XQZ3, a Chlorella pyrenoidosa polysaccharide suppresses cancer progression by restraining mitochondrial bioenergetics via HSP90/AKT signaling pathway.

The mitochondria are known to exert significant influence on various aspects of cancer cell physiology. The suppression of mitochondrial function represents a novel avenue for the advancement of anti-cancer pharmaceuticals. The heat shock protein HSP90 functions as a versatile regulator of mitochondrial metabolism in cancer cells, rendering as a promising target for anticancer interventions. In this work, a novel acid polysaccharide named as XQZ3 was extracted from Chlorella pyrenoidosa and purified by DEAE-cellulose and gel-filtration chromatography. The structural characteristic of XQZ3 was evaluated by monosaccharides composition, methylation analysis, TEM, FT-IR, and 2D-NMR. It was found that XQZ3 with a molecular weight of 29.13 kDa was a complex branched polysaccharide with a backbone mainly composed of galactose and mannose. It exhibited good antitumor activity in vitro and in vivo by patient-derived 3D organoid models and patient-derived xenografts models. The mechanistic investigations revealed that XQZ3 specifically interacted with HSP90, impeding the activation of the HSP90/AKT/mTOR signaling cascade. This, in turn, led to the induction of mitochondrial dysfunction, autophagy, and apoptosis, ultimately resulting in the demise of cancer cells due to nutrient deprivation. This study offers a comprehensive theoretical foundation for the advancement of XQZ3, a novel polysaccharide inhibitor targeting HSP90, with potential as an effective therapeutic agent against cancer.

Diterpenoid tanshinones inhibit gastric cancer angiogenesis through the PI3K/Akt/mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge is a kind of Chinese herbal medicine known for activating blood circulation and removing blood stasis, with the effect of cooling blood and eliminating carbuncles, and has been proven to have the effect of treating tumors. However, the inhibitory effect of Salvia miltiorrhiza Bunge extracts (Diterpenoid tanshinones) on tumors by inhibiting angiogenesis has not been studied in detail. AIM OF THE STUDY: This study aimed to investigate the anti-gastric cancer effect of diterpenoid tanshinones (DT) on angiogenesis, including the therapeutic effects and pathways. MATERIALS AND METHODS: This experiment utilized network pharmacology was used to identify relevant targets and pathways of Salvia miltiorrhiza Bunge-related components in the treatment of gastric cancer. The effects of DT on the proliferation and migration of human gastric cancer cell line SGC-7901 and human umbilical vein endothelial cell line HUVECs were evaluated, and changes in the expression of angiogenesis-related factors were measured. In vivo, experiments were conducted on nude mice to determine tumor activity, size, immunohistochemistry, and related proteins. RESULTS: The findings showed that DT could inhibit the development of gastric cancer by suppressing the proliferation of gastric cancer cells, inducing apoptosis, and inhibiting invasion and metastasis. In addition, the content of angiogenesis-related factors and proteins was significantly altered in DT-affected cells and animals. CONCLUSIONS: Results suggest that DT has potential as a therapeutic agent for the treatment of gastric cancer, as it can inhibit tumor growth and angiogenesis. It was also found that DT may affect the expression of the angiogenic factor VEGF through the PI3K/Akt/mTOR pathway, leading to the regulation of tumor angiogenesis. This study provides a new approach to the development of anti-tumor agents and has significant theoretical and clinical implications for the treatment of gastric cancer.

Phytohemagglutinin from Phaseolus vulgaris enhances the lung cancer cell chemotherapy sensitivity by changing cell membrane permeability.

Chemotherapy is still a prevalent strategy for clinical lung cancer treatment. However, the inevitable emerged drug resistance has become a great hurdle to therapeutic effect. Studies have demonstrated that the primary cause of drug resistance is a decrease in the chemotherapeutic medicine concentration. Several lectins have been confirmed to be effective as chemotherapy adjuvants, enhancing the anti-tumor effects of chemotherapy drugs. Here, we combined phytohemagglutinin (PHA), which has been reported possess anti-tumor effects, with chemotherapy drugs Cisplatin (DDP) and Adriamycin (ADM) on lung cancer cells to detect the sensitivities of PHA as a chemotherapy adjuvant. Our results demonstrated that the PHA significantly enhanced the sensitivity of lung cancer cells to DDP and ADM, and Western blot showed that PHA combined with DDP or ADM enhance cytotoxic effects by inhibiting autophagy and promoting apoptosis. More importantly, we found PHA enhanced the chemotherapeutic drugs cytotoxicity by changing the cell membrane to increase the intracellular chemotherapeutic drugs concentration. Besides, the combination of PHA and ADM increased the ADM concentration in the multidrug-resistant strain A549-R cells and achieved the drug sensitization effect. Our results suggest that PHA combined with chemotherapy can be applied in the treatment of lung cancer cells and lung cancer multidrug-resistant strains, and provide a novel strategy for clinical tumor chemotherapy and a new idea to solve the problem of drug resistance in clinical lung cancer.

Jolkinolide B ameliorates rheumatoid arthritis by regulating the JAK2/STAT3 signaling pathway.

BACKGROUND: Jolkinolide B (JB), an ent­abietane-type diterpenoid in Euphorbia plants, has various pharmacological activities, including anticancer, anti-inflammatory, and anti-tuberculosis activities. However, no previous studies have proven whether JB can be regarded as a targeted drug for the treatment of rheumatoid arthritis (RA). PURPOSE: This study aimed to evaluate the anti-RA effects of JB and explore the potential mechanisms. METHODS: Components and targets of JB and RA were identified in different databases, and potential targets and pathways were predicted by protein-protein interaction (PPI) network analysis and pathway enrichment analysis. Then, molecular docking and surface-plasmon resonance (SPR) were used to confirm the predict. The anti-arthritic effects of JB were studied in vivo with collagen-induced arthritis (CIA) rat model and in vitro with lipopolysaccharide (LPS) and interleukin-6 (IL-6)-induced RAW264.7 macrophage. Potential mechanisms were further verified by in vivo and in vitro experiments. RESULTS: The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that Th17 cell differentiation, prolactin signaling pathway, and JAK/STAT signaling pathway might be associated with anti-RA effects of JB. Molecular docking and SPR results showed that JB bound effectively to JAK2. JB significantly decreased body weight loss, arthritis index, paw thickness, and synovial thickness in CIA rats. Histomorphological results suggested the protective effects of JB on CIA rats with ankle joint injury. Molecular biology analysis indicated that JB suppressed the mRNA expression of inflammatory factors in ankle joints for CIA rats and reduced the concentration of these factors in LPS- induced RAW264.7 macrophage. The protein expression level of the JAK2/STAT3 pathway was also significantly decreased by JB. CONCLUSION: JB had a novel inhibitory effect on inflammation and bone destruction in CIA rats, and the mechanism might be related to the JAK2/STAT3 signaling pathway.

Development of a nomogram based on body composition analysis of quantitative computed tomography combined with clinical prognostic factors to predict disease-free survival after surgery and adjuvant chemotherapy in patients with gastric cancer.

Background: Patients with gastric cancer (GC) have a high recurrence rate after surgery. To predict disease-free survival (DFS), we investigated the value of body composition changes (BCCs) measured by quantitative computed tomography (QCT) in assessing the prognosis of patients with GC undergoing resection combined with adjuvant chemotherapy and to construct a nomogram model in combination with clinical prognostic factors (CPFs). Methods: A retrospective study of 60 patients with GC between February 2015 and June 2019 was conducted. Pre- and posttreatment CT images of patients was used to measure bone mineral density (BMD), subcutaneous fat area (SFA), visceral fat area (VFA), total fat area (TFA), paravertebral muscle area (PMA), and the rate of BCC was calculated. CPFs such as maximum tumor diameter (MTD), human epidermal growth factor receptor-2 (HER2), and Ki-67 were derived from postoperative pathological findings. Independent prognostic factors affecting DFS in GC were screened via univariate and multivariate Cox regression analysis. The Kaplan-Meier method and log-rank test were used to plot survival curves and compare the curves between groups, respectively. Receiver operating characteristic (ROC) curves, calibration curves, and decision curves to evaluate the efficacy of the nomogram. Results: The results of multivariate Cox regression analysis showed that ΔBMD [hazard ratio (HR): 4.577; 95% confidence interval (CI): 1.483-14.132; P=0.008], ΔPMA (HR: 5.784; 95% CI: 1.251-26.740; P=0.025), HER2 (HR: 4.819; 95% CI: 2.201-10.549; P<0.001), and maximal tumor diameter (HR: 3.973; 95% CI: 1.893-8.337; P<0.001) were independent factors influencing DFS. ΔBMD, ΔSFA, ΔVFA, ΔTFA, and ΔPMA were -3.86%, -23.44%, -19.57%, -22.45%, and -5.94%, respectively. The prognostic model of BCCs combined with CPFs had the highest predictive performance. Decision curve analysis (DCA) indicated good clinical benefit for the prognostic nomogram. The concordance index of the prognostic nomogram was 0.814, and the area under the curve (AUC) of predicting 2- and 3-year DFS were 0.879 and 0.928, respectively. The calibration curve showed that the nomogram-predicted DFS aligned well with the actual DFS. Conclusions: The prognostic nomogram combining BCCs and CPFs was able to reliably predict the DFS of patients with GC.

Bioinformatic Analysis on the Prognostic Value of Neurotransmitter Receptor-Related Genes in Kidney Renal Clear Cell Carcinoma.

Context: Kidney renal clear-cell carcinoma (KIRC) is a malignant tumor. At an early stage, KIRC patients may experience only mild fever and fatigue or even no symptoms, and these early nonspecific indications can delay treatment. Neurotransmitters and their receptors may be very useful in determining tumorigenesis and predicting metastasis. Objective: The study intended to investigate the predictive value of neurotransmitter receptor-related genes (NRRGs) using public KIRC data, by determining the biological processes that implicate the prognostic NRRGs and establishing a predictive NR-related risk model, to provide an empirical basis for identifying and treating KIRC patients. Design: The research team performed a genetic case-control study. Setting: The study took place at Research Center of Health, Big Data Mining and Applications, Wannan Medical College, Wuhu, China. Methods: The research team: (1) obtained the transcriptome data related to KIRC from the Cancer Genome Atlas (TCGA) and ArrayExpress databases; (2) developed the differentially expressed NRRGs (DENRRGs) by identifying the NRRGs that intersected with DEGs in KIRC and normal samples; (3) carried out functional enrichment analyses of the DENRRGs; (4) screened the characteristic genes of the DENRRGs using machine learning; (5) created a predictive model using multivariate Cox analyses of the distinctive genes; (6) obtained independent prognostic factors for KIRC patients and established a nomograph model; (7) investigated the sensitivity of KIRC patients to therapeutic agents to examine the variations in immunological features between high-risk and low-risk individuals. Results: Differential analysis found that 115 NRRGs intersected with 5275 DEGs to provide 52 DENRRGs. Functional enrichment showed that DENRRGs were mainly involved in signal transduction in the nervous system. The machine learning on the 52 DENRRGs filtered out nine characteristic genes. Subsequently, the research team found eight prognostic biomarkers-histamine receptor H2 (HRH2), gamma-aminobutyric acid (GABA) receptor subunit epsilon (GABRE), cholinergic receptor nicotinic delta subunit (CHRND), glutamate receptor ionotropic subunit 2D (GRIN2D), glutamate metabotropic receptor 4 (GRM4), glycine receptor alpha 3 (GLRA3), cholinergic receptor nicotinic beta 4 subunit (CHRNB4), and cholinergic receptor muscarinic-1 (CHRM1)-and established a predictive model. Furthermore, the team precisely predicted the KIRC patients' prognoses using a nomogram that combined their ages, risk scores, and M stages. The infiltration levels of 21 immune cells also significantly differed between the high-risk and low-risk groups, with neutrophils having a significant positive correlation with GABRE and HRH2 and a significant negative correlation with CHRNB4 and GRM4. Finally, the 50% inhibitory concentration (IC50) values for various drugs, such as 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR), 8-hydroxy-7-(6-sulfonaphthalen-2-yl)diazenyl-quinoline-5-sulfonic acid (NSC-87877), Sunitinib, c-Jun N-terminal kinase (JNK) inhibitor VIII, and tanespimyci (X17.AAG) were significantly lower for high-risk group. Conclusions: By studying the relevance of biomarkers to the immunological microenvironment of KIRC, the current research team was able to propose a new predictive model for KIRC based on NRRGs, to offer a novel viewpoint for investigating KIRC. The study's results suggest new avenues for research into the pathophysiology and therapy of KIRC. Determining the precise molecular processes by which predictive biomarkers regulate KIRC requires further evidence and analysis.

Oxymatrine ameliorates rheumatoid arthritis by regulation of Tfr/Tfh cell balance via the TLR9-MyD88-STAT3 signaling pathway.

BACKGROUND: Oxymatrine (OMT) is one of the authentic Chinese herbal medicines which has rich and complex active ingredients. however,the relevant potential targets of oxymatrine on rheumatoid arthritis and the mechanism remains unreported. The aim of this study was to determine the regulation of oxymatrine on rheumatoid arthritis using a collagen-induced arthritis (CIA) mice models and blood samples from RA patients. RESULTS: Our results indicated that Tfr cells in RA patients express low levels of Blimp-1 and CTLA-4. Oxymatrine treatment of CIA mice alleviated joint swelling, reduced the arthritis score, and improved joint damage. While flow cytometry results showed that oxymatrine treatment reduced Tfh cells and B cells, and increased Tfr cells in the spleen of CIA mice. In addition, oxymatrine treatment significantly down-regulated the expression of TLR9（Toll-like Receptors 9), IL-21, MyD88, STAT3, p-STAT3, and CXCR5 in the synovial tissues of CIA mice, and up-regulated the expression of Foxp3, Blimp-1, and CTLA-4. CONCLUSION: Oxymatrine can alleviate rheumatoid arthritis by regulating the TLR9-MyD88-STAT3 signaling pathway to maintain immune balance between Tfr-Tfh cells. © 2023 Society of Chemical Industry.

Photobiomodulation for knee osteoarthritis: a model-based dosimetry study.

LED-based photobiomodulation (LED-PBM) for the treatment of knee osteoarthritis (KOA) is a promising technology. However, the light dose at the targeted tissue, which dominates the phototherapy effectiveness, is difficult to measure. This paper studied the dosimetric issues in the phototherapy of KOA by developing an optical model of the knee and performing Monte Carlo (MC) simulation. The model was validated by the tissue phantom and knee experiments. In the study, we investigated the effect of luminous characteristics of the light source, such as divergence angle, wavelength and irradiation position, on the treatment doses for PBM. The result showed that the divergence angle and the wavelength of the light source have a significant impact on the treatment doses. The optimal irradiation location was on both sides of the patella, where the largest dose could reach the articular cartilage. This optical model can be used to determine the key parameters in phototherapy and help the phototherapy of KOA patients.

Effects of Nemacystus decipiens polysaccharide on mice with antibiotic associated diarrhea and colon inflammation.

Antibiotic associated diarrhea (AAD) is a common side effect of antibiotic therapy in which gut microbiota plays an important role in the disease. However, the function of gut microbiota in this disease is still not entirely clear. Polysaccharides have shown strong activity in shaping gut microbiota. Whether the polysaccharide can intervene with the microbiota to improve ADD has not been determined. In this study, we extract crude polysaccharides from Nemacystus decipiens (N. decipiens), a traditional Chinese medicine (TCM), named NDH0. The crude polysaccharide NDH0 might significantly relieve the symptom of mice with AAD, including a reduction in body weight, shortening of cecum index and the infiltration of inflammatory cells into the colon. NDH0-treated mice exhibited more abundant gut microbial diversity; significantly increased the abundance of Muribaculum, Lactobacillus, and Bifidobacterium and decreased the abundance of Enterobacter and Clostridioides at genus level. NDH0 treatment down-regulated the level of pro-inflammatory cytokines, including IL-1ß and IL-6 in colon tissue. NDH0 protected the integrity of colon tissues and partially inactivated the related inflammation pathway by maintaining occludin and SH2-containing Inositol 5'-Phosphatase (SHIP). NDH0 could alleviate symptoms of diarrhea by modulating gut microbiota composition, improving intestinal integrity and reducing inflammation. The underlying protective mechanism was to reduce the abundance of opportunistic pathogens and maintain SHIP protein expression. Collectively, our results demonstrated the role of NDH0 as a potential intestinal protective agent in gut dysbiosis.

Epimedii Herba: An ancient Chinese herbal medicine in the prevention and treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, progressive inflammatory and systemic autoimmune disease resulting in severe joint destruction, lifelong suffering and considerable disability. Diverse prescriptions of traditional Chinese medicine (TCM) containing Epimedii Herba (EH) achieve greatly curative effects against RA. The present review aims to systemically summarize the therapeutic effect, pharmacological mechanism, bioavailability and safety assessment of EH to provide a novel insight for subsequent studies. The search terms included were "Epimedii Herba", "yinyanghuo", "arthritis, rheumatoid" and "Rheumatoid Arthritis", and relevant literatures were collected on the database such as Google Scholar, Pubmed, Web of Science and CNKI. In this review, 15 compounds from EH for the treatment of RA were summarized from the aspects of anti-inflammatory, immunoregulatory, cartilage and bone protective, antiangiogenic and antioxidant activities. Although EH has been frequently used to treat RA in clinical practice, studies on mechanisms of these activities are still scarce. Various compounds of EH have the multifunctional traits in the treatment of RA, so EH may be a great complementary medicine option and it is necessary to pay more attention to further research and development.

The difference of human gut microbiome in colorectal cancer with and without metastases.

Metastasis of colorectal cancer is deemed to be closely related to the changes in the human gut microbiome. The purpose of our study is to distinguish the differences in gut microbiota between colorectal cancer with and without metastases. Firstly, this study recruited colorectal cancer patients who met the established inclusion and exclusion criteria in the Oncology Department of Zhejiang Hospital of Traditional Chinese Medicine from February 2019 to June 2019. Fresh stool samples from healthy volunteers, non-metastatic patients, and metastatic patients were collected for 16S rRNA gene sequencing, to analyze the diversity and abundance of intestinal microorganisms in each group. The results showed that the microbial composition of the control group was more aplenty than the experimental group, while the difference also happened in the Tumor and the metastases group. At the phylum level, the abundance of Bacteroidetes significantly declined in the Tumor and the metastases group, compared with the control group. At the class level, Bacilli increased in experimental groups, while its abundance in the Tumor group was significantly higher than that in the metastases group. At the order level, the Tumor group had the highest abundance of Lactobacillales, followed by the metastases group and the control group had the lowest abundance. Overall, our study showed that the composition of the flora changed with the occurrence of metastasis in colorectal cancer. Therefore, the analysis of gut microbiota can serve as a supplement biological basis for the diagnosis and treatment of metastatic colorectal cancer which may offer the potential to develop non-invasive diagnostic tests.

The new exploration of pure total flavonoids extracted from Citrus maxima (Burm.) Merr. as a new therapeutic agent to bring health benefits for people.

The peel and fruit of Citrus varieties have been a raw material for some traditional Chinese medicine (TCM). Pure total flavonoids from Citrus maxima (Burm.) Merr. (PTFC), including naringin, hesperidin, narirutin, and neohesperidin, have been attracted increasing attention for their multiple clinical efficacies. Based on existing in vitro and in vivo research, this study systematically reviewed the biological functions of PTFC and its components in preventing or treating liver metabolic diseases, cardiovascular diseases, intestinal barrier dysfunction, as well as malignancies. PTFC and its components are capable of regulating glycolipid metabolism, blocking peroxidation and persistent inflammation, inhibiting tumor progression, protecting the integrity of intestinal barrier and positively regulating intestinal microbiota, while the differences in fruit cultivation system, picking standard, manufacturing methods, delivery system and individual intestinal microecology will have impact on the specific therapeutic effect. Thus, PTFC is a promising drug for the treatment of some chronic diseases, as well as continuous elaborate investigations are necessary to improve its effectiveness and bioavailability.

The antitumor properties of atractylenolides: Molecular mechanisms and signaling pathways.

Drugs that exhibit a high degree of tumor cell selectivity while minimizing normal cell toxicity are an area of active research interest as a means of designing novel antitumor agents. The pharmacological benefits of Chinese herbal medicine-based treatments have been the focus of growing research interest in recent years. Sesquiterpenoids derived from the Atractylodes macrocephala volatile oil preparations exhibit in vitro and in vivo antitumor activity. Atracylenolides exhibit anti-proliferative, anti-metastatic, and immunomodulatory activity in a range of tumor cell lines in addition to being capable of regulating metabolic activity such that it is a promising candidate drug for the treatment of diverse cancers. The present review provides a summary of recent advances in Atractylenolide-focused antitumor research efforts.

Synthesis of Enantioenriched Sulfoxides by an Oxidation-Reduction Enzymatic Cascade.

Chiral sulfoxides are versatile synthons and have gained a particular interest in asymmetric synthesis of active pharmaceutical and agrochemical ingredients. Herein, a linear oxidation-reduction bienzymatic cascade to synthesize chiral sulfoxides is reported. The extraordinarily stable and active vanadium-dependent chloroperoxidase from Curvularia inaequalis (CiVCPO) was used to oxidize sulfides into racemic sulfoxides, which were then converted to chiral sulfoxides by highly enantioselective methionine sulfoxide reductase A (MsrA) and B (MsrB) by kinetic resolution, respectively. The combinatorial cascade gave a broad range of structurally diverse sulfoxides with excellent optical purity (>99 %  ee) with complementary chirality. The enzymatic cascade requires no NAD(P)H recycling, representing a facile method for chiral sulfoxide synthesis. Particularly, the envisioned enzymatic cascade not only allows CiVCPO to gain relevance in chiral sulfoxide synthesis, but also provides a powerful approach for (S)-sulfoxide synthesis; the latter case is significantly unexplored for heme-dependent peroxidases and peroxygenases.

Next-generation sequencing and targeted quantitative real-time polymerase chain reaction for detection of Akebiae Caulis in the traditional Chinese medical formula Longdan Xiegan Wan.

Background: Akebiae Caulis (Mu Tong) is commonly misused by Aristolochiae Manshuriensis Caulis (Guan Mutong) and Clematidis Armandii Caulis (Chuan Mutong), which are nephrotoxic and carcinogenic. However, in the Pharmacopoeia of the People's Republic of China (2015 Edition), the method for determining Akebiae Caulis remains undefined. Methods: We used DNA barcode-based next-generation sequencing (NGS) combined with quantitative real-time polymerase chain reaction (qPCR) to detect Akebiae Caulis in Longdan Xiegan Wan (LDXGW) for the first time. Compared with chromatographic studies, NGS enables better evaluation of the ingredient components of traditional Chinese medicine (TCM) preparations. The feasibility of qPCR using species-specific primers to determine the authenticity of species has been validated. In this study, the constituents of Akebiae Caulis in LDXGW from three different manufacturers were scanned by NGS. The independently developed qPCR detection primers of Akebiae Caulis, Aristolochiae Manshuriensis Caulis, and Clematidis Armandii Caulis were specifically used to analyze the LDXGW mentioned above. Results: The results showed that qPCR detected Clematidis Armandii Caulis in all commercial samples. Meanwhile, NGS detected the counterfeit species Clematis peterae (Tie-Xian Lian) in all samples. We found that qPCR shows a difference in detecting Akebiae Caulis, but it was not able to identify the unknown additives and adulterants for the primer pairs of Clematidis Armandii Caulis. Conclusions: Hence, it is sensitive and rapid, qPCR is not suitable for detection alone. The NGS approaches offer important novel insights that complement the qPCR method. The combination of NGS and qPCR will be a powerful complement to traditional identification methods of TCM substances.

Insights into complex infection by two Pectobacterium species causing potato blackleg and soft rot.

Pectobacterium spp. are causative agents of blackleg and soft rot of potato. However, little is known about the relationship between the pathogenicity of mixed infections of different Pectobacterium spp. at different temperatures. In this study, two pectinolytic strains of Pectobacterium spp. were isolated from the same potato plant with typical symptoms of blackleg and identified as P. brasiliense and P. carotovorum by multilocus sequence analysis (MLSA), whole-genome phylogenetic tree construction, average nucleotide identity (ANI) analysis and digital DNA-DNA hybridization (dDDH). Plant cell wall degrading enzyme, including pectinases, cellulases and proteases, as the most important virulence factors, as well as pathogenicity toward potato tuber, were compared between the strains P. brasiliense BL-2 and P. carotovorum BL-4 at 28 â„ƒ. The results showed that P. carotovorum had higher cell wall-degrading enzyme activities and brought more severe disease symptoms to potato tubers than P. brasiliense. Moreover, the pathogenicity of P. carotovorum and P. brasiliense increased with increasing temperature (20, 25, 28, 32 â„ƒ). The pathogenicity was more severe when P. carotovorum strain BL-4 was co-inoculated with P. brasiliense strain BL-2, especially when the former exhibited an advantage in bacterial number at the initial time. The results of this study provide new insight for understanding the pathogenicity caused by mixed infections with different species of Pectobacterium spp., and they may provide some guidance for controlling potato blackleg and soft rot.

Reduction of lactoferrin aggravates neuronal ferroptosis after intracerebral hemorrhagic stroke in hyperglycemic mice.

Diabetic hyperglycemia aggravates the prognosis of intracerebral hemorrhagic stroke (ICH) in the clinic. In addition to hematoma expansion and increased inflammation, how diabetic hyperglycemia affects the outcomes of ICH is still unclear. We found that streptozotocin-induced diabetic hyperglycemia not only increased neutrophil infiltration, but also changed the gene expression profile of neutrophils, including lactoferrin (Ltf) encoding gene Ltf. Peroxisome proliferator-activated receptor γ (PPARγ) transcribed Ltf and the lack of neutrophilic Ltf transcription and secretion exacerbated neuronal ferroptosis by accumulating intraneuronal iron. Furthermore, the administration of recombinant Ltf protected against neuronal ferroptosis and improved neurobehavior in hyperglycemic ICH mice, and vice versa. These results indicate that supplementing Ltf or inhibiting neuronal ferroptosis are promising potential strategies to improve the acute outcomes of diabetic ICH in the clinic.

Advances in Chemical Composition, Extraction Techniques, Analytical Methods, and Biological Activity of Astragali Radix.

Astragali Radix (AR) is one of the well-known traditional Chinese medicines with a long history of medical use and a wide range of clinical applications. AR contains a variety of chemical constituents which can be classified into the following categories: polysaccharides, saponins, flavonoids, amino acids, and trace elements. There are several techniques to extract these constituents, of which microwave-assisted, enzymatic, aqueous, ultrasonic and reflux extraction are the most used. Several methods such as spectroscopy, capillary electrophoresis and various chromatographic methods have been developed to identify and analyze AR. Meanwhile, this paper also summarizes the biological activities of AR, such as anti-inflammatory, antioxidant, antitumor and antiviral activities. It is expected to provide theoretical support for the better development and utilization of AR.

[Mechanism of oxymatrine in treatment of collagen-induced arthritis in mice].

Sophorae Flavescentis Radix, the root of Sophora flavescens Ait., has been widely applied in the medical field due to its anti-inflammatory, analgesic, bacteriostatic, antiviral, antitumor, and other pharmacological effects. The present study investigated the anti-rheumatoid arthritis effect of oxymatrine(OMT), the active component of Sophorae Flavescentis Radix by observing its effect on the function of B lymphocytes in collagen-induced arthritis(CIA) mice through the Toll-like receptor 9(TLR9)/myeloid differentiation factor 88(MyD88)/signal transducer and activator of transcription 3(STAT3) pathway. The CIA model in DBA/1 J mice was induced by bovine type Ⅱ collagen and complete Freund's adjuvant(CFA). Fifteen days after the primary immunization, mice were treated with OMT for 30 days by intraperitoneal injection. Paw swelling and arthritis index(AI) score were evaluated every 3 days. Joint histopathologic changes were observed by HE staining. Magnetic-activated cell sorting(MACS) was used to isolate B lymphocytes from the spleen of CIA mice spleen. The serum expression level of interleukin(IL)-21 was examined by the enzyme-linked immunosorbent assay(ELISA). The expression of TLR9, STAT3, p-STAT3, and IL-21 in B lymphocytes was detected by Western blot. The mRNA expression of TLR9, STAT3, and IL-21 in B lymphocytes was detected by real-time fluorescence-based quantitative PCR(qRT-PCR). The results showed that OMT could significantly alleviate the paw swelling, decrease the AI score, relieve synovial inflammatory cell infiltration and hyperplasia, reduce the level of inflammatory cytokines, and inhibit the expression of TLR9, STAT3, p-STAT3, and IL-21 of B lymphocytes in CIA mice. Therefore, OMT may alleviate rheumatoid arthritis by regulating TLR9/MyD88/STAT3 pathway in B lymphocytes, providing a valuable reference for the application of OMT in the clinical treatment of rheumatoid arthritis.

Longitudinal Changes of Sensorimotor Resting-State Functional Connectivity Differentiate between Patients with Thalamic Infarction and Pontine Infarction.

Purpose. We investigated the disparate influence of lesion location on functional damage and reorganization of the sensorimotor brain network in patients with thalamic infarction and pontine infarction. Methods. Fourteen patients with unilateral infarction of the thalamus and 14 patients with unilateral infarction of the pons underwent longitudinal fMRI measurements and motor functional assessment five times during a 6-month period (<7 days, at 2 weeks, 1 month, 3 months, and 6 months after stroke onset). Twenty-five age- and sex-matched controls underwent MRI examination across five consecutive time points in 6 months. Functional images from patients with left hemisphere lesions were first flipped from the left to the right side. The voxel-wise connectivity analyses between the reference time course of each ROI (the contralateral dorsal lateral putamen (dl-putamen), pons, ventral anterior (VA), and ventral lateral (VL) nuclei of the thalamus) and the time course of each voxel in the sensorimotor area were performed for all five measurements. One-way ANOVA was used to identify between-group differences in functional connectivity (FC) at baseline stage (<7 days after stroke onset), with infarction volume included as a nuisance variable. The family-wise error (FWE) method was used to account for multiple comparison issues using SPM software. Post hoc repeated-measure ANOVA was applied to examine longitudinal FC reorganization. Results. At baseline stage, significant differences were detected between the contralateral VA and ipsilateral postcentral gyrus (cl_VA-ip_postcentral), contralateral VL and ipsilateral precentral gyrus (cl_VL-ip_precentral). Repeated measures ANOVA revealed that the FC change of cl_VA-ip_postcentral differ significantly among the three groups over time. The significant changes of FC between cl_VA and ip_postcentral at different time points in the thalamic infarction group showed that compared with 7 days after stroke onset, there was significantly increased FC of cl_VA-ip_postcentral at 1 month, 3 months, and 6 months after stroke onset. Conclusions. The different patterns of sensorimotor functional damage and reorganization in patients with pontine infarction and thalamic infarction may provide insights into the neural mechanisms underlying functional recovery after stroke.