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.

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.

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.

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.

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.

Application of thorium-normalized airborne radiospectrometric survey data of Wadi Araba area, North-eastern Desert, Egypt, as a guide to the recognition of probable subsurface petroleum accumulations.

A new exploration method has been developed by Saunders et al. (Geophysics 58(10) (1993) 1417) using surface and aerial gamma-ray spectral measurements in prospecting for petroleum in stratigraphic and structural traps. Wadi Araba area, North-eastern Desert, Egypt, was selected to apply this method on its recorded aerial gamma-ray spectrometric survey data, due to its distinct stratigraphic and structural setting as well as its situation in close connection with the Gulf of Suez, which represents one of the important sites of oil production in Egypt. The three variables (eU, eTh, and K) registered for the whole study area, in the form of three contour maps, were digitized along the flight paths every 1.0 km. The DRAD arithmetic means plus three standard deviations for the data set were computed. Any single profile value greater than this quantity should have a probability of 99.87% that it represents a valid anomaly and is not caused by random variations in the background values. The use of these criteria has identified one flight line which has a valid anomaly that is not caused by random variations in the background values. This might indicate a prospective possibility for petroleum accumulation in the Wadi Araba area. North-eastern Desert, Egypt.