Bainherman6158

Rosmarinic acid exerted chemo-preventive and therapeutic potential alone or in combination with Paclitaxel. Moreover, rosmarinic acid targets numerous signaling pathways associated with breast cancer.NF-κB is activated in a variety of human cancers. However, its role in osteosarcoma (OS) remains unknown. Here, we have elucidated the implication of NF-κB in the oncogenic phenotype of OS tumor cells. We reported that activation of NF-κB was a common event in the human OS. Inhibition of NF-κB using inhibitor Bay 11-7085 repressed proliferation, survival, migration, and invasion but increased apoptosis in 143B and MG63 OS cells, indicating that NF-κB is critically implicated in the oncogenesis of OS. Notably, Bay 11-7085 not only inactivated NF-κB but also reduced the phosphorylation of AKT via its induction of PTEN, suggesting the existence of a novel NF-κB/PTEN/PI3K/AKT axis. In vivo, Bay 11-7085 suppressed tumor growth in the bone by targeting NF-κB and AKT. Interestingly, combined treatment with Bay 11-7085 and the PI3K inhibitor, LY294002, triggered an augmented antitumor effect. Our results demonstrate that NF-κB potentiates the growth and aggressiveness of OS. Pharmacological inhibition of NF-κB represents a promising therapy for the treatment of OS.

Cancer stem cells (CSCs) are a theorized subset of cells within the tumor that is thought to drive disease recurrence and metastatic spread. The aim of this study is to investigate mRNA and protein levels of ganglioside GD2 synthase (GD2S), in breast cancer (BC) patients.

65 PBMCs of preoperative BC patients without chemotherapy were compared to PBMCs after chemotherapy and controls.

GD2S were significantly higher in BC patients after chemotherapy compared to pre-chemotherapy at both mRNA and protein. GD2S was higher in pre-chemotherapy blood samples compared to control samples.

Higher expression of GD2S in BC samples compared to healthy control indicates the potential utility of GD2S as a marker of malignancy.

Higher expression of GD2S in BC samples compared to healthy control indicates the potential utility of GD2S as a marker of malignancy.

Despite the many benefits that follow antiretroviral therapy (ART) initiation, its chronic use contributes to the early aging of people living with HIV/AIDS (PLWHA). The aim of this cross-sectional study was to trace the prevalence of and investigate possible renal, bone and metabolic changes, as well as cardiovascular risk in 94 asymptomatic PLWHA, relating them to the duration of ART use.

Four groups were evaluated according to ART use G1 (n = 21), ART-naïve individuals; G2 (n = 17), <2 years; G3 (n = 40), 2-10 years; and G4 (n = 16) on ART for more than 10 years.

Our results showed a high prevalence of dyslipidemic individuals (64%), especially in those under ART. Lower creatine phosphokinase levels were observed in G1 as compared to the others (p < 0.05). Regarding the Framingham score, 12.1% of PLWHA showed moderate and high risk, and the highest proportion (38.5%) occurred in G4 (p = 0.003). A decrease in glomerular filtration rates occurred in 20% of patients, which was also more significant in G3 and G4 (p = 0.007). High prevalences of osteopenia and osteoporosis (53.2%) were found, especially in G1 and G4; however, G1 showed the lowest means for alkaline phosphatases (AP, p = 0.04 and BAP, p = 0.005) and osteocalcin (p = 0.005), in addition to higher vitamin-D concentrations (p = 0.04).

Our study showed the possible contributory role of ART in these changes, which leads us to reflect on the need for specific conducts and patient care, pointing out the importance of individualized care in an attempt to increase life expectancy.

Our study showed the possible contributory role of ART in these changes, which leads us to reflect on the need for specific conducts and patient care, pointing out the importance of individualized care in an attempt to increase life expectancy.This study aimed at evaluating the role played by insulin resistance, lipid metabolism disorder, oxidative stress, resistin, vaspin, Interleukin-18 and asymmetric dimethyl arginine as a marker for endothelial dysfunction in the pathogenesis of preeclampsia. This prospective observational cohort study involved 60 women who were classified into 20 non-pregnant women (group 1 or control group), 20 normally pregnant women (group 2) and 20 preeclamptic women (group 3) at their third trimester. The pregnant women were assessed at their third trimester and further re-evaluated four weeks after delivery. The assessment included demography, assessment of proteinuria and urinary protein to creatinine ratio, blood pressure measurement and assessment of fasting blood glucose, fasting insulin level, lipid panel and the circulating levels of malondialdehyde, resistin, vaspin, interleukin-18 and asymmetric dimethyl arginine. Preeclamptic women showed more atherogenic lipid profile, significantly higher Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and significantly elevated levels of malondialdehyde, resistin, vaspin and interleukin-18 than the other study groups. Serum asymmetric dimethyl arginine concentration showed non-significant difference among the three study groups. The levels of resistin and vaspin showed significant decrease four weeks postpartum in preeclamptic group. We concluded that, preeclampsia was associated with insulin resistance, dyslipidemia, oxidative stress, inflammation and significant changes in adipokines; resistin and vaspin. Furthermore, the significant increase in the serum levels of resistin and vaspin at the third trimester and their significant decline four weeks postpartum in preeclamptic group focus the attention on the role played by these adipokines in the pathogenesis of preeclampsia.Fabry disease (FD) is a lysosomal storage disorder caused by pathogenic mutations in the alpha-galactosidase A (AGALA) encoding gene region. This rare disease affects several organs including the cochlea-vestibular system. Tinnitus and sensorineural hearing loss (SNHL) are reported among otoneurological symptoms. Early and correct diagnosis of FD is important with a view to available therapy. The aim of the study was to screen for alpha-galactosidase deficiency in men with tinnitus/SNHL. A prospective multicentric study including consecutive patients with SNHL confirmed by tone audiometry or tinnitus evaluated (10/2016-8/2019). The diagnosis of AGALA deficiency was done by dry blood spot method using a threshold of 1.2 µmol/l/h. Only men aged 18-60 were included. 181 patients were subject to evaluation. SNHL was reported in 126 (70%) patients, 50 (28%) patients had unilateral, 76 (42%) patients had bilateral SNHL. Tinnitus was found in 161 (89%) patients, unilateral in 96 (53%) and bilateral in 65 (36%) patients. Suspected FD was not detected in any patient; alpha-galactosidase The AGALA values ranged 1.5-8.8 µmol/l/h, an average of 3.4 µmol/l/h. None of the 181 patients participating in the study had AGALA levels below the threshold 1.2 µmol/l/h. The occurrence of tinnitus and sensorineural hearing loss in men appears to be an irrelevant clinical sign for FD systematic screening.

Diabetic neuropathy has been identified as a common complication caused by diabetes. However, its pathophysiological mechanisms are not fully understood yet. Statins, also known as HMG-CoA reductase inhibitors, alleviate the production of cholesterol. Despite this cholesterol-reducing effect of statins, several reports have demonstrated their beneficial properties in neuropathic pain. In this study, we used streptozotocin (STZ)-induced diabetic model to investigate the possible role of nitric oxide (NO) in the antineuropathic-like effect of atorvastatin.

Diabetes was induced by a single injection of STZ. Male rats orally received different doses of atorvastatin for 21 days. To access the neuropathy process, the thermal threshold of rats was assessed using hot plate and tail-flick tests. Moreover, sciatic motor nerve conduction velocity (MNCV) studies were performed. To assess the role of nitric oxide, N(G)-nitro-L-arginine methyl ester (L-NAME), aminoguanidine (AG), and 7-nitroindazole (7NI) were intraperitoneally administered along with some specific doses of atorvastatin.

Atorvastatin significantly reduced the hyperalgesia in diabetic rats. L-NAME pretreatment with atorvastatin showed the antihyperalgesic effect, suggesting the possible involvement of the NO pathway in atorvastatin protective action. Furthermore, co-administration of atorvastatin with AG and 7NI resulted in a significant increase in pain threshold in diabetic rats.

Our results reveal that the atorvastatin protective effect on diabetic neuropathy is mediated at least in a part via the nitric oxide system.

Our results reveal that the atorvastatin protective effect on diabetic neuropathy is mediated at least in a part via the nitric oxide system.

Clausena excavata Burm. f is a plant used in folklore medicine for the treatment of various ailments in South East Asia. The plant parts contain chemical components that are cytotoxic to many cancer cells.

The study investigated the cytotoxic effects of ethyl acetate, methanol and chloroform C. excavata leaf extracts on the non-small-lung cancer, NCI-H460, cell line.

Based on the 3-(4,5-dimethylthiazol-2-yl)-2,5,-diphenyltetrazolium bromide (MTT) assay, among extracts, ethyl acetate C. CI-1040 cost excavata leaf extract (EACE) was the most potent anti-NCI-H460 cells, with IC50 value of 47.1 ± 6.1 μg/ml. The effects of EACE on NCI-H460 cells were also determined by clonogenic, 4', 6-diamidino-2-phenylindole (DAPI), and annexin-V-fluorescein isothiocyanate/propidium iodide-PI flow cytometric assays. Reactive oxygen species (ROS) production and apoptotic gene expressions was determined via flow cytometry and real-time quantitative PCR, respectively.

EACE-treated NCI-H460 cells after 48 h underwent apoptosis as evident by loss of cell viability, cell shrinkage, and chromatin condensation. The results also showed EACE mediated increase in ROS production by the NCI-H460 cells. After 48 h treatment, EACE increased the pro-apoptotic BAX and decreased the anti-apoptotic Bcl-2, Survivin and c-Myc gene expressions.

EACE is a potential anti-lung cancer by increasing cancer cell ROS production and apoptosis.

EACE is a potential anti-lung cancer by increasing cancer cell ROS production and apoptosis.The present study explores pharmacological potential and phytochemicals profiling of Picrorhiza kurroa extracts against mammalian cancer cell lines and pathogenic microbes. Bioactive extracts from roots of Picrorhiza kurroa were recovered in the methanol, 50% aqueous dichloromethane (50 50 v/v) and n-hexane. Antimicrobial activity of the bioactive extracts was assessed against selected strains of bacteria and pathogenic fungi. Aqueous dichloromethane extract showed highest zone of growth inhibition (39.06 ± 1.0 mm) towards Staphylococcus aureus bacteria while methanolic extract showed the lowest inhibition (6.3 ± 4.1 mm) to Escherichia coli bacteria. The tested extracts such as methanol and aqueous dichloromethane exhibited higher inhibition antifungal activity against Aspergillus flavus compared to Fusarium oxysporum. As far as cytotoxicity (MTT assay) of the tested extracts is concerned, n-hexane and aqueous dichloromethane extracts were found to be very active against all cancer cell lines (breast cancer MCF7, MDA-MB-231, SKBR3 and ovarian cancer SKOV3).