Single-cell sequencing analysis reveals the dynamic tumour ecosystems of primary and metastatic lymph nodes in nasopharyngeal carcinoma.

Lymph node metastasis contributed to the leading cause and treatment failure in nasopharyngeal carcinoma (NPC). The microenvironment and the cellular communications of lymph node metastasized tumours determine the tumour progression and therapeutic effect, but the ecosystems about the lymph node metastasis (LNM) for NPC patients remain poorly characterized. Here, we integrated the transcriptomes of 47,618 single cells from eight samples related to NPC LNM. The dynamic immune ecosystems and immunosuppressive microenvironment including T cells, myeloid cells and B cells were observed in the lymph node metastatic samples compared with primary tumours. Additionally, the heterogeneity of epithelial cells was also revealed, and several clusters with expression programs that were associated with the progression-free survival of NPC patients were identified. Additionally, our data revealed the complex intercellular communications from primary to lymph node metastasis. The rewiring of CCL signalling which plays an important role in tumour metastasis was further identified. Altogether, we systematically characterized the ecosystem of NPC primary and lymph node metastasized tumours, which may shed light on the development of a therapeutic strategy to improve clinical outcomes of NPC patients with lymph node metastasis.

In Situ Pipe Prover Volume Measurement Method.

To improve the accuracy of in situ measurement of the standard volumes of pipe provers and to shorten the traceability chain, a new method of in situ pipe prover volume measurement was developed alongside a supporting measurement device. This method is based on the geometric dimension approach, which measures the inner diameter and length of a pipe prover to calculate its volume. For inner diameter measurement, a three-probe inner-diameter algorithm model was established. This model was calibrated using a standard ring gauge of Φ313 mm, with the parameters calculated through fitting. Another standard ring gauge of Φ320 mm was used to verify the inner diameters determined by the algorithmic model. A laser interferometer was employed for the segmented measurement of the pipe prover length. The comprehensive measurement system was then used for in situ measurement of the standard pipe prover. The newly developed system achieved an expanded uncertainty of 0.012% (k = 2) in volume measurement, with the deviation between the measured and nominal pipe prover volumes being merely 0.007%. These results demonstrate that the proposed in situ measurement method offers ultra-high-precision measurement capabilities.

Atractylenolide-III alleviates osteoarthritis and chondrocyte senescence by targeting NF-κB signaling.

Atractylenolide-III (AT-III) is well known as its role in antioxidant and anti-inflammatory. Present study was aimed to figure out its effects on osteoarthritis and potential mechanisms. Rat model, human osteoarthritis cartilage explants as well as rat/human chondrocyte cultures were prepared to test AT-III's effects on osteoarthritis progression and chondrocyte senescence. Potential targeted molecules of AT-III were predicted using network pharmacology and molecular docking, assessed by Western blotting and then verified with rescue experiments. AT-III treatment alleviated osteoarthritis severity (shown by OARSI grading score and micro-CT) and chondrocyte senescence (indexed by levels of SA-ß-gal, P16, P53, MMP13, ROS and ratio of healthy/collapsed mitochondrial membrane potentials). Network pharmacology and molecular docking suggested that AT-III might play role through NF-κB pathway. Further experiments revealed that AT-III reduced phosphorylation of IKKα/ß, IκBα and P65 in NF-κB pathway. As well as nuclear translocation of p65. Both in vivo and in vitro experiments indicated that AT-III's effects on osteoarthritis and anti-senescence were reversed by an NF-κB agonist. AT-III could alleviate osteoarthritis by inhibiting chondrocyte senescence through NF-κB pathway, which indicated that AT-III is a prospective drug for osteoarthritis treatment.

Cyclo-(Phe-Tyr) as a novel cyclic dipeptide compound alleviates ischemic/reperfusion brain injury via JUNB/JNK/NF-κB and SOX5/PI3K/AKT pathways.

Ischemic/reperfusion (IR) can cause adverse reactions including apoptosis, oxidative stress, and inflammation, but the existing therapeutic strategies have been limited. Moreover, the regulation of microglia plays an important role in brain injury after reperfusion. Hence, it is imperative to find new and effective drugs for modulating microglia to treat IR brain injury. Cyclic peptide compound cyclo-(Phe-Tyr) (Sparganin C, SC) is a compound isolated from Sparganii Rhizoma. However, the protective effects of SC on the central nervous system are rather unclear. In an attempt to elucidate the protective effects and mechanism of SC on cerebral damage induced by the IR, we used a middle cerebral artery occlusion reperfusion (MCAO/R) model in rats and discovered that SC significantly decreased the size of cerebral infarcts, improved neurological scores, and blocked inflammatory and oxidative factor release. Using RNA-Seq and metabolomics association analyses, SC was shown to have a protective impact through the JUNB and SOX5-related pathways. Metabolomic analysis revealed twenty-eight differentially expressed biomarkers. In addition, the detection of SC content in brain tissue using LC/MS revealed that SC had blood-brain barrier penetration. To investigate the mechanism, we established an in vitro BV2 cell oxygen-glucose deprivation/reperfusion (OGD/R) model and used siRNA as well as an inhibitor. The protective effects of SC were dependent on the JUNB and SOX5 to inhibit inflammation and apoptosis in microglia. Our findings revealed for the first that SC against IR injury by reducing inflammation and apoptosis while simultaneously acting as potential therapeutic lead compound for ischemic stroke.

Recent advances in the treatment of renal stones using flexible ureteroscopys.

Upper urinary tract stones are a common urological disease that can be treated by flexible ureteroscopy (FURS) through the natural urinary tract, in addition to extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy. The advantages of FURS are less trauma, faster recovery, and fewer complications, while its disadvantages include poor results of lithotripsy and stone extraction when dealing with larger stones, and prolonged operation time. Over the last two decades, the emergence of new technologies such as FURS combined with negative pressure suction, robot-assisted FURS, and artificially intelligent FURS, coupled with improvements in laser technology (the use of thulium fiber lasers and the invention of single-use flexible ureteroscopes (su-fURS) suitable for primary level application, have significantly increased the global adoption of FURS. This surge in usage holds a promising future in clinical application, benefiting a growing number of patients with renal calculi. Accompanied by changes in technical concepts and therapeutic modalities, the scope of indications for FURS is broadening, positioning it as a potential primary choice for urolithiasis treatment in the future. This review outlines the progress in employing FURS for the treatment of renal calculi in order to generate insights for further research.

Network analysis of microbiome and metabolome to explore the mechanism of raw rhubarb in the protection against ischemic stroke via microbiota-gut-brain axis.

Ischemic stroke (IS) has attracted worldwide attention due to the high mortality and disability rate. Raw rhubarb (RR) is a traditional medicinal plant and whole-food that has been used in China for its various pharmacological activities, such as antioxidant and anti-inflammatory properties. Recent pharmacological research has shown the role of RR against IS, but its mechanism of action remains unclear, particularly in the context of the brain-gut axis. To address this gap in knowledge, the present study was conducted in the middle cerebral artery occlusion/reperfusion (MCAO/R) model with the aim of investigating the effects of RR on regulating the intestinal microbiota barrier and metabolism and thereby reducing inflammatory response so as to improve the IS. The results showed that pre-treatment of RR attenuated cerebral infarct area and inflammation response in MCAO rats. Furthermore, RR also improved intestinal barrier function, including the integrity and permeability of the intestinal barrier. Additionally, RR intervention significantly attenuated gut microbiota dysbiosis caused by ischemic stroke, especially the increased Firmicutes. Notably, the pseudo-germ-free (PGF) rats further demonstrated that the anti-stroke effect of RR might rely on intestinal microbiota. In addition, the UPLC/Q-Orbitrap-MS-Based metabolomics revealed the disrupted metabolic profiles caused by MCAO/R, and a total of 11 differential metabolites were modulated by RR administration, especially bile acids. Further correlation analysis and network pharmacology analysis also demonstrated a strong association between specific bacteria, such as Firmicutes and bile acids. In conclusion, our work demonstrated that RR could effectively ameliorate ischemic stroke by modulating the microbiota and metabolic disorders.

Mapping enhancer and chromatin accessibility landscapes charts the regulatory network of Alzheimer's disease.

BACKGROUND: Enhancers are regulatory elements that target and modulate gene expression and play a role in human health and disease. However, the roles of enhancer regulatory circuit abnormalities driven by epigenetic alterations in Alzheimer's disease (AD) are unclear. METHODS: In this study, a multiomic integrative analysis was performed to map enhancer and chromatin accessibility landscapes and identify regulatory network abnormalities in AD. We identified differentially methylated enhancers and constructed regulatory networks across brain regions using AD brain tissue samples. Through the integration of snATAC-seq and snRNA-seq datasets, we mapped enhancers with DNA methylation alterations (DMA) and chromatin accessibility landscapes. Core regulatory triplets that contributed to AD neuropathology in specific cell types were further prioritized. RESULTS: We revealed widespread DNA methylation alterations (DMA) in the enhancers of AD patients across different brain regions. In addition, the genome-wide transcription factor (TF) binding profiles showed that enhancers with DMA are pervasively regulated by TFs. The TF-enhancer-gene regulatory network analysis identified core regulatory triplets that are associated with brain and immune cell proportions and play important roles in AD pathogenesis. Enhancer regulatory circuits with DMA exhibited distinct chromatin accessibility patterns, which were further characterized at single-cell resolutions. CONCLUSIONS: Our study comprehensively investigated DNA methylation-mediated regulatory circuit abnormalities and provided novel insights into the potential pathogenesis of AD.

Activation of the hypoxia response in the aging cerebrovasculature protects males against cognitive impairment.

Alzheimer's disease (AD) is a neurodegenerative disorder with a distinct sex bias. Age-related vascular alterations, a hallmark of AD onset and progression, are consistently associated with sexual dimorphism. Here, we conducted an integrative meta-analysis of 335,803 single-nucleus transcriptomes and 667 bulk transcriptomes from the vascular system in AD and normal aging to address the underlying sex-dependent vascular aging in AD. All vascular cell types in male AD patients exhibited an activated hypoxia response and downstream signaling pathways including angiogenesis. The female AD vasculature is characterized by increased antigen presentation and decreased angiogenesis. We further confirmed that these sex-biased alterations in the cerebral vascular emerged and were primarily determined in the early stages of AD. Sex-stratified analysis of normal vascular aging revealed that angiogenesis and various stress-response genes were downregulated concurrently with female aging. Conversely, the hypoxia response increased steadily in males upon aging. An investigation of upstream driver transcription factors (TFs) revealed that altered communication between estrogen receptor alpha (ESR1) and hypoxia induced factors during menopause contributes to the inhibition of angiogenesis during normal female vascular aging. Additionally, inhibition of CREB1, a TF that targets estrogen, is also related to female AD. Overall, our study revealed a distinct cerebral vascular profile in females and males, and revealed novel targets for precision medicine therapy for AD.

Development of an m6A-Related lncRNAs Signature Predicts Tumor Stemness and Prognosis for Low-Grade Glioma Patients.

Background: Growing evidence has revealed that m6A modification of long noncoding RNAs (lncRNAs) dynamically controls tumor stemness and tumorigenesis-related processes. However, the prognostic significance of m6A-related lncRNAs and their associations with stemness in low-grade glioma (LGG) remain to be clarified. Methods: A multicenter transcriptome analysis of lncRNA expression in 1,247 LGG samples was performed in this study. The stemness landscape of LGG tumors was presented and associations with clinical features were revealed. The m6A-related lncRNAs were identified between stemness groups and were further prioritized via least absolute shrinkage and selection operator Cox regression analysis. A risk score model based on m6A-related lncRNAs was constructed and validated in external LGG datasets. Results: Based on the expression of LINC02984, PFKP-DT, and CRNDE, a risk model and nomogram were constructed; they successfully predicted the survival of patients and were extended to external datasets. Significant correlations were observed between the risk score and tumor stemness. Moreover, patients in different risk groups exhibited distinct tumor immune microenvironments and immune signatures. We finally provided several potential compounds suitable for specific risk groups, which may aid in LGG treatment. Conclusions: This novel signature presents noteworthy value in the prediction of prognosis and stemness status for LGG patients and will foster future research on the development of clinical regimens.

Investigation of factors influencing abnormal pulmonary ventilation function in occupational exposed populations and the establishment of a risk prediction model.

The purpose of this study is to investigate the influencing factors of abnormal pulmonary ventilation function in occupational exposed populations and to establish a risk prediction model. The findings will provide a basis for formulating corresponding strategies for the prevention and treatment of occupational diseases. The study focused on workers who underwent occupational health examinations in the year 2020. Statistical analysis was conducted using methods such as t-tests, chi-square tests, and multiple logistic regression analysis. Additionally, machine learning methods were employed to establish multiple models to address classification problems. Among the 7472 workers who participated in the occupational health examination, 1681 cases of abnormal pulmonary ventilation function were detected, resulting in a detection rate of 22.6%. Based on the analysis of occupational hazard data, a risk prediction model was established. Age, work tenure, type of the employing enterprise, and type of dust exposure are all identified as driving factors for abnormal pulmonary function. These factors were used as predictive variables for establishing the risk prediction model. Among the various models evaluated, the logistic regression model was found to be the optimal model for predicting abnormal pulmonary ventilation function.

MicroRNA-301a knockout attenuates peripheral nerve regeneration by delaying Wallerian degeneration.

Our recent study demonstrated that knockout of microRNA-301a attenuates migration and phagocytosis in macrophages. Considering that macrophages and Schwann cells synergistically clear the debris of degraded axons and myelin during Wallerian degeneration, which is a prerequisite for nerve regeneration, we hypothesized that microRNA-301a regulates Wallerian degeneration and nerve regeneration via impacts on Schwann cell migration and phagocytosis. Herein, we found low expression of microRNA-301a in intact sciatic nerves, with no impact of the microRNA-301a knockout on nerve structure and function. By contrast, we found significant upregulation of microRNA- 301a in injured sciatic nerves. We established a sciatic nerve crush model in microRNA-301a knockout mice, which exhibited attenuated morphological and functional regeneration following sciatic nerve crush injury. The microRNA-301a knockout also led to significantly inhibited Wallerian degeneration in an in vivo sciatic nerve-transection model and in an in vitro nerve explant block model. Schwann cells with the microRNA-301a knockout showed inhibition of phagocytosis and migration, which was reversible under transfection with microRNA-301a mimics. Rescue experiments involving transfection of microRNA-301a-knockout Schwann cells with microRNA-301a mimics or treatment with the C-X-C motif receptor 4 inhibitor WZ811 indicated the mechanistic involvement of the Yin Yang 1/C-X-C motif receptor 4 pathway in the role of microRNA-301a. Combined with our previous findings in macrophages, we conclude that microRNA-301a plays a key role in peripheral nerve injury and repair by regulating the migratory and phagocytic capabilities of Schwann cells and macrophages via the Yin Yang 1/C-X-C motif receptor 4 pathway.

Spatio-Temporal Changes in Land Use and Habitat Quality of Hobq Desert along the Yellow River Section.

As a key area in the Yellow River basin for sand control and management, the land change process in the Hobq Desert plays a crucial role in keeping the river and desert ecosystems and promoting the construction of ecological civilization in human systems. Based on multi-temporal remote sensing from 1991 to 2019 in the Hobq Desert along the Yellow River section, this study selected spatial statistical methods (land-use monitoring and landscape metrics) to examine land-use change dynamics. Then, we evaluated habitat quality using the InVEST model and quantitatively analyzed the factors causing spatial changes in habitat quality using geographic detectors. Finally, this paper predicted the pattern of land use and habitat quality in 2030 using the PLUS model. The results reveal that (1) from 1991 to 2019, the total area of forest grassland increased by 3572.5 km2, providing the most vegetation cover, and the sandy land and water area decreased continuously, while the cultivated land and construction land increased. There were 38.01% conversions of land types, with the land-use dynamic decreasing the greatest in sandy land (-12.66%) and increasing the greatest in construction land (9.26%); the comprehensive land-use dynamics were the highest in 2010-2019 (1.68%), which was the most active stage during our study period. (2) Both of the landscape indices NP and PD showed "N" type fluctuations during 1991-2019, and CONTAG and LSI rose from 69.19% to 70.29% and 36.01% to 38.89%, respectively, indicating that the land-use degree of landscape fragmentation increased, landscape connectivity turned better, and landscape dominance was enhanced, balanced, and developed evenly in overall landscape type. (3) From the overall region analysis, the average habitat quality in 1991, 2000, 2010, and 2019 was 0.3565, 0.5108, 0.5879, and 0.6482, respectively, with the overall habitat value showing a gradually increasing trend. Spatially, the habitat quality along the Yellow River section of the Hobq Desert has a certain regularity, and the overall pattern there is high in the south and low in the north, high in the east and west, and low in the middle. (4) The change in land use between 2019 and 2030 is similar to the previous period, but the change rate is generally lower. The habitat quality improved significantly, with the growth of high and medium habitat quality.

A CaCO3-based nanoplatform with sonodynamic and tumor microenvironment activated for combined in vitro cancer therapy.

INTRODUCTION: Sonodynamic therapy (SDT) has potential clinical applications for cancer therapy, and is yet restricted by complex tumor microenvironmental (TME) factors. Thus, the research problem of TME modulation as well as efficient tumor treatment still needs to be clarified. METHOD: In this study, a calcium carbonate (CaCO3) nanoplatform was designed for ultrasound (US) and TME response-triggered, which encapsulated Ag2S and loaded with l-Arg, and further wrapped with RBC/Platelet membrane, named as QD@Ca/ML-Arg. RESULTS: Non-invasive US-triggered SDT by Ag2S and acidic environment-responsive drug release were achieved. In vitro experiments validated the efficacy of SDT, Ca-ion interference and nitric oxide (NO) gas therapy as combined therapy for cancer treatment. By means of RNA sequencing, the cancer therapeutic mechanism of SDT in redox-related pathways was elucidated. The immunosuppressive TME was simulated with a M2-macrophage/cancer cell co-culture system to confirm the immune activating effect of immunogenic cell death (ICD). CONCLUSION: Accordingly, the potential of QD@Ca/ML-Arg-was demonstrated for in vitro TME modulation, cancer therapeutic efficacy and clinical translation.

Identification and functional analysis of N6-methyladenine (m6 A)-related lncRNA across 33 cancer types.

BACKGROUND: N6-methyladenosine (m6 A) plays an essential role in tumorigenesis and cancer progression. Long noncoding RNAs (lncRNAs) are discovered to be important targets of m6 A modification, and they play fundamental roles in diverse biological processes. However, there is still a lack of knowledge with regards to the association between m6 A and lncRNAs in human tumors. METHODS: The relationship between lncRNAs and 21 m6 A regulators was comprehensively explored, through the integration of multi-omics data from M6A2Target, m6A-Atlas, and TCGA (The Cancer Genome Atlas). In order to explore the potential roles of m6A-related lncRNAs in human tumors, three applicable methods were introduced, which include the construction of ceRNA networks, drug sensitivity estimation, and survival analysis. RESULTS: A substantial number of positive correlation events across 33 cancer types were found. Moreover, cancer-specific lncRNAs were associated with tissue specificity, and cancer-common lncRNAs were conserved in cancer-related biological function. In particular, the m6 A-related lncRNA FGD5-AS1 was found to be associated with cancer treatment, through its influence on cisplatin resistance in breast cancer patients. Finally, a user-friendly interface Lnc2m6A, which is enriched with various browsing sections resource for the exhibition of relationships and putative biogenesis between lncRNAs and m6 A modifications, is offered in http://hainmu-biobigdata.com/Lnc2m6A. CONCLUSIONS: In summary, the results from this paper will provide a valuable resource that guides both mechanistic and therapeutic roles of m6 A-related lncRNAs in human tumors.

SATB1/SLC7A11/HO-1 Axis Ameliorates Ferroptosis in Neuron Cells After Ischemic Stroke by Danhong Injection.

Neuronal damage after ischemic stroke (IS) is frequently due to ferroptosis, contributing significantly to ischemic injury. However, the mechanism against ferroptosis in IS remained unclear. The aim of this study was to investigate the potential mechanism of Danhong injection (DHI) and the critical transcription factor SATB1 in preventing neuronal ferroptosis after ischemic stroke in vivo and in vitro. The results showed that DHI treatment significantly reduced the infarct area and associated damage in the brains of the pMCAO mice, and enhanced the viability of OGD-injured neurons. And several characteristic indicators of ferroptosis, such as mitochondrial necrosis and iron accumulation, were regulated by DHI after IS. Importantly, we found that the expression and activity of SATB1 were decreased in the pMCAO mice, especially in neuron cells. Meanwhile, the SATB1/SLC7A11/HO-1 signaling pathway was activated after DHI treatment in ischemic stroke and was found to improve neuronal ferroptosis. Inhibition of SATB1 significantly reduced SLC7A11-HO-1 and significantly attenuated the anti-ferroptosis effects of DHI in the OGD model. These findings indicate that neuronal ferroptosis after IS can be alleviated by DHI through SATB1/SLC7A11/HO-1 pathway, and SATB1 may be an attractive therapeutic target for treating ischemic stroke.

Pan-cancer analyses reveal multi-omic signatures and clinical implementations of the forkhead-box gene family.

BACKGROUND: Forkhead box (FOX) proteins belong to one of the largest transcription factor families and play crucial roles in the initiation and progression of cancer. Prior research has linked several FOX genes, such as FOXA1 and FOXM1, to the crucial process of carcinogenesis. However, the overall picture of FOX gene family across human cancers is far from clear. METHODS: To investigate the broad molecular signatures of the FOX gene family, we conducted study on multi-omics data (including genomics, epigenomics and transcriptomics) from over 11,000 patients with 33 different types of human cancers. RESULTS: Pan-cancer analysis reveals that FOX gene mutations were found in 17.4% of tumor patients with a substantial cancer type-dependent pattern. Additionally, high expression heterogeneity of FOX genes across cancer types was discovered, which can be partially attributed to the genomic or epigenomic alteration. Co-expression network analysis reveals that FOX genes may exert functions by regulating the expression of both their own and target genes. For a clinical standpoint, we provided 103 FOX gene-drug target-drug predictions and found FOX gene expression have potential survival predictive value. All of the results have been included in the FOX2Cancer database, which is freely accessible at http://hainmu-biobigdata.com/FOX2Cancer. CONCLUSION: Our findings may provide a better understanding of roles FOX genes played in the development of tumors, and help to offer new avenues for uncovering tumorigenesis and unprecedented therapeutic targets.

Integrated 16S rRNA gene sequencing and LC/MS-based metabolomics ascertained synergistic influences of the combination of acupuncture and NaoMaiTong on ischemic stroke.

ETHNOPHARMACOLOGICAL RELEVANCE: Acupuncture is an effective therapy for ischemic stroke, which has been widely used in China and gradually accepted in more countries and regions recently. In addition, Chinese medicine also plays an important role in stroke treatment, among which NaoMaiTong (NMT) is an example of an effective herbal formula for the treatment of stroke. A therapeutic strategy that combines acupuncture and medicine was widely used in stroke patients. However, the synergistic influences and mechanisms of combined acupuncture and medicine on ischemic stroke have not yet been entirely elucidated. AIM OF THIS STUDY: The purpose of this study is to explore whether acupuncture and medicine combination treatments can produce synergism by using NMT, a clinically effective Chinese medicinal formula for the treatment of ischemic stroke for decades and has been demonstrated to be effective against ischemic brain injury, as a probe. Meanwhile, the potential mechanisms were investigated via cecal microbiome and plasma metabolomics to provide more strategies and basis for acupuncture-medicine combination for stroke. MATERIALS AND METHODS: Adopted middle-cerebral artery occlusion/reperfusion (MCAO/R) rat models, the effect for the stroke of the combination treatment consisting of acupuncture and NMT was evaluated by detecting neurological issues, cerebral infarct dimensions, levels of inflammatory factors (IL-6, IL-1ß, TNF-α) and oxidative stress factors (SOD, MDA) and brain-derived neurotrophic factor (BDNF). Subsequently,16S rRNA gene sequencing and LC/MS-based metabolomic analysis were utilized to explore the characteristics of cecal-contents microecology and plasma metabolic profile, respectively. Finally, the correlation between intestinal microecological characteristics and plasma metabolic characteristics was analyzed to explore the potential mechanism of the acupuncture-NMT combination. RESULTS: The efficacy of acupuncture-NMT therapy was more effective than a single treatment on ischemic stroke, with more effectively reduced infarct sizes, improved neurobehavioral deficits, and alleviated oxidative stress and inflammatory responses. Besides, the combination therapy not only adjusted gut microbiota disturbances by enriching species diversity, reducing the abundance of pathogenic bacteria (such as Escherichia-Shaigella), as well as increasing the abundance of beneficial bacteria (such as Turicibacter, Bifidobacterium), but also improved metabolic disorders by reversing metabolite plasma levels to normality. The results of the correlation analysis demonstrated a significant association between intestinal microbiota and plasma metabolic profile, especially the strong correlation of Turicibacter and isoflavones phyto-estrogens metabolites. CONCLUSION: The combination of acupuncture and NMT could produce synergism, suggesting acupuncture-medicine combination therapy might be more conducive to the recovery of ischemic stroke. And the potential mechanism was probably related to the mediation of intestinal microecology and plasma metabolism. Turicibacter and isoflavones phyto-estrogens metabolites might be the targets for acupuncture-NMT combination for stroke. Our current findings could provide a potential therapeutic strategy against ischemic stroke.

Cyclo-(Phe-Tyr) reduces cerebral ischemia/reperfusion-induced blood-brain barrier dysfunction through regulation of autophagy.

Cerebral ischemia/reperfusion (I/R) injury is the result of ischemic stroke, a serious threat to public health. I/R injury can damage the blood-brain barrier (BBB), adversely affecting the brain environment and aggravating the injury. Cyclo-(Phe-Tyr) (sparganin C, SC) is a small molecule derived from the Chinese yam Dioscorea opposita Thunb. or Sparganii rhizoma. In our previous study, SC mitigates I/R injury both in vivo and in vitro through the action of JUNB and SOX5. However, the exact pharmacological effects of SC on BBB protection after an I/R injury remain unclear. We constructed a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R) injury to evaluate the therapeutic actions of SC, and the integrity of the BBB was evaluated by ELISA, western blotting, and Evans blue staining. It was found that SC significantly reduced the amount of Evans blue staining in the brain, inhibited the expression of inflammatory factors IL-6, IL-1ß, IL-17, IL-23, and TNF-α as well as TIPM1/MMP proteins, and promoted the expression of the tight junction proteins occludin, ZO-1, and claudin-5. SC was found to inhibit the excess autophagy induced by I/R injury to protect BBB integrity through the PI3K/AKT/mTOR pathway, and the PI3K inhibitor LY294002 significantly reduced the SC-mediated protection. Overall, this is the first demonstration of the alleviation of BBB damage caused by I/R injury by SC and suggests a potential treatment for the effects of an ischemic stroke.

Aloe-emodin prevents nerve injury and neuroinflammation caused by ischemic stroke via the PI3K/AKT/mTOR and NF-κB pathway.

Ischemic stroke (IS) caused by cerebral arterial occlusion is the leading cause of global morbidity and mortality. Cellular oxidative stress and inflammation play a vital role in the pathological process of neural damage in IS. It is necessary to develop functional food or drugs, which target neuroinflammation and oxidation mechanisms against IS. The molecule compound aloe-emodin (AE) is derived from aloe and rhubarb. However, the exact mechanism of the pharmacological action of AE on IS remains unclear. Here, for aiming to demonstrate the mechanism of AE, our study explored the middle cerebral occlusion reperfusion (MCAO/R) rats in vivo, oxygen and glucose deprivation reperfusion (OGD/R), and lipopolysaccharide (LPS)-stimulated cells in vitro. We found that AE significantly improved the infarct size and behavioral score of MCAO/R rats, decreased the expression of TNF-α, MDA, LDH, Caspase 3, and increased the expression of SOD, Bcl-2/Bax. Liquid chromatography-mass spectrometry (LC/MS) results showed that AE could penetrate the blood-brain barrier in the sham group and MCAO/R group. In vitro, AE significantly protected SH-SY5Y cells from the insult of OGD/R and reduced the production of inflammatory cytokines in BV2 cells stimulated by LPS. In vivo and in vitro, western blot analysis results showed that AE significantly increased the expression of PI3K, AKT and mTOR proteins. In addition, AE significantly decreased NF-κB protein expression in BV2 cells. The use of AKT-specific inhibitor MK-2206 2HCL to inhibit AKT expression can block the protective effect of AE on SH-SY5Y cells subjected to OGD/R insults. Overall, our study suggests that AE protected against cerebral ischemia-reperfusion injury probably via the PI3K/AKT/mTOR and NF-κB signaling pathways. Thus, these results indicated that AE could be a promising first-line therapy for preventing and treating ischemic stroke and can be used as functional food.

Structural characterization, anti-inflammatory and glycosidase inhibitory activities of two new polysaccharides from the root of Pueraria lobata.

Diabetes seriously endangers public health and brings a heavy economic burden to the country. Inflammation is one of the main inducing factors of type-2 diabetes (T2D) and may cause some complications of diabetes, such as diabetic encephalopathy and peripheral neuropathy. In-depth research and development of drugs to cure diabetes and complications are of great significance. Pueraria lobate is a medicinal herb used in several countries to treat many diseases. Here, two new polysaccharides (PLB-1-1 and PLB-1-2) were isolated and purified from the root of Pueraria lobata with molecular weights of 9.1 × 103 Da and 3.8 × 103 Da, respectively. The structure was evaluated by monosaccharide composition, GC-MS and NMR spectroscopy. It was determined that PLB-1-1 comprised →4)-α-d-Glcp-(1→, α-d-Glcp-(1→, →6)-ß-d-Galp-(1→, →3)-α-l-Araf-(1→, →3,6)-ß-d-Manp-(1→ and →4,6)-ß-d-Manp-(1→, and PLB-1-2 consisted of →4)-α-d-Glcp-(1→, ß-d-Glcp-(1→, →4,6)-ß-d-Glcp-(1→, →3,6)-ß-d-Manp-(1→ and α-l-Fucp-(1→. Furthermore, both PLB-1-1 and PLB-1-2 showed anti-inflammatory and inhibitory activities of α-glucosidase and α-amylase in vitro. Therefore, the new polysaccharides, i.e., PLB-1-1 and PLB-1-2, may be considered candidates for the treatment of diabetes and its related complications.