamol-administered rats (one dose of 1 g/kg) were evaluated by measuring blood liver function markers, hepatic pro-oxidants as malondialdehyde (MDA) and nitric oxide (NO), antioxidants as glutathione (GSH) and glutathione peroxidase (GPx), proinflammatory markers as inducible nitric oxide synthase (iNOS), interleukin 1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and liver histology. The crude fucoidan yield was 15.6% and 14.8% of C. sinuosa and S. prismaticum dry weights, respectively. The antioxidant effects and cytotoxic activity on hepatic cancer cell were higher for FCS than FSP. Moreover, in vivo data showed that FCS administration at both doses significantly improved liver functions and alleviated histological alterations, hepatic inflammation, and oxidative stress following paracetamol intake. In conclusion, fucoidan exerts anti-inflammatory, antidigestive enzyme activity, antioxidant, anticancer, and hepatoprotective effects.

Design, Synthesis and Evaluation of New Bioactive Oxadiazole Derivatives as Anticancer Agents Targeting Bcl-2.

A series of 2-(1H-indol-3-yl)-5-substituted-1,3,4-oxadiazoles, 4a-m, were designed, synthesized and tested in vitro as potential pro-apoptotic Bcl-2 inhibitory anticancer agents based on our previously reported hit compounds. Synthesis of the target 1,3,4-oxadiazoles was readily accomplished through a cyclization reaction of indole carboxylic acid hydrazide 2 with substituted carboxylic acid derivatives 3a-m in the presence of phosphorus oxychloride. New compounds 4a-m showed a range of IC50 values concentrated in the low micromolar range selectively in Bcl-2 positive human cancer cell lines. The most potent candidate 4-trifluoromethyl substituted analogue 4j showed selective IC50 values of 0.52-0.88 µM against Bcl-2 expressing cell lines with no inhibitory effects in the Bcl-2 negative cell line. Moreover, 4j showed binding that was two-fold more potent than the positive control gossypol in the Bcl-2 ELISA binding affinity assay. Molecular modeling studies helped to further rationalize anti-apoptotic Bcl-2 binding and identified compound 4j as a candidate with drug-like properties for further investigation as a selective Bcl-2 inhibitory anticancer agent.