Lung cancer (LC) is the leading cause of cancer-related deaths. Downregulation of CDK1, 4 and 6, key regulators of cell cycle progression, correlates with decreased LC cell proliferation. Enforced expression of miRNAs (miRs) is a promising approach to regulate genes. Here, we study the combinatorial treatment of miR-143 and miR-506 to target the CDK1, 4/6 genes, respectively. We analyzed the differential expression of CDK genes by qPCR, and western blot, and evaluated changes in the cell cycle distribution upon combinatorial treatment. We used an antibody microarray analysis to evaluate protein expression, focusing on the cell cycle pathway, and performed RNA-sequencing for pathway analysis. The combinatorial miR treatment significantly downregulated CDK1, 4 and 6 expression, and induced a shift of the cell cycle populations, indicating a G1 and G2 cell cycle block. The two miRs induces strong cytotoxic activity, with potential synergism, and a significant Caspase 3/7 activation. We identified a strong inhibition of tube formation in the presence or absence VEGF in an in vitro angiogenesis model. Together with the pathways analysis of the RNA-sequencing data, our findings establish the combinatorial miR transfection as a viable strategy for lung cancer treatment that merits further investigation.
Imbalanced angiogenesis is a characteristic of several diseases. Rho GTPases regulate multiple cellular processes, such as cytoskeletal rearrangement, cell movement, microtubule dynamics, signal transduction and gene expression. Among the Rho GTPases, RhoA, Rac1 and Cdc42 are best characterized. The role of endothelial Rac1 and Cdc42 in embryonic development and retinal angiogenesis has been studied, however the role of endothelial RhoA is yet to be explored. Here, we aimed to identify the role of endothelial RhoA in endothelial cell functions, in embryonic and retinal development and explored compensatory mechanisms.
In vitro
, RhoA is involved in cell proliferation, migration and tube formation, triggered by the angiogenesis inducers Vascular Endothelial Growth Factor (VEGF) and Sphingosine-1 Phosphate (S1P).
In vivo
, through constitutive and inducible endothelial RhoA deficiency we tested the role of endothelial RhoA in embryonic development and retinal angiogenesis. Constitutive endothelial RhoA deficiency, although decreased survival, was not detrimental for embryonic development, while inducible endothelial RhoA deficiency presented only mild deficiencies in the retina. The redundant role of RhoA
in vivo
can be attributed to potential differences in the signaling cues regulating angiogenesis in physiological versus pathological conditions and to the alternative compensatory mechanisms that may be present in the
in vivo
setting.
Magnesium levels do not correspond with age, BMI, waist circumference, insulin sensitivity, glycemic levels, blood pressure, or lipid levels in reproductive-age women with PCOS. Magnesium concentrations are similar across PCOS phenotypes and indistinguishable from women without PCOS.
Background Cannabinoid hyperemesis syndrome is a condition characterized by chronic cannabis use and cyclic episodes of nausea, vomiting, and abdominal pain, relieved by compulsive bathing. The syndrome is likely to be underdiagnosed in pregnant women due to its similarity with hyperemesis gravidarum in the presentation. Case We report a 20-year-old pregnant woman with multiple admissions for recurrent nausea and vomiting who was observed to be taking frequent hot showers. Without other identifiable causes, she was diagnosed with cannabinoid hyperemesis syndrome and managed with antiemetics and abstinence. Conclusion Abstinence from cannabis use is highly recommended in pregnant women due to its potential harm in fetal development and stimulation of intractable nausea and vomiting. Recognizing the symptoms and proper history taking prompt early diagnosis, allowing timely and adequate treatment.
The development of a screening test for cervical dysplasia has been a major force in diminishing the worldwide incidence of invasive cervical cancer. Screening intervals recommended by professional organizations have changed over the past half century. Recognition of the human papillomavirus (HPV) as the causative agent and enhanced understanding of the natural history of HPV and cervical dysplasia in different age groups have prompted the American College of Obstetricians and Gynecologists and other professional societies to defer Pap smear screening to intervals no less than 2 years apart in women 21-29, and every 3 years in women 30 and over assuming no prior history of cervical dysplasia. Screening should start no sooner than age 21. These recommendations more closely resemble those currently practiced in Europe and other parts of the developed world. Those who have undergone hysterectomy no longer need screening unless high-grade dysplasia was present. Although the value of pelvic examination is not debated in women with symptoms referable to the female genital tract, the endorsement by several professional societies of less than annual cervical cancer screening in healthy women also begs the question of whether annual pelvic examination (speculum and/or bimanual examination) benefits asymptomatic women. Some sexually transmitted infections are amenable to self-insertion of a vaginal probe or detectable by voided urine specimen. Bimanual examination is insensitive in detecting early ovarian cancer with a high false-positive rate leading to patient anxiety, excessive diagnostic testing, and unnecessary surgical procedures. Future study should focus on the frequency in which healthy asymptomatic women should undergo pelvic examination.
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