Genipin versus Ferric Chloride cross-linked unmodified Gum Arabic/Chitosan/nano-Hydroxyapatite nanocomposite hydrogels as potential scaffolds for bone regeneration.

Ferric chloride (FeCl3) and Genipin were utilized as cross-linkers to create two types of nanocomposite hydrogels through physical and covalent cross-linking methods, respectively. The hydrogels were composed of unmodified Gum Arabic (GA), Chitosan (Ch), and natural nano-Hydroxyapatite (nHA) using an acrylic acid solvent. Both the natural nHA and the FeCl3 vs. genipin cross-linked GA/Ch/nHA nano-composite hydrogels were prepared and characterized using various in vitro and in vivo analysis techniques. The use of FeCl3 and genipin cross-linkers resulted in the formation of novel hydrogels with compressive strengths of (15.43-22.20 MPa), which are comparable to those of natural cortical bone. In vivo evaluation was conducted by creating calvarial defects (6 mm) in Sprague-Dawley male rats. The results showed the formation of new, full-thickness bone at the implantation sites in all groups, as evidenced by digital planar tomography and histological staining with Hematoxylin and Eosin stain (H & E). Additionally, the use of genipin as a cross-linker positively affected the hydrogel's hydrophilicity and porosity. These findings justify further investigation into the potential of these nanocomposite hydrogels for bone regeneration applications.

Regional Variations in Pesticide Residue Detection Rates and Concentrations in Saudi Arabian Crops.

There is a scarcity of evidence on the levels of pesticide residues among common crops grown in the different regions of the Kingdom of Saudi Arabia (KSA). The present study aims to fill this gap. We collected samples across four regions of KSA (N = 41 from the west, N = 146 from the central, N = 131 from the north and N = 74 samples from the east). Food samples were extracted and cleaned using the modified quick, easy, cheap, effective, rugged and safe (QuEChERS) methodology. Tandem mass (LC-MS/MS and GC-MS/MS) was used to detect pesticide residues. The highest pesticide residue detection rate was 89.7% in the central region, followed by 88.5% in the north, 83.8% in the east and 70.7% in the western region (p = 0.01). Pesticide residue detection rates were significantly higher in fruits than vegetables (p = 0.02). Cypermethrin detection was most common overall, particularly in the Western region (p = 0.002), and pyraclostrobin concentration was the highest among all residues investigated. In conclusion, high detection rates of moderately hazardous pesticide residues were found in various crops across regions in KSA. Routine biomonitoring programs across KSA regions should be implemented, as well as public health campaigns to decrease pesticide residue consumption and exposure.

Hydrothermally reinforcing hydroxyaptatite and bioactive glass on carbon nanofiber scafold for bone tissue engineering.

As a bone tissue engineering scaffold, the objective of this study was to design hierarchical bioceramics based on an electrospun composite of carbon nanofibers (CNF) reinforced with hydroxyapatite (HA) and bioactive glasses (BGs) nanoparticles. The performance of the nanofiber as a scaffold for bone tissue engineering was enhanced by reinforcing it with hydroxyapatite and bioactive glass nanoparticles through a hydrothermal process. The influence of HA and BGs on the morphology and biological properties of carbon nanofibers was examined. The prepared materials were evaluated for cytotoxicity in vitro using the water-soluble tetrazolium salt assay (WST-assay) on Osteoblast-like (MG-63) cells, and oste-ocalcin (OCN), alkaline phosphatase (ALP) activity, total calcium, total protein, and tar-trate-resistant acid phosphatase (TRAcP) were measured. The WST-1, OCN, TRAcP, total calcium, total protein, and ALP activity tests demonstrated that scaffolds reinforced with HA and BGs had excellent in vitro biocompatibility (cell viability and proliferation) and were suitable for repairing damaged bone by stimulating bioactivity and biomarkers of bone cell formation.

Fentanyl analog structure-activity relationships demonstrate determinants of diverging potencies for antinociception and respiratory depression.

Opioid overdoses, particularly those involving fentanyl-related substances (FRS), present a significant public health challenge in the United States. This structure-activity relationship (SAR) study evaluated the relationship between the chemical structure of seventeen FRS and their in vivo mu-opioid-receptor (MOR) mediated effects. SAR evaluations included fluorine substitutions on the aniline or phenethyl ring and variations in N-acyl chain length. Adult male Swiss Webster mice were administered fluorinated regioisomers of fentanyl, butyrylfentantyl and valerylfentanyl, and compared to MOR standards including morphine, buprenorphine, and fentanyl to determine if they would elicit prototypical opioid-like effects including hyperlocomotion (open-field test), antinociception (warm-water tail-withdrawal test), and hypoventilation (whole-body plethysmography test). To determine if the MOR was the pharmacological mechanism responsible for these effects, naltrexone or naloxone pretreatments were administered to evaluate their actions on FRS-induced antinociception and hypoventilation. There were three main findings. First, FRS elicited hyperlocomotion, antinociception, and hypoventilation in mice to varying degrees, similar to prototypical MOR standards. Second, the rank order of potencies for hypoventilatory effects of FRS were different for each series including FRS with increasing N-acyl chain length (i.e., acetylfentanyl, fentanyl, butyrylfentanyl, valerylfentanyl, hexanoylfentanyl), phenethyl-fluorinated regioisomers (e.g., 2'-fluorofentanyl, 3'-fluorofentanyl, 4'-fluorofentanyl), and aniline-fluorinated regioisomers (e.g., ortho-fluorofentanyl, meta-fluorofentanyl, para-fluorofentanyl). Third, the degree of separation in potencies observed for the antinociceptive and hypoventilatory effects of these drugs did not always follow that which was observed for their antinociceptive and hyperlocomotor effects. This study clarifies the in vivo activities for these FRS and elucidates a SAR for MOR-mediated effects among structural isomers.

Bioavailability of Orally Administered Drugs in Critically Ill Patients.

Critically ill patients managed in the Intensive Care Unit (ICU) suffer from several pathophysiological alterations due to critical illness resulting in potential changes in the pharmacokinetics of drugs including systemic absorption. Nevertheless, these patients are still given some medications in unadjusted doses thereby putting the patients at a risk for therapy failure. The objective for this study was to summarize the available evidence regarding oral drug absorption in the ICU. A literature search of the databases MEDLINE, EMBASE, and PubMed was conducted on (February 24, 2020). Articles discussing the rate and/or extent of orally administered drugs in critically ill patients were included. A total of 58 studies were found: 17 interventional studies, 33 observational studies (30 prospective, 3 retrospective) and 8 case reports. A total of 43 articles reported altered drug absorption in critically ill patients suggesting the need for alternative measures to facilitate treatment success. The absorption of orally administered drugs may be altered in critically ill patients. Measures for altered drug absorption in critically ill patients were suggested such as holding tube feeding before and after medication administration, increasing doses of orally administrated drugs and using alternate routes of administration.

Cytosolic Sodium Influx in Mesophyll Protoplasts of Arabidopsis thaliana, wt, sos1:1 and nhx1 Differs and Induces Different Calcium Changes.

The sodium influx into the cytosol of mesophyll protoplasts from Arabidopsis thaliana cv. Columbia, wild type, was compared with the influx into sos1-1 and nhx1 genotypes, which lack the Na+/H+ antiporter in the plasma membrane and tonoplast, respectively. Changes in cytosolic sodium and calcium concentrations upon a 100 mM NaCl addition were detected by use of epifluorescence microscopy and the sodium-specific fluorescent dye SBFI, AM, and calcium sensitive Fura 2, AM, respectively. There was a smaller and mainly transient influx of Na+ in the cytosol of the wild type compared with the sos1-1 and nhx1 genotypes, in which the influx lasted for a longer time. Sodium chloride addition to the protoplasts' medium induced a significant increase in cytosolic calcium concentration in the wild type at 1.0 mM external calcium, and to a lesser extent in nhx1, however, it was negligible in the sos1-1 genotype. LiCl inhibited the cytosolic calcium elevation in the wild type. The results suggest that the salt-induced calcium elevation in the cytosol of mesophyll cells depends on an influx from both internal and external stores and occurs in the presence of an intact Na+/H+ antiporter at the plasma membrane. The Arabidopsis SOS1 more effectively regulates sodium homeostasis than NHX1.

Novel Magnetic Mixed Cellulose Acetate Matrix Membranes with Oxygen-Enrichment Potential.

This work presents novel magnetic mixed cellulose-based matrix membranes that combine the advantages of a low-cost common polymer matrix, such as cellulose acetate (CA), and a low-cost magnetic filler. Moreover, the presented magnetic mixed CA matrix membranes were fabricated and used without applying an external magnetic field during either the membrane casting or the separating process. Poly(methylmethacrylate) and lithium chloride were used in order to improve the mechanical properties and porosity of the fabricated membranes. The iron-nickel magnetic alloys used were prepared through a simple chemical reduction method with unique morphologies (Fe10Ni90-starfish-like and Fe20Ni80-necklace-like). The novel magnetic mixed CA matrix membranes fabricated were characterized using different analysis techniques, including SEM, EDX, XRD, TGA, and FTIR-ATR analyses. Furthermore, the static water contact angle, membrane thickness, surface roughness, tensile strength, and membrane porosity (using ethanol and water) were determined. In addition, vibrating sample magnetometer (VSM) analysis was conducted and the oxygen transition rate (OTR) was studied. The magnetic mixed CA matrix membrane containing starfish-like Fe10Ni90 alloy was characterized by high coercivity (109 Oe) and an efficient 1.271 × 10-5 cm3/(m2·s) OTR compared to the blank CA membrane with 19.8 Oe coercivity and no OTR. The effects of the polymeric matrix composition, viscosity, and compatibility with the alloys/fillers used on the structure and performance of the fabricated mixed CA matrix membranes compared to the previously used poly(ethersufone) polymeric matrix are discussed and highlighted. The novel magnetic mixed CA matrix membranes presented have good potential for use in the oxygen-enrichment process.

Novel magnetic iron-nickel/poly(ethersulfone) mixed matrix membranes for oxygen separation potential without applying an external magnetic field.

This work presents novel magnetic mixed matrix poly(ethersulfone) (PES) membranes that combine the advantages of low-cost common PES polymer and low-cost iron-nickel magnetic alloys. Moreover, the presented magnetic mixed matrix PES membranes were fabricated and used without applying an external magnetic field during either the membrane casting or the separating process. The fabricated magnetic membranes were prepared using the phase inversion technique and N-methylpyrrolidone and N,N-Dimethylformamide solvents mixture with volumetric ratio 1:9 and Lithium chloride as an additive. The used iron-nickel magnetic alloys were prepared by a simple chemical reduction method with unique morphologies (Fe10Ni90; starfish-like and Fe20Ni80; necklace-like). The fabricated membranes were characterized using Scanning Electron Microscope (SEM) and Scanning-Transmission Electron Microscope (STEM) imaging, energy dispersive X-ray (EDX), Thermogravimetric (TGA), and X-ray diffraction (XRD). Also, static water contact angle, membrane thickness, surface roughness, membrane porosity, membrane tensile strength as well as Vibrating Sample Magnetometer (VSM) analysis and oxygen transition rate (OTR) were determined. Moreover, the effect of alloy concentration and using Lithium chloride as an additive on the properties of the fabricated blank PES and magnetic mixed matrix PES membranes were studied. The presented novel magnetic mixed matrix PES membranes have high coercivity up to 106 (emu/g) with 3.61 × 10-5 cm3/cm2·s OTR compared to non-oxygen permeable blank PES membranes. The presented novel magnetic mixed matrix PES membranes have good potential in (oxygen) gas separation.

A generalized framework for elliptic curves based PRNG and its utilization in image encryption.

In the last decade, Elliptic Curves (ECs) have shown their efficacy as a safe fundamental component in encryption systems, mainly when used in Pseudorandom Number Generator (PRNG) design. This paper proposes a framework for designing EC-based PRNG and maps recent PRNG design techniques into the framework, classifying them as iterative and non-iterative. Furthermore, a PRNG is designed based on the framework and verified using the National Institute of Standards and Technology (NIST) statistical test suite. The PRNG is then utilized in an image encryption system where statistical measures, differential attack measures, the NIST statistical test suite, and system key sensitivity analysis are used to demonstrate the system's security. The results are good and promising as compared with other related work.

Unmodified Gum Arabic/Chitosan/Nanohydroxyapatite Nanocomposite Hydrogels as Potential Scaffolds for Bone Regeneration.

In this work, physical cross-linking was used to create nanocomposite hydrogels composed of unmodified gum arabic (GA), chitosan (Ch), and natural nanohydroxyapatite (nHA), using an acrylic acid (AA) solvent. Different GA/chitosan contents (15%, 25%, and 35% of the used AA) as well as different nHA contents (2, 5, and 10 wt.%), were used and studied. The natural nHA and the fabricated GA/Ch/nHA nanocomposite hydrogels were characterized using different analysis techniques. Using acrylic acid solvent produced novel hydrogels with compressive strength of 15.43-22.20 MPa which is similar to that of natural cortical bone. The addition of natural nHA to the hydrogels resulted in a significant improvement in the compressive strength of the fabricated hydrogels. In vitro studies of water absorption and degradation-and in vivo studies-confirmed that the nanocomposite hydrogels described here are biodegradable, biocompatible, and facilitate apatite formation while immersed in the simulated body fluid (SBF). In light of these findings, the GA/Ch/nHA nanocomposite hydrogels are recommended for preparing bioactive nanoscaffolds for testing in bone regeneration applications.

Sex-Specific Catabolic Metabolism Alterations in the Critically Ill following High Dose Vitamin D.

Pharmacological interventions are essential for the treatment and management of critical illness. Although women comprise a large proportion of the critically ill, sex-specific pharmacological properties are poorly described in critical care. The sex-specific effects of vitamin D3 treatment in the critically ill are not known. Therefore, we performed a metabolomics cohort study with 1215 plasma samples from 428 patients from the VITdAL-ICU trial to study sex-specific differences in the metabolic response to critical illness following high-dose oral vitamin D3 intervention. In women, despite the dose of vitamin D3 being higher, pharmacokinetics demonstrated a lower extent of vitamin D3 absorption compared to men. Metabolic response to high-dose oral vitamin D3 is sex-specific. Sex-stratified individual metabolite associations with elevations in 25(OH)D following intervention showed female-specific positive associations in long-chain acylcarnitines and male-specific positive associations in free fatty acids. In subjects who responded to vitamin D3 intervention, significant negative associations were observed in short-chain acylcarnitines and branched chain amino acid metabolites in women as compared to men. Acylcarnitines and branched chain amino acids are reflective of fatty acid B oxidation, and bioenergesis may represent notable metabolic signatures of the sex-specific response to vitamin D. Demonstrating sex-specific pharmacometabolomics differences following intervention is an important movement towards the understanding of personalized medicine.

Local Autograft Versus Iliac Crest Bone Graft PSF-Augmented TLIF in Low-Grade Isthmic and Degenerative Lumbar Spondylolisthesis.

STUDY DESIGN: Prospective randomized controlled cohort study. OBJECTIVE: To compare the outcome of local autograft versus iliac crest bone graft (ICBG) stand-alone transforaminal lumbar interbody fusion (TLIF) in lumbar spondylolisthesis. METHODS: One hundred eight patients with low-grade single-level spondylolisthesis underwent operation with pedicular screw fixation (PSF)-augmented stand-alone TLIF. Patients were randomly divided into groups according to bone graft: group I, autograft group; and group II, ICBG group, with 54 patients each. Fifty-nine patients had isthmic spondylolisthesis and 49 had degenerative spondylolisthesis. Clinical outcome parameters included Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), and patient's satisfaction, while the radiological parameters included fusion rate, slip reduction, segmental angle, and disc height. The mean follow-up period was 38 ± 19 months, with a minimum 24 of months. RESULTS: The preoperative VAS of back pain improved from 8 ± 3.1 to 3.4 ± 2.9 and from 8 ± 3.2 to3.6 ± 2.6 in group I and group II, respectively. The preoperative ODI improved from 41.4 ± 8 to 12.3 ± 7 and from 39 ± 9 to 13 ± 8 in group I and group II, respectively. The fusion rate was 93% in group I and 94.5% in group II. The percentage of slip was reduced from 26.7 ± 7.1% to 16.5 ± 6.1% in group I and from 27.4 ± 8.25 to 15.8 ± 5.2% in group II. Intervertebral disc height increased from 25.27 ± 14.62 to 46.38 ± 15.41 in group I and from 22.29 ± 13.72 to 45.15 ± 16.77 in group II. Segmental angle improved from 10.5 ± 8.1° to 16.7 ± 5.4° in group I and from 11.6 ± 5.3° to 15.9 ± 6.2° in group II. There was no significant difference of the above-mentioned parameters between the 2 groups. CONCLUSION: Patients with single-level low-grade spondylolisthesis can be effectively treated with PSF-augmented stand-alone TLIF using either local autograft or ICBG with no outcome differences between the 2 groups.

Respiratory depressant effects of fentanyl analogs are opioid receptor-mediated.

Opioid-related fatalities involving synthetic opioids have reached unprecedented levels. This study evaluated the respiratory depressant effects of seven fentanyl analogs that have either emerged in the illicit drug supply or been identified in toxicological analyses following fatal or non-fatal intoxications. Adult male Swiss Webster mice were administered fentanyl analogs (isobutyrylfentanyl, crotonylfentanyl, para-methoxyfentanyl, para-methoxybutyrylfentanyl, 3-furanylfentanyl, thiophenefentanyl, and benzodioxolefentanyl) and their effects on minute volume as compared to mu-opioid receptor (MOR) agonist standards (fentanyl, morphine, and buprenorphine) were measured using whole body plethysmography (WBP). All drugs elicited significant (p ≤ 0.05) hypoventilation relative to vehicle for at least one dose tested: morphine (1, 3.2, 10, 32 mg/kg), buprenorphine, (0.032, 0.1, 0.32, 1, 3.2 mg/kg), fentanyl (0.0032, 0.01, 0.032, 0.1, 1, 32 mg/kg), isobutyrylfentanyl (0.1, 0.32, 1, 3.2, 10 mg/kg), crotonylfentanyl (0.1, 0.32, 1, 3.2, 10 mg/kg), para-methoxyfentanyl (0.1, 0.32, 1, 3.2, 10 mg/kg), para-methoxybutyrylfentanyl (0.32, 1, 3.2, 10 mg/kg), 3-furanylfentanyl (0.1, 0.32, 1, 3.2, 10 mg/kg), thiophenefentanyl (1, 3.2, 10, 32, 100 mg/kg), and benzodioxolefentanyl (3.2, 10, 32, 100 mg/kg). The ED50 values for hypoventilation showed a rank order of potency as follows: fentanyl (ED50 = 0.96 mg/kg) > 3-furanylfentanyl (ED50 = 2.60 mg/kg) > crotonylfentanyl (ED50 = 2.72 mg/kg) > para-methoxyfentanyl (ED50 = 3.31 mg/kg) > buprenorphine (ED50 = 10.8 mg/kg) > isobutyrylfentanyl (ED50 = 13.5 mg/kg) > para-methoxybutyrylfentanyl (ED50 = 16.1 mg/kg) > thiophenefentanyl (ED50 = 18.0 mg/kg) > morphine (ED50 = 55.3 mg/kg) > benzodioxolefentanyl (ED50 = 10,168 mg/kg). A naloxone pretreatment (10 mg/kg) attenuated the hypoventilatory effects of all drugs. These results establish that the respiratory depressant effects of these fentanyl analogs are at least in part mediated by the MOR.

Bone Health Assessed by Calcaneal Quantitative Ultrasound among Cohort of Pregnant Egyptian Women.

AIM: The aim was to assess the risk of osteopenia and osteoporosis and to identify possible risk factors affecting bone density (BD) during pregnancy as parity, body mass index (BMI), Vitamin D, and calcium supplementation using quantitative ultrasound (QUS) of the calcaneus among first- and third-trimester pregnant women. METHODS: It is a case-control study conducted at Ain Shams Maternity Hospital, Egypt, from May 7 to December 14, 2015. One hundred and thirty-two women in the third trimester and 33 matched controls in the first trimester were screened for BD at the calcaneus by QUS. Stiffness index (SI), QUS-T, and Z scores were measured. RESULTS: Comparing both the groups regarding QUS-T score, Z score, and SI showed a statistically significant difference between both groups. Third-trimester participants had lower scores (-0.72 ± 1.0, -0.63 ± 0.99, and 88.53 ± 14.81, respectively) compared to their matched controls (1.05 ± 0.89, 1.16 ± 0.91, and 113.79 ± 12.49, respectively). According to QUS-T scores, 82 women (62.1%) in the third-trimester group were assessed as having normal BD, whereas 47 women (35.6%) were at risk of being osteopenic and 3 women (2.3%) were at risk of being osteoporotic. All women of the first trimester were assessed as having normal BD. Logistic regression was performed to identify possible risk factors affecting BD among third-trimester patients. BMI was the only statistically significant predictor for changes in bone health in those women (P = 0.001, odds ratio: 0.857, 95% confidence interval: 0.786-0.936). CONCLUSION: With one-unit rise in BMI, a 14% reduction in risk of decreased bone health is obtained.

Iron-Nickel Alloy with Starfish-like Shape and Its Unique Magnetic Properties: Effect of Reaction Volume and Metal Concentration on the Synthesized Alloy.

Iron-nickel alloy is an example of bimetallic nanostructures magnetic alloy, which receives intensive and significant attention in recent years due to its desirable superior ferromagnetic and mechanical characteristics. In this work, a unique starfish-like shape of an iron-nickel alloy with unique magnetic properties was presented using a simple, effective, high purity, and low-cost chemical reduction. There is no report on the synthesis of such novel shape without complex precursors and/or surfactants that increase production costs and introduce impurities, so far. The synthesis of five magnetic iron-nickel alloys with varying iron to nickel molar ratios (10-50% Fe) was undertaken by simultaneously reducing Fe(II) and Ni(II) solution using hydrazine hydrate as a reducing agent in strong alkaline media for 15 min at 95-98 °C. The effect of reaction volume and total metal concentration on the properties of the synthesized alloys was studied. Alloy morphology, chemical composition, crystal structure, thermal stability, and magnetic properties of synthesized iron-nickel alloys were characterized by means of SEM, TEM, EDX, XRD, DSC and VSM. ImageJ software was used to calculate the size of the synthesized alloys. A deviation from Vegard's law was recorded for iron molar ration higher than 30%., in which superstructure phase of FeNi3 was formed and the presence of defects in it, as well as the dimensional effects of nanocrystals. The saturation magnetization (Ms), coercivity (Hc), retentivity (Mr), and squareness are strongly affected by the molar ratio of iron and nickel and reaction volume as well as the total metal concentration.

Feasibility and Safety of Goel-Harms Posterior C1-C2 Fusion in the Management of Pediatric Reducible Atlantoaxial Instability.

BACKGROUND: Pediatric atlantoaxial instability (AAI) is not common and could be a serious clinical condition. The Goel-Harms technique is one of the most used techniques in adults and needs more evaluation in pediatric populations. This study reports the feasibility and safety of the Goel-Harms technique in the treatment of pediatric reducible AAI. METHODS: In this retrospective cohort study we reported all pediatric patients who underwent Goel-Harms technique for AAI with a minimum 1-year follow up. Patients were clinically assessed using the Japanese Orthopedic Association (JOA) score and radiologically with plain radiographs, computed tomography scan, and magnetic resonance imaging of the craniocervical region. Postoperatively, patients were followed up according to our clinical and radiographic imaging protocol. The following parameters were recorded: JOA score, construct stability, fusion, and abnormal events. RESULTS: A total of 25 patients have completed a 1-year follow-up and fulfilled our criteria. The mean age was 10.68 ± 4.47 (range, 3-17) years. Fifteen patients were male and 10 were female. The final diagnosis included Down syndrome (DS) in 8, type II dens fracture in 7, os odontoideum in 3, and atlantoaxial rotatory fixation in 7. The mean follow-up was 21.76 ± 8.22 months. The preoperative JOA score improved from 15.96 ± 1.46 to 16.76 ± 1.92 at the last follow-up. Sound bone fusion was reported in 92% of patients. CONCLUSIONS: Our data suggest that the Goel-Harms technique is a safe, feasible, and effective procedure in managing pediatric reducible AAI. Special perioperative care should be offered to young AAI patients with DS.

Novel promising reproductive and metabolic effects of Cicer arietinum L. extract on letrozole induced polycystic ovary syndrome in rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Chickpea was used in both greek and indian traditional medicine for hormonal related conditions as menstrual induction, acceleration of parturation, treatment of retained placenta and stimulation of lactation. Chickpea (Cicer arietinum) sprout isoflavone isolates exhibited reasonable estrogenic activities. Isoflavones, a subtype of phytoestrogens, are plant derivatives with moderate estrogenic activity that tend to have protective effects on hormonal and metabolic abnormalities of women with polycystic ovary syndrome (PCOS). AIM OF THE STUDY: In this study, we investigated the effect of UPLC/ESI-MS characterized Cicer arietinum L. seeds ethanol extract (CSE) on ovarian hormones, oxidative response and ovarian histological changes on induced PCOS rat model. MATERIALS AND METHODS: Thirty-five rats were divided into five groups including negative control, PCOS, and treatment groups. PCOS was induced using letrozole (1 mg/kg) daily orally for 21 days. Each treatment group was treated with one of the following for 28 days after induction of PCOS: clomiphene citrate (1 mg/kg), and CSE at 250 and 500 mg/kg. Ovaries and uteri were excised, weighed and their sections were used for quantitative real-time reverse transcriptase polymerase chain reaction, antioxidant assays and histomorphometric study of the ovaries. The antioxidant assays, histopathological examination, hormonal and metabolic profiles, and Cyp11a1(steroidogenic enzyme) mRNA expression were measured. RESULTS: In all treatment groups, ovarian weight was significantly decreased despite having no significant effect on uterine weight. Histomorphometric study in the treatment groups revealed a significant decrease in the number and diameter of cystic follicles, a significant increase in granulosa cell thickness while, thickness of theca cells was significantly decreased when compared to PCOS. Hormone levels, metabolic profile and antioxidant status were improved in the treatment groups. Moreover, Cyp11a1 mRNA expression was significantly downregulated in the treatment groups compared to PCOS. CONCLUSIONS: In the current study, CSE enhanced the reproductive and metabolic disorders which were associated with PCOS induction. For the first time, we have highlighted the effect of CSE in treating PCOS and its associated manifestations.

Preparation and Characterization of a Novel Poly(vinylidene fluoride-co-hexafluoropropylene)/Poly(ethersulfone) Blend Membrane Fabricated Using an Innovative Method of Mixing Electrospinning and Phase Inversion.

In this work, a novel polymeric membrane was innovated in terms of composition and preparation techniques. A blend of poly(vinylidene fluoride-co-hexafluoropropylene) (PcH) and poly(ethersulfone) (PES) (18 wt.% total polymer concentration) was prepared using a N-methylpyrrolidone (NMP) and N, N-Dimethylformamide (DMF) solvents mixture, while Lithium chloride (0.05-0.5 wt.%) was used as an additive. The electrospinning and phase inversion techniques were used together to obtain a novel membrane structure. The prepared membranes were characterized using scanning electron microscope imaging, energy dispersive X-Ray, differential scanning calorimeter, thermogravimetric analysis, and Fourier transfer infrared spectroscopy-attenuated total reflectance analyses. Moreover, the static water contact angle, membrane thickness, porosity, surface roughness as well as water vapor permeability were determined. ImageJ software was used to estimate the average fiber diameter. Additionally, the effect of the change of PcH concentration and coagulation bath temperature on the properties of the fabricated membrane was studied. The novel developed membrane has shown a good efficiency in terms of properties and features, as a membrane suitable for membrane distillation (MD); a high porosity (84.4% ± 0.6), hydrophobic surface (136.39° ± 3.1 static water contact angle), and a water vapor permeability of around 4.37 × 10-5 g·m/m2·day·Pa were obtained. The prepared membrane can be compared to the MD membranes commercially available in terms of properties and economic value.

In-Vitro Cytotoxicity Study: Cell Viability and Cell Morphology of Carbon Nanofibrous Scaffold/Hydroxyapatite Nanocomposites.

Electrospun carbon nanofibers (CNFs), which were modified with hydroxyapatite, were fabricated to be used as a substrate for bone cell proliferation. The CNFs were derived from electrospun polyacrylonitrile (PAN) nanofibers after two steps of heat treatment: stabilization and carbonization. Carbon nanofibrous (CNF)/hydroxyapatite (HA) nanocomposites were prepared by two different methods; one of them being modification during electrospinning (CNF-8HA) and the second method being hydrothermal modification after carbonization (CNF-8HA; hydrothermally) to be used as a platform for bone tissue engineering. The biological investigations were performed using in-vitro cell counting, WST cell viability and cell morphology after three and seven days. L929 mouse fibroblasts were found to be more viable on the hydrothermally-modified CNF scaffolds than on the unmodified CNF scaffolds. The biological characterizations of the synthesized CNF/HA nanofibrous composites indicated higher capability of bone regeneration.

Modulation of steroidogenesis by Actaea racemosa and vitamin C combination, in letrozole induced polycystic ovarian syndrome rat model: promising activity without the risk of hepatic adverse effect.

BACKGROUND: Complementary remedies such as the Chinese herb 'Sheng Ma' (Black cohosh; Actaea racemosa 'AR') are being sought to overcome the shortcomings of conventional hormonal and surgical therapies developed for the treatment of polycystic ovary syndrome (PCOS). However, AR-induced hepatotoxicity necessitates a cautionary warning to be labeled on its products as recommended by the United States Pharmacopeia, where four out of seven hepatotoxic cases in Sweden were possibly associated with black cohosh products. METHODS: We investigated the effects, safety, and molecular targets of black cohosh ethanolic extract and/or vitamin C on ovarian functionality and oxidative response in hyperandrogenism-induced PCOS rats. A well-established rat model using oral letrozole, daily, for 21 days was employed. The rats then received the AR extract with and without vitamin C for 28 days. The hormonal evaluation, antioxidant status, histopathological examination, immunohistochemical analysis, cell proliferation, and the expression ratio of the aromatase (Cyp19α1) gene were evaluated. Additionally, holistic profiling of the AR arsenal of secondary metabolites was performed using ultra-high-performance liquid chromatography (UHPLC) coupled with quadrupole high-resolution time of flight mass spectrometry (QTOF-MS). RESULTS: Beneficial effects were exerted by AR in PCOS rats as antioxidant status, hormonal profile, lipid profile, glucose level, liver functions, and the induced Ki-67 expression in the granulosa, theca cell layers and interstitial stromal cells were all improved. Notably, the combination of AR with vitamin C was not only more effective in reversing the dysregulated levels of testosterone, luteinizing hormone, and mRNA level of Cyp19α1 gene in the PCOS rat, but also safer. The combination regulated both ovarian and hepatic malondialdehyde (MDA) and glutathione (GSH) levels with histological improvement observed in the liver and ovaries. In addition, the untargeted metabolomic profiling enabled the identification of 61 metabolites allocated in five major chemical classes. CONCLUSION: This study demonstrated the benefit of the combinatorial effects of AR and vitamin C in mitigating the reproductive and metabolic disorders associated with PCOS with the elimination of AR hepatotoxic risk.