Effect of autologous platelet-rich plasma on the fertility and quality of cryopreserved buffalo bull semen: a comparative study using OptiXcell® and tris egg yolk extenders.

BACKGROUND: Buffalo spermatozoa have a distinct membrane structure that makes them more vulnerable to cryopreservation, resulting in lower-quality post-thawed sperm. This decreases the success rate of artificial insemination in buffaloes. Understanding and addressing these specific vulnerabilities are essential for improving reproductive techniques in buffalo populations. The properties of cryopreserved buffalo bull semen were examined in this study regarding the impact of adding autologous platelet-rich plasma (PRP) to OptiXcell® or Tris egg yolk-based extenders. Ten buffalo bulls were used to collect semen. Each bull's ejaculate was separated into two main equal amounts, each of which was then diluted with either OptiXcell® or Tris egg yolk-based extender, supplemented with various PRP concentrations (5%, 10%, and 15%), and the control (0%), before being cryopreserved according to established protocols. Following equilibration and thawing, the quality and functionality of the sperm were evaluated, along with the antioxidant enzyme activities (GSH and TAC), malondialdehyde (MDA) content, and in vivo fertilization rate of the thawed semen. RESULTS: All PRP concentrations in both extenders, particularly 10% PRP, improved the quality and functionality of the sperm in both equilibrated and frozen-thawed semen. Additionally, the antioxidant enzyme activities in both extenders were higher in the PRP-supplemented groups compared to the control group in thawed semen (P < 0.05). All post-thaw sperm quality, antioxidant enzyme activities, and functionality aside from DNA integrity were higher (P < 0.05) in the PRP-supplemented OptiXcell® than in the PRP-supplemented Tris egg yolk-based extender. The fertility of cryopreserved semen in the extenders supplemented with 10% and 15% PRP increased (P < 0.05) significantly more than that of the control extenders, with 10% PRP being the optimum concentration in OptiXcell® (80%) compared to that of Tris egg yolk-based extender (66.67%) and control of two extenders (53.33% and 46.67%, respectively). CONCLUSIONS: Even though autologous PRP-supplemented extenders have a protective impact on equilibrated and cryopreserved semen, 10% PRP-supplemented OptiXcell® extenders are more effective at preserving post-thaw semen quality, functionality, and antioxidant capacity, which increases the in vivo fertility of buffalo bulls.

Rosemary and neem: an insight into their combined anti-dandruff and anti-hair loss efficacy.

Dandruff, a common scalp disorder characterized by flaking dead skin, is often treated with conventional topical products. However, limitations exist due to potential side effects and high costs. Therefore, searching for natural, cost-effective solutions for dandruff and hair loss is crucial. Rosemary herb and neem tree, both cultivated in Egypt, possess well-documented anti-inflammatory properties derived from their rich phenolic phytoconstituents. This study formulated a standardized combined extract of rosemary and neem (RN-E 2:1) into hair gel and leave-in tonic formats. This extract demonstrated superior efficacy against Malassezia furfur (a causative agent of dandruff) and Trichophyton rubrum (associated with scalp disorders) compared to the conventional antifungal agent, ketoconazole. The combined extract (RN-E 2:1) also exhibited potent anti-inflammatory activity. Additionally, the suppression of iNOS expression is considered concentration-dependent. Quality control verified formulation stability, and ex-vivo studies confirmed effective ingredient penetration into the epidermis, the primary site of fungal presence. Remarkably, both formulations outperformed the standard treatment, minoxidil in hair growth trials. These findings highlight the potential of natural extracts for scalp and hair health.

Evaluating estrus synchronization and early pregnancy detection in Ossimi sheep: The influence of fluorogestone acetate treatment duration and dosage.

Estrus synchronization is important for improving sheep reproduction. To enhance sheep reproduction efficiency, this study investigated the impact of different durations (7 vs. 14 days) and fluorogestone acetate (FGA) doses in intravaginal sponges on estrus synchronization and early pregnancy detection in Ossimi sheep. Two hundred ewes were evenly divided into two groups, each receiving a full 40 mg or a halved 20 mg FGA sponge for their respective durations. The study aimed to optimize breeding efficiency by examining the effectiveness of these treatments in synchronizing estrous cycles and by evaluating the use of serum levels of pregnancy-associated glycoprotein 1 (PAG1) and progesterone (P4) as markers for early pregnancy identification. Prostaglandin F2α and equine chorionic gonadotropin were administered to enhance the synchronization process. Results highlighted that the 7-day treatment protocol significantly improved estrus, pregnancy, and lambing rates compared to the 14-day protocol. Furthermore, pregnant ewes demonstrated elevated levels of PAG1 and P4, with PAG1 levels particularly higher in ewes with multiple pregnancies. The findings underscore that the shorter duration of FGA treatment is more effective for reproductive management in Ossimi sheep without significantly affecting PAG1 levels based on the dose or duration of FGA. PAG1 also proved to be a reliable marker for early pregnancy detection, offering a promising approach to identifying fetal numbers early in pregnancy. This research suggests optimizing FGA sponge use could be cost-efficient for improving reproductive efficiency and early pregnancy management in sheep.

PD-L1 Immunohistochemical Expression in Endometrial Carcinoma: Egyptian Cross-Sectional Study.

OBJECTIVE: Endometrial carcinoma (EC) is the most common cancer of the female genital tract. According to the recently evolved strategies of cancer immunotherapy, immune checkpoints inhibitors are one of the most crucial strategies. Programmed Death Ligand 1 (PD-L1) is an important immune checkpoint regulator. PD-L1 antibodies have shown efficacy in clinical trials of some malignancies. Some of these antibodies have been approved for clinical usage by the Food and Drug Administration (FDA). METHODS: This retrospective study included a total of 100 ECs, collected from archived, formalin-fixed, paraffin-embedded tissue blocks of hysterectomy specimens of Egyptian females. The samples were immunohistochemically analyzed for PD-L1 expression (in both tumor cells; TCs and tumor infiltrating leucocytes; TILs) by a semiquantitative score (0 to 4), with cutoff points of (0: <1% of the cells, 1: 1% to 4%, 2: 5% to 9%, 3: 10% to 49%, and 4: ≥ 50%). Membranous staining only was considered positive. RESULTS: PD-L1 was highly expressed in ECs (67% TCs+ and 61% TILs+), with statistically significant relationships with age, lympho-vascular space invasion (LVSI) and TILs score (P = 0.006, 0.016 and <0.005 respectively).  However, no statistically significant relationships were detected between PD-L1 expression and the following parameters: histological type, histological grade, pathological stage (pT) or FIGO stage, myometrial, cervical, adnexal/serosal, parametrial involvements and nodal metastasis, as well as ESMO risk stratification system. Moreover, statistically significant relationships were achieved when correlating TILs score with tumor grade and LVSI (P = 0.034 and 0.012 respectively). Also, comparing endometrial hyperplasia (EH) PD-L1 and TCs PDL1 median scores achieved statistically significant relationship (P = 0.001). CONCLUSION: Our results concluded that PD-L1 expression was greater in both TCs and TILs in a subgroup of patients that have advanced age, LVSI and are TILs-rich, identifying them as potential candidates for anti-PD-1/PD-L1 immunotherapy.

Nanotechnology in leukemia: diagnosis, efficient-targeted drug delivery, and clinical trials.

Leukemia is a group of malignant disorders which affect the blood and blood-forming tissues in the bone marrow, lymphatic system, and spleen. Many types of leukemia exist; thus, their diagnosis and treatment are somewhat complicated. The use of conventional strategies for treatment such as chemotherapy and radiotherapy may develop many side effects and toxicity. Hence, modern research is concerned with the development of specific nano-formulations for targeted delivery of anti-leukemic drugs avoiding toxic effects on normal cells. Nanostructures can be applied not only in treatment but also in diagnosis. In this article, types of leukemia, its causes, diagnosis as well as conventional treatment of leukemia shall be reviewed. Then, the use of nanoparticles in diagnosis of leukemia and synthesis of nanocarriers for efficient delivery of anti-leukemia drugs being investigated in in vivo and clinical studies. Therefore, it may contribute to the discovery of novel and emerging nanoparticles for targeted treatment of leukemia with less side effects and toxicities.

A novel lupene derivative from Thymus capitatus possesses an apoptosis-inducing effect via Let-7 miRNA/Cyclin D1/VEGF cascade in the A549 cell line.

Non-small-cell lung carcinoma (NSCLC) is a type of epithelial lung cancer accounting for about 85% of all lung cancers. In our research, a novel lupene derivative namely acetoxy-lup-5(6), 20(29)-diene (ALUP), as well as two known triterpenes; lupeol (LUP) and betulinic acid (BA) were isolated through the chromatographic purification of the 95% ethanolic extract of Thymus capitatus. Identification of the compounds was carried out by physicochemical properties as well as spectral 1D and 2D NMR analysis. The anti-cancer activity of the three triterpenes was assessed on non-small cell lung cancer cell line; A549 using MTT assay and cell cycle analysis using annexin V/propidium iodide. The molecular mechanism underlying anti-apoptotic effects was determined by analyzing Let-7 miRNA and miRNA-21 expression, the mRNA gene expression level of Bax, CASP-8, CD95, Bcl2, KRAS, VEGF, Cyclin D1 using qRT-PCR. Our results revealed that the three isolated compounds ALUP, LUP, and BA caused cell cycle arrest at the G2/M phase with an increase in the apoptosis which may be attributed to their significant effect on raising Bax, CASP-8, and CD95 and reducing the mRNA expression levels of Bcl-2, KRAS, VEGF, and Cyclin D1 compared to control cells. RT-PCR results showed that the ALUP, LUP, and BA significantly downregulated miRNA-21 expression. Meanwhile, the three compounds caused significant overexpression of Let-7 miRNA. This is the first report on the anti-cancer activity of acetoxy-lup-5(6), 20(29)-diene (ALUP) in reducing the proliferation and differentiation of the A549 cell line through inducing apoptosis. Finally, by targeting the Let-7 miRNA/Cyclin D1/VEGF cascade, acetoxy-lup-5(6), 20(29)-diene could be a potential therapeutic agent for lung cancer.

Moesin and Ezrin as New Promising Markers for Early Detection of Endometrial Carcinoma: An Immunohistochemical Study.

OBJECTIVE: the aim of this study is to evaluate immunohistochemically the expression of ezrin, and moesin, in endometrial lesion cases in order to detect EC at early stages which will have an important implication on the patients' outcome. METHOD: 100 stored, formalin-fixed, paraffin-embedded tissue blocks of endometrial curettage obtained due to abnormal uterine bleeding or postmenopausal bleeding were collected. Each paraffin block was re-cut by rotatory microtome at 4 µm thickness then mounted on a glass slide and stained by hematoxylin and eosin for routine histopathological examination and on charged slides for immunohistochemistry using an automated staining system (Dako autostainer link 48) with antibodies against Moesin and Ezrin. Cytoplasmic staining was evaluated for both Moesin and Ezrin based on the intensity and extent of staining and scored for each sample. RESULT: Both Moesin and Ezrin were significantly higher in atypical endometrial hyperplasia compared to benign hyperplasia and significantly higher in endometrial carcinoma compared to atypical hyperplasia. Moesin also significantly correlated with higher tumor grades while Ezrin was significantly higher in postmenopausal women denoting their role in tumor progression and poor prognosis. CONCLUSION: Both Moesin and Ezrin could be potentially used as predictive markers for endometrial carcinoma screening programmes as well as indicators for cancer progression.

Anti-Obesity Effect of a Tea Mixture Nano-Formulation on Rats Occurs via the Upregulation of AMP-Activated Protein Kinase/Sirtuin-1/Glucose Transporter Type 4 and Peroxisome Proliferator-Activated Receptor Gamma Pathways.

White, green, and oolong teas are produced from the tea plant (Camellia sinensis (L.) Kuntze) and are reported to have anti-obesity and hypolipidemic effects. The current study aims to investigate the anti-obesity effects of a tea mixture nano-formulation by targeting the AMPK/Sirt-1/GLUT-4 axis in rats. In vitro lipase and α-amylase inhibition assays were used to determine the active sample, which was then incorporated into a nanoparticle formulation subjected to in vivo anti-obesity testing in rats by measuring the expression level of different genes implicated in adipogenesis and inflammation using qRT-PCR. Moreover, metabolomic analysis was performed for each tea extract using LC/ESI MS/MS coupled to chemometrics in an attempt to find a correlation between the constituents of the extracts and their biological activity. The in vitro pancreatic lipase and α-amylase inhibition assays demonstrated more effective activity in the tea mixture than the standards, orlistat and acarbose, respectively, and each tea alone. Thus, the herbal tea mixture and its nanoparticle formulation were evaluated for their in vivo anti-obesity activity. Intriguingly, the tea mixture significantly decreased the serum levels of glucose and triglycerides and increased the mRNA expression of GLUT-4, P-AMPK, Sirt-1, and PPAR-γ, which induce lipolysis while also decreasing the mRNA expression of TNF-α and ADD1/SREBP-1c, thereby inhibiting the inflammation associated with obesity. Our study suggests that the tea mixture nano-formulation is a promising therapeutic agent in the treatment of obesity and may also be beneficial in other metabolic disorders by targeting the AMPK/Sirt-1/Glut-4 pathway.

Topoisomerase IIalpha (TopoIIa) A New Promising Marker for Early Detection of Laryngeal Squamous Cell Carcinoma: An Immunohistochemical Study.

OBJECTIVE: the aim of this study is evaluation of Topo IIa expression in laryngeal squamous cell carcinomas and correlation of this expression with various clinicopathological parameters. METHODS: ninety cases of laryngeal squamous cell carcinoma archived paraffin blocks were collected in the form of total laryngectomies. Each paraffin block was re-cut by rotatory microtome at 4 µm thickness and stained by hematoxylin and eosin for routine histopathological examination and on charged slides for immunohistochemistry using an automated staining system with antibodies against Topo IIa. Mainly nuclear and slightly cytoplasmic staining was considered positive. Percentage of positive Topo IIa cells was graded then grouped into low expression and overexpression. RESULTS: Topo IIa overexpression was seen in 91.1% of cases, while low expression was noticed in the remaining 8.9% of cases. There were statistically significant correlations between Topo IIa expression and tumor histological grade, lymph node metastasis and T stage as well as statistically significant positive correlation between Topo IIa expression as we progress from normal to dysplastic/in situ up to malignant transformation. CONCLUSION: High expression of Topo IIa may indicate more aggressive tumor and may play a role in tumorogenesis in laryngeal squamous cell carcinoma.

Effect of platelet-rich plasma (PRP) on post-thaw quality, kinematics and in vivo fertility of fertile and subfertile buffalo (Bubalus bubalis) spermatozoa.

This study investigated the effect of adding platelet-rich plasma (PRP) in semen extender prior cryopreservation on post-thaw quality, kinematics, and in vivo fertility of fertile and subfertile buffalo spermatozoa. Eleven buffalo bulls were classified based on their conception rate (CR) into fertile (n = 8, CR > 55%) and subfertile (n = 3, CR < 35%) groups. Ejaculates were collected with artificial vagina, pooled, and dispensed into 6 aliquots, diluted with Tris-egg yolk-glycerol extender supplemented with different proportions of PRP [0% (control), 5%, 10%, 15%, 20%, and 25%] followed by cryopreservation using standard procedures. Post-thaw sperm quality, kinematics, antioxidant activity, cryosurvival rate, and in vivo fertility were compared between fertile and subfertile groups and among proportions of PRP within each group. The results showed that 15% PRP greatly (P < 0.001) improved sperm characteristics, average path velocity, and curvilinear velocity of the subfertile group. Interestingly, 5%, 10%, and 15% PRP greatly (P < 0.001) reduced malondialdehyde content and improved enzymatic (glutathione peroxidase and superoxide dismutase) and total antioxidant capacity in fertile and subfertile groups. However, these three proportions of PRP significantly (P < 0.001) improved the cryosurvival rate of the subfertile group; only 15% PRP greatly improved CR of subfertile (60.83% vs. 34.17%) animals to be comparable with that of fertile ones treated with 5 (59.17%) and 10% (60.83%) PRP. In conclusion, adding 15% PRP to semen extender before cryopreservation is recommended to improve post-thaw quality, antioxidant activity, and in vivo fertility of buffalo semen particularly of the subfertile animals.

Comparative metabolite profiling of four polyphenol rich Morus leaves extracts in relation to their antibiofilm activity against Enterococcus faecalis.

Enterococci are a common cause of urinary tract infections. The severity of enterococcal infections is associated with their ability to form biofilms. Morus leaves are known as a natural antibacterial, however, their antibiofilm activity against Enterococcus remains unveiled. This study aimed to evaluate the ability of four polyphenol-rich Morus leaves extracts (Morus nigra, M. rubra, M. macroura, and M. alba) to inhibit biofilm formed by enterococcal clinical isolates in relation to their metabolic profiling. Results revealed that 48% of the isolates formed strong biofilm, 28% formed moderate biofilm, 20% formed weak biofilm, and only 4% did not form a biofilm. The strong biofilm-forming isolates were E. faecalis, and hence were chosen for this study. The antibiofilm activity of the four polyphenol-rich Morus leaves extracts revealed that the M. nigra extract exhibited the highest percentage of biofilm inhibition followed by M. rubra then M. macroura and the least inhibition was detected in M. alba, and these results were in accordance with the phenolic and flavonoid contents of each extract. UPLC-ESI-MS/MS identified 61 polyphenolic compounds in the four extracts. Further, multivariate analysis confirmed clear segregation of M. nigra from the other species suggesting disparity in its metabolome, with accumulation of flavonoids, anthocyanidins, phenolic acids and coumarin derivatives. Quercetin and kaempferol glycosides were found to be positively and significantly correlated to the antibiofilm activity. In conclusion, M. nigra ethanolic extracts showed the highest phenolic content and antibiofilm activity and they could be developed as a complementary treatment for the development of antimicrobial agents.

Immunohistochemical Expression of Programmed Death Ligand 1(PDL1) in Endometrial Carcinoma and Its Relation to CD4 and CD8 Positive Immune Cells.

OBJECTIVES: Endometrial cancer (EC) is the most common cancer of the female genital tract. Egypt showed a significant increase in incidence lately of which 25% were premenopausal. Advanced or recurrent disease are mostly unresectable and the traditional adjuvant therapy give modest results with devastating side effects. Late discoveries of immune checkpoint inhibitors have produced promising results. Programmed cell death 1 (PD1) is an immune inhibiting receptor on surface of lymphocytes, which plays critical roles in maintaining immunological self-tolerance. There are two ligands for this receptor, PDL1 and PDL2. PD-L1 is expressed on tumor cells; attaches to PD1, allowing tumor cells to escape from the host immune response. Its prognostic significance in various tumors is controversial and its significance in ECs has just begun to be investigated. Therefore, we investigated the relationship between PDL1 expression and different clinicopathologic parameters in EC cases and its correlation with CD4 and CD8 immune cells, in order to identify the predictive biomarkers for the outcome by immune therapy. METHODS: Hundred, paraffin tissue blocks of EC cases were collected and stained with antibodies against PDL1,CD4 and CD8. RESULTS: PDL1 was positive in 67% of cases in tumor cells and in 61% of cases in immune cells. CD4 and CD8 were expressed in 79% of cases. Statistically significant correlations were observed between PDL1 expression and patients mean age, LVSI, TILS score and CD4+/CD8+ expression. CONCLUSION: Those variables can stratify candidates who can benefit most from immunotherapy, or can be chosen for further high cost molecular investigations application.

Non-polar metabolites of green beans (Phaseolus vulgaris L.) potentiate the antidiabetic activity of mesenchymal stem cells in streptozotocin-induced diabetes in rats.

Green beans (Phaseolus vulgaris L.) are consumed as pods or mature seeds (common beans). The pods were extracted with 95% ethanol and processed to prepare non-polar and polar fractions. Comparing the antihyperglycemic activity of both fractions, non-polar fraction (NPF, 200 mg kg-1  day-1 ) lowered blood glucose in streptozotocin diabetic rats by 65% compared to 57% for the polar fraction at the same dose. When NPF treatment was combined with injection of mesenchymal stem cells (MSC) a 4.4-fold increase in serum insulin and a 73.6% reduction in blood glucose were observed compared to untreated control. Additionally, a significant decrease in malondialdehyde (76.2%), nitric oxide (68.2%), cholesterol (76.1%), and triglycerides (69.5%) and a 1.75-fold increase in HDL concentrations were observed in the group treated with this combination compared to diabetic animals. Interestingly, NPF increased homing of MSC in pancreas potentiating their antidiabetic activity. Finally, 26 compounds were identified in NPF using LC/MS analysis and four were isolated in pure form. The isolated compounds namely calotroproceryl acetate, fridelin, calotroproceryl A, and stigmasterol showed good inhibitory activity against pancreatic lipase with IC50 at 1.93, 1.07, 1.34 and 1.44-1 µg/ml, respectively. Additionally, these compounds inhibited α-amylase, albeit at higher concentration, with IC50 at 248, 212, 254, and 155 µg/ml for calotroproceryl acetate, fridelin, calotroproceryl A, and stigmasterol, respectively. Our results suggest that green beans extract can potentiate effect of MSC in diabetes directly due to its own antidiabetic effect and indirectly by increasing MSC homing in pancreatic tissues. PRACTICAL APPLICATIONS: It has been suggested in this study that green beans can improve hyperglycemia, oxidative balance in diabetes, so green beans can be promoted as a healthy nutrient for diabetic patients. Green beans also can enhance homing and differentiation of mesnchymal stem cells in the pancreas for future stem cell therapy of type I diabetes.

Polo-Like Kinase 1(PLK1) Immunohistochemical Expression in Triple Negative Breast Carcinoma: A Probable Therapeutic Target.

BACKGROUND: Breast cancer is the most commonly diagnosed female cancer and is a major cause of cancer-related deaths in women. Triple-negative breast cancer (TNBC) is defined as ER, PR and HER2 negative, which are characterized by rapid progression with low survival rates with limited therapeutic choices. Polo-like kinase 1 protein acts as a cell division regulator which is highly expressed in many tumors making it a potentially valuable target for antiproliferative therapies. In this study we tried to evaluate the value of this marker as a possible therapeutic target in TNBC. METHODS: This research studied the immunohistochemical expression of PLK1 done on 49 paraffin blocks of TNBC female patients and then correlated with the different clinicopathological parameters. RESULTS: Our results showed high PLK1 expression in 91.9% of cases. Most of the high grade tumors showed high PLK1 high score (76.9%). All cases showing lymph node metastasis showed high PLK1 expression, implying a statistically significant correlation between PLK1 expression and tumor grade as well as N stage. CONCLUSION: PLK1, although a negative prognostic factor, but is a promising therapeutic target for treating TNBC patients.

Phenolics from Physalis peruviana fruits ameliorate streptozotocin-induced diabetes and diabetic nephropathy in rats via induction of autophagy and apoptosis regression.

The objective of our study was to evaluate the effect of Physalis peruviana L. fruits in the management of diabetes and diabetic nephropathy in relation to its metabolic profile. In-vitro α-amylase, ß-glucosidase, and lipase inhibition activities were assessed for the ethanolic extract (EtOH) and its subfractions. Ethyl acetate (EtOAc) fraction showed the highest α-amylase, ß-glucosidase, and lipase inhibition effect. In vivo antihyperglycemic testing of EtOAc in streptozotocin (STZ)-induced diabetic rats showed that it decreased the blood glucose level, prevented the reduction in body weight, improved serum indicators of kidney injury (urea, uric acid, creatinine), and function (albumin and total protein). EtOAc increased autophagic parameters (LC3B, AMPK) and depressed mTOR contents. Histopathology revealed that EtOAc ameliorated the pathological features and decreased the glycogen content induced by STZ. The immunohistochemical analysis showed that EtOAc reduced P53 expression as compared to the STZ-diabetic group. UPLC-ESI-MS/MS metabolite profiling of EtOAc allowed the identification of several phenolic compounds. Among the isolated compounds, gallic acid, its methylated dimer and the glycosides of quercetin had promising α-amylase and ß-glucosidase inhibition activity. The results suggest that the phenolic-rich fraction has a protective effects against diabetic nephropathy presumably via enhancing autophagy (AMPK/mTOR pathway) and prevention of apoptosis (P53 suppression).

Downregulation of MMP1 expression mediates the anti-aging activity of Citrus sinensis peel extract nanoformulation in UV induced photoaging in mice.

Aging of the skin is a complicated bioprocess that is affected by constant exposure to ultraviolet irradiation. The application of herbal-based anti-aging creams is still the best choice for treatment. In the present study, Citrus sinensis L. fruit peels ethanolic extract (CSPE) was formulated into lipid nanoparticles (LNPs) anti-aging cream. Eight different formulations of CSEP-LNPs were prepared and optimized using 23 full factorial designs. In vivo antiaging effect of the best formula was tested in Swiss albino mice where photo-aging was induced by exposure to UV radiation. HPLC-QToF-MS/MS metabolic profiling of CSPE led to the identification of twenty-nine metabolites. CSPE was standardized to a hesperidin content of 15.53 ± 0.152 mg% using RP-HPLC. It was suggested that the optimized formulation (F7) had (245 nm) particle size, (91.065%) EE, and (91.385%) occlusive effect with a spherical and smooth surface. The visible appearance of UV-induced photoaging in mice was significantly improved after topical application on CSPE-NLC cream for 5 weeks, levels of collagen and SOD were significantly increased in CSPE- NLC group, while levels of PGE2, COX2, JNK, MDA, and elastin was reduced. Finally, The prepared anti-aging CSPE-NLC cream represents a safe, convenient, and promising skincare cosmetic product.

Cattleianal and Cattleianone: Two New Meroterpenoids from Psidium cattleianum Leaves and Their Selective Antiproliferative Action against Human Carcinoma Cells.

The Myrteacae family is known as a rich source of phloroglucinols, a group of secondary metabolites with notable biological activities. Leaves of Psidium cattleianum were extracted with chloroform: methanol 8:2 to target the isolation of phloroglucinol derivatives. Isolated compounds were characterized using different spectroscopic methods: nuclear magnetic resonance (NMR), ultra-violet (UV) and mass spectrometry (MS). Two new phloroglucinols were evaluated for cytotoxicity against a panel of six human cancer cell lines, namely colorectal adenocarcinoma cells (HT-29 and HCT-116); hepatocellular carcinoma cells (HepG-2); laryngeal carcinoma (Hep-2); breast adenocarcinoma cells (MCF7 and MDA-MB231), in addition to normal human melanocytes HFB-4. Additionally, cell cycle analysis and annexin-V/FITC-staining were used to gain insights into the mechanism of action of the isolated compounds. The new phloroglucinol meroterpenoids, designated cattleianal and cattleianone, showed selective antiproliferative action against HT-29 cells with IC50's of 35.2 and 32.1 µM, respectively. Results obtained using cell cycle analysis and annexin-V/FITC-staining implicated both necrosis and apoptosis pathways in the selective cytotoxicity of cattleianal and cattleianone. Our findings suggest that both compounds are selective antiproliferative agents and support further mechanistic studies for phloroglucinol meroterpenoids as scaffolds for developing new selective chemotherapeutic agents.

A randomized controlled trial of ibuprofen versus ketorolac versus diclofenac for acute, nonradicular low back pain.

OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line medication for acute low back pain (LBP). It is unclear if the choice of NSAID impacts outcomes. We compared ibuprofen, ketorolac, and diclofenac for the treatment of acute, nonradicular LBP. METHODS: This was a three-armed, double-blind, comparative effectiveness study, in which we enrolled patients at the conclusion of an ED visit for musculoskeletal LBP and determined outcomes by telephone 5 days later. Patients were randomized to receive a 5-day supply of 600 mg of ibuprofen, 10 mg of ketorolac, or 50 mg of diclofenac, each to be used every 8 h as needed. Every participant also received LBP education. The primary outcome was improvement in Roland-Morris Disability Questionnaire (RMDQ), a 24-item instrument on which lower scores indicate better LBP functional outcomes, between ED visit and day 5. Secondary outcomes included pain intensity, measured using the descriptors none, mild, moderate, and severe, and the presence of stomach irritation. RESULTS: A total of 868 patients were screened and 66 patients were enrolled in each of the three arms. Baseline characteristics were similar. Improvements in RMDQ by day 5 were as follows: ibuprofen 9.4, ketorolac 11.9, and diclofenac 10.9 (p = 0.34). Mild or no pain on day 5 was as follows: ibuprofen 38 of 61 (62%), ketorolac 47 of 59 (80%), and diclofenac 45 of 62 (71%; 95% CI for rounded mean difference of 17% between ibuprofen and ketorolac = 1, 33%, p = 0.04, number needed to treat = 6 [95% CI = 3-69]). Stomach irritation was reported by 16 of 62 (26%) ibuprofen patients versus three of 61 (5%) in the ketorolac arm and six of 64 (9%) in the diclofenac arm (p < 0.01). CONCLUSION: There were no important differences between groups with regard to the primary outcome. These data do not rule out that possibility that ketorolac results in better pain relief and less stomach irritation than ibuprofen.

Anti-estrogenic and anti-aromatase activities of citrus peels major compounds in breast cancer.

Estrogen signaling is crucial for breast cancer initiation and progression. Endocrine-based therapies comprising estrogen receptor (ER) modulators and aromatase inhibitors remain the mainstay of treatment. This study aimed at investigating the antitumor potential of the most potent compounds in citrus peels on breast cancer by exploring their anti-estrogenic and anti-aromatase activities. The ethanolic extract of different varieties of citrus peels along with eight isolated flavonoids were screened against estrogen-dependent breast cancer cell lines besides normal cells for evaluating their safety profile. Naringenin, naringin and quercetin demonstrated the lowest IC50s and were therefore selected for further assays. In silico molecular modeling against ER and aromatase was performed for the three compounds. In vivo estrogenic and anti-estrogenic assays confirmed an anti-estrogenic activity for the isolates. Moreover, naringenin, naringin and quercetin demonstrated in vitro inhibitory potential against aromatase enzyme along with anticancer potential in vivo, as evidenced by decreased tumor volumes. Reduction in aromatase levels in solid tumors was also observed in treated groups. Overall, this study suggests an antitumor potential for naringenin, naringin and quercetin isolated from citrus peels in breast cancer via possible modulation of estrogen signaling and aromatase inhibition suggesting their use in pre- and post-menopausal breast cancer patients, respectively.

Role of Napsin A and Survivin Immunohistochemical Expression in Bronchogenic Adenocarcinoma.

BACKGROUND: Lung cancer, being the leading cause of cancer deaths with most patients diagnosed at a late stage, represents a major burden in developing countries especially with both air pollution and tobacco use increasing. With the evolution of new, successful therapies that target lung adenocarcinoma, it became of utmost importance to diagnose lung adenocarcinoma. Despite considering TTF-1 as the predominant marker for identifying lung adenocarcinoma but it has limited sensitivity and specificity, which means that its expression decreases in relation to the degree of tumor differentiation. AIM OF WORK: this study intended to evaluate the use of Napsin A in lung adenocarcinoma, and observe if it can withstand along the different lines of tumor differentiation and Survivin as a marker of poor prognosis. MATERIALS AND METHODS: Forty paraffin blocks of bronchogenic carcinoma were collected and studied immunohistochemically against Napsin A and Survivin. RESULTS: There was a statistically significant relation between Napsin A reactivity and tumor grade as 72% of grade II as well as all cases of grade I were strongly positive compared to none of grade III cases. Another statistically significant relation between Survivin reactivity and tumor grade was observed as all grades I and II cases showed labeling index <10%, while all grade III cases showed labeling index >10%. CONCLUSION: Napsin A is a good prognostic marker while Survivin stands as a poor one for lung adenocarcinoma with a statistically inverse relation between the two, which means that Napsin A can't be used as a marker for diagnosing poorly differentiated tumors.
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