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Background. It is widely accepted that inflammation may contribute to cognitive impairment in patients with vascular dementia (VD). Our prior clinical researches have reported that acupuncture can alleviate cognitive function in VD, but the underlying mechanisms are still unclear. The purpose of this research was to explore whether acupuncture alleviates cognitive impairment by suppressing the microRNA-93- (miR-93-) mediated Toll-like receptor (TLR) signaling pathway, which triggers inflammatory responses in the central nervous system. Methods. VD was established by permanent bilateral common carotid artery occlusion in male Wistar rats. Three days after operation, the rats began daily treatment with acupuncture for two weeks. The levels of miR-93, Toll-like receptors (TLR2 and TLR4), intracellular signaling molecules (myeloid differentiation factor 88 (MyD88) and nuclear factor-kappa B (NF-κB)), and inflammatory cytokines were subsequently detected. TLR4 colocalized with neurons, microglia, and astrocytes in the hippocampus was evaluated. Neuroinflammation and cognitive function were determined after intracerebroventricular injection of TLR4 antagonist TAK-242 or agonist lipopolysaccharide (LPS) with or without acupuncture. Results. We found that acupuncture notably repressed the expression of inflammatory cytokines in the hippocampus and plasma of VD rats. The expression of TLR4, but not TLR2, was markedly downregulated by acupuncture, accompanied by a decrease in miR-93 and MyD88/NF-κB signaling pathway activation. The overexpression of TLR4 in microglia, but not in astrocytes and neurons, was reversed by acupuncture. Furthermore, intracerebroventricular injection of TAK-242 had similar effects to acupuncture on inflammation and cognitive function, while LPS injection abolished the beneficial effects of acupuncture. Conclusions. Taken together, these findings provide evidence that acupuncture attenuates cognitive impairment associated with inflammation through inhibition of the miR-93-mediated TLR4/MyD88/NF-κB signaling pathway in experimental VD. Acupuncture serves as a promising alternative therapy and may be an underlying TLR4 inhibitor for the treatment of VD.

To address the limitations of traditional cadmium telluride (CdTe) photovoltaic (PV) windows in comprehensively considering overall building energy consumption, indoor lighting comfort, and outdoor visibility, this study proposes a three-domain division CdTe PV window design, which divides the window into three areas, each undertaking different functions. This study utilized the Energy Plus 9.3.0 software and Radiance 1.6.0 software for numerical simulation to explore the impact of different design parameters (such as coverage rate and arrangement mode of PV) of the three-domain division PV windows on building energy consumption and the proportion of indoor effective natural lighting (UDI300lx–2000lx) in single-story office buildings in Yan’an. Additionally, this study employed the entropy weight–TOPSIS method to conduct a comprehensive evaluation of 84 schemes. The results indicate that both the coverage rate and the arrangement mode of PV significantly influence building energy-saving and indoor lighting environment. The energy-saving rate initially increases and then decreases with higher PV coverage, while UDI300lx–2000lx generally exhibits an upward trend and slightly decreases later. The V3-V1 or H3-V1 arrangement mode demonstrates superior energy-saving performance, whereas the H3-V1 or V3-H1 arrangement mode provides better indoor lighting comfort. The evaluation weights for energy-saving rate and effective daylighting are 0.38 and 0.62, respectively. Based on the comprehensive evaluation, the optimal configuration is determined to be V1-90%-V2-10%-H3-90%, achieving an energy-saving rate of 11.1% and a UDI300lx–2000lx value of 56.95%.

Ischemic stroke is a major cause of mortality and disability worldwide. As a part of Traditional Chinese Medicine (TCM), acupuncture has been shown to be effective in promoting recovery after stroke. In this article, we review the clinical and experimental studies that demonstrated the mechanisms of acupuncture treatment for cerebral ischemia. Clinical studies indicated that acupuncture activated relevant brain regions, modulated cerebral blood flow and related molecules in stroke patients. Evidence from laboratory indicated that acupuncture regulates cerebral blood flow and metabolism after the interrupt of blood supply. Acupuncture regulates multiple molecules and signaling pathways that lead to excitoxicity, oxidative stress, inflammation, neurons death and survival. Acupuncture also promotes neurogenesis, angiogenesis as well as neuroplasticity after ischemic damage. The evidence provided from clinical and laboratory suggests that acupuncture induces multi-level regulation via complex mechanisms and a single factor may not be enough to explain the beneficial effects against cerebral ischemia.

To evaluate the long-term clinical efficacy of ultrasound cyclo-plasty (UCP) in the treatment of moderate glaucoma and molecular effects in animal experiments. An 18-month clinical study was conducted among 32 patients with moderate glaucoma. The primary outcome was surgical success, defined as a reduction in intraocular pressure (IOP) of greater than or equal to 20% from the baseline and an IOP value of greater than 5 mmHg at the last follow-up. The secondary outcomes were related to the quality of life, complications, and mean IOP value at each follow-up. In the animal experiment, 20 New Zealand rabbits were used to establish a high-IOP model and implement UCP. The distribution of aquaporin 4 (AQP4) in the ciliary body and the tissue changes under electron microscopy were observed after surgery. The mean patient IOP decreased from 34.9 ± 4.9 mmHg before surgery to 23.5 ± 5.2 mmHg at 18 months after UCP. No vision loss occurred in any patient. Some patients had postoperative complications, but the symptoms were mild and disappeared within 3 months after the surgery. Most patients had good postoperative quality of life. Histology showed that AQP4 remained in the ciliary muscle after UCP, and only the bilayered epithelial cells showed coagulative necrosis. Furthermore, electron microscopic observation revealed the destruction of ciliary process cells covered by ultrasound after UCP. UCP is associated with mild postoperative reactions and the mild treatment of ciliary tissue and is a safe and effective method for reducing IOP in moderate glaucoma.

The complexity of hard-to-treat diseases such as ischemic stroke strongly undermines the therapeutic potential of available treatment options. Therefore, current developments have gently shifted from a focus on monotherapy to combined or multiple therapies. Both dexmedetomidine and Netrin-1 have anti-neuronal apoptosis effects, but the mechanism is still unclear. The study aimed to estimate the efficacy of dexmedetomidine and Netrin-1 combination therapy against ERS-induced apoptosis after cerebral ischemia injury in vivo and in vitro , and whether the mechanism is related to the ERK5/MEF2A pathway. Adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) in vivo , 90 min ischemia and 24 h reperfusion. The hippocampus slices used to establish oxygen-glucose deprivation (OGD) injury model in vitro . Neterin-1 and Dexmedetomidine were pretreated and post-treated, respectively, before and after the model establishment. MEF2A knockdown was performed by microinjection of AAV9-MEF2A RNAi vector. Orthodromic population spike (OPS) at the end of reoxygenation were recorded. Neurobehavioral tests, TTC staining, Nissl staining, TUNEL staining were performed to assess the effect of the drugs. The expression of CHOP, GRP78, MEF2A, ERK5, and p-ERK5 were investigated by Western blot and immunofluorescence staining. Neurological deficit score, infarct volume, the expression of GRP78, CHOP, and neural apoptotic rate of MCAO group increased markedly. Combination of dexmedetomidine and Netrin-1 resulted in lower infarct volumes and fewer neurological impairments, higher OPS recovery rate, and less damaged and apoptotic cells after cerebral ischemia injury. Furthermore, expression levels of GRP78 and CHOP decreased in the combination therapy group, and it was more effective than the single drug group. Meanwhile, Combination of dexmedetomidine and Netrin-1 increased MEF2A expression and promoted ERK5 phosphorylation. However, the protective effect of dexmedetomidine combined with Netrin-1 in improving neurological function was significantly eliminated by pre-knockdown MEF2A. The neuroprotective effects of dexmedetomidine combined with Netrin on cerebral ischemia-reperfusion injury and hippocampal hypoxia injury in terms of ERS. The synergistic effect of combination therapy is related to the activation of ERK5/MEF2A signaling pathway.

Background The renal risk score (RRS) is a useful tool to predict end-stage renal disease (ESRD) in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The current study aimed to validate the predictive performance of RRS and to further modify this model in Chinese AAV patients. Methods Two hundred and seventy-two patients diagnosed with AAV confirmed by renal biopsies were retrospectively enrolled from a single center. The RRS was calculated based on 3 categorical variables, i.e., the proportion of normal glomeruli, the proportion of interstitial fibrosis and tubular atrophy (IF/TA), and eGFR at biopsy, classifying these patients into low-, medium-, and high-risk groups. In addition, a modified model was developed based on the RRS and was further validated in another independent cohort of 117 AAV patients. The predictive performance of each model was evaluated according to discrimination and calibration. Results Patients were classified by the RRS into low- (26.5%), medium- (46.7%), and high-risk (26.8%) groups, with 120-month renal survival rates of 93.3%, 57.2%, and 18.4%, respectively ( P  < 0.001). The RRS showed good discrimination but less satisfactory calibration. Therefore, a modified model with improved discrimination and calibration was developed in Chinese AAV patients, with eGFR, proportion of normal glomeruli (both as continuous variables), and IF/TA (< 25%, 25–50%, > 50%) included. Internal and external validation of the modified model were performed. Finally, an online risk prediction tool was developed based on the modified model. Conclusions The RRS was an independent predictor of ESRD of AAV patients. The modified model could predict the probability of ESRD for AAV patients with improved performance in Chinese AAV patients.

The sympathetic nervous system, via epinephrine and norepinephrine, regulates β-adrenergic receptor (β-AR) expression, and renal sympathetic activation causes sustained increases in blood pressure by enhanced renin release. In this study, we aim to investigate the effect and underlying mechanism of acupuncture at Taichong (LR3) on renal sympathetic activity in spontaneously hypertensive rats. Unanesthetized rats were subject to daily acupuncture for 2 weeks. Mean blood pressure (MBP) and heart rate variability (HRV) were monitored at days 0, 7, and 14 by radiotelemetry. After euthanasia on the 14th day, blood and the kidneys were collected and subject to the following analyses. Epinephrine and norepinephrine were detected by ELISA. The expression of β-ARs was studied by western blotting and PCR. The renin content was analyzed by radioimmunoassay. 14-day acupuncture significantly attenuates the increase of MBP. The HRV indices, the standard deviation of all normal NN intervals (SDNN), and the ratio of the low-frequency component to the high-frequency component (LF/HF) were improved following acupuncture. Renal sympathetic activation induced upregulation of epinephrine, norepinephrine, and renin content were attenuated by acupuncture. In addition, acupuncture decreased β1-AR expression and improved β2-AR expression. These results indicated that acupuncture relieves the increased MBP via the regulation of renal sympathetic activity and β-ARs.

It is widely accepted that the synaptic dysfunction and synapse loss contribute to the cognitive deficits of vascular dementia (VD) patients. We have previously reported that acupuncture improved cognitive function in rats with VD. However, the mechanisms involved in acupuncture improving cognitive ability remain to be elucidated. The present study aims to investigate the pathways and molecules involved in the neuroprotective effect of acupuncture. We assessed the effects of acupuncture on hippocampal long-term potentiation (LTP), the most prominent cellular model of memory formation. Acupuncture enhanced LTP and norepinephrine (NE) levels in the hippocampus. Inhibition of the β-adrenergic receptor (AR), but not the α-AR, was able to block the effects of acupuncture on hippocampal LTP. Furthermore, inhibition of β1-AR, not β2-AR, abolished the enhanced LTP induced by acupuncture. The expression analysis revealed a significant upregulation of β1-AR and unchanged β2-AR with acupuncture, which supported the above findings. Specifically, increased β1-ARs in the dentate gyrus were expressed on neurons exclusively. Taken together, the present data supports a beneficial role of acupuncture in synaptic plasticity challenged with VD. A likely mechanism is the increase of NE and activation of β1-AR in the hippocampus.

Immune cell infiltration in response to myocyte death regulates extracellular matrix remodeling and scar formation after myocardial infarction (MI). Caspase-recruitment domain family member 9 (CARD9) acts as an adapter that mediates the transduction of pro-inflammatory signaling cascades in innate immunity; however, its role in cardiac injury and repair post-MI remains unclear. We found that Card9 was one of the most upregulated Card genes in the ischemic myocardium of mice. CARD9 expression increased considerably 1 day post-MI and declined by day 7 post-MI. Moreover, CARD9 was mainly expressed in F4/80-positive macrophages. Card9 knockout (KO) led to left ventricular function improvement and infarct scar size reduction in mice 28 days post-MI. Additionally, Card9 KO suppressed cardiomyocyte apoptosis in the border region and attenuated matrix metalloproteinase (MMP) expression. RNA sequencing revealed that Card9 KO significantly suppressed lipocalin 2 ( Lcn2 ) expression post-MI. Both LCN2 and the receptor solute carrier family 22 member 17 (SL22A17) were detected in macrophages. Subsequently, we demonstrated that Card9 overexpression increased LCN2 expression, while Card9 KO inhibited necrotic cell-induced LCN2 upregulation in macrophages, likely through NF-κB. Lcn2 KO showed beneficial effects post-MI, and recombinant LCN2 diminished the protective effects of Card9 KO in vivo. Lcn2 KO reduced MMP9 post-MI, and Lcn2 overexpression increased Mmp9 expression in macrophages. Slc22a17 knockdown in macrophages reduced MMP9 release with recombinant LCN2 treatment. In conclusion, our results demonstrate that macrophage CARD9 mediates the deterioration of cardiac function and adverse remodeling post-MI via LCN2.