Head Acupuncture Plus Schuell's Language Rehabilitation for Post-Stroke Aphasia: A Systematic Review and Meta-Analysis of 32 Randomized Controlled Trials.

OBJECTIVE: To evaluate the existing randomized controlled trials (RCTs) for evidence of the efficacy and safety of head acupuncture (HA) plus Schuell's language rehabilitation (SLR) in post-stroke aphasia. METHODS: Seven databases including Embase, PubMed, Cochrane Library, Technology Periodical Database, the China National Knowledge Infrastructure, SinoMed and Wanfang Data Information Site were searched for RCTs published from database inception until November 14, 2021. RCTs that compared HA plus SLR with sham (or blank) control, acupuncture therapy alone, certain language rehabilitation therapy alone or other therapies for post-stroke aphasia were included. Data were extracted and assessed, and the quality of RCTs was evaluated. Fixed-effects model was used, with meta-inflfluence analysis, meta-regression, and regression-based sub-group analyses applied for exploration of heterogeneity. Publication bias was estimated by funnel plots and Egger's tests. RESULTS: A total of 32 RCTs with 1,968 patients were included and 51 comparisons were conducted classified as types of strokes and aphasia. (1) For patients with aphasia after ischemic stroke, HA plus PSA showed significantly higher accumulative markedly effective rate [relative risk (RR)=1.55, 95% confidence interval (CI): 1.19-2.02, I2=0%] and accumulative effective rate (RR=1.22, 95% CI: 1.09-1.36, I2=0%). (2) For patients with comprehensive types of stroke, HA plus PSA was more effective in increasing recovery rate (RR=1.89, 95% CI: 1.39-2.56, I2=0%), accumulative markedly effective rate (RR=1.53, 95% CI: 1.36-1.72, I2=9%) and accumulative effective rate (RR=1.14, 95% CI: 1.09-1.19, I2=34%). (3) For patients with aphasia after stroke, HA plus PSA was superior to PSA alone with statistical significance in increasing recovery rate (RR=2.08, 95% CI: 1.24-3.46, I2=0%), accumulative markedly effective rate (RR=1.49, 95% CI: 1.24-1.78, I2=0%) and accumulative effective rate (RR=1.15, 95% CI: 1.06-1.24, I2=39%). (4) For patients with multiple types of aphasia, HA plus PSA also demonstrated significantly higher recovery rate (RR=1.86, 95% CI: 1.28-2.72, I2=0%), accumulative markedly effective rate (RR=1.55, 95% CI: 1.35-1.78, I2=22%), and accumulative effective rate (RR=1.17, 95% CI: 1.11-1.23, I2=41%). (5) For patients with motor aphasia after ischemic stroke, compared with PSA alone, HA plus PSA showed significantly higher accumulative markedly effective rate (RR=1.38, 95% CI: 1.06-1.79, I2=0%) and accumulative effective rate (RR=1.20, 95% CI: 1.05-1.37, I2=0%). Meta-regression analyses were performed without significant difference, and publication bias was found in some comparisons. CONCLUSION: HA plus SLR was significantly associated with better language ability and higher effective rate for patients with post-stroke aphasia, and HA should be operated cautiously especially during acupuncture at eye and neck. (Registration No. CRD42020154475).

[Effect of calorie-enriched formula on postoperative catch-up growth in infants with cyanotic congenital heart disease: a propective randomized controlled study].

OBJECTIVE: To study the effect of calorie-enriched formula on postoperative catch-up growth in infants with cyanotic congenital heart disease (CHD). METHODS: A total of 100 infants with cyanotic CHD who underwent surgical operation from January to December, 2017, were randomly divided into a high-calorie group (receiving calorie-enriched formula after surgery) and a conventional group (receiving standard formula after surgery), with 50 infants in each group. All infants were followed up for 6 months. The observation indices included body height, body weight, prealbumin, and N-terminal pro-brain natriuretic peptide before surgery, at the time of ventilator weaning and extubation after surgery, and at 1, 3, and 6 months after surgery. Height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), and weight-for-height Z-score (WHZ) were also assessed. Adverse reactions were recorded for both groups. RESULTS: There were 25 cases (50%) and 21 cases (42%) of malnutrition in the high-calorie group and the conventional group respectively before surgery (P > 0.05). The nutritional status of the two groups improved 6 months after surgery (P < 0.05). At 6 months after surgery, compared with the conventional group, the high-calorie group had a lower proportion of infants with malnutrition (18% vs 36%, P < 0.05) and also a lower proportation of infants with a WAZ score of < -2 (P < 0.05). The infants with malnutrion in the high-calorie group had higher HAZ, WAZ, and WHZ than those in the conventional group (P < 0.05). No gastrointestinal intolerance was observed in both groups during hospitalization. CONCLUSIONS: Compared with the standard formula, calorie-enriched formula can better help with postoperative catch-up growth in infants with cyanotic CHD.

Deletion of Glycogen Synthase Kinase-3ß in D2 Receptor-Positive Neurons Ameliorates Cognitive Impairment via NMDA Receptor-Dependent Synaptic Plasticity.

BACKGROUND: Cortical dopaminergic systems are critically involved in prefrontal cortex (PFC) functions, especially in working memory and neurodevelopmental disorders such as schizophrenia. GSK-3ß (glycogen synthase kinase-3ß) is highly associated with cAMP (cyclic adenosine monophosphate)-independent dopamine D2 receptor (D2R)-mediated signaling to affect dopamine-dependent behaviors. However, the mechanisms underlying the GSK-3ß modulation of cognitive function via D2Rs remains unclear. METHODS: This study explored how conditional cell-type-specific ablation of GSK-3ß in D2R+ neurons (D2R-GSK-3ß-/-) in the brain affects synaptic function in the medial PFC (mPFC). Both male and female (postnatal days 60-90) mice, including 140 D2R, 24 D1R, and 38 DISC1 mice, were used. RESULTS: This study found that NMDA receptor (NMDAR) function was significantly increased in layer V pyramidal neurons in mPFC of D2R-GSK-3ß-/- mice, along with increased dopamine modulation of NMDAR-mediated current. Consistently, NR2A and NR2B protein levels were elevated in mPFC of D2R-GSK-3ß-/- mice. This change was accompanied by a significant increase in enrichment of activator histone mark H3K27ac at the promoters of both Grin2a and Grin2b genes. In addition, altered short- and long-term synaptic plasticity, along with an increased spine density in layer V pyramidal neurons, were detected in D2R-GSK-3ß-/- mice. Indeed, D2R-GSK-3ß-/- mice also exhibited a resistance of working memory impairment induced by injection of NMDAR antagonist MK-801. Notably, either inhibiting GSK-3ß or disrupting the D2R-DISC1 complex was able to reverse the mutant DISC1-induced decrease of NMDAR-mediated currents in the mPFC. CONCLUSIONS: This study demonstrates that GSK-3ß modulates cognition via D2R-DISC1 interaction and epigenetic regulation of NMDAR expression and function.

Celastrol Alleviates Chronic Obstructive Pulmonary Disease by Inhibiting Cellular Inflammation Induced by Cigarette Smoke via the Ednrb/Kng1 Signaling Pathway.

Chronic obstructive pulmonary disease (COPD) is a debilitating disease caused by chronic exposure to cigarette smoke (CS). Celastrol is a pentacyclic triterpenoid compound exhibits potent antioxidant and anti-inflammatory activities. Also it is presently known to protect against liver damage induced by type II diabetes. However, its role in COPD is unclear. In this study, we investigated the effects of Celastrol on cellular inflammation in mice exposed to CS and Beas-2B cells treated with CS extract (CSE). C57BL/6 mice and Beas-2B cells were randomly divided into three groups: control group, COPD or CSE group, and Celastrol treatment group. The COPD mice models were subjected to smoke exposure and cell models were treated with CSE. Bioinformatics analysis was performed to identify differentially expressed genes following treatment with Celastrol in COPD, the molecular networks was mapped by Cytoscape. The levels of inflammatory cytokinesinterleukin-8, tumor necrosis factor α, monocyte chemoattractant protein-1, and oxidative stress factors superoxide dismutase and catalase were measured by enzyme-linked immunosorbent assay. Hematoxylin and eosin staining to detect the injury of mouse lung tissue. mRNA and protein levels of Ednrb and Kng1 in the tissues and cells were measured by quantitative polymerase chain reaction (PCR) and western blotting, respectively. Apoptosis was measured by flow cytometry and TUNEL staining. Compared to mice in the COPD group, mice treated with Celastrol had significantly reduced levels of inflammatory cytokines interleukin-8, tumor necrosis factor α and monocyte chemoattractant protein-1 in the serum and bronchoalveolar lavage fluid, and significantly increased levels of oxidative stress factors superoxide dismutase and catalase. The same results were obtained at the cellular level using Beas-2B cells. Compared to the model groups, Celastrol reduced lung injury in mice and significantly reduced cellular apoptosis. Bioinformatics analysis showed that Ednrb is a target gene of Celastrol and differentially expressed in COPD. Quantitative PCR analysis showed that Ednrb expression in patients with COPD was significantly increased compared to that in healthy controls. Additionally, Celastrol effectively reduced Ednrb/Kng1 expression in both cell and animal models. Celastrol has a therapeutic effect on COPD and may alleviate COPD by inhibiting inflammation development by suppressing the Ednrb/Kng1 signaling pathway.

Mitochondrial pathways are involved in Eimeria tenella-induced apoptosis of chick embryo cecal epithelial cells.

Accumulating evidence suggests that Eimeria tenella severely damages the intestinal mucosa in infected poultry, resulting in deadly haemorrhagic typhlocolitis and major economic losses. Damage to host tissue is believed to arise mainly from apoptosis, which is, in general, intimately related to mitochondrial function. However, it is unclear whether mitochondria-dependent apoptotic pathways are specifically involved in parasite-induced apoptosis of chick embryo cecal epithelial cells. Because the mitochondrial permeability transition pore (MPTP) and caspase-9 are important elements in these pathways, we studied the effects of their respective inhibitors (i.e., cyclosporine A [CsA] and Z-LEHD-FMK, respectively) in primary cultures of chicken embryonic cecum epithelial cells using histopathological techniques, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assays, flow cytometry (FCM) and ELISA. Results indicated that the inhibitors significantly decreased (p < 0.01) DNA injury, apoptosis and caspase-9 and caspase-3 activity of chick embryo cecal epithelial cells at 24, 48, 72, 96 and 120 h after E. tenella infection. Thus, our data supported that mitochondria-dependent apoptotic pathways were involved in apoptosis of parasitised chick embryo cecal epithelial cells.

Dynamic changes in the main regulatory genes of mitochondrial permeability transition pore in Eimeria tenella host cells.

The purpose of the present study was to investigate the dynamic changes in the main regulatory genes of the mitochondrial permeability transition pore in E. tenella host cells. Primary chick embryo cecum epithelial cell culture techniques, spectrophotometer technology, Hoechst-Annexin V-PI apoptosis staining and ELISA were used to detect the apoptosis rate and dynamic changes of Bcl-2, Bcl-xl, Bax, Bak, Bid, Bad, HK-II, and ATP content in E. tenella host cells at 4, 24, 48, 72, 96, and 120 h. The rates of early apoptosis, late apoptosis, and necrosis of group T0 were significantly lower (P < 0.05) or highly significantly lower (P < 0.01) than those of group C at 4 h, but higher (P < 0.05 or P < 0.01) at varying degrees than those of the same group at 24-120 h. Compared to group C, the amount of Bcl-2, ATP, Bax and Bad in group T0 were visibly lower (P < 0.05 or P < 0.01) at 4 h, whereas Bcl-xl/Bax was highly significantly higher (P < 0.01) at 4 h. In addition, group T0 had less ATP at 24-120 h than group C, whereas the amount of Bcl-2, Bcl-xl, Bax, Bak, Bid, Bad and HK-II in group T0 inversely increased in varying degrees at 24-120 h compared with group C. Moreover, Bcl-2/Bax was lower (P < 0.01) at 24, 48, and 96 h, and Bcl-xl/Bax was lower (P < 0.05) at 48 h in group T0 than in group C, respectively. Taken together, these observations indicate that in the early developmental stages of E. tenella, the host-cell apoptosis rate decreased; although the amount of anti- and pro-apoptotic genes in host cells decreased, the ratios of anti-apoptotic to pro-apoptotic bcl-2 gene-family members increased. In the middle and later developmental stages of E. tenella, the host-cell apoptosis rate increased; the amount of anti- and pro-apoptotic genes increased, while the ratios of anti-apoptotic to pro-apoptotic bcl-2 gene-family members decreased. In addition, ATP decreased at all developmental stages of E. tenella.

The effect of the mitochondrial permeability transition pore on apoptosis in Eimeria tenella host cells.

Although the mitochondrial permeability transition pore (MPTP) is associated with cellular apoptosis and necrosis, its effect in host response to Eimeria infections is not well understood. In an effort to better understand the effect of MPTP on apoptosis in Eimeria tenella host cells, an MPTP inhibitor (cyclosporin A) was used to inhibit MPTP opening in vitro. Cecal epithelial cells from chick embryos, which were either treated or non-treated with cyclosporin A, were used as Eimeria tenella host cells. In addition, primary chick embryo cecum epithelial cell culture techniques and flow cytometry were used to detect the dynamic changes in MPTP opening, mitochondrial transmembrane potential, and cell apoptosis rate of Eimeria tenella host cells. Compared with the control group, cytometric techniques showed that untreated host cells exhibited a significantly higher (P < 0.01) degree of MPTP opening but lower (P < 0.01 or P < 0.05) mitochondrial transmembrane potential. Moreover, untreated group cells had less apoptosis (P < 0.01) at 4 h and more apoptosis (P < 0.05 or P < 0.01) at 24 to 120 h as compared with control group cells. After the application of cyclosporin A, the degree of MPTP opening in the treated group was significantly lower (P < 0.01) at 4 to 120 h compared to the untreated group, whereas the treated group had higher (P < 0.05 or P < 0.01) mitochondrial transmembrane potentials at 24 to 120 h. Flow cytometry assays also showed that there was less (P < 0.05 or P < 0.01) apoptosis after 24 h in the treated group than in the untreated group. Taken together, these observations indicate that MPTP is a key node that plays a predominant role in the mitochondrial apoptosis pathway in the host cell induced by Eimeria tenella.

MiR-769 promoted cell proliferation in human melanoma by suppressing GSK3B expression.

MicroRNAs (miRNAs) are short, non-coding RNAs with post-transcriptional regulatory function, playing crucial roles in cancer development and progression of human melanoma. Previous studies have indicated that miR-769 was implicated in diverse biological processes. However, the underlying mechanism of miR-769 in human melanoma has not been intensively investigated. In this present study, we aimed to investigate the role of miR-769 and its target genes in human melanoma. We found that miR-769 expression was strongly increased in human melanoma cells and clinical tissues compared with their corresponding controls. Overexpression of miR-769 promoted cell proliferation in human melanoma cell line A375, whereas miR-769-in reverses the function. Glycogen synthase kinase-3 Beta (GSK3B), a potential target gene of miR-769, and was validated by luciferase assay. Further studies revealed that miR-769 regulated cell proliferation of human melanoma by directly suppressing GSK3B expression and the knockdown of GSK3B expression reversed the effect of miR-769-in on human melanoma cell proliferation. In summary, our data demonstrated that miR-769 might act as a tumor promoter by targeting GSK3B during development of human melanoma.

Disruption of Akt signaling decreases dopamine sensitivity in modulation of inhibitory synaptic transmission in rat prefrontal cortex.

Akt is a serine/threonine kinase, which is dramatically reduced in the prefrontal cortex (PFC) of patients with schizophrenia, and a deficiency in Akt1 results in PFC function abnormalities. Although the importance of Akt in dopamine (DA) transmission is well established, how impaired Akt signaling affects the DA modulation of synaptic transmission in the PFC has not been characterized. Here we show that Akt inhibitors significantly decreased receptor sensitivity to DA by shifting DA modulation of GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) in prefrontal cortical neurons. Akt inhibition caused a significant decrease in synaptic dopamine D2 receptor (D2R) levels with high-dose DA exposure. In addition, Akt inhibition failed to affect DA modulation of IPSCs after blockade of ß-arrestin 2. ß-arrestin 2-mediated interaction of clathrin with D2R was enhanced by co-application of a Akt inhibitor and DA. Taken together, the reduced response in DA modulation of inhibitory transmission mainly involved ß-arrestin 2-dependent D2R desensitization.

Calcium homeostasis in mitochondrion-mediated apoptosis of chick embryo cecal epithelial cells induced by Eimeria tenella infection.

In this study, the process of Eimeria tenella-induced apoptosis and the effect of calcium homeostasis were investigated in chick embryo cecal epithelial cells. In particular, we examined cytochrome c release into the cytoplasm, mitochondrial permeability transition pore (MPTP) opening, and changes in [Ca(2+)]c and apoptosis in host cells. Apoptosis, MPTP opening, cytochrome c release, and [Ca(2+)]c in host cells increased following infection. This trend was reversed by blocking the increase in [Ca(2+)]c using BAPTA/AM and EGTA (intra- and extracellular chelators of Ca(2+), respectively) and by applying heparin sodium and ryanodine (blockers of the inositol triphosphate and ryanodine receptors of the endoplasmic reticulum, respectively). These results indicate that [Ca(2+)]c plays a significant role in host cell mitochondrial apoptosis, which is induced via modulation of extracellular Ca(2+) levels and endoplasmic reticulum Ca(2+) channels. Thus, agents that restore Ca(2+) homeostasis may be useful for managing E. tenella infection in chickens.