Comparative transcriptome analysis reveals the importance of phenylpropanoid biosynthesis for the induced resistance of 84K poplar to anthracnose.

BACKGROUND: Poplar anthracnose, which is one of the most important tree diseases, is primarily caused by Colletotrichum gloeosporioides, which has been detected in poplar plantations in China and is responsible for serious economic losses. The characteristics of 84K poplar that have made it one of the typical woody model plants used for investigating stress resistance include its rapid growth, simple reproduction, and adaptability. RESULTS: In this study, we found that the resistance of 84K poplar to anthracnose varied considerably depending on how the samples were inoculated of the two seedlings in each tissue culture bottle, one (84K-Cg) was inoculated for 6 days, whereas the 84K-DCg samples were another seedling inoculated at the 6th day and incubated for another 6 days under the same conditions. It was showed that the average anthracnose spot diameter on 84K-Cg and 84K-DCg leaves was 1.23 ± 0.0577 cm and 0.67 ± 0.1154 cm, respectively. Based on the transcriptome sequencing analysis, it was indicated that the upregulated phenylpropanoid biosynthesis-related genes in 84K poplar infected with C. gloeosporioides, including genes encoding PAL, C4H, 4CL, HCT, CCR, COMT, F5H, and CAD, are also involved in other KEGG pathways (i.e., flavonoid biosynthesis and phenylalanine metabolism). The expression levels of these genes were lowest in 84K-Cg and highest in 84K-DCg. CONCLUSIONS: It was found that PAL-related genes may be crucial for the induced resistance of 84K poplar to anthracnose, which enriched in the phenylpropanoid biosynthesis. These results will provide the basis for future research conducted to verify the contribution of phenylpropanoid biosynthesis to induced resistance and explore plant immune resistance-related signals that may regulate plant defense capabilities, which may provide valuable insights relevant to the development of effective and environmentally friendly methods for controlling poplar anthracnose.

Dietary salt promotes cognitive impairment through repression of SIRT3/PINK1-mediated mitophagy and fission.

Dietary salt is increasingly recognized as an independent risk factor for cognitive impairment. However, the exact mechanisms are not yet fully understood. Mitochondria, which play a crucial role in energy metabolism, are implicated in cognitive function through processes such as mitochondrial dynamics and mitophagy. While mitochondrial dysfunction is acknowledged as a significant determinant of cognitive function, the specific relationship between salt-induced cognitive impairment and mitochondrial health has yet to be fully elucidated. Here, we explored the underlying mechanism of cognitive impairment of mice and N2a cells treated with high-salt focusing on the mitochondrial homeostasis with western blotting, immunofluorescence, electron microscopy, RNA sequencing, and more. We further explored the potential role of SIRT3 in salt-induced mitochondrial dysfunction and synaptic alteration through plasmid transfection and siRNA. High salt diet significantly inhibited mitochondrial fission and blocked mitophagy, leading to dysfunctional mitochondria and impaired synaptic plasticity. Our findings demonstrated that SIRT3 not only promote mitochondrial fission by modulating phosphorylated DRP1, but also rescue mitophagy through promoting PINK1/Parkin-dependent pathway. Overall, our data for the first time indicate that mitochondrial homeostasis imbalance is a driver of impaired synaptic plasticity in a cognitive impairment phenotype that is exacerbated by a long-term high-salt diet, and highlight the protective role of SIRT3 in this process.

High salt diet induces cognitive impairment and is linked to the activation of IGF1R/mTOR/p70S6K signaling.

A high-salt diet (HSD) has been associated with various health issues, including hypertension and cardiovascular diseases. However, recent studies have revealed a potential link between high salt intake and cognitive impairment. This study aims to investigate the effects of high salt intake on autophagy, tau protein hyperphosphorylation, and synaptic function and their potential associations with cognitive impairment. To explore these mechanisms, 8-month-old male C57BL/6 mice were fed either a normal diet (0.4% NaCl) or an HSD (8% NaCl) for 3 months, and Neuro-2a cells were incubated with normal medium or NaCl medium (80 mM). Behavioral tests revealed learning and memory deficits in mice fed the HSD. We further discovered that the HSD decreased autophagy, as indicated by diminished levels of the autophagy-associated proteins Beclin-1 and LC3, along with an elevated p62 protein level. HSD feeding significantly decreased insulin-like growth factor-1 receptor (IGF1R) expression in the brain of C57BL/6 mice and activated mechanistic target of rapamycin (mTOR) signaling. In addition, the HSD reduced synaptophysin and postsynaptic density protein 95 (PSD95) expression in the hippocampus and caused synaptic loss in mice. We also found amyloid ß accumulation and hyperphosphorylation of tau protein at different loci both in vivo and in vitro. Overall, this study highlights the clinical significance of understanding the impact of an HSD on cognitive function. By targeting the IGF1R/mTOR/p70S6K pathway or promoting autophagy, it may be possible to mitigate the negative effects of high salt intake on cognitive function.

Effects of modified BOPPPS-based SPOC and Flipped class on 5th-year undergraduate oral histopathology learning in China during COVID-19.

BACKGROUND: Colleges and universities in China have offered courses based on online teaching platforms as required by the Ministry of Education since the beginning of the COVID-19 pandemic. This emergency action was not an expedient measure, but a powerful impetus to improve extant education and implement teaching reform. Oral histopathology is a basic subject in oral medicine education, which combines theory with practice. The course aims to improve the ability of students to observe, think, analyze and identify oral diseases. METHOD: We adjusted and modified the original Bridge-In, Outcomes, Pre-assessment, Participatory Learning, Post-assessment, and Summary (BOPPPS) teaching method to fit the characteristics and needs of oral histopathology. We then combined the characteristics of Small Private Online Courses (SPOCs) and a Flipped class to complete teaching material online, and assessed the effects of such teaching using a questionnaire and interviews. Fifty 5th-year undergraduates in stomatology at the School of Stomatology of Harbin Medical University of China participated in online classes. All were in the junior second half of the semester at the beginning of 2020. Teachers investigated from various medical colleges were responsible for delivering courses associated with stomatology or ophthalmology. RESULT & CONCLUSION: The results showed that the modified BOPPPS combined with SPOC and the Flipped class improved teaching satisfaction. Modified BOPPPS combined with SPOC and the Flipped class is a useful complement to offline teaching on 5th-year undergraduate oral histopathology learning in China during COVID-19, and it can meet the multiple needs of students participating in the course.

[Mechanism of Xinfeng Capsules improving rheumatoid arthritis based on CD19~+B cells regulating FAK/CAPN/PI3K pathway].

To observe the effect of Xinfeng Capsules on rheumatoid arthritis (RA) B lymphocytes,inflammatory mediators,FAK/CAPN/PI3K pathway,in order to explore the mechanism of Xinfeng Capsules in improving clinical symptoms of RA.Joint and systemic symptoms of RA patients were observed,and laboratory indicators[hemoglobin (HGB),platelet count (PLT),erythrocyte sedimentation (ESR),immunoglobulin (Ig) G,Ig A,Ig M,rheumatoid factor (RF),anti-cyclic citrulline antibody (CCP-AB),C-reactive protein (CRP)]were detected.ELISA was used to detect serum interleukin (IL)-1ß，IL-10,IL-33,chemokine 5 (CCL5),and vascular endothelial growth factor (VEGF).CD3~-CD19~+B cells were measured by flow cytometry.Western blot was used to detect FAK,p-FAK,CAPN,PI3K protein.The results showed that Xinfeng Capsules could significantly alleviate RA joint and systemic symptoms and improve clinical efficacy.And Xinfeng Capsules could increase HGB,decrease PLT,CCP-AB,CRP,ESR index,upregulate IL-10 expression,and down-regulate IL-1ß，IL-33,CCL5,VEGF,CD3~-CD19~+B cells,FAK,p-FAK,CAPN,PI3K expressions (P<0.01).Based on the above results,Xinfeng Capsules may reduce the expression of CD3~-CD19~+,regulate the balance of inflammatory cytokines and chemokines,inhibit abnormal activation of FAK/CAPN/PI3K pathway,and improve clinical symptoms of RA.

Evaluation of Clinical Features and Stroke Etiology in Patients with Bilateral Middle Cerebellar Peduncle Infarction.

OBJECTIVE: The aim of this study was to characterize clinical features, etiologies, and mechanisms of strokes due to bilateral middle cerebellar peduncle infarction (BMCPI). METHODS: Cases diagnosed as BMCPI in our hospital were retrieved, and a literature review was performed. Data on clinical features and brain MRI were obtained. Extracranial and intracranial segments of the vertebrobasilar artery were assessed by using digital subtraction angiography, magnetic resonance angiography, or computed tomography angiography. RESULTS: Thirteen cases (11 men and 2 women) of BMCPI were identified. A high-intensity signal of diffusion-weighted imaging sequence involving the bilateral middle cerebellar peduncle was observed in all patients. Most patients experienced vertigo, dysarthria, ataxia, and hearing disorders. Eleven of these cases were classified as large artery atherosclerosis, one as traumatic vertebral artery (VA) dissection, and one as giant cell arteritis. CONCLUSION: BMCPI is a rare cerebrovascular disease characterized by vertigo, ataxia, and dysarthria, which may also be accompanied by a hearing deficit or clinical signs of brainstem damage. BMCPI may be associated with hypoperfusion secondary to occlusive disease of the bilateral VA or proximal basilar artery.

Prognostic implication of NOTCH1 in early stage oral squamous cell cancer with occult metastases.

OBJECTIVE: The objective of this study was to explore the prognostic value of cancer stem cell markers, namely CD133, NANOG, and NOTCH1, in early stage oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: One hundred forty-four patients with early stage (cT1T2N0) OSCC were identified from a pre-existing database of patients with oral cancer. We examined the impact of the immunohistochemical expression of CD133, NANOG, and NOTCH1 in OSCC. Overall survival (OS) curves were calculated using the Kaplan-Meier method. Predictors of outcome were identified using multivariate analysis. RESULTS: We found that CD133, NANOG, and NOTCH1 were significantly associated with lymph node metastasis, and NOTCH1 was also significantly associated with depth of invasion and locoregional recurrence. CONCLUSIONS: NOTCH1 was identified as an independent prognostic factor for OS. CLINICAL RELEVANCE: NOTCH1 might prove to be a useful indicator for high-risk patients with occult metastases from early stage OSCC.

Prognostic significance of VEGF-C, semaphorin 3F, and neuropilin-2 expression in oral squamous cell carcinomas and their relationship with lymphangiogenesis.

BACKGROUND: Neuropilin-2 (NRP2), a receptor for vascular endothelial growth factor C (VEGF-C) and semaphorin 3 F (SEMA3F), is a possible regulator of tumor progression and angiogenesis. However, little evidence of a correlation between NRP2 expression and lymphangiogenesis has been reported. SEMA3F might suppress lymphangiogenesis by competing with VEGF-C for binding to NRP2. METHODS: We evaluated lymphatic vessel density (LVD), lymphatic vessel invasion (LVI), the expression levels of VEGF-C, SEMA3F, and NRP2 by immunohistochemistry in 80 cases of oral squamous cell carcinomas (OSCCs). RESULTS: In these tumors, the expression of NRP2 was positively associated with T stage classification, lymph node metastasis, LVD, LVI, and the expression of VEGF-C. In contrast, low expression of SEMA3F was significantly related to poor differentiation and higher incidence of lymph node metastasis. Patients expressing high levels of VEGF-C or NRP2, or low levels of SEMA3F had a higher risk of recurrence and shorter overall survival. Multivariate analysis showed that VEGF-C and NRP2 were independent prognostic markers for overall survival. CONCLUSIONS: Results indicate SEMA3F is an inhibitor of tumor progression and provide evidence for an association between NRP2 and VEGF-C, lymphangiogenesis, lymph node metastasis. This suggests the prognostic significance and potential therapeutic value of the VEGF-C/SEMA3F/NRP2 axis for OSCCs.

A natural phenylpropionate derivative from Mirabilis himalaica inhibits cell proliferation and induces apoptosis in HepG2 cells.

Bioactivity-guided study led to the isolation of a natural phenylpropionate derivative, (E)-3-(4-hydroxy-2-methoxyphenyl)-propenoic acid 4-hydroxy-3-methoxyphenyl ester from the roots of Mirabilis himalaica. Cellular analysis showed that compound 1 specifically inhibited the cancer cell growth through the S phase arrest. Mechanistically, compound 1 was able to induce the apoptosis in HepG2 cells through mitochondrial apoptosis pathway in which Bcl-2 and p53 were required. Interestingly, the cellular phenotype of compound 1 were shown specifically in cancer cells originated from hepatocellular carcinoma (HepG2) while compromised influence by compound 1 were detected within the normal human liver cells (L-02). Consistently, the in vivo inhibitory effects of compound 1 on tumor growth were validated by the in xenograft administrated with HepG2 cells. Our results provided a novel compound which might serve as a promising candidate and shed light on the therapy of the hepatocellular carcinoma.

Use of xinfeng capsule to treat abarticular pathologic changes in patients with rheumatoid arthritis.

OBJECTIVE: To observe the influence of Xinfengcapsule (XFC) on abarticular pathologic changes (APCs) and other indices of patients with rheumatoid arthritis (RA) and explore the mechanism of action of XFC in improving such changes. METHODS: Three-hundred RA patients were divided randomly into a treatment group (n = 150) and control group (n = 150). A normal control (NC) group (n = 90) was also created. Changes in cardiac function, pulmonary function, anemia indices and platelet parameters of RA patients were measured. Curative effects of the two groups were compared, and comparison carried out with the NC group. RESULTS: In 300 RA patients, late diastolic peak flow velocity (A peak) was much higher (P < 0.01) and early diastolic peak flow velocity (E peak), E/A, and left ventricular fraction shortening much lower(P < 0.01) than those in the NC group. Vital capacity (VC), forced vital capacity in one second, forced vitalcapacity (FVC), maximal voluntary ventilation (MVV), maximal expiratory flow in 50% of VC (FEF50) and FEF75 were lowered remarkably (P < 0.05 or P < 0.01). Platelet count (PLT), plateletcrit (PCT) and mean platelet volume (MPV) increased markedly (P < 0.05 or P < 0.01), and hemoglobin (Hb) level decreased significantly (P < 0.05). After XFC treatment, the A peak and PLT and PCT were much lower (P < 0.05), and E/A and the number of red blood cells as well as Hb level were much higher (P < 0.05), as were FVC, MVV and FEF50 (P < 0.05 or P < 0.01), in the treatment group than those in the NC group. Total score of pain and swelling in joints, uric-acid level and high-sensitivity C-reactive protein level were much lower, and superoxide dismutase level as well as the number of CD4 + CD25+ regulation T cells (Treg) and CD4+ CD25+ CD127- Treg were much higher (P < 0.05 or P < 0.01) in the treatment group than those in the NC group. CONCLUSION: RA patients with pathologic changes in joints also suffer from lower cardiac and pulmonary functions and from parameters of anemia and platelet factors. XFC can improve the symptoms of RA patients, ameliorate their cardiac and pulmonary functions and reduce the parameters of anemia and platelet factors. XFC lowers the immune inflammatory reaction to improve APCs in RA patients.