FKA‐A NPs enhances PTX‐A NPs efficacy to suppress ovarian cancer via regulating Skp2/YAP pathway

alexandrossfakianakis shared this article with you from Inoreader FKA‐A NPs enhances PTX‐A NPs efficacy to suppress ovarian cancer via regulating Skp2/YAP pathway via Fundamental & Clinical Pharmacology Abstract Recurrence and distant metastasis after paclitaxel (PTX)-based chemotherapy in ovarian cancer (OC) patients remains a clinical obstacle. Flavokawain A (FKA) is a novel chalcone from kava plant which can induce G2/M arrest and inhibit invasion and metastasis in different tumor cells. In this study, we examined the effects and the molecular mechanism of sodium aescinate (Aes)-stabilized nanoparticles FKA-A NPs in enhancing the efficacy of PTX-A NPs in vitro and in vivo. We showed that FKA-A NPs combined with PTX-A NPs notably inhibited the proliferation, migration and reduced the expression of EMT-related markers in OCs. YAP nuclear translocation and its downstream signaling pathway was remarkably activated after PTX-A NPs treatment in OCs. FKA-A NPs obviously inhibited YAP nuclear translocation and reduced the transcriptional activity of YAP target genes. Simultaneously, FKA-A NPs dose- and time-dependently inhibited Skp2 expression in A2780 and Skov3 cells. In contra st, overexpression of Skp2 significantly attenuated the inhibition of FKA-A NPs on YAP nuclear translocation. In OC homograft mice, treatment with FKA-A NPs and PTX-A NPs significantly suppressed the growth of homograft tumor compared with PTX-A NPs, but did not decrease mice's body weight. In summary, we demonstrate that FKA-A NPs enhance the efficacy of PTX-A NPs against OCs in vitro and in vivo via reducing Skp2 expression, thus suppressing YAP nuclear translocation and activity of its target genes. View on Web

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Safety and Immunogenicity of a Recombinant Receptor Binding Domain‐Based Protein Subunit Vaccine (Noora Vaccine™) Against COVID‐19 in Adults: A Randomized, Double‐Blind, Placebo‐Controlled, Phase 1 Trial

alexandrossfakianakis shared this article with you from Inoreader Safety and Immunogenicity of a Recombinant Receptor Binding Domain‐Based Protein Subunit Vaccine (Noora Vaccine™) Against COVID‐19 in Adults: A Randomized, Double‐Blind, Placebo‐Controlled, Phase 1 Trial via Journal of Medical Virology Abstract The development of a safe and effective vaccine is essential to protect populations against COVID-19. There are several vaccine candidates under investigation with different mechanisms of action. In the present study, we have evaluated the safety and immunogenicity of a recombinant RBD-based protein subunit vaccine (Noora vaccine) against COVID-19 in adults. This phase 1 trial is a randomized, double-blind, placebo-controlled study to evaluate the safety and immunogenicity of the recombinant RBD-based protein subunit vaccine (Noora vaccine) against COVID-19 in healthy adults volunteers. Eligible participants were included in this study after evaluating their health status and considering the exclusion criteria. They were then randomized into three groups and received three doses of vaccine (80 µg, 120 µg, and placebo) on days 0, 21, and 35. Primary outcomes including solicited, unsolicited, and medically attended adverse events were recorded during this st udy. Secondary outcomes including the humoral and cellular immunity (including anti-RBD IgG antibody and neutralizing antibody) were measured on days 0, 21, 28, 35, 42, and 49 by using the ELISA kit and the Virus Neutralization Test (VNT) was performed on day 49. Totally 70 cases were included in this phase 1 trial and 60 of them completed the study. Safety assessments showed no severe adverse events. Local pain at the vaccine injection site occurred in 80% of the vaccinated volunteers. Induration and redness at the injection site were the other adverse reactions of this vaccine. There was no significant difference between the studied groups regarding adverse reactions. Anti-RBD IgG antibody and neutralizing antibody assessment showed significant seroconversion in comparison to the placebo group (80%, and 100% respectively, P<0.001). The cellular immunity panel also showed mild to moderate induction of TH1 responses and the VNT showed 78% of seroprotection. The results of this ph ase 1 trial showed acceptable safety without serious adverse events and significant seroconversions in the humoral and cellular immunity panel. The dose of 80 µg is an appropriate dose for injection in the next phases of the trial. This article is protected by copyright. All rights reserved. View on Web

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Curcumin reduces inflammation in rat apical periodontitis

alexandrossfakianakis shared this article with you from Inoreader Curcumin reduces inflammation in rat apical periodontitis via International Endodontic Journal Abstract Aim To evaluate the effect of systemic curcumin administration on the severity of apical periodontitis (AP). Methodology Forty male Wistar rats weighing 250-280g each, age 2.5 months, were distributed into four groups (n=10): control untreated rats (C), control rats treated with curcumin (CUR), rats with pulp exposure-induced apical periodontitis (AP), and rats with pulp exposure-induced apical periodontitis treated with curcumin (AP-CUR). Curcumin treatment was administered orally once daily for 15 days before pulp exposure and continued for 30 days after pulp exposure. The rats were sacrificed at 30 days, and the jaws were collected and reconstructed in a program specific for micro-CT. The jaws were processed for analysis of the inflammatory process using Haemotoxylin and Eosin staining and immunohistochemical assays for interleukin tumour necrosis factor alpha (TNF-α), interleukin (Il)-6, and Il-1β. Tartrate-resistant acid phosphatase (TRAP) and osteocalcin (OCN) staining were used to analyze the resorptive process on the bone surface of periapical area. Kruskal–Wallis with Dunn's test was performed for nonparametric data, and ANOVA with Tukey's test for parametric data, p < .05. Results Micro-CT revealed no statistically significant differences in bone resorption between the AP and AP-CUR groups (p > .05). The levels of inflammatory cell infiltration and immunoreactivity for the proinflammatory cytokines TNF-α, Il-6, and Il-1β were significantly higher in the periapical lesions of the AP group than in the AP-CUR group (p < .05). The number of TRAP-positive multinucleated cells was higher in the AP group than in the AP-CUR group (p < .05). In OCN-positive cells, no differences were observed between the AP and AP-CUR groups (p > .05). Conclusions Oral supplementation with curcumin had a significant effect on the AP severity in rats, suggesting an anti-inflammatory effect of curcumin on AP development. View on Web

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The Effects of Tongue Elevation using a Weighted Plastic Bottle on the Tongue Pressure and Activity of Suprahyoid Muscles

alexandrossfakianakis shared this article with you from Inoreader The Effects of Tongue Elevation using a Weighted Plastic Bottle on the Tongue Pressure and Activity of Suprahyoid Muscles via Journal of Oral Rehabilitation Abstract Background A rise in tongue pressure coincides with an increase in the suprahyoid muscles activity. Objectives The aim was to investigate the effects of holding a weighted plastic bottle on tongue pressure and the suprahyoid muscles activity. Methods Eighteen participants (8 men and 10 women; mean age 42 ± 16 years) participated in this study. All participants had no history of speech, language, hearing, or swallowing disorders and no tooth loss, and they did not require dentures. Healthy participants held gauzes connected with a plastic bottle with increasing resistive loads of 0 g, 250 g, 500 g, and 750 g, between their palate and tongue. The maximum tongue pressure and average tongue pressure were measured during a 5-second hold. The average tongue pressure was defined as the mean tongue-pressure data in each task. The suprahyoid muscles activity was measured using the electromyogram (EMG). The root mean square of the EMG signals measured while lifting different loads and while performing the head lifting exercises were compared. All variables were examined using the Friedman's test and Wilcoxon signed-rank test. Results The maximum tongue pressure (p < .05) and average tongue pressure values (p < .05) increased gradually in the anterior–median region with increasing resistive loads, and the root mean square amplitudes for 250 g, 500 g, and 750 g were not significant compared to head lifting exercises. Conclusion These results indicated that Plastic bottle holding could be a potential strength-training tool for the tongue and the suprahyoid muscles. View on Web

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Risk Factors for Recurrence of Peritonsillar Abscess

alexandrossfakianakis shared this article with you from Inoreader Risk Factors for Recurrence of Peritonsillar Abscess via The Laryngoscope Objectives This study aimed to investigate the risk factors associated with peritonsillar abscess (PTA) recurrence in adult patients. Methods This retrospective cohort study used a nationwide insurance claims database in Japan. Adult patients (aged ≥ 20 years) who received intravenous antibiotics or surgical therapy within 5 days of their first PTA diagnosis were included. Multivariable Cox proportional modeling was used to investigate the risk factors for PTA recurrence using the variables: age, sex, comorbidities, tobacco use, history of recurrent tonsillitis, duration of intravenous antibiotics, and surgical therapy for PTA. Results This study included 12,012 patients (8784 men, 73.1%). Of them, 1358 (11.3%) experienced PTA recurrence. An age ≥40 years and treatment with intravenous antibiotics for 3 days or more were associated with a lower risk of PTA recurrence (aged ≥ 40 years: adjusted hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.62–0.78, treated with intravenous antibiotics for 3 days or more: adjusted HR: 0.85; 95% CI: 0.76–0.96). Patients with a history of recurrent tonsillitis were associated with a higher risk of recurrence (adjusted HR: 1.79; 95% CI: 1.47–2.19). Conclusion A median age of 20–39 years, a history of recurrent tonsillitis, and less than 3 days of intravenous antibiotic therapy may be risk factors for PTA recurrence among adult patients. Further studies exploring more detailed clinical data are necessary to confirm the risk factors for PTA recurrence. Level of Evidence 3 Laryngoscope, 2022 View on Web

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Monovalent rotavirus vaccine efficacy against different rotavirus genotypes: a pooled analysis of Phase II and III trial data

alexandrossfakianakis shared this article with you from Inoreader Monovalent rotavirus vaccine efficacy against different rotavirus genotypes: a pooled analysis of Phase II and III trial data via Clinical Infectious Diseases Advance Access Abstract Background Rotavirus vaccine performance appears worse in countries with high rotavirus genotype diversity. Evidence suggests diminished vaccine efficacy (VE) against G2P[4], which is heterotypic with existing monovalent rotavirus vaccine formulations. Most studies assessing genotype-specific VE have been underpowered and inconclusive. Methods We pooled individual-level data from ten Phase II and III clinical trials of rotavirus vaccine containing G1 and P[8] antigens (RV1) conducted between 2000 and 2012. We estimated VE against both any-severity and severe (Vesikari score ≥11) rotavirus gastroenteritis (RVGE) using binomial and multinomial logistic regression models for non-specific VE against any RVGE, genotype-specific VE, and RV1-typic VE against genotypes homotypic, partially heterotypic, or fully heterotypic with RV1 antigens. We adjusted models for concomitant oral poliovirus and RV1 vaccination and the country's de signated child mortality stratum. Results Analysis included 87,644 infants from 22 countries in the Americas, Europe, Africa, and Asia. For VE against severe RVGE, non-specific VE was 91% (95% confidence interval (CI): 87-94%). Genotype-specific VE ranged from 96% (95% CI: 89-98%) against G1P[8] to 71% (43-85%) against G2P[4]. RV1-typic VE was 92% (95% CI: 84-96%) against partially heterotypic genotypes but 83% (67-91%) against fully heterotypic genotypes. For VE against any-severity RVGE, non-specific VE was 82% (95% CI: 75-87%). Genotype-specific VE ranged from 94% (95% CI: 86-97%) against G1P[8] to 63% (41-77%) against G2P[4]. RV1-typic VE was 83% (95% CI: 72-90%) against partially heterotypic genotypes but 63% (40-77%) against fully heterotypic genotypes. Conclusions RV1 VE is comparatively diminished against fully heterotypic genotypes including G2P[4]. View on Web

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Fra‐1 induces apoptosis and neuroinflammation by targeting S100A8 to modulate TLR4 pathways in spinal cord ischemia/reperfusion injury

alexandrossfakianakis shared this article with you from Inoreader Fra‐1 induces apoptosis and neuroinflammation by targeting S100A8 to modulate TLR4 pathways in spinal cord ischemia/reperfusion injury via Brain Pathology Schematic illustration depicting the mechanism by which Fra-1-mediated S100A8/TLR4/NF-κB and ERK signaling in the regulation of apoptosis and neuroinflammation during spinal I/R. Abstract Spinal cord ischemia/reperfusion injury (SCII) is a severe complication driven by apoptosis and neuroinflammation. An increase in the expression of c-Fos, a member of the AP-1 family, is known as a neuronal activation marker in SCII. The AP-1 family is composed of Jun, Fos, and is associated with the regulation of cytokines expression and apoptosis. Fra-1 is a member of the Fos family, however, the contribution of Fra-1 to SCII is still unclear. In our study, Fra-1 was highly upregulated especially in neurons and microglia and promoted apoptosis by changing the expression of Bax/Bcl-2 after SCII. Furthermore, we found that Fra-1 directly regulated the transcription expression of S100A8. We demonstrated that knockdown of Fra-1 alleviated S100A8 mediated neuronal apoptosis and inflammatory factor release, thus improved motor function after SCII. Interestingly, we showed that administration of TAK-242, the TLR4 inhibitor, to the ischemia/reperfusion (I/R) injury induced rats suppress ed the activation of the ERK and NF-κB pathways, and further reduced Fra-1 expression. In conclusion, we found that Fra-1-targeted S100A8 was expressed the upstream of Fra-1, and the Fra-1/S100A8 interaction formed a feedback loop in the signaling pathways activated by SCII. View on Web

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The emergence, spread and vanishing of a French SARS‐CoV‐2 variant exemplifies the fate of RNA virus epidemics and obeys the Mistigri rule

alexandrossfakianakis shared this article with you from Inoreader The emergence, spread and vanishing of a French SARS‐CoV‐2 variant exemplifies the fate of RNA virus epidemics and obeys the Mistigri rule via Journal of Medical Virology Abstract The nature and dynamics of mutations associated with the emergence, spread and vanishing of SARS-CoV-2 variants causing successive waves are complex. We determined the kinetics of the most common French variant ("Marseille-4") for 10 months since its onset in July 2020. Here, we analysed and classified into subvariants and lineages 7,453 genomes obtained by next-generation sequencing. We identified two subvariants, Marseille-4A, which contains 22 different lineages of at least 50 genomes, and Marseille-4B. Their average lifetime was 4.1±1.4 months, during which 4.1±2.6 mutations accumulated. Growth rate was 0.079±0.045, varying from 0.010 to 0.173. Most of the lineages exhibited a bell-shaped distribution. Several beneficial mutations at unpredicted sites initiated a new outbreak, while the accumulation of other mutations resulted in more viral heterogenicity, increased diversity and vanishing of the lineages. Marseille-4B emerged when the other Marse ille-4 lineages vanished. Its ORF8 gene was knocked out by a stop codon, as reported in SARS-CoV-2 of mink and in the Alpha variant. This subvariant was associated with increased hospitalization and death rates, suggesting that ORF8 is a nonvirulence gene. We speculate that the observed heterogenicity of a lineage may predict the end of the outbreak. This article is protected by copyright. All rights reserved. View on Web

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Epidemiology and Etiology of Chronic Rhinosinusitis in Asia – a Narrative Review

alexandrossfakianakis shared this article with you from Inoreader Epidemiology and Etiology of Chronic Rhinosinusitis in Asia – a Narrative Review via Clinical Otolaryngology Abstract Background Despite having a similar prevalence to Western populations, literature on chronic rhinosinusitis (CRS) in the Asian population is sparse. There is limited data on the epidemiology and etiology of CRS in Asia. Objectives To review the current literature on the epidemiology and etiology of chronic rhinosinusitis (CRS) in Asia. Methods This is a narrative review of published data on the epidemiology and etiology of CRS. Studies on CRS in Asian countries, published in English and indexed on PubMed or Google Scholar were reviewed. Where available, data extracted included epidemiology, endotype and cytokine profiles and genetic profiles. Results and Conclusion The prevalence of CRS in Asia ranges widely from 2.1% -28.4%. Type 2 inflammation has been reported in 5-55% of Asian patients, with lower levels of Type 2 cytokines reported in head to head comparisons of Western vs Asian patients. Notably, there exists marked heterogeneity in criterion of the tissue eosinophilic infiltration for diagnosis of type 2 chronic rhinosinusitis. Our review suggests that differences in prevalence of CRS and proportion of eosinophilic CRS between Asia and Europe and the Americas requires further study. Large-scale Asian studies utilizing standardized definitions are needed to bridge this gap. Head to head genetic and microbiomal analysis may also be useful in understanding differences in CRS between the Asian and Western populations. View on Web

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