Aim: to evaluate the antitumor effect of ionizing radiation on non-transfected and transfected (with NEK2 gene knockdown) prostate cancer cell lines by analyzing their viability in vitro. Material and methods. The study was performed using human prostate cancer cell lines PC-3 and DU145, as well as a primary culture of tumor cells (PCa-PC) obtained from a patient with acinar prostate adenocarcinoma (Gleason score 7: 4+3). NEK2 gene knockdown was achieved by RNA interference using miRNA. Irradiation was carried out using a Theratron Equinox unit as a single dose of 6 Gy 48 h after transfection. Cell viability was assessed 24 h later by trypan blue staining. Results were expressed as percentages (M ± SD). Radiosensitization was evaluated using the enhancement index (EI). Statistical analysis was performed using two-way analysis of variance (ANOVA) with Holm correction; a p 0.05 was considered statistically significant. Results. Irradiation without NEK2 knockdown caused a moderate decrease in cell viability in PC-3 and PCa-PC cells, whereas no statistically significant effect was observed in the DU145 cell line. NEK2 knockdown alone resulted in a pronounced reduction in cell viability in all studied cell lines (p 0.0001). Combined treatment with ionizing radiation and NEK2 knockdown produced the maximum cytotoxic effect, reducing cell viability by more than threefold compared with control. EI values exceeded 1 and ranged from 2.5 to 3.7 depending on the cell line. Conclusion. Suppression of NEK2 gene expression significantly reduces the viability of prostate cancer cells and increases their radiosensitivity, suggesting NEK2 as a promising molecular target for radiosensitization. The obtained results require further validation in in vivo models.
In this article, we report the interim results of a prospective non-interventional ValerEE study analyzing the efficacy and safety of ribociclib therapy in combination with endocrine therapy compared to other combination chemotherapy regimens in the first-line treatment of patients with hormone-sensitive HER2-negative advanced breast cancer in routine clinical practice in Russia. We analyzed the data of 188 patients, of whom 146 patients received ribociclib in combination with endocrine therapy, while 27 patients received other combination chemotherapy. Fifteen patients were excluded from the analysis as they did not meet the inclusion criteria (received monochemotherapy). The majority of participants were women (99.4 %) with a mean age of 59.1 years; most of them (76.9 %) reached menopause. Mastectomy with lymphadenectomy were the most common surgeries (47.4 % of cases). Ductal cancer was diagnosed in 83.2 % of patients. Expression of estrogen and progesterone receptors was detected in 100 % and 89.6 % of participants, respectively. Metastases were primarily located in the bones (60.7 %), lungs (53.8 %) and liver (50.3 %). Anastrozole was the most common endocrine agent used in combination with ribociclib (65.8 %); paclitaxel plus carboplatin were the most common (33.3 %) combination chemotherapy. The ratio of therapeutic options observed in this study reflects current clinical recommendations and routine clinical practice in the Russian Federation. Patient groups were well balanced with no significant differences between them, which will ensure accurate assessment of the effectiveness of different therapeutic regimens later.
Pharmacological treatment of tension-type headache (TTH) attacks involves the selection of the most effective and safe analgesic. However, the choice of medication is limited by the insufficient number of evidence-based studies for this type of headache (HA). Objective: to evaluate the efficacy, safety, and tolerability of fast-release lornoxicam (Xefocam rapid) compared to standard lornoxicam (Xefocam), naproxen, and ibuprofen in relieving headache episodes in patients with frequent episodic TTH in routine clinical practice. Material and methods. The multicenter, observational (non-interventional), prospective RAPID study was conducted in 10 clinical centers across the Russian Federation and included 400 adult patients (74.5% women, 25.5% men) aged 18 to 76 years (mean age: 39.83±12.58 years) with frequent episodic TTH who were prescribed one of the following NSAIDs in routine practice: Xefocam, Xefocam rapid, ibuprofen, or naproxen. The following outcomes were assessed: the number of completely relieved TTH episodes, changes from baseline in the mean number of headache days, mean number of TTH episodes per month, mean duration of TTH episodes, and mean pain intensity on a numerical rating scale, time from drug intake to partial and complete relief of a TTH episode, mean number of days with intake of the drugs in question, number of patients using NSAIDs ≥15 days per month, number of patients taking additional medications for TTH relief, patient satisfaction with the prescribed treatment, number of patients who discontinued treatment, and the frequency of adverse events during therapy. Results. The study demonstrated overall high efficacy of Xefocam and Xefocam rapid in relieving TTH attacks. At the same time, the data obtained allow the identification of some priority effects of investigated drugs. Thus, Xefocam and Xefocam rapid showed the highest efficacy in achieving complete headache relief within 2 hours after intake. Moreover, Xefocam rapid was the most effective across all groups in achieving complete headache relief within the first 30 minutes. The greatest reduction in the numerical rating scale (NRS) score was also observed in the Xefocam rapid and Xefocam groups. In addition, Xefocam and Xefocam use demonstrated the lowest need for additional medications for pain relief among all groups, which may be related to the rapid onset of analgesic action and high safety profile of these drugs. Patients in the Xefocam rapid group more frequently rated their satisfaction with the therapy as excellent. Conclusion. Xefocam rapid showed a high safety profile and excellent tolerability, with the lowest incidence of adverse events among all study groups.
This review presents an analysis of publications on chronic venous diseases in patients with obesity (body mass index ≥ 30.0 kg/m 2 ). The data were searched in the Pubmed and Cochrane database. Studies have shown that obesity is a significant risk factor not only for the onset of chronic venous disorders but also for the occurrence of complications and relapses after minimally invasive treatments. In this context, bariatric surgery is gaining popularity, as weight reduction has been shown to correlate with improvements in the clinical severity of chronic venous disease. There is growing interest in pharmacotherapy for this category of comorbid patients. The complex effect combination of bioflavonoids hesperidin and diosmin leads to reduction in venous symptoms. Hesperidin has been proven to have anti-inflammatory, angioprotective, andlipid-lowering properties. It can prevent weight gain and reduce the severity of visceral obesity. Phlebotropic therapy with Venarus® at a daily dose of 1000 mg (100 mg of hesperidin and 900 mg of diosmin) has demonstrated potential for effective use not only in conservative management of chronic venous diseases in patients with overweight and obesity, but also in comprehensive treatment protocols before and after bariatric surgery. Fixed dosages of the two components of the drug Venarus® contribute to a stable therapeutic effect. We present a clinical case report to illustrate the impact of bariatric surgeries on the course of chronic venous disease in the immediate postoperative period: patient M., 42 years old, weight 127 kg, BMI 49 kg/m 2 , CEAP 4b chronic venous disease, who underwent laparoscopic longitudinal gastric resection. In the postoperative period, the patient received pharmacotherapy with Venarus® at a dose of 1000 mg once a day for 3 months, and was recommended to use class 2 compression stockings.
This study provides insight into the synthesis, optimization, and characterization of zinc oxide nanoparticles (ZnONPs) employing a highly promising Trichoderma isolate. The effectiveness of the synthesized ZnONPs was assessed against two plant pathogenic fungi, Phomopsis vexans, which causes Phomopsis blight in brinjal, and Colletotrichum capsici, which causes fruit rot in chili. ZnONP synthesis was optimized through systematic parameter adjustments, including different ratios of Zn to culture filtrate, varying pH ranges, and different time intervals of synthesis. The synthesized nanoparticles were characterized through diverse analytical techniques, including UV‒vis spectroscopy, scanning electron microscopy (SEM) and energy-dispersive analysis of X-rays (EDAX), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and others. The UV–visible spectra exhibited absorption peaks within the range of 240–380 nm, indicating the formation of ZnO nanoparticles. The size of ZnONPs during SEM and TEM analysis was found to be 20–30 nm and 9–25 nm, respectively. These analyses yielded valuable insights into the morphology, size distribution, crystalline structure, and functional groups present in the nanoparticles and their antimicrobial properties. Furthermore, the antifungal efficacy of the synthesized ZnONPs was assessed against P. vexans and C. capsici at various concentrations. The nanoparticles demonstrated strong antifungal activity in vitro at 200–500 ppm concentrations against both pathogens. The outcome of this study highlights the potential of using Trichoderma-derived ZnONPs as a sustainable and effective approach for managing plant fungal diseases. Overall, this research contributes to the expanding field of nanoparticle-based agricultural solutions and underscores the significance of understanding nanoparticle-fungus interactions for practical applications in crop protection.
