Revision to the musculoskeletal domain of the BILAG-2004 index to incorporate ultrasound findings.

OBJECTIVES: To improve the definitions of inflammatory arthritis within the musculoskeletal (MSK) domain of the BILAG-2004 index by incorporating imaging findings and clinical features predictive of response to treatment. METHODS: The BILAG MSK Subcommittee proposed revisions to the BILAG-2004 index definitions of inflammatory arthritis, based on review of evidence in two recent studies. Data from these studies were pooled and analysed to determine the impact of the proposed changes on the severity grading of inflammatory arthritis. RESULTS: The revised definition for severe inflammatory arthritis includes definition of 'basic activities of daily living'. For moderate inflammatory arthritis, it now includes synovitis, defined by either observed joint swelling or MSK US evidence of inflammation in joints and surrounding structures. For mild inflammatory arthritis, the definition now includes reference to symmetrical distribution of affected joints and guidance on how US may help re-classify patients as moderate or no inflammatory arthritis. Data from two recent SLE trials were analysed (219 patients). A total of 119 (54.3%) were graded as having mild inflammatory arthritis (BILAG-2004 Grade C). Of these, 53 (44.5%) had evidence of joint inflammation (synovitis or tenosynovitis) on US. Applying the new definition increased the number of patients classified as moderate inflammatory arthritis from 72 (32.9%) to 125 (57.1%), while patients with normal US (n = 66/119) could be recategorized as BILAG-2004 Grade D (inactive disease). CONCLUSIONS: Proposed changes to the definitions of inflammatory arthritis in the BILAG-2004 index will result in more accurate classification of patients who are more or less likely to respond to treatment.

Mechanistic Insights into Bisphenol A-Mediated Male Infertility: Potential Role of Panax Ginseng Extract.

. The escalating prevalence of male infertility in the contemporary era across the globe can be largely attributed to environmental pollution, which is the common etiological factor due to the ubiquitous presence of the environmental contaminants. Bisphenol A is recognized as an endocrine-disrupting chemical that has adverse effects on both male and female reproductive systems. On the other hand, numerous studies have demonstrated that Panax ginseng possessed the potential to improve male infertility parameters; promote spermatogenesis, recover the quality and motility of sperm and enhance testicular functions as it acted as a natural androgen supplement. The objective of this review is to offer a summary of the findings obtained from the current research data on the insult of bisphenol A (BPA) on male infertility and its supposed mode of action, as well as shed light on the potent ameliorative role of Panax ginseng extract, with a special focus on the mechanism behind its action. This review delivers a clear understanding of BPA mechanism of action on male infertility and the presumed risks deriving from its exposure. Also, this review provides evidence for the functional role of Panax ginseng extract in restoring male fertility.

Vitamin D ameliorates diethylnitrosamine-induced liver preneoplasia: A pivotal role of CYP3A4/CYP2E1 via DPP-4 enzyme inhibition.

Growing evidence has indicated that vitamin D (Vit D) regulates cell proliferation and differentiation in cancer cells. Accordingly, the present study was conducted to investigate the possible beneficial effects of Vit D on diethylnitrosamine (DEN)-induced liver preneoplasia. The effect of Vit D on HepG2 cells was investigated using MTT assay. Additionally, liver preneoplasia was induced in Swiss male albino mice by giving overnight fasted animals 5 consecutive doses of DEN (75 mg/kg/week). Oral treatment with Vit D (200 IU/kg/day) was initiated either 2 weeks before DEN (first protocol) or 1 week after the first dose of DEN injection (second protocol). At the end of the experiment, tissue levels of GGT, DPP-4, TNF-α, IL-6, CYP2E1, and CYP3A4 were also estimated. Moreover, the histopathological study of liver tissue and immunohistochemical detection of GST-P, PCNA, and NF-κB were performed. Vit D exerted a significant cytotoxic effect on HepG2 cells via significantly increasing BAX, p53, and BAX/Bcl2 ratio, and significantly decreasing Bcl2 mRNA expression. In both in vivo protocols, Vit D was capable of normalizing relative liver weight, PCNA, altered hepatocellular foci, and ductular proliferation. Moreover, Vit D significantly reduced the DEN-induced elevation of AST, ALT, ALP, GGT, DDP-4, TNF-α, IL-6, CYP2E1, liver DNA damage, GST-P, NF-κB, nuclear hyperchromasia/pleomorphism, cholestasis, and inflammatory cell aggregates, but significantly increased CYP3A4 content. In conculsion, current results reflect the potential impact of Vit D in the management of early stages of liver cancer.

Determinants of vaccine adherence among non-dialysis chronic kidney disease patients in Qatar.

INTRODUCTION: Chronic kidney disease (CKD) is a global health problem. Reduced innate and adaptive immunological responses predispose CKD patients to infections. Despite the clinical and epidemiological importance of CKD and the great value of vaccination as a prophylactic measure, the utilization of recommended vaccines in Qatar has not yet been evaluated. METHODS: We conducted a cross-sectional study to estimate the level of influenza, pneumococcal, and hepatitis B vaccination and the predictors of adherence to these recommended vaccines among non-dialysis CKD patients receiving renal ambulatory care in Qatar from 1 September 2020 to 30 April 2021. Complete vaccination was defined as receiving the three vaccines, and partial vaccination was defined as receiving one or two vaccines. The full and partial vaccination predictors were assessed using multivariate logistic regression and reported as odds ratio (OR) with p<0.05 indicating statistical significance. RESULTS: 416 non-dialysis CKD patients were included in our analysis. 73% were males; the mean age was 56 ± 15 years. More than 50% of the patients were from the Middle East, followed by 36% from Asia. Most patients had concurrent hypertension, concurrent diabetes mellitus, and were stage V CKD. Only 12% of the patients were fully vaccinated, while 73% received partial vaccination. The predictors of vaccination included age, gender, Asian origin, employment, living conditions, concurrent medical conditions, CKD stage, allergy to medications, and use of injectable medications. Only stage V CKD positively predicted adherence to full and partial vaccinations in non-dialysis CKD patients. CONCLUSION: There is very low adherence to the recommended vaccines in CKD patients, with a prevalence of complete vaccination of 12% only. Increased public awareness about the importance of vaccination in CKD may improve the adherence rates among these patients in Qatar.

Regulatory T-cell phenotypes in children with sickle cell disease.

BACKGROUND: Regulatory T cells (Tregs) are linked to a reduction in alloreactive immune responses, but few studies have investigated the impact of hydroxyurea (HU) therapy on Tregs in sickle cell disease (SCD). METHODS: Our case-controlled study presented here included two groups, the first comprising 60 pediatric SCD patients, 30 of whom did not receive any treatment and 30 who received HU, and the second group consisting of 30 healthy controls. Flow cytometry was used to evaluate the percentage of CD4+CD25+highFoxp3+ Tregs present and their phenotypes. RESULTS: The percentage of CD4+CD25+high Tregs was significantly increased in untreated SCD patients in comparison to treated SCD patients and controls. Conversely, treated SCD children had a lower percentage of CD4+CD25+high Tregs than controls. In addition, a significant increase in the percentage of CD4+CD25+highFoxp3+ Tregs was found in untreated SCD patients, compared to in HU-treated patients and controls. The percentage of naive CD45RA+ Tregs was significantly decreased in untreated SCD patients when compared to other groups. CONCLUSIONS: Among children with SCD, HU treatment exhibited significant qualitative and quantitative effects on Tregs by decreasing their frequency, and increasing the proportion of naive CD45RA+ Tregs and reducing levels of the most suppressive Tregs: HLA-DR+, CD39+, and CD69+. IMPACT: Among children with, SCD, HU treatment exhibited significant qualitative and quantitative effects on Tregs. HU treatment in SCD decreases the frequency of Tregs, as well as the levels of the most suppressive Tregs: HLA-DR+, CD39+, and CD69+. At the same time, HU increases the proportion of naive CD45RA+ Tregs. Our study showed the impact of HU therapy on Tregs in children with SCD.

Regulatory T-lymphocyte subsets in children with chronic immune thrombocytopenia after high-dose of dexamethasone.

BACKGROUND: Immune thrombocytopenia (ITP) is an acquired autoimmune disease. This study's objective was to estimate the variations in the population of CD4+CD25+High FoxP3+ cells (CD4+ regulatory T-lymphocytes; Tregs) in previously untreated children with chronic ITP managed in Assiut University Hospitals, as well as to evaluate the efficacy of high-dose dexamethasone (HD-DXM) in these patients. METHODS: In this study, we investigated the frequencies of T-lymphocyte subsets in 27 untreated children with chronic ITP. RESULTS: Prior to treatment, the percentages of CD4+CD25High cells and Tregs were significantly lower in the chronic ITP group compared to the control group (p = 0.018 and p < 0.0001, respectively). After treatment with HD-DXM, Tregs and platelets were significantly increased in these patients (p < 0.0001 for both). CONCLUSIONS: Our results suggest that Tregs are deficient in children with chronic ITP and that HD-DXM immunosuppressive therapy can restore the levels of these cells. IMPACT: CD4+CD25High cells and Tregs were significantly lower in children chronic ITP compared to healthy control. HD-DXM treatment led to significantly increased Tregs and platelets in these patients. Our results suggest that Tregs are deficient in children with chronic ITP and that HD-DXM immunosuppressive therapy can restore the levels of these cells.

Ruthenium-Doping-Induced Amorphization of VS4 Nanostructures with a Rich Sulfur Vacancy for Enhanced Hydrogen Evolution Reaction in a Neutral Electrolyte Medium.

The generation of pure H2 from a neutral electrolyte solution represents a transformative route with low cost and environmentally friendly nature. However, the complex kinetics of hydrogen evolution reaction (HER) via water electrolysis make its practical application to be difficult. Herein, we have reported Ru-doping-induced formation of VS4 nanostructures with a rich S vacancy for neutral HER in a 0.2 M phosphate buffer solution. The Ru-doped VS4 demands an overpotential value of 160 mV at 10 mA/cm2 current density with a lower catalyst loading of 0.1 mg/cm2, while pristine VS4 demands a 374 mV overpotential with the same mass loading. 60 hours of chronoamperometric study reveals the excellent stability of Ru-doped VS4 materials, which is the highest amount of time ever reported for neutral HER. The marginal degradation of a catalyst under a long-term stability study was confirmed through inductively coupled plasma mass spectrometry (ICP-MS) analysis. The introduction of Ru to the VS4 lattice leads to a 4.35-fold increase in the turnover-frequency values compared to those of bare VS4 nanostructures. The higher HER activity of S-vacancy-enriched VS4 materials is thought to originate through effective water adsorption in S vacancy and Ru3+ sites followed by the dissociation of a H2O molecule, and S22- efficiently converts Had to H2. Also, post-HER characterization reveals that the transformation of some Ru3+ to Ru0 additionally favored the HER by providing a better H adsorption site under a static cathodic potential.

Lipid based nanoparticles as a novel treatment modality for hepatocellular carcinoma: a comprehensive review on targeting and recent advances.

Liver cancer is considered one of the deadliest diseases with one of the highest disease burdens worldwide. Among the different types of liver cancer, hepatocellular carcinoma is considered to be the most common type. Multiple conventional approaches are being used in treating hepatocellular carcinoma. Focusing on drug treatment, regular agents in conventional forms fail to achieve the intended clinical outcomes. In order to improve the treatment outcomes, utilizing nanoparticles-specifically lipid based nanoparticles-are considered to be one of the most promising approaches being set in motion. Multiple forms of lipid based nanoparticles exist including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion, nanoemulsion, phytosomes, lipid coated nanoparticles, and nanoassemblies. Multiple approaches are used to enhance the tumor uptake as well tumor specificity such as intratumoral injection, passive targeting, active targeting, and stimuli responsive nanoparticles. In this review, the effect of utilizing lipidic nanoparticles is being discussed as well as the different tumor uptake enhancement techniques used.

Anticancer activity of novel 3-(furan-2-yl)pyrazolyl and 3-(thiophen-2-yl)pyrazolyl hybrid chalcones: Synthesis and in vitro studies.

Twelve novel chalcone derivatives were prepared using the Claisen-Schmidt condensation reaction. The reaction of 4-acetyl-5-furan/thiophene-pyrazole derivatives 5 with the corresponding aldehydes 6 afforded the targeted chalcone derivatives 7a-l in good yields. The newly synthesized chalcones were fully characterized by spectrometric and elemental analyses. The in vitro anticancer activities of the novel compounds 7a-l were evaluated against four human cancer cell lines: HepG2 (human hepatocellular carcinoma), MCF7 (human Caucasian breast adenocarcinoma), A549 (lung carcinoma), and BJ1 (normal skin fibroblasts). Compound 7g emerged as the most promising compound, with IC50 = 27.7 µg/ml against A549 cells compared to the reference drug doxorubicin (IC50 = 28.3 µg/ml), and IC50 = 26.6 µg/ml against HepG2 cells compared to the reference drug doxorubicin (IC50 = 21.6 µg/ml). The gene expression and DNA damage values and the DNA fragmentation percentages for compound 7g were determined on the lung and liver cell lines. The expression levels of the AMY2A and FOXG1 genes increased significantly (p < 0.01) in the negative samples of lung cancer cells compared with treated cells. Also, the expression values of the PKM and PSPH genes improved significantly (p < 0.01) in the negative samples compared with treated samples of liver cancer cells. The DNA damage values increased significantly (p < 0.01) in treated lung cell line samples (7g) and the positive control. The results showed a significant decrease (p < 0.05) in DNA damage values in the negative samples of liver cancer cells compared to those treated with 7g. However, the DNA fragmentation values increased significantly (p < 0.01) in the treated lung and liver cell line samples compared with the negative control.

Antibacterial Mechanism of Multifunctional MXene Nanosheets: Domain Formation and Phase Transition in Lipid Bilayer.

MXenes, two-dimensional metal carbides or nitrides with multifunctional surfaces, are one of the most promising antibacterial nanoscale materials. However, their putative bactericidal mechanism is elusive. To study their bactericidal mechanism, we investigated the interaction between a MXene nanosheet and a model bacterial membrane by molecular dynamics simulations and found that an adsorbed MXene on a membrane surface induced a local phase transition in a domain where the fluidity of the phospholipid in this domain at room temperature was comparable with that of the gel phase. The domain also showed a denser and thinner phospholipid membrane structure than the peripheral phospholipids. By comparing it with our previous experiments of the bactericidal activity of MXenes, we proposed the leakage of intercellular molecules at the phase boundary defects as a possible bactericidal mechanism of MXenes that leads to cell lysis. This study provides a useful model for tailoring new bactericidal nanomaterials.

Serum Galanin in Children with Autism Spectrum Disorder.

Recent studies have attempted to measure several biomarkers to understand the complex interactions of the anatomic systems that may be involved in autism spectrum disorder (ASD). In CNS, galanin takes part in a variety of pathological and physiological processes. Prior research has indicated it is involved in several neuropsychiatric disorders and has a role in inhibiting the neuronal firing and release of serotonin, norepinephrine, and acetylcholine. To date, serum galanin levels have not been investigated in the context of ASD. This study aimed, therefore, to compare the serum galanin levels of children with ASD and healthy controls and to reveal any association between galanin level and the severity of ASD, as well as other psychological and demographic parameters. Serum galanin levels were measured by radioimmunoassay in 116 children with ASD and 98 healthy children. We observed significantly increased serum concentrations of galanin in children with ASD relative to healthy children. Moreover, children with severe ASD had significantly higher galanin levels than those with less severe disease. We also confirmed significant positive correlations between galanin and psychiatric parameters in children with ASD. For the first time, we suggest a possible correlation between serum galanin and the degree of ASD severity. Increased galanin levels may play a role in the pathogenesis of ASD.

Optimized Green Extraction of Polyphenols from Cassia javanica L. Petals for Their Application in Sunflower Oil: Anticancer and Antioxidant Properties.

The total phenolic content (TPC) from Cassia javanica L. petals were extracted using ethanolic solvent extraction at concentrations ranging from 0 to 90% and an SCF-CO2 co-solvent at various pressures. Ultrasound-assisted extraction parameters were optimized using response surface methodology (RSM). Antioxidant and anticancer properties of total phenols were assessed. An SCF-CO2 co-solvent extract was nano-encapsulated and applied to sunflower oil without the addition of an antioxidant. The results indicated that the best treatment for retaining TPC and total flavonoids content (TFC) was SCF-CO2 co-solvent followed by the ultrasound and ethanolic extraction procedures. Additionally, the best antioxidant activity by ß-carotene/linoleic acid and DPPH free radical-scavenging test systems was observed by SCF-CO2 co-solvent then ultrasound and ethanolic extraction methods. SCF-CO2 co-solvent recorded the highest inhibition % for PC3 (76.20%) and MCF7 (98.70%) and the lowest IC50 value for PC3 (145 µ/mL) and MCF7 (96 µ/mL). It was discovered that fortifying sunflower oil with SCF-CO2 co-solvent nanoparticles had a beneficial effect on free fatty acids and peroxide levels. The SCF-CO2 method was finally found to be superior and could be used in large-scale processing.

Ultrasound to identify systemic lupus erythematosus patients with musculoskeletal symptoms who respond best to therapy: the US Evaluation For mUsculoskeletal Lupus longitudinal multicentre study.

OBJECTIVES: To determine whether SLE patients with inflammatory joint symptoms and US synovitis/tenosyovitis achieve better clinical responses to glucocorticoids compared with patients with normal scans. Secondary objectives included identification of clinical features predicting US synovitis/tenosynovitis. METHODS: In a longitudinal multicentre study, SLE patients with physician-diagnosed inflammatory joint pain received intramuscular methylprednisolone 120 mg once. Clinical assessments, patient-reported outcomes and bilateral hand/wrist USs were collected at 0, 2 and 6 weeks. The primary outcome (determined via internal pilot) was the early morning stiffness visual analogue scale (EMS-VAS) at 2 weeks, adjusted for baseline, comparing patients with positive (greyscale ≥2 and/or power Doppler ≥1) and negative US. Post hoc analyses excluded FM. RESULTS: Of 133 patients, 78 had a positive US. Only 53 (68%) of these had one or more swollen joint. Of 66 patients with one or more swollen joint, 20% had a negative US. A positive US was associated with joint swelling, symmetrical small joint distribution and serology. The primary endpoint was not met: in the full analysis set (N = 133) there was no difference in baseline-adjusted EMS-VAS at week 2 [-7.7 mm (95% CI -19.0, 3.5); P = 0.178]. After excluding 32 patients with FM, response was significantly better in patients with a positive US at baseline [baseline-adjusted EMS-VAS at 2 weeks -12.1 mm (95% CI -22.2, -0.1); P = 0.049]. This difference was greater when adjusted for treatment [-12.8 mm (95% CI -22, -3); P = 0.007]. BILAG and SLEDAI responses were higher in US-positive patients. CONCLUSION: In SLE patients without FM, those with a positive US had a better clinical response to therapy. Imaging-detected synovitis/tenosynovitis may be considered to decide on therapy and enrich clinical trials.

Dendritic cells and monocyte subsets in children with Gaucher disease.

BACKGROUND: There are minimal data on the frequencies of monocyte subsets and dendritic cells (DCs) in children with Gaucher disease (GD), as nearly all previous studies have involved adult patients. Consequently, we aimed to describe the changes in these cell subpopulations in children with GD type 1 who were on regular enzyme replacement therapy (ERT). METHODS: This case-control study included 25 children with GD1 and 20 healthy controls. All participants underwent investigations such as complete blood count and flow cytometric assessment of DC and monocyte frequencies and phenotype. RESULTS: We found that GD1 children had significantly reduced percentages of both types of DCs, i.e., plasmacytoid DCs and myeloid DCs, compared to the control group. There was also a significant reduction in absolute monocyte numbers and percentage of classical monocyte. Moreover, the GD1 children had higher frequencies of non-classical and intermediate monocytes than the control group. CONCLUSIONS: Our results so far indicate that, when compared to the control group, the GD1 children had significantly reduced total and classical monocyte, with significantly decreased frequencies for both types of DCs. These changes can contribute to immunological abnormalities in pediatric patients with GD1. IMPACT: Children with Gaucher disease type 1 (GD1) have significantly reduced total and classical monocyte frequencies, with decreasing percentages for both types of dendritic cells. GD1 children had significantly reduced frequencies of myeloid and plasmacytoid dendritic cells as compared to the controls. The GD1 children also had significant changes in monocyte subsets when compared to the controls. Our results show that monocytes and dendritic cells' significant changes could contribute to immunological abnormalities in pediatric patients with GD1.

Unprecedented environmental and energy impacts and challenges of COVID-19 pandemic.

The rapid transmission tendency, severity, and wide geographical spread of newly emerged novel coronavirus (SARS-CoV-2) in different environmental matrices, including water, air, and soil, has posed severe health, environmental, energy, and economic challenges worldwide. Despite the severe health effects, unprecedented improvements in air quality in many countries due to emergency measures, and public behavior changes have been reported. SARS-CoV-2 has been detected in air and sewage samples in several studies across the globe. The use of wastewater-based epidemiology (WBE) could be a valuable method to monitor the outbreak of COVID-19, which requires fast and reliable methods for virus detection in sewage. However, water treatment companies face many pressures due to potential for aerosolization, PPE shortages, and changed usage patterns. In addition, the unprecedented impact of the COVID-19 outbreak on the worldwide economy especially the energy sector, and its impact on our ecosystem required instant responses. This article discusses the recent developments and challenges faced in water, air, and energy resources, including renewables and non-renewables as the significant and interrelated components of the ecosystem. Furthermore, some recommendations have been directed, which may serve as a guideline to the scientists, legislators, and other stakeholders. A future roadmap has been proposed to overcome the tragic effects of COVID-19 and developing a sustainable environmental system to minimize the impact of such infectious outbreaks in the future.

Effects of lead, cadmium, copper and zinc levels on the male reproductive function.

This study aimed to investigate the effects of heavy metals on measures of male fertility. One hundred and two infertile men with occupational exposure and thirty fertile men were included in this study. Blood and urinary levels of lead, cadmium, zinc and copper were measured by atomic absorption spectrophotometry. Semen parameters and a motile sperm organelle morphology examination were also performed. Measures of hormonal levels, oxidation-reduction potential, DNA fragmentation index and chromatin condensation were assessed for all participants. Heavy metals levels, oxidative stress and DNA quality were significantly higher in the infertile group compared to controls. FSH and testosterone levels were lower in the infertile group. A urinary cadmium level was positively associated with abnormal sperm morphology (r = .225, p < .05). Normal morphology was inversely correlated with the duration of the exposure (r = -.227, p = .022). The blood lead level was positively related to the level of testosterone (r = .223, p = .031). Cadmium and lead blood levels were positively correlated with the level of chromatin decondensation (r = .528, p < .001; r = .280, p = .017). Our study showed that occupational exposure to heavy metals is very harmful to reproductive health. DNA quality and oxidative stress investigations must be recommended for reprotoxic exposed patients prior to in vitro fertilisation treatment.

Formulation, Pharmacokinetics evaluation, and IVIVC Assessment of Gliclazide Multiparticulates in Rat Model.

In vitro and in vivo studies of gliclazide (GLZ)-loaded freeze-dried alginate-gelatin (AL-GL) beads were carried out, aiming to modify its oral bioavailability. Crosslinked freeze-dried GLZ AL-GL beads (particle size: 1.5- and 3.0-mm) were prepared. In vitro evaluation of GLZ AL-GL beads included SEM, DSC, FT-IR, and release rate study in gradient media. In vivo study was single-dose (4 mg/kg), randomized, parallel-group design, two-treatment (T: test GLZ AL-GL beads and R: reference product Diamicron® 30-mg MR tablet) conducted in 96 healthy rats. Each group was subdivided into 2 sub-groups (G1 and G2) having different blood sampling schemes for up to 72 h. Assessment of level A in-vitro-in-vivo correlation (IVIVC) model was carried out. AL-GL beads successfully increased GLZ release rate compared to R. GLZ percent released (Q4h) was 109.34, 86.85, and 43.43% for 1.5-mm and 3.0-mm beads and R, respectively. DSC analysis confirmed the interaction of AL-GL via crosslinking. No chemical interaction of GLZ has occurred as proved by FT-IR. Relative bioavailability (T/R) for AUC0-∞ was 132.45% for G1 and 146.16% for G2. No significant differences between T and R in the primary pharmacokinetic parameters were determined. Tmax values were found to be earlier in the case of G1 than those of G2. A secondary absorption peak of GLZ was clearly detected in the case of R while its sharpness was minimized in T. High IVIVC was established, and hence, the proposed in vitro release model perfectly correlated with the in vivo study. The current study design might be a platform to enable panoramic view for GLZ variability in vivo.

Novel 2-cyanoacrylamido-4,5,6,7-tetrahydrobenzo[b]thiophene derivatives as potent anticancer agents.

Ethyl 2-acrylamido-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate as well as its corresponding bis-derivatives, 5-10, with aliphatic linkers were synthesized, fully characterized, and tested as novel anticancer agents. The targeted compounds, 5-10, were obtained by the Knoevenagel condensation reactions of bis-o- or -p-aldehyde with a molar ratio of ethyl 2-(2-cyanoacetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate of 2 in the presence of piperidine in excellent yields (93-98%). The in vitro anticancer activities of the prepared compounds were evaluated against HepG2, MCF-7, HCT-116, and BJ1 cells. Compounds 7 and 9 emerged as the most promising compounds, with IC50 values of 13.5 and 32.2 µg/ml, respectively, against HepG2 cells, compared with the reference drug doxorubicin (IC50 : 21.6 µg/ml). Real-time reverse-transcription polymerase chain reaction was used to measure the changes in expression levels of the COL10A1 and COL11A1, ESR1, and ERBB2, or AXIN1 and CDKN2A genes within the treated cells, as genetic markers for colon, breast, or liver cancers, respectively. Treatment of the colon cancer cells with compounds 5, 9, and 10, or breast and liver cancers cells with compounds 7, 8, 9, and 10 downregulated the expression of the investigated tumor markers. The DNA damage values (depending on comet and DNA fragmentation assays) increased significantly upon treatment of colon cancer cells with compounds 5, 9, and 10, and breast and liver cells with compounds 8, 9, and 10. The structure-activity relationship suggested that the increase of the chain of the alkyl linker increases the anticancer activity and the compounds with bis-cyanoacrylamide moieties are more active than those with one cyanoacrylamide moiety.

Influence of Nanoencapsulation Using High-Pressure Homogenization on the Volatile Constituents and Anticancer and Antioxidant Activities of Algerian Saccocalyx satureioides Coss. et Durieu.

The nanoencapsulation of essential oils enhances their applicability in several areas, such as pharmaceuticals and food biopreservation. This study focuses on the encapsulation of Saccocalyx satureioides Coss. et Durieu essential oil into nanoemulsions by high-pressure homogenization (HPH) and its effect on the volatile constituents and the antioxidant and anticancer activities of the essential oil. The analysis of hydrodistilled (HD) S. satureioides essential oil using gas chromatography-mass spectrometry revealed a total of 28 constituents, representing 99.80%, while only 13 constituents were identified in nanoemulsions, representing 98.65% of the total volatile material. The use of HPH led to qualitative and quantitative differences between the volatile profiles of the HD and the nanoemulsion of S. satureioides essential oil. Whereas borneol, α-terpineol, and thymol were the predominant constituents in the HD oil, carvacrol, thymol, and γ-terpinene were the major constituents in the nanoemulsion. The antioxidant activity of the S. satureioides essential oil nanoemulsion displayed was lower as compared to that of HD oil using DPPH free radical-scavenging, CUPRAC, and ABTS assays. This is consistent with the differences in total flavonoid, total phenolic, and volatiles detected in both HD oil and its nanoemulsion. Meanwhile, the cytotoxicity on liver cancer cells (Hep-G2) was stronger using nanoemulsions (106 µg/mL) than using HD oil (274.8 µg/mL).

Responsiveness of clinical and ultrasound outcome measures in musculoskeletal systemic lupus erythematosus.

OBJECTIVE: To assess the responsiveness of clinical outcome measures in musculoskeletal SLE compared with US. METHODS: A prospective pilot study was conducted in consecutive SLE patients with inflammatory musculoskeletal symptoms. Clinical assessments including SLEDAI, BILAG, 28 tender and swollen joint counts, physician and patient visual analogue scales (VAS), and US were performed at 0, 2 and 4 weeks following 120 mg i.m. methylprednisolone acetate. Responsiveness was analysed using changes and effect sizes using Cohen's criteria. RESULTS: Twenty patients were recruited. Fifteen out of 20 had clinical swelling at baseline. All clinical and US parameters were significantly improved at week 4 (all P ⩽ 0.01). Musculoskeletal-BILAG score improved in 16/20. Musculoskeletal-SLEDAI improved in 7/20. SLE responder index 4 criteria were assessed in 19 patients with SLEDAI ⩾4 at baseline and were met in 9/19 at 4 weeks. Effect sizes at 4 weeks were large (>0.5) for US, physician VAS and BILAG, and medium (>0.3) for joint counts and SLEDAI. Large effect sizes for improvement in US grey-scale and power Doppler were observed in both SLE responder index 4 responders (r = -0.51 and -0.56, respectively) and non-responders (r = -0.62 and -0.59, respectively) at 4 weeks. CONCLUSION: This is the first study to measure the responsiveness of clinical outcome measures in musculoskeletal SLE against an objective inflammation measure. BILAG and physician VAS were the most responsive clinical instruments. US was highly responsive in musculoskeletal SLE, while SLEDAI and joint counts appeared suboptimal for detection of improvement. These results suggest that clinical trials based on the SLEDAI and SLE responder index 4 may underestimate the efficacy of therapy in SLE.