Molecular Processes Involved in the Shared Pathways between Cardiovascular Diseases and Diabetes.

Cardiovascular diseases and diabetes mellitus are currently among the diseases with the highest morbidity and mortality. The pathogenesis and development of these diseases remain strongly connected, along with inflammation playing a major role. Therefore, the treatment possibilities showing a positive impact on both of these diseases could be especially beneficial for patients. SGLT-2 inhibitors and GLP-1 receptor agonists present this dual effect. Moreover, the hostile composition of the gut microbiota could influence the progression of these conditions. In this review, the authors present the latest knowledge on and innovations in diabetes mellitus and CVD-with the focus on the molecular mechanisms and the role of the microbiota.

An elevated systemic inflammation index is related to an inferior response to pomalidomide and dexamethasone treatment in patients with relapsed and refractory multiple myeloma.

Introduction: The systemic inflammation index (SII) might serve as an indicator of the equilibrium between the inflammatory and immune responses. The aim of the study was to determine the clinical value and prognostic significance of SII in the cohort of multiple myeloma (MM) patients treated with a regimen of pomalidomide and dexamethasone (Pd). Material and methods: This retrospective, real-life study included patients who received a Pd regimen in our centre between November 2018 and July 2022. The systemic inflammation index was calculated from peripheral blood counts of platelets, neutrophils, and lymphocytes collected shortly before commencement of Pd treatment using the equation: SII = N × P/L, where N, P, and L are the respective counts per litre of peripheral blood for neutrophils, platelets, and lymphocytes. Results: The study group consisted of 54 patients. Most patients received Pd as the third (38.9%) or fourth (37.0%) line of treatment. The median number of completed treatment cycles was 5 (IQR: 1-12). The median progression-free survival (PFS) was 6.8 months and overall survival (OS) 14.8 months. High SII (> 374) was an independent prognostic factor for PFS (HR = 3.0, 95% CI: 1.4-6.3, p < 0.01) and OS (HR = 2.2, 95% CI: 1.0-4.6, p = 0.04). In the low SII group, the respective median PFS and OS values were 9.6 and 21.7 months, compared to 2.6 (p = 0.018) and 5.5 months (p = 0.035) in the high SII group. Conclusions: The systemic inflammation index has prognostic significance in MM patients treated with Pd. A high SII predicts a poorer outcome in pretreated MM patients undergoing Pd treatment evaluation. As such, it may well be a key factor for guiding subsequent treatment decisions.

Risk Factors of Infection in Relapsed/Refractory Multiple Myeloma Patients Treated with Lenalidomide and Dexamethasone (Rd) Regimen: Real-Life Results of a Large Single-Center Study.

Lenalidomide-based regimens are effective treatment options for patients with relapsed/refractory multiple myeloma (RRMM). However, they are associated with an increased risk of infectious complications. This study examines the clinical factors influencing the occurrence of infection in MM patients treated with lenalidomide and dexamethasone (Rd). A retrospective analysis of all patients who received the Rd regimen between 2017 and 2021 at our institution was performed. The study group consisted of 174 patients and the median age was 65 years. Most patients (n = 110, 63.2%) received the Rd treatment in second-line treatment. The majority of patients (64.3%) received bortezomib-based regimens in the first line of treatment. The median progression-free survival was 12.6 (95% CI: 9.5-16.2) months, and the median overall survival was 22.3 (95% CI: 15.9-28.6) months. The overall response rate was 64.1%, 12.7% of patients achieved complete response, and 20.4% had a very good partial response. In multivariate logistic regression analysis, hypoalbuminemia (OR 4.2, 95% CI: 1.6-11.2, p = 0.0039), autologous hematopoietic stem cell transplantation (AHSCT) before Rd (OR 2.6, 95% CI: 1.0-6.7, p = 0.048), and anemia grade ≥3 (OR 5.0, 95% CI: 1.8-14.0, p = 0.002) were independent factors related to the occurrence of infections. In conclusion, in this large cohort of RRMM patients, AHSCT before Rd regimen therapy, hypoalbuminemia, and anemia during treatment were identified as three independent factors influencing the frequency of infections during Rd therapy. Patients with established risk factors may benefit from optimal supportive therapy.

Influence of silybin on biophysical properties of phospholipid bilayers.

AIM: Silybin (silibinin) is major biologically active flavonolignan extracted from milk thistle (Sylibum marianum). Its biological activities include hepato-protection, anticancer properties, and antioxidant- and membrane-stabilizing functions. Although membranes are postulated to be one of the cellular targets for silybin, little is known about its interaction with phospholipid bilayers. METHODS: In the present work, the interactions of silybin with phosphatidylcholine bilayers were studied in detail using fluorescence spectroscopy, microcalorimetry and electron spin resonance techniques. RESULTS: The results showed that silybin interacted with the surface of lipid bilayers. It affected the generalized polarization of the fluorescent probe Prodan, while not influencing the more deeply located Laurdan. Silybin lowered the main phospholipid phase transition temperature as judged by microcalorimetry, and caused the immobilization of spin probe Tempo-palmitate located on the surface of membranes. The mobility of spin probes 5- and 16-doxyl stearic acid was not affected by silybin. Silybin-induced quenching of 1,6-diphenyl-1,3,5-hexatriene fluorescence indicated that some flavonoid molecules partitioned into the hydrophobic region of membranes, which did not change significantly the biophysical properties of the deeper membrane regions. CONCLUSION: Such a behavior of silybin in membranes is in accordance with its postulated biological functions and neglectable side effects of therapies using silybin.

A study on the perturbation of model lipid membranes by phenoxazines.

The interactions of six newly synthesized phenoxazine derivatives with lipid bilayers were studied by means of calorimetry, fluorescence spectroscopic methods and electron spin resonance. Depending on their structure studied compounds decreased membrane fluidity and increased lipid order in liquid-crystalline bilayers to different degrees. These studies showed also that phenoxazine molecules are located close to the polar/apolar interface of bilayer. The results allow to conclude that phenoxazines rather weakly interact with lipid bilayers.