In vitro and in vivo antitumour effects of phenylboronic acid against mouse mammary adenocarcinoma 4T1 and squamous carcinoma SCCVII cells

The cytotoxic activity of phenylboroxine acid was evaluated in vitro on mouse mammary adenocarcinoma 4T1, mouse squamous cell carcinoma SCCVII, hamster lung fibroblast V79 and mouse dermal fibroblasts L929 cell lines. The cytotoxic effects were dose dependent for all tested tumour and non-tumour cell lines. Under in vivo conditions, three application routes of phenylboronic acid were studied: intra-peritoneal (i.p.), intra-tumour (i.t.) and per-oral. After tumour transplantation in syngeneic mice, phenylboronic acid was shown to slow the growth of both tumour cell lines (4T1 and SCCVII) compared with the control. The inhibitory effects were pronounced during the application of phenylboronic acid. For both tested tumour cell lines, the most prominent antitumour effect was obtained by intraperitoneal administration, followed significantly by oral administration.     

Ultrasonographic observations of the maturation of basic movements in guinea pig fetuses

Ultrasonography has not previously been used for studying fetal movements in precocial rodents. The objective of this study was to ultrasonographically determine the sequence of the appearance of basic movements in a guinea pig fetus. The research included eight guinea pig females carrying one fetus each. Fetal movements were observed for 10 minutes each day, from the 25th to 38th day of gestation. The time and sequence of the appearance of movements was observed as follows: whole body flexion (mean 27.6 SD ± 1.68), whole body extension (mean 28.1 SD ± 1.12), head flexion (mean 28.1 SD ± 1.80), head extension (mean 30.5 SD ± 2.67) forelimbs flexion (mean 30.5 SD ± 2.32), forelimbs extension (mean 30.7 SD ± 1.84), trunk rotation (mean 31.9 SD ± 2.23), forelimbs alternating flexion and extension (mean 32.1 SD ± 2.1), hind limbs extension (mean 32.2 SD ± 3.2), hind limbs flexion (mean 32.4 SD ± 3.16), and hind limbs alternating flexion and extension (mean 33.5 SD ± 2.39). The identical sequences of basic movement appearances in guinea pigs, sheep, and rats suggest that the rostrocaudal gradient of basic movement appearance could be a general developmental pattern in mammalian species.     

Efficacy and acceptability of pharmacological,psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review

Top‐tier evidence on the safety/tolerability of 80 medications in children/adolescents with mental disorders has recently been reviewed in this jour­nal. To guide clinical practice, such data must be combined with evidence on efficacy and acceptability. Besides medications, psychosocial inter­ventions and brain stimulation techniques are treatment options for children/adolescents with mental disorders. For this umbrella review, we systematically searched network meta‐analyses (NMAs) and meta‐analyses (MAs) of randomized controlled trials (RCTs) evaluating 48 medications, 20 psychosocial interventions, and four brain stimulation techniques in children/adolescents with 52 different mental disorders or groups of mental disorders, reporting on 20 different efficacy/acceptability outcomes. Co‐primary outcomes were disease‐specific symptom reduction and all‐cause discontinuation (“acceptability”). We included 14 NMAs and 90 MAs, reporting on 15 mental disorders or groups of mental disorders. Overall, 21 medications outperformed placebo regarding the co‐primary outcomes, and three psychosocial interventions did so (while seven outperformed waiting list/no treatment). Based on the meta‐analytic evidence, the most convincing efficacy profile emerged for amphetamines, methylphenidate and, to a smaller extent, behavioral therapy in attention‐deficit/hyperactivity disorder; aripiprazole, risperidone and several psychosocial interventions in autism; risperidone and behavioral interventions in disruptive behavior disorders; several antipsychotics in schizophrenia spectrum disorders; fluoxetine, the combination of fluoxetine and cognitive behavioral therapy (CBT), and interpersonal therapy in depression; aripiprazole in mania; fluoxetine and group CBT in anxiety disorders; fluoxetine/selective serotonin reuptake inhibitors, CBT, and behavioral therapy with exposure and response prevention in obsessive‐compulsive disorder; CBT in post‐traumatic stress disorder; imipramine and alarm behavioral intervention in enuresis; behavioral therapy in encopresis; and family therapy in anorexia nervosa. Results from this umbrella review of interventions for mental disorders in children/adolescents provide evidence‐based information for clinical decision making.     

Humans as regulators of plant-herbivore-insectivore system in the urban environment

Man affects the sanitary and decorative state of urban plantations by carrying out various agrotechnical measures, in particular topiary. The human activity was shown to affect the members of the plant-herbivore-insectivore system in different ways. The agrotechnical measures positively affect humans and plants and negatively, phytophagous and entomophagous insects. The spatial and temporal changes in the urban environment are responsible for different microsuccessions in colonization of plants by insects.     

Niemann–Pick type C cells show cholesterol dependent decrease of APP expression at the cell surface and its increased processing through the β-secretase pathway

The link between cholesterol and Alzheimer's disease has recently been revealed in Niemann–Pick type C disease. We found that NPC1^?/? cells show decreased expression of APP at the cell surface and increased processing of APP through the β-secretase pathway resulting in increased C99, sAPPβ and intracellular Aβ40 levels. This effect is dependent on increased cholesterol levels, since cholesterol depletion reversed cell surface APP expression and lowered Aβ/C99 levels in NPC1^?/? cells to the levels observed in wt cells. Finding that overexpression of C99, a direct γ-secretase substrate, does not lead to increased intracellular Aβ levels in NPC1^?/? cells vs. CHOwt suggests that the effect on intracellular Aβ upon cholesterol accumulation in NPC1^?/? cells is not due to increased APP cleavage by γ-secretase. Our results indicate that cholesterol may modulate APP processing indirectly by modulating APP expression at the cell surface and thus its cleavage by β-secretase.     

Prevalence of rare F5 variants in general population from Bosnia and Herzegovina

Molecular Biology Reports - Human gene F5, encoding coagulation factor V, was previously reported to be highly polymorphic. Apart from FV Leiden, several other rare variants have been detected in...     

Elimination of self-tolerogen turns nonresponder mice into responders

Two sets of genes control the immune response ofH-2 ^d mice to the synthetic antigen poly(Glu⁵⁰Tyr⁵⁰) (GT). One set involves class II major histocompatibility complex (Mhc) loci encoding an A^d product that serves as a recognition context to GT-reactive helper T cells (T_h). The other one is a background gene, the product of which, in association with the same Mhc-restricting element, mimics the GT/A^d complex. Mice expressing the GT-mimicking background-encoded structure (Im^gt), which is preferentially displayed on B lymphoblasts, do not respond to GT as a consequence of self-tolerance. On the other hand, elimination of cells bearing Im^gt renders these mice responsive to GT, demonstrating that tolerance to self can impoverish the immune system. Im^gt is probably not identical to GT, but resembles it in the way it forms complexes with A^d molecules ofMhc.