Determination of a strength index for upper body local endurance strength in sedentary individuals: a cross sectional analysis

A range of balance between flexor and extensor muscles is fundamental in order to prevent pathologies caused by bad postures or to ensure health of the joint as a measure of prevention of overtraining in specific muscle groups. Therefore, the aim of this study is to examine the ratio between "pulling" and "pushing" strength in sedentary individuals. 212 healthy participants, of both genders (139 male and 73 female; age 32 \ub1 13.3 years, weight 70.2 \ub1 14.1 kg, height 173 \ub1 9 cm) were retained for investigation. Strength was assessed through a new methodology: Pulling through a lat-pulldown test while pushing strength through a chest-press test. Both tests were performed to exhaustion with an overload of 30 % of each participants bodyweight. Such method aims to prevent excessive overloads in sedentary individuals. Pearson's correlations and a t test to assess differences were analyzed. Subsequently, the ratio for both genders of pulling and pushing local endurance strength was assessed by means. A mean number of 57 repetitions was shown with the lat-pulldown while 34 repetition with the chest press. A correlation of 0.42 has been found between the number of repetitions of the two tests. A significant difference (p < 0.001) was found between such performances. No correlation was found between the strength measures and the anthropometric parameters of the participants. The lat machine to chest press ratio was 1.36:1 for male while 2.69:1 for female. The results indicate that sedentary participants have higher pulling rather than pushing local endurance strength. Such ratio should be considered as a normative value when starting to perform exercise protocols. Resistance training should be performed in order to improve strength measures of the weaker muscles and reduce such ratio

Pain perception and stabilometric parameters in people with chronic low back pain after a pilates exercise program: A randomized controlled trial

Various exercise interventions, such as Pilates exercises and traditional physical therapy methods, are employed to decrease low back pain (LBP). Nonspecific low back pain (NSLBP) is distinct from LBP, however, as the distribution of pain is restricted to the region between the costal margin and the inferior gluteal. The aim of our randomized controlled trial was to evaluate the effects of a program of Pilates exercises on pain perception and stabilometric parameters in patients with NSLBP.Thirty-eight participants were randomly allocated, using a 1:1 scheme, to either the experimental group (EG) or control group (CG). The EG completed a 14-week program of Pilates exercises, performed thrice per week under the supervision of an exercise specialist, while the CG was managed with a social program only. Measures of posturography and Oswestry Disability Index (ODI) for pain perception were obtained at baseline (T0) and after the 14 weeks of intervention (T)1.Posturography measures improved for patients in the EG, with both eyes open and eyes closed (P\u200a<\u200a0.05). There were no statistical differences in posturography in the CG. ODI decreased significantly in both groups over the 14 weeks of the study protocol: EG, T0, 13.7\u200a\ub1\u200a5.0 compared with T1, 6.5\u200a\ub1\u200a4.0 (P\u200a<\u200a0.001); and CG, T0, 10.7\u200a\ub1\u200a7.8 compared with T1, 8.4\u200a\ub1\u200a7.8 (P\u200a<\u200a0.01). A greater extent of reduction in pain was achieved in the EG.The Pilates exercise program yielded improvements in pain and posturography outcomes. Our study also confirms the applicability of posturography in evaluating postural instability in patients with NSLBP. Due to our relatively small study group, future studies would be necessary to confirm our findings

EZH2, HIF-1, and their inhibitors: An overview on pediatric cancers

During the past decades, several discoveries have established the role of epigenetic modifications and cellularmicroenvironment in tumor growth and progression. One of the main representatives concerning epigenetic modification is the polycomb group (PcG). It is composed of different highly conserved epigenetic effector proteins preserving, through several post-translational modifications of histones, the silenced state of the genes implicated in a wide range of central biological events such as development, stem cell formation, and tumor progression. Proteins of the PcG can be divided in polycomb repressive complexes (PRCs): PRC1 and PRC2. In particular, enhancer of zeste homolog 2 (EZH2), the catalytic core subunit of PRC2, acts as an epigenetic silencer ofmany tumor suppressor genes through the trimethylation of lysine 27 on histone H3, an essential binding site for DNA methyl transferases and histone deacetylases. A growing number of data suggests that overexpression of EZH2 associates with progression and poor outcome in a large number of cancer cases. Hypoxia inducible factor (HIF) is an important transcription factor involved in modulating cellular response to the microenvironment by promoting and regulating tumor development such as angiogenesis, inflammation, metabolic reprogramming, invasion, and metastatic fate. The HIF complex is represented by different subunits (α and β) acting together and promoting the expression of vascular endothelial growth factor (VEGF), hexokinase II (HKII), receptor for advanced glycation end products (RAGE), carbonic anhydrase (CA), etc., after binding to the hypoxia-response element (HRE) binding site on the DNA. In this review, we will try to connect these two players by detailing the following: (i) the activity and influence of these two important regulators of cancer progression in particular for what concerns pediatric tumors, (ii) the possible correlation between them, and (iii) the feasibility and efficiency to contrast them using several inhibitors

The multivalency game ruling the biology of immunity

Macrophages play a crucial role in our immune system, preserving tissue health and defending against harmful pathogens. This article examines the diversity of macrophages influenced by tissue-specific functions and developmental origins, both in normal and disease conditions. Understanding the spectrum of macrophage activation states, especially in pathological situations where they contribute significantly to disease progression, is essential to develop targeted therapies effectively. These states are characterized by unique receptor compositions and phenotypes, but they share commonalities. Traditional drugs that target individual entities are often insufficient. A promising approach involves using multivalent systems adorned with multiple ligands to selectively target specific macrophage populations based on their phenotype. Achieving this requires constructing supramolecular structures, typically at the nanoscale. This review explores the theoretical foundation of engineered multivalent nanosystems, dissecting the key parameters governing specific interactions. The goal is to design targeting systems based on distinct cell phenotypes, providing a pragmatic approach to navigating macrophage heterogeneity's complexities for more effective therapeutic interventions

Cellular delivery of antibodies: effective targeted subcellular imaging and new therapeutic tool

It is already more than a century since the pioneering work of the Nobel Laureate Ehrlich gave birth to the side chain theory1, which helped to define antibodies and their ability to target specific biological sites. However, the use of antibodies is still restricted to the extracellular space due to the lack of a suitable delivery vehicle for the efficient transport of antibodies into live cells without inducing toxicity. In this work, we report the efficient encapsulation and delivery of antibodies into live cells with no significant loss of cell viability or any deleterious affect on the cell metabolic activity. This delivery system is based on poly(2-(methacryloyloxy)ethyl phosphorylcholine)-block-(2-(diisopropylamino)ethyl methacrylate), (PMPC-PDPA), a pH sensitive diblock copolymer that self-assembles to form nanometer-sized vesicles, also known as polymersomes, at physiological pH. These polymersomes can successfully deliver relatively high antibody payloads within live cells. Once inside the cells, we demonstrate that these antibodies can target their epitope by immune-labelling of cytoskeleton, Golgi, and transcription factor proteins in live cells. We also demonstrate that this effective antibody delivery mechanism can be used to control specific subcellular events, as well as modulate cell activity and pro-inflammatory process

Abnormal hippocampal melatoninergic system: a potential link between absence epilepsy and depression-like behavior in WAG/Rij rats?

Absence epilepsy and depression are comorbid disorders, but the molecular link between the two disorders is unknown. Here, we examined the role of the melatoninergic system in the pathophysiology of spike and wave discharges (SWDs) and depression-like behaviour in the Wistar Albino Glaxo from Rijswijk (WAG/Rij) rat model of absence epilepsy. In WAG/Rij rats, SWD incidence was higher during the dark period of the light-dark cycle, in agreement with previous findings. However, neither pinealectomy nor melatonin administration had any effect on SWD incidence, suggesting that the melatoninergic system was not involved in the pathophysiology of absence-like seizures. Endogenous melatonin levels were lower in the hippocampus of WAG/Rij rats as compared to non-epileptic control rats, and this was associated with higher levels of melatonin receptors in the hippocampus, but not in the thalamus. In line with the reduced melatonin levels, cell density was lower in the hippocampus ofWAG/Rij rats and was further reduced by pinealectomy. As expected, WAG/Rij rats showed an increased depression-like behaviour in the sucrose preference and forced swim tests, as compared to non-epileptic controls. Pinealectomy abolished the difference between the two strains of rats by enhancing depression-like behaviour in non-epileptic controls. Melatonin replacement displayed a significant antidepressant-like effect in bothWAG/Rij and control rats. These findings suggest that a defect of hippocampal melatoninergic system may be one of the mechanisms underlying the depression-like phenotype inWAG/Rij rats and that activation of melatonin receptors might represent a valuable strategy in the treatment of depression associated with absence epilepsy

N-acetyl-cysteine, a drug that enhances the endogenous activation of group-II metabotropic glutamate receptors, inhibits nociceptive transmission in humans.

Emerging research seeking novel analgesic drugs focuses on agents targeting group-II metabotropic glutamate receptors (mGlu2 and mGlu3 receptors). N-Acetylcysteine (NAC) enhances the endogenous activation of mGlu2/3 receptors by activating the glial glutamate:cystine membrane exchanger. Here, we examined whether NAC inhibits nociceptive responses in humans and animals. We tested the effect of oral NAC (1.2 g) on thermal-pain thresholds and laser-evoked potentials in 10 healthy volunteers, according to a crossover, double-blind, placebo-controlled design, and the effect of NAC (100 mg/kg, i.p.) on the tail-flick response evoked by radiant heat stimulation in mice.In healthy subjects, NAC treatment left thermal-pain thresholds unchanged, but significantly reduced pain ratings to laser stimuli and amplitudes of laser-evoked potentials. NAC induced significantly greater changes in these measures than placebo. In the tail-flick test, NAC strongly reduced the nocifensive reflex response to radiant heat. The action of NAC was abolished by the preferential mGlu2/3 receptor antagonist, LY341495 (1 mg/kg, i.p.).Our findings show for the first time that NAC inhibits nociceptive transmission in humans, and does the same in mice by activating mGlu2/3 receptors. These data lay the groundwork for investigating the therapeutic potential of NAC in patients with chronic pain