In Vitro Study of Cytotoxic Mechanisms of Alkylphospholipids and Alkyltriazoles in Acute Lymphoblastic Leukemia Models.

This study investigates the efficacy of miltefosine, alkylphospholipid, and alkyltriazolederivative compounds against leukemia lineages. The cytotoxic effects and cellular and molecular mechanisms of the compounds were investigated. The inhibitory potential and mechanism of inhibition of cathepsins B and L, molecular docking simulation, molecular dynamics and binding free energy evaluation were performed to determine the interaction of cathepsins and compounds.

Impact of physiotherapy with telerehabilitation on caregivers of patients with neurological disorders: A systematic review protocol.

Introduction: Caregivers are essential during and after rehabilitation but exhibit intense physical and mental burdens due to responsibilities, resulting in stress, irritability, depression, anxiety, pain, and financial distress. Telerehabilitation offers several remote health services that improve time, engagement, and physical and mental health care access. Thus, we outlined a systematic review protocol to evaluate the impact of telerehabilitation on the burden, stress, pain, and quality of life of caregivers of patients with neurological disorders.

Semysinthetic biflavonoid Morelloflavone-7,4',7″,3‴,4‴-penta-O-butanoyl is a more potent inhibitor of Proprotein Convertases Subtilisin/Kexin PC1/3 than Kex2 and Furin.

Background: Garcinia brasiliensis is a species native to the Amazon forest. The white mucilaginous pulp is used in folk medicine as a wound healing agent and for peptic ulcer, urinary, and tumor disease treatments. The activity of the proprotein convertases (PCs) Subtilisin/Kex is associated with the development of viral, bacterial and fungal infections, osteoporosis, hyperglycemia, atherosclerosis, cardiovascular, neurodegenerative and neoplastic diseases.

Cyclopalladated compounds containing 2,6-lutidine: Synthesis, spectral and biological studies.

Bridge splitting reactions between [Pd(C,N-dmba)(μ-X)] (dmba = N,N-dimethylbenzylamine; X = Cl, I, N, NCO) and 2,6-lutidine (lut) in the 1:2 molar ratio at room temperature afforded cyclopalladated compounds of general formulae [Pd(C,N-dmba)(X)(lut)] {X = Cl (1), I(2), NNN(3), NCO(4)}, which were characterized by elemental analyses and infrared (IR), H NMR spectroscopy. The molecular structures of all synthesized palladacycles have been solved by single-crystal X-ray crystallography. The cytotoxicity of the cyclopalladated compounds has been evaluated against a panel of murine {mammary carcinoma (4T1) and melanoma (B16F10-Nex2)} and human {melanoma (A2058, SK-MEL-110 and SK-MEL-5) tumor cell lines.

Effects of motor imagery training of Parkinson's disease: a protocol for a randomized clinical trial.

Background: Gait disorders in individuals with Parkinson's disease (PD) may be associated with alterations in the motor control system and aggravated by psychoemotional and cognitive issues. Therapeutic strategies aimed at self-perception and motor regulation seem to be promising. Motor imagery (MI) has been shown to be one of these strategies, but there is still no clear evidence of its applicability in this population.

4'-Hydroxy-6,7-methylenedioxy-3-methoxyflavone: A novel flavonoid from Dulacia egleri with potential inhibitory activity against cathepsins B and L.

A new flavone, 4'-hydroxy-6,7-methylenedioxy-3-methoxyflavone 1, and two other nucleosides, ribavirin 2 and adenosine 3, were isolated from the leaves of Dulacia egleri. The nucleosides were identified by spectroscopic techniques (1D, 2D-NMR) while the structure of the flavonoid was established by 1D, 2D-NMR analysis, including HRESIMS data. The results obtained in the biological assays showed that the compound 1 was able to inhibit cathepsins B and L with IC of 14.

Salt-sensitive (Rapp) rats from Envigo spontaneously develop accelerated hypertension independent of ovariectomy on a low-sodium diet.

Inbred salt-sensitive (SS) rats developed by John Rapp and distributed by Harlan (SS/JrHsd) were shown to model ovariectomy-induced hypertension because on a low-sodium (LS) diet, ovariectomized SS (SS-OVX) animals became hypertensive in contrast to their sham-operated (SS-SHAM) normotensive littermates. After Harlan merged with Envigo in 2015, inconsistencies in the LS normotensive phenotype were reported. To further investigate these inconsistencies, we studied the effects of ovariectomy on SS and salt-resistant (SR) rats purchased from Envigo (SS/JrHsd/Env) between 2015 and 2017.

Estrogen receptor β activation within dorsal raphe nucleus reverses anxiety-like behavior induced by food restriction in female rats.

Severe food restriction (FR), as observed in disorders like anorexia nervosa, has been associated to the reduction of estrogen levels, which in turn could lead to anxiety development. Estrogen receptors, mainly ERβ type, are commonly found in the dorsal raphe nucleus (DRN) neurons, an important nucleus related to anxiety modulation and the primary source of serotonin (5-HT) in the brain. Taking together, these findings suggest an involvement of estrogen in anxiety modulation during food restriction, possibly mediated by ERβ activation in serotonergic DRN neurons.

Thermodynamic analysis of Kex2 activity: The acylation and deacylation steps are potassium- and substrate-dependent.

Kex2 is the prototype of a large family of eukaryotic subtilisin-related proprotein-processing proteases that cleave at sites containing pairs of basic residues. Here, we studied the effects of KCl on the individual rate constants of association, dissociation, acylation and deacylation and determined the thermodynamic parameters at each step of the Kex2 reaction. Potassium bound Kex2 with K=20.

Chronic Glibenclamide Treatment Attenuates Walker-256 Tumour Growth in Prediabetic Obese Rats.

Background/aims: The sulphonylurea glibenclamide (Gli) is widely used in the treatment of type 2 diabetes. In addition to its antidiabetic effects, low incidences of certain types of cancer have been observed in Gli-treated diabetic patients. However, the mechanisms underlying this observation remain unclear.

High fat diet induced-obesity facilitates anxiety-like behaviors due to GABAergic impairment within the dorsomedial hypothalamus in rats.

Overweight and obesity are conditions associated with an overall range of clinical health consequences, and they could be involved with the development of neuropsychiatric diseases, such as generalized anxiety disorder (GAD) and panic disorder (PD). A crucial brain nuclei involved on the physiological functions and behavioral responses, especially fear, anxiety and panic, is the dorsomedial hypothalamus (DMH). However, the mechanisms underlying the process whereby the DMH is involved in behavioral changes in obese rats still remains unclear.

New insights on amygdala: Basomedial amygdala regulates the physiological response to social novelty.

The amygdala has been associated with a variety of functions linked to physiological, behavioral and endocrine responses during emotional situations. This brain region is comprised of multiple sub-nuclei. These sub-nuclei belong to the same structure, but may be involved in different functions, thereby making the study of each sub-nuclei important.

Early treatment with metformin induces resistance against tumor growth in adult rats.

It is known that antidiabetic drug metformin, which is used worldwide, has anti-cancer effects and can be used to prevent cancer growth. We tested the hypothesis that tumor cell growth can be inhibited by early treatment with metformin. For this purpose, adult rats chronically treated with metformin in adolescence or in adulthood were inoculated with Walker 256 carcinoma cells.

Increased α1-adrenoreceptor activity is required to sustain blood pressure in female rats under food restriction.

Aims: We evaluated the effect of food restriction (FR) on the various reflexes involved in short term cardiovascular regulation; we also evaluated the contribution of the sympathetic nervous systemand of the plasmatic nitric oxide (NO) in the development of the counterregulatory cardiovascular changes triggered by FR.

Main Methods: Female rats were subjected to FR for 14 days, and after this period biochemical measurements of biochemical parameters were performed. For physiological tests, animals were anaesthetised, and a catheter was inserted into the femoral artery and vein for the acquisition of blood pressure and heart hate, and drug infusion, respectively.