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  • Carney Jantzen posted an update 2 weeks, 3 days ago

    In this mini-review, we will focus on the molecular mechanisms of these two diseases.α-Solanine, a bioactive compound mainly found in potato, exhibits anti-cancer activity towards multiple cancer cells. However, its effects on human choriocarcinoma have not been evaluated. In the present study, we investigated the effect of α-solanine on cell proliferation and apoptosis in human choriocarcinoma in vitro and in vivo. The results showed that α-solanine, at concentrations of 30 μM or below, did not affect the cell viability of the choriocarcinoma cell line JEG-3. However, colony formation was significantly decreased and cell apoptosis was increased in response to 30 μM α-solanine. In addition, α-solanine (30 μM) reduced the migration and invasion abilities of JEG-3 cells, which was associated with a downregulation of matrix metalloproteinases (MMP)-2/9. The in vivo findings provided further evidence of the inhibition of α-solanine on choriocarcinoma tumor growth. α-Solanine suppressed the xenograft tumor growth of JEG-3 cells, resulting in smaller tumor volumes and lower tumor weights. GSK-LSD1 chemical structure Apoptosis was promoted in xenograft tumors of α-solanine-treated mice. Moreover, α-solanine downregulated proliferative cellular nuclear antigen (PCNA) and Bcl-2 levels and promoted the expression of Bax. Collectively, α-solanine inhibits the growth, migration, and invasion of human JEG-3 choriocarcinoma cells, which may be associated with the induction of apoptosis.A major obstacle of sterile insect technique (SIT) programs is the availability of robust sex-separation systems for conditional removal of females. Sterilized male-only releases improve SIT efficiency and cost-effectiveness for agricultural pests, whereas it is critical to remove female disease-vector pests prior to release as they maintain the capacity to transmit disease. Some of the most successful Genetic Sexing Strains (GSS) reared and released for SIT control were developed for Mediterranean fruit fly (Medfly), Ceratitis capitata, and carry a temperature sensitive lethal (tsl) mutation that eliminates female but not male embryos when heat treated. The Medfly tsl mutation was generated by random mutagenesis and the genetic mechanism causing this valuable heat sensitive phenotype remains unknown. Conditional temperature sensitive lethal mutations have also been developed using random mutagenesis in the insect model, Drosophila melanogaster, and were used for some of the founding genetic research published in the fields of neuro- and developmental biology. Here we review mutations in select D. melanogaster genes shibire, Notch, RNA polymerase II 215kDa, pale, transformer-2, Dsor1 and CK2α that cause temperature sensitive phenotypes. Precise introduction of orthologous point mutations in pest insect species with CRISPR/Cas9 genome editing technology holds potential to establish GSSs with embryonic lethality to improve and advance SIT pest control.17β-estradiol (E2) exerts its physiological effects through the estrogen receptor α (i.e., ERα). The E2ERα signaling allows the regulation of cell proliferation. Indeed, E2 sustains the progression of ERα positive (ERα+) breast cancers (BCs). The presence of ERα at the BC diagnosis drives their therapeutic treatment with the endocrine therapy (ET), which restrains BC progression. Nonetheless, many patients develop metastatic BCs (MBC) for which a treatment is not available. Consequently, the actual challenge is to complement the drugs available to fight ERα+ primary and MBC. Here we exploited a novel anti-estrogen discovery platform to identify new Food and Drug Administration (FDA)-approved drugs inhibiting E2ERα signaling to cell proliferation in cellular models of primary and MBC cells. We report that the anti-fungal drugs clotrimazole (Clo) and fenticonazole (Fenti) induce ERα degradation and prevent ERα transcriptional signaling and proliferation in cells modeling primary and metastatic BC. The anti-proliferative effects of Clo and Fenti occur also in 3D cancer models (i.e., tumor spheroids) and in a synergic manner with the CDK4/CDK6 inhibitors palbociclib and abemaciclib. Therefore, Clo and Fenti behave as “anti-estrogens”-like drugs. Remarkably, the present “anti-estrogen” discovery platform represents a valuable method to rapidly identify bioactive compounds with anti-estrogenic activity.Forklifts are commonly used in industrial supply chains to transport heavy loads. Forklift drivers have the risk of developing musculoskeletal discomfort derived from the movement pattern required at work. This research aimed to investigate the spinal range of motion (ROM) and musculoskeletal discomfort of forklift drivers and compare it with a control group. Forklift drivers (39 males) and office workers (31 males) were recruited to assess cervical, thoracic, and lumbar ROM with an electronic double inclinometer. Additionally, musculoskeletal discomfort was registered with the Cornell Discomfort Musculoskeletal Questionnaire. Forklift drivers showed a higher cervical discomfort and ROM of lateral lumbar bending than office workers. Both groups reported lower ROM in cervical and lumbar lateral bending on the right side versus the left side. No differences of asymmetry were reported for any variable between groups. Specific exercise programs may correct these mobility imbalances.The objective of our study was to identify blood pressure (BP) and pulse wave velocity (PWV) changes during orthostatic loading, using a new the head-up tilt test (HUTT), which incorporates the usage of a standardized hydrostatic column height.

    40 healthy subjects 20-32 years performed HUTT, which was standardized to a height of the hydrostatic column at 133 cm. Exposure time was 10 min in each of 3 positions horizontal supine 1, HUTT, and horizontal supine 2. The individual tilt up angle made it possible to set the standard value of the hydrostatic column. Hemodynamic parameters were recorded beat to beat using “Task Force Monitor 3040 i”, pulse-wave velocity (PWV) was measured with a sphygmograph-sphygmomanometer VaSera VS1500N.

    Orthostatic loading caused a significant increase in heart rate (HR) and a decrease in stroke volume (SV) (

    < 0.05) but no significant reductions in cardiac output, changes in total vascular resistance (TVR), or BP. An analysis of personalized data on systolic blood pressure (SBP) changes in tilt up position as compared to horizontal position (ΔSBP) revealed non-significant changes in this index in 48% of subjects (orthostatic normotension group), in 32% there was a significant decrease in it (orthostatic hypotension group) and in 20% there was a significant increase in it (orthostatic hypertension group).