Molecular analysis of age and sex-related gene expression in meniscal tears with and without a concomitant anterior cruciate ligament tear

BACKGROUND: The meniscus plays critical roles in the knee, contributing to load transmission, shock absorption, and joint stability. Little is known about gene expression in meniscal tears, particularly in relation to injury pattern and patient age and sex. The purpose of this study was to test the hypothesis that gene expression in meniscal tears varies depending on patient age and sex and whether the anterior cruciate ligament (ACL) is also torn. METHODS: Meniscal tissue from twenty-eight patients with an isolated meniscal tear or a meniscal tear with a concomitant ACL tear was collected at the time of clinically indicated partial meniscectomy. Messenger RNA (mRNA) expression was examined by quantitative real-time polymerase chain reaction for molecular markers of osteoarthritis including proinflammatory cytokines (interleukin [IL]-1α, IL-1β, IL-6, and tumor necrosis factor-alpha [TNFα]), chemokines (IL-8, CCL3, CCL3L1, CXCL1, CXCL3, CXCL6, and CCL20), aggrecanases (ADAMTS-4 [a disintegrin and metalloproteinase with thrombospondin type-4 motifs] and ADAMTS-5), matrix metalloproteinases (MMP-1, MMP-3, MMP-9, and MMP-13), transcription factors (NFκB2 [nuclear factor kappa B2], NFκBIA [NF-kappa B inhibitor alpha], and IκBA [inhibitor of kappa B alpha]), and matrix components (bone morphogenetic protein [BMP]-2, type-I collagen alpha 1 [Col1a1], Col2a1, and aggrecan). RESULTS: Expression of IL-1β (p = 0.02), ADAMTS-5 (p = 0.001), MMP-1 (p = 0.007), MMP-9 (p = 0.002), MMP-13 (p = 0.01), and NFκB2 (p = 0.01) was significantly higher in patients with a meniscal tear who were under the age of forty years than it was in those over the age of forty years. Similarly, the expression of ADAMTS-4 (p = 0.002), ADAMTS-5 (p = 0.02), MMP-1 (p = 0.02), and MMP-13 (p = 0.0002) was higher in patients with a meniscal tear and an ACL tear who were under the age of forty years than it was in those over forty years. In patients with a meniscal tear and an ACL tear, the expression of IL-1β (p = 0.01), TNFα (p = 0.02), MMP-13 (p = 0.004), CCL3 (p = 0.03), and CCL3L1 (p = 0.03) was significantly higher, while that of aggrecan (p = 0.03) was lower, than that in patients with a meniscal tear alone. The only sex-based difference in gene expression was higher levels of CCL3L1 in female patients (p < 0.05) of all ages with combined injuries. CONCLUSIONS AND CLINICAL RELEVANCE: These findings suggest clinically relevant differences in the response of the knee to meniscal tears on the basis of patient age and sex. Elevated expression levels of arthritis-related markers indicate an increased catabolic response in patients under forty years old. Higher expression of catabolic markers in patients with meniscal and ACL tears suggests this combined injury pattern is more likely to lead to the development of osteoarthritis. Catabolic activity in meniscal tissue may predict patients who are at risk for progression of osteoarthritis following partial meniscectomy

Факторы, влияющие на общую выживаемость при протоковой аденокарциноме головки поджелудочной железы. Опыт одного центра

Purpose. To identify major factors affecting the overall survival (OS). To select the cohort of patients with the best prognosis.Materials and methods. A retrospective analysis included data of 268 patients, 128 men and 140 women, with median age of 59±10,53 (30 to 83) years. For multivariate analysis of survival, patients were selected who underwent pancreaticoduodenectomy (PD) for ductal adenocarcinoma of the pancreatic head.Results. Our study demonstrated that histologically verified vascular invasion (detected only in 30 % of patients who underwent PD with resection of the major vessels) statistically significantly affected the OS. The increased CA19-9 level over 500 U / L (detected in 32,3 % of cases) is the factor that significantly worsens the OS. Patients with high grade adenocarcinoma have significantly better survival rates compared with patients who have moderately or poorly differentiated adenocarcinoma (p = 0.014; median 26 months, 95 % CI 4.4–47.6 versus median 17 months, 95 % CI 15–19, an median: 13 months, 95 % CI 5–21, respectively). Also, the use of adjuvant chemotherapy has a positive effect on long-term outcomes (p = 0.0001; median 26 months, 95 % CI 21.7–30.3 versus median 13 months, 95 % CI 11.3–14.7).Conclusion. A well-differentiated tumor and the use of adjuvant chemotherapy significantly increase the OS of patients. Poorly differentiated tumor, CA19-9 level over 500 U / mL and the histologically confirmed vascular invasion significantly worsen the prognosis of these patients.Цель. Определить ведущие факторы, оказывающие влияние на общую выживаемость (ОВ). Выделить когорту пациентов с наилучшим прогнозом заболевания.Материалы и методы. В ретроспективный анализ были включены 268 пациентов, 128 мужчин и 140 женщин средним возрастом 59±10,53 (от 30 до 83) лет. Для многофакторного анализа и анализа выживаемости отобраны больные, которым была выполнена гастропанкреатодуоденальная резекция (ГПДР) по поводу протоковой аденокарциномы головки поджелудочной железы.Результаты. В нашем исследовании показано, что на ОВ статистически значимо влияет морфологически подтвержденная инвазия опухоли в сосудистую стенку, которая выявилась лишь у 30% больных, перенесших ГПДР с резекцией магистральных сосудов. Уровень онкомаркера CА19-9 более 500 ЕД/л был выявлен в 32,3% случаях и является фактором, достоверно ухудшающим ОВ. Пациенты с высокодифференцированной аденокарциномой имеют достоверно лучшие показатели выживаемости по сравнению с больными, у которых выявлена умеренно-или низкодифференцированная аденокарцинома (р =0,014; медиана 26 месяцев, 95% ДИ 4,4–47,6 против медианы 17 месяцев, 95% ДИ 15–19, и медианы 13 месяцев, 95% ДИ 5–21). Кроме того, положительное влияние на отдаленные результаты оказывает применение адъювантной химиотерапии (ХТ) (р =0,0001; медиана 26 месяцев, 95% ДИ 21,7–30,3 против медианы 13 месяцев, 95% ДИ 11,3–14,7).Заключение. Высокая степень дифференцировки опухоли и применение ХТ в адъювантном режиме достоверно увеличивают ОВ пациентов. Низкая степень дифференцировки опухоли, уровень СА19-9 более 500 Ед/мл и гистологически верифицированная инвазия опухоли в стенку магистральных сосудов достоверно ухудшают прогноз этих пациентов

Effects of low intensity electromagnetic irradiation of 70.6 and 73 GHz frequencies and antibiotics on energy-dependent proton and potassium ion transport by<i> E. coli</i>

428-434The effects of low intensity (flux capacity 0.06 mW/cm2) coherent electromagnetic irradiation (EMI) of 70.6 and 73 GHz frequencies and their combined effects with antibiotics — ceftriaxone or kanamycin (0.4 or 15 µM, correspondingly) on E. coli K12 growth and survival have been reported previously. To further study the effects of EMI and antibiotics and mechanisms, decrease in overall energy (glucose)-dependent H+ and K+ fluxes across the cell membrane was investigated in E. coli. The depression of H+ and K+ fluxes rate was maximally achieved with the 73 GHz frequency. The EMI strengthened the effect of N,N’-dicyclohexycarbodiimide (DCCD, an inhibitor of the F0F1-ATPase). The 73 GHz EMI had more influence on H+ efflux inhibition, whereas 70.6 GHz on K+ influx. Also, EMI strengthened the depressive effects of ceftriaxone and kanamycin on the overall and DCCD-inhibited H+ and K+ fluxes. The 73 GHz EMI strengthened the effect of ceftriaxone on both ions fluxes. Kanamycin depressed H+ efflux more as compared to ceftriaxone, which was also strengthened with EMI. The results of E. coli H+ and K+ transport systems activities depression by irradiation and the irradiation effect on DCCD and antibiotics action indicated the EMI and antibiotics causing primary changes in the bacterial membrane

Protective effect of some amino acids synthesized derivatives and their chelates on <i style="mso-bidi-font-style: normal">Escherichia coli</i> under X-ray irradiation

289-295The protective effects of novel synthesized derivatives of some amino acids — nicotinyl-L-tyrosinate and nicotinyl-L-tryptophanate schiff bases and their Cu(II) and Mn(II) chelates on growth, survival and membrane-associated ATPase activity of E. coli under X-ray irradiation were investigated. The specific growth rate and survival of E. coli were decreased at 10, 20 and 30 Gy doses. However, as 30 Gy was found to be the most effective irradiation dose, it was chosen for studying the radio-protective properties of different compounds. These compounds could increase the bacterial cell protection against X-ray irradiation in concentration-dependent manner. They had a role in stimulation of synthesis or regulation of activity of metal-dependent enzymes, required for reversing the X-ray irradiation damage. The study may prove useful for further estimation of the effectiveness of different compounds as radio-protectors on bacteria and other cells, especially mammalian cells under X-ray irradiation

Monitoring membrane viscosity in differentiating stem cells using BODIPY-based molecular rotors and FLIM

Membrane fluidity plays an important role in many cell functions such as cell adhesion, and migration. In stem cell lines membrane fluidity may play a role in differentiation. Here we report the use of viscosity-sensitive fluorophores based on a BODIPY core, termed “molecular rotors”, in combination with Fluorescence Lifetime Imaging Microscopy, for monitoring of plasma membrane viscosity changes in mesenchymal stem cells (MSCs) during osteogenic and chondrogenic differentiation. In order to correlate the viscosity values with membrane lipid composition, the detailed analysis of the corresponding membrane lipid composition of differentiated cells was performed by time-of-flight secondary ion mass spectrometry. Our results directly demonstrate for the first time that differentiation of MSCs results in distinct membrane viscosities, that reflect the change in lipidome of the cells following differentiation