Autophagy Regulation Attenuates Neuroinflammation and Cognitive Decline in an Alzheimer's Disease Mouse Model with Chronic Cerebral Hypoperfusion.

This study investigates the role of autophagy regulation in modulating neuroinflammation and cognitive function in an Alzheimer's disease (AD) mouse model with chronic cerebral hypoperfusion (CCH). Using the APP23/PS1 mice plus CCH model, we examined the impact of autophagy regulation on cognitive function, neuroinflammation, and autophagic activity. Our results demonstrate significant cognitive impairments in AD mice, exacerbated by CCH, but mitigated by treatment with the autophagy inhibitor 3-methyladenine (3-MA). Dysregulation of autophagy-related proteins, accentuated by CCH, underscores the intricate relationship between cerebral blood flow and autophagy dysfunction in AD pathology. While 3-MA restored autophagic balance, rapamycin (RAPA) treatment did not induce significant changes, suggesting alternative therapeutic approaches are necessary. Dysregulated microglial polarization and neuroinflammation in AD+CCH were linked to cognitive decline, with 3-MA attenuating neuroinflammation. Furthermore, alterations in M2 microglial polarization and the levels of inflammatory markers NLRP3 and MCP1 were observed, with 3-MA treatment exhibiting potential anti-inflammatory effects. Our findings shed light on the crosstalk between autophagy and neuroinflammation in AD+CCH and suggest targeting autophagy as a promising strategy for mitigating neuroinflammation and cognitive decline in AD+CCH.

Applications of MRI in Schizophrenia: Current Progress in Establishing Clinical Utility.

Schizophrenia is a severe mental illness that significantly impacts the lives of affected individuals and with increasing mortality rates. Early detection and intervention are crucial for improving outcomes but the lack of validated biomarkers poses great challenges in such efforts. The use of magnetic resonance imaging (MRI) in schizophrenia enables the investigation of the disorder's etiological and neuropathological substrates in vivo. After decades of research, promising findings of MRI have been shown to aid in screening high-risk individuals and predicting illness onset, and predicting symptoms and treatment outcomes of schizophrenia. The integration of machine learning and deep learning techniques makes it possible to develop intelligent diagnostic and prognostic tools with extracted or selected imaging features. In this review, we aimed to provide an overview of current progress and prospects in establishing clinical utility of MRI in schizophrenia. We first provided an overview of MRI findings of brain abnormalities that might underpin the symptoms or treatment response process in schizophrenia patients. Then, we summarized the ongoing efforts in the computer-aided utility of MRI in schizophrenia and discussed the gap between MRI research findings and real-world applications. Finally, promising pathways to promote clinical translation were provided. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Carbon monoxide polyhemoglobin improves the therapeutic effect and relieves inflammation in the colon tissue of haemorrhagic shock/resuscitation rats.

OBJECTIVE: The objective of this study was to test the therapeutic effect of carbon monoxide polyhemoglobin (polyCOHb) in haemorrhagic shock/resuscitation and its underlying mechanisms. METHODS: 48 rats were divided into two experimental parts, and 36 rats in the first experiment and 12 rats in the second experiment. In the first experimental part, 36 animals were randomly assigned to the following groups: hydroxyethyl starch group (HES group, n = 12), polyhemoglobin group (polyHb group, n = 12), and carbon monoxide polyhemoglobin group (polyCOHb group, n = 12). In the second experimental part, 12 animals were randomly assigned to the following groups: polyHb group (n = 6), and polyCOHb group (n = 6). Then the anaesthetised rats were haemorrhaged by withdrawing 50% of the animal's blood volume (BV), and resuscitated to the same volume of the animal's withdrawing BV with HES, polyHb, polyCOHb. In the first experimental part, the 72h survival rates of each groups animals were measured. In the second experimental part, the rats' mean arterial pressure (MAP), heart rate (HR), blood gas levels and other indicators were dynamically monitored in baseline, haemorrhagic shock (HS), at 0point resuscitation (RS 0h) and after 1 h resuscitation (RS 1h). The concentrations of malondialdehyde (MDA), superoxide dismutase (SOD), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured by ELISA kits in both groups of rats at RS 1h. Changes in pathological sections were examined by haematoxylin-eosin (HE) staining. Nuclear factor erythroid 2-related factor 2 (Nrf2) and haem oxygenase-1 (HO-1) levels were detected by immunohistochemical analysis, while myeloperoxidase (MPO) levels were detected by immunofluorescence. DHE staining was used to determine reactive oxygen species (ROS) levels. RESULTS: The 72h survival rates of the polyHb and polyCOHb groups were 50.00% (6/12) and 58.33% (7/12) respectively, which were significantly higher than that of the 8.33% (1/12) in the HES group (p < 0.05). At RS 0h and RS 1h, the HbCO content of rats in the polyCOHb group (1.90 ± 0.21, 0.80 ± 0.21) g/L were higher than those in the polyHb group (0.40 ± 0.09, 0.50 ± 0.12)g/L (p < 0.05); At RS 1h, the MDA (41.47 ± 3.89 vs 34.17 ± 3.87 nmol/ml) in the plasma, Nrf2 and HO-1 content in the colon of rats in the polyCOHb group were lower than the polyHb group. And the SOD in the plasma (605.01 ± 24.46 vs 678.64 ± 36.37) U/mg and colon (115.72 ± 21.17 vs 156.70 ± 21.34) U/mg and the MPO content in the colon in the polyCOHb group were higher than the polyHb group (p < 0.05). CONCLUSIONS: In these haemorrhagic shock/resuscitation models, both polyCOHb and polyHb show similar therapeutic effects, and polyCOHb has more effective effects in maintaining MAP, correcting acidosis, reducing inflammatory responses than that in polyHb.

Prognostic value of plasma Aß1-40 for Alzheimer's disease.

OBJECTIVE: To investigate the clinical significance of plasma p-amyloid 1-40 (Aß1-40) in patients with Alzheimer's disease (AD). METHODS: In this retrospective study, the clinical data of 305 patients, with or without Alzheimer's disease (AD), who were treated at the Affiliated Hospital of Youjiang Medical University for Nationalities and the People's Hospital of Baise between January 2018 and December 2021 were analyzed. Patients were divided into two groups: an AD group (n=147) and a non-AD group (without AD, n=158 cases). Blood test indices, including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CRE), high-sensitivity C-reactive protein (hsCRP), and plasma ß-amyloid 1-40 were collected and compared between the two groups. RESULTS: The plasma ß-amyloid 1-40 in the AD group was (3.71±3.45) mol/L, which was significantly higher than (2.8±1.35) mmol/L in the non-AD group (P<0.05). Similarly, hsCRP expression was significantly higher in the AD group than that in the non-AD group (P<0.05). There were no significant differences in AST, ALT, UA, T-tau, NFL or Cr levels between the two groups (all P>0.05). Moreover, univariate regression analysis showed that plasma ß-amyloid 1-40 and hsCRP were significantly correlated with AD. Multiple regression analysis demonstrated that plasma p-amyloid 1-40 (P<0.0001) and hsCRP (P=0.002) were independent predictors of AD. CONCLUSION: Plasma p-amyloid 1-40 and hsCRP are closely related to AD, and may serve as important clinical predictors of AD.

The difference in volumetric alternations of the orbitofrontal-limbic-striatal system between major depressive disorder and anxiety disorders: A systematic review and voxel-based meta-analysis.

BACKGROUND: Major depressive disorder (MDD) and anxiety disorders (ANX) are psychiatric disorders with high mutual comorbidity rates that might indicate some shared neurobiological pathways between them, but they retain diverse phenotypes that characterize themselves specifically. However, no consistent evidence exists for common and disorder-specific gray matter volume (GMV) alternations between them. METHODS: A systematic review and meta-analysis on voxel-based morphometry studies of patients with MDD and ANX were performed. The effect of comorbidity was explicitly controlled during disorder-specific analysis and particularly investigated in patient with comorbidity. RESULTS: A total of 45 studies with 54 datasets comprising 2196 patients and 2055 healthy participants met the inclusion criteria. Deficits in the orbitofrontal cortex, striatum, and limbic regions were found in MDD and ANX. The disorder-specific analyses showed decreased GMV in the bilateral anterior cingulate cortex, right striatum, hippocampus, and cerebellum in MDD, while decreased GMV in the left striatum, amygdala, insula, and increased cerebellar volume in ANX. A totally different GMV alternation pattern was shown involving bilateral temporal and parietal gyri and left fusiform gyrus in patients with comorbidity. LIMITATIONS: Owing to the design of included studies, only partial patients in the comorbid group had a secondary comorbidity diagnosis. CONCLUSION: Patients with MDD and ANX shared a structural disruption in the orbitofrontal-limbic-striatal system. The disorder-specific effects manifested their greatest severity in distinct lateralization and directionality of these changes that differentiate MDD from ANX. The comorbid group showed a totally different GMV alternation pattern, possibly suggesting another illness subtype that requires further investigation.

Cardiovascular disease and depression: a narrative review.

In clinical practice, it is frequently observed that cardiac and psychological disorders frequently co-occur, leading to the emergence of a field known as cardiovascular disease with depression. Depression, in particular, poses a remarkable risk for the evolution of cardiovascular disease and intimately relates to adverse cardiovascular outcomes and mortality. Moreover, individuals who are depressed exhibit a higher susceptibility to developing cardiovascular disease compared to those in good health. Patients diagnosed with cardiovascular disease with depression disease face a heightened risk of mortality within a 5-year timeframe, and their prognosis remains unsatisfactory even after receiving treatment targeting a single disorder, with a notable recurrence rate. Psychological interventions in conjunction with medications are commonly employed in clinical settings for treating patients with cardiovascular disease and depression diseases, albeit with limited effectiveness and unfavorable prognosis. Traditional Chinese medicine (TCM), such as Shuangxinfang, Chaihujialonggumuli, and Yixin Ningshen Tablet, etc., have been reported and have Therapeutic effects in patients with cardiovascular disease combined with depression. Despite numerous articles documenting a notable association between heart disease and depression, there exists a dearth of studies elucidating the precise pathogenesis and target of action for cardiovascular disease with depression diseases. This article endeavors to consolidate the epidemiological data, potential pathogenic mechanisms, and available treatment modalities for cardiovascular disease with depression diseases. Its primary objective is to unveil plausible co-morbid mechanisms and suitable treatment approaches, thereby offering novel insights for the prevention, diagnosis, and management of cardiovascular disease with depression diseases.

Multiple uremic tumoral calcinosis in periarticular soft tissues with chronic renal failure: a case report.

Uremic tumoral calcinosis (UTC) is an uncommon and severe complication of hemodialysis therapy. The most important pathogenic factor involved in UTC is an increase in calcium-phosphorus products. We report here a patient undergoing hemodialysis for renal failure caused by hypertensive nephropathy who presented multiple UTCs in the right shoulder, left elbow and wrist. After surgical excision, they all recurred, with a similar UTC in the left shoulder. By observing the imaging features of various imaging examinations during the whole period of this case, including X-ray, computed tomography (CT), magnetic resonance imaging (MRI), and single-photon emission computed tomography (SPECT), we highlight the importance of imaging for evaluating the state of UTC regarding treatment options, further deepening our understanding of the imaging manifestations for this disease and their clinical significance.

The acute effects of repetitive transcranial magnetic stimulation on laminar diffusion anisotropy of neocortical gray matter.

Repetitive transcranial magnetic stimulation (rTMS) is increasingly used to treat neuropsychiatric disorders. Inhibitory and excitatory regimens have been both adopted but the exact mechanism of action remains unclear, and investigating their differential effects on laminar diffusion profiles of neocortex may add important evidence. Twenty healthy participants were randomly assigned to receive a low-frequency/inhibitory or high-frequency/excitatory rTMS targeting the left dorsolateral prefrontal cortex (DLPFC). With the brand-new submillimeter diffusion tensor imaging of whole brain and specialized surface-based laminar analysis, fractional anisotropy (FA) and mean diffusion (MD) profiles of cortical layers at different cortical depths were characterized before/after rTMS. Inhibitory and excitatory rTMS both showed impacts on diffusion metrics of somatosensory, limbic, and sensory regions, but different patterns of changes were observed-increased FA with inhibitory rTMS, whereas decreased FA with excitatory rTMS. More importantly, laminar analysis indicated laminar specificity of changes in somatosensory regions during different rTMS patterns-inhibitory rTMS affected the superficial layers contralateral to the DLPFC, while excitatory rTMS led to changes in the intermediate/deep layers bilateral to the DLPFC. These findings provide novel insights into acute neurobiological effects on diffusion profiles of rTMS that may add critical evidence relevant to different protocols of rTMS on neocortex.

Analysis of the Glycoside Hydrolase Family 1 from Wild Jujube Reveals Genes Involved in the Degradation of Jujuboside A.

Jujubosides are the major medicinal ingredients of Ziziphi Spinosae Semen (the seed of wild jujube). To date, a complete understanding of jujuboside's metabolic pathways has not been attained. This study has systematically identified 35 ß-glucosidase genes belonging to the glycoside hydrolase family 1 (GH1) using bioinformatic methods based on the wild jujube genome. The conserved domains and motifs of the 35 putative ß-glucosidases, along with the genome locations and exon-intron structures of 35 ß-glucosidase genes were revealed. The potential functions of the putative proteins encoded by the 35 ß-glucosidase genes are suggested based on their phylogenetic relationships with Arabidopsis homologs. Two wild jujube ß-glucosidase genes were heterologously expressed in Escherichia coli, and the recombinant proteins were able to convert jujuboside A (JuA) into jujuboside B (JuB). Since it has been previously reported that JuA catabolites, including JuB and other rare jujubosides, may play crucial roles in the jujuboside's pharmacological activity, it is suggested that these two proteins can be used to enhance the utilization potential of jujubosides. This study provides new insight into the metabolism of jujubosides in wild jujube. Furthermore, the characterization of ß-glucosidase genes is expected to facilitate investigations involving the cultivation and breeding of wild jujube.

Revealing the Roles of the JAZ Family in Defense Signaling and the Agarwood Formation Process in Aquilaria sinensis.

Jasmonate ZIM-domain family proteins (JAZs) are repressors in the signaling cascades triggered by jasmonates (JAs). It has been proposed that JAs play essential roles in the sesquiterpene induction and agarwood formation processes in Aquilaria sinensis. However, the specific roles of JAZs in A. sinensis remain elusive. This study employed various methods, including phylogenetic analysis, real-time quantitative PCR, transcriptomic sequencing, yeast two-hybrid assay, and pull-down assay, to characterize A. sinensis JAZ family members and explore their correlations with WRKY transcription factors. The bioinformatic analysis revealed twelve putative AsJAZ proteins in five groups and sixty-four putative AsWRKY transcription factors in three groups. The AsJAZ and AsWRKY genes exhibited various tissue-specific or hormone-induced expression patterns. Some AsJAZ and AsWRKY genes were highly expressed in agarwood or significantly induced by methyl jasmonate in suspension cells. Potential relationships were proposed between AsJAZ4 and several AsWRKY transcription factors. The interaction between AsJAZ4 and AsWRKY75n was confirmed by yeast two-hybrid and pull-down assays. This study characterized the JAZ family members in A. sinensis and proposed a model of the function of the AsJAZ4/WRKY75n complex. This will advance our understanding of the roles of the AsJAZ proteins and their regulatory pathways.

Preparation and exchange transfusion effect of a double polymerization human umbilical cord haemoglobin of red blood cell substitute.

The development of haemoglobin-based oxygen carrier (HBOC) is an excellent supplement to pre-hospital emergency blood transfusions. In this study, a new type of HBOC was prepared by using human cord haemoglobin (HCHb) and glutaraldehyde (GDA) and Bis(3,5-dibromosalicyl) fumarate (DBBF) to modify (DBBF-GDA-HCHb), the changes of physicochemical indexes during its preparation were evaluated, while a traditional type of GDA-HCHb was prepared, and the oxygen-carrying capacity of two type of HBOC was evaluated by a rat model of 135.0% exchange transfusion (ET). Eighteen SD male rats were selected, and were randomly divided into control group (5.0% albumin), DBBF-GDA-HCHb group and GDA-HCHb group. The 12 h survival rate of the C group was 16.67%, and the two HBOC groups were both 83.33%. Compared with GDA-HCHb, DBBF-GDA-HCHb can reduce lactic acid content by supplying oxygen to hypoxic tissues in a more timely manner, and can also can improve the reduction of MAP due to ischaemia.

Convergent and distinct neural structural and functional patterns of mild cognitive impairment: a multimodal meta-analysis.

Mild cognitive impairment (MCI) is regarded as a transitional stage between normal aging and Alzheimer's disease. Numerous voxel-based morphometry (VBM) and resting-state fMRI (rs-fMRI) studies have provided strong evidence of abnormalities in the structure and intrinsic function of brain regions in MCI. Studies have recently begun to explore their association but have not employed systematic information in this pursuit. Herein, a multimodal meta-analysis was performed, which included 43 VBM datasets (1,247 patients and 1,352 controls) of gray matter volume (GMV) and 42 rs-fMRI datasets (1,468 patients and 1,605 controls) that combined 3 metrics: amplitude of low-frequency fluctuation, the fractional amplitude of low-frequency fluctuation, and regional homogeneity. Compared to controls, patients with MCI displayed convergent reduced regional GMV and altered intrinsic activity, mainly in the default mode network and salience network. Decreased GMV alone in ventral medial prefrontal cortex and altered intrinsic function alone in bilateral dorsal anterior cingulate/paracingulate gyri, right lingual gyrus, and cerebellum were identified, respectively. This meta-analysis investigated complex patterns of convergent and distinct brain alterations impacting different neural networks in MCI patients, which contributes to a further understanding of the pathophysiology of MCI.

Detecting individuals with severe mental illness using artificial intelligence applied to magnetic resonance imaging.

BACKGROUND: Identifying individuals at risk for severe mental illness (SMI) is crucial for prevention and early intervention strategies. While MRI shows potential for case identification even before illness onset, no practical model for mental health risk monitoring has been developed. This study aims to develop an initial version of an efficient and practical model for mental health screening among at-risk populations. METHODS: A deep learning model known as Multiple Instance Learning (MIL) was adopted to train and test a SMI detection model with clinical MRI scans of 14,915 patients with SMI (age 32.98 ± 12.01 years, 9102 women) and 4538 healthy controls (age 40.60 ± 10.95 years, 2424 women) in the primary dataset. Validation analysis was conducted in an independent dataset with 290 patients (age 28.08 ± 10.95 years, 169 women) and 310 healthy participants (age 33.55 ± 11.09 years, 165 women). Another three machine learning models of ResNet, DenseNet and EfficientNet were used for comparison. We also recruited 148 individuals receiving high-stress medical school education to characterize the potential real-world utility of the MIL model in detecting risk of mental illness. FINDINGS: Similar performance of successful differentiation of individuals with SMI and healthy controls was observed for the MIL model (AUC: 0.82) and other models (ResNet, DenseNet, EfficientNet, 0.83, 0.81, and 0.80 respectively). MIL had better generalization in the validation test than other models (AUC: 0.82 vs 0.59, 0.66 and 0.59), and less drop-off in performance from 3.0T to 1.5T scanners. The MIL model did better in predicting clinician ratings of distress than self-ratings with questionnaires (84% vs 22%) in the medical student sample. Brain regions that contributed to SMI identification were mainly neocortical, including right precuneus, bilateral temporal regions, left precentral/postcentral gyrus, bilateral medial prefrontal cortex and right cerebellum. INTERPRETATION: Our digital model based on brief clinical MRI protocols identified individual SMI patients with good accuracy and high sensitivity, suggesting that with incremental improvements the approach may offer potentially useful aid for early identification and intervention to prevent illness onset in vulnerable at-risk populations. FUNDING: This study was supported by the National Natural Science Foundation of China, National Key Technologies R&D Program of China, and Sichuan Science and Technology Program.

Correlation Analysis of Neutrophil/Albumin Ratio and Leukocyte Count/Albumin Ratio with Ischemic Stroke Severity.

Ischemic stroke (IS) is a common neurological disease in the elderly, but the relationship between neutrophil/albumin ratio (NAR) and leukocyte count/albumin ratio (LAR) and the severity of neurological function injury and early neurological deterioration (END) occurrence remain elusive in acute IS. A total of 299 patients with acute IS and 56 healthy controls were enrolled. According to the NIHSS score at admission, the disease group was divided into three groups (mild, moderate and severe IS), and the differences in five indexes NAR, LAR, neutrophil count, leukocyte count and albumin among the four groups were analyzed. Furthermore, explore the correlation between the above indicators and the severity of IS and END occurrence. The results showed that higher NAR, LAR, neutrophil count, leukocyte count levels and lower albumin levels were associated with acute IS, and the levels of NAR and LAR increased gradually in three groups of IS. NAR and LAR were positively and albumin was negatively correlated with the severity of IS. Meanwhile, NAR and LAR showed a good predictive value in identifying patients with END after acute IS. NAR and LAR may be predictors of the severity of IS and END occurrence after acute IS.

The cortical hypogyrification pattern in antipsychotic-naive first-episode schizophrenia.

Schizophrenia is thought to be a neurodevelopmental disease with high genetic heritability, and evidence from neuroimaging studies has consistently shown widespread cortical local gyrification index (LGI) alterations; however, genes accounting for LGI alterations in schizophrenia remain unknown. The present study examined the LGI alterations in first-episode antipsychotic-naive schizophrenia compared with controls (235 patients and 214 controls); transcription-neuroimaging association analysis was used to evaluate the relationship between LGI deficits and specific risk genes. The expression profiles of 232 schizophrenia risk genes were extracted from six donated normal brains from the Allen Human Brain Atlas database. The correlation between LGI alterations and clinical symptoms was also tested. We found lower LGI values involved in frontotemporal regions and limbic systems. Nonparametric correlation analysis showed that 83 risk genes correlated with the hypogyrification pattern in schizophrenia. These identified risk genes were functionally enriched for the development of the central nervous system. The LGI in the left superior temporal gyrus was negatively associated with Positive and Negative Syndrome Scale negative symptoms. In summary, the present study provides a set of risk genes possibly related to the hypogyrification pattern in antipsychotic-naive first-episode schizophrenia, which could help to unveil the neurobiological underpinnings of cortical impairments in early-stage schizophrenia.

Disrupted subcortical functional connectome gradient in drug-naïve first-episode schizophrenia and the normalization effects after antipsychotic treatment.

Antipsychotics are thought to improve schizophrenia symptoms through the antagonism of dopamine D2 receptors, which are abundant mainly in subcortical regions. By introducing functional gradient, a novel approach to identify hierarchy alterations by capturing the similarity of whole brain fucntional connectivity (FC) profiles between two voxels, the present study aimed to characterize how the subcortical gradient is associated with treatment effects and response in first-episode schizophrenia in vivo. Two independent samples of first-episode schizophrenia (FES) patients with matched healthy controls (HC) were obtained: the discovery dataset included 71 patients (FES0W) and 64 HC at baseline, and patients were re-scanned after either 6 weeks (FES6W, N = 33) or 12 months (FES12M, N = 57) of antipsychotic treatment, of which 19 patients finished both 6-week and 12-month evaluation. The validation dataset included 22 patients and 24 HC at baseline and patients were re-scanned after 6 weeks. Gradient metrics were calculated using BrainSpace Toolbox. Voxel-based gradient values were generated and group-averaged gradient values were further extracted across all voxels (global), three systems (thalamus, limbic and striatum) and their subcortical subfields. The comparisons were conducted separately between FES0W and HC for investigating illness effects, and between FES6W/FES12M and FES0W for treatment effects. Correlational analyses were then conducted between the longitudinal gradient alterations and the improvement of clinical ratings. Before treatment, schizophrenia patients exhibited an expanded range of global gradient scores compared to HC which indicated functional segregation within subcortical systems. The increased gradient in limbic system and decreased gradient in thalamic and striatal system contributed to the baseline abnormalities and led to the disruption of the subcortical functional integration. After treatment, these disruptions were normalized and the longitudinal changes of gradient scores in limbic system were significantly associated with symptom improvement. Similar illness and treatment effects were also observed in the validation dataset. By measuring functional hierarchy of subcortical organization, our findings provide a novel imaging marker that is sensitive to treatment effects and may make a promising indicator of treatment response in schizophrenia.

p75NTR enhances cognitive dysfunction in a mouse Alzheimer's disease model by inhibiting microRNA-210-3p-mediated PCYT2 through activation of NF-κB.

Alzheimer's disease (AD) is a main cause of dementia and exhibits abnormality in cognitive behaviors. Here, we probed into the role of p75 neurotrophin receptor (p75NTR) in cognitive dysfunction in AD. Primarily, C57BL/6 mouse and neuroblastoma cells were treated by amyloid-beta1-42 (Aß1-42), respectively, to establish the in vivo and in vitro models of AD. The downstream genes of p75NTR were predicted by RNA-sequencing and bioinformatics analysis. Then the interaction among p75NTR, nuclear factor kappa B (NF-κB), microRNA-210-3p (miR-210-3p) and phosphoethanolamine cytidylyltransferase 2 (PYCT2) was verified, followed by analysis of their effects on cognitive behaviors and biological characteristics of hippocampal neurons of mouse with AD-like symptoms. p75NTR knockout alleviated cognitive dysfunction in mice with AD-like symptoms and reduced Aß1-42-induced hippocampal neuron damage and apoptosis. p75NTR up-regulated miR-210-3p expression by activating NF-κB, thereby limiting PCYT2 expression. PCYT2 silencing in p75NTR-/- mice promoted neuronal apoptosis and aggravated cognitive dysfunction in AD mouse models. In summary, p75NTR is capable of accelerating cognitive dysfunction in AD by mediating the NF-κB/miR-210-3p/PCYT2 axis.

Quantitative analysis of multi-components by single marker method combined with UPLC-PAD fingerprint analysis based on saikosaponin for discrimination of Bupleuri Radix according to geographical origin.

Background: Saikosaponins are regarded as one of the most likely antipyretic constituents of Bupleuri Radix, establishing a comprehensive method that can reflect both the proportion of all constituents and the content of each saikosaponin is critical for its quality evaluation. Methods: In this study, the combination method of quantitative analysis of multiple components with a single marker (QAMS) and fingerprint was firstly established for simultaneous determination of 7 kinds of saikosaponins in Bupleuri Radix by ultra-high performance liquid chromatography (UPLC). Results: The results showed that saikosaponin d was identified as the optimum IR by evaluating the fluctuations and stability of the relative calibration factors (RCFs) under four different conditions. The new QAMS method has been confirmed to accurately quantify the 7 kinds of saikosaponins by comparing the obtained results with those obtained from external standard method and successfully classify the 20 batches of Bupleuri Radix from 8 provinces of China. The experimental time of fingerprint was significantly reduced to approximate 0.5 h through UPLC-PAD method, a total of 17 common peaks were identified. Conclusion: The QAMS-fingerprint method is feasible and reliable for the quality evaluation of Bupleuri Radix. This method could be considered to be spread in the production enterprises of Bupleuri Radix.

Protective effect and mechanism of low P50 haemoglobin oxygen carrier on isolated rat heart.

The protection of the isolated heart is very important in heart transplantation surgery, meanwhile, the ischaemia/reperfusion (I/R) of the isolated heart is the main cause of its damage. A timely supply of oxygen can significantly improve the prevention of myocardial ischaemia, however, the cardioprotective solution does not have an oxygen supply function. Haemoglobin Based on Oxygen Carriers (HBOCs) is a kind of nano-oxygen drug, which can effectively and timely supply oxygen to hypoxic organs and tissues. However, the oxygen-carrying and releasing capacity (P50) is different with different HBOCs. The aim of our study was to investigate whether STS (a kind of cardioprotective solution, St Thomas Solution) +different P50 HBOCs provide superior myocardial protection and decrease myocardial injury compared to only STS in rats Langendorff isolated heart perfusion model. The results showed that STS + HBOCs can improve cardiac function at 37 °C for 35 min and 120 min, and reduce myocardial infarctions, pathological changes, and apoptosis of cardiomyocytes, and the STS + low P50 HBOCs is more effective than the other two higher P50 HBOCs. We further demonstrated the outstanding protective effect of STS + low P50 HBOCs on cardiac function, reducing myocardial infarctions and apoptosis of cardiomyocytes in rat Langendorff isolated heart perfusion model.

Identification of the original plants of cultivated Bupleuri Radix based on DNA barcoding and chloroplast genome analysis.

Bupleuri Radix is the dry root of certain species of the genus Bupleurum and is commonly used in traditional Chinese medicine. The increasing global demand for Bupleuri Radix cannot be fulfilled with wild populations only. Therefore, cultivated Bupleurum is now the main commercial source of this medicinal product. Different species of Bupleurum show different medicinal properties and clinical effects, making reliable authentication and assignment of correct botanical origin for medicinal species critical. However, accurate identification of the cultivated Bupleurum species is difficult due to dramatic morphological variations resulting from cultivation. In this study, we sampled 56 cultivated Bupleurum populations of six different morphotypes (Types A-F) from the main production areas of China, and 10 wild populations of four species were used as reference materials. Conventional DNA barcoding was conducted to identify cultivated Bupleurum species. Additionally, verification based on complete chloroplast genomes was performed and new chloroplast markers were developed and evaluated. The combination of these methods resulted in the successful identification of all cultivated Bupleurum individuals. Three chloroplast regions are recommended as additional barcodes for the genus: ycf4_cemA, psaJ_rpl33, and ndhE_ndhG. This is a reliable and promising strategy that can be applied to the authentication of natural products and the identification of other medicinal plant species with similar taxonomic problems.