Enhancement of targeted therapy in combination with metformin on human breast cancer cell lines.

BACKGROUND: Breast cancer remains a primary global health concern due to its limited treatment options, frequent disease recurrence, and high rates of morbidity and mortality. Thereby, there is a need for more effective treatment approaches. The proposal suggests that the combination of targeted therapy with other antitumoral agents could potentially address drug resistance. In this study, we examined the antitumoral effect of combining metformin, an antidiabetic drug, with targeted therapies, including tamoxifen for estrogen receptor-positive (MCF-7), trastuzumab for HER2-positive (SKBR-3), and antibody against ROR1 receptor for triple-negative breast cancer (MDA-MB-231). METHODS: Once the expression of relevant receptors on each cell line was confirmed and appropriate drug concentrations were selected through cytotoxicity assays, the antitumor effects of both monotherapy and combination therapy on colony formation, migration, invasion were assessed in in vitro as well as tumor area and metastatic potential in ex ovo Chick chorioallantoic membrane (CAM) models. RESULTS: The results exhibited the enhanced effects of tamoxifen when combined with targeted therapy. This combination effectively inhibited cell growth, colony formation, migration, and invasion in vitro. Additionally, it significantly reduced tumor size and metastatic potential in an ex ovo CAM model. CONCLUSIONS: The findings indicate that a favorable strategy to enhance the efficacy of breast cancer treatment would be to combine metformin with targeted therapies.

Comparison of neutralization potency across passive immunotherapy approaches as potential treatments for emerging infectious diseases.

The use of passive immunotherapy, either as plasma or purified antibodies, has been recommended to treat the emerging infectious diseases (EIDs) in the absence of alternative therapeutic options. Here, we compare the neutralization potency of various passive immunotherapy approaches designed to provide the immediate neutralizing antibodies as potential EID treatments. To prepare human plasma and purified IgG, we screened and classified individuals into healthy, convalescent, and vaccinated groups against SARS-CoV-2 using qRT-PCR, anti-nucleocapsid, and anti-spike tests. Moreover, we prepared purified IgG from non-immunized and hyperimmunized rabbits against SARS-CoV-2 spike protein. Human and rabbit samples were used to evaluate the neutralization potency by sVNT. All vaccinated and convalescent human plasma and purified IgG groups, as well as purified IgG from hyperimmunized rabbits, had significantly greater levels of spike-specific antibodies than the control groups. Furthermore, when compared to the other groups, the purified IgG from hyperimmunized rabbits exhibited superior levels of neutralizing antibodies, with an IC50 value of 2.08 µg/ml. Additionally, our results indicated a statistically significant positive correlation between the neutralization IC50 value and the positive endpoint concentration of spike-specific antibodies. In conclusion, our study revealed that purified IgG from hyperimmunized animals has greater neutralization potency than other passive immunotherapy methods and may be the most suitable treatment of critically ill patients in EIDs.

Enhancement of immunogenicity and neutralizing responses against SARS-CoV-2 spike protein using the Fc fusion fragment.

AIMS: Vaccination has played an important role in protecting against death and the severity of COVID-19. The recombinant protein vaccine platform has a long track record of safety and efficacy. Here, we fused the SARS-CoV-2 spike S1 subunit to the Fc region of IgG and investigated immunogenicity, reactivity to human vaccinated sera, and neutralizing activity as a candidate protein vaccine. MATERIALS AND METHOD: We evaluated the immunogenicity of CHO-expressed S1-Fc fusion protein and tag-free S1 protein in rabbits via the production of S1-specific polyclonal antibodies. We subsequently compared the neutralizing activities of sera from immunized rabbits and human-vaccinated individuals using a surrogate Virus Neutralization Test (sVNT). KEY FINDINGS: The results indicate that S1-specific polyclonal antibodies were induced in all groups; however, antibody levels were higher in rabbits immunized with S1-Fc fusion protein than tag-free S1 protein. Moreover, the reactivity of human vaccinated sera against S1-Fc fusion protein was significantly higher than tag-free S1 protein. Lastly, the results of the virus-neutralizing activity revealed that vaccination with S1-Fc fusion protein induced the highest level of neutralizing antibody response against SARS-CoV-2. SIGNIFICANCE: Our results demonstrate that the S1 protein accompanied by the Fc fragment significantly enhances the immunogenicity and neutralizing responses against SARS-CoV-2. It is hoped that this platform can be used for human vaccination.

Prevalence, risk factors, and molecular analysis of vancomycin-resistant Enterococci colonization in a referral neonatal intensive care unit: a prospective study in northern Iran.

OBJECTIVES: Vancomycin-resistant enterococcus (VRE) is an emerging drug-resistant organism responsible for increasing nosocomial infections. Few data are available on the epidemiology of VRE colonization or infection in neonates, and is of recent interest. This study analyzes the prevalence of neonatal VRE colonization in a neonatal intensive care unit (NICU), and describes risk factors and molecular phenotypes associated with VRE colonization. METHODS: We performed a prospective epidemiological study on neonates admitted to an NICU. We compared neonates with VRE isolates detected in rectal swab cultures to those without. Association of VRE colonization with risk factors was tested by using univariate and multivariate methods. RESULTS: During a period of 18 months, amongst 180 neonates enrolled in the study, 76 (42.2%) were colonized by VRE. VRE isolates were resistant to amikacin in 68%, gentamicin in 26%, and ampicillin in 17.1% of cases. Molecular analysis showed the vanA gene in all isolates. Two VRE-positive patients developed infection during the observation time. No deaths occurred during this period. Prematurity (P = 0.023), low birth weight (P = 0.019), history of admission in other hospitals (P = 0.00), and antibiotic therapy for more than seven days (P = 0.01) were identified as risk factors for VRE colonization. CONCLUSION: Newborn susceptibility to early colonization with VRE in NICUs is increased in preterm and low birth weight newborns. All VRE colonization in the NICU was related to the acquisition of the vanA gene. Adherence to infection control policies and antimicrobial stewardship strategies are of the highest importance.

Anti-perinuclear Factor as Diagnostic Marker in Rheumatoid Arthritis.

INTRODUCTION: Rheumatoid Arthritis (RA) is a systemic autoimmune disease. It is associated with several auto antibodies which can serve as diagnostic and prognostic markers. AIM: In this study, Anti perinuclear Factor (APF) was evaluated as a biomarker in comparison with Rheumatoid Factor (RF) in Rheumatoid Arthritis. MATERIALS AND METHODS: Fifty two sera of patients with RA (mean age 48±15.8), 23 sera of Patient control group (mean age 32.5 ± 16.9) and 30 sera of Healthy control group (mean age 32.1± 16.9) were analysed. The method is based on the binding of APF to perinuclear keratohyalin granules of buccal mucosal cell and its detection using a fluorescently labeled anti human total antiserum. RESULTS: APF were found in 71.2 %(37/52) of patients with RA. The sensitivity and specificity for APF from 1/5 serum dilution was 71.2% and 94.3% respectively. RF test had higher sensitivity (88.5%) compare to the APF test (71.2%), but its specificity was (86.8%) less than APF (94.3%). There was no significant relationship between the onset of APF and severity of disease but there was significant relationship between the APF titer and severity of disease (p<0.05). CONCLUSION: It is concluded that APF test is a valuable serological tool for the diagnosis of the disease and a useful serological marker to differentiate from the other inflammatory rheumatoid diseases.