Intensity-dependent Manner Research Articles

How does light facilitate vitamin C biosynthesis in leaves?

Plants store ascorbate in high concentrations, particularly in their leaves. Ascorbate is an excellent antioxidant that acts as an indispensable photoprotectant. The d-mannose/l-galactose pathway is responsible for ascorbate biosynthesis in plants. Light facilitates ascorbate biosynthesis in a light intensity-dependent manner to enhance ascorbate pool size in leaves, and photosynthesis is required for this process. Light- and photosynthesis-dependent activation of the rate-limiting enzyme GDP-l-galactose phosphorylase (GGP) plays a critical role in ascorbate pool size regulation. In addition, the tight regulation of ascorbate biosynthesis by ascorbate itself has been proposed. Ascorbate represses GGP translation in a dose-dependent manner through the upstream open reading frame in the 5'-untranslated regions of the gene, which may compete with the light-dependent activation of ascorbate biosynthesis. This review focuses on ascorbate biosynthesis based on past and latest findings and critically discusses how light activates this process.

The exercise pressor reflex: An update.

The exercise pressor reflex is a feedback mechanism engaged upon stimulation of mechano- and metabosensitive skeletal muscle afferents. Activation of these afferents elicits a reflex increase in heart rate, blood pressure, and ventilation in an intensity-dependent manner. Consequently, the exercise pressor reflex has been postulated to be one of the principal mediators of the cardiorespiratory responses to exercise. In this updated review, we will discuss classical and recent advancements in our understating of the exercise pressor reflex function in both human and animal models. Particular attention will be paid to the afferent mechanisms and pathways involved during its activation, its effects on different target organs, its potential role in the abnormal cardiovascular response to exercise in diseased states, and the impact of age and biological sex on these responses. Finally, we will highlight some unanswered questions in the literature that may inspire future investigations in the field.

Effects of Gamma Irradiation on Inhibition of Urease Activity and Fishy Smell in Mackerel (Scomber japonicus) during Refrigerated Storage.

In this study, gamma-irradiated mackerel (Scomber japonicus) meat was stored in a refrigerator for 20 days to examine the physicochemical changes related to fishy smell. The effect of gamma irradiation on the inhibition of the activity of crude urease extracted from Vibrio parahaemolyticus was also evaluated. Increased levels of trimethylamine (TMA) and volatile basic nitrogen (VBN) content, which are the main components causing fishy smell, were significantly reduced by day 20 of storage after gamma irradiation, indicating that freshness was maintained during storage. The ammonia nitrogen contents of 3, 7, 10, and 20 kGy gamma-irradiated groups were significantly decreased by 6.5, 15.2, 17.4, and 23.9%, respectively, compared to non-irradiated groups on day 20 of storage. In addition, urease activity decreased in a gamma irradiation intensity-dependent manner. Volatile organic compounds (VOCs) were measured during the storage of gamma-irradiated mackerel meat. The contents of ethanol, 2-butanone, 3-methylbutanal, and trans-2-pentenal, which are known to cause off-flavors due to spoilage of fish, were significantly reduced by day 20 of storage. Therefore, gamma irradiation can be considered useful for inhibiting urease activity and reducing fishy smell during fish storage.

The Autophagic Response to Passive and Exercise‐induced Increases in Body Core Temperature in Young Adults

Autophagy is an essential cellular survival mechanism that involves the degradation and recycling of aged or damaged organelles and protein aggregates to maintain cellular homeostasis. While autophagic dysfunction occurs with aging and is associated with many disease‐related pathologies, methods to modulate autophagic activity remain poorly understood in the context of human physiology. Recently, we demonstrated that autophagy is activated in an intensity‐dependent manner during both exercise and passive heat stress, however it is unknown if the autophagic response to elevations in body core temperature (Tcore) during passive heat exposure are comparable to those elicited through exercise. Therefore, we sought to assess the autophagic response to an elevated state of hyperthermia associated with intense exercise and compare responses to a similar rate and magnitude of increase in Tcore elicited through warm water immersion (WI). We evaluated the hypothesis that autophagic stimulation would occur during both exercise and WI, although responses would be greater during the exercise bout. To assess this hypothesis, 6 young men (mean [SD] 23 [3] years) performed 30 min of intense (70% of maximal oxygen consumption (VO2max)) semi‐recumbent cycling. On a separate day (at least 72h after the exercise bout), the same participants were immersed in warm water (up to the clavicle) for 30 min, with the water temperature adjusted to elicit the same relative increase in Tcore (as estimated by rectal temperature) as was achieved during the prior exercise session. Given Tcore during WI was matched to the prior exercise bout, all WI trials were conducted after the exercise session. Autophagic activity was assessed in peripheral blood mononuclear cells prior to, immediately post‐exercise or WI, and following a seated recovery (3 and 6h). Western blot was used to assess changes in autophagy via microtubule‐associated light chain 3 beta (LC3‐II) and normalized to β‐actin (expressed as relative fold change to the respective baseline). Area under the curve was used to assess the Tcore response between conditions and protein data were analyzed via a two‐way repeated measures ANOVA with Fisher’s LSD (α=0.05). A similar average relative increase in Tcore was observed during the exercise and WI bouts (0.65 [0.21]°C vs 0.61 [0.19]°C, respectively; p=0.80) with a return to baseline within 3h in both conditions. In response to 30‐min of exercise, LC3‐II significantly increased immediately after exercise (1.69 [0.12]; p<0.01) and remained elevated above baseline at 3h (1.51 [0.23]; p<0.01) and 6h (1.38 [0.16]; p<0.01). A similar pattern of response was observed following WI (1.86 [0.77]; p=0.04), however, LC3‐II returned to pre‐WI levels within the first 3h of recovery. Our preliminary findings show similar increases in autophagy following a similar elevation in core temperature associated induced by exercise and WI. However, the autophagic response only remained elevated after exercise, likely caused by exercise‐associated metabolic perturbations. Further research is warranted to delineate the underlying pathways of autophagic activation during these different thermal stressors.

Limb Hemodynamic Responses to a Single Bout of Inspiratory Muscle Strength Training

BackgroundInspiratory muscle strength training (IMST) has been shown to bring about improvements in respiratory muscle strength and reductions in blood pressure after 6 weeks of daily high intensity training. However, there has been little investigation into the effects of IMST on limb blood flow, and it is unclear how hemodynamics are altered within a single bout of training.PurposeTo investigate the acute effects of one session of either low or high intensity IMST on blood flow in the upper and lower limbs.MethodsParticipants (n=7, 57% female) aged 20 to 47 years completed two randomized laboratory visits wherein resting blood flow was measured via duplex Doppler ultrasound at the left brachial and popliteal arteries. Following baseline measures, participants' maximal inspiratory pressure (PImax) was measured using a PowerBreathe K3 device. Participants performed one session (30 breaths) of IMST at either 15% or 75% of their PImax, and blood flow was measured again at each artery for five breaths during the final ten breaths of the training. At their second visit, subjects performed whichever training level had yet to be completed and blood flow was assessed as described above.ResultsMean blood flow at the brachial artery appeared reduced during both 15% (p=0.070) and 75% training (p=0.078), which may be attributed to a significant increase in retrograde blood flow in both cases (p=0.014 and p=0.037, respectively). This increase in retrograde blood flow tended to be greater during the 75% training (p=0.066). Popliteal artery blood flow showed similar trends to brachial artery blood flow.ConclusionsWhile IMST appears to reduce brachial artery mean blood flow during a single training session, this may be due to alterations in retrograde blood flow, which tended to increase in an intensity‐dependent manner. Further investigation into the chronic hemodynamic effects of IMST is warranted.

Region-Dependent Increase of Cerebral Blood Flow During Electrically Induced Contraction of the Hindlimbs in Rats

Elevation of cerebral blood flow (CBF) may contribute to the cerebral benefits of the regular practice of physical exercise. Surprisingly, while electrically induced contraction of a large muscular mass is a potential substitute for physical exercise to improve cognition, its effect on CBF remains to be investigated. Therefore, the present study investigated CBF in the cortical area representing the hindlimb, the hippocampus and the prefrontal cortex in the same anesthetized rats subjected to either acute (30 min) or chronic (30 min for 7 days) electrically induced bilateral hindlimb contraction. While CBF in the cortical area representing the hindlimb was assessed from both laser doppler flowmetry (LDFCBF) and changes in p-eNOSSer1177 levels (p-eNOSCBF), CBF was evaluated only from changes in p-eNOSSer1177 levels in the hippocampus and the prefrontal cortex. The contribution of increased cardiac output and increased neuronal activity to CBF changes were examined. Stimulation was associated with tachycardia and no change in arterial blood pressure. It increased LDFCBF with a time- and intensity-dependent manner as well as p-eNOSCBF in the area representing the hindlimb. By contrast, p-eNOSCBF was unchanged in the two other regions. The augmentation of LDFCBF was partially reduced by atenolol (a ß1 receptor antagonist) and not reproduced by the administration of dobutamine (a ß1 receptor agonist). Levels of c-fos as a marker of neuronal activation selectively increased in the area representing the hindlimb. In conclusion, electrically induced bilateral hindlimb contraction selectively increased CBF in the cortical area representing the stimulated muscles as a result of neuronal hyperactivity and increased cardiac output. The absence of CBF changes in cognition-related brain regions does not support flow-dependent neuroplasticity in the pro-cognitive effect of electrically induced contraction of a large muscular mass.

Kinetics of neuropeptide Y, catecholamines, and physiological responses during moderate and heavy intensity exercises

Neuropeptide Y 1–36 (NPY1–36) is a vasoconstrictor peptide co-secreted with norepinephrine (NE) by nerve endings during sympathetic activation. NPY1–36 potentiates NE action post-synaptically through the stimulation of the Y1 receptor, whereas its metabolite NPY3–36 resulting from DPP4 action activates Y2 presynaptic receptors, inhibiting NE and acetylcholine secretion. The secretions of NPY1–36 and NPY3–36 in response to sympathetic nervous system activation have not been studied due to the lack of analytical techniques available to distinguish them. We determined in healthy volunteers NPY1–36, NPY3–36 and catecholamine kinetics and how these neurotransmitters modulate the physiological stress response during and after moderate- and heavy-intensity exercises.Six healthy males participated in this randomized, double-blind, saxagliptin vs placebo crossover study. The volunteers performed an orthostatic test, a 30-min exercise at moderate intensity and a 15-min exercise at heavy intensity each followed by 50 min of recovery in two separate sessions with saxagliptin or placebo. Oxygen consumption (V̇O2), ventilation and heart rate were continuously recorded. NE, epinephrine, NPY1–36 and NPY3–36 were quantified by tandem mass spectrometry.We found that exercise triggers NPY1–36 and NE secretion in an intensity-dependent manner and that NE returns faster to the baseline concentration than NPY1–36 after exercise. NPY3–36 rises during recovery parallel to the decline of NPY1–36. Saxagliptin reverses the NPY1–36/NPY3–36 ratio but does not affect hemodynamics, nor NPY1–36 and catecholamine concentrations.We found that NPY1–36 half-life is considerably shorter than previously established with immunoassays. NPY1–36 and NE secretions are finely regulated to prevent an excessive physiological Y1 stimulating response to submaximal exercise.

The effects of exercise intensity and duration on the relationship between the slow component of V̇O2 and peripheral fatigue.

If the development of the oxygen uptake slow component (V̇O2SC ) and muscle fatigue are related, these variables should remain coupled in a time- and intensity-dependent manner. 16 participants (7 females) visited the laboratory on 7 separate occasions: (1) three 6-minutes moderate-intensity cycling exercise bouts proceeded by a ramp incremental test; (2-3) 30-minutes constant power output (PO) exercise bout to determine the maximal lactate steady state (MLSS); (4-7) constant-PO exercise bouts to task failure (TTF), pseudorandomized order, at (i) 15% below the PO at MLSS; (ii) 10W below MLSS; (iii) MLSS; (iv) 10W above MLSS (first intensity and randomized order thereafter). Neuromuscular fatigue was characterized by isometric maximal voluntary contractions and femoral nerve electrical stimulation of knee extensors to measure peripheral fatigue at baseline, at min 5, 10, 20, 30 and TTF. Pulmonary oxygen uptake (V̇O2 ) was continuously recorded during the constant-PO bouts and V̇O2SC was characterized based on each individual V̇O2 kinetics during moderate transitions. The development of V̇O2SC and peripheral fatigue were correlated across time (r2 adj range of 0.64-0.80) and amongst each exercise intensity (r2 adj range of 0.26-0.30) (all P<.001). Also, TTF was correlated with V̇O2SC and neuromuscular fatigue parameters (r2 adj range of 0.52-0.82, all P<.001). The V̇O2SC and peripheral fatigue development are correlated throughout the exercise in a time- and intensity-dependent manner, suggesting that the V̇O2SC may depend on muscle fatigue even if the mechanisms of reduced contractile function are different amongst intensities.

Efficacy profile of noninvasive vagus nerve stimulation on cortical spreading depression susceptibility and the tissue response in a rat model

BackgroundNoninvasive vagus nerve stimulation (nVNS) has recently emerged as a promising therapy for migraine. We previously demonstrated that vagus nerve stimulation inhibits cortical spreading depression (CSD), the electrophysiological event underlying migraine aura and triggering headache; however, the optimal nVNS paradigm has not been defined.MethodsVarious intensities and doses of nVNS were tested to improve efficacy on KCl-evoked CSD frequency and electrical threshold of CSD in a validated rat model. Chronic efficacy was evaluated by daily nVNS delivery for four weeks. We also examined the effects of nVNS on neuroinflammation and trigeminovascular activation by western blot and immunohistochemistry.ResultsnVNS suppressed susceptibility to CSD in an intensity-dependent manner. Two 2-minute nVNS 5 min apart afforded the highest efficacy on electrical CSD threshold and frequency of KCl-evoked CSD. Daily nVNS for four weeks did not further enhance efficacy over a single nVNS 20 min prior to CSD. The optimal nVNS also attenuated CSD-induced upregulation of cortical cyclooxygenase-2, calcitonin gene-related peptide in trigeminal ganglia, and c-Fos expression in trigeminal nucleus caudalis.ConclusionsOur study provides insight on optimal nVNS parameters to suppress CSD and suggests its benefit on CSD-induced neuroinflammation and trigeminovascular activation in migraine treatment.

High sensitivity of melatonin suppression response to evening light in preschool-aged children.

Light at night in adults suppresses melatonin in a nonlinear intensity-dependent manner. In children, bright light of a single intensity before bedtime has a robust melatonin suppressing effect. To our knowledge, whether evening light of different intensities is related to melatonin suppression in young children is unknown. Healthy, good-sleeping children (n=36; 3.0-4.9years; 39% male) maintained a stable sleep schedule for 7days followed by a 29.5-h in-home dim-light circadian assessment (~1.5lux). On the final night of the protocol, children received a 1-h light exposure (randomized to one of 15light levels, ranging 5-5000lux, with ≥2 participants assigned to each light level) in the hour before habitual bedtime. Salivary melatonin was measured to calculate the magnitude of melatonin suppression during light exposure compared with baseline levels from the previous evening, as well as the degree of melatonin recovery 50min after the end of light exposure. Melatonin levels were suppressed between 69.4% and 98.7% (M=85.4±7.2%) during light exposure across the full range of intensities examined. Overall, we did not observe a light intensity-dependent melatonin suppression response; however, children exposed to the lowest quartile of light intensities (5-40lux) had an average melatonin suppression (77.5±7.0%) which was significantly lower than that observed at each of the three higher quartiles of light intensities (86.4±5.6%, 89.2±6.3%, and 87.1±5.0%, respectively). We further found that melatonin levels remained below 50% baseline for at least 50min after the end of light exposure for the majority (62%) of participants, and recovery was not influenced by light intensity. These findings indicate that preschool-aged children are highly sensitive to light exposure in the hour before bedtime and suggest the lighting environment may play a crucial role in the development and the maintenance of behavioral sleep problems through impacts on the circadian timing system.

Dim Light at Night Affects the Locomotor Activity of Nocturnal African Pygmy Mice (Mus Minutoides) in an Intensity Dependent Manner

Dim Light at Night Affects the Locomotor Activity of Nocturnal African Pygmy Mice (Mus Minutoides) in an Intensity Dependent Manner

OsBIC1 Directly Interacts with OsCRYs to Regulate Leaf Sheath Length through Mediating GA-Responsive Pathway.

Cryptochrome 1 and 2 (CRY1 and CRY2) are blue light receptors involved in the regulation of hypocotyl elongation, cotyledon expansion, and flowering time in Arabidopsis thaliana. Two cryptochrome-interacting proteins, Blue-light Inhibitor of Cryptochrome 1 and 2 (BIC1 and BIC2), have been found in Arabidopsis. BIC1 plays critical roles in suppressing the physiological activities of CRY2, which include the blue light-dependent dimerization, phosphorylation, photobody formation, and degradation process, but the functional characterization of BIC protein in other crops has not yet been performed. To investigate the function of BIC protein in rice (Oryza sativa), two homologous genes of Arabidopsis BIC1 and BIC2, namely OsBIC1 and OsBIC2 (OsBICs), were identified. The overexpression of OsBIC1 and OsBIC2 led to increased leaf sheath length, whereas mutations in OsBIC1 displayed shorter leaf sheath in a blue light intensity-dependent manner. OsBIC1 regulated blue light-induced leaf sheath elongation through direct interaction with OsCRY1a, OsCRY1b, and OsCRY2 (OsCRYs). Longitudinal sections of the second leaf sheath demonstrated that OsBIC1 and OsCRYs controlled leaf sheath length by influencing the ratio of epidermal cells with different lengths. RNA-sequencing (RNA-seq) and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) analysis further proved that OsBIC1 and OsCRYs regulated similar transcriptome changes in regulating Gibberellic Acids (GA)-responsive pathway. Taken together, these results suggested that OsBIC1 and OsCRYs worked together to regulate epidermal cell elongation and control blue light-induced leaf sheath elongation through the GA-responsive pathway.

The Role of Central Command in the Increase in Muscle Sympathetic Nerve Activity to Contracting Muscle During High Intensity Isometric Exercise.

We previously demonstrated that muscle sympathetic nerve activity (MSNA) increases to contracting muscle as well as to non-contracting muscle, but this was only assessed during isometric exercise at ∼10% of maximum voluntary contraction (MVC). Given that high-intensity isometric contractions will release more metabolites, we tested the hypothesis that the metaboreflex is expressed in the contracting muscle during high-intensity but not low-intensity exercise. MSNA was recorded continuously via a tungsten microelectrode inserted percutaneously into the right common peroneal nerve in 12 participants, performing isometric dorsiflexion of the right ankle at 10, 20, 30, 40, and 50% MVC for 2 min. Contractions were immediately followed by 6 min of post-exercise ischemia (PEI); 6 min of recovery separated contractions. Cross-correlation analysis was performed between the negative-going sympathetic spikes of the raw neurogram and the ECG. MSNA increased as contraction intensity increased, reaching mean values (± SD) of 207 ± 210 spikes/min at 10% MVC (P = 0.04), 270 ± 189 spikes/min at 20% MVC (P < 0.01), 538 ± 329 spikes/min at 30% MVC (P < 0.01), 816 ± 551 spikes/min at 40% MVC (P < 0.01), and 1,097 ± 782 spikes/min at 50% MVC (P < 0.01). Mean arterial pressure also increased in an intensity-dependent manner from 76 ± 3 mmHg at rest to 90 ± 6 mmHg (P < 0.01) during contractions of 50% MVC. At all contraction intensities, blood pressure remained elevated during PEI, but MSNA returned to pre-contraction levels, indicating that the metaboreflex does not contribute to the increase in MSNA to contracting muscle even at these high contraction intensities.

CXCL12/CXCR4 Mediates Orthodontic Root Resorption via Regulating the M1/M2 Ratio

Mechanical force–induced external root resorption is a major clinical side effect of orthodontic treatment. Recent work has revealed that M1 macrophages play a vital role in promoting orthodontic root resorption (ORR), but the mechanism of how mechanical force stimulation increases the M1/M2 macrophage ratio in periodontal tissue is poorly understood. In the current study, we showed that C-X-C motif chemokine 12 (CXCL12)+ periodontal ligament cells (PDLCs) and C-X-C chemokine receptor type 4 (CXCR4)+ monocytes in the periodontal ligament (PDL) were significantly increased after force application with ongoing root resorption, and these effects were partially rescued after force removal in mice. The expression of CXCL12 in PDLCs was increased by force stimulation in a time- and intensity-dependent manner in vitro. Blockage of the CXCL12/CXCR4 axis using CXCR4 antagonist AMD3100 was sufficient to alleviate ORR and reverse the force-enhanced M1/M2 macrophage ratio. Further mechanism exploration showed that Ly6Chi inflammatory monocytes homed in a CXCL12/CXCR4 axis-dependent manner. The number and proportion of CD11b+ Ly6Chi inflammatory monocytes in cervical lymph nodes were significantly increased by force loading, accompanied by decreased CD11b+ Ly6Chi monocytes in the blood. These changes were blunted by intraperitoneal injection of AMD3100. In addition, blockage of the CXCL12/CXCR4 axis effectively reversed M2 suppression and promoted M1 polarization. Collectively, results indicate that force-induced CXCL12/CXCR4 axis mediates ORR by increasing the M1/M2 ratio in periodontal tissues through attracting Ly6Chi inflammatory monocytes and modulating macrophage polarization. The results also imply that AMD3100 is potentially inhibitory to root resorption.

Corticospinal and intracortical excitability is modulated in the knee extensors after acute strength training

ABSTRACT The corticospinal responses to high-intensity and low-intensity strength-training of the upper limb are modulated in an intensity-dependent manner. Whether an intensity-dependent threshold occurs following acute strength training of the knee extensors (KE) remains unclear. We assessed the corticospinal responses following high-intensity (85% of maximal strength) or low-intensity (30% of maximal strength) KE strength-training with measures taken during an isometric KE task at baseline, post-5, 30 and 60-min. Twenty-eight volunteers (23 ± 3 years) were randomized to high-intensity (n = 11), low-intensity (n = 10) or to a control group (n = 7). Corticospinal responses were evoked with transcranial magnetic stimulation at intracortical and corticospinal levels. High- or low-intensity KE strength-training had no effect on maximum voluntary contraction force post-exercise (P > 0.05). High-intensity training increased corticospinal excitability (range 130–180%) from 5 to 60 min post-exercise compared to low-intensity training (17–30% increase). Large effect sizes (ES) showed that short-interval cortical inhibition (SICI) was reduced only for the high-intensity training group from 5–60 min post-exercise (24–44% decrease) compared to low-intensity (ES ranges 1–1.3). These findings show a training-intensity threshold is required to adjust CSE and SICI following strength training in the lower limb.

Potential Protective Role of TRPM7 and Involvement of PKC/ERK Pathway in Blue Light-Induced Apoptosis in Retinal Pigment Epithelium Cells in Vitro.

Purpose:Blue light triggers apoptosis of retinal pigment epithelium (RPE) cells and causes retinal damage. The aim of this study was to elucidate the protective role of transient receptor potential melastatin 7 (TRPM7) in photodamaged RPE cells.Methods:RPE cells were isolated from Sprague-Dawley (SD) rats and exposed to varying intensities of blue light (500–5000 lux) in vitro. Cell proliferation and metabolic activity were respectively assessed by bromodeoxyuridine (BrdU) incorporation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays. Real-time polymerase chain reaction (RT-PCR) and western blotting were used to analyze the TRPM7, protein kinase C (PKC), extracellular signal-regulated kinase (ERK) and Bcl2-associated x/B-cell lymphoma 2 (Bax/Bcl-2) messenger RNA (mRNA) and protein expression levels. The cells were transfected with TRPM7 small interfering RNA (siRNA) or transduced with TRPM7-overexpressing lentiviruses and cultured with or without the pigment epithelium-derived factor (PEDF).Results:Blue light inhibited the proliferation and metabolic activity of RPE cells in an intensity-dependent manner when compared to nonirradiated controls (P < 0.05). Compared to the control, photodamaged RPE cells showed decreased levels of TRPM7, PKC, ERK, and Bax, and an increase in Bcl-2 levels (P < 0.01). Forced expression of TRPM7 partially rescued the proliferative capacity of RPE cells (P < 0.01) and restored the levels of TRPM7, PKC, ERK, and Bax (P < 0.01), whereas TRPM7 knockdown had the opposite effects (P < 0.01). TRPM7 and PEDF synergistically alleviated the damaging effects of blue light.Conclusions:Blue light triggers apoptosis of RPE cells, and its deleterious effects can be partially attenuated by the synergistic action of TRPM7 and PEDF via the PKC/ERK signaling pathway.

Profiles of Cytokines Secreted by ARPE-19 Cells Exposed to Light and Incubated with Anti-VEGF Antibody.

The retinal pigment epithelium (RPE) is the major source of cytokines in the retina regulating the intraocular immune environment, and a primary target of photodamage. Here, we examined 27 types of cytokines secreted by ARPE-19 cells exposed to visible light and incubated with aflibercept or ranibizumab, which are two anti-vascular endothelial growth factor (VEGF) antibodies. The cells were cultured for 24 h in the dark or under 2000 lux irradiation from a daylight-colored fluorescent lamp, and cytokine levels in the culture supernatant were measured. In the light-irradiated culture, the levels of IL-9, IL-17A and bFGF were higher, and the levels of IL-6, IL-7, IL-8 and MCP-1 were lower than those in the dark culture, while there was no significant difference with the VEGF-A level. In subgroup analyses of the light-irradiated culture, the bFGF level under 250 to 2000 lux irradiation was elevated in a light intensity-dependent manner. In culture exposed to blue, green or red light, the bFGF level was elevated by blue light and was high compared to that by green or red light. In culture with aflibercept or ranibizumab in the dark, the levels of IL-6, IL-8, bFGF and MCP-1 were increased, and the IL-12 level decreased synchronously with a reduction in the VEGF-A level. Our findings indicate that continuous irradiation of visible light and VEGF suppression may be an influential factor in expression patterns of inflammatory cytokines secreted by human RPE cells.

Comparisons of different exercise interventions on glycemic control and insulin resistance in prediabetes: a network meta-analysis

BackgroundIn order to recommend the optimal type of exercise for type 2 diabetes prevention, different exercise interventions were compared with respect to their effects on glycemic control and insulin resistance.MethodsStudies on the curative effect of aerobic exercise training (AET), resistance training (RT), or control training (CT) on prediabetes were retrieved from the PubMed, Embase, SPORTDiscus, and Cochrane Library databases. Body mass index (BMI); homeostasis model assessment of insulin resistance index (HOMA-IR); and fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and insulin levels were used as outcome indicators. The Q statistic was calculated to evaluate heterogeneity within studies. A fixed- or random-effects model was used for pooling data based on nonsignificant or significant heterogeneities. A consistency test was conducted using a node-splitting analysis.ResultsA total of 13 eligible studies were included. The results of the direct meta-analysis indicated that AET or RT could significantly reduce the HbA1c level in prediabetic individuals compared to CT [AET vs. CT: standardized mean difference (SMD) = − 0.6739, 95% confidence interval (CI) = − 0.9424 to − 0.4055 to RT vs. CT: SMD = − 1.0014, 95% CI = − 1.3582 to − 0.6446]. The findings from the network meta-analysis showed that there were no statistical differences among the four comparisons for all the indicators except for lower HbA1c level (SMD = − 0.75, 95% CI = − 1.31 to − 0.19) and HOMA-IR (SMD = − 1.03, 95% CI = − 1.96 to − 0.10) in the AET group than in the CT group. In addition, prediabetic individuals in the AET + RT group showed greater control of BMI and insulin and FBG levels than those in the other groups, whereas AET was the most effective in controlling HbA1c and HOMA-IR levels in prediabetic individuals.ConclusionAET, AET + RT, and RT exerted beneficial effects on insulin resistance and glycemic control in prediabetic patients. From the existing data, AET or AET + RT is preferentially recommended for these patients, although further studies may unveil RT as a promising therapy. Benefits from all types of exercise seem to occur in an intensity-dependent manner.

Vagus Nerve Stimulation Amplifies Task-Induced Cerebral Blood Flow Increase.

BackgroundVagus nerve stimulation (VNS) is an established palliative surgical treatment for refractory epilepsy. Recently, pairing VNS with rehabilitation received growing attention for their joint effect on neural plasticity. However, objective biological measurements proving the interaction between VNS effects and cortical recruitment are lacking. Studies reported that VNS induced little blood flow increase in the cerebral cortex.ObjectiveThis study tested the hypothesis that pairing VNS with a cognitive task amplifies task-induced cerebral blood flow (CBF).MethodsThis study included 21 patients implanted with vagus nerve stimulator to treat refractory epilepsy. Near-infrared spectroscopy (NIRS) with sensors on the forehead measured CBF changes in the frontal cortices in response to VNS. Cerebral blood flow was measured when VNS was delivered during a resting state or a verbal fluency task. We analyzed the VNS effect on CBF in relation to stimulation intensity and clinical responsiveness.ResultsWe observed no CBF change when VNS was delivered during rest, irrespective of stimulation intensity or responsiveness. Cerebral blood flow changed significantly when a verbal fluency task was paired with VNS in a stimulation intensity-dependent manner. Cerebral blood flow changes in the non-responders showed no intensity-dependency.ConclusionOur results could be an important biological proof of the interaction between VNS effects and cortical recruitment, supporting the validity of pairing VNS with rehabilitation.

Characterization of SH-SY5Y Neurons Subject to 92kHz Ultrasound Stimulation

Cellular microstructural changes due to ultrasound exposure are critical to understand and characterize in order to further the establishment of ultrasonics in cell and tissue engineering and medicine. In this study, neurite length, nuclear morphology, and cellular toxicity are assessed at varying intensities of 92 kHz ultrasound provided by a piezoceramic disk element and incident upon SH- SY5Y neurons in vitro. Findings suggest that stimulation increases neurite length up to 2.73 fold tested at α = 0.05 in an intensity dependent manner. Additionally, stimulation causes a statistically significant (α = 0.05) decrease in nuclear area and less elongated nuclei, by 1.78 fold and 1.38 fold respectively, also in an intensity dependent manner. For maximum transducer surface intensities ranging from 0 to 39.11 W/cm2, the toxicity of 92 kHz ultrasound is assessed and a nontoxic range is determined using Caspase-3 and Annexin V staining, in addition to Calcium imaging via Calcein-AM staining. Intensities of up to 1.6 W/cm2 are found to be nontoxic for the cells under the parameters used in this study.