Effects of aerobic exercise on inflammatory factors in healthy adults: a meta-analysis.

OBJECTIVE: With this meta-analysis we aimed at systematically evaluating the intervention effects of aerobic exercise on inflammatory factors in healthy adults and identifying an optimal aerobic exercise program with anti-inflammatory effects. MATERIALS AND METHODS: Four databases, including PubMed, Web of Science, Cochrane Library and SPORTDiscus, were searched from inception until April 30, 2021. Stata version 11.0 was used for data analysis. RESULTS: A total of 15 studies with 1160 participants were included. The pooled estimates showed that aerobic exercise could significantly reduce TNFα levels (SMD=-0.30, 95% CI: -0.58 - -0.03, p=0.032), while the levels of IL-6 (SMD=-0.14, 95% CI: -0.32-0.03, p=0.109) and CRP (SMD=-0.09, 95% CI: -0.34-0.16, p=0.484) were not significantly affected. CONCLUSIONS: Aerobic exercise exerts a positive effect by preventing inflammation-related diseases.

Expression of proteinase-activated receptor-2 and transient receptor potential A1 in vagal afferent nerve of rat after lung schemia-reperfusion injury.

Lung ischemia-reperfusion injury (LIRI) is a common and severe clinical complication. As the injury occurs, the pulmonary afferent nerves play an important role in regulating respiratory functions under pathophysiological conditions. The purpose of this study was to examine expression of proteinaseactivated receptor-2 (PAR2) and transient receptor potential A1 (TRPA1) in pulmonary vagal afferent nerves of LIRI and further to determine molecular mediators linking activation of PAR2 and TRPA1. A rat model of LIRI was used. Enzyme-linked immunosorbent assay (ELISA) and Western blot analysis were employed to examine pro-inflammatory cytokines (PICs, i.e., IL-1ß, IL-6 and TNF-α), and the protein levels of PIC receptors, PAR2, TRPA1, and intracellular signals. In the results, IL-1ß, IL-6 and TNF-α along with their receptors were amplified in afferent nerves of LIRI rats as compared with control rats. Sensory PAR2 and TRPA1 were also upregulated by LIRI. Blocking PAR2 by infusion of FSLLRY-NH2 attenuated upregulation of TRPA1 via intracellular signals, namely p38-MAPK and JNK. Moreover, blocking individual PIC receptor attenuated PAR2 and TRPA1 in pulmonary vagal afferent nerves. Our data showed specific signaling pathways leading LIRI to activation of PIC signal and activation of PAR2 and TRPA1 in pulmonary vagal afferent nerves via intracellular mediators. Targeting one or more of these signaling molecules may present opportunities to improve the abnormalities in vagal afferent nerve-mediated respiratory functions observed as LIRI occurs.

MicroRNA 34b inhibits cell proliferation in pediatric acute myeloid leukemia via regulating LDHA.

OBJECTIVE: To elucidate the regulatory effect of microRNA-34b on the occurrence of pediatric acute myeloid leukemia and the underlying mechanism. PATIENTS AND METHODS: The expression of microRNA-34b in the bone marrow of 72 children with newly diagnosed acute myeloid leukemia (AML) was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between microRNA-34b expression and pathological characteristics was analyzed. Kaplan-Meier curve was introduced for evaluating the prognostic value of microRNA-34b in pediatric AML. The regulatory effects of microRNA-34b on proliferation, cell cycle, and apoptosis of leukemia cells were accessed by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Bioinformatics prediction and dual-luciferase reporter gene assay were conducted to evaluate the binding between microRNA-34b and lactate dehydrogenase A (LDHA). LDHA expression after overexpression of microRNA-34b was determined by qRT-PCR and Western blot. Rescue experiments were conducted to verify whether microRNA-34b could regulate proliferative and apoptotic behaviors of leukemia cells by suppressing LDHA expression. RESULTS: MicroRNA-34b was markedly downregulated in AML children. Low expression of microRNA-34b was correlated to FAB typing, cytogenetic abnormality, and day 7 response to the treatment of pediatric AML. By collecting the follow-up data, it was found that low expression of microRNA-34b was correlated to the poor prognosis of AML. Overexpression of microRNA-34b inhibited proliferative ability and cell cycle progression, but accelerated apoptosis of AML cells. Dual-luciferase reporter gene assay verified that microRNA-34b could bind to LDHA, thereafter inhibiting LDHA expression. Overexpression of LDHA reversed the regulatory effects of microRNA-34b on proliferation, cell cycle, and apoptosis of AML cells. CONCLUSIONS: We found that microRNA-34b is lowly expressed in pediatric AML patients, and low expression of microRNA-34b may serve as an indicator of malignant progression and poor prognosis of pediatric AML. MicroRNA-34b may affect the proliferation and apoptosis of leukemia cells by regulating the expression of LDHA.

MiR-410 regulates malignant biological behavior of pediatric acute lymphoblastic leukemia through targeting FKBP5 and Akt signaling pathway.

OBJECTIVE: The aim of this study was to investigate the role of miR-410 in regulating the proliferation and apoptosis of pediatric acute lymphoblastic leukemia (ALL) cells and to explore the possible underlying mechanism. PATIENTS AND METHODS: The expression level of miR-410 in ALL cases and cells was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Luciferase reporter gene assay was performed to evaluate the interaction between miR-410 and FKBP5. MTT and colony formation assay were used to determine the effect of miR-410 on the proliferation and colony formation ability of ALL cells. The effect of miR-410 on cell apoptosis was measured by Annexin V-fluorescein isothiocyanate 1 (FITC) and propidium iodide (PI). Western blot was used to analyze the effect of miR-410 on the protein expression levels of phosphorylated Akt (p-Akt) and cleaved caspase-3. RESULTS: In our investigation, miR-410 was significantly up-regulated in ALL cases and cells. We searched three public databases to predict the potential target of miR-410, and found that FKBP5 was a direct target of miR-410. Meanwhile, Luciferase reporter gene assay confirmed our hypothesis. The overexpression of miR-410 accelerated the proliferation and colony formation ability of ALL cells, whereas remarkably decreased cell apoptosis rate. Western blotting showed that miR-410 inhibited the activation of Akt signaling pathway. However, FKBP5 could reverse the effects of miR-410. CONCLUSIONS: MiR-410 regulated the proliferation, colony formation and apoptosis of ALL cells through targeting FKBP5 and Akt signal pathway, indicating that miR-410 might be a potential therapeutic target for the treatment of ALL.

Anatomic correlates of the face and oral cavity representations in the somatosensory cortical area 3b of monkeys.

We determined the somatotopy of the face and the oral cavity representation in cortical area 3b of New World owl monkeys and squirrel monkeys. Area 3b is apparent as a densely myelinated strip in brain sections cut parallel to the surface of flattened cortex. A narrow myelin-light septum that we have termed the "hand-face septum" separates the hand representation from the more lateral face and mouth representation. The face and oral cavity representation is further divided into a series of myelin-dense ovals. We show that three ovals adjacent to the hand representation correspond to the upper face, upper lip, and chin plus lower lip, whereas three or four more rostral ovals successively represent the contralateral teeth, tongue, and the ipsilateral teeth and tongue. Strips of cortex lateral and medial to the area 3b ovals, possibly corresponding to area 1 and area 3a, respectively, have similar somatotopic sequences. Although previous results suggest the existence of great variability within and across primate species, we conclude that the representations of the face and mouth are highly similar across individuals of the same species, and there are extensive overall similarities across these two species of New World monkeys.

Reorganization of primary motor cortex in adult macaque monkeys with long-standing amputations.

The organization of primary motor cortex (M1) of adult macaque monkeys was examined years after therapeutic amputation of part of a limb or digits. For each case, a large number of sites in M1 were electrically stimulated with a penetrating microelectrode, and the evoked movements and levels of current needed to evoke the movements were recorded. Results from four monkeys with the loss of a forelimb near or above the elbow show that extensive regions of cortex formerly devoted to the missing hand evoked movements of the stump and the adjoining shoulder. Threshold current levels for stump movements were comparable to those for normal arm movements. Few or no sites in the estimated former territory of the hand evoked face movements. Similar patterns of reorganization were observed in all four cases, which included two monkeys injured as adults, one as a juvenile, and one as an infant. In a single monkey with a hindlimb amputation at the knee as an infant, stimulation of cortex in the region normally devoted to the foot moved the leg stump, again at thresholds in the range for normal movements. Finally, in a monkey that had lost digit 5 and the distal phalanges of digits 2-4 at 2 yr of age, much of the hand portion of M1 was devoted to movements of the digit stumps.

Growth of new brainstem connections in adult monkeys with massive sensory loss.

Somatotopic maps in the cortex and the thalamus of adult monkeys and humans reorganize in response to altered inputs. After loss of the sensory afferents from the forelimb in monkeys because of transection of the dorsal columns of the spinal cord, therapeutic amputation of an arm or transection of the dorsal roots of the peripheral nerves, the deprived portions of the hand and arm representations in primary somatosensory cortex (area 3b), become responsive to inputs from the face and any remaining afferents from the arm. Cortical and subcortical mechanisms that underlie this reorganization are uncertain and appear to be manifold. Here we show that the face afferents from the trigeminal nucleus of the brainstem sprout and grow into the cuneate nucleus in adult monkeys after lesions of the dorsal columns of the spinal cord or therapeutic amputation of an arm. This growth may underlie the large-scale expansion of the face representation into the hand region of somatosensory cortex that follows such deafferentations.

Pallidal and cerebellar afferents to pre-supplementary motor area thalamocortical neurons in the owl monkey: a multiple labeling study.

In the present study, we determined where thalamic neurons projecting to the pre-supplementary motor area (pre-SMA) are located relative to pallidothalamic and cerebellothalamic inputs and nuclear boundaries. We employed a triple-labeling technique in the same owl monkey (Aotus trivirgatus). The cerebellothalamic projections were labeled with injections of wheat germ agglutinin conjugated to horseradish peroxidase, and the pallidothalamic projections were labeled with biotinylated dextran amine. The pre-SMA was identified by location and movement patterns evoked by intracortical microstimulation and injected with the retrograde tracer cholera toxin subunit B. Brain sections were processed sequentially using different chromogens to visualize all three tracers in the same section. Alternate sections were processed for Nissl cytoarchitecture or acetylcholinesterase chemoarchitecture for nuclear boundaries. The cerebellar nuclei primarily projected to posterior (VLp), medial (VLx), and dorsal (VLd) divisions of the ventral lateral nucleus; the pallidum largely projected to the anterior division (VLa) of the ventral lateral nucleus and the parvocellular part of the ventral anterior nucleus (VApc). However, we also found zones of overlapping projections, as well as interdigitating foci of pallidal and cerebellar label, particularly in border regions of the VLa and VApc. Thalamic neurons labeled by pre-SMA injections occupied a wide band and were especially concentrated in the VLx and VApc, cerebellar and pallidal territories, respectively. Labeled thalamocortical neurons overlapped cerebellar inputs in the VLd and VApc and overlapped pallidal inputs in the VLa and the ventral medial nucleus. The results demonstrate that inputs from both the cerebellum and globus pallidus are relayed to the pre-SMA.

Context-dependent force coding in motor and premotor cortical areas.

In three monkeys trained to finely grade grip force in a visuomotor step-tracking task, the effect of the context on neuronal force correlates was quantitatively assessed. Three trial types, which differed in force range, number, and direction of the force steps, were presented pseudo-randomly and cued with the color of the cursor serving as feedback of the exerted force. Quantitative analyses were made on 85 neurons with similar discharge patterns in the three trial types and significant linear positive (54 cells) or negative (31 cells) correlation coefficients between firing rate and force. An analysis of covariance (ANCOVA) showed that the population slopes for 2-step were steeper than for 3-step trials. Another ANCOVA at the population level, computed on the differences in firing rate and force between force steps, persistently disclosed a significant effect of trial type. For the first two force steps, the differences in firing rate were significantly larger in the 2-step than in the 3-step increase trials. Further analyses revealed that neither the force range nor the number of steps was a unique factor. A small group of neurons was tested in an additional trial series with a uniform cue for all three trials, leading to either a loss of context-dependency or to unexpected changes in firing rate. This demonstrates that the cue color was an important instruction for task performance and neuronal activity. The most important findings are that the context-dependent changes were occurring "on-line", and that neurons displaying context-dependency were found in all three lateral premotor cortex hand regions and in the primary motor cortex. Finger muscle activity did not show any context dependency. The context-dependent effect leads to a normalization of the cortical activity. The advantage of normalization is discussed and mechanisms for the gain regulation are proposed.

Inverted pyramidal neurons in chimpanzee sensorimotor cortex are revealed by immunostaining with monoclonal antibody SMI-32.

We used the monoclonal antibody SMI-32 to label pyramidal cells of sensorimotor cortex in two chimpanzees. The majority of the pyramidal cells had typical vertically oriented apical dendrites that extended towards the pial surface. A small population of pyramidal cells varied from this orientation, so that the apical dendrites were 20 degrees or more from radial, and were often inverted, extending away from the pial surface. When numbers of non-inverted and inverted pyramidal cells were compared, less than 1% were found to be inverted.

Do superior colliculus projection zones in the inferior pulvinar project to MT in primates?

In order to determine the relationship of superior colliculus inputs to thalamic neurons projecting to the middle temporal visual area (MT), injections of wheat germ agglutinin conjugated with horseradish peroxidase were placed in the superior colliculus of three owl monkeys, with injections of Fast Blue in the MT. The locations of labelled terminals and neurons in the posterior thalamus were related to four architectonically distinct nuclei of the inferior pulvinar (Stepniewska & Kaas, Vis. Neurosci. 14, pp.1043-1060, 1997). Fast Blue injections in the MT labelled neurons largely in the medial nucleus of the inferior pulvinar. A few labelled neurons were found in the adjoining central medial nucleus of the inferior pulvinar, as well as in the lateral pulvinar and the dorsal lateral geniculate nucleus. Superior colliculus inputs were most dense in the posterior and medial nuclei of the inferior pulvinar. There were sparser inputs to the central lateral nucleus of the inferior pulvinar, locations in the lateral and medial pulvinar, and the dorsal lateral geniculate nucleus. The results indicate that the medial nucleus of the inferior pulvinar, the major projection zone to the MT, does not receive a significant input from the superior colliculus.

[Effect of injection of enkephalin and bestatin in caudate-putamen on operant conditioning in rats].

Female Wistar rats were trained in a Skinner-box, 30 trials per day in a dark room to establish operant defence conditioning. Training started with a light (15 s), then combined with footshock for further 8 s. When the rats learned to press the key to avoid footshock within 15 s, conditioned response was considered established. After the rats reached a conditioning rate (CR) above 80% for 5 days, cannulae were implanted into caudate-putamen. Two to three days later, Met-enkephalin (MEK) or bestatin (an aminopeptidase inhibitor) was injected bilaterally into caudate-putamen. 30 min, 2 h, 24 h and 48 h after injection, conditioning tests were conducted, with each session consisting of 30 trials. Control experiments were done when 0.9% NaCl (NS) was injected. After injection of NS, CR maintained above 80% in all 4 test sessions. MEK (60 ng/rat) or bestatin (10 micrograms/rat) significantly lowered the CR during the 30 min and 2 h test session. In the latter case, the latency (L) was also prolonged. However both CR and L returned to the control level in the 24 h and 48 h test sessions. Naloxone (2 mg/kg, i.p.) blocked the conditioning-depression effect of bestatin. No significant alteration was seen in locomotor activity after MEK or bestatin injection. The results suggest that enkephalin in caudate-putamen may be involved in the regulation of retrieval of conditioning. Bestatin mimics the effect of MEK on conditioning reflex probably by increasing production of endogenous enkephalin.