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This is a collection of essays and short stories inspired by the work of Stanis±aw Lem featuring a number of stories written by leading figures in contemporary science fiction, as well as fellow Polish writers.

Angiotensinogen (AGT), a precursor of angiotensin II (AngII), contributes to regulating (patho)physiological conditions, including blood pressure changes, inflammation, and kidney fibrosis. However, the precise role of tissue-specific AGT in kidney fibrosis independent of blood pressure remains to be fully understood. This study investigated the source of intrarenal AGT and its role in kidney injury and fibrosis during obstructive nephropathy. Proximal tubule- (PT, major source secreting AGT in the kidney; PKO) or liver- (major source of circulating AGT; LKO) AGT knockout (KO) mice were subjected to unilateral ureteral obstruction (UUO), a blood pressure-independent fibrosis model. UUO increased AGT mRNA and protein levels in the kidneys. PKO decreased AGT mRNA, but LKO enhanced it in UUO kidneys compared with the control. In contrast, the intrarenal protein levels of AGT increased in PKO, but not in LKO in UUO kidneys, indicating that the liver is a major source of intrarenal AGT protein. Expression of megalin, a PT receptor involved in the uptake of circulating AGT, was down-regulated in UUO kidneys and was independent of PKO or LKO. However, none of these changes prevented UUO-induced tubular injury and kidney fibrosis. Hepatic and proximal tubule AGT play distinct roles in contributing to intrarenal AGT levels during UUO, and their genetic inhibitions fail to prevent kidney injury and fibrosis, suggesting a highly complicated signaling pathway of the renin-angiotensin system and an associated compensatory mechanism in obstructive nephropathy.

Despite evidence regarding the impact of childhood abuse perpetrated by close others, or high betrayal trauma, a number of barriers continue to impede research efforts, including concerns that research may do more harm than good. Research conducted with Western samples has indicated that contrary to such concerns, participants rate the benefit of participating in trauma research as outweighing costs, even when they have a history of high betrayal trauma. Certain non-Western values, such as interpersonal harmony, could play a role in perceptions regarding trauma research participation. The current study evaluated perceptions of 79 Japanese undergraduate students who participated in an online study of child abuse. Japanese students rated the importance of participating in trauma research as greater than any immediate distress it caused. Interpersonal harmony was not related to perceptions of participating in trauma research, nor was a history of high betrayal child trauma. Taken together, these findings support continued research on childhood abuse in non-Western samples.

The trigger-tube apparatus and method was developed for mixing solutes and tracers for injection tests. The apparatus is a cap-trigger tube segment and the technique mixes solutes in boreholes in 2 min. Trigger-tube with solute / tracer is introduced into the well, the trigger is released, the tube is withdrawn and the solute / tracer mixes with well water instantaneously to give a homogeneous mixture. Field tests using this method and apparatus for point dilution tests gave a Darcy velocity of 4.06 m/d, seepage velocity of 122.89 m/d and effective porosity of 0.33. Natural gradient tests gave a Darcy velocity of 4.06 m/d and natural velocity of 123 m/d, using tracer, for the same fracture at 21 m in borehole UO5, University of the Free State campus test site. The apparatus enables a comparatively shorter time for carrying out SWIW tests than is possible using the pump mixing method. Field tests gave results of 13 min for the trigger-tube method and 25 min for the pump mixing method, for a point dilution test using NaCl as a conservative tracer. The trigger-tube apparatus can be used for any borehole test that requires the introduction of a homogenous mixture.

The concentrations of the heavy metals cadmium (Cd), mercury (Hg), lead (Pb), chromium, silver, nickel, copper, and zinc in the edible portions of 105 marine invertebrates representing 16 mollusk and crustacean species were accurately determined to evaluate their hazard for human consumption. The samples were collected in 2011 from major fish markets on the coast of Korea and analyzed for Hg using a direct Hg analyzer and for other metals using inductively coupled plasma mass spectrometry. Estimated dietary exposure (EDE) was determined, and a risk assessment was made of the heavy metals to provide information concerning consumer safety. The Cd concentrations, which were the highest for the three hazardous metals (Cd, Hg, and Pb), were significantly higher (P < 0.05) in the bivalves and crabs than in the gastropods and cephalopods. However, the concentrations of these metals in all samples were within the regulatory limits set by Korea and other countries. The EDE was compared with the provisional tolerable daily intake (PTDI) adopted by the Joint FAO/WHO Expert Committee on Food Additives or the U.S. Environmental Protection Agency. The EDE of Cd, Hg, and Pb for each class of marine invertebrate were 0.07 to 2.64, 0.01 to 0.43, and 0.001 to 0.16% of the PTDI, respectively. The total EDE of Cd, Hg, and Pb for marine invertebrates accounted for 4.03, 0.96, and 0.21%, respectively, of the PTDI. The EDE of other metals in each class of marine invertebrate was less than 2% of the PTDI. The hazard index is a reasonable parameter for assessing the risk of heavy metal consumption associated with contaminated food. In the present study, the hazard index for all of the species was less than 1.0, which indicates that the intake of heavy metals from consumption of these marine invertebrates does not represent an appreciable hazard to humans.

Licochalcone A (Lico-A) is a natural phenol licorice compound with multiple bioactivities, including anti-inflammatory, anti-microbial, anti-fungal and osteogenesis-inducing properties. In the present study, we investigated the Lico-A-induced apoptotic effects and examined the associated apoptosis pathway in KB human oral cancer cells. Lico-A decreased the number of viable KB oral cancer cells. However, Lico-A did not have an effect on primary normal human oral keratinocytes. In addition, the IC50 value of Lico-A was determined to be ~50 μM following dose-dependent stimulation. KB oral cancer cells stimulated with Lico-A for 24 h showed chromatin condensation by DAPI staining, genomic DNA fragmentation by agarose gel electrophoresis and a gradually increased apoptotic cell population by FACS analysis. These data suggest that Lico-A induces apoptosis in KB oral cancer cells. Additionally, Lico-A-induced apoptosis in KB oral cancer cells was mediated by the expression of factor associated suicide ligand (FasL) and activated caspase-8 and −3 and poly(ADP-ribose) polymerase (PARP). Furthermore, in the KB oral cancer cells co-stimulation with a caspase inhibitor (Z-VAD-fmk) and Lico-A significantly abolished the apoptotic phenomena. Our findings demonstrated that Lico-A-induced apoptosis in KB oral cancer cells involves the extrinsic apoptotic signaling pathway, which involves a caspase-dependent FasL-mediated death receptor pathway. Our data suggest that Lico-A be developed as a chemotherapeutic agent for the management of oral cancer.

Purpose We conducted a prospective observational study for premenopausal women receiving adjuvant adriamycin and cyclophosphamide-containing regimens to define the pattern of chemotherapy-induced amenorrhea (CIA), the menopause-specific quality of life (MENQOL), and the hormone profiles. Methods From October 2003 to July 2007, 387 patients with breast cancer who underwent curative surgery were prospectively included. Patient self-assessment by MENQOL questionnaires and blood samples for hormone assays were taken before chemotherapy, and 1, 6, and 12 months after chemotherapy was completed. Results Patients were categorized into three groups according to their duration and reversibility of amenorrhea, with 312 eligible patients split into long-term CIA ( n  = 180, 57.7 %), temporary CIA ( n  = 113, 36.2 %), and menstrual irregularity ( n  = 19, 6.1 %) groups. Risk factors for long-term CIA were identified as age ≥40 years ( p  < 0.001), the addition of taxane ( p  = 0.01), and tamoxifen use ( p  = 0.03). MENQOL was worst immediately after the completion of adjuvant chemotherapy, and this was not fully recovered even 12 months after chemotherapy had finished. Age ≥40 years and tamoxifen exposure were inversely associated with MENQOL. In long-term CIA patients, the level of follicle-stimulating hormone increased after chemotherapy; this level, however, was reduced in patients who received tamoxifen, but remained high and stable in those who did not ( p  < 0.001 at 6 months; p  < 0.001 at 12 months). Conclusion This study showed that most premenopausal breast cancer patients who received adjuvant chemotherapy experienced clinically significant CIA, followed by impaired MENQOL. Our findings may be relevant in the decision-making processes for premenopausal women with breast cancer.

Eclipta alba (L.) Hassk (E. alba) is a traditionally acclaimed medicinal herb used for the promotion of hair growth. However, to the best of our knowledge, no report has been issued to date on its effects on genetically distorted hair follicles (HFs). In this study, we aimed to identify an agent (stimuli) that may be beneficial for the restoration of human hair loss and which may be used as an alternative to synthetic drugs. We investigated the effects of petroleum ether extract (PEE) and different solvent fractions of E. alba on HFs of nude mice. Treatment was performed by topical application on the backs of nude mice and the changes in hair growth patterns were evaluated. Histological analysis was carried out to evaluate the HF morphology and the structural differences. Immunohistochemical (IHC) staining was performed to visualize follicular keratinocyte proliferation. The histological assessments revealed that the PEE-treated skin specimens exhibited prominent follicular hypertrophy. Subsequently, IHC staining revealed a significant increase (p<0.001) in the number of follicular keratinocytes in basal epidermal and matrix cells. Our results also demonstrated that PEE significantly (p<0.001) reduced the levels of transforming growth factor-β1 (TGF-β1) expression during early anagen and anagen-catagen transition. Our results suggest that PEE of E. alba acts as an important exogenous mediator that stimulates follicular keratinocyte proliferation and delays terminal differentiation by down-regulating TGF-β1 expression. Thus, this study highlights the potential use of PEE of E. alba in the treatment of certain types of alopecia.

Reactive oxygen species mediate high glucose–induced plasminogen activator inhibitor-1 up-regulation in mesangial cells and in diabetic kidney. Plasminogen activator inhibitor-1 (PAI-1) plays an important role in remodeling of extracellular matrix (ECM) in the glomeruli. PAI-1 is up-regulated by high glucose and is overexpressed in diabetic kidney. Since reactive oxygen species (ROS) mediate ECM accumulation in diabetic glomeruli and was recently found to mediate transforming growth factor-β1 (TGF-β1)-induced PAI-1 up-regulation in glomerular mesangial cells, we examined the role of ROS in high glucose–induced PAI-1 expression in cultured glomerular mesangial cells and in streptozotocin-induced diabetic rat glomeruli. Growth arrested and synchronized primary rat mesangial cells were treated with different concentrations of glucose in the presence or absence of N-acetylcysteine (NAC) or trolox, or after cellular reduced form of glutathione (GSH) depleted with DL-buthionine-(S,R)-sulfoximine (BSO). Taurine was administered to diabetic rats from 2 days to 4 weeks after streptozotocin injection. Urinary protein excretion, glomerular volume, and fractional mesangial area were measured as markers of renal injury and lipid peroxide (LPO) as an oxidative stress marker. PAI-1 mRNA expression was measured by Northern blot analysis in mesangial cells and reverse transcription-polymerase chain reaction (RT-PCR) in glomeruli, PAI-1 protein by Western blot analysis and enzyme-linked immunosorbent assay (ELISA), and plasmin activity by fluorometry. High glucose significantly increased PAI-1 mRNA and protein expression and decreased plasmin activity in mesangial cells. Equimolar concentrations of L-glucose or mannitol did not affect PAI-1 expression. BSO pretreatment significantly increased basal PAI-1 expression and amplified the response to high glucose. NAC effectively inhibited high glucose–induced, but not basal, PAI-1 expression. Reduced plasmin activity in mesangial cells by high glucose was rescued by antioxidants. Anti-TGF-β antibody inhibited both high glucose– and H2O2-induced PAI-1 up-regulation. Taurine significantly reduced plasma LPO, glomerular PAI-1 expression, glomerular volume, fractional mesangial area, and proteinuria in streptozotocin-induced diabetic rats. These results demonstrate that ROS mediate high glucose–induced up-regulation of PAI-1 expression in cultured mesangial cells and in diabetic glomeruli. Since both high glucose and TGF-β1 induce cellular ROS and ROS mediate both high glucose– and TGF-β1–induced PAI-1, ROS appear to amplify TGF-β1 signaling in high glucose–induced PAI-1 up-regulation. Antioxidants can prevent accumulation of ECM protein in diabetic glomeruli partly by abrogating up-regulation of PAI-1 and suppression of plasmin activity.

The BRAF V600E mutation is found in approximately 40% of papillary thyroid cancers (PTC). Mice with thyroid-specific expression of Braf V600E (TPO– Braf V600E ) develop PTC rapidly with high levels of serum thyroid-stimulating hormone (TSH). It is unclear to what extent the elevated TSH contributes to tumor progression. To investigate the progression of Braf V600E -induced PTC (BVE–PTC) under normal TSH, we transplanted BVE–PTC tumors subcutaneously into nude and TPO– Braf WT mice. Regression of the transplanted tumors was observed in both nude and TPO– Braf WT mice. They were surrounded by heavy lymphocyte infiltration and oncogene-induced senescence (OIS) was demonstrated by strong β-gal staining and absence of Ki-67 expression. In contrast, BVE–PTC transplants continued to grow when transplanted into TPO– Braf V600E mice. The expression of Trp53 was increased in tumor transplants undergoing OIS. Trp53 inactivation reversed OIS and enabled tumor transplants to grow in nude mice with characteristic cell morphology of anaplastic thyroid cancer (ATC). PTC-to-ATC transformation was also observed in primary BVE–PTC tumors. ATC cells derived from Trp53 knockout tumors had increased PI3K/AKT signaling and became resistant to Braf V600E inhibitor PLX4720, which could be overcome by combined treatment of PI3K inhibitor LY294002 and PLX4720. In conclusion, BVE–PTC progression could be contained via p53-dependent OIS and TSH is a major disruptor of this balance. Simultaneous targeting of both MAPK and PI3K/AKT pathways offer a better therapeutic outcome against ATC. The current study reinforces the importance of rigorous control of serum TSH in PTC patients.