Changes in Anti-SARS-CoV-2 IgG Subclasses over Time and in Association with Disease Severity

IgG is the most prominent marker of post-COVID-19 immunity. Not only does this subtype mark the late stages of infection, but it also stays in the body for a timespan of at least 6 months. However, different IgG subclasses have different properties, and their roles in specific anti-COVID-19 responses have yet to be determined. We assessed the concentrations of IgG1, IgG2, IgG3, and IgG4 against different SARS-CoV-2 antigens (N protein, S protein RBD) using a specifically designed method and samples from 348 COVID-19 patients. We noted a statistically significant association between severity of COVID-19 infection and IgG concentrations (both total and subclasses). When assessing anti-N protein and anti-RBD IgG subclasses, we noted the importance of IgG3 as a subclass. Since it is often associated with early antiviral response, we presumed that the IgG3 subclass is the first high-affinity IgG antibody to be produced during COVID-19 infection.     

New alternatives for erythropoietin therapy in chronic renal failure

Erythropoietin (EPO) is one of the main cytokines involved in the regulation of erythropoiesis. The main site of EPO production are the kidneys. An altered EPO production leads to pathological conditions such as anemia and polycythaemia. Due to the progressive loss of renal peritubular cells, patients with chronic kidney disease (CKD) have low EPO plasma levels. This decreases erythron stimulation with the direct consequence of developing anemia. Before the introduction in the clinical practice of rHuEpo, in the late 1980s, the only solution for treating this type of anemia were blood transfusions and anabolic steroids. Even rHuEpo has proven to be safe and effective for treatment of anemias, there are some concerns about its cost, the need for frequent parenteral administration, and development of anti-EPO antibodies. These inconveniences prompted the search for novel erythropoiesis stimulating agents. Different strategies lead to isolation or chemical synthesis of such agents as darbepoetin alfa and EPO mimetics. In this review, we present some general aspects of EPO biology, with emphasis on chronic renal failure, and expose some of the alternatives to EPO used for anemia correction.     

Triple Therapy-Based on Tegoprazan,a New Potassium-Competitive Acid Blocker,for First-Line Treatment of Helicobacter pylori Infection: A Randomized,Double-Blind,Phase III,Clinical Trial

Background/AimsWe examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication.MethodsA randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)-based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases.ResultsIn total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences.ConclusionsTPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea (ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT03317223","term_id":"NCT03317223"}}NCT03317223).     

Utility of Direct Peroral Cholangioscopy Using a Multibending Ultraslim Endoscope for Difficult Common Bile Duct Stones

Background/AimsTreatment options for difficult bile duct stones are limited. Direct peroral cholangioscopy (POC)-guided lithotripsy may be an option. A newly developed multibending (MB) ultraslim endoscope has several structural features optimized for direct POC. We evaluated the utility of direct POC using an MB ultraslim endoscope for lithotripsy in patients with difficult bile duct stones.MethodsTwenty patients with difficult bile duct stones, in whom stone removal using conventional endoscopic methods, including mechanical lithotripsy, had failed were enrolled from March 2018 to August 2019. Direct POC-guided lithotripsy was performed by electrohydraulic lithotripsy or laser lithotripsy. The primary outcome was complete ductal clearance, defined as the retrieval of all bile duct stones after lithotripsy confirmed by balloon-occluded cholangiography and/or direct POC.ResultsThe technical success rate of direct POC was 100% (20/20), and the free-hand insertion rate was 95% (19/20). Direct POC-guided lithotripsy, attempted by electrohydraulic lithotripsy in nine patients (45%) and laser lithotripsy in 11 patients (55%), was successful in 95% (19/20) of the patients. Complete ductal clearance after direct POC-guided lithotripsy was achieved in 95% (19/20) of patients. Patients required a median of 2 (range, 1–3) endoscopic retrograde cholangiopancreatography sessions for complete stone removal. Adverse event was observed in one patient (5%) with hemobilia and was treated conservatively.ConclusionsDirect POC using an MB ultraslim endoscope was safe and effective for lithotripsy in patients with difficult bile duct stones.     

Design and Evaluation of Orally Dispersible Tablets Containing Amlodipine Inclusion Complexes in Hydroxypropyl-β-cyclodextrin and Methyl-β-cyclodextrin

The development of new orally dispersible tablets containing amlodipine (AML) inclusion complexes in hydroxypropyl-β-cyclodextrin (HP-β-CD) and in methyl-β-cyclodextrin (Me-β-CD) was studied. The methods of obtaining amlodipine and the physical and chemical properties of the inclusion complexes using the two cyclodextrins was investigated separately. Solid inclusion complexes were obtained by three methods: kneading, coprecipitation, and lyophilization, at a molar ratio of 1:1. For comparison, a physical mixture in the same molar ratio was prepared. The aim of the complexation process was to improve the drug solubility. As the lyophilization method leads to a complete inclusion of the drug in the guest molecule cavity, for both used cyclodextrins, these types of compounds were selected as active ingredients for the design of orally dispersible tablets. Subsequently, the formulation of the orodispersible tablets containing AML-HP-β-CD and AML-Me-β-CD inclusion complexes and quality parameters of the final formulation were evaluated. The results prove that F1 and F4 formulations, based on silicified microcrystalline cellulose, which contains insignificant proportions of very small or very large particles, had the lowest moisture degree (3.52% for F1 and 4.03% for F4). All of these demonstrate their porous structure, which led to good flowability and compressibility performances. F1 and F4 formulations were found to be better to manufacture orally dispersible tablets.     

Metallic and Metal Oxides Nanoparticles for Sensing Food Pathogens—An Overview of Recent Findings and Future Prospects

Nowadays, special importance is given to quality control and food safety. Food quality currently creates significant problems for the industry and implicitly for consumers and society. The effects materialize in economic losses, alterations of the quality and organoleptic properties of the commercial products, and, last but not least, they constitute risk factors for the consumer’s health. In this context, the development of analytical systems for the rapid determination of the sanitary quality of food products by detecting possible pathogenic microorganisms (such as Escherichia coli or Salmonella due to the important digestive disorders that they can cause in many consumers) is of major importance. Using efficient and environmentally friendly detection systems for identification of various pathogens that modify food matrices and turn them into food waste faster will also improve agri-food quality throughout the food chain. This paper reviews the use of metal nanoparticles used to obtain bio nanosensors for the purpose mentioned above. Metallic nanoparticles (Au, Ag, etc.) and their oxides can be synthesized by several methods, such as chemical, physical, physico-chemical, and biological, each bringing advantages and disadvantages in their use for developing nanosensors. In the “green chemistry” approach, a particular importance is given to the metal nanoparticles obtained by phytosynthesis. This method can lead to the development of good quality nanoparticles, at the same time being able to use secondary metabolites from vegetal wastes, as such providing a circular economy character. Considering these aspects, the use of phytosynthesized nanoparticles in other biosensing applications is also presented as a glimpse of their potential, which should be further explored.     

Eating Habits in Patients with Familial Hypercholesterolemia from North-Eastern Romania

(1) Background: Familial hypercholesterolemia (FH) is a genetic autosomal dominant disorder characterized by elevated levels of low-density lipoprotein cholesterol (LDL) that develops deposits of lipids in the arterial wall. Since it is underdiagnosed and undertreated, the disease has a high risk of premature cardiovascular disease and death. Patients are not always aware of the changes they should make in their diet. Thus, our study aimed to evaluate through a food frequency questionnaire their eating habits. (2) Methods: We included 70 patients with FH and 20 subjects in a control group that were evaluated through a physical examination and blood tests. They also completed a food frequency questionnaire. (3) Results: Throughout our study, we observed several aspects: regardless of age, patients with FH had higher carbohydrate intakes compared to the control group; from the same group, a positive correlation was observed between salami intake and the levels of glucose and glycated hemoglobin. Moreover, the sour cream preference was associated with higher liver function tests. In the control group, we observed a higher intake of pasta and fast food and fewer fruit portions. (4) Conclusions: As far as we know, this is the first study from Romania that evaluated the eating habits of patients diagnosed with FH. Our study reveals that, although patients with FH avoid junk food, they still have a high intake of carbohydrates when compared to the control group. Further research is needed in order to get a comprehensive nutritional evaluation of these patients.     

The Five Factor Model of personality applied to adults who stutter

Previous research has not explored the Five Factor Model of personality among adults who stutter. Therefore, the present study investigated the five personality domains of Neuroticism, Extraversion, Openness, Agreeableness and Conscientiousness, as measured by the NEO Five Factor Inventory (NEO-FFI), in a sample of 93 adults seeking speech treatment for stuttering, and compared these scores with normative data from an Australian and a United States sample. Results revealed that NEO-FFI scores for the stuttering group were within the ‘average’ range for all five personality domains. However, adults who stutter were characterized by significantly higher Neuroticism, and significantly lower Agreeableness and Conscientiousness, than normative samples. No significant differences were found between groups on the dimensions of Extraversion and Openness. These results are discussed with reference to the relationship between personality factors among adults who stutter, their directionality, and implications for predicting treatment outcome.Learning outcomes: The reader will be able to: (1) describe the Five Factor Model of personality, including the NEO-FFI personality domains of Extraversion, Neuroticism, Openness, Agreeableness, and Conscientiousness, and (2) discuss differences in NEO-FFI domain scores between adults who stutter and normative samples, and (3) understand the clinical implications of personality profiles in terms of treatment process and outcome for adults who stutter.     

Changes in antioxidant,inflammatory and metabolic markers during 1 week cultivation of human skin explants

Human skin explant (HSE) seems to be a useful model for dermatological/cosmetic testing. HSE prepared from donor superfluous skin from plastic surgery operations is cheap and easily obtainable compared to reconstructed models. The HSE use, however, may be limited by the degeneration processes during cultivation. The aim was to monitor changes in metabolic activity and selected apoptotic, inflammatory and antioxidant parameters during 7 day cultivation. The significant changes were found in the superoxide dismutase‐2 level from day 5, glutathione S‐reductase level from day 6, metabolic activity and fibulin‐5 level from day 4, cyclooxygenase‐2, interleukin‐6 and interleukin‐10 from day 1 to 2. Other selected markers (lipid peroxidation products and glutathione level, glutathione S‐transferase, catalase, superoxide dismutase and glutathione S‐reductase activity, glutathione peroxidase and glutathione S‐reductase levels) were not modified significantly due to high inter‐individual variability of skin donors. The HSE microstructure as well as cytokeratin‐10 and proliferation marker Ki67 expression was also only minimally affected during cultivation. Collectively, the results demonstrate that HSE represents a good model for short‐term studies focused on the physical and chemical agent toxicity, protective potential of compounds or metabolic biotransformation. However, reduced metabolic activity, increased inflammation and the high inter‐individual variability and sensitivity of donors have to be taken into consideration.     

A fluorescent curcumin-based Zn(II)-complex reactivates mutant (R175H and R273H) p53 in cancer cells

Background

Mutations of the p53 oncosuppressor gene are amongst the most frequent aberration seen in human cancer. Some mutant (mt) p53 proteins are prone to loss of Zn(II) ion that is bound to the wild-type (wt) core, promoting protein aggregation and therefore unfolding. Misfolded p53 protein conformation impairs wtp53-DNA binding and transactivation activities, favouring tumor growth and resistance to antitumor therapies. Screening studies, devoted to identify small molecules that reactivate mtp53, represent therefore an attractive anti-cancer therapeutic strategy. Here we tested a novel fluorescent curcumin-based Zn(II)-complex (Zn-curc) to evaluate its effect on mtp53 reactivation in cancer cells.

Methods

P53 protein conformation was examined after Zn-curc treatment by immunoprecipitation and immunofluorescence assays, using conformation-specific antibodies. The mtp53 reactivation was evaluated by chromatin-immunoprecipitation (ChIP) and semi-quantitative RT-PCR analyses of wild-type p53 target genes. The intratumoral Zn-curc localization was evaluated by immunofluorescence analysis of glioblastoma tissues of an ortothopic mice model.

Results

The Zn-curc complex induced conformational change in p53-R175H and -R273H mutant proteins, two of the most common p53 mutations. Zn-curc treatment restored wtp53-DNA binding and transactivation functions and induced apoptotic cell death. In vivo studies showed that the Zn-curc complex reached glioblastoma tissues of an ortothopic mice model, highlighting its ability to crossed the blood-tumor barrier.

Conclusions

Our results demonstrate that Zn-curc complex may reactivate specific mtp53 proteins and that may cross the blood-tumor barrier, becoming a promising compound for the development of drugs to halt tumor growth.