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Protective antibodies in the upper respiratory tract prevent the spread of COVID-19 in the community. Intranasal vaccines could raise the specific secretory IgA and IgG levels. This is a single-center, randomized, double-blind, placebo-controlled clinical trial to evaluate the safety and immunogenicity of Razi Cov Pars (RCP) intranasal recombinant protein subunit COVID-19 vaccine as a booster in adults. We compared specific IgG and IgA levels in the intranasal RCP group ( n = 97) versus placebo ( n = 96) in serum, saliva, and nasal mucosal secretions on days 0 and 14 and reported their Geometric Mean Ratios (GMR) and 95% confidence intervals (CI). We showed significant increases in IgA and IgG anti-RBD in the nasal mucosa in the RCP group, but their increase was not detectable in the serum and saliva. Anti-spike IgA in the nasal mucosa also increased in the RCP group compared to the placebo. This increase against the COVID-19 variant Omicron was also similar to that of the Wuhan. We detected no serious adverse reactions or anaphylaxis and all adverse events resolved completely during the follow-up period and were similar in both groups. Intranasal RCP is safe, stimulates the respiratory mucosal immunity, and could be a booster on various COVID-19 vaccines and be effective against new virus variants.

Background: Heart failure is a growing cardiovascular disease burden with high mortality rates, primarily attributed to myocardial ischemia. Previous studies have shown promising effects of Photobiomodulation in heart failure treatment. In this study, we aimed to investigate the effect of Photobiomodulation on myocardial function of patients with advanced ischemic heart failure., Method: A non-randomized case series study involving 10 advanced heart failure patients was conducted. Patients received 15 sessions of transcutaneous and intravenous Photobiomodulation therapy using low-level red (658 nm) and infrared lasers (810 nm). All participants were evaluated by six-minute walk tests, dyspnea function classes, and echocardiography. 3 months after the sessions, the mentioned tests were reevaluated RESULT: The study included ten cardiomyopathic patients, 90 % male and the mean age was 63.20±6.01 years. The six-minute walk test change and shortness of breath function class change has 0.852 (p-value=0.006) correlation and the correlation between the Six-minute walk test change and the Systolic ejection fraction rate change, was 0.73 (p-value=0.025)., Conclusion: Based on the results of the study, it can be concluded that interventions in cardiomyopathic patients have shown promising improvements in certain cardiac function parameters. Specifically, the significant enhancement in the six-minute walk test post-intervention (p = 0.013) suggests a positive impact on functional capacity. Although the increase in systolic ejection fraction rate was not statistically significant (p = 0.197), the correlations identified provide valuable insights into the interplay between variables such as shortness of breath function class and the six-minute walk test. These findings underscore the complexity of managing cardiomyopathy and highlight the importance of further research to elucidate the relationships between different clinical parameters and patient outcomes in this population., (Copyright © 2024. Published by Elsevier B.V.)

Background: The immunity induced by primary vaccination is effective against COVID-19; however, booster vaccines are needed to maintain vaccine-induced immunity and improve protection against emerging variants. Heterologous boosting is believed to result in more robust immune responses. This study investigated the safety and immunogenicity of the Razi Cov Pars vaccine (RCP) as a heterologous booster dose in people primed with Beijing Bio-Institute of Biological Products Coronavirus Vaccine (BBIBP-CorV)., Methods: We conducted a randomized, double-blind, active-controlled trial in adults aged 18 and over primarily vaccinated with BBIBP-CorV, an inactivated SARS-CoV-2 vaccine. Eligible participants were randomly assigned (1:1) to receive a booster dose of RCP or BBIBP-CorV vaccines. The primary outcome was neutralizing antibody activity measured by a conventional virus neutralization test (cVNT). The secondary efficacy outcomes included specific IgG antibodies against SARS-CoV-2 spike (S1 and receptor-binding domain, RBD) antigens and cell-mediated immunity. We measured humoral antibody responses at 2 weeks (in all participants) and 3 and 6 months (a subgroup of 101 participants) after the booster dose injection. The secondary safety outcomes were solicited and unsolicited immediate, local, and systemic adverse reactions., Results: We recruited 483 eligible participants between December 7, 2021, and January 13, 2022. The mean age was 51.9 years, and 68.1% were men. Neutralizing antibody titers increased about 3 (geometric mean fold increase, GMFI = 2.77, 95% CI 2.26-3.39) and 21 (GMFI = 21.51, 95% CI 16.35-28.32) times compared to the baseline in the BBIBP-CorV and the RCP vaccine groups. Geometric mean ratios (GMR) and 95% CI for serum neutralizing antibody titers for RCP compared with BBIBP-CorV on days 14, 90, and 180 were 6.81 (5.32-8.72), 1.77 (1.15-2.72), and 2.37 (1.62-3.47) respectively. We observed a similar pattern for specific antibody responses against S1 and RBD. We detected a rise in gamma interferon (IFN-γ), tumor necrosis factor (TNF-α), and interleukin 2 (IL-2) following stimulation with S antigen, particularly in the RCP group, and the flow cytometry examination showed an increase in the percentage of CD3 + /CD8 + lymphocytes. RCP and BBIBP-CorV had similar safety profiles; we identified no vaccine-related or unrelated deaths., Conclusions: BBIBP-CorV and RCP vaccines as booster doses are safe and provide a strong immune response that is more robust when the RCP vaccine is used. Heterologous vaccines are preferred as booster doses., Trial Registration: This study was registered with the Iranian Registry of Clinical Trial at www.irct.ir , IRCT20201214049709N4. Registered 29 November 2021., (© 2024. The Author(s).)

Background: The coronavirus 2019 (COVID-19) has affected the lives of many people worldwide. Patients with chronic underlying morbidities are vulnerable to get the severe form of the infection. The goal of this study was to evaluate the outcome of patients with pulmonary arterial hypertension during the COVID-19 pandemic in Iran., Methods: This cross-sectional study was conducted at a large tertiary center for pulmonary artery hypertension (PAH) patients. The primary end point was the prevalence of SARS-CoV-2 infection in PAH patients. The secondary end points were investigating the severity and mortality of COVID-19 infection in PAH patients during the COVID-19 pandemic., Results: Totally 75 patients were enrolled in the study from December 2019 to October 2021 and 64% were female. The mean ± SD age was 49 ± 16 years. The prevalence of COVID-19 in PAH/chronic thromboembolic pulmonary hypertension patients was 44%. About 66.7% of patients had comorbidities, which was a prognostic factor for COVID-19 infection in PAH patients (P < 0.001). Fifty-six percent of infected patients were asymptomatic. The most reported symptoms in symptomatic patients were fever (28%) and malaise (29%). Twelve percent of patients were admitted with severe symptoms. The mortality rate in infected individuals was 3.7%., Conclusions: COVID-19 infection in PAH/chronic thromboembolic pulmonary hypertension patients seems to be associated with high mortality and morbidity. More scientific proof is needed to clarify different aspect of COVID-19 infection in this population., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Various severe acute respiratory syndrome coronavirus 2 vaccines with different platforms have been administered worldwide; however, their effectiveness in critical cases of COVID-19 has remained a concern. In this national cohort study, 24 016 intensive care unit (ICU) coronavirus disease-2019 (COVID-19) admissions were included from January to April 2022. The mortality and length of ICU stay were compared between the vaccinated and unvaccinated patients. A total of 9428 (39.25%) patients were unvaccinated, and 14 588 (60.75%) patients had received at least one dose of the vaccine. Compared with the unvaccinated, the first, second, and third doses of vaccine resulted in 8%, 20%, and 33% lower risk of ICU mortality in the adjusted model, with risk ratio (RR): 0.92, 95% confidence interval (CI): 0.84-1.001, RR: 0.80, 95% CI: 0.77-0.83, and RR: 0.67, 95% CI: 0.64-0.71, respectively. The mean survival time was significantly shorter in the unvaccinated versus the fully vaccinated patients (hazard ratio [HR]: 0.84, 95% CI: 0.80-0.88); p < 0.001). All vaccine platforms successfully decreased the hazard of ICU death compared with the unvaccinated group. The duration of ICU stay was significantly shorter in the fully vaccinated than in unvaccinated group (MD, -0.62, 95% CI: -0.82 to -0.42; p < 0.001). Since COVID-19 vaccination in all doses and platforms has been able to reduce the risk of mortality and length of ICU-stay, universal vaccination is recommended based on vaccine availability., (© 2023 Wiley Periodicals LLC.)

Objectives : This study aimed to determine the safety and immunogenicity of a combined intramuscular/intranasal recombinant spike protein COVID-19 vaccine (RCP). Methods : We conducted a randomized, double-blind, placebo-controlled, phase I trial. Three vaccine strengths were compared with an adjuvant-only preparation. It included two intramuscular and a third intranasal dose. Eligible participants were followed for adverse reactions. Specific IgG, secretory IgA, neutralizing antibodies, and cell-mediated immunity were assessed. Results : A total of 153 participants were enrolled (13 sentinels, 120 randomized, 20 non-randomized open-labeled for IgA assessment). No related serious adverse event was observed. The geometric mean ratios (GMRs) and 95% CI for serum neutralizing antibodies compared with placebo two weeks after the second injection were 5.82 (1.46-23.13), 11.12 (2.74-45.09), and 20.70 (5.05-84.76) in 5, 10, and 20 µg vaccine groups, respectively. The GMR for anti-RBD IgA in mucosal fluid two weeks after the intranasal dose was 23.27 (21.27-25.45) in the 10 µg vaccine group. The humoral responses were sustained for up to five months. All vaccine strengths indicated a strong T-helper 1 response. Conclusion : RCP is safe and creates strong and durable humoral and cellular immunity and good mucosal immune response in its 10 µg /200 µL vaccine strengths. Trial registration : IRCT20201214049709N1.

Background: Remdesivir is effective against SARS-Cov-2 with little evidence of its adverse effect on the cardiac system. The aim of the present study is investigating the incidence of bradycardia in COVID-19 patients treated with Remdesivir. Methods: This prospective longitudinal study was conducted in a tertiary center on COVID-19 patients for Remdesivir therapy. The objectives were to investigate the incidence of sinus bradycardia, and also the association between their demographics, underlying diseases, and the disease severity with developing bradycardia in COVID-19 patients treated with Remdesivir. Results: Of 177 patients, 44% were male. The mean (±standard deviation) age of patients was 49.79 ± 15.16 years old. Also, 33% were hospitalized due to more severe symptoms. Oxygen support was required for all hospitalized subjects. A total of 40% of the patients had comorbidities, with the most common comorbidity being hypertension. The overall incidence of bradycardia (heart rate<60 bpm) in patients receiving Remdesivir was 27%, of whom 70% had extreme bradycardia (heart rate <50 bpm). There was also a statistically significant reduction in heart rate after five doses of Remdesivir compared to the baseline heart rates. In the multivariable model, none of the covariates including age above 60 years, female sex, CRP>50 mg/L, O2 saturation<90%, underlying cardiovascular disease, hypertension and diabetes mellitus, and beta-blockers were associated with Remdesivir-induced bradycardia. No association was found between the COVID-19 severity indicators and bradycardia. Conclusion: As sinus bradycardia is a prevalent adverse cardiac effect of Remdesivir, it is recommended that all COVID-19 patients receiving Remdesivir, be evaluated for heart rate based on examination; and in the case of bradyarrhythmia, cardiac monitoring should be performed during administration to prevent adverse drug reactions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hajimoradi, Sharif Kashani, Dastan, Aghdasi, Abedini, Naghashzadeh, Mohamadifar, Keshmiri, Noorali, Lookzadeh, Alizadeh, Siri, Tavasolpanahi, Abdolmohammadi, Shafaghi, Rouhani and Shafaghi.)

Signal transducer and activator of transcription 3 (STAT3) has been recognized with dual effects in provision of cancer; either tumor inductive or immune suppressive. Recent findings considering the role of STAT3 in stem cells and cancer stem cell regulation, but its role in gastric cancer stem cells (GCSCs) and modulating the Th17/Treg balance is unknown. In the present study, we aimed to evaluate the role of activated STAT3 in GCSCs and Th17/ Treg cell paradigm. In completion of our previous results, the findings here indicate that gastro-spheroids, as a model of GCSCs, represent higher level of STAT3 activity, up-regulation of TGF-b and VEGF with downregulation of IL-6. On the other hand, treatment of normal naïve T cells with conditioned medium derived from gastro-spheroids promotes T cell differentiation toward cells with a higher level of FOXP3, TGF-b, and IL-10 expression which is indicative of Treg cells. Suppression of STAT3 activation in cancer cells by using Stattic small molecule treatment, decreases stemness features (i.e. spheroid formation and integrity, stemness gene expression and in vivo tumorigenicity capacity) and downregulates TGF-b in the cancer cells. Furthermore, co-culture of conditioned medium of STAT3 inhibited cancer cells with normal PBMCs leads to reduction in the percentage of Treg accompanied with increase of Th17 cells with a decrease in the secretion of TGF-b and increase in IFN-γ in T cells under differentiation. Therefore, targeting the STAT3 pathway in cancer cells seems to control the tumor formation and also impact on immune cells shifting to antitumor Th17 population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Several vaccine candidates for COVID-19 have been developed, and few vaccines received emergency approval with an acceptable level of efficacy and safety. We herein report the development of the first recombinant protein-based vaccine in Iran based on the recombinant SARS-CoV-2 spike protein in its monomeric (encompassing amino acid 1-674 for S1 and 685-1211 for S2 subunits) and trimer form (S-Trimer) formulated in the oil-in-water adjuvant system RAS-01 (Razi Adjuvant System-01). The safety and immunity of the candidate vaccine, referred to as RAZI-COV PARS, were evaluated in Syrian hamster, BALB/c mice, Pirbright guinea pig, and New Zeeland white (NZW) rabbit. All vaccinated animals received two intramuscular (IM) and one intranasal (IN) candidate vaccine at 3-week intervals (days 0, 21, and 51). The challenge study was performed intranasally with 5×10 6 pfu of SARS-CoV-2 35 days post-vaccination. None of the vaccinated mice, hamsters, guinea pigs, or rabbits showed any changes in general clinical observations; body weight and food intake, clinical indicators, hematology examination, blood chemistry, and pathological examination of vital organs. Safety of vaccine after the administration of single and repeated dose was also established. Three different doses of candidate vaccine stimulated remarkable titers of neutralizing antibodies, S1, Receptor-Binding Domain (RBD), and N-terminal domain (NTD) specific IgG antibodies as well as IgA antibodies compared to placebo and control groups (P<0.01). Middle and high doses of RAZI-COV PARS vaccine significantly induced a robust and quick immune response from the third-week post-immunization. Histopathological studies on vaccinated hamsters showed that the challenge with SARS-CoV-2 did not induce any modifications in the lungs. The protection of the hamster was documented by the absence of lung pathology, the decreased virus load in the lung, rapid clearance of the virus from the lung, and strong humoral and cellular immune response. These findings confirm the immunogenicity and efficacy of the RAZI-COV PARS vaccine. Of the three tested vaccine regimens, the middle dose of the vaccine showed the best protective immune parameters. This vaccine with heterologous prime-boost vaccination method can be a good candidate to control the viral infection and its spread by stimulating central and mucosal immunity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Banihashemi, Es-haghi, Fallah Mehrabadi, Nofeli, Mokarram, Ranjbar, Salman, Hajimoradi, Razaz, Taghdiri, Bagheri, Dadar, Hassan, Eslampanah, Salehi Najafabadi, Lotfi, Khorasani and Rahmani.)

After the outbreak of the novel coronavirus at the end of December 2019 in China, it has become a global pandemic. Clinical manifestation of coronavirus disease 2019 (COVID-19) has a wide range of presentations from asymptomatic to severe multi-organ involvement. Hemoptysis appears to be one of the major manifestations of severe acute respiratory syndrome that is related to COVID-19 infection. The occurrence of hemoptysis is multifactorial. However, massive hemoptysis is usually related to pulmonary aspergillosis or severe bronchiectasis due to corticosteroid pulse therapy that can be life-threatening. This manuscript presents five cases of successful life-saving bronchial artery embolization in patients with COVID-19 infection who were suffering from massive hemoptysis that was mostly related to aspergillosis and bronchiectasis. These cases are followed by a review of the literature., Competing Interests: Conflict of Interest None declared., (International College of Angiology. This article is published by Thieme.)

Coronavirus disease 2019 (COVID-19), a highly contagious infectious disease, has had a catastrophic effect on the world's demographics resulting in more than 2.9 million deaths worldwide till January 2021. It can lead to systemic multi-organ complications; in particular, venous and arterial thromboembolism risk is significantly increased. Venous thromboembolism (VTE) occurs in 22.7% of patients with COVID-19 in the ICU and 8% in non-ICU hospitalized patients. Studies evaluating thromboprophylaxis strategies in patients with COVID-19 are needed to improve the prevention of VTE. VTE is the most commonly reported thrombotic complication, with higher incidence rates among critically ill patients. Several vaccines have been licensed and are currently used to combat the COVID-19 pandemic. Also, several cases of vaccine-induced thrombosis have been reported. Vaccination remains the most critical measure to curb the COVID-19 pandemic. There is a broad consensus that the benefits of vaccination greatly outweigh the potential risks of rare vaccine side effects, such as vaccine-induced immune thrombotic thrombocytopenia (VITT). Therefore, the importance of vaccination should be emphasized. This statement aims to focus on VITT., (Copyright© 2022 National Research Institute of Tuberculosis and Lung Disease.)

Beta-thalassemia is a heterogeneous group of anemic disorders caused by the absence or defective production of beta-globin chains. Their clinical manifestations vary from asymptomatic to severe symptoms leading to a transfusion-dependent anemic state. The genes that cause thalassemia are prevalent in Asian and African populations, particularly concentrated in the Middle East, Mediterranean region, parts of India, and South East Asia. Over time, the disease causes various musculoskeletal abnormalities with complex pathophysiology secondary to chronic anemia. The compensatory mechanisms result in diffuse marrow hyperplasia, yellow to red marrow reconversion, osteopenia, and pathologic fractures. Inability to remove excess iron and inevitable iron overload as a result of multiple blood transfusions in patients with thalassemia major and intermedia is another face of the disease. Musculoskeletal manifestations include osteopenia, coarse trabeculae, bone expansion, synovitis, joint effusion, and metaphyseal dysplasia. These complications have long-lasting effects on the skeletal growth pattern resulting in bone deformity, short stature, premature closure of physes, and predisposition to infection. Additionally, there are radiologic features of iron-chelator therapy, which are unique and unrelated to the disease process itself. Familiarity of radiologists with the imaging features of beta-thalassemia is crucial in both diagnosis and timely management of the disease and its complications., (© 2021. ISS.)

Background: Gastric cancer remains one of the leading causes of cancer-associated mortalities globally. Accumulating evidence support the presence of gastric cancer stem cells (CSCs) and their role in the pathogenesis and therapeutic challenges of gastric cancer. MicroRNAs (miRNAs) may be influenced by the cellular differentiative state and as critical regulators of the cellular fate in development and cancer, can modulate the behavior of CSCs too. Here, we aimed to investigate the expression relevance of three prognostic miRNAs (miR-21, miR-10b, and miR-146a) in CSCs of AGS and MKN-45 gastric cancer cell lines., Methods: Serial sphere-forming assay in serum-free culture medium was used to enrich the cellular population with stem-like properties. Gastro-spheres were characterized by evaluating the stemness gene expression, clonogenicity, and resistance to docetaxel and cisplatin in comparison with their parental cells. The expression level of miRNAs in gastro-spheres and their parental cells was measured using quantitative reverse transcription polymerase chain reaction., Results: Gastro-spheres from both cell lines exhibit stem-like properties: upregulated stemness associated genes (P < 0.05), more colonogenicity and more resistance to docetaxel (P < 0.05). MKN-45 gastro-spheres exhibited upregulated expression of miR-21 (1.8-folds), miR-10b (1.34-folds) and miR-146a (4.8-folds; P < 0.05) compared with the parental cells. AGS-derived gastro-spheres showed upregulation of miR-21 (4.7-folds; P < 0.01), miR-10b (15.2-folds; P < 0.001) and miR-146a (39.3-folds; P < 0.05)., Conclusion: Our data exhibited upregulation of miR-21, miR-10b, and miR-146a in the stem-like gastro-spheres; however; their function in gastric CSCs remains to be verified by further experiments., (© 2019 Wiley Periodicals, Inc.)

Objective: Gastric cancer (GC) is widely associated with chronic inflammation. The pro inflammatory microenvironment provides conditions that disrupt stem/progenitor cell proliferation and differentiation. The signal transducer and activator of transcrip- tion-3 (STAT3) signaling pathway is involved in inflammation and also contributes to the maintenance of embryonic stem cell (ESCs) pluripotency. Here, we have investi- gated the activation status of STAT3 in GC stem-like cells (GCSLCs)., Materials and Methods: In this experimental research, CSLCs derived from the human GC cell line MKN-45 and patient specimens, through spheroid body formation, character- ized and then assayed for the STAT3 transcription factor expression in mRNA and protein level further to its activation., Results: Spheroid cells showed higher potential for spheroid formation than the pa- rental cells. Furthemore, stemness genes NANOG, c-MYC and SOX-2 were over expressed in spheroids of MKN-45 and in patient samples. In MKN-45 spheroid cells, epithelial mesenchymal transition (EMT) related markers CDH2, SNAIL2, TWIST and VIMENTIN were upregulated (P<0.05), but we observed no change in expression of the E-cadherin epithelial marker. These cells exhibited more resistance to docetaxel (DTX) when compared with parental cells (P<0.05) according to the MTS assay. Al- though immunostaining and Western blotting showed expression of the STAT3 pro- tein in both spheroids and parents, the mRNA level of STAT3 in spheroids was higher than the parents. Nuclear translocation of STAT3 was accompanied by more intensive phospho-STAT3 (p-STAT3) in spheroid structures relative to the parent cells accord- ing to flow cytometry analysis (P<0.05)., Conclusion: The present findings point to STAT3 over activation in GCSLCs. Com- plementary experiments are required to extend the role of STAT3 in stemness fea- tures and invasion properties of GCSCs and to consider the STAT3 pathway for CSC targeted therapy.

Objective: The aim of present study was to evaluate the effects of oral administration of gallic acid (GA) for 21 days alone and in combination with exercise on nerve conduction velocity and sensory and motor functions in rats with sciatic nerve crush., Materials and Methods: Seventy adult male Wistar rats (250-300 g) were divided randomly into 7 groups with 10 in each: 1) Control (Cont), 2) Crushed + Vehicle (Cr +Veh), 3-5) Crushed + gallic acid (Cr+GA) (50, 100, and 200 mg/kg/2 mL, orally), 6) Crushed + exercise (Cr+Exe), and 7) Crushed + exercise + effective dose of gallic acid (Cr+Exe +GA200) for 21 days. In order to establish an animal model of sciatic nerve crush, equivalent to 7 kg of force pressed on 2-3 mm of sciatic nerve for 30 s, three times with 30 s intervals. Pain sense reflex in hot plate, motor coordination in rotarod, and sciatic nerve conduction velocity (SNCV) in all groups were tested. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test and p<0.05 has assigned as the significant difference., Results: Pain threshold was increased significantly in untreated crushed rats while motor function and SNCV were decreased in all groups with nerve crush (p<0.05, p<0.01, p<0.001 vs. control). Pain reflex latency was not changed in treated groups. Motor coordination and SNCV were improved in groups Cr+GA200 and Cr+Exe + GA200 (p<0.05, p<0.01 vs. Cr+Veh)., Conclusion: GA, dose-dependently, may have therapeutic potential to improve the peripheral nerve degeneration, which is most likely related, at least in part, to its antioxidant and therapeutic properties.