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The incidence of acute pancreatitis (AP), a condition characterized by inflammation in the pancreas, has been increasing globally and is associated with several complications. This review elaborated on the etiology, clinical presentation, severity assessment, and treatment modalities of AP, mainly in the critical care setting. Patients with severe AP, as indicated by organ failure (>48 hours from onset), warrant treatment in the intensive care unit setting. The most common etiologies, biliary disease and alcohol consumption, and the advanced diagnostic tools used for the identification of the cause are highlighted. Different severity assessment tools are utilized for grading the severity of the disease, predicting patient outcomes, determining the associated risk, and guiding treatment decisions. The treatment interventions comprise various approaches, such as anti-infective therapy enteral nutrition, analgesics for pain, or minimally invasive surgical procedures, thereby demonstrating an evolving landscape of AP management. Furthermore, various complications such as necrosis, organ failure, and hemorrhage, necessitate disease monitoring and differential diagnosis and are crucial for optimal management of patients. Novel treatment modalities and advancements in multidisciplinary care emphasize the potential for reducing the burden of AP in critical care settings.

Abstract The process of creating a series of 3-amino-1-aryl-8-methoxy-1H-benzo[f]chromene-2-carbonitriles (4a-q) involved reacting 6-methoxynaphthalen-2-ol (1), the appropriate aromatic aldehydes (2a-q), and malononitrile (3) in an absolute ethanol/piperidine solution under Ultrasonic irradiation. However, the attempt to create 3-amino-1-aryl-1H-benzo[f]chromene-2,8-dicarbonitrile (6a, d, e) was unsuccessful when 6-cyanonaphthalen-2-ol (5) was stirred at room temperature, reflux, Microwave irradiation, or Ultrasonic irradiation. In addition, the target molecules were screened against Staphylococcus aureus (MRSA), Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, Escherichia coli and Klebsiella pneumonia, as well as a panel of three human cancer cells lines such as MCF-7, HCT-116, HepG-2 and two normal cell lines HFL-1 and WI-38. The obtained results confirmed that the pyran derivatives (4 m, i, k) which have a double chlorine at 3,4/2,3/2,5-positions, a single halogen atom 3-Cl/4-Br (4c, e) and a double bromine at 3,5-positions with a single methoxy group at 2-position (4n), of phenyl ring, and, to a lesser extent, other pyran derivatives with monoihalogenated (4a, b, d, f), dihalogenated (4 g, h, j, l) or trisubstituent phenyl ring (4o, p, q). Furthermore, compounds 4b-e, g, i, j, m, and n showed negligible activity against the two normal cell lines, HFL-1 and WI-38. Moreover, compound 4 g exhibited the strongest antimicrobial activity among the other pyran derivatives (4a-f, g-q) when compared to Ciprofloxacin. The MIC was assessed and screened for compound 4 g, revealing bactericidal effects. Lastly, SAR and molecular docking were studied.

Abstract P-glycoprotein (P-gp) imparts multi-drug resistance (MDR) on the cancers cell and malignant tumor clinical therapeutics. We report a class of newly designed and synthesized oxygen-heterocyclic-based pyran analogues (4a–l) bearing different aryl/hetaryl-substituted at the 1-postion were synthesized, aiming to impede the P-gp function. These compounds (4a–l) have been tested against cancerous PC-3, SKOV-3, HeLa, and MCF-7/ADR cell lines as well as non-cancerous HFL-1 and WI-38 cell lines to determine their anti-proliferative potency.The findings demonstrated the superior potency of 4a–c with 4-F, 2-Cl, and 3-Cl derivatives and 4h,g with 4-NO2, 4-MeO derivatives against PC-3, SKOV-3, HeLa, and MCF-7/ADR cell lines.Compounds 4a–c were tested for P-gp inhibition and demonstrated significant vigour against MCF-7/ADR cells with IC50 = 5.0–10.7 μM. The Rho123 accumulation assay showed that compounds 4a–c adequately inhibited P-gp function, as predicted. Furthermore, 4a or 4b administration resulted in MCF-7/ADR cell accumulation in the S phase, while compound 4c induced apoptosis by causing cell cycle arrest at G2/M. The molecular docking was applied to understand the likely modes of action and guide us in the rational design of more potent analogs. The investigate derivatives showed their good binding potential for p-gp active site with excellent docking scores and interactions. Finally, the majority of investigated derivatives 4a–c derivatives showed high oral bioavailability, but they did not cross the blood–brain barrier. These results suggest that they have favorable pharmacokinetic properties. Therefore, these compounds could serve as leads for designing more potent and stable drugs in the future.

Targeting neutrophil function has gained attention as a propitious therapeutic strategy for diverse inflammatory diseases. Accordingly, a series of enone-based derivatives were developed to inhibit neutrophil-mediated inflammation, showing promise for treating inflammatory diseases. These compounds fall into two clusters with distinct effects: one inhibits neutrophilic superoxide (SO) anion production and elastase release triggered by N-formyl-Met-Leu-Phe (fMLF), with compound 6a being most effective (IC50 values of 1.23 and 1.37 μM, respectively), affecting c-Jun N-terminal kinase (JNK) and Akt phosphorylation. The second cluster suppresses formation of SO anion without affecting elastase levels, surpassed by compound 26a (IC50 of 1.56 μM), which attenuates various mitogen-activated protein kinases (MAPKs) with minimal Akt impact. Notably, none of the tested compounds showed cytotoxicity in human neutrophils, underscoring their potential as therapeutic agents against inflammatory diseases.

Liver cancer represents a substantial global health challenge, contributing significantly to worldwide morbidity and mortality. It has long been understood that tumors are not composed solely of cancerous cells, but also include a variety of normal cells within their structure. These tumor-associated normal cells encompass vascular endothelial cells, fibroblasts, and various inflammatory cells, including neutrophils, monocytes, macrophages, mast cells, eosinophils, and lymphocytes. Additionally, tumor cells engage in complex interactions with stromal cells and elements of the extracellular matrix (ECM). Initially, the components of what is now known as the tumor microenvironment (TME) were thought to be passive bystanders in the processes of tumor proliferation and local invasion. However, recent research has significantly advanced our understanding of the TME’s active role in tumor growth and metastasis. Tumor progression is now known to be driven by an intricate imbalance of positive and negative regulatory signals, primarily influenced by specific growth factors produced by both inflammatory and neoplastic cells. This review article explores the latest developments and future directions in understanding how the TME modulates liver cancer, with the aim of informing the design of novel therapies that target critical components of the TME.

This research examines the interplay between Business Intelligence tools and digital marketing strategy optimization, with a focus on the moderating role of customer orientation. Utilizing a quantitative research design, the study explores how BI tools enhance digital marketing strategies and how customer orientation amplifies this effect among 207 respondents from the Jordanian telecommunications sector, reflecting a diverse range of experiences and perceptions within the industry. Through Structural Equation Modeling - Partial Least Squares (SEM-PLS), based on a stratified sample of these employees, the results confirmed that BI tools positively influence digital marketing strategy optimization. Additionally, customer orientation was found to significantly moderate this relationship, highlighting the importance of aligning technological capabilities with a customer-centric approach. The findings contribute valuable insights to marketing and business intelligence fields, suggesting strategies for organizations to enhance their market competitiveness and customer satisfaction, underpinned by a substantial engagement rate from the targeted demographic.

Toxoplasmosis continues to be a prevalent parasitic zoonosis with a global distribution. This disease is caused by an intracellular parasite known as Toxoplasma gondii, and the development of effective novel drug targets to combat it is imperative. There is limited information available on the potential advantages of wheat germ oil (WGO) and propolis, both individually and in combination, against the acute phase of toxoplasmosis. In this study, acute toxoplasmosis was induced in Swiss albino mice, followed by the treatment of infected animals with WGO and propolis, either separately or in combination. After 10 days of experimental infection and treatment, mice from all groups were sacrificed, and their brains, uteri, and kidneys were excised for histopathological assessment. Additionally, the average parasite load in the brain was determined through parasitological assessment, and quantification of the parasite was performed using Real-Time Polymerase Chain Reaction targeting gene amplification. Remarkably, the study found that treating infected animals with wheat germ oil and propolis significantly reduced the parasite load compared to the control group that was infected but not treated. Moreover, the group treated with a combination of wheat germ oil and propolis exhibited a markedly greater reduction in parasitic load compared to the other groups. Similarly, the combination treatment effectively restored the histopathological changes observed in the brain, uterus, and kidney, and the scoring of these reported lesions confirmed these findings. In summary, the present results reveal intriguing insights into the potential therapeutic benefits of wheat germ oil and propolis in the treatment of acute toxoplasmosis.

A simple approach was used to create Fe3O4-methylcellulose (MC) nanocomposites, which were then analyzed using XRD, FTIR, and FE-SEM to determine their structure. The effective factors for enhancing the ratio of magnetite NPs in the samples were investigated using RTFM and optical absorbance. Fe3O4 was synthesized utilizing the reverse co-precipitation technique and magnetic characteristics. Fe3O4/MC nanocomposites with magnetite/MC weight ratios of 0, 0.07, 0.15, and 0.25 have been developed. The diffraction pattern of magnetite is well indexed in accordance with the spinal reference pattern of Fe3O4 (space group: R¯3m), as confirmed by the Rietveld analysis of XRD data of magnetite NPs with an average crystallite size of 50 nm. Magnetite’s insertion into the MC network causes a red shift in the band gap energy (Eg) as the weight percentage of magnetite nanoparticles in the samples rises. The MC, MC-7, MC-15, and MC-25 samples have Eg values of 5.51, 5.05, 2.84, and 2.20 eV, respectively.

Background and Aim: Subclinical mastitis (SCM) caused by erythromycin-resistant Staphylococcus aureus is a significant disease in lactating animals. Therefore, it is crucial to understand the genetic factors contributing to erythromycin resistance in S. aureus. This study aimed to estimate the prevalence of S. aureus in milk from subclinical mastitic cattle and buffaloes and tank milk samples as identified by probe-based real-time polymerase chain reaction (PCR) and the genotypic assessment of macrolide and erythromycin resistance profiles, as well as to analyze the phylogenetic relatedness of our local isolates of S. aureus. Materials and Methods: In total, 285 milk samples were analyzed using the California mastitis test to detect SCM. Milk samples were cultured on different specific Staphylococcus media. The presence of S. aureus was confirmed by Gram staining, the catalase and coagulase tests, the detection of hemolytic activity, DNase agar testing, and biofilm activity in Congo red medium. The genotypic identification of S. aureus (nuc) was performed. The determinants of erythromycin (ermA, ermB, ermC, and ermT) and macrolide resistance (msrA) were screened in all isolates. DNA sequencing of our local isolates of S. aureus was used to analyze their phylogenetic relatedness. Moreover, histopathological examination of tissue specimens of mammary gland was performed. Results: The S. aureus positivity rates were 36.4%, 48.8%, and 63.6% in cattle, buffalo, and bulk tank milk, respectively. Probe-based real-time PCR molecularly confirmed all 62 S. aureus isolates. Thirty-one isolates were subjected to PCR to create profiles of their genotypic erythromycin resistance. ermA, ermB, ermC, and ermT were present in 5 (8%), 26 (41.9%), 18 (29%), and 15 (24.1%) S. aureus isolates, respectively. Moreover, msrA was found in three (4.8%) strains. Eight PCR products were produced using standard PCR for DNA sequencing. Multiple sequence alignment, phylogenetic tree construction, and analysis of nuc in S. aureus revealed a high degree of homology (100%) with S. aureus strains isolated from milk in cases of bovine mastitis in India and Kenya. Histological analysis of udder tissues revealed extensive aggregation of mononuclear inflammatory cells in the interstitial connective tissue, primarily lymphocytes, and macrophages. Conclusion: This study showed a high prevalence of erythromycin resistance in S. aureus isolates. This information is vital for controlling mastitis and the spread of resistance genes between bacterial strains and hosts. Moreover, the probe-based real-time PCR approach is helpful for the rapid screening of S. aureus isolates and the consequent efficient treatment and control of S. aureus mastitis.

Manufacturing of novel transformer oil-based nanofluids has become necessary to improve dielectric and cooling properties. The current study was carried out to examine the dielectric and thermal characteristics of transformer oil incorporated by Mn0.5 Zn0.5 Fe2O4 nanoparticles (Mn-Zn ferrite NPs) that were synthesized by an auto-combustion technique. The microstructure and morphology of the synthesized Mn-Zn ferrite NPs were characterized using X-ray diffraction (XRD), Fourier transform infrared (FTIR), and high-resolution transmission electron microscopy (HRTEM). The formation of a single-phase cubic spinel structure for the Mn-Zn ferrite NPs was confirmed by XRD results. The average crystallite sizes of about 26.7 nm obtained from XRD are very close to the measured value obtained from HRTEM. VSM measurements ensure a high saturation magnetization of 57 emu/g for the Mn-Zn ferrite sample and which makes it a very good candidate as a transformer oil filler. The as-synthesized Mn-Zn ferrite NPs were then introduced into transformer oil with concentrations up to 0.4 g/L to form Mn-Zn nano ferrite-fluid. The dielectric properties of the prepared nano ferrite-fluid samples were investigated by measuring the dielectric constant (ε′) and dissipation factor (tan δ) in the frequency range of 30 Hz − 1 MHz. Moreover, the AC breakdown voltage of the investigated nano ferrite-fluid samples was measured at a constant 500 V/s ramp, and it showed a pronounced enhancement with the addition of Mn-Zn ferrite NPs. It reached 80 % for 0.2 g/L of NPs. Moreover, the convective heat transfer of the nano ferrite-fluid was examined through the heating–cooling process, which is indicating a significant reduction in the thermal time constant in cooling with the introduction of the Mn-Zn ferrite NPs into the oil.

Abstract Background Very long‐chain fatty acids (VLCFAs) composed of more than 20 carbon atoms are essential in the biosynthesis of cell membranes in the brain, skin, and retina. VLCFAs are elongated beyond 28 carbon atoms by ELOVL4 enzyme. Variants in ELOVL4 are associated with three Mendelian disorders: autosomal dominant (AD) Stargardt‐like macular dystrophy type 3, AD spinocerebellar ataxia, and autosomal recessive disorder congenital ichthyosis, spastic quadriplegia and impaired intellectual development (ISQMR). Only seven subjects from five unrelated families with ISQMR have been described, all of which have biallelic single‐nucleotide variants. Methods We performed clinical exome sequencing on probands from four unrelated families with neuro‐ichthyosis. Results We identified three novel homozygous ELOVL4 variants. Two of the families originated from the same Saudi tribe and had the exact homozygous exonic deletion in ELOVL4, while the third and fourth probands had two different novel homozygous missense variants. Seven out of the eight affected subjects had profound developmental delay, epilepsy, axial hypotonia, peripheral hypertonia, and ichthyosis. Delayed myelination and corpus callosum hypoplasia were seen in two of five subjects with brain magnetic rosonance imaging and cerebral atrophy in three. Conclusion Our study expands the allelic spectrum of ELOVL4‐related ISQMR. The detection of the same exonic deletion in two unrelated Saudi family from same tribe suggests a tribal founder mutation.

Neurodegenerative diseases such as Alzheimer’s disease (AD) are multifactorial with several different pathologic mechanisms. Therefore, it is assumed that multitargeted-directed ligands (MTDLs) which interact with different biological targets relevant to the diseases, might offer an improved therapeutic alternative than using the traditional “one-target, one-molecule” approach. Herein, we describe new benzothiazole-based derivatives as a privileged scaffold for histamine H3 receptor ligands (H3R). The most affine compound, the 3-(azepan-1-yl)propyloxy-linked benzothiazole derivative 4b, displayed a Ki value of 0.012 μM. The multitargeting potential of these H3R ligands towards AChE, BuChE and MAO-B enzymes was evaluated to yield compound 3s (pyrrolidin-1-yl-(6-((5-(pyrrolidin-1-yl)pentyl)oxy)benzo[d]thiazol-2-yl)methanone) as the most promising MTDL with a Ki value of 0.036 μM at H3R and IC50 values of 6.7 µM, 2.35 µM, and 1.6 µM towards AChE, BuChE, and MAO-B, respectively. These findings suggest that compound 3s can be a lead structure for developing new multi-targeting anti-AD agents.

Abstract Background The indications and benefits of anti-reflux surgery (ARS) in neonates and infants are uncertain. Prematurity, operation before 1 year of age, neurological impairment (NI), and chronic lung disease (CLD) are risk factors for surgical failure. We aim to document the indications, management, and outcomes of ARS in this age group and compare them among primary and secondary gastroesophageal reflux (GERD). Results Between January 2008 and December 2019, 24 males and 22 females had ARS; 13 (28.3%) for primary while 33 (71.7%) for secondary GERD. The mean gestational age was 34.6 weeks (range 24–41) and mean birth weight was 2000 gm (range 600–3300). The weight at time of referral ranged from 1.4 kg to 4 kg (mean 2.2 kg). There were no significant differences between the two groups regarding the previous data. The group of primary GERD presented mainly with recurrent aspiration (n = 8), recurrent apnea (n = 5), and recurrent desaturations with or shortly after feeds (n = 4). The group of secondary GERD were referred for poor sucking with failure to thrive (FTT) (n = 25), recurrent aspiration (n = 20), and gastrostomy request (n = 14). The risk factors for secondary GERD were neurologically impaired (n = 22), post-esophageal atresia (EA) repair (n = 9), hiatus hernia (n = 4), thoracic stomach (n = 2), N-type tracheoesophageal fistula (TEF, n = 4), and congenital esophageal stenosis (CES, n = 4). The operations included open Nissen’s fundoplication (ONF) (n = 4) and modified open Thal’s fundoplication (MOTF) (n = 42). There were 8 mortalities in the secondary group, unrelated to surgery. Morbidities after Nissen’s fundoplication included wrap migration, gas bloat, and reoperation in one, laparotomy for intestinal obstruction (IO) in one. Following MOTF, there were two cases of transient recurrent GERD which improved with time and laparotomy in one for IO. Conclusions Diagnostic tests remain a challenge. Isolated TEF and CES may require fundoplication for staged management. Cases of the primary group did better with MTFO. Prematurity, CLD and age

CDK2 is a key player in cell cycle processes. It has a crucial role in the progression of various cancers. Hepatocellular carcinoma (HCC) and colorectal cancer (CRC) are two common cancers that affect humans worldwide. The available therapeutic options suffer from many drawbacks including high toxicity and decreased specificity. Therefore, there is a need for more effective and safer therapeutic agents. A series of new pyrazolo[3,4-d]pyrimidine analogs was designed, synthesized, and evaluated as anticancer agents against the CRC and HCC cells, HCT116, and HepG2, respectively. Pyrazolo[3,4-d]pyrimidinone derivatives bearing N5-2-(4-halophenyl) acetamide substituents were identified as the most potent amongst evaluated compounds. Further evaluation of CDK2 kinase inhibition of two potential cytotoxic compounds 4a and 4b confirmed their CDK2 inhibitory activity. Compound 4a was more potent than the reference roscovitine regarding the CDK2 inhibitory activity (IC50 values: 0.21 and 0.25 µM, respectively). In silico molecular docking provided insights into the molecular interactions of compounds 4a and 4b with important amino acids within the ATP-binding site of CDK2 (Ile10, Leu83, and Leu134). Overall, compounds 4a and 4b were identified as interesting CDK2 inhibitors eliciting antiproliferative activity against the CRC and HCC cells, HCT116 and HepG2, respectively, for future further investigations and development.

Phenylpyrazolo[3,4-d]pyrimidine is considered a milestone scaffold known to possess various biological activities such as antiparasitic, antifungal, antimicrobial, and antiproliferative activities. In addition, the urgent need for selective and potent novel anticancer agents represents a major route in the drug discovery process. Herein, new aryl analogs were synthesized and evaluated for their anticancer effects on a panel of cancer cell lines: MCF-7, HCT116, and HePG-2. Some of these compounds showed potent cytotoxicity, with variable degrees of potency and cell line selectivity in antiproliferative assays with low resistance. As the analogs carry the pyrazolopyrimidine scaffold, which looks structurally very similar to tyrosine and receptor kinase inhibitors, the potent compounds were evaluated for their inhibitory effects on three essential cancer targets: EGFRWT, EGFRT790M, VGFR2, and Top-II. The data obtained revealed that most of these compounds were potent, with variable degrees of target selectivity and dual EGFR/VGFR2 inhibitors at the IC50 value range, i.e., 0.3–24 µM. Among these, compound 5i was the most potent non-selective dual EGFR/VGFR2 inhibitor, with inhibitory concentrations of 0.3 and 7.60 µM, respectively. When 5i was tested in an MCF-7 model, it effectively inhibited tumor growth, strongly induced cancer cell apoptosis, inhibited cell migration, and suppressed cell cycle progression leading to DNA fragmentation. Molecular docking studies were performed to explore the binding mode and mechanism of such compounds on protein targets and mapped with reference ligands. The results of our studies indicate that the newly discovered phenylpyrazolo[3,4-d]pyrimidine-based multitarget inhibitors have significant potential for anticancer treatment.

Phosphodiesterase 5 (PDE5) inhibitors presented themselves as important players in the nitric oxide/cGMP pathway, thus exerting a profound impact on various physiological and pathological processes. Beyond their well-known efficacy in treating male erectile dysfunction (ED) and pulmonary arterial hypertension (PAH), a plethora of studies have unveiled their significance in the treatment of a myriad of other diseases, including cognitive functions, heart failure, multiple drug resistance in cancer therapy, immune diseases, systemic sclerosis and others. This comprehensive review aims to provide an updated assessment of the crucial role played by PDE5 inhibitors (PDE5-Is) as disease-modifying agents taking their limiting side effects into consideration. From a medicinal chemistry and drug discovery perspective, the published PDE5-Is over the last 10 years and their binding characteristics are systemically discussed, and advancement in properties is exposed. A persistent challenge encountered with these agents lies in their limited isozyme selectivity; considering this obstacle, this review also highlights the breakthrough development of the recently reported PDE5 allosteric inhibitors, which exhibit an unparalleled level of selectivity that was rarely achievable by competitive inhibitors. The implications and potential impact of these novel allosteric inhibitors are meticulously explored. Additionally, the concept of multi-targeted ligands is critically evaluated in relation to PDE5-Is by inspecting the broader spectrum of their molecular interactions and effects. The objective of this review is to provide insight into the design of potent, selective PDE5-Is and an overview of their biological function, limitations, challenges, therapeutic potentials, undergoing clinical trials, future prospects and emerging uses, thus guiding upcoming endeavors in both academia and industry within this domain.

Abstract Background Obesity is an independent risk factor for chronic kidney disease (CKD) and is the strongest known modifiable risk factor for hyperuricemia and gout. We aimed to discover the outcome of serum uric acid (SUA), gouty arthritis, and kidney function in obese patients after bariatric surgery and possible links with BMI variations. Methods Retrospective study has been performed in National Hospital in Riyadh, KSA, between Jan. 2018 to Jan. 2020. We studied only 98 patients who met our inclusion criteria. Patients followed-up at 1 month (for gouty attack only) postoperative, 3 months postoperative, and 6 months postoperative for body mass index (BMI), serum creatinine, dipstick urinalysis, SUA, and estimated glomerular filtration rate (eGFR). Radiological studies, medical history, follow up radiological studies, and clinical follow up were obtained from the hospital data system. Results A total of 98 patients with mean eGFR were 90.65 ± 29.34 ml/min/1.73 m2, mean SUA 5.56 ± 1.84 mg/dl, and mean BMI was 45.28 ± 7.25 kg/m2, at surgery. Mean BMI had decreased significantly to 38.52 ± 6.05 kg/m2 at 3 months and to 34.61 ± 5.35 kg/m2 at 6 months (P < 0.001). The mean GFR had improved significantly (99.14 ± 23.32 ml/min/1.73 m2) at 6 months (P < 0.001). Interestingly, proteinuria had resolved in 17 patients out of 23 patients at 6 months. Number of gouty attacks was decreased during the first month post-surgery (P < 0.001). SUA level was significantly decreased (4.32 ± 1.27 mg/dl) (P < 0.001). SUA showed significant negative correlations with eGFR at 3 months and positively significant correlations with BMI at 3 and 6 months. By multinomial logistic regression, BMI and initial eGFR were the independent predictive variables for the outcome of eGFR at 6 months, while male gender and initial SUA were the independent predictive variables on the outcome of SUA at 6 months. Postoperatively in gouty arthritis patients, the number of joints affected, patient global VAS assessment, and number of gouty attacks were significantly reduced (P < 0.001). Conclusion Bariatric surgery has been associated with reduction of BMI and subsequently reduction of SUA levels, gouty attacks, and improvement of eGFR.

The use of apitherapy and natural herbal medicines for combating toxoplasmosis has garnered major attention from many researchers. However, there is no available information regarding the potential use of a combination of propolis and wheat germ oil (WGO) in the treatment of toxoplasmosis. In the present study, the potential effects of propolis, WGO, and their combination in the treatment of chronic toxoplasmosis in Swiss albino mice were investigated. Following induction of chronic toxoplasmosis, the potential antiparasitic effects of these substances were evaluated by parasitological assessment and by counting of Toxoplasma cysts. Additionally, the effects of the treatments on parasite loads were analyzed using TaqMan real-time quantitative PCR targeting the Toxoplasma P29 gene followed by investigation of the major histopathological changes in the brain, uterus, and kidney. Interestingly, the combination of propolis and WGO significantly (P ≤ 0.05) decreased the parasite burden in experimental animals compared with burdens seen in groups treated with propolis or WGO alone. Furthermore, the quantification of the DNA concentrations of Toxoplasma P29 gene after the treatment with propolis and WGO revealed a reduction in parasite load in treated groups versus the control group (infected untreated animals). Importantly, the severity of histopathological lesions was significantly (P ≤ 0.05) improved following treatment with propolis and WGO. Collectively, the present study indicated a potential novel role for propolis and WGO as an active apitherapy and natural herbal medication for treating chronic toxoplasmosis, combat the disease, and which could also help overcome the side effects of chemical drugs.

Maryam Abolhasani,1,&ast; Nastaran Maghbouli,2,&ast; Shahrokh Karbalai Saleh,3 Ziba Aghsaeifar,4 Faeze Sazgara,5 Maryam Tahmasebi,6 Haleh Ashraf,7 Jemal Haidar Ali8,&ast; 1Cardiac Primary Prevention Research Center (CPPRC), Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran; 2Physical Medicine and Rehabilitation Department, Tehran University of Medical Sciences, Tehran, Iran; 3Department of Cardiology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran; 4Department of Internal Medicine, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran; 5Department of Radiology, Guilan University of Medical Sciences, Rasht, Guilan, Iran; 6Department of Cardiology, Amir Al Momenin Hospital, Islamic Azad University of Medical Sciences, Tehran, Iran; 7Cardiac Primary Prevention Research Center (CPPRC), Tehran Heart Center and Research Development Center, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran; 8Department of Public Health Nutrition, School of Public Health, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia&ast;These authors contributed equally to this workCorrespondence: Jemal Haidar AliAddis Ababa University, College of Health Sciences, School of Public Health, Department of Public Health Nutrition, P.O. Box: 27285, Addis Ababa, 1000, EthiopiaTel +251 115547465; +251 911505465Email hjemal@gmail.comHaleh AshrafResearch Development Center, Sina Hospital, Emam Khomeini St., Tehran, 1136746911, IranFax +98 21-66348553Email hashraf@sina.tums.ac.irBackground: Although the effectiveness of some combined anthropometric and metabolic scores were evaluated in hypertension prediction, none of them had addressed their accuracy in association with overweight/obese populations. This study examined the accuracy of several anthropometric parameters in this regard and compared the novel indices to the ancient ones.Methods: Through a cross-sectional study, 5115 patients have been evaluated at the weight loss clinic. Data on demographic information, anthropometric indices, and biochemical measurements were assembled into a checklist. Multivariable regression modeling and the area under the receiver-operating characteristic (ROC) were analyzed using SPSS version 20. To find new combined scores, SEM (structural equation modeling) analysis was also adopted. P-values < 0.05 were considered statistically significant.Results: Considering ancient indices, WHtR (waist-to-height ratio) showed a sufficient area under the curve in predicting hypertension among both genders concomitant with WC (waist circumference) in men, and BRI (body roundness index) in women as highest AUC. The highest odds ratio (OR) for the presence of hypertension, based on the age-adjusted model, was BRI in females (OR, 3.335; 95% confidence interval [CI], 1.58– 7.28) and WC in males (OR, 13.478; 95% CI: 1.99– 45.02). The combined scores were not superior to the single ones.Conclusion: The most powerful association between hypertension and sufficient discrimination ability of normotensives from hypertensive patients was detected for BRI in women and WC among men. However, neither the BSI and BAI nor FMI and FFMI showed superiority to WC or WHtR in predicting the presence of hypertension.Keywords: prediction, hypertension, obesity, anthropometric indices, novel indices, Iran

Aberrant CXCR4/CXCL12 signaling is involved in many pathophysiological processes such as cancer and inflammatory diseases. A natural fragment of serum albumin, named EPI-X4, has previously been identified as endogenous peptide antagonist and inverse agonist of CXCR4 and is a promising compound for the development of improved analogues for the therapy of CXCR4-associated diseases. To generate optimized EPI-X4 derivatives we here performed molecular docking analysis to identify key interaction motifs of EPI-X4/CXCR4. Subsequent rational drug design allowed to increase the anti-CXCR4 activity of EPI-X4. The EPI-X4 derivative JM#21 bound CXCR4 and suppressed CXCR4-tropic HIV-1 infection more efficiently than the clinically approved small molecule CXCR4 antagonist AMD3100. EPI-X4 JM#21 did not exert toxic effects in zebrafish embryos and suppressed allergen-induced infiltration of eosinophils and other immune cells into the airways of animals in an asthma mouse model. Moreover, topical administration of the optimized EPI-X4 derivative efficiently prevented inflammation of the skin in a mouse model of atopic dermatitis. Thus, rationally designed EPI-X4 JM#21 is a novel potent antagonist of CXCR4 and the first CXCR4 inhibitor with therapeutic efficacy in atopic dermatitis. Further clinical development of this new class of CXCR4 antagonists for the therapy of atopic dermatitis, asthma and other CXCR4-associated diseases is highly warranted.

Nowadays, the use of natural materials and especially “waste” valorization has evolved and attracted the wide attention of scientists and academia. In this regard, the use of rice husk (RH) powder as a naturally abundant and cheap byproduct material is gaining superior attention. However, improving the physicochemical properties of such RH is still under research. In the current investigation, the modification of rice husk (RH) via γ-irradiation has shown to be a promising green tool to meet such a need. Clean, prepared, powdered RH samples were subjected to various γ-radiation doses, namely 5, 10, 15 and 25 kGy, and the corresponding samples were named as RH-0, RH-5, RH-10, RH-15, RH-15 and RH-25. Then, the samples were characterized via scanning electron microscopy (SEM). After irradiation, the samples showed an increase in their surface roughness upon increasing the γ-radiation up to 15 kGy. Furthermore, the sorption capacity of the irradiated RH samples was investigated for eliminating Urolene Blue (UB) dye as a model pharmaceutical effluent stream. The highest dye uptake was recorded as 14.7 mg/g, which corresponded to the RH-15. The adsorption operating parameters were also investigated for all of the studied systems and all adsorbents showed the same trend, of a superior adsorption capacity at pH 6.6 and high temperatures. Langmuir and Freundlich isotherm models were also applied for UB adsorption and an adequate fitted isotherm model was linked with Langmuir fitting. Moreover, the pseudo-second-order kinetic model provided the best fit for the adsorption data. Experimental assays confirmed that the UB dye could be successfully eradicated feasibly from the aqueous stream via a sustainable green methodology.

In this paper, as-synthesized and oleic acid (OA)-surface-treated zinc oxide (ZnO) nanocrystals were successfully synthesized and investigated for cool-nanopigment applications. ZnO nanocrystals were synthesized using the thermal decomposition method. The OA-surface-treated ZnO sample was obtained with an OA:ZnO ratio of 1:1. The structural, optical and morphological properties of the samples were characterized via X-ray diffraction (XRD), Fourier transform infrared (FTIR), UV-VIS-NIR diffused reflectance spectroscopy (DRS) and field-emission scanning electron microscopy (FE-SEM) techniques. ZnO nanocrystals possess a well-known zincate phase of ZnO, as confirmed for the as-synthesized sample with a reduction in the integrity of the ZnO crystalline structure upon the application of the OA coating. XRD peaks broadening and decreasing in crystallite size were obtained upon the surface modification of the ZnO by OA. The average crystallite size decreased from 31.5 to 17.4 nm, and the surface area changed from 23.37 to 7.48 m2/g upon OA treatment. These changes were attributed to the well-capping of the ZnO nanoparticles by OA, and, furthermore, OA increased the dispersion of the nanoparticles. The optical band gap of the investigated samples demonstrated a blue shift from 3.06 eV to 3.22 eV upon treatment. Both samples showed high NIR reflectance (RNIR∗) values, which makes them well qualified for use as cool nanopigments. Additionally, the as-synthesized sample showed an RNIR∗ value higher than that of the treated sample.

Background and aim Investigating the influence of intramyometrial carbetocin injections and rectal misoprostol on bleeding throughout myomectomy surgeries. Fibroids are firm benign tumors consisting of smooth muscle cells and fibrous connective tissues. Benign uterine leiomyomas (fibroids) are the commonest pelvic tumor in females, impacting 20–40% of all women, over the age of 35 and 50% of African–American women. This work aims to compare the effectiveness of intramyometrial carbetocin injections and rectal misoprostol on blood-loss amounts throughout myomectomy surgeries. Patients and methods A prospective randomized comparative study was performed on 120 females having myoma(s) recruited from the clinic. The 120 study participants were divided into three groups: group I involved 40 women who received intramyometrial injection of 100 µg of carbetocin, group II involved 40 women who received 400 µg of misoprostol, and group III involved 40 women who received nothing during the myomectomy operation. Results The mean blood loss was more in group III in comparison with misoprostol (group II) in comparison with carbetocin (group I) with a statistically significant difference among the three groups, it was 177.43±21.25 ml in group I, 238.00±43.87 ml in group II, and 288.00±29.72 ml in group III. Conclusion The usage of intramyometrial carbetocin injections throughout abdominal myomectomy surgery is more efficient in reducing the blood loss than the usage of rectal misoprostol than using nothing at all.

Maryam Abolhasani,1 Nastaran Maghbouli,2 Faeze Sazgara,3 Shahrokh Karbalai Saleh,4 Maryam Tahmasebi,5 Haleh Ashraf1,4 1Cardiac Primary Prevention Research Center (CPPRC), Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran; 2Physical Medicine and Rehabilitation Department, Tehran University of Medical Sciences, Tehran, Iran; 3Department of Radiology, Guilan University of Medical Sciences, Rasht, Guilan, Iran; 4Department of Cardiology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran; 5Amir Al Momenin Hospital, Department of Cardiology, Islamic Azad University of Medical Sciences, Tehran, IranCorrespondence: Haleh AshrafResearch Development Center,Sina Hospital, Emam Khomeini Street, Tehran 1136746911, IranFax +66348553Email hashraf@sina.tums.ac.irAim: Rapid and growing rise in obesity and diabetes mellitus, as serious human health-threatening issues, is alarming. The aim of the present study was assessing the accuracy of several obesity indices to predict hyperglycemia in overweight and obese Iranian populations and determining the value of such indices in comparison to the conventional parameters. We also evaluated new latent combined scores in this matter.Patients and Methods: Overall, there were 2088 patients recruited from the weight loss clinic of Sina Hospital, an educational hospital of Tehran University of Medical Sciences for this cross-sectional study. Demographic information, anthropometric indices and biochemical measurements were collected and calculated. The multivariable regression modeling as well as area under the receiver-operating characteristic (ROC) analysis was used. To detect the existence of new combined scores, we used SEM (structural equation modeling) analysis through SmartPLS.Results: Combined latent scores and WHtR (waist-to-height ratio) gave us a higher area under the curve in predicting hyperglycemia associated with WC (waist circumference) in women, whereas FFMI (fat-free mass index) gave low values. Additionally, BRI (body roundness index) and latent scores had slightly higher AUC values in predicting hyperglycemia in men. According to the age-adjusted odds ratio (OR) in the presence of hyperglycemia, OR was the highest for WHR (waist to hip ratio) in women (OR, 7.74; 95% confidence interval [CI], 1.71– 15.13). The association of WHR and hyperglycemia remained significant by adjusting for BMI (body mass index), WC and menopausal status.Conclusion: WHR had the strongest association with hyperglycemia in women with only sufficient discrimination ability. However, neither BSI (body shape index) and BAI (body adiposity index) nor FMI (fat mass index) and FFMI were superior to BMI (body mass index), WC or WHtR in predicting hyperglycemia. It was revealed that BRI and combined scores had a more predictive power compared to the BSI, BAI, FMI and FFMI, simplifying hyperglycemia evaluation.Keywords: diabetes mellitus, obesity, anthropometric indices

Abstract Background Spontaneous intestinal perforation (SIP) is usually an isolated perforation occurring most commonly in the terminal ileum of neonates with very low birth weight (VLBW) and extreme low birth weight (ELBW) of unknown etiology. It can be identical to perforated necrotizing enterocolitis (NEC) both clinically and radiologically raising a diagnostic challenge. In such cases, the differentiation is only possible by laparotomy and histopathology. This is important because the differentiation has management and prognostic consideration. The authors are presenting a case of SIP which was followed by NEC after 4 days only of its onset. Case presentation The authors report on a unique case of SIP which was followed by perforated NEC after 4 days of its onset in a 28-week gestational age with an ELBW. On the 3rd day of life, abdominal X-ray showed a significant pneumoperitoneum with neither pneumatosis intestinalis nor portal venous gas. The diagnosis of SIP was made at laparotomy. On the 4th post-operative day the patient developed pneumoperitoneum again due to perforated NEC as confirmed later on by histology. In this odd case (which we believe to be the youngest in the literature), the sequence of SIP followed after few days by perforated NEC is presented. Methods of differentiating these two conditions and their management are discussed. Conclusion SIP should be differentiated from perforated NEC by laparotomy and histopathology if this is not possible clinically and radiologically, and the patient is stable. Primary peritoneal drainage (PPD) is reserved as a step to stabilize the patient only in both conditions.

Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal disease, with a median survival of ∼2–5 years. The main target of treatment was to stabilize or reduce the rate of disease progression. Nintedanib and pirfenidone are new drugs that could be considered a breakthrough in the management of IPF as anti-inflammatory and antifibrotic agents. Aim The aim was to evaluate the efficacy, tolerability, and adverse effects of pirfenidone and nintedanib in the management of IPF. Patients and methods A total of 50 patients (38 males and 12 females) were included in our study. IPF diagnosis was established according to the international guidelines. The patients were started on antifibrotic therapy with either pirfenidone or nintedanib. Clinical, functional, and radiological follow-ups were done for all patients prospectively at baseline, at 6 months, and at 12 months of therapy. Result The mean age of nintedanib group was significantly higher (78.41±6.8 vs 62.34±6.3 years for pirfenidone group; P

Sustainable waste reduction strategies and innovative waste reduction concepts, as well as their application in the creation of compounds and products with added value, can benefit the economy while reducing environmental pressures. This research aimed to use biopolymeric nanomaterials to reduce the negative effects of salinity on tomato yield and quality. Three types of biopolymers (cellulose, pectin, and starch) were synthesized and characterized using natural materials such as rice straw, orange peel, and potato peel. The polymer’s ability to retain sodium ions was investigated. A greenhouse experiment was conducted to assess the potential of natural polymers (cellulose, starch, and pectin individually or in combination) to reduce the salinity side effects on tomato plants (Solanum Lycopersicon L.) cultivar (Super Strain B). Tomato seeds were germinated on soil bits for 20 days before planting five seedlings in each pot (20 cm diameter) with three replicates and filling each pot with sandy loam soil, with or without natural polymers at a rate of 2 g/Kg. The results revealed that all the polymers utilized had a superlative capability to hold sodium ions for both soluble and exchanged sodium. The use of various natural polymer hydrogels increased the number and fresh weight of tomato fruits. Data showed that using biopolymers hydrogels reduced salinity stress by rising the content of phenol, flavonoid, and antioxidant enzymes such as catalase and peroxidase. The use of natural biopolymers significantly improved total soluble solids, pH, and juice substance. Implementing biopolymeric materials could reduce environmental pressures while increasing farm income. Innovative waste reduction strategies, such as the creation of value-added products, will benefit the economy, and this work is a good start in that direction.

It has been shown that phosphodiesterase 5 (PDE5) inhibitors have anticancer effects in a variety of malignancies in both in vivo and in vitro experiments. The role of cGMP elevation in colorectal carcinoma (CRC) has been extensively studied. Additionally, DNA topoisomerase II (Topo II) inhibition is a well-established mechanism of action that mediates the effects of several approved anticancer drugs such as doxorubicin and mitoxantrone. Herein, we present 9-benzylaminoacridine derivatives as dual inhibitors of the PDE5 and Topo II enzymes. We synthesized 31 derivatives and evaluated them against PDE5, whereby 22 compounds showed micromolar or sub-micromolar inhibition. The anticancer activity of the compounds was evaluated with the NCI 60-cell line testing. Moreover, the effects of the compounds on HCT-116 colorectal carcinoma (CRC) were extensively studied, and potent compounds against HCT-116 cells were studied for their effects on Topo II, cell cycle progression, and apoptosis. In addition to exhibiting significant growth inhibition against HCT116 cells, compounds 11, 12, and 28 also exhibited the most superior Topo II inhibitory activity and low micromolar PDE5 inhibition and affected cell cycle progression. Knowing that compounds that combat cancer through multiple mechanisms are among the best candidates for effective therapy, we believe that the current class of compounds merits further optimization and investigation to unleash their full therapeutic potential.

For the photocatalytic removal of the Reactive Blue 4 dye from an aqueous stream, new polyaniline/multi walled carbon nanotube nanocomposites (PANI-MWCNTs) were applied as a promising photocatalyst. The PANI-MWCNT nanocomposites were fabricated by aniline oxidation in the presence of MWCNTs using the typical direct oxidation polymerization route. The morphology, the Fourier transform infrared (FTIR) spectra and the UV-Vis absorbance spectra of the fabricated nanocomposites were studied and the attained data confirmed the good interaction between the MWCNTs and PANI matrix. The PANI-MWCNTs nanocomposites were varied according to the wt%, the MWCNTs, which ranged from 0–10 wt% and the corresponding resultant samples are labeled as P-0, P-3, P-5, P-5, P-7 and P-10, respectively. Such composites showed the high potential for the removal of the Reactive Blue 4 dye containing pollutants from wastewater. The starting concentration of the dye pollutants was halved during the first 5 min of UV illumination. The oxidation technique of Reactive Blue 4 over the prepared nanocomposites were processed in a different way and the highest catalytic activity corresponded to P-7. The process reached the complete dye removal in low concentrations of contaminants. The kinetics of the removal followed the pseudo-second order regime which possesses high correlation coefficients with the k2 in the range of 0.0036–0.1115 L.mg−1.min−1 for the Reactive Blue 4 oxidation. In this regard, the combination of the PANI and MWCNTs showed a superior novel photocatalytic activity in the oxidation of commercial textile dying wastewater, namely Reactive Blue 4. This study is the starting point for future applications on an industrial scale since the successful performances of the PANI-MWCNT on commercial dye oxidation.

Abstract This paper is devoted to study the existence of at least one continuous mild solution to semilinear fractional differential inclusion with deviated-advanced nonlocal conditions. We develop the results obtained, by exchanging the deviated-advanced nonlocal condition to an integral form. Our results will be accomplished by using the nonlinear Leray-Schauder’s alternative fixed point theorem. The main results are well illustrated with the aid of an example.

Masoomeh Eghtedari,1,2 Vahid Beigi,2 Mehrnoosh Maalhagh,2 Hossein Ashraf21Pathology Department, Shiraz University of Medical Sciences, Shiraz, Iran; 2Ophthalmology Department, Shiraz University of Medical Sciences, Shiraz, IranCorrespondence: Masoomeh EghtedariPoostchi Ophthalmic Research Center, Poostchi Street, Shiraz, IranTel +98 713 230 2830Fax +98 713 629 1779Email eghtedarim@sums.ac.irPurpose: Interleukin-6 (IL-6) is an important cytokine in the cascade of inflammation and cancer progression. The aim of this study was to identify IL-6 expression in ocular surface squamous neoplasia (OSSN) in comparison with non-neoplastic conjunctival tissue.Methods: Twenty paraffin-embedded tissue sections of conjunctiva from patients with OSSN including conjunctival intraepithelial neoplasia (CIN) in all grades of severity and squamous cell carcinoma (SCC) were assessed by immunohistochemistry staining for IL-6. Twenty non-neoplastic conjunctival sections from age matched patients were selected as the control group. Tissues with more than one focus of inflammatory cell infiltration were excluded from the study. The mean area of positive staining was recorded and the intensity of staining was scored in both groups and compared by statistical methods.Results: The mean staining area in the dysplasia group was significantly more than non-neoplastic conjunctival tissue (63.5±25.96 and 30±15.98 percent respectively; P-value of

Abstract Background Tracheal intubation is the second most dangerous procedures reflected in the ICU. It includes passing a plastic tube named endotracheal tube (ET) through the vocal cords into the trachea. Errors of this procedure like the placement of ET in the oesophagus or advancing the ET too far into one of the two lungs are life threatening. Objectives This work was designed to provide cheap and quick technique to confirm proper ET tube placement by utilizing simple video laryngoscopy and using dogs as an animal model. Materials and methods This study was conducted on 20 dogs divided into two equal group (n = 10). The first group, in which a semi-flexible video laryngoscope (VLS) fitted with endotracheal tube was introduced and placed into the trachea of the experimental dogs. In the second group, dogs were intubated through soft and flexible video laryngoscope (VLS) fitted with the endotracheal tube. Number and time of the first attempt for introduction of ET were recorded. Results The number of attempts was significantly (P

Background: Anti-carbamylated protein (anti-CarP) antibodies are present in patients with Rheumatoid arthritis (RA) and may present before disease onset. Our aim is to investigate the diagnostic value of anti-CarP antibody in Egyptian RA patients. Methods: This cross-sectional study included 96 RA patients (56 patients with early disease and 40 patients with established disease) and 60 healthy controls. Demographic and clinical data, smoking status, and disease activity score were recorded. Laboratory tests included erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, anti-citrullinated protein antibodies, and anti-CarP antibody. Results: Anti-CarP antibody levels in RA patients were significantly higher than in controls (8.80 ± 5.95 vs. 2.19 ± 1.01, P < 0.0001). Out of 96 RA patients; 74 (77.1%) were positive for anti -CarP anti body including 47patients with early RA while only 5 subjects (8.3%) in control group were positive. Receiver-operating characteristic curve study for diagnostic efficacy of anti-CarP antibody in early RA diagnosis demonstrated a significant area under the curve, 0.950 (95% confidence interval, 0.912–0.987, P < 0.0001) and yielded a sensitivity of 85.4%, a specificity of 93.3%, a positive predictive value of 0.90, and a negative predictive value of 0.86. Conclusion: Anti-CarP antibody is a useful biomarker for early RA diagnosis.

Context The use of small incision lenticule extraction (SMILE) for compound myopic astigmatism has been subject to experimentation in the recent years. Furthermore, examination of corneal alterations has revealed conflicting conclusions, which could be attributable to demographic variation. Aims The aim of this study was to measure visual and keratometric efficacy of SMILE and correlate spherical equivalent (SE) decrements to keratometric alterations. Settings and design This was a prospective nonrandomized study. Thirty eyes of 15 patients were included in the study. Preoperative assessment included oculus Pentacam analysis. Patients were followed-up for up to 3 months, after which tomography was repeated. Statistical analysis used Descriptive statistics, t test, and linear regression analysis were carried out. Results There was a statistically significant improvement in postoperative uncorrected distance visual acuity and SE and a statistically significant change in Q value (P

For many inflammatory diseases, new effective drugs with fewer side effects are needed. While it appears promising to target the activation of the central pro-inflammatory transcription factor NF-κB, many previously discovered agents suffered from cytotoxicity. In this study, new alkylthiourea quinazoline derivatives were developed that selectively inhibit the activation of NF-κB in macrophage-like THP−1 cells while showing low general cytotoxicity. One of the best compounds, 19, strongly inhibited the production of IL-6 (IC50 = 0.84 µM) and, less potently, of TNFα (IC50 = 4.0 µM); in comparison, the reference compound, caffeic acid phenethyl ester (CAPE), showed IC50s of 1.1 and 11.4 µM, respectively. Interestingly, 19 was found to block the translocation of the NF-κB dimer to the nucleus, although its release from the IκB complex was unaffected. Furthermore, 19 suppressed the phosphorylation of NF-κB-p65 at Ser468 but not at Ser536; however, 19 did not inhibit any kinase involved in NF-κB activation. The only partial suppression of p65 phosphorylation might be associated with fewer side effects. Since several compounds selectively induced cell death in activated macrophage-like THP−1 cells, they might be particularly effective in various inflammatory diseases that are exacerbated by excess activated macrophages, such as arteriosclerosis and autoimmune diseases.

Fusarium graminearum is a major global pathogen of cereals and is considered the main causal agent of Fusarium head blight disease in wheat. Infection with Fusarium graminearum causes a significant reduction in crop yield and quality; therefore, it is very important to improve wheat pathogen resistance. In the present study, the plasmid pAHCht-2 harboring the rice chitinase (Cht-2) gene for pathogen resistance and the plasmid pAB6 containing the gus reporter and bar selectable marker genes were used for genetic transformation of immature embryo-derived calli of the Egyptian wheat cultivar Giza 164 using particle bombardment. Associated changes in defense mechanisms in the transgenic plants were investigated. The transgenic plants had significantly decreased total protein content, phenolic compounds and antioxidant enzyme activities (peroxidase and catalase), and significantly increased phenylalanine ammonia lyase and chitinase activities compared with non-transgenic plants under biotic stress conditions caused by F. graminearum infection. Our results show that activating a specific program of gene expression related to environmental stress conditions can reduce the cost of the stress on plant metabolism.

In today’s global plan to completely eradicate hepatitis C virus (HCV), the essential list of medications used for HCV treatment are direct-acting antivirals (DAAs), as interferon-sparing regimens have become the standard-of-care (SOC) treatment. HCV nonstructural protein 5A (NS5A) inhibitors are a very common component of these regimens. Food and Drug Administration (FDA)-approved NS5A inhibitors, although very potent, do not have the same potency against all eight genotypes of HCV. Therefore, this study aims to synthesize NS5A inhibitor analogues with high potency pan-genotypic activity and high metabolic stability. Starting from an NS5A inhibitor scaffold previously identified by our research group, we made several modifications. Two series of compounds were created to test the effect of changing the length and spatial conformation (para-para vs. meta-meta-positioned bis-imidazole-proline-carbamate), replacing amide groups in the linker with imidazole groups, as well as different end-cap compositions and sizes. The frontrunner inhibits genotype 1b (Con1) replicon, with an EC50 value in the picomolar range, and showed high genotypic coverage with nanomolar range EC50 values against four more genotypes. This together with its high metabolic stability (t½ > 120 min) makes it a potential preclinical candidate.

Selective estrogen receptor modulators (SERMs) act as estrogen receptor (ERα) agonists or antagonists depending on the target issue. Tamoxifen (TAM) (a non-steroidal triphenylethylene derivative) was the first SERM approved as anti-estrogen for the treatment of metastatic breast cancer. On the hunt for novel SERMs with potential growth inhibitory activity on breast cancer cell lines yet no potential to induce endometrial carcinoma, we designed and synthesized 28 novel TAM analogs. The novel analogs bear a triphenylethylene scaffold. Modifications on rings A, B, and C aim to attenuate estrogenic/anti-estrogenic activities of the novel compounds so they can potentially inhibit breast cancer and provide positive, beneficial estrogenic effects on other tissues with no risk of developing endometrial hyperplasia. Compound 12 (E/Z-1-(2-{4-[1-(4-Chloro-phenyl)-2-(4-methoxy-phenyl)-propenyl]-phenoxy}-ethyl)-piperidine) showed an appreciable relative ERα agonistic activity in a yeast estrogen screen (YES) assay. It successfully inhibited the growth of the MCF-7 cell line with GI50 = 0.6 µM, and it was approximately three times more potent than TAM. It showed no potential estrogenicity on Ishikawa endometrial adenocarcinoma cell line via assaying alkaline phosphatase (AlkP) activity. Compound 12 was tested in vivo to assess its estrogenic properties in an uterotrophic assay in an ovariectomized rat model. Compared to TAM, it induced less increase in wet uterine wet weight and showed no uterotrophic effect. Compound 12 is a promising candidate for further development due to its inhibition activity on MCF-7 proliferation with moderate AlkP activity and no potential uterotrophic effects. The in vitro estrogenic activity encourages further investigations toward potential beneficial properties in cardiovascular, bone, and brain tissues.

Pulmonary administration provides a useful alternative to oral and invasive routes of administration while enhancing and prolonging the accumulation of drugs into the lungs and reducing systemic drug exposure. In this study, chloroquine, as a model drug, was loaded into niosomes for potential pulmonary administration either via dry powder inhalation or intratracheally. Chloroquine-loaded niosomes have been prepared and extensively characterized. Furthermore, drug-loaded niosomes were lyophilized and their flowing properties were evaluated by measuring the angle of repose, Carr’s index, and Hausner ratio. The developed niosomes demonstrated a nanosized (100–150 nm) spherical morphology and chloroquine entrapment efficiency of ca. 24.5%. The FT-IR results indicated the incorporation of chloroquine into the niosomes, whereas in vitro release studies demonstrated an extended-release profile of the drug-loaded niosomes compared to the free drug. Lyophilized niosomes exhibited poor flowability that was not sufficiently improved after the addition of lactose or when cryoprotectants were exploited throughout the lyophilization process. In vivo, intratracheal administration of chloroquine-loaded niosomes in rats resulted in a drug concentration in the blood that was 10-fold lower than the oral administration of the free drug. Biomarkers of kidney and liver functions (i.e., creatinine, urea, AST, and ALT) following pulmonary administration of the drug-loaded nanoparticles were of similar levels to those of the control untreated animals. Hence, the use of a dry powder inhaler for administration of lyophilized niosomes is not recommended, whereas intratracheal administration might provide a promising strategy for pulmonary administration of niosomal dispersions while minimizing systemic drug exposure and adverse reactions.

Objective: To demonstrate a benefit in diminished adverse events such as hypotension and hematuria with gradual drainage of the bladder when compared to rapid decompression in patients with acute urinary retention (AUR) due to benign prostatic hyperplasia in a case–control study. Methods: Sixty-two patients matched our selection criteria presenting with AUR. They were divided into two groups – the first was managed by rapid drainage of the bladder, the second was managed by gradual drainage through a urethral catheter (The first 100 mL immediately evacuated, then the rest evacuated gradually over 2 h). Results: The mean age was 64.4 and 63.2 years in the first and second group, respectively. Diagnosed cause was benign hyperplasia of the prostate. Hematuria occurred in two patients in the first group and none in the second group. The two cases of hematuria were mild and treated conservatively. After the relief of the obstruction, the mean blood pressure was noticed to decrease by 15 mmHg and 10 mmHg in the first and second group, respectively, however, no one developed significant hypotension. Pain relief was achieved after complete drainage in the first group and after the evacuation of 100 mL in the second group. Conclusions: We conclude that there is no significant difference between rapid and gradual decompression of the bladder in patients with AUR. Hematuria and hypotension may occur after rapid decompression of the obstructed urinary bladder, but these complications are rarely clinically significant.

Background/Objective: Limited animal and human studies have shown function, albeit inadequate, of implanted thyroid tissue in muscles. This work aimed to ascertain results in a larger number of patients, finding practical method for implantation, studying the effect of changing weight of implant and effect of passage of time on its function. Methods: Forty patients had total thyroidectomy for simple multinodular goiters. A piece of the excised gland was finely minced, mixed with saline as emulsion, and injected in thigh muscles. Twelve patients had 5-g implants, while 28 patients had 10-g implants. Four parameters were studied at 2 months, 6 months, and 12 months: technetium isotope uptake by the implant; thyroid stimulating hormone (TSH); free T3 (FT3); and free T4 (FT4). Results: All autotransplanted thyroid tissue survived and functioned. After 12 months, mean values (± standard deviation) of isotope uptake, TSH, FT3, and FT4 of the 5-g implants were 0.44 ± 0.16%, 27.74 ± 30.4 UI/mL, 3.07 ± 1.10 pg/mL, and 1.01 ± 0.3 ng/dL, repectively. Those for the 10 g implants were 0.71 ± 0.20%, 22.78 ± 19.7 UI/mL, 3.92 ± 1.2 pg/mL, and 1.05 ± 0.3 ng/dL, repectively. Ten-gram implants showed significantly higher isotope uptake than 5-g. TSH, FT3, and FT4 significantly improved over the period of 1 year. Conclusion: Injection of thyroid tissue suspension is a simple method for thyroid autotransplantation. TSH was elevated in the majority to maintain normal or near normal thyroid hormones. Ten-gram implants showed higher isotope uptake than 5-g, although this difference was not reflected by thyroid hormone profile. The implant seemed to function better with the passage of time from 2 months to 12 months.

A new series of 8-methoxy-2-trimethoxyphenyl-3-substituted quinazoline-4(3)-one compounds were designed, synthesized, and screened for antitumor activity against three cell lines, namely, Hela, A549, and MDA compared to docetaxel as reference drug. The molecular docking was performed using Autodock Vina program and 20 ns molecular dynamics (MD) simulation was performed using GROMACS 2018.1 software. Compound 6 was the most potent antitumor of the new synthesized compounds and was evaluated as a VEGFR2 and EGFR inhibitor with (IC50, 98.1 and 106 nM respectively) compared to docetaxel (IC50, 89.3 and 56.1 nM respectively). Compounds 2, 6, 10, and 8 showed strong cytotoxic activities against the Hela cell line with IC50 of, 2.13, 2.8, 3.98, and 4.94 µM, respectively, relative to docetaxel (IC50, 9.65 µM). Compound 11 showed strong cytotoxic activity against A549 cell line (IC50, 4.03 µM) relative to docetaxel (IC50, 10.8 µM). Whereas compounds 6 and 9 showed strong cytotoxic activity against MDA cell line (IC50, 0.79, 3.42 µM, respectively) as compared to docetaxel (IC50, 3.98 µM).

In the current work, the nanocomposites that consist chiefly of three components—α-Fe2O3, NiO and Ni2FeO4, in two different ratios 2:2:1 (FNN-221) and 2:1:1 (FNN-211), respectively—were produced. The synthesis was done in two steps by following the chemical co-precipitation and mechanical ball-milling route. The presence of individual phase was identified from the XRD data without the detection of any additional impurities. The phase fraction of each component estimated from the profile fitting of XRD patterns were found to be 41.2%, 39.7%, 19.1% in FNN-221 sample and 49.5%, 26.4%, 24.1% for FNN-211 sample, respectively, which were consistent with the experimental values. The total magnetization at 300 K was obtained to be 13.41 emu/g and 10.95 emu/g for FNN-221 and FNN-211 samples, respectively. In FNN-211 compound the zero field coercivity (HC) expanded towards the higher field values thereby signifying the exchange bias behavior. Furthermore, the exchange bias field (Hex) for FNN-211 was obtained as 35.1 Oe.

Hepatitis C virus (HCV) is an international challenge. Since the discovery of NS5A direct-acting antivirals, researchers turned their attention to pursue novel NS5A inhibitors with optimized design and structure. Herein we explore highly potent hepatitis C virus (HCV) NS5A inhibitors; the novel analogs share a common symmetrical prolinamide 2,7-diaminofluorene scaffold. Modification of the 2,7-diaminofluorene backbone included the use of (S)-prolinamide or its isostere (S,R)-piperidine-3-caboxamide, both bearing different amino acid residues with terminal carbamate groups. Compound 26 exhibited potent inhibitory activity against HCV genotype (GT) 1b (effective concentration (EC50) = 36 pM and a selectivity index of >2.78 × 106). Compound 26 showed high selectivity on GT 1b versus GT 4a. Interestingly, it showed a significant antiviral effect against GT 3a (EC50 = 1.2 nM). The structure-activity relationship (SAR) analysis revealed that picomolar inhibitory activity was attained with the use of S-prolinamide capped with R- isoleucine or R-phenylglycine residues bearing a terminal alkyl carbamate group.

Clks have been shown by recent studies to be promising targets for cancer therapy, as they are considered key regulators in the process of pre-mRNA splicing, which in turn affects every aspect of tumor biology. In particular, Clk1 and -4 are overexpressed in several human tumors. Most of the potent Clk1 inhibitors reported in the literature are non-selective, mainly showing off-target activity towards Clk2, Dyrk1A and Dyrk1B. Herein, we present new 5-methoxybenzothiophene-2-carboxamide derivatives with unprecedented selectivity. In particular, the introduction of a 3,5-difluoro benzyl extension to the methylated amide led to the discovery of compound 10b (cell-free IC50 = 12.7 nM), which was four times more selective for Clk1 over Clk2 than the previously published flagship compound 1b. Moreover, 10b showed an improved growth inhibitory activity with T24 cells (GI50 = 0.43 µM). Furthermore, a new binding model in the ATP pocket of Clk1 was developed based on the structure-activity relationships derived from new rigidified analogues.

Purpose: To describe the effect of prolonging the standard suction duration during laser-assisted in-situ keratomileusis (LASIK) and its effect on flap thickness and hinge length using sub-Bowman keratomileusis (SBK) microkeratome. Methods: Fifty-six eyes (28 patients) were included and divided into 2 groups; Group-A: eyes with flatter corneas (36 eyes, 18 patients) and mean keratometric readings ranging from 40.13 to 43.71 diopters (D). Group-B: eyes with steeper corneas (20 eyes, 10 patients) with mean keratometric readings ranging from 43.85 to 46.72 D. One-Use-Plus SBK microkeratome was used for flap creation. For right eyes, flap was created immediately once suction was built up. In left eyes, the surgeon waited for 10 s after suction was built up before flap creation. Flap hinge length and flap thickness were measured using surgical caliper and ultrasonic pachymetry, respectively. Results: Statistically significant differences were observed in corneal flap hinge size between right eyes versus left eyes, with a mean of 3.98 ± 0.48 vs. 3.78 ± 0.55 mm (p

A series of new 6-methoxyquinoline-3-carbonitrile derivatives were synthesized using a variety of synthetic routes. The newly synthesized compounds have been characterized by IR, 1H NMR, and mass spectral data followed by elemental analysis. All of the synthesized compounds were evaluated for their in-vitro antimicrobial activity against Streptococcus pneumonia and Bacillus subtilis as examples for Gram-positive bacteria, Pseudomonas aeruginosa and Escherichia coli as examples for Gram-negative bacteria, and Aspergillus fumigatus, Syncephalastrum racemosum, Geotriucum candidum and Candida albicans as representative examples of fungi. The majority of tested compounds showed moderate activities against wide range of selected organisms. Among the tested compounds, the ester derivative 7b and the thioether derivative 9c showed the highest antimicrobial activity against gram-positive strains while the highest activity against gram-negative strains was observed in case of 7b, 7d and 9b while compound 7e found more active than Amphotericin B against three fungal species.

Gallium (Ga) doped zinc oxide (ZnO) nanocrystals were successfully synthesized via a γ-radiation-assisted polymer-pyrolysis route. Ga doped ZnO samples with Ga and ZnO precursor salts with molar ratios of 0%, 3%, 5%, and 10% were produced. A γ-radiation dosage of 1.5 kGy was used for polymerization initiation during the sample preparation. The properties of the obtained nanocrystal samples were characterized using X-ray diffraction (XRD), Fourier transform infrared (FTIR), UV-visible absorption, NIR-VIS-UV diffused reflectance, and high-resolution transmission electron microscopy (HR-TEM) characterization techniques. XRD results revealed the formation of ZnO nanocrystals with wurtzite structure for both Ga-doped and undoped ZnO samples. Noticeable increasing in the line broadening of the XRD peaks as well as pronounced decreasing of crystallite size were observed with the increasing Ga ratio in the samples. Optical peaks around Ga:ZnO samples showed a blueshift in the optical absorption peaks with increasing Ga content. These results are in good agreement with the dependency of crystallites size as well as grain size on Ga ratio obtained from XRD and TEM images, which make them fit well for the powder cool-pigment applications. The doped samples showed high values of NIR reflectance (RNIR*) with percentage varied from 84.25% to 89.05% that enabled them to qualify for cool-nanopigment applications. Furthermore, such doped samples registered low values of visible reflectance (RVIS*) that enabled to reduce the glare from the reflected visible sunlight.

Thermal degradation of polystyrene/ZnO (PS/ZnO) nanocomposites was investigated in this study. PS/ZnO polymer nanocomposites were prepared by using ZnO nanorods as nanofillers that were prepared via the sol-gel route. The as-prepared ZnO nanoparticles showed nanocrystallites in rod-like shapes with a non-uniform hexagonal cross-section and diameter varying from 40 to 75 nm. PS/ZnO nanocomposites with ZnO nanoparticles content ranging from 0–3 wt% are prepared via the common casting method. Even dispersion for ZnO nanoparticles within as-prepared PS/ZnO nanocomposites was verified through SEM/EDX measurements. Thermal degradation of the samples was checked by using the thermogravimetric (TG) analysis and differential scanning calorimetry (DSC) under non-isothermal conditions and a constant heating rate of 10 °C min. The thermal stability of the nanocomposite is elevated compared to that of pristine PS due to the addition of the ZnO nanoparticles. The homogeneity of the PS/ZnO nanocomposites is verified by systematic increases in thermal degradation with increasing ZnO content. The characterization degradation temperatures at different weight loss percentages of ZnO nanoparticles increase at high ZnO wt%. Static activation energy of decomposing is based on TGA data. Activation energies showed some enhancement after the addition of ZnO nanorods into the PS matrix. Enhancing the thermal stability of PS with ZnO addition within the investigated ZnO concentration range is verified by TG, DSC results.