Motor Skills, Heart Rate Variability, and Arterial Stiffness in Children with Autism Spectrum Disorder.

The prevalence of autism spectrum disorder (ASD) among children has been recently increasing. The severity of symptoms greatly varies between individuals with ASD, ranging from relatively mild to extremely severe. It is important to have a clearer understanding of the possible adverse consequences resulting from this disorder, such as delayed motor development, autonomic dysregulation, and arterial stiffness. Thus, the objective of this study was to investigate differences in motor skills, heart rate variability (HRV), and arterial stiffness between children with ASD and typically developing children. In this study, the school-aged children with mild symptoms of ASD (n = 17, 11.1 ± 1.0 years old) and typically developing peers (n = 15, 11.0 ± 0.5 years old) were recruited. Motor skills, HRV, and arterial stiffness were measured in these two groups. Motor skills were evaluated by the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition. Moreover, HRV was measured through a short-term recording using the Polar heart rate monitor, and arterial stiffness was assessed by non-invasive computerized oscillometry. Compared with the typically developing group, children with ASD displayed significant deficits in some areas of motor skills, including manual coordination, strength and agility, and total motor composite. Moreover, children with ASD exhibited significantly reduced HRV, including time- and frequency-domain measures. However, the results did not demonstrate any statistically significant differences in arterial stiffness between the groups. Our findings demonstrated the presence of motor skill deficits and autonomic dysregulation in children with ASD.

Chondrocyte Thrombomodulin Protects against Osteoarthritis.

Osteoarthritis (OA) is a prevalent form of arthritis that affects over 32.5 million adults worldwide, causing significant cartilage damage and disability. Unfortunately, there are currently no effective treatments for OA, highlighting the need for novel therapeutic approaches. Thrombomodulin (TM), a glycoprotein expressed by chondrocytes and other cell types, has an unknown role in OA. Here, we investigated the function of TM in chondrocytes and OA using various methods, including recombinant TM (rTM), transgenic mice lacking the TM lectin-like domain (TMLeD/LeD), and a microRNA (miRNA) antagomir that increased TM expression. Results showed that chondrocyte-expressed TM and soluble TM [sTM, like recombinant TM domain 1 to 3 (rTMD123)] enhanced cell growth and migration, blocked interleukin-1ß (IL-1ß)-mediated signaling and protected against knee function and bone integrity loss in an anterior cruciate ligament transection (ACLT)-induced mouse model of OA. Conversely, TMLeD/LeD mice exhibited accelerated knee function loss, while treatment with rTMD123 protected against cartilage loss even one-week post-surgery. The administration of an miRNA antagomir (miR-up-TM) also increased TM expression and protected against cartilage damage in the OA model. These findings suggested that chondrocyte TM plays a crucial role in counteracting OA, and miR-up-TM may represent a promising therapeutic approach to protect against cartilage-related disorders.

Anti-apoptotic and anti-fibrotic efficacy of exercise training in hypertensive hearts: A systematic review.

Background: This review aims to summarize the antiapoptotic, pro-survival, and antifibrotic effects of exercise training in hypertensive hearts. Methods: Keyword searches were conducted in PubMed, Web of Science, and Scopus in May 2021. Research published in English on the effects of exercise training on the apoptosis, survival, and fibrosis pathways in hypertension was included. The CAMARADES checklist was used to determine the quality of the studies. Two reviewers independently implemented predesigned protocols for the search and selection of studies, the assessment of study quality, and the evaluation of the strength of evidence. Results: Eleven studies were included after selection. The duration of the exercise training ranged from 5 to 27 weeks. Nine studies showed that exercise training improved cardiac survival rates by increasing IGF-1, IGF-1 receptor, p-PI3K, Bcl-2, HSP 72, and p-Akt. Furthermore, 10 studies showed that exercise training reduced apoptotic pathways by downregulating Bid, t-Bid, Bad, Bak, Bax, TNF, and FADD. Finally, two studies reported the modification and subsequent improvement of physiological characteristics of fibrosis and decreased MAPK p38 and PTEN levels by exercise training in the left ventricle of the heart. Conclusions: The findings of the review showed that exercise training could improve cardiac survival rates and attenuate cardiac apoptotic and fibrotic pathways in hypertension, suggesting that exercise training could act as a therapeutic approach to prevent hypertension-induced cardiac apoptosis and fibrosis. Systematic Review Registration: https://www.crd.york.ac.uk, identifier: CRD42021254118.

Defecation enhances cerebral perfusion and delays fatigue in elite triathletes.

BACKGROUND: Rectal distension increases regulatory burden to autonomic nervous system in the brain. PURPOSE: To determine the effect of rectal defecation on endurance performance and blood supply to the prefrontal brain and sub-navel regions of elite triathletes. METHODS: Thirteen elite triathletes completed a cycling time trial (80% VO2max) under defecated and non-defecated conditions, using a counterbalanced crossover design. Oxygenation and blood distribution in prefrontal brain and sub-navel regions were monitored by near-infrared spectroscopy (NIRS) during cycling. RESULTS: Defecation moderately decreased systolic blood pressure (-4 mmHg, p < 0.05, d = 0.71), suggesting an alleviation of autonomic nervous activity. During the exercise trials, fatigue (cycling time to exhaustion) occurred when cerebral oxygenation decreased to ~ 5 % below baseline regardless of treatment conditions, suggesting a critical deoxygenation point for sustaining voluntary exertions. Cerebral blood (estimated by total hemoglobin) increased progressively throughout the entire exercise period. Defecation decreased sub-navel oxygenation levels below the non-defecated level, suggesting an increased sub-navel oxygen consumption. Exercise also decreased sub-navel blood distribution, with minimal difference between non-defecated and defecated conditions. Defecation improved blood pooling in the prefrontal brain during exercise (p < 0.05) and enhanced cycling performance in triathletes (Non-defecated: 1624 ± 138 s vs. defecated: 1902 ± 163 s, d = 0.51, p < 0.05). CONCLUSION: Our results suggest that improved exercise performance after defecation is associated with greater blood availability to compensate deoxygenation in the prefrontal brain region during exercise. Further investigation is needed to examine the role of increasing sub-navel oxygen consumption in the performance improvement after defecation.

Effects of Dextromethorphan on Nicotine-Induced Reward, Behavioral Sensitization, Withdrawal Signs, and Drug Seeking-Related Behavior in Rats.

INTRODUCTION: Tobacco products are addictive, with nicotine serving as the major addictive ingredient. Chronic tobacco use or chronic administration of nicotine alone results in both physiological and psychological dependence. Our previous studies indicated that dextromethorphan (DM) could effectively attenuate the dependence of morphine and methamphetamine. Thus, we further investigated the possible effects of DM on nicotine dependence. AIMS AND METHODS: Conditioned place preference (CPP) test was used to examine nicotine-induced rewarding effects as well as the drug-seeking-related behavior in rats. Nicotine dependence was induced by continuous subcutaneous infusion of nicotine via an osmotic minipump for 7 days and abstinence was initiated by removal of the pump. Withdrawal signs were observed and quantified. Locomotor activity was measured to determine the behavioral sensitization induced by nicotine. To investigate the activity of mesolimbic dopaminergic neuronal activity in correlation with the effects of nicotine, the animals were sacrificed and the nucleus accumbens (NAc), dorsal striatum (DS), and medial prefrontal cortex (mPFC) were dissected and used to determine the contents of dopamine (DA) and its metabolites using high-performance liquid chromatography (HPLC). RESULTS: Our results showed that DM could suppress nicotine-induced rewarding effect and drug-seeking-related behavior. In addition, co-administration and post-treatment of DM could both attenuate nicotine withdrawal signs. Moreover, DM could suppress nicotine-induced behavioral sensitization. Neurochemical experiments show that co-administration and post-treatment of DM abolished nicotine-induced increase of the DA turnover rate in the mPFC, but not in the NAc and DS. CONCLUSIONS: The results suggest that DM has a great therapeutic potential in the treatment of nicotine dependence. IMPLICATIONS: Our results showed that DM could suppress nicotine-induced rewarding effect and drug-seeking-related behavior. In addition, co-administration and post-treatment of DM could both attenuate nicotine withdrawal signs. Moreover, DM could suppress nicotine-induced behavioral sensitization. Neurochemical experiments show that co-administration and post-treatment of DM abolished nicotine-induced increase of the DA turnover rate in the mPFC, but not in the NAc and DS. These results suggest that DM has a great therapeutic potential in the treatment of nicotine dependence.

Branched-Chain Amino Acids Supplementation Does Not Accelerate Recovery after a Change of Direction Sprinting Exercise Protocol.

BCAAs supplementation has been widely used for post-exercise recovery. However, no evidence is currently available to answer the question of whether BCAAs supplementation can attenuate muscle damage and ameliorate recovery after a bout of change of direction (COD) sprinting, which is an exercise motion frequently used during team sport actions. This study aimed to assess the effect of BCAAs supplementation on muscle damage markers, subjective muscle soreness, neuromuscular performance, and the vascular health of collegiate basketball players during a 72 h recovery period after a standardized COD protocol. Participants orally received either BCAAs (0.17 g/kg BCAAs + 0.17 g/kg glucose) or placebo (0.34 g/kg glucose) supplementation before and immediately after a COD exercise protocol in a randomized, crossover, double-blind, and placebo-controlled manner. Creatine kinase increased immediately after exercise and peaked at 24 h, muscle soreness remained elevated until 72 h, whilst arterial stiffness decreased after exercise for both supplemented conditions. A negligibly lower level of interleukin-6 was found in the BCAAs supplemented condition. In conclusion, the results of this study do not support the benefits of BCAAs supplementation on mitigating muscle damage and soreness, neuromuscular performance, and arterial stiffness after COD for basketball players.

Craniofacial Growth and Asymmetry in Newborns: A Longitudinal 3D Assessment.

OBJECTIVE: To evaluate the development of the craniofacial region in healthy infants and analyze the asymmetry pattern in the first year of life. METHODS: The participants were grouped by sex and age (1, 2, 4, 6, 9, and 12 months) to receive three-dimensional (3D) photographs. Stereoscopic craniofacial photos were captured and transformed into a series of craniofacial meshes in each group. The growth patterns of the anthropometric indices and the degree of craniofacial asymmetry were measured, and average craniofacial meshes and color-asymmetry maps with craniofacial asymmetry scores were calculated. RESULTS: A total of 373 photographs from 66 infants were obtained. In both genders, the highest and lowest growth rates for all anthropometric indices were noted between 1 and 2 months and between 9 and 12 months, respectively. Overall, male infants had higher anthropometric indices, head volume, and head circumference than female infants. The craniofacial asymmetry score was presented with a descending pattern from 1 to 12 months of age in both sex groups. Both sex groups showed decreased left-sided laterality in the temporal-parietal-occipital region between 1 and 4 months of age and increased right frontal-temporal prominence between 6 and 12 months of age. CONCLUSIONS: A longitudinal evaluation of the craniofacial growth of healthy infants during their first year of life was presented.

Effects of Acute Aquatic High-Intensity Intermittent Exercise on Blood Pressure and Arterial Stiffness in Postmenopausal Women with Different ACE Genotypes.

The present study investigated the effects of acute aquatic high-intensity intermittent jumping (HIIJ) on blood pressure (BP) and arterial stiffness in postmenopausal women with different angiotensin-converting enzyme genotypes (ACE). We recruited 12 postmenopausal women carrying the ACE deletion/deletion (DD) genotype and 61 carrying the insertion/insertion or insertion/deletion (II/ID) genotype. The participants performed 12 trials of 30 s, 75% heart rate reserve (HRR) jumping, and 60 s, 50% HRR recovery, and 3 trials of 40 s upper limb resistance exercises were performed as fast as possible. The heart rate (HR) and BP were measured before exercise, immediately, 10 min, and 45 min after exercise. The brachial-ankle pulse wave velocity (baPWV) was measured before and after exercise. The systolic blood pressure (SBP) of the DD genotype increased more significantly than those with the II/ID genotype post-exercise (30.8 ± 4.48 vs. 20.4 ± 2.00 mmHg, p = 0.038). The left and right sides of baPWV increased significantly after exercise (1444.8 ± 29.54 vs. 1473.4 ± 32.36 cm/s, p = 0.020; 1442.1 ± 30.34 vs. 1472.0 ± 33.09, p = 0.011), and there was no significant difference between the two groups. The HIIJ increased baPWV. The postmenopausal women with the DD genotype have a higher SBP increased post-exercise than those with II/ID genotype. These findings suggest that the aquatic exercise program has better effects in decreasing blood pressure in postmenopausal women with the II/ID genotype. Those with the DD genotype should pay attention to the risk of increasing blood pressure after aquatic HIIJ exercise.

Combined exploration of the mechanism of Sang Xing Decoction in the treatment of smoke-induced acute bronchitis from protein and metabolic levels.

Sang Xing decoction (SXD) is a typical prescription for treating "warm dryness" in traditional Chinese medicine (TCM), which is equivalent to respiratory diseases such as acute bronchitis in modern medicine. However, its mechanism of action remains unclear. In this study, the representative components of SXD were characterized using liquid chromatography-tandem mass spectrometry (LC-MS). The key targets, signaling pathways, and metabolic pathways associated with SXD in the treatment of acute bronchitis were identified via network prediction and metabolomics. A rat model of acute bronchitis was also established using mixed smoke, systematic in vivo experiments such as histopathological analyses, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, immunohistochemistry and western blotting were conducted to evaluate the network prediction results. An in-depth analysis of the targeted quantitative results was performed using the SIMCA software and MetaboAnalyst website. The results revealed that 50 active compounds and 45 key targets were screened and clustered with 20 approved drugs. The NF-κB signaling pathway, oxidative stress, and glutamine metabolism were associated with the therapeutic mechanism of SXD in acute bronchitis. In vivo experiments showed that SXD may maintain the production of inflammatory factors by regulating the PI3K/Akt/NF-κB signaling pathway, improving the metabolism of glutamine and glutamate to reduce oxidative stress, and inhibiting apoptosis. Simultaneously, the possibility of using SXD as an adjuvant drug for COVID-19 treatment was also revealed. This research will lay the foundation for the modern clinical application of SXD and promote the promotion and innovation of TCM.

Exercise intervention prevents early aged hypertension-caused cardiac dysfunction through inhibition of cardiac fibrosis.

BACKGROUND: An inappropriate accumulation of fibrillar collagen is a common pathologic feature of early aged hypertensive heart disease, but little information regarding the effects of exercise training on cardiac fibrosis in hypertension is available. The purpose of this study was to evaluate the effects of exercise training on cardiac fibrotic pathways in early aged hypertensive rats. METHODS: Masson's trichrome staining and Western blotting were performed on the excised left ventricle from twenty male spontaneously hypertensive rats at age of 48 weeks, which were randomly divided into either a sedentary hypertensive group (SHR) or exercise hypertensive group (SHR-EX, running on a treadmill running occurred 5 days/week for 60 min/day, for 12 weeks), and from age-matched male Wistar-Kyoto normotensive controls (WKY). RESULTS: Interstitial fibrosis was reduced in the SHR-Ex group when compared with the SHR group. The fibrotic-related protein levels of AT1R, FGF23, LOX-2, TGF-ß, CTGF, p-Smad 2/3, MMP-2/TIMP-2, MMP-9/TIMP-1, uPA and collagen I were decreased in the SHR-EX group, when compared with the SHR group. CONCLUSIONS: Exercise training suppresses early aged hypertensive heart-induced LOX-2/TGF-ß-mediated fibrotic pathways associated with decreasing AT1R and FGF23, which might provide a new therapeutic effect for exercise training to prevent adverse cardiac fibrosis and myocardial abnormalities in early aged hypertension.

Differences between Elite Male and Female Badminton Athletes Regarding Heart Rate Variability, Arterial Stiffness, and Aerobic Capacity.

Cardiovascular health and aerobic capacity play crucial roles in determining the performance of athletes in the highly competitive sport of badminton. Few studies have directly compared heart rate variability (HRV), arterial stiffness, and aerobic capacity between male and female athletes, especially among badminton athletes. This study investigated sex differences in HRV, arterial stiffness, and aerobic capacity in badminton athletes. Elite badminton athletes were recruited and divided into male (n = 20, 21.0 ± 1.8 years old) and female (n = 16, 21.2 ± 2.3 years old) groups. Both groups performed an incremental treadmill running test for the evaluation of maximal oxygen consumption (V.O2max), anaerobic threshold, and time to exhaustion. They started exercising at a treadmill speed of 2.7 km/h and an inclination of 10% gradient for 3 min, and the speed and inclination were gradually increased every 3 min until they were exhausted or fatigued volitionally. HRV was examined using the Polar heart rate monitor over a period of 5 min at rest in the supine position. Subsequently, the index of arterial stiffness was examined under the same condition. Our results revealed significant differences between the male and female athletes in V.O2max (men: 60.38 ± 8.98 mL/kg/min, women: 48.13 ± 7.72 mL/kg/min, p < 0.05), anaerobic threshold (men: 41.50 ± 7.26 mL/kg/min, women: 32.51 ± 6.19 mL/kg/min, p < 0.05), time to exhaustion (men: 902.15 ± 120.15 s, women: 780.56 ± 67.63 s, p < 0.05), systolic blood pressure (men: 125.27 ± 7.76 mmHg, women: 107.16 ± 11.09 mmHg, p < 0.05), and arterial stiffness index (men: 63.56 ± 12.55, women: 53.83 ± 8.03, p < 0.05). However, no significant differences in HRV measures were observed between the two groups. These findings suggested that the male badminton athletes demonstrated significantly higher aerobic capacity than did the female athletes, but there were no significant differences in HRV measures. The female athletes exhibited superior arterial function, compared with their male counterparts.

Choriocarcinoma in a viable pregnancy with the rare presentation of intractable lower back pain.

OBJECTIVE: We present a case of choriocarcinoma in a viable pregnancy with the rare presentation of intractable lower back pain. CASE REPORT: The patient is a 34-year-old multiparous woman with her second pregnancy, and a history of scoliosis with spinal fixation. Her first pregnancy was uneventful, with a term vaginal delivery. She was hospitalized four times due to intractable back pain from 25 to 31 weeks, and terminated at 31 weeks. The placenta was unremarkable on gross examination. Postpartum, the patient developed obstructive ileus, requiring a rectosigmoid resection. She was diagnosed with metastatic choriocarcinoma to the liver, para-aortic lymph nodes, and mesentery. A week later, she developed micro-thrombosis of all limbs, massive ascites, pleural effusion. Patient refused chemotherapy and died on post-operative Day 15. CONCLUSION: Presentation of choriocarcinoma in pregnancy varies widely. Clinicians should consider the differential diagnosis of choriocarcinoma when faced with abnormal unexplained symptoms during pregnancy.

Cerebral Cortex Apoptosis in Early Aged Hypertension: Effects of Epigallocatechin-3-Gallate.

This study aimed to investigate cerebral cortex apoptosis on the early aged hypertension and the effects of green tea flavonoid epigallocatechin-3-gallate (EGCG). Twenty-four rats were divided into three groups: a control Wistar-Kyoto group (WKY, n = 8), a spontaneously early aged hypertensive group (SHR, n = 8), and an early aged hypertension with EGCG treatment group (SHR-EGCG, n = 8; daily oral EGCG 200 mg/kg-94%, 12 weeks). At 48 weeks old, blood pressures (BPs) were evaluated and cerebral cortexes were isolated for TUNEL assay and Western blotting. Systolic, diastolic, and mean blood pressure levels in the SHR-EGCG were reduced compared to the SHR. The percentage of neural cell deaths, the levels of cytosolic Endonuclease G, cytosolic AIF (Caspase-independent apoptotic pathway), Fas, Fas Ligand, FADD, Caspase-8 (Fas-mediated apoptotic pathway), t-Bid, Bax/Bcl-2, Bak/Bcl-xL, cytosolic Cytochrome C, Apaf-1, Caspase-9 (Mitochondrial-mediated apoptotic pathway), and Caspase-3 (Fas-mediated and Mitochondria-mediated apoptotic pathways) were increased in the SHR relative to WKY and reduced in SHR-EGCG relative to SHR. In contrast, the levels of Bcl-2, Bcl-xL, p-Bad, 14-3-3, Bcl-2/Bax, Bcl-xL/Bak, and p-Bad/Bad (Bcl-2 family-related pro-survival pathway), as well as Sirt1, p-PI3K/PI3K and p-AKT/AKT (Sirt1/PI3K/AKT-related pro-survival pathway), were reduced in SHR relative WKY and enhanced in SHR-EGCG relative to SHR. In conclusion, green tea flavonoid epigallocatechin-3-gallate (EGCG) might prevent neural apoptotic pathways and activate neural survival pathways, providing therapeutic effects on early aged hypertension-induced neural apoptosis.

Anti-apoptotic and pro-survival effect of exercise training on early aged hypertensive rat cerebral cortex.

The anti-apoptotic and pro-survival effects of exercise training were evaluated on the early aged hypertensive rat cerebral cortex. The brain tissues were analysed from ten sedentary male Wistar Kyoto normotensive rats (WKY), ten sedentary spontaneously 12 month early aged hypertensive rats (SHR), and ten hypertensive rats undergoing treadmill exercise training (60 min/day, 5 days/week) for 12 weeks (SHR-EX). TUNEL-positive apoptotic cells, the expression levels of endonuclease G (EndoG) and apoptosis-inducing factor (AIF) (caspase-independent apoptotic pathway), Fas ligand, Fas death receptor, tumor necrosis factor (TNF)-α, TNF receptor 1, Fas-associated death domain, active caspase-8 and active caspase-3 (Fas-mediated apoptotic pathways) as well as t-Bid, Bax, Bak, Bad, cytochrome c, active caspase 9 and active caspase-3 (mitochondria-mediated apoptotic pathways) were reduced in SHR-EX compared with SHR. Pro-survival Bcl2, Bcl-xL, p-Bad, 14-3-3, insulin-like growth factor (IGF)-1, pPI3K/PI3K, and pAKT/AKT were significantly increased in SHR-EX compared to those in SHR. Exercise training suppressed neural EndoG/AIF-related caspase-independent, Fas/FasL-mediated caspase-dependent, mitochondria-mediated caspase-dependent apoptotic pathways as well as enhanced Bcl-2 family-related and IGF-1-related pro-survival pathways in the early aged hypertensive cerebral cortex. These findings indicated new therapeutic effects of exercise training on preventing early aged hypertension-induced neural apoptosis in cerebral cortex.

Aging Additively Influences Insulin- and Insulin-Like Growth Factor-1-Mediated Endothelial Dysfunction and Antioxidant Deficiency in Spontaneously Hypertensive Rats.

This study aimed to investigate the aging-related endothelial dysfunction mediated by insulin and insulin-like growth factor-1 (IGF-1) and antioxidant deficiency in hypertension. Male spontaneously hypertensive rats (SHRs) and age-matched normotensive Wistar-Kyoto rats (WKYs) were randomly divided into 24-week-old (younger) and 48-week-old (older) groups, respectively. The endothelial function was evaluated by the insulin- and IGF-1-mediated vasorelaxation of aortic rings via the organ bath system. Serum levels of nitric oxide (NO), malondialdehyde (MDA), catalase, and total antioxidant capacity (TAC) were examined. The insulin- and IGF-1-mediated vasorelaxation was significantly impaired in both 24- and 48-week-old SHRs compared with age-matched WKYs and was significantly worse in the 48-week-old SHR than the 24-week-old SHR. After pretreatments of phosphoinositide 3-kinase (PI3K) or NO synthase (NOS) inhibitors, the insulin- and IGF-1-mediated vasorelaxation became similar among four groups. The serum level of MDA was significantly increased, while the NO, catalase, and TAC were significantly reduced in the 48-week-old SHR compared with the 24-week-old SHR. This study demonstrated that the process of aging additively affected insulin- and IGF-1-mediated endothelial dysfunction in SHRs, which could be partly attributed to the reduced NO production and antioxidant deficiency.

Granulocyte Colony Stimulating Factor (GCSF) Can Attenuate Neuropathic Pain by Suppressing Monocyte Chemoattractant Protein-1 (MCP-1) Expression, through Upregulating the Early MicroRNA-122 Expression in the Dorsal Root Ganglia.

Our previous animal studies and several human clinical trials have shown that granulocyte-colony stimulating factor (GCSF) can attenuate neuropathic pain through various mechanisms. GCSF itself is also a multipotent cytokine that can modulate microribonucleic acid (microRNA) expression profiles in vitro. In this study, we used the NanoString nCounter analysis system to screen the expression of different rodent microRNAs at early stage after nerve injury and studied the expression of related cytokines/chemokines in the dorsal root ganglia (DRGs) of rats that underwent chronic constriction injury (CCI) to explore the underlying mechanisms of the analgesic effects of GCSF. We found that microRNA-122 expression was downregulated by CCI; in contrast, GCSF treatment significantly upregulated microRNA-122 expression in the DRGs of CCI rats on the 1st day after nerve injury. We further studied the expression of different cytokines/chemokines (IL-1ß, IL-6, and monocyte chemoattractant protein-1 (MCP-1)) that were modulated by microRNA-122. MCP-1 has been reported to participate in neuropathic pain development, and its expression on the DRGs of vehicle-treated CCI rats was significantly higher than that on the DRGs of sham-operated rats; in contrast, GCSF-treated rats exhibited significantly lower MCP-1 expression in the DRG than vehicle-treated rats on the 7th day after nerve injury. An early GCSF treatment can suppress MCP-1 expressions, through upregulating microRNA-122 expressions in the DRGs of CCI rats at an earlier stage, thus indirectly attenuating neuropathic pain development.

Exercise training attenuates cardiac inflammation and fibrosis in hypertensive ovariectomized rats.

This study investigated the effects of exercise training on cardiac inflammatory and cardiac fibrotic pathways in female spontaneously hypertensive rats (SHR), which were divided into a sham-operated sedentary hypertensive group (SHR-S), a sedentary hypertensive ovariectomized group (SHR-O), or a hypertensive ovariectomized group with treadmill exercise training (SHR-OT; 60 min/day, 5 days/wk) for 8 wk. Normotensive female Wistar-Kyoto rats (WKY) served as controls. SOD and catalase (CAT) activities were significantly increased in the SHR-OT group, when compared with the SHR-S or SHR-O groups. The protein levels of estrogen receptor (ER)-α and ER-ß became decreased in the SHR-O group, when compared with the WKY or SHR-S groups, but were not changed in the SHR-OT group. The protein level of the angiotensin II type I receptor (AT1R) was increased in the SHR-S group but did not further change in the SHR-O group, whereas it was decreased in the SHR-OT group. The inflammatory-related protein levels of TNF-α, p-NF-κB, cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS), and IL-6, as well as the fibrotic-related protein levels of transforming growth factor-ß (TGF-ß), p-Smad2/3, connective tissue growth factor (CTGF), tissue-type plasminogen activator (tPA), matrix metalloproteinase (MMP)-9, and collagen I were increased in the SHR-S group and increased further in the SHR-O group, whereas they were decreased in the SHR-OT group. The coexistence of hypertension and ovariectomy additively increased cardiac inflammatory and fibrotic pathways partially through hypertension-enhanced AT1R and ovariectomy-depressed estrogen receptors. Exercise training appeared to suppress hypertensive ovariectomized heart-induced inflammatory and fibrotic pathways possibly through decreasing AT1R but not through estrogen receptors.NEW & NOTEWORTHY The coexistence of hypertension and ovariectomy appeared to increase cardiac inflammatory and fibrotic pathways likely through hypertension-enhanced angiotensin II type I receptor and ovariectomy-depressed estrogen receptors. Exercise training on a treadmill could prevent hypertensive ovariectomized heart-induced cardiac inflammation and fibrosis via an inflammatory pathway [TNF-α, p-IKK-α/ß, p-NF-κB, cyclooxygenase 2 (COX-2), iNOS, and IL-6] and fibrotic pathway [transforming growth factor-ß (TGF-ß), p-Smad2/3, connective tissue growth factor (CTGF), tissue-type plasminogen activator (tPA), matrix metalloproteinase (MMP)-9, and collagen I] possibly through decreasing angiotensin II type I receptor but not through estrogen receptors.

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To solve the problem of soil acidification in the cultivation of Codonopsis tangshen, laboratory experiments were carried out to investigate C. tangshen seed germination, seedling growth and soil exchangeable acid, microbial community structure after applying quicklime (QL) and calcium magnesium phosphate fertilizer (CMP). The results showed that QL and CMP treatments significantly improved the survival rate of C. tangshen seedlings from 147.7% to 326.7% and from 270.1% to 311.2%, respectively. The maximum increase rates of the height of C. tangshen seedlings were 516.7% and 546.3%, and that of root length were 798.0% and 679.2% in the treatments of QL and CMP, respectively. 1‰-4‰ QL or CMP treatments increased the relative chlorophyll content, antioxidant enzyme activity and the content of soluble protein of C. tangshen seedlings, decreased the content of malondialdehyde and superoxide anion radical of seedlings, increased soil pH by 0.88-2.02 units and 0.23-1.19 units, and decreased the exchangeable aluminum content in soil by 53.0%-95.3% and 17.6%-81.3%, respectively. Soil bacterial and actinomycetic abundances were significantly higher in 2‰-4‰ QL or CMP treatments than that in the control. Soil fungal abundance was significantly lower in the QL treatment of 2‰ and CMP treatment of 4‰. 1‰-4‰ QL or CMP treatments significantly increased fresh weight of C. tangshen tubers by 40.5%-78.5% and 28.4%-78.8%, respectively. In conclusion, the suitable quantity of QL and CMP for acidified soil (pH=4.12, ρb=1.15 g·cm-3, tillage layer=15 cm) amendment were 1.73-3.45 t·hm-2 and 3.45-6.90 t·hm-2, and QL and CMP amendment could fit the optimum soil pH (5.5-6.5) for the growth of C. tangshen seedlings.

Amine functionalized ZIF-8 as a visible-light-driven photocatalyst for Cr(VI) reduction.

Hexavalent chromium (Cr(VI)) is one of the most toxic and carcinogenic species known to living beings, the environment, and our eco-system. Thus, it is urgent to develop a facile and effective approach for Cr(VI) removal. Zinc-based zeolitic imidazolate frameworks (ZIF-8), a typical metal organic framework, have high porosity, large specific surface area, high chemical stability, and abundant surface grafting sites. These sites can be easily modified with ethylenediamine (EDA) using a solvothermal process to generate a material that can serve as a potential candidate for photocatalytic Cr(VI) reduction under visible light irradiation. Various EDA contents and synthetic conditions were adopted in an attempt to investigate the correlation between ZIF-8 amine-functionalization and photocatalytic Cr(VI) reduction. The amine functionalization and the grafting sites on ZIF-8 were determined to be located at the -CH3 site of the 2-methylimidazole chains via X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and nuclear magnetic resonance spectroscopy (NMR). Under optimum conditions, amine-functionalized ZIF-8 exhibited a normalized rate constant (k/specific surface area, kSSA), which was 9.8 times higher than that of unmodified ZIF-8 one for photocatalytic Cr(VI) reduction. The increased catalytic activity and range of visible light absorption of amine-functionalized ZIF-8 can be attributed to the increase in electron density due to the lone pairs of the surface grafted amines. In summary, amine-functionalized ZIF-8 could serve as a promising visible-light-active photocatalyst for environmental remediation.

Twelve-Week Protocatechuic Acid Administration Improves Insulin-Induced and Insulin-Like Growth Factor-1-Induced Vasorelaxation and Antioxidant Activities in Aging Spontaneously Hypertensive Rats.

Protocatechuic acid (PCA), a strong antioxidant, has been reported for its cardiovascular-protective effects. This study aimed to investigate the effects of PCA administration on vascular endothelial function, mediated by insulin and insulin-like growth factor-1 (IGF-1), and antioxidant activities in aging hypertension. Thirty-six-week-old male aging spontaneously hypertensive rats were randomly divided into vehicle control (SHR) and PCA (SHR+PCA) groups, while age-matched Wistar⁻Kyoto rats (WKY) served as the normotensive vehicle control group. The oral PCA (200 mg/kg/day) was administered daily for a total of 12 weeks. When the rats reached the age of 48 weeks, the rat aortas were isolated for the evaluation of vascular reactivity and Western blotting. Also, nitric oxide (NO) production and antioxidant activities were examined among the three groups. The results showed that, when compared with the SHR group, the insulin-induced and IGF-1-induced vasorelaxation were significantly improved in the SHR+PCA group. There was no significant difference in the endothelium-denuded vessels among the three groups. After the pre-incubation of phosphatidylinositol 3-kinase (PI3K) or NO synthase (NOS) inhibitors, the vasorelaxation was abolished and comparable among the three groups. The protein levels of insulin receptors, IGF-1 receptors, phospho-protein kinase B (p-Akt)/Akt, and phospho-endothelial NOS (p-eNOS)/eNOS in aortic tissues were significantly enhanced in the SHR+PCA group when compared with the SHR group. Moreover, significant improvements of nitrate/nitrite concentration and antioxidant activities, including superoxide dismutase, catalase, and total antioxidants, were also found in the SHR+PCA group. In conclusion, the 12 weeks of PCA administration remarkably improved the endothelium-dependent vasorelaxation induced by insulin and IGF-1 in aging hypertension through enhancing the PI3K⁻NOS⁻NO pathway. Furthermore, the enhanced antioxidant activities partly contributed to the improved vasorelaxation.