Predictive significance of pretreatment 18F-FDG PET volumetric parameters on survival outcomes in pediatric patients with locally advanced undifferentiated nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a rare pediatric cancer. Most children are first diagnosed with advanced locoregional disease. Identification of patients at higher risk of treatment failure is crucial as they may benefit from more aggressive initial treatment approaches. 18Fluorine-labeled fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET) has shown promise as a prognostic tool for predicting outcomes. METHODS: Retrospective study of pediatric patients with locally advanced undifferentiated NPC who underwent 18F-FDG PET/CT prior to intial treatment. Predictive significance of metabolic PET parameters on survival outcomes were estimated. RESULTS: Thirty-two children were included, age range was 7.1-18 years at the time of diagnosis. The median follow-up duration was 46.1 months. Three patients (9.4%) were classified as AJCC stage IIb, 13 patients (40.6%) as stage IIIa, eight patients (25%) as stage IIIb, and eight patients (25%) as stage IVa. Our findings revealed that high whole-body metabolic tumor volume at the threshold of hepatic reference SUVmean (WB-MTV-HR) (>135 mL) was associated with significantly lower event-free survival (EFS) compared to the low WB-MTV-HR group (≤135 mL) (3-year EFS: 50% ± 18% vs. 82% ± 8%; p = .015). Additionally, the 3-year overall survival (OS) rates differed significantly between the high whole-body metabolic tumor volume at the threshold of an SUV of 2.5 isocontour (WB-MTV-2.5) group (MTV >74 mL) and the low WB-MTV-2.5 group (MTV ≤74 mL) (63% ± 18% vs. 100%; p = .021). CONCLUSION: Our study suggests that WB-MTV parameters could serve as significant prognostic factors for disease progression in pediatric patients with locally advanced undifferentiated NPC. However, further prospective studies with larger sample sizes are needed to validate these findings.

New prospective insecticidal agents based on thiazolo[4,5-b]quinoxaline derivatives against cotton leafworm Spodoptera litura (Fabricius): Design, synthesis, toxicological, morphology, histological, and biomedical studies.

In this study, a new series of thiazolo[4,5-b]quinoxaline derivatives 3-8 were synthesized by treating 2,3-dichloroquinoxaline with thiosemicarbazone and thiourea derivatives under reflux conditions. The chemical structure of the newly designed derivatives was conducted using spectroscopic techniques. The insecticidal bioassay of the designed derivatives was evaluated against the 2nd and 4th larvae of S. litura after five days as toxicity agents via median lethal concentration (LC50) and the lethal time values (LT50). The results indicated that all the tested compounds had insecticidal effects against both instar larvae of S. litura with variable values. Among them, thiazolo[4,5-b]quinoxaline derivative 3 was the most toxic, with LC50 = 261.88 and 433.68 ppm against 2nd and 4th instar larvae, respectively. Moreover, the thiazolo[4,5-b]quinoxaline derivative 3 required the least time to kill the 50% population (LT50) of 2nd larvae were 20.88, 13.2, and 15.84 hs with 625, 1250, and 2500 ppm, respectively, while for the 4th larval instar were 2.75, 2.08, and 1.76 days with concentrations of 625, 1250, and 2500 ppm, respectively. Larvae's morphological and histological studies for the most active derivative 3 were investigated. According to SEM analysis, the exterior morphology of the cuticle and head capsule was affected. In addition, there were some histological alterations in the cuticle layers and the midgut tissues. Columnar cells began breaking down, and vacuolization occurred in the peritrophic membrane. Moreover, treating 4th S litura larvae hemolymph with compound 3 showed significant changes in biochemical analysis, such as total proteins, GPT, GOT, acetylcholinesterase (AChE), and alkaline phosphatase (AlP). Finally, the toxicity prediction of the most active derivative revealed non-corrosive, non-irritant to the eye, non-respiratory toxicity, non-sensitivity to the skin, non-hepatotoxic, and don't have toxicity on minnow toxicity and T. pyriformis indicating a good toxicity profile for human.

Interactive effects of dietary protein and nano-chitosan on growth performance, immune response, and histological aspects of lymphoid organs in broiler chickens.

A feeding trial was conducted to assess the effect of partial replacement of dietary soybean meal by three plant protein sources: coconut, rocket seed, and black cumin meals with their combination in the presence or absence of nano-chitosan (NCH) on growth performance and immune response in broiler chickens. Five starter and grower diets were formulated and used from 1 to 42 days of age. The NCH was added to starter and grower diets at 1.0 g/kg. Five-hundred-fifty-day-old Arbor Acres Plus broiler chicks were randomly divided into ten treatments with five equal replications. Final body weight (FBW), body weight gain (BWG), feed intake (FI), feed conversion ratio (FCR), and blood plasma parameters were investigated. Histological aspects of lymphoid organs (thymus: T, bursa of Fabricius: B, and spleen: S) were characterized. Apart from added NCH, the FBW, BWG, and FCR of broilers fed the diets containing the tested plant proteins were significantly superior to the control ones. However, FI of birds fed the diets containing CM alone or combined with RSM plus BCM was significantly reduced. All experimental broilers displayed high plasma levels of IgG compared with the control group. There were significant increases in plasma concentrations of IgM, IgA, and T4 for groups that fed the diets containing RSM, BCM, and mixture of CM, RSM, and BCM compared with their controls. The T3 levels of broilers fed the tested plant proteins were significantly increased compared with the controls. Aside from plant protein source, broilers fed the NCH-enriched diets achieved significant increases in levels of IgM, TAC, and FSH and activities of CAT and SOD but reduced the MDA level compared with control. The interactions between plant protein source and added nano-chitosan were not interrelated. Furthermore, CM, RSM, and BCM can be used as complementary dietary proteins singly or combined with NCH with no adverse effects on growth performance. Addition of NCH molecules has a positive effect on live body weight and increases feed intake compared with control chicks.

Development of certain aminoquinazoline scaffolds as potential multitarget anticancer agents with apoptotic and anti-proliferative effects: Design, synthesis and biological evaluation.

Newly designed 4 - aminoquinazoline derivatives (5a-f, 6a, b, 7, 8, 9, 10a-c, 11a, b, 12a, b and 13a, b) have been synthesized and evaluated for their potential multitarget anticancer activities, apoptotic and anti-proliferative effects. Thereupon, in vitro cytotoxic activities of all the synthesized compounds were screened against NCI 60 human cancer cell lines (nine subpanels) at NCI, USA. Successfully, 2-morpholino-N-(quinazolin-4-yl) acetohydrazide 5e was granted an NSC code, owing to its significant potency and broad spectrum of activity against various cancer cell lines; leukemia K-562, non-small cell lung cancer NCI-H522 cells, colon cancer SW-620, melanoma LOX IMVI, MALME-3M, renal cancer RXF 393, ACHN and breast cancer MDA-MB231/ATCC (GI% = 99.6, 161, 126.03, 90.22, 174.47, 139.7, 191 and 97, respectively). Compound 5e showed the best inhibitory activity (GI50 = 1.3 µM) against melanoma LOX IMVI, when tested at five doses against NCI 60 cell lines. Furthermore, compound 5e showed comparable EGFR and CDK2 inhibitory activity results (IC50 = 0.093 ± 0.006 µM and 0.143 ± 0.008 µM, respectively) to those of lapatinib and ribociclib (IC50 = 0.03 ± 0.002 µM and 0.067 ± 0.004 µM, respectively). Western blotting analysis of compound 5e against melanoma LOX IMVI marked out significant reduced EGFR and CDK2 protein expression percentages, up to 32.97% and 34.09%, respectively, if compared to lapatinib (31.18%) and ribociclib (29.66%). Moreover, compound 5e caused clear cell cycle arrests at S phase of renal UO-31 cells and at G1 phase of both breast cancer MCF7 and ovarian cancer IGROV1, associated with remarkable increase of DNA content of the controls. In accordance, it demonstrated promising anti- proliferative and apoptotic activities, showing a significant increase in total apoptotic percentages of renal cancer UO-31, breast cancer MCF7 and ovarian IGROV1 cancer cell lines, if compared to the control untreated cells (from 1.79% to 46.72%, 2.19% to 39.02% and 1.66 to 42.51%, respectively). Molecular modelling and dynamic simulation study results supported the main objectives of the present work.

Predictors of depression among school adolescents in Northwest, Ethiopia, 2022: institutional based cross-sectional.

BACKGROUND: Adolescent depression is a serious mental disorder that makes family problems, learning challenges, drug addiction, and increases absenteeism from school. It also has a major impact on a person's ability to manage his or her daily tasks. In the end, the condition may result in self-destruction. Research is scarce among high schools in the study setting. Therefore, this study aimed to assess the prevalence and its associated factors of depression among high school adolescent students in Bahirdar City, Northwest Ethiopia in 2022. METHODS: An institutional-based cross-sectional study was done from June 18 to July 16, 2022, among public and private high school adolescent students in Bahir Dar City, Amhara region, Ethiopia. A two-stage sampling technique was utilized. First, stratification by school type was made and schools were selected 30-40% by using a simple random sampling technique. Finally, an updated sampling frame was taken from each school director to select a sample of 584 study participants after proportional allocation by simple random sampling from six high schools. Patient Health Questionnaires were used to assess depression in high school students. The independent variables, like substance-related factors, were assessed by yes-or-no questions, and the academic stressor by academic stress in secondary education, was assessed by structured questionnaires. Binary and multivariate logistic regressions were used to identify factors associated with depression. Statistical significance was declared at a 95% confidence interval when the value of p was less than or equal to 0.05. RESULTS: The response rate of the participants was 96.9%. The overall magnitude of adolescent depression was found to be 22.1% (95%CI 18.7, 25.7%). Being female (AOR: 3.43; 95%CI 2.11, 5.56), small family size (AOR: 3.01; 95%CI 1.47, 6.15); ever alcohol use (AOR: 2.40; 95%CI 1.51, 3.81); attending a public school (AOR: 3.01; 95%CI 1.68, 5.40), and having a history of abuse (AOR: 1.92; 95%CI 2.2, 3.08) were associated with depression. CONCLUSION: In this study, the magnitude of depression among high school students in Bahir Dar City was higher than the national threshold. There was a significant association between sex, family size of parents, ever alcohol use, public schools, and having a history of abuse with depression among adolescents. Hence, it is better for schools to screen and provide intervention for depression in public high school students and offer therapies, especially in females and those with a history of abuse, small family size, or alcohol use.

Impacts of selenium nanoparticles and spirulina alga to alleviate the deleterious effects of heat stress on reproductive efficiency, oxidative capacity and immunity of doe rabbits.

Effects of dietary inclusion of spirulina platensis (SP) and selenium nanoparticles (SeNPs) combination (SP-SeNPs) on the reproductive performance in vivo and in vitro, reproductive and metabolic hormones, hemato-bichemical parameters, oxidative stress, and immunity of heat-stressed doe rabbis were evaluated. All supplements significantly increased live litter size at birth and weaning, viability rate at birth, hemoglobin and red blood cells, and plasma T3, T4, insulin, total proteins and albumin compared with control. Plasma estradiol 17-ß (pre-mating), progesterone (mid-pregnancy), and prolactin (day -7 postpartum) were significantly increased only by SeNPs (0.3, 0.4, and 0.5 mg/kg). All dietary supplements significantly reduced WBCs, cortisol, lipid profile, and improved liver and kidney functions. Immunoglobulins levels, antioxidants capacity were significantly increased, superoxide dismutase was increased by SeNPs (0.4 and 0.5 mg/kg), while malondialdehyde was reduced by 0.3, 0.4 and 0.5 SeNPs mg/kg. Sexual receptivity, pregnancy rate, viability rate at weaning, ovulation rate, and embryo quality were significantly increased by increasing SeNPs above 0.1 mg, while embryo yield was increased by >0.2 mg SeNPs/kg. A combination of SP and SeNPs, could be potentially used as a strong antioxidant to enhance heat regulation and doe rabbit reproduction via improving reproductive and metabolic hormones, antioxidant status and immunological parameters.

Biosynthesized silver nanoparticles (Ag NPs) from isolated actinomycetes strains and their impact on the black cutworm, Agrotis ipsilon.

Nanomaterials have been produced with the use of bio-nanotechnology, which is a low-cost approach. Currently, research is being conducted to determine whether actinomycetes isolated from Egyptian soil can biosynthesize Ag nanoparticles (Ag NPs) and characterized by using the following techniques: Transmission electron microscopy (TEM), Dynamic light scattering (DLS), Fourier transforms infrared (FT-IR), Energy-dispersive X-ray spectroscopy (EDX), UV-Vis spectroscopy and X-ray diffraction (XRD). The most promising actinomycetes isolate were identified, morphologically, biochemically, and molecularly. Streptomyces avermitilis Azhar A.4 was found to be able to reduce silver metal nanoparticles from silver nitrate in nine isolates collected from Egyptian soil. Toxicity of biosynthesized against 2nd and 4th larval instar of Agrotis ipsilon (Hufn.) (Lepidoptera: Noctuidae) was estimated. In addition, activity of certain vital antioxidant and detoxifying enzymes as well as midgut histology of treated larvae were also investigated. The results showed appositive correlations between larval mortality percentage (y) and bio-AgNPs concentrations (x) with excellent (R2). The 4th larval instar was more susceptible than 2nd larval instar with LC50 (with 95% confirmed limits) =8.61 (2.76-13.89) and 26.44(13.25-35.58) ppml-1, respectively of 5 days from treatment. The initial stages of biosynthesized AgNps exposure showed significant increases in carboxylesterase (CarE) and peroxidases (PODs) activity followed by significant suppression after 5 days pos-exposure. While protease activity was significantly decreased by increasing time post-exposure. Midgut histology showed abnormality and progressive damage by increasing time post exposure leading to complete destruction of midgut cells after 5 days from exposure. These results make biosynthesized AgNPs an appropriate alternative to chemical insecticide in A. ipsilon management.

Testing P2Y12 platelet inhibitors generics beyond bioequivalence: a parallel single-blinded randomized trial.

Cardiovascular diseases are the leading cause of death worldwide. Ticagrelor is an oral antiplatelet drug used in acute coronary syndrome. Although generic drugs are approved for their bioequivalence to the original product, they are not necessarily to be therapeutically equivalent. This study was conducted to prove the efficacy and safety of ticagrelor generically named Ticaloguard® compared to its brand Brilique® in healthy volunteers. A loading dose of 180 mg ticagrelor named Brilique® or Ticaloguard® followed by a 90 mg twice daily regimen as maintenance dose was given to 14 and 15 volunteers in Tica and Brili groups, respectively. The platelet aggregation on the ADP agonist was assessed at baseline and repeated 1 h and 3 h after the loading dose, on day 4 (after reaching steady-state), 12 and 24 h after discontinuation of the antiplatelet drug. Adverse effects from trial medications were noted by direct questions. It was shown that generic Ticaloguard® provides a similar therapeutic effect and safety as its branded Brilique® (p > 0.05). This will permit safe and trusted use of the generic Ticaloguard® when treating it in the same manner as Brilique®. Testing generic drug effects rather than simple bioequivalency, especially for drugs that are used in critical life-threatening situations, is crucial. We advocate applying this form of a clinical trial to test surrogate clinical efficacy for generics used in critical indications before having real-world data whenever possible.

Tranexamic Acid Microinjection Alone Versus Its Combination With Fractional Carbon Dioxide Laser in Melasma Treatment: A Dermoscopic Evaluation.

BACKGROUND: Melasma is a challenging pigmentation disorder. OBJECTIVE: To assess and compare the efficacy of tranexamic acid (TXA) intradermal microinjection alone versus its combination with low-power, low-density fractional CO2 laser in a sequential pattern in melasma. PATIENTS AND METHODS: This study included 29 patients with melasma. Half of the face was randomly assigned to fractional CO2 laser; the other half to TXA. This split-face session was repeated every 6 weeks for 3 sessions. In between, TXA was applied to the full face every 2 weeks. Treatment duration was 4 months. Dermoscopy, melanin index (M.I), and erythema index (E.I) were evaluated at baseline and 4 weeks after the last session. RESULTS: Melanin index, E.I, total dermoscopic score and different dermoscopic patterns of pigmentation, and vascular features showed significant reduction posttreatment on both sides of the face. No statistically significant difference was found regarding the degree and percentage of improvement in M.I, E.I, and total dermoscopic score between both sides. CONCLUSION: Tranexamic acid microinjection alone or combined with low-power, low-density fractional CO2 laser in a sequential pattern are comparatively effective and safe for melasma treatment; however, combined treatment is recommended. Dermoscopy is an essential noninvasive tool in the assessment of melasma and monitoring patients' response to treatment.

Tranilast abrogates cisplatin-induced testicular and epididymal injuries: An insight into its modulatory impact on apoptosis/proliferation.

Cisplatin is a chemotherapeutic agent whose therapeutic use is greatly limited by the associated organs' toxicity and particularly, testicular toxicity. Cisplatin-induced testicular damage reported being mediated through mitochondria-mediated apoptosis, inflammation, and oxidative stress. Evidence showed that tranilast (TRN) has the ability to restore the oxidative status and modulate TRAIL/caspase-8 signaling. This led us to hypothesize that TRN could abrogate cisplatin-induced testicular and epididymal injuries via inhibiting oxidative stress and modulating proliferation and TRAIL/caspase-8/cJNK signaling. Cisplatin injection induced oligospermia and abnormalities in testicular and epididymal structure along with impaired oxidative status. TRN administration (100 or 300 mg/kg) for 7 days post-cisplatin injection preserved spermatogenesis and restored testicular and epididymal architecture, but restoration was more so in TRN300 than TRN100. This was in line with the restoration of balanced oxidative status as indicated by the increased total antioxidant capacity, glutathione and superoxide dismutase activity, and the decreased malondialdehyde content in testes (p < 0.05 vs. cisplatin). TRN increased the cell proliferation revealed by the increased expression of proliferating cell nuclear antigen in a dose-dependent manner (p < 0.05 vs. cisplatin) whereas only TRN300 decreased testicular cJNK, TRAIL, and caspase-8 expression (p < 0.05 vs. cisplatin). Moreover, TRN dose-dependently inhibited the pro-inflammatory transcription factor NF-kB and the cytokine TNF-α expressions in testes. In conclusion, TRN300 was more effective than TRN100 in alleviating cisplatin-induced testicular and epididymal injuries and in enhancing spermatogenesis. This curative effect of TRN might be mediated through its antioxidant and anti-inflammatory impacts along with its modulatory impact on cJNK/TRAIL/caspase-8 signaling favoring proliferation rather than apoptosis.

Oxidative stress and the cholinergic system in non-segmental vitiligo: Effect of narrow band ultraviolet b.

BACKGROUND: Despite exhaustive research, melanocyte disappearance and the evolution of vitiligo remain enigmatic, and although multi-factorial, oxidative stress appears as a major player. The role of cutaneous cholinergic system in vitiligo pathogenesis has also been reported in some studies. OBJECTIVE: To evaluate and correlate the influence of phototherapy on cutaneous cholinergic system and oxidative stress in vitiligo. METHODS: Acetyl choline (ACh), its receptors; nicotinic (nAChR) and muscarinic (mAChR); acetylcholine esterase (AChE) and H2 O2 levels were estimated in de-pigmented and re-pigmented lesions of 30 vitiligo patients before and after NB-UVB phototherapy and in 30 controls. ACh and H2 O2 levels were measured by colorimetry. AChE and acetylcholine receptors expression were measured by quantitative real-time PCR. RESULTS: Mean ACh and H2 O2 levels were significantly higher in vitiligo lesions before NB-UVB (P < .001) whereas AChE enzyme level was significantly lower (P < .001) compared to both re-pigmented and control skin. Additionally, mean mAChR was significantly higher and mean nAChR was significantly lower in vitiligo lesions before NB-UVB versus controls and re-pigmented skin (P < .001). Also, H2 O2 and AChE showed negative correlation whereas ACh and mAChR showed significant positive correlation. Although all the studied parameters showed significant changes after treatment and subsequent re-pigmentation, a significant difference continued to exist between all vitiligo skin and controls. CONCLUSION: Cholinergic system is strongly involved in vitiligo pathogenesis through H2 O2 inhibition of AChE which could be reversed by NB-UVB. Moreover, the strong activation of mAChRs may reflect genetic and/or acquired errors, direct up-regulation by ACh and H2 O2 or both.

Nanogold Particles Suppresses 5-Flurouracil-Induced Renal Injury: An Insight into the Modulation of Nrf-2 and Its Downstream Targets, HO-1 and γ-GCS.

The development of the field of nanotechnology has revolutionized various aspects in the fields of modern sciences. Nano-medicine is one of the primary fields for the application of nanotechnology techniques. The current study sheds light on the reno-protective impacts of gold nano-particles; nanogold (AuNPs) against 5-flurouracil (5-FU)-induced renal toxicity. Indeed, the use of 5-FU has been associated with kidney injury which greatly curbs its therapeutic application. In the current study, 5-FU injection was associated with a significant escalation in the indices of renal injury, i.e., creatinine and urea. Alongside this, histopathological and ultra-histopathological changes confirmed the onset of renal injury. Both gene and/or protein expression of nuclear factor erythroid 2-related factor 2 (Nrf-2) and downstream antioxidant enzymes revealed consistent paralleled anomalies. AuNPs administration induced a significant renal protection on functional, biochemical, and structural levels. Renal expression of the major sensor of the cellular oxidative status Nrf-2 escalated with a paralleled reduction in the renal expression of the other contributor to this axis, known as Kelch-like ECH-associated protein 1 (Keap-1). On the level of the effector downstream targets, heme oxygenase 1 (HO-1) and gamma-glutamylcysteine synthetase (γ-GCS) AuNPs significantly restored their gene and protein expression. Additionally, combination of AuNPs with 5-FU showed better cytotoxic effect on MCF-7 cells compared to monotreatments. Thus, it can be inferred that AuNPs conferred reno-protective impact against 5-FU with an evident modulatory impact on Nrf-2/Keap-1 and its downstream effectors, HO-1 and γ-GCS, suggesting its potential use in 5-FU regimens to improve its therapeutic outcomes and minimize its underlying nephrotoxicity.

Psoriatic arthritis among Egyptian patients with psoriasis attending the dermatology clinic: prevalence, comorbidities, and clinical predictors.

OBJECTIVES: Early diagnosis and treatment of psoriatic arthritis (PsA) help to prevent progressive joint involvement and disabilities. There is a problem in the early diagnosis of PsA worldwide, which may be attributed to the dermatologists missing PsA symptoms and signs and a lack of effective screening tools. AIM OF THE STUDY: The current study was designed to assess the prevalence, comorbidities, and clinical predictors associated with the development of PsA in psoriasis patients. MATERIAL AND METHODS: A cross-sectional observational study was performed. Screening questionnaires - the Psoriasis Epidemiology Screening Tool (PEST) and Early Arthritis for Psoriatic Patients (EARP) - were applied to 200 psoriasis patients; among them n = 22 (11% of all tested patients) were in developmental age. Those with positive questionnaires were classified as having PsA or not according to the classification for psoriatic arthritis criteria. Body surface area, psoriasis area and severity index, and psoriasis disability index tools were used for assessing psoriasis patients. A full rheumatological and dermatological evaluation were carried out for PsA patients. RESULTS: The prevalence of PsA was found to be 30%, with a mean age of 45.48 ±10.79 years. Further, psoriasis preceded the onset of PsA in 46 patients (76.6%), arthritis began before psoriasis in 6 individuals (10%), and both psoriasis and arthritis coincided in 8 (13.3%) patients. Obesity (OR 7.0, 95% CI: 2.61-18.85), nail psoriasis (OR 5.02, 95% CI: 2.02-12.476), and intergluteal cleft site (OR 12.659, 95% CI: 4.302-37.255) were associated with increased risk of PsA. However, classic plaque psoriasis (OR 0.149, 95% CI: 0.051-0.433) and flexure site (OR 0.238, 95% CI: 0.076-0.746) were linked with a decreased risk of PsA development. CONCLUSIONS: Screening for PsA in patients with psoriasis revealed a significant number of undiagnosed cases of PsA that should be treated early. Obesity, nail psoriasis, and psoriasis at the intergluteal sites can help predict the PsA development.

Tranilast attenuates methotrexate-induced renal and hepatic toxicities: Role of apoptosis-induced tissue proliferation.

Drug-induced organ toxicity is a frequently encountered obstacle in the field of medical practice that limits the use of numerous pharmacologically valuable drugs. Methotrexate (MTX)-induced organ toxicity is unfortunately the rate-limiting factor for its clinical application. In the current study, MTX injection induced significant renal and hepatic toxicities manifested on functional, biochemical, and histopathological scales. This was associated with a significant elevation in both renal and hepatic contents of TNF-related apoptosis-inducing ligand (TRAIL) and caspase-8, biomarkers of tissue apoptosis. Inline, immunohistochemical analysis confirmed that tissue increased expression of Ki67 as a biomarker of tissue regeneration in both organs. Tranilast (TRAN) is a small molecular weight anti-inflammatory and antiallergic agent. TRAN's coadministration with MTX in the current study induced a significant tissue recovery via modulation of TRAIL/caspase-8 signaling and modulation of apoptosis-induced tissue proliferation confirmed by quantification of Ki67 expression. In conclusion, TRAN can be proposed as an effective drug to attenuate MTX-induced organ toxicity via modulation of apoptosis-induced tissue proliferation pathway.

Design, synthesis, molecular docking and antiproliferative activity of some novel benzothiazole derivatives targeting EGFR/HER2 and TS.

Multi-targeted anticancer drugs are in focus as a promising research topic. A new series of benzothiazoles hybridized with pyrimidine moiety was designed and synthesized using the lead compound 4a. Various chemical modifications on the pyrimidine ring of 4a at four different positions were done in a trial to get new multi-targeted anticancer agents. The structures of the newly synthesized compounds were established on their elemental analyses and spectral data. All final synthesized derivatives were submitted to the National Cancer Institute (NCI), USA, to be screened for their in vitro anticancer activity. Further evaluation for the cytotoxic activity of the most active compounds was performed using the MTT assay method. Compounds 4d, 8d, 8h, 8i and 17 were then selected for examining their in vitro enzyme inhibitory activities against EGFR, HER2 and TS enzymes using lapatinib and 5FU as standards. Furthermore, cell cycle analysis and apoptosis induction detection were also evaluated. Finally, molecular docking studies were carried out for compounds 4d, 8d, 8h, 8i and 17 to interpret their observed enzymatic activities based on the ligand-protein interactions.

Correlation between LincR-Gng2-5'and LincR-Epas1-3'as with the severity of multiple sclerosis in Egyptian patients.

Introduction: Multiple sclerosis (MS) is an immune-mediated disorder. Long noncoding RNAs (lncRNAs, LncR, Linc RNA) have role in many autoimmune and inflammatory disorders, including MS. LincR-Gng2-5 AS locus in T helper 1 cell (TH1) and LincR-Epas1-3AS in T helper 2 cell (TH2) cell were located in a genomic region rich in genes code for proteins with immune regulatory function. Our aim was to evaluate the LincR-Gng2-5' and LincR-Epas1-3'AS fold change in blood of MS patients versus healthy controls and correlate it with disease severity, assessed based on Expanded Disability Status Scale (EDSS).Material and Methods: Sixty MS patients 42 relapsing remitting (RR, RRMS), 18 Secondary progressive (SP, SPMS) and sixty controls (age-matched and sex-matched) were studied. Blood of patients and control group undergone the investigation of LincR-Gng2-5' and LincR-Epas1-3'AS fold change by real-time PCR. Fold change >2 and p < .05 represent significant result.Results: LincR-Gng2-5' was significantly upregulated in MS patients with mean fold change (2.559) and (p = .03). Meanwhile, LincR-Epas1-3'AS levels were significantly downregulated with mean fold change (0.5964) and (p < .004). Patients with SP showed a significantly higher level of LincR-Gng2-5-fold change (3.71 ± 0.7) than that of RR (1.33 ± 0.3). LincR-Epas1-3'AS was markedly reduced among SP (0.43 ± 0.2) than that of RR (0.66 ± 0.1) but with no significant difference. As regards disease severity (EDSS); there was a significant positive correlation with LincR-Gng2-5 and negative correlation with LincR-Epas1-3'AS. LincR- Gng2-5and LincR-Epas1-3'AS, both are dysregulated in MS patient suggesting a role in disease pathogenesis.Conclusion: LincR-Gng2-5 AS and LincR-Epas1-3'AS fold change are correlated to MS severity (EDSS).

Acylated catalpol diglycoside ameliorates lipopolysaccharides-induced acute lung injury through inhibition of iNOS and TNF-α expression.

Acute lung injury (ALI) is a universal cause of respiratory failure and death especially after sepsis. The current study evaluates the protective efficacy of acylated catalpol diglycoside (ACD), a plant iridoid glycoside, against lipopolysaccharides (LPS)-induced ALI in rats. ACD prevented LPS-induced elevations in total and differential cell counts and total protein content in bronchoalveolar lavage fluid, lung malondialdehyde content, and serum lactate dehydrogenase activity. Moreover, ACD significantly increased lung glutathione and superoxide dismutase and improved lung histopathology with significant reduction in lung tumor necrosis factor-α (TNF-α) content mediated mainly via inhibition of TNF-α messenger RNA (mRNA) expression. In addition, ACD significantly reduced lung total nitrate concentration content through downregulation of inducible nitric oxide synthase (iNOS) mRNA expression, negating the excessive undesired vasodilatation characteristic to sepsis. In conclusion, the reduction of oxidative stress, amelioration of inflammatory cytokines expression, and antagonism of sepsis associated-excessive vasodilatation are main contributors in ACD's protective effect in LPS-induced ALI in rats.

Novel diphenylthiazole derivatives with multi-target mechanism: Synthesis, docking study, anticancer and anti-inflammatory activities.

Over the last few decades, a growing body of studies addressed the anticancer activity of NSAIDs, particularly selective COX-2 inhibitors. However, their exact molecular mechanism is still unclear and is not fully investigated. In this regard, a novel series of compounds bearing a COXs privilege scaffold, diphenyl thiazole, was synthesized and evaluated for their anticancer activity against a panel of cancer cell lines. The most active compounds 10b, 14a,b, 16a, 17a,b and 18b were evaluated in vitro for COX-1/COX-2 inhibitory activity. These compounds were suggested to exert their anticancer activity through a multi-target mechanism based on their structural features. Thus, compounds 10b and 17b with the least IC50 values in MTT assay were tested against three known anticancer targets; EGFR, BRAF and tubulin. Compounds 10b and 17b showed remarkable activity against EGFR with IC50 values of 0.4 and 0.2µM, respectively and good activity against BRAF with IC50 values of 1.3 and 1.7µM, respectively. In contrast, they showed weak activity in tubulin polymerization assay. The in vivo anti-inflammatory potential was assessed and interestingly, compound 17b was the most potent compound. Together, this study offers some important insights into the correlation between COXs inhibition and cancer treatment. Additionally, the results demonstrated the promising activity of these compounds with a multi-target mechanism as good candidates for further development into potential anticancer agents.

Sulforaphane protects against sodium valproate-induced acute liver injury.

Drug-induced hepatotoxicity is one of the most commonly encountered obstacles in the field of medical practice. Sodium valproate (VPA) is among many drugs with reported hepatotoxic effects. Sulforaphane (SFN) is a thiol compound found in wide abundance in cruciferous plants that has numerous reported therapeutic efficacies. The current investigation sheds light on the potential hepatoprotective effect of SFN against VPA-induced liver injury in rats. Twice daily VPA (700 mg/kg, i.p.) for 7 days induced significant biochemical alterations and hepatic histopathological damage. SFN (0.5 mg/kg, orally) for 7 days significantly boosted liver function biomarkers; it reduced serum alanine transaminase, aspartate aminotransferase, and alkaline phosphatase, and restored serum albumin concentration in a significant manner. Meanwhile, SFN significantly mitigated VPA-induced histopathological alterations. To highlight the mechanisms implicated in the observed hepatoprotective action, hepatic malondialdehyde and tumour necrosis factor α content significantly declined with concomitant increase in hepatic heme oxygenase-1 content and glutathione concentration with SFN treatment. In conclusion, SFN can significantly ameliorate VPA-induced hepatotoxicity and liver injury primarily by direct association between antioxidant and anti-inflammatory properties.