Astrocyte-derived exosomal miR-378a-5p mitigates cerebral ischemic neuroinflammation by modulating NLRP3-mediated pyroptosis.

Objective: This study aimed to investigate the regulatory role of astrocyte-derived exosomes and their microRNAs (miRNAs) in modulating neuronal pyroptosis during cerebral ischemia. Methods: Astrocyte-derived exosomes were studied for treating cerebral ischemia in both in vitro and in vivo models. The effects of astrocyte-derived exosomes on neuroinflammation were investigated by analyzing exosome uptake, nerve damage, and pyroptosis protein expression. High throughput sequencing was used to identify astrocyte-derived exosomal miRNAs linked to pyroptosis, followed by validation via qRT‒PCR. The relationship between these miRNAs and NLRP3 was studied using a dual luciferase reporter assay. This study used miR-378a-5p overexpression and knockdown to manipulate OGD injury in nerve cells. The impact of astrocyte-derived exosomal miR-378a-5p on the regulation of cerebral ischemic neuroinflammation was assessed through analysis of nerve injury and pyroptosis protein expression. Results: Our findings demonstrated that astrocyte-derived exosomes were internalized by neurons both in vitro and in vivo. Additionally, Astrocyte-derived exosomes displayed a neuroprotective effect against OGD-induced neuronal injury and brain injury in the ischemic cortical region of middle cerebral artery occlusion (MCAO) rats while also reducing pyroptosis. Further investigations revealed the involvement of astrocyte-derived exosomal miR-378a-5p in regulating pyroptosis by inhibiting NLRP3. The overexpression of miR-378a-5p mitigated neuronal damage, whereas the knockdown of miR-378a-5p increased NLRP3 expression and exacerbated pyroptosis, thus reversing this neuroprotective effect. Conclusion: Astrocyte-derived exosomal miR-378a-5p has a neuroprotective effect on cerebral ischemia by suppressing neuroinflammation associated with NLRP3-mediated pyroptosis.Further research is required to comprehensively elucidate the signaling pathways by which astrocyte-derived exosomal miR-378a-5p modulates neuronal pyroptosis.

Complex phenotype in Fanconi renotubular syndrome type 1: Hypophosphatemic rickets as the predominant presentation.

GATM-related Fanconi renotubular syndrome 1 (FRTS1) is a form of renal Fanconi syndrome (RFS), which is a disorder of solute and water reabsorption caused by defects in the function of the entire proximal tubule. Recent findings reveal the molecular basis of FRTS1: Intramitochondrial fiber aggregation triggered by mutant GATM provides a starting point for proximal tubule damage and drives disease progression. As a rare and newly recognized inherited kidney disease, the complex manifestations of FRTS1 are easily underdiagnosed or misdiagnosed. We discuss the complex phenotype of a 26-year-old woman with onset in infancy and a long history of hypophosphatemic rickets. We also identified a novel heterozygous missense variant in the GATM gene in this patient. The novel variant and phenotype we report expand the disease spectrum of FRTS1. We recommend screening for GATM in children with RFS, especially in patients with resistant rickets who have previously had negative genetic testing. In addition, we found pathological deposition of mutant GATM proteins within mitochondria in the patient's urinary sediment cells by a combination of electron microscopy and immunofluorescence. This unique urine cytology experiment has the potential to be a valuable tool for identifying patients with RRTS1.

Glycosylation in autoimmune diseases: A bibliometric and visualization study.

An increasing amount of research has shown that glycosylation plays a crucial role in autoimmune diseases (ADs), prompting our interest in conducting research on the knowledge framework and hot topics in this field based on bibliometric analysis. Studies on glycosylation in the field of ADs from 2003 to 2023 were collected by searching the Web of Science Core Collection database. Bibliometric analysis was conducted using VOSviewer, CiteSpace, and Bibliometrix software. This study included a total of 530 studies. According to the H, G, and M indices, the United States has made the most contributions worldwide, with China making significant contributions in recent years. Leiden University from the Netherlands ranks among the top institutions in terms of publication and citation rankings, with the institution's author Manfred Wuhrer contributing the most to this field. Frontiers in Immunology is the journal with the highest H-index. Research in this field has focused on antibody glycosylation, particularly the specific glycosylation of IgG and IgA, and its role in various ADs. The application of glycoengineering glycosylated proteins in the synthesis of targeted monoclonal antibodies, drug delivery, and regenerative medical materials may be a new trend in the treatment of ADs. Artificial intelligence is an emerging tool in glycobiology. This study summarizes the objective data on glycosylation in the field of AD publications in recent years, providing a reference for researchers in this field.

Glycosides of Buyang Huanwu decoction inhibits inflammation associated with cerebral ischemia-reperfusion via the PINK1/Parkin mitophagy pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: A classic stroke formula is Buyang Huanwu Decoction (BYHWD), Glycosides are the pharmacological components found in BYHWD, which are utilized for the prevention and management of cerebral ischemia-reperfusion (CIR), as demonstrated in a previous study. Its neuroprotective properties are closely related to its ability to modulate inflammation, but its mechanism is as yet unclear. AIM OF THE STUDY: A research was undertaken to investigate the impact of glycosides on the inflammation of CIR through the PTEN-induced putative kinase-1 (PINK1)/Parkin mitophagy pathway. MATERIALS AND METHODS: Analyzing glycosides containing serum components was performed with ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS). Glycosides were applied to rat of Middle cerebral artery occlusion/reperfusion (MCAO/R) model and primary neural cell of Oxygen glucose deprivation/reperfusion (OGD/R) model. The neuroprotective effect and the regulation of mitophagy of glycosides were evaluated through neural damage and PINK1/Parkin mitophagy activation. Moreover, the assessment of the relationship between glycosides regulation of mitophagy and its anti-inflammatory effects subsequent to mitophagy blockade was conducted by examining neural damage, PINK1/Parkin mitophagy activation, and levels of pyroptosis. RESULTS: (1) It was observed that the administration of glycosides resulted in a decrease in neurological function scores, a reduction in cerebral infarction volume, an increase in mitochondrial autophagosome, and the maintenance of a high expression status of light chain 3 (LC3) II/LC3Ⅰ protein. Additionally, there was a significant inhibition of p62 protein expression and an enhancement of PINK1 and Parkin protein expression. Furthermore, it was found that the effect of glycosides at a dosage of 0.128 g · kg-1 was significantly superior to that of glycosides at a dosage of 0.064 g · kg-1. Notably, the neuroprotective effect and inhibition of pyroptosis protein of glycosides at a dosage of 0.128 g · kg-1 were attenuated when mitochondrial autophagy was blocked. (2) Glycosides repaired cellular morphological damage, enhanced cell survival, and reduced Lactate dehydrogenase (LDH) leakage, with glycosides (2.36 µg·mL-1 and 4.72 µg·mL-1) neuronal protection being the strongest. Glycosides (4.72 µg·mL-1) maintained LC3II/LC3Ⅰ protein high expression state, inhibited p62 protein expression, and promoted PINK1 and Parkin protein expression, which was stronger than glycosides (2.36 µg·mL-1). The blockade of mitophagy resulted in a reduction of neuroprotection and inhibition of pyroptosis protein exerted by glycosides. CONCLUSION: Glycosides demonstrate the ability to hinder inflammation through the activation of the PINK1/Parkin mitophagy pathway, thereby leading to subsequent neuroprotective effects on CIR.

The EMT-Related Genes GALNT3 and OAS1 are Associated with Immune Cell Infiltration and Poor Prognosis in Lung Adenocarcinoma.

BACKGROUND: Lung cancer is the main cause of cancer-related death, with epithelial-mesenchymal transition (EMT) playing an important role in the development of this disease. The EMT-related genes Polypeptide N-Acetylgalactosaminyltransferase 3 (GALNT3) and 2'-5'-Oligoadenylate Synthetase 1 (OAS1) are involved in numerous tumor processes. Although these genes have been extensively studied in cancer, they have yet to be analyzed by multi-omics in lung adenocarcinoma (LUAD). METHODS: EMT-related genes were identified by R and Venn diagram. Cox regression and Kaplan-Meier analysis were performed to evaluate patient survival, and the Gene Expression Profiling Interactive Analysis (GEPIA) database was used for correlation analysis. GeneCards and R packages were used to explore gene characterization and functional annotation. The Tumor Immune Estimation Resource (TIMER), Human Protein Atlas (HPA), University of Alabama at Birmingham Cancer (UALCAN), and The Cancer Genome Atlas (TCGA) databases were used to investigate gene expression, which was then confirmed by RT-PCR. Clinicopathological analysis was carried out using the UALCAN database. Functional mechanisms and multi-omics analysis were performed using DNA Methylation Interactive Visualization Database (DNMIVD), Targetscan, TIMER, Tumor-immune System Interactions Database (TISIDB) and cBioportal. Diagnostic values were calculated using ROC curve analysis. RESULTS: A total of 320 EMT-related genes were identified in LUAD. Their characteristics were confirmed in the Database for Annotation, Visualization and Integrated Discovery (DAVID) database by the intersection of 855 and 3600 different genes from the Gene Expression Omnibus (GEO) and EMTome databases, respectively. Expression of the EMT-related genes GALNT3 and OAS1 was associated with the prognosis of LUAD patients. A positive correlation was observed between the expression of GALNT3 and OAS1, and their expression was higher in LUAD tissue than in normal lung tissue. This was confirmed using RT-PCR. Multi-omics analysis revealed that GALNT3 and OAS1 expression was associated with gene mutation and methylation, cellular immune infiltration, and several immune subtypes. A miRNA-GALNT3/OAS1 regulatory network was also found. Receiver operating characteristic (ROC) curve analysis found that GALNT3 and OAS1 expression combined had superior diagnostic value to that of each marker alone. CONCLUSIONS: GALNT3 and OAS1 expression are associated with immune cell infiltration and poor prognosis in LUAD. Their combined expression has high diagnostic value; hence, GALNT3 and OAS1 may be valuable biomarkers for the early detection of LUAD.

Effectiveness and safety of 99Tc-methylene diphosphonate as a disease-modifying anti-rheumatic drug (DMARD) in combination with conventional synthetic (cs) DMARDs in the treatment of rheumatoid arthritis: A systematic review and meta-analysis of 34 randomized controlled trials.

Background: Technetium [99Tc] methylene diphosphonate injection (99Tc-MDP) is widely used for the treatment of rheumatoid arthritis (RA), but there is still insufficient evidence for its application. Through the utilization of meta-analysis and systematic reviews, this study aimed to evaluate the effectiveness and safety of 99 TC-MDP in combination with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) for RA. Methods: This study was registered on PROSPERO in advance (CRD42021220780). A systematic search was conducted in PubMed, Embase, the Cochrane Library, and multiple international public databases from their inception to April 2023 to identify clinical randomized controlled trials exploring the use of 99Tc-MDP combined with csDMARDs in the treatment of RA. Each outcome was subjected to meta-analysis, and the quality of evidence was assessed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The American College of Rheumatology's 50 %/70 % response criteria scores (ACR50/70) scores were utilized as the primary effectiveness outcomes, and risks were measured by assessing the rates of AEs. Moreover, secondary efficacy outcomes were evaluated, including the Disease Activity Score 28 (DAS28) and bone mineral density (BMD) as joint function indicators and the erythrocyte sedimentation rate (ESR) and interleukin-17 (IL-17) as inflammatory indicators. Results: In this meta-analysis, a total of 34 studies (2296 patients) were included out of 1149 retrieved studies. The summarized results showed that the treatment group treated with the combination of 99Tc-MDP and csDMARDs had significantly higher ACR50 (RR = 1.32, 95 % CI: 1.13-1.55, P = 0.0004) and ACR70 (RR = 1.40, 95 % CI: 1.07-1.82, P = 0.01) scores than the control group receiving csDMARDs alone. In addition, the overall incidence of AEs was lower with the combination of 99Tc-MDP and csDMARDs than with csDMARDs alone (RR = 0.75, 95 % CI: 0.60-0.93, P = 0.009), but the possibility of phlebitis was higher in the treatment group (RR = 4.15, 95 % CI: 1.04-16.50, P = 0.04). In addition, the combination of 99Tc-MDP and csDMARDs had advantages over csDMARDs alone in improving DAS28 (WMD = 1.56, 95 % CI: 0.86-2.25, P < 0.0001), BMD (SMD = 1.12, 95 % CI 0.46-1.78, P = 0.0008), ESR (SMD = 0.71, 95 % CI 0.45-0.97, P < 0.00001), and IL-17 (WMD = 5.82, 95 % CI 3.86-7.77, P < 0.00001). However, the above results might have been influenced by the 99Tc-MDP dosage, csDMARD category, and treatment duration. Combining methotrexate and leflunomide, administering continuous treatment for 24 weeks, or using 3 sets of 99Tc-MDP doses (16.5 mg) may be the optimal 99Tc-MDP treatment plan for RA. Conclusion: Compared with csDMARD therapy alone, the combination therapy with 99Tc-MDP is more effective for RA patients and is associated with a lower overall incidence of adverse events, although the possibility of phlebitis was higher. However, due to the inherent limitations of the included RCTs, high-quality clinical trials are still needed to further assess the effectiveness and safety of this combination therapy.

Glycosides of Buyang Huanwu decoction inhibits pyroptosis associated with cerebral ischemia-reperfusion through Nrf2-mediated antioxidant signaling pathway both in vivo and in vitro.

BACKGROUND: Glycosides are the pharmacodynamic substances of Buyang Huanwu Decoction (BYHWD) and they exert a protective effect in the brain by inhibiting neuronal pyroptosis of cerebral ischemia-reperfusion (CIR). However, the mechanism by which glycosides regulate neuronal pyroptosis of CIR is still unclear. PURPOSE: A significant part of this study aimed to demonstrate whether glycosides have an anti-pyroptotic effect on CIR by nuclear factor erythroid 2-related factor (Nrf2)-mediated antioxidative mechanism. METHODS: Rats were used in vivo models of middle cerebral artery occlusion and reperfusion (MCAO/R). Neuroprotective effect of glycosides after Nrf2 inhibiting was observed by nerve function score, Nissl staining, Nrf2 fluorescence staining and pyroptotic proteins detection. SH-SY5Y cells were used in vitro models of oxygen-glucose deprivation/reperfusion (OGD/R). Glycosides was evaluated for their effects by measuring cell morphology, survival rate, lactate dehydrogenase (LDH) rate and expression of pyroptotic proteins. Nrf2 si-RNA 54-1 interference with lentivirus was used to create silenced Nrf2 SH-SY5Y cells (si-Nrf2-SH-SY5Y). Glycosides were evaluated on si-Con-SH-SY5Y and si-Nrf2-SH-SY5Y cells based on the expression of Nrf2 signaling pathway, pyroptotic proteins and cell damage manifestation. RESULTS: In vivo, glycosides significantly promoted the fluorescence level of nuclear Nrf2, added more Nissl bodies, reduced neurological function scores and inhibited the pyroptotic proteins level. In vitro, glycosides significantly repaired the morphological damage of cells, promoted the survival rate, reduced the LDH rate, inhibited the pyroptosis. Moreover, antioxidant activity of glycosides was enhanced via Nrf2 activation. Both Nrf2 blocking in vivo and Nrf2 silencing in vitro significantly weakened the pyroptosis inhibitory and neuroprotective effects of glycosides. CONCLUSION: These results suggested for the first time that glycosides inhibited neuronal pyroptosis by regulating the Nrf2-mediated antioxidant stress pathway, thereby exerting brain protection of CIR. As a result of this study, This study improved understanding of the pharmacodynamics and mechanism of BYHWD, as well as providing a Traditional Chinese Medicine (TCM) treatment strategy for CIR .

Effects of organic fertilizers on yield, soil physico-chemical property, soil microbial community diversity and structure of Brassica rapa var. Chinensis.

The amount of chemical fertilizer for vegetables is on the high level in China. The use of organic fertilizers to meet the nutrient requirement of crops will be an inevitable practice in sustainable agriculture. In this study, we compared the effects of pig manure fertilizer, rabbit manure fertilizer and chemical fertilizer on yield, quality of Brassica rapa var. Chinensis, soil physico-chemical properties and microbial community by using two consecutive seasons of three fertilizers in a pot experiment. The results were as follows: (1) In the first season, the fresh yield of Brassica rapa var. Chinensis applying chemical fertilizer was significantly (p ≤ 5%) higher than those of applying the pig manure and rabbit manure fertilizer, and the results were the opposite in the second season. The total soluble sugar concentration of fresh Brassica rapa var. Chinensis applying rabbit manure fertilizer was significantly (p ≤ 5%) higher than those of applying pig manure fertilizer and chemical fertilizer in the first season, and the NO3-N content of fresh Brassica rapa var. Chinensis on the contrary. (2) The organic fertilizer increased the concentration of total nitrogen, total phosphorus and organic carbon in soil in both two seasons. Rabbit manure fertilizer increased the soil pH and EC and significantly (p ≤ 5%) reduced the soil NO3-N content. (3) The pig manure and rabbit manure fertilizer significantly (p ≤ 5%) increased the diversity and abundance of soil bacterial of Brassica rapa var. Chinensis, but had no significant effect on soil fungi. Pearson correlation analysis showed that soil TN, TP, organic carbon content and EC were significantly correlated with soil bacterial α - diversity. There were significant differences (p ≤ 5%) in the bacterial community structures between three treatments in two seasons, and significant differences (p ≤ 5%) in the fungal community structures between fertilizer treatments while not between two seasons. Pig manure and rabbit manure fertilizer decreased the relative abundance of soil Acidobacteria and Crenarchaeota, rabbit manure fertilizer significantly increased the abundance of Actinobacteria in the second season. Distance-based redundancy analysis (dbRDA) showed that soil EC, TN, and organic carbon content were key physico-chemical factors in determining bacterial community structure in Brassica rapa var. Chinensis soil, and soil NO3-N, EC, SOC concentration and soil pH in the fungal community structure.

The Circadian System Is Essential for the Crosstalk of VEGF-Notch-mediated Endothelial Angiogenesis in Ischemic Stroke.

Ischemic stroke is a major public health problem worldwide. Although the circadian clock is involved in the process of ischemic stroke, the exact mechanism of the circadian clock in regulating angiogenesis after cerebral infarction remains unclear. In the present study, we determined that environmental circadian disruption (ECD) increased the stroke severity and impaired angiogenesis in the rat middle cerebral artery occlusion model, by measuring the infarct volume, neurological tests, and angiogenesis-related protein. We further report that Bmal1 plays an irreplaceable role in angiogenesis. Overexpression of Bmal1 promoted tube-forming, migration, and wound healing, and upregulated the vascular endothelial growth factor (VEGF) and Notch pathway protein levels. This promoting effect was reversed by the Notch pathway inhibitor DAPT, according to the results of angiogenesis capacity and VEGF pathway protein level. In conclusion, our study reveals the intervention of ECD in angiogenesis in ischemic stroke and further identifies the exact mechanism by which Bmal1 regulates angiogenesis through the VEGF-Notch1 pathway.

ß-Elemene enhances erlotinib sensitivity through induction of ferroptosis by upregulating lncRNA H19 in EGFR-mutant non-small cell lung cancer.

Nearly half of all Asian non-small cell lung cancer (NSCLC) patients harbour epidermal growth factor receptor (EGFR) mutations, and first-generation EGFR tyrosine kinase inhibitors (TKIs) are one of the first-line treatments that have improved the outcomes of these patients. Unfortunately, 20% of these patients can not benefit from the treatment. The basis of this primary resistance is poorly understood. Therefore, overcoming EGFR-TKI primary resistance and maintaining the efficacy of TKIs has become a key issue. ß-Elemene, a sesquiterpene compound extracted from Curcuma aromatica Salisb. (wenyujing), has shown potent antitumor effects. In this research, we found that ß-elemene combined with erlotinib enhanced the cytotoxicity of erlotinib to primary EGFR-TKI-resistant NSCLC cells with EGFR mutations and that ferroptosis was involved in the antitumor effect of the combination treatment. We found that lncRNA H19 was significantly downregulated in primary EGFR-TKI-resistant NSCLC cell lines and was upregulated by the combination treatment. Overexpression or knockdown of H19 conferred sensitivity or resistance to erlotinib, respectively, in both in vitro and in vivo studies. The high level of H19 enhanced the cytotoxicity of erlotinib by inducing ferroptosis. In conclusion, our data showed that ß-elemene combined with erlotinib could enhance sensitivity to EGFR-TKIs through induction of ferroptosis via H19 in primary EGFR-TKI-resistant lung cancer, providing a promising strategy to overcome EGFR-TKI resistance in NSCLC patients.

N6-methyladenosine-modified lncRNA and mRNA modification profiles in cerebral ischemia-reperfusion injury.

Cerebral ischemia-reperfusion injury (CIRI) is common in ischemic stroke and seriously affects the prognosis of patients. At present, N6-methyladenosine (m6A) modification of lncRNAs and mRNAs has been reported in other diseases, such as cancer, but its role in CIRI has not been clarified. In this study, we aimed to investigate the m6A lncRNA and m6A mRNA modification profiles in CIRI. First, we detected the total level of m6A and the changes in related m6A methyltransferases and demethylases in the brain tissue of rats with CIRI and then identified differentially modified lncRNAs and mRNAs in CIRI by lncRNA and mRNA epigenetic transcriptomic microarray. In addition, bioinformatics analysis was used to predict the underlying functions and related pathways of related lncRNAs and mRNAs. We found that the total m6A methylation level was significantly increased, and the expression of fat mass and obesity-associated protein (FTO) was downregulated after CIRI. In addition, a large number of m6A-modified lncRNAs and mRNAs appeared after CIRI, and these genes were mainly enriched for the Toll-like receptor signaling pathway, peroxisome proliferator-activated receptor (PPAR) signaling pathway, and mitogen-activated protein kinase (MAPK) signaling pathway. Our findings provide the basis and insights for further studies on m6A modification in CIRI.

The Synergism of Natural Compounds and Conventional Therapeutics against Colorectal Cancer Progression and Metastasis.

Cancer progression and metastases are the leading causes of poor outcomes in patients with colon cancer. Colon cancer metastasis is a multigene, multistep, multistage complex process in which target genes, microRNAs, epithelial-stromal transformation, tumour stem cells, the tumour microenvironment, and various cell signalling pathways are implicated in the progression and metastasis of colon cancer. Although conventional therapies have made significant advances in treating the progression and metastasis of colorectal cancer, they have failed to improve survival outcomes. Natural compounds may have more significant potential in preventing and treating colon cancer. Active natural compounds exert their antitumor effects by inducing tumour cell differentiation, promoting tumour cell apoptosis, inhibiting tumour vascular growth, and regulating immunity. Natural compounds, combined with conventional therapies, can target mutant genes and various cellular signalling pathways, inhibit epithelial-stromal transformation, and improve the tumour microenvironment to inhibit tumour progression and metastasis. The synergism of natural compounds and conventional therapeutics has the potential to become a promising therapy for treating colorectal cancer progression and metastases.

A Sperm Quality Detection System Based on Microfluidic Chip and Micro-Imaging System.

Sperm quality assessment is the main method to predict the reproductive ability of livestock. The detection of sperm quality of livestock is of great significance to the application of artificial insemination and in vitro fertilization. In order to comprehensively evaluate sperm quality and improve the real-time and portability of sperm quality detection, a portable microscopic imaging system based on microfluidic chip is developed in this paper. The system can realize the comprehensive evaluation of sperm quality by detecting sperm vitality and survival rate. On the hardware side, a microfluidic chip is designed, which can automatically mix samples. A set of optical system with a magnification of 400 times was developed for microscopic observation of sperm. In the aspect of software, aiming at the comprehensive evaluation of sperm quality based on OpenCV, a set of algorithms for identifying sperm motility and survival rate is proposed. The accuracy of the system in detecting sperm survival rate is 94.0%, and the error rate is 0.6%. The evaluation results of sperm motility are consistent with those of computer-aided sperm analysis (CASA). The system's identification time is 9 s. Therefore, the system is absolutely suitable for sperm quality detection.

An evidence-based evaluation of Buyang Huanwu decoction for the treatment of the sequelae of stroke: A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Buyang Huanwu decoction (BYHWD) is a famous traditional Chinese formula that has been widely prescribed for sequelae of stroke in China. However, the efficacy and safety of BYHWD in treating sequelae of stroke have never been systematically evaluated. PURPOSE: To evaluate the effectiveness and safety of BYHWD in the treatment of sequelae of stroke. STUDY DESIGN: A Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-compliant systematic review and meta-analysis of randomized clinical trials (RCTs). MATERIALS AND METHODS: A systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. Five common electronic databases were searched for relevant RCTs from their inception until May 20, 2022. The Cochrane risk-of-bias tool was used to evaluate the methodological quality and the risk of bias of the included RCTs. Review Manager 5.4 was used to analyse all the data obtained. The clinical effective rate (CER) was the primary outcome, and National Institutes of Health Stroke Scale (NIHSS) and Fugl-Meyer Assessment (FMA) scores were the secondary outcomes. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system was used to evaluate the quality of evidence for each outcome. RESULTS: Thirty-two clinical studies that recruited 2,527 eligible patients were included in this meta-analysis. The results of the meta-analysis suggested that compared with conventional treatment alone, the addition of BYHWD significantly improved the CER (RR = 1.24, 95% CI: 1.20-1.29, p < 0.00001), decreased the NIHSS score (MD = -5.42, 95% CI: -5.87-4.97, p < 0.00001), and increased the FMA score (MD = 17.28, 95% CI: 15.12-19.45, p < 0.00001). There were no reported adverse events in the included studies. Most results were robust, and the quality of evidence was moderate. CONCLUSION: Our study is the first meta-analysis of RCTs evaluating the effects of BYHWD on sequelae of stroke. The addition of BYHWD to conventional treatment for sequelae of stroke significantly improved the CER and promoted neurological rehabilitation in patients, and there were no reported adverse events associated with this combination therapy. The findings of our study support the use of BYHWD as an adjunct treatment to conventional treatment in this clinical population. However, due to the limitations of the included clinical trials, high-quality clinical trials with longer follow-ups are needed to assess the long-term effectiveness and safety of BYHWD for treating the sequelae of stroke.

Expression of sphingosine-1-phosphate receptor 2 is correlated with migration and invasion of human colon cancer cells: A preliminary clinical study.

Sphingosine-1-phosphate (S1P) is a bioactive phospholipid that serves as a potent mediator of cell proliferation, differentiation and apoptosis by binding to S1P receptors (S1PRs). S1P signalling is involved in the pathogenesis of numerous types of disease, including cancer. To the best of our knowledge, however, little is known about the expression patterns of S1PRs and their role in human colorectal cancer (CRC) cell migration and invasion. The aim of the present study was to investigate the role of S1P signalling in the metastasis of colon cancer cells and the expression of S1PRs in patients with CRC. The protein and mRNA expression levels of S1PRs and sphingosine kinases (SPHKs) in 55 patients with CRC were detected by western blotting (WB), immunohistochemical (IHC) analysis and reverse transcription-quantitative PCR. The levels of S1P in serum from patients and healthy individuals were quantified by ELISA. S1PRs antagonists JTE013, FTY720 and S1PR2-small interfering (si)RNA were used to determine the role of S1PR2 in human CRC LOVO and SW480 cell lines. Migration and invasion assays were performed for functional analysis. The levels of S1P in serum were significantly increased in patients with CRC compared with healthy individuals. The relative mRNA expression levels of S1PR2 were significantly downregulated in tumour compared with normal tissue, whereas S1PR1 and SPHK1 were upregulated. WB showed that 58% (32/55 cases) of patients presented downregulated S1PR2 protein expression. IHC analysis indicated that expression of S1PR2 was lower in tumour than in normal tissue in 65.5% (36/55 cases) of patients. Exogenous addition of S1P promoted migration and invasion in the different cell types. S1P stimulated the migration and invasion of SW480 cells. The inhibition of S1PR2 by JTE013 or S1PR2-siRNA significantly promoted the migration and invasion of SW480 cells, while FTY720 reversed these effects. The present study indicated that expression levels of S1PRs, particularly S1PR2, were associated with migration and invasion of CRC cells. The present findings revealed a novel mechanism by which S1P inhibited tumour cell migration and invasion via a S1PR2-dependent pathway, suggesting that S1PR2 may be a therapeutic target for treatment of colon cancer.

The effects of light colour on female rabbit reproductive performance and the expression of key genes in follicular development.

The purpose of this study was to analyse the effects of light colour on rabbit reproductive performance and the expression of key follicular development genes. Rabbits (n = 1,068, 5 months old, 3.6-4.4 kg live body weight) were divided randomly into four groups, housed individually in wire mesh cages and exposed to red, green, blue, and white light-emitting diode (LED) light (control). The lighting schedule was 16 L : 8 D-15 d / 150 lx / 6:00 am-22:00 pm (3 d preartificial insemination to 12 d postartificial insemination). Red light and white light affected the conception rate and kindling rate and increased the total litter size at birth (p < 0.05). The effects of red light on litter size at weaning, litter weight at weaning, and individual weight at weaning increased compared with the green and blue groups. The effects of red light on live litter size at birth were increased compared with those in the blue group (p < 0.05). Compared to white light, green and blue light reduced the number of secondary follicles (p < 0.05). Compared to red light, green and blue light reduced the number of tertiary follicles (p < 0.05). Compared with white light, red LED light resulted in greater ovarian follicle stimulating hormone receptor and luteinizing hormone receptor mRNA expression (p < 0.05). Compared with green and blue LED light, red LED light resulted in greater B-cell lymphom-2 mRNA expression (p < 0.05). Compared with green LED light, red LED light inhibited FOXO1 mRNA expression in rabbit ovaries (p < 0.05). Red light can affect the reproductive performance of female rabbits and the expression of key genes for follicular development.

Impact of Video Technology on the Comprehension of Patients With First Insulin Injection and the Efficiency of Nurse Education.

This study aims to compare the effectiveness of video and paper materials used for teach-back education on the first insulin injection for patients with diabetes. The study enrolled 110 patients hospitalized for diabetes who had received education on their first insulin injection in the endocrinology department. The patients were divided into an intervention group (n = 55) and a control group (n = 55) using convenience sampling. Video materials were employed for the teach-back education of the intervention group, while paper materials were employed for the teach-back education of the control group. We compared cases who answered correctly to the common parts (selection and management of injection devices, selection and rotation of injection sites, proper use of injection angles and pinching, insulin storage, injection-related complications and their prevention, selection of the correct needle length, and safe disposal of needles after use) for the first time, the number of educational sessions and total education duration between the two groups and employed the "My View on Insulin" questionnaire to survey the two groups before and 28 days after the intervention. The intervention group had a shorter total education duration than the control group, a difference that was statistically significant (p < .001). The intervention group had more advantages over the control group in terms of rotation education at the injection site (p < .05). There was no statistically significant difference in the questionnaire scores between the two groups after the intervention (p > .05); however, both groups scored significantly higher than before the intervention, a difference that was statistically significant (p < .001). The teach-back method combined with video materials applied for educating patients on their first insulin injection could reduce the education duration by healthcare providers and improve the patients' psychological insulin resistance. The key to successfully teaching patients to self-administer insulin, and allowing them to master the steps involved, is to focus on "why" rather than "what" to do.

ß-elemene enhances the antitumor activity of erlotinib by inducing apoptosis through AMPK and MAPK pathways in TKI-resistant H1975 lung cancer cells.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) significantly improve the outcome of non-small-cell lung cancer (NSCLC) patients with EGFR mutations, however, most TKI-treated patients will develop resistance to TKIs. ß-elemene, extracted from Curcuma aromatica Salisb., has been widely used to treat various malignant tumors, including TKI-resistant NSCLC, but, the effects and the molecular mechanisms remain unclear. In this study, the NCI-H1975 cell line harboring double mutations L858R/T790M was treated with varying concentrations of ß-elemene and/or erlotinib. The effects of ß-elemene on cell proliferation, migration, apoptosis, and the expression of relevant proteins of NCI-H1975 cells were evaluated. The results revealed that ß­elemene significantly inhibited the growth, colony formation capacity, wound healing ability of NCI-H1975 cells, and improved the sensitivity of NCI-H1975 cells to erlotinib. Compared with erlotinib alone, ß-elemene plus erlotinib significantly promoted the apoptosis of NCI-H1975 cells, accompanied by the down-regulated expression of P-mTOR, P-EGFR, CHOP proteins and up-regulated expression of P-AMPKα and Bax proteins. Taken together, these findings demonstrate that ß-elemene suppresses the proliferation and migration of TKI-resistant H1975 cells, and enhances the antitumor activity of erlotinib by inducing apoptosis through AMPK and MAPK pathways in TKI-resistant H1975 lung cancer cells, indicating that ß-elemene is a promising anti-cancer therapeutic candidate for TKI-resistant NSCLC.

DeSiphering receptor core-induced and ligand-dependent conformational changes in arrestin via genetic encoded trimethylsilyl 1H-NMR probe.

Characterization of the dynamic conformational changes in membrane protein signaling complexes by nuclear magnetic resonance (NMR) spectroscopy remains challenging. Here we report the site-specific incorporation of 4-trimethylsilyl phenylalanine (TMSiPhe) into proteins, through genetic code expansion. Crystallographic analysis revealed structural changes that reshaped the TMSiPhe-specific amino-acyl tRNA synthetase active site to selectively accommodate the trimethylsilyl (TMSi) group. The unique up-field 1H-NMR chemical shift and the highly efficient incorporation of TMSiPhe enabled the characterization of multiple conformational states of a phospho-ß2 adrenergic receptor/ß-arrestin-1(ß-arr1) membrane protein signaling complex, using only 5 µM protein and 20 min of spectrum accumulation time. We further showed that extracellular ligands induced conformational changes located in the polar core or ERK interaction site of ß-arr1 via direct receptor transmembrane core interactions. These observations provided direct delineation and key mechanism insights that multiple receptor ligands were able to induce distinct functionally relevant conformational changes of arrestin.