Fenofibrate for COVID-19 and related complications as an approach to improve treatment outcomes: the missed key for Holy Grail

Financiado para publicación en acceso aberto: Universidade de Vigo/CISUGIntroduction Fenofbrate is an agonist of peroxisome proliferator activated receptor alpha (PPAR-α), that possesses antiinfammatory, antioxidant, and anti-thrombotic properties. Fenofbrate is efective against a variety of viral infections and diferent infammatory disorders. Therefore, the aim of critical review was to overview the potential role of fenofbrate in the pathogenesis of SARS-CoV-2 and related complications. Results By destabilizing SARS-CoV-2 spike protein and preventing it from binding angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV-2 entry, fenofbrate can reduce SARS-CoV-2 entry in human cells Fenofbrate also suppresses infammatory signaling pathways, which decreases SARS-CoV-2 infection-related infammatory alterations. In conclusion, fenofbrate anti-infammatory, antioxidant, and antithrombotic capabilities may help to minimize the infammatory and thrombotic consequences associated with SARSCoV-2 infection. Through attenuating the interaction between SARS-CoV-2 and ACE2, fenofbrate can directly reduce the risk of SARS-CoV-2 infection. Conclusions As a result, fenofbrate could be a potential treatment approach for COVID-19 control

Panton-Valentine Leukocidin (PVL) genes may not be a reliable marker for community-acquired MRSA in the Dakahlia Governorate, Egypt

Abstract Background Methicillin-resistant Staphylococcus aureus is linked to both nosocomial and community infections. One of the key virulence factors of S. aureus is Panton-Valentine leukocidin (PVL). The PVL genes are mostly associated with community-acquired MRSA (CA-MRSA). This study evaluates the prevalence of PVL genes as a marker for CA-MRSA at tertiary hospitals in Mansoura, Dakahlia, Egypt. S. aureus was isolated from clinical specimens obtained from different departments of tertiary hospitals, outpatient clinics, and hospital healthcare workers (HCWs). PCR was used to detect the mecA, PVL, and SCCmec genes among the recovered isolates. Standard broth microdilution method was used to determine the minimum inhibitory concentrations (MIC) of nine antibiotics against S. aureus. Results Two hundred S. aureus isolates were recovered and identified out of the total isolates (n = 320). The mecA gene was detected in 103 S. aureus isolates (51.5%). Among the MRSA isolates, 46.60% were PVL-positive. The incidence of the PVL genes of MRSA in nosocomial (HA), outpatient clinics (CA), and HCWs was 46.66%, 56.52%, and 42%, respectively. All MRSA isolates showed resistance to cefoxitin. The percentage of resistance to most tested antibiotics was high, except for ciprofloxacin (6.85%). Both antibiotic resistance and multidrug resistance among MRSA isolates were generally higher in PVL-positive isolates than in PVL-negative isolates in HA- and CA-MRSA isolates. While SCCmec type V was the most prevalent in PVL-positive MRSA stains, type I was the most prevalent in PVL-negative isolates. Conclusion This study revealed that PVL genes are generally highly prevalent among mecA-positive MRSA isolates, whether they are CA-MRSA, HA-MRSA, or HCW isolates. Therefore, PVL is not a valid marker for CA-MRSA in Mansoura, Dakahlia Governorate, Egypt, as has been reported in other countries. Further epidemiologic studies are required to track the incidence of PVL in HA-MRSA, CA-MRSA, and HCW isolates in other Egyptian governorates

The Potential Nexus between Helminths and SARS-CoV-2 Infection: A Literature Review

Chronic helminth infections (CHIs) can induce immunological tolerance through the upregulation of regulatory T cells. In coronavirus disease 2019 (COVID-19), abnormal adaptive immune response and exaggerated immune response may cause immune-mediated tissue damage. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) and CHIs establish complicated immune interactions due to SARS-CoV-2-induced immunological stimulation and CHIs-induced immunological tolerance. However, COVID-19 severity in patients with CHIs is mild, as immune-suppressive anti-inflammatory cytokines counterbalance the risk of cytokine storm. Since CHIs have immunomodulatory effects, therefore, this narrative review aimed to clarify how CHIs modulate the immunoinflammatory response in SARS-CoV-2 infection. CHIs, through helminth-derived molecules, may suppress SARS-CoV-2 entry and associated hyperinflammation through attenuation of the inflammatory signaling pathway. In addition, CHIs may reduce the COVID-19 severity by reducing the SARS-CoV-2 entry points in the initial phase and immunomodulation in the late phase of the disease by suppressing the release of pro-inflammatory cytokines. In conclusion, CHIs may reduce the severity of SARS-CoV-2 infection by reducing hyperinflammation and exaggerated immune response. Thus, retrospective and prospective studies are recommended in this regard

New insights into the anticancer effects of Polycladia crinita aqueous extract and its selenium nanoformulation against the solid Ehrlich carcinoma model in mice via VEGF, notch 1, NF-кB, cyclin D1, and caspase 3 signaling pathway

Background: Phaeophyceae species are enticing interest among researchers working in the nanotechnology discipline, because of their diverse biological activities such as anti-inflammatory, antioxidant, anti-microbial, and anti-tumor. In the present study, the anti-cancer properties of Polycladia crinita extract and green synthesized Polycladia crinita selenium nanoparticles (PCSeNPs) against breast cancer cell line (MDA-MB-231) and solid Ehrlich carcinoma (SEC) were investigated.Methods: Gas chromatography–mass spectroscopy examinations of Polycladia crinita were determined and various analytical procedures, such as SEM, TEM, EDX, and XRD, were employed to characterize the biosynthesized PCSeNPs. In vitro, the anticancer activity of free Polycladia crinita and PCSeNPs was evaluated using the viability assay against MDA-MB-231, and also cell cycle analysis by flow cytometry was determined. Furthermore, to study the possible mechanisms behind the in vivo anti-tumor action, mice bearing SEC were randomly allocated into six equal groups (n = 6). Group 1: Tumor control group, group 2: free SeNPs, group 3: 25 mg/kg Polycladia crinita, group 4: 50 mg/kg Polycladia crinita, group 5: 25 mg/kg PCSeNPs, group 6: 50 mg/kg PCSeNPs.Results: Gas chromatography–mass spectroscopy examinations of Polycladia crinita extract exposed the presence of many bioactive compounds, such as 4-Octadecenoic acid-methyl ester, Tetradecanoic acid, and n-Hexadecenoic acid. These compounds together with other compounds found, might work in concert to encourage the development of anti-tumor activities. Polycladia crinita extract and PCSeNPs were shown to inhibit cancer cell viability and early cell cycle arrest. Concentrations of 50 mg/kg of PCSeNPs showed suppression of COX-2, NF-кB, VEGF, ki-67, Notch 1, and Bcl-2 protein levels. Otherwise, showed amplification of the caspase 3, BAX, and P53 protein levels. Moreover, gene expression of caspase 3, caspase 9, Notch 1, cyclin D1, NF-кB, IL-6, and VEGF was significantly more effective with PCSeNPs than similar doses of free extract.Conclusion: The PCSeNPs mediated their promising anti-cancerous action by enhancing apoptosis and mitigating inflammation, which manifested in promoting the total survival rate and the tumor volume decrease

New investigation of anti-inflammatory activity of Polycladia crinita and biosynthesized selenium nanoparticles: isolation and characterization

Abstract Background Marine macroalgae have gained interest recently, mostly due to their bioactive components. Polycladia crinita is an example of marine macroalgae from the Phaeophyceae class, also known as brown algae. They are characterized by a variety of bioactive compounds with valuable medical applications. The prevalence of such naturally active marine resources has made macroalgae-mediated manufacturing of nanoparticles an appealing strategy. In the present study, we aimed to evaluate the antioxidant and anti-inflammatory features of an aqueous extract of Polycladia crinita and biosynthesized P. crinita selenium nanoparticles (PCSeNPs) via a carrageenan-induced rat paw edema model. The synthesized PCSeNPs were fully characterized by UV–visible spectroscopy, FTIR, XRD, and EDX analyses. Results FTIR analysis of Polycladia crinita extract showed several sharp absorption peaks at 3435.2, 1423.5, and 876.4 cm−1 which represent O–H, C=O and C=C groups. Moreover, the most frequent functional groups identified in P. crinita aqueous extract that are responsible for producing SeNPs are the –NH2–, –C=O–, and –SH– groups. The EDX spectrum analysis revealed that the high percentages of Se and O, 1.09 ± 0.13 and 36.62 ± 0.60%, respectively, confirmed the formation of SeNPs. The percentages of inhibition of the edema in pretreated groups with doses of 25 and 50 mg/kg, i.p., of PCSeNPs were 62.78% and 77.24%, respectively. Furthermore, the pretreated groups with 25, 50 mg/kg of P. crinita extract displayed a substantial decrease in the MDA levels (P < 0.00, 26.9%, and 51.68% decrease, respectively), indicating potent antioxidant effect. Additionally, the pretreated groups with PCSeNPs significantly suppressed the MDA levels (P < 0.00, 54.77%, and 65.08% decreases, respectively). The results of immune-histochemical staining revealed moderate COX-2 and Il-1β expressions with scores 2 and 1 in rats pre-treated with 25 and 50 mg/kg of free extract, respectively. Additionally, the rats pre-treated with different doses of PCSeNPs demonstrated weak COX-2 and Il-1β expressions with score 1 (25 mg/kg) and negative expression with score 0 (50 mg/kg). Both antioxidant and anti-inflammatory effects were dose-dependent. Conclusions These distinguishing features imply that this unique alga is a promising anti-inflammatory agent. Further studies are required to investigate its main active ingredients and possible side effects

Clinical validation of sensitest colistin, a broth microdilution-based method to evaluate colistin MICs

The global spread of multidrug-resistant Gram-negative bacteria has led to the return of colistin for treating severe infections. Recently, different plasmidmediated genes conferring resistance to this drug were described and reported worldwide. International committees (EUCAST/CLSI) reevaluated inconsistencies surrounding colistin antimicrobial susceptibility testing (AST), concluding that broth microdilution (BMD) should serve as the reference method for AST. The development of an accurate, reproducible commercial test based on BMD is therefore highly desirable. SensiTest Colistin (STC), a BMD-based compact 4-test panel containing the lyophilized antibiotic in 7 2-fold dilutions (0.25 to 16 g/ml) was here compared with the EUCAST-CLSI standard reference method (BMD) and, for some isolates, with the automated Phoenix 100 system (PHX). A total of 353 bacterial strains were evaluated by two different laboratories; 137 isolates were resistant to colistin (19 were intrinsically resistant, 83 harbored the mcr-1 gene). Essential agreement (EA) between STC and BMD was obtained for 339 out of the 353 strains tested (96.0%). Overall categorical agreement was obtained for 349 out of the 353 strains analyzed (98.9%). Two major errors (MEs; 0.93%) and two very major errors (VMEs; 1.46%) were documented. STC appeared to be a simple but highly reliable test with good reproducibility even with panels stored at room temperature or at 35°C. Moreover, STC showed a good performance with strains carrying the mcr-1 gene, with a 98.8% EA. As the secondary endpoint of our study, VMEs for PHX were documented for 6 isolates (10%

Long COVID and risk of erectile dysfunction in recovered patients from mild to moderate COVID-19

Abstract Patients with coronavirus disease 2019 (COVID-19) were shown to have reduced serum testosterone levels compared to healthy individuals. Low testosterone levels are linked with the development of erectile dysfunction (ED). In this case-controlled study, 20 healthy controls and 39 patients with ED 3 months after recovering from mild-to-moderate COVID-19 pneumonia were studied. The patients ranged in age from 31 to 47 years. To identify early and late COVID-19 infections, real-time polymerase-chain reaction (RT-PCR) and COVID-19 antibody testing were done. The levels of luteinizing hormone (LH), follicular stimulating hormone (FSH), total testosterone (TT), free testosterone (FT), free androgenic index (FAI), and sex hormone-binding globulin (SHBG) were measured. The sexual health inventory for patients (SHIM) score was used to measure the erectile function of the patients and controls. When compared to the controls, the TT serum level in long COVID-19 (LC) patients with ED was low (p = 0.01). In contrast to controls, FT and FAI were both lower in LC patients with ED. (p = 0.001). FSH serum levels did not significantly differ (p = 0.07), but in ED patients, LH serum levels were elevated. SHIM scores were associated with low TT (p = 0.30), FT (p = 0.09), and high LH (p = 0.76) in LC patients with ED. Male patients with decreased serum levels of LH and testosterone may have hypothalamic-pituitary–gonadal axis dysfunction, which could lead to the development of LC-induced ED. Therefore, an in-depth research is necessary to confirm the causal link between COVID-19 and ED in LC patients

Development and validation of a predictive scoring system for in-hospital mortality in COVID-19 Egyptian patients: a retrospective study

Abstract SARS-CoV-2 virus has rapidly spread worldwide since December 2019, causing COVID-19 disease. In-hospital mortality is a common indicator for evaluating treatment outcomes. Therefore, the developing and validating a simple score system from observational data could assist in modulating the management procedures. A retrospective cohort study included all data records of patients with positive PCR for SARS-CoV-2. The factors that associated with mortality were analyzed, then allocation of potential predictors of mortality was executed using different logistic regression modeling, subsequently scoring system was developed from the most weighted predictors. The mortality rate of patients with COVID-19 pneumonia was 28.5% and 28.74%, respectively. The most significant factors that affected in-hospital mortality were old age (> 60 years), delay in hospital admission (> 4 days), high neutrophil/lymphocyte ratio “NLR” (> 3); higher computed tomography severity score; and CT-SS (> 20), in addition to using remdesivir and tocilizumab in the treatment protocol (P < 0.001 for all). The validity of the newly performed score was significant; the AUC was 85%, P < 0.001, and its prognostic utility was good; the AUC was 75%, P < 0.001. The prognostic utility of newly developed score system (EGY.Score) was excellent and could be used to adjust the treatment strategy of highly at-risk patients with COVID-19 pneumonia