Ligands for peroxisome proliferator-activated receptorγ and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice

Induction of differentiation and apoptosis in cancer cells through ligands of nuclear hormone receptors (NHRs) is a novel and promising approach to cancer therapy. All-trans-retinoic acid (ATRA), an RA receptor-specific NHR ligand, is now used for selective cancers. The NHR, peroxisome proliferator-activated receptor γ (PPARγ) is expressed in breast cancer cells. Activation of PPARγ through a synthetic ligand, troglitazone (TGZ), and other PPARγ-activators cause inhibition of proliferation and lipid accumulation in cultured breast cancer cells. TGZ (10⁻⁵ M, 4 days) reversibly inhibits clonal growth of MCF7 breast cancer cells and the combination of TGZ (10⁻⁵ M) and ATRA (10⁻⁶ M, 4 days) synergistically and irreversibly inhibits growth and induces apoptosis of MCF7 cells, associated with a dramatic decrease of their bcl-2 protein levels. Similar effects are noted with in vitro cultured breast cancer tissues from patients, but not with normal breast epithelial cells. The observed apoptosis mediated by TGZ and ATRA may be related to the striking down-regulation of bcl-2, because forced over-expression of bcl-2 in MCF7 cells cultured with TGZ and ATRA blocks their cell death. TGZ significantly inhibits MCF7 tumor growth in triple immunodeficient mice. Combined administration of TGZ and ATRA causes prominent apoptosis and fibrosis of these tumors without toxic effects on the mice. Taken together, this combination may provide a novel, nontoxic and selective therapy for human breast cancers.     

Gastrointestinal perforation secondary to COVID-19: Case reports and literature review

Introduction:Corona virus disease-2019 (COVID-19) presents primarily with respiratory symptoms. However, extra respiratory manifestations are being frequently recognized including gastrointestinal involvement. The most common gastrointestinal symptoms are nausea, vomiting, diarrhoea and abdominal pain. Gastrointestinal perforation in association with COVID-19 is rarely reported in the literature.Patient concerns and diagnosis:In this series, we are reporting 3 cases with different presentations of gastrointestinal perforation in the setting of COVID-19. Two patients were admitted with critical COVID-19 pneumonia, both required intensive care, intubation and mechanical ventilation. The first one was an elderly gentleman who had difficult weaning from mechanical ventilation and required tracheostomy. During his stay in intensive care unit, he developed Candidemia without clear source. After transfer to the ward, he developed lower gastrointestinal bleeding and found by imaging to have sealed perforated cecal mass with radiological signs of peritonitis. The second one was an obese young gentleman who was found incidentally to have air under diaphragm. Computed tomography showed severe pneumoperitoneum with cecal and gastric wall perforation. The third case was an elderly gentleman who presented with severe COVID-19 pneumonia along with symptoms and signs of acute abdomen who was confirmed by imaging to have sigmoid diverticulitis with perforation and abscess collection.Interventions:The first 2 cases were treated conservatively. The third one was treated surgically.Outcome:Our cases had a variable hospital course but fortunately all were discharged in a good clinical condition.Conclusion:Our aim from this series is to highlight this fatal complication to clinicians in order to enrich our understanding of this pandemic and as a result improve patients’ outcome.     

Physico-chemical characterization and pharmacological evaluation of sulfated polysaccharides from three species of Mediterranean brown algae of the genus Cystoseira

Background

Seaweed polysaccharides are highly active natural substances having valuable applications. The present study was conducted to characterize the physico-chemical properties of sulphated polysaccharides from three Mediterranean brown seaweeds (Cystoseira sedoides, Cystoseira compressa and Cystoseira crinita) and to evaluate their anti-radical, anti-inflammatory and gastroprotective activities.

Methods

The different rates of neutral sugars, uronic acids, L-fucose and sulphate content were determined by colorimetric techniques. The different macromolecular characteristics of isolated fucoidans were identified by size exclusion chromatography equipped with a triple detection: multiangle light scattering, viscometer and differential refractive index detectors, (SEC/MALS/VD/DRI). Anti-inflammatory activity was evaluated, using the carrageenan-induced rat paw edema test in comparison to the references drugs Acetylsalicylate of Lysine and Diclofenac. The gastroprotective activity was determined using HCl/EtOH induced gastric ulcers in rats and to examine the antioxidant effect of fucoidans in the three species, the free radical scavenging activity was determined using 1,1-diphenyl-2-picrylhydrazyl.

Results

The pharmacological evaluation of the isolated fucoidans for their anti-inflammatory, and their gastroprotective effect established that these products from C. sedoides, C. compressa and C. crinita exhibited a significant anti-inflammatory activity at a dose of 50 mg/kg, i.p; the percentages of inhibition of the oedema were 51%, 57% and 58% respectively. And, at the same dose, these fucoidans from C. sedoides and C. compressa showed a significant decrease of the intensity of gastric mucosal damages compared to a control group by 68%, whereas, the fucoidan from C. crinita produced a less gastroprotective effect. Furthermore, the isolated fucoidans exhibited a radical scavenging activity.

Conclusion

The comparative study of fucoidans isolated from three species of the genus Cystoseira showed that they have similar chemicals properties and relatives anti-radical, anti-inflammatory and gastroprotective activities which are found to be promising.     

HIV,pathology and epigenetic age acceleration in different human tissues

GeroScience - Epigenetic clocks based on patterns of DNA methylation have great importance in understanding aging and disease; however, there are basic questions to be resolved in their...     

Serum interleukin-23 levels: relation to depression,anxiety, and disease activity in psoriatic arthritis patients

Clinical Rheumatology - Assessment of serum levels of IL-23 in PsA patients and its correlation with depression, anxiety, and disease activity. Eighty psoriatic arthritis (PsA) patients and eighty...     

Is 30-Day Mortality after Admission for Heart Failure an Appropriate Metric for Quality?

Background

The Centers for Medicare and Medicaid Services (CMS) model for publicly reporting national 30-day-risk-adjusted mortality rates for patients admitted with heart failure fails to include clinical variables known to impact total mortality or take into consideration the culture of end-of-life care. We sought to determine if those variables were related to the 30-day mortality of heart failure patients at Geisinger Medical Center.

Knowledge and attitudes of family doctors,dermatologists, and endocrinologists on sun exposure and vitamin D

Objectives: Vitamin D is an important component of bone metabolism. Skin cells synthesize vitamin D when exposed to the sun. However, prolonged sun exposure damages the skin and increases the risk for skin cancer. The objective is to evaluate and compare the attitudes and recommendations of family doctors, dermatologists, and endocrinologists on exposure to the sun and vitamin D.

Methods: In a cross-sectional study, a questionnaire was completed by personal interview in a study population of 78 family doctors, 21 dermatologists, and 22 endocrinologists.

Results: On a scale of 1–10, the mean score for recommendations to reduce sun exposure was 4.7 for dermatologists, 4.2 for endocrinologists, and 6.4 for family doctors (p < 0.001). Family doctors recommended a mean daily exposure to the sun of 67.4 min compared to 41.4 by dermatologists, and 47.1 by endocrinologists (p = 0.007). Dermatologists and endocrinologists were more likely to recommend protective measures such as hats and long sleeves during sun exposure than family doctors (p < 0.0001). There were no statistically significant differences between male and female doctors for the entire study population.

Conclusions: There is little consensus among these medical practitioners, whether specialists or primary care doctors, concerning sun exposure. Further studies should evaluate the optimal duration and intensity of sun exposure and doctors’ recommendations should be based on the findings.     

Fabrication of novel electrochemical sensors based on modification with different polymorphs of MnO2 nanoparticles. Application to furosemide analysis in pharmaceutical and urine samples

A novel MnO₂ nanoparticles/chitosan-modified pencil graphite electrode (MnO₂ NPs/CS/PGE) was constructed using two different MnO₂ polymorphs (γ-MnO₂ and ε-MnO₂ nanoparticles). X-ray single phases of these two polymorphs were obtained by the comproportionation reaction between MnCl₂ and KMnO₄ (molar ratio of 5 : 1). The temperature of this reaction is the key factor governing the formation of the two polymorphs. Their structures were confirmed by powder X-ray diffraction (XRD), Fourier transform infrared (FTIR) and energy dispersive X-ray (EDX) analysis. Scanning electron microscopy (SEM) was employed to investigate the morphological shape of MnO₂ NPs and the surface of the bare and modified electrodes. Moreover, cyclic voltammetry and electrochemical impedance spectroscopy (EIS) were used for surface analysis of the modified electrodes. Compared to bare PGE, MnO₂ NPs/CS/PGE shows higher effective surface area and excellent electrocatalytic activity towards the oxidation of the standard K₃[Fe(CN)₆]. The influence of different suspending solvents on the electrocatalytic activity of MnO₂ was studied in detail. It was found that tetrahydrofuran (THF) is the optimum suspending solvent regarding the peak current signal and electrode kinetics. The results reveal that the modified γ-MnO₂/CS/PGE is the most sensitive one compared to the other modified electrodes under investigation. The modified γ-MnO₂/CS/PGE was applied for selective and sensitive determination of FUR. Under the optimized experimental conditions, γ-MnO₂/CS/PGE provides a linear response over the concentration range of 0.05 to 4.20 μmol L⁻¹ FUR with a low limit of detection, which was found to be 4.44 nmol L⁻¹ (1.47 ng mL⁻¹) for the 1^st peak and 3.88 nmol L⁻¹ (1.28 ng mL⁻¹) for the 2^nd one. The fabricated sensor exhibits a good reproducibility and selectivity and was applied successfully for the determination of FUR in its dosage forms and in spiked urine samples with good accuracy and precision.

A novel MnO₂ nanoparticles/chitosan-modified pencil graphite electrode (MnO₂ NPs/CS/PGE) was constructed using two different MnO₂ polymorphs (γ-MnO₂ and ε-MnO₂ nanoparticles).