Catalpol attenuates ischemic stroke by promoting neurogenesis and angiogenesis via the SDF-1α/CXCR4 pathway.

BACKGROUND: Stroke is a leading cause of disability and death worldwide. Currently, there is a lack of clinically effective treatments for the brain damage following ischemic stroke. Catalpol is a bioactive compound derived from the traditional Chinese medicine Rehmannia glutinosa and shown to be protective in various neurological diseases. However, the potential roles of catalpol against ischemic stroke are still not completely clear. PURPOSE: This study aimed to further elucidate the protective effects of catalpol against ischemic stroke. METHODS: A rat permanent middle cerebral artery occlusion (pMCAO) and oxygen-glucose deprivation (OGD) model was established to assess the effect of catalpol in vivo and in vitro, respectively. Behavioral tests were used to examine the effects of catalpol on neurological function of ischemic rats. Immunostaining was performed to evaluate the proliferation, migration and differentiation of neural stem cells (NSCs) as well as the angiogenesis in each group. The protein level of related molecules was detected by western-blot. The effects of catalpol on cultured NSCs as well as brain microvascular endothelial cells (BMECs) subjected to OGD in vitro were also examined by similar methods. RESULTS: Catalpol attenuated the neurological deficits and improved neurological function of ischemic rats. It stimulated the proliferation of NSCs in the subventricular zone (SVZ), promoted their migration to the ischemic cortex and differentiation into neurons or glial cells. At the same time, catalpol increased the cerebral vessels density and the number of proliferating cerebrovascular endothelial cells in the infracted cortex of ischemic rats. The level of SDF-1α and CXCR4 in the ischemic cortex was found to be enhanced by catalpol treatment. Catalpol was also shown to promote the proliferation and migration of cultured NSCs as well as the proliferation of BMECs subjected to OGD insult in vitro. Interestingly, the impact of catalpol on cultured cells was inhibited by CXCR4 inhibitor AMD3100. Moreover, the culture medium of BMECs containing catalpol promoted the proliferation of NSCs, which was also suppressed by AMD3100. CONCLUSION: Our data demonstrate that catalpol exerts neuroprotective effects by promoting neurogenesis and angiogenesis via the SDF-1α/CXCR4 pathway, suggesting the therapeutic potential of catalpol in treating cerebral ischemia.

Damage mechanism of calcium peroxide on Microcystis aeruginosa PCC7806 and its potential application.

Calcium peroxide (CP) is an oxidizing agent that can gradually release hydrogen peroxide (HP) to achieve selective killing of cyanobacteria in water blooms, and reduce the phosphorus content in the water column. Despite the potential of CP for use in cyanobacterial water bloom disposal, there is a lack of research on the mechanism of oxidative damage on cyanobacterial cells by calcium peroxide. Further studies are required to comprehend the underlying scientific principles and potential risks and benefits of applying this approach to cyanobacteria disposal. In this investigation, we employed varying doses of CP for the treatment of Microcystis aeruginosa (M. aeruginosa), which resulted in the following findings: (1) the HP released from CP can damage the photosystem II of M. aeruginosa, reduce cell photosynthetic pigment content, intensify the degree of membrane lipid peroxidation, and increase the extracellular protein content; (2) CP significantly increased the soluble extracellular polysaccharide (sEPS) and bound extracellular polysaccharide (bEPS) content of cells (p < 0.05), causing the cells to exist as agglomerates and effectively allowing them to flocculate and precipitate, reducing the turbidity of the water body; (3) The increased dose elevated the pH and calcium ions significantly decreased the orthophosphate content, resulting in an increase in extracellular alkaline phosphatase activity, but possibly increasing the total extracellular nitrogen content. These results suggested that CP is an effective chemical algaecide for cyanobacteria, and has the potential to be applied to dispose of cyanobacterial blooms while reducing the phosphorus content of the water column and further inhibiting the growth and proliferation of cells.

Utility of Trimethylamine Oxide (TMAO) in Predicting Early Neurological Deterioration after Acute Ischemic Stroke.

OBJECTIVE:  To investigate whether plasma trimethylamine N-oxide (TMAO) levels might predict early neurological deterioration (END) in individuals with acute ischemic stroke. STUDY DESIGN: Cohort study. Place and Duration of the Study: Jiulongpo District Hospital of Traditional Chinese Medicine, Chongqing City, China, from January 2020 to December 2021. METHODOLOGY:  Patients presenting with ischemic stroke were classified into the END group and the non-END group. The National Institutes of Health Stroke Scale (NIHSS) total increasing by 2 points or more within 72 hours of admission was the definition of the END. Plasma TMAO levels were determined by high-performance liquid chromatographic and tandem mass spectrometry. RESULTS:  Twenty-six (25%) of the 104 patients, diagnosed with END exhibited higher TMAO levels after admission (median 1.438 vs. 0.449 nmol/mL, p=0.001). Elevated plasma TMAO levels were significant predictors of END in univariate logistic analysis. After controlling for age, gender, and cardiovascular risk factors in the multivariate conditional logistic regression model, the plasma TMAO levels in the END group remained significantly higher than those in the non-END group (OR=6.646, 95% CI 2.434-18.147, p<0.001). In receiver operator characteristic (ROC) analysis, the sensitivity and specificity of TMAO in distinguishing the END group and the non-END group at 0.564 nmol/mL cutoff value were 0.885 and 0.679, respectively. CONCLUSION: According to this research, the development of END on admission in patients with acute ischemic stroke may be positively correlated with the elevation in plasma TMAO levels. KEY WORDS:  Trimethylamine N-oxide level, Acute ischemic stroke, Early neurological deterioration, NIHSS score.

Catalpol Alleviates Ischemic Stroke Through Promoting Angiogenesis and Facilitating Proliferation and Differentiation of Neural Stem Cells via the VEGF-A/KDR Pathway.

Stroke is one of the leading causes of disability and death globally with a lack of effective therapeutic strategies. Catalpol is a bioactive compound derived from the traditional Chinese medicine Rehmannia glutinosa and it has been shown to be protective against various neurological diseases. The potential roles of catalpol against ischemic stroke are still not completely clear. In this study, we examined the effect and mechanism of catalpol against ischemic stroke using in vivo rat distal middle cerebral artery occlusion (dMCAO) and in vitro oxygen-glucose deprivation (OGD) models. We demonstrated that catalpol indeed attenuated the neurological deficits caused by dMCAO and improved neurological function. Catalpol remarkably promoted angiogenesis, promoted proliferation and differentiation of neural stem cells (NSCs) in the subventricular zone (SVZ), and prevented neuronal loss and astrocyte activation in the ischemic cortex or hippocampal dentate gyrus (DG) in vivo. The vascular endothelial growth factor receptor 2 (KDR, VEGFR-2) inhibitor SU5416 and VEGF-A shRNA were used to investigate the underlying mechanisms. The results showed that SU5416 administration or VEGF-A-shRNA transfection both attenuated the effects of catalpol. We also found that catalpol promoted the proliferation of cultured brain microvascular endothelial cells (BMECs) and the proliferation and differentiation of NSCs subjected to OGD insult in vitro. Interestingly, the impact of catalpol on cultured cells was also inhibited by SU5416. Moreover, catalpol was shown to protect NSCs against OGD indirectly by promoting BMEC proliferation in the co-cultured system. Taken together, catalpol showed therapeutic potential in cerebral ischemia by promoting angiogenesis and NSC proliferation and differentiation. The protective effects of catalpol were mediated through VEGF-A/KDR pathway activation.

Intracellular and extracellular enzymatic responsive micelle for intelligent therapy of cancer.

Recently, the incidence of cancer keeps increasing, seriously endangers human health, and has evolved into the main culprit of human death. Conventional chemotherapeutic drugs, such as paclitaxel and doxorubicin (DOX), have some disadvantages, including low therapeutic effect, poor water solubility, high toxic side effects, short blood circulation time in the body, and so on. To improve the anti-tumor effect of the drug in vivo and reduce its side effects on the body, researchers have designed and developed a variety of responsive nanocarriers. In this work, we synthesized D-α-tocopherol polyethylene glycol 3350 succinate (TPGS3350)-Gly-Pro-Leu-Gly-Val-Arg (GPLGVR)-DOX (TPD) prodrugs in response to extracellular enzymes of matrix metalloproteinase (MMP-9) in the tumor microenvironment and FA-Asp-Glu-Val-Asp (DEVD)-DOX (FPD) prodrugs responsive to intracellular enzymes of caspase-3. Then, intracellular and extracellular enzyme-responsive TPD&FPD micelles with DOX (TPD&FPD&D) were successfully prepared through dialysis method. The outer layer of TPGS3350 can prolong the blood circulation time of micelles in vivo, followed by accumulation of micelles at tumor tissue through enhanced permeability and retention (EPR) effect. The peptide of GPLGVR can be cleaved by MMP-9 enzymes to remove the outer layer of TPGS3350, exposing the targeting molecule of folate, and then the micelles are engulfed by tumor cells through folate receptor-mediated endocytosis. After entering the tumor cells, the free DOX loaded in the micelles is released, which induces tumor cell apoptosis to activate caspase-3 in the cells, cutting the peptide DEVD to accelerate the intracellular release of the DOX, which further enhances cytotoxicity to improve antitumor effect. Electronic Supplementary Material: Supplementary material () is available in the online version of this article at 10.1007/s12274-022-4967-1.

Phototherapy and Mechanism Exploration of Biofilm and Multidrug-Resistant Helicobacter pylori by Bacteria-Targeted NIR Photosensitizer.

Helicobacter pylori (H. pylori) infection has been the leading cause of gastric cancer development. In recent years, the resistance of H. pylori against antibiotic treatment has been a great challenge for most countries worldwide. Since biofilm formation is one of the reasons for the antibiotic resistance of H. pylori, and phototherapy has emerged as a promisingly alternative antibacterial treatment, herein the bacteria-targeted near-infrared (NIR) photosensitizer (T780T-Gu) by combining positively-charged guanidinium (Gu) with an efficient phototherapeutic agent T780T is developed. The proposed molecule T780T-Gu exhibits synergistic photothermal therapy/photodynamic therapy effect against both H. pylori biofilms and multidrug-resistant (MDR) clinical strains. More importantly, the phototherapy mechanism of T780T-Gu acquired by the RNA-seq analysis indicates that structural deficiency as well as a decrease in metabolism and defense activity are the possible reasons for the efficient H. pylori phototherapy.

Efficacy of Wen-Luo-Tong on Peripheral Neuropathy Induced by Chemotherapy or Target Therapy: A Randomized, Double-Blinded, Placebo-Controlled Trial.

OBJECTIVE: To evaluate the efficacy of Wen-Luo-Tong Granules (WLT) local administration in the treatment of patients with peripheral neuropathy (PN) induced by chemotherapy or target therapy. METHODS: This study is a randomized, double-blinded, and placebo-controlled trial. Seventy-eight patients with PN induced by chemotherapy or target therapy were enrolled from China-Japan Friendship Hospital between July 2019 and January 2020. They were randomly assigned to WLT (39 cases) and control groups (39 cases) using a block randomization method. The WLT group received WLT (hand and foot bath) plus oral Mecobalamin for 1 week, while the control group received placebo plus oral Mecobalamin. The primary endpoint was PN grade evaluated by the National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE). The secondary endpoints included quantitative touch-detection threshold, neuropathy symptoms, Quality of Life Questionnaire-Chemotherapy Induced Peripheral Neuropathy (QLQ-CIPN20), and Quality of Life Questionnaire-Core30 (QLQ-C30). RESULTS: After treatment, the PN grade in the WLT group was significantly lower than that in the control group (1.00 ± 0.29 vs. 1.75 ± 0.68, P<0.01). The total effective rate in the WLT group was significantly higher than that in the control group (82.05% vs. 51.28%, P<0.01). Compared with the control group, the touch-detection thresholds at fingertips, neuropathy symptom score, QLQ-CIPN 20 (sensory scale, motor scale, autonomic scale, and sum score), and QLQ-C30 (physical functioning, role functioning, emotional functioning, and global health) in the WLT group significantly improved after treatment (P<0.01 or P<0.05). CONCLUSION: WLT local administration was significantly effective in the treatment of patients with PN induced by chemotherapy or target therapy. (Trial registration No. ChiCTR1900023862).

Simultaneous denitrification and phosphorus removal: A review on the functional strains and activated sludge processes.

Eutrophication has attracted extensive attention owing to its harmful effects to the organisms and aquatic environment. Studies on the functional microorganisms with the ability of simultaneously nitrogen (N) and phosphorus (P) removal is of great significance for alleviating eutrophication. Thus far, several strains from various genera have been reported to accomplish simultaneous N and P removal, which is primarily observed in Bacillus, Pseudomonas, Paracoccus, and Arthrobacter. The mechanism of N and P removal by denitrifying P accumulating organisms (DPAOs) is different from the traditional biological N and P removal. The denitrifying P removal (DPR) technology based on the metabolic function of DPAOs can overcome the problem of carbon source competition and sludge age contradiction in traditional biological N and P removal processes and can be applied to the treatment of urban sewage with low C/N ratio. This paper reviews the mechanism of N and P removal by DPAOs from the aspect of the metabolic pathways and enzymatic processes. The research progress on DPR processes is also summarized and elucidated. Further research should focus on the efficient removal of N and P by improving the performance of functional microorganisms and development of new coupling processes. This review can serve as a basis for screening DPAOs with high N and P removal efficiency and developing new DPR processes in the future.

Correlation between Intestinal Flora and Serum Inflammatory Factors in Post-stroke Depression in Ischemic Stroke.

OBJECTIVE: To investigate the correlation between intestinal flora and serum inflammatory factors IL-1, IL-2, IL-6 and hs-CRP in post-stroke depression (PSD) in ischemic stroke patients. STUDY DESIGN: Observational study. Study Place and Duration of Study: Jiulongpo District Hospital of Traditional Chinese Medicine, Chongqing City, China, from October 2018 to May 2020. METHODOLOGY: One hundred and sixty-three patients with ischemic stroke were divided into Group A (PSD) and Group B (no PSD), according to whether they had PSD. Intestinal flora indexes (Enterococcus faecalis, Escherichia coli and Bifidobacterium) and serum IL-1, IL-2, IL-6 and hs-CRP were detected. RESULTS: Among 163 patients with ischemic stroke, 67 (41.10%) had PSD (Group A) and 96 (58.90%) had no PSD (Group B). Contents of Enterococcus faecalis and Escherichia coli in Group A were higher than those in Group B (both p <0.001), and content of Bifidobacterium in Group A was lower than that in Group B (p <0.001). Serum IL-1, IL-2, IL-6 and hs-CRP levels in Group A were higher than those in Group B (all p <0.001). Pearson correlation test showed that contents of Enterococcus faecalis and Escherichia coli in Group A were positively correlated with IL-1, IL-2, IL-6 and hs-CRP, and content of Bifidobacterium was negatively correlated with IL-1, IL-2, IL-6 and hs-CRP. CONCLUSION: There are intestinal flora imbalance and Bifidobacterium undergrowth in patients with PSD, which can lead to overexpression of serum inflammatory factors. Both may be involved in occurrence and progress of PSD in patients with ischemic stroke. Key Words: Ischemic stroke, Post-stroke depression (PSD), Intestinal flora, Inflammatory factors.

Complete chloroplast genome of a wild-type Gardenia jasminoides ellis (rubiaceae) adapted to island climate.

Gardenia jasminoides Ellis is a traditional aromatic and medicinal plant in China. Here, the complete chloroplast genome of a wild-type gardenia adapted to island climate was assembled. The assembled genome was 155,247 bp in length, with four typical regions, i.e., a large single-copy (LSC) region (85,414 bp), a small single-copy (SSC) region (18,235 bp) and two inverted repeats (IRs) regions (25,799 bp each). In total, 138 genes were predicted, including 90 protein-coding genes, 40 tRNA genes and eight rRNA genes. The overall GC content of the chloroplast genome was 37.5%. The chloroplast genome would provide more information for the phylogeography and phylogeny study of G. jasminoides.

Network Pharmacology-Based Prediction of Catalpol and Mechanisms against Stroke.

AIM: To apply the network pharmacology method to screen the target of catalpol prevention and treatment of stroke, and explore the pharmacological mechanism of Catalpol prevention and treatment of stroke. METHODS: PharmMapper, GeneCards, DAVID, and other databases were used to find key targets. We selected hub protein and catalpol which were screened for molecular docking verification. Based on the results of molecular docking, the ITC was used to determine the binding coefficient between the highest scoring protein and catalpol. The GEO database and ROC curve were used to evaluate the correlation between key targets. RESULTS: 27 key targets were obtained by mapping the predicted catalpol-related targets to the disease. Hub genes (ALB, CASP3, MAPK1 (14), MMP9, ACE, KDR, etc.) were obtained in the key target PPI network. The results of KEGG enrichment analysis showed that its signal pathway was involved in angiogenic remodeling such as VEGF, neurotrophic factors, and inflammation. The results of molecular docking showed that ACE had the highest docking score. Therefore, the ITC was used for the titration of ACE and catalpol. The results showed that catalpol had a strong binding force with ACE. CONCLUSION: Network pharmacology combined with molecular docking predicts key genes, proteins, and signaling pathways for catalpol in treating stroke. The strong binding force between catalpol and ACE was obtained by using ITC, and the results of molecular docking were verified to lay the foundation for further research on the effect of catalpol on ACE. ROC results showed that the AUC values of the key targets are all >0.5. This article uses network pharmacology to provide a reference for a more in-depth study of catalpol's mechanism and experimental design.

Noncovalent Indocyanine Green Conjugate of C-Phycocyanin: Preparation and Tumor-Associated Macrophages-Targeted Photothermal Therapeutics.

Fabrication of a multifunctional near-infrared (NIR) theranostic nanoplatform has attracted increasing attention. Indocyanine green (ICG), a clinic-approved NIR fluorescence-imaging agent, is an excellent photothermal agent candidate. However, the stability and tumor targeting are still great obstacles for its wide application. In this work, C-phycocyanin (CPC) as a tumor-associated macrophages (TAMs) targeted vehicle was used to fabricate noncovalent ICG conjugate of CPC (ICG@CPC) via self-assembly in aqueous media. Compared to free ICG, ICG@CPC displays improved stabilities in aqueous solutions and under light irradiation and threefold increase in photothermal conversion efficiency. The in vitro results indicated that ICG@CPC could be selectively internalized into J774A.1 cells via SR-A-mediated endocytosis and lead to enhanced photocytotoxicity against J774A.1 cells. In vivo results showed that ICG@CPC had significantly improved drug accumulation in the tumor and photothermal therapeutic efficacy relative to ICG alone. This study for the first time utilizes CPC as a TAMs-targeted nanocarrier for ICG and may promote further rational design of ICG-based photothermal nanodrugs for precise and efficient cancer theranosis.

A Novel Chinese Medicine, Xinfeng Capsule, Modulates Proinflammatory Cytokines via Regulating the Toll-Like Receptor 4 (TLR4)/Mitogen-Activated Protein Kinase (MAPK)/Nuclear Kappa B (NF-κB) Signaling Pathway in an Adjuvant Arthritis Rat Model.

BACKGROUND Rheumatoid arthritis (RA) is a chronic autoimmune disease targeting joints. This research aimed to explore the effects of Xinfeng capsules (XFC) on cardiac injury in adjuvant arthritis (AA) model rats and assessed the associated mechanism. MATERIAL AND METHODS An adjuvant arthritis (AA) rat model was established by intracutaneously injection with Freund's complete adjuvant (FCA). Model rats were divided into 4 groups: an AA model group, an astragalus polysaccharides (APS) group, a methotrexate (MTX) group, and an XFC and triptolide (TPT) group. Hematoxylin-eosin (HE) staining was used to observe histopathologic changes. TUNEL assay was utilized to evaluate the apoptosis of cardiomyocytes. ELISA was utilized to evaluate levels of tumor necrosis factor alpha (TNF-alpha), interleukin 17 (IL-17), and interleukin 6 (IL-6) in myocardial tissues. Quantitative RT-PCR (qRT-PCR) was used to detect microRNA-21 (miRNA21) levels. Mitogen-activated protein kinase (MAPK)/p38, Toll-like receptor 4 (TLR4), and nuclear kappa B (NF-kappaB)/p65 levels were evaluated using Western blot. RESULTS XFC significantly improved proinflammatory response compared to the AA model group (p<0.05). XFC treatment significantly decreased the number of cells staining TUNEL-positive compared with the model group (p<0.05). XFC treatment significantly reduced TNF-alpha, IL-17, and IL-6 levels in myocardial tissues compared to the model group (p<0.05). Levels of miRNA21 were significantly lower in the XFC group compared to the AA model group (p<0.05). TLR4, MAPK/p38, and NF-kappaB/p65 expression levels were significantly lower in the XFC group than in the model group (p<0.05). CONCLUSIONS Xinfeng capsule, a traditional Chinese medicine preparation, protects against cardiac injury in AA rats by modulating proinflammatory cytokines expression via the TLR4/MAPK/NF-kappaB signaling pathway.

[Treatment Ideas and Methods for Treating Breast Cancer Guided by Molecular Classification].

The gene types of breast cancer can be classified into three types according to its molecules: Luminal type A, Luminal type B, HER-2-positive type, triple negative type. Authors combined pathological characteristics of breast cancer, biological characteristics, and comprehensive treatment, used syndrome typing based medication, and explored treatment meticulous ideas and methods of "treating the same disease with different methods" as well as "different treatment methods in accordance with patients individually".

The Quaternary evolutionary history, potential distribution dynamics, and conservation implications for a Qinghai-Tibet Plateau endemic herbaceous perennial, Anisodus tanguticus (Solanaceae).

Various hypotheses have been proposed about the Quaternary evolutionary history of plant species on the Qinghai-Tibet Plateau (QTP), yet only a handful of studies have considered both population genetics and ecological niche context. In this study, we proposed and compared climate refugia hypotheses based on the phylogeographic pattern of Anisodus tanguticus (three plastid DNA fragments and nuclear internal transcribed spacer regions from 32 populations) and present and past species distribution models (SDMs). We detected six plastid haplotypes in two well-differentiated lineages. Although all haplotypes could be found in its western (sampling) area, only haplotypes from one lineage occurred in its eastern area. Meanwhile, most genetic variations existed between populations (F ST = 0.822). The SDMs during the last glacial maximum and last interglacial periods showed range fragmentation in the western area and significant range contraction in the eastern area, respectively, in comparison with current potential distribution. This species may have undergone intraspecific divergence during the early Quaternary, which may have been caused by survival in different refugia during the earliest known glacial in the QTP, rather than geological isolation due to orogenesis events. Subsequently, climate oscillations during the Quaternary resulted in a dynamic distribution range for this species as well as the distribution pattern of its plastid haplotypes and nuclear genotypes. The interglacial periods may have had a greater effect on A. tanguticus than the glacial periods. Most importantly, neither genetic data nor SDM alone can fully reveal the climate refugia history of this species. We also discuss the conservation implications for this important Tibetan folk medicine plant in light of these findings and SDMs under future climate models. Together, our results underline the necessity to combine phylogeographic and SDM approaches in future investigations of the Quaternary evolutionary history of species in topographically complex areas, such as the QTP.

Xinfeng capsule for the treatment of rheumatoid arthritis patients with decreased pulmonary function--a randomized controlled clinical trial.

OBJECTIVE: To determine the effectiveness and safety of Xinfeng Capsules (XFC) for the treatment of rheumatoid arthritis (RA) patients with decreased pulmonary function. METHODS: This was a randomized controlled clinical trial of 80 RA patients. Participants were assigned to the trial group (40 cases) and the control group (40 cases) by block randomization. The trial group was treated with XFC, three pills each time three times daily for 2 months. The control group was treated with tripterygium glycoside (TPT), two pills each time three times daily for 2 months. Both groups were followed up after 2 months. The clinical effects, changes in joint and pulmonary function, and quality of life before and after treatment were observed; safety indices were also evaluated. RESULTS: Pain, swelling, tenderness, and duration of morning stiffness of joints were obviously decreased after treatment in both the trial and the control groups compared with baseline (P<0.01). Compared with before treatment, hand grip strength increased significantly after treatment in the trial group (P=0.0000); pulmonary function parameters such as forced expiratory volume in the first second of expiration/forced vital capacity (FEV1/FVC), 50% of the expiratory flow of forced vital capacity (FEF50), carbon monoxide diffusing capacity (DLco) were increased (P<0.01 or P<0.05); measures of quality of life such as role-physical, body pain, vitality and mental health were also improved after treatment in the trial group (all P<0.05). Joint swelling in the trial group decreased compared with the control group (P=0.0043), while hand grip strength was increased after treatment (P=0.0000). The increase in FEF50, DLco, and the dimensions of quality of life such as vitality and mental health were all significantly greater in the trial group than the control group (P<0.05 or P<0.01). CONCLUSIONS: XFC not only relieved joint pain in RA patients, but also significantly improved the ventilation and diffusion function of the lungs. Therefore, XFC could improve the whole body function and enhance the quality of life of RA patients.

Effects and mechanisms of Bazhen decoction, Siwu decoction, and Sijunzi decoction on 5-fluorouracil-induced anemia in mice.

OBJECTIVE: To investigate the effects of Bazhen decoction (BZD), Siwu decoction (SWD) and Sijunzi decoction (SJZD) in mice with anemia induced by 5-fluorouracil (5-FU) and discussed the possible pharmacological hematopoietic mechanism to provide experimental evidence for the clinical use of the three classical prescriptions in the treatment of anemia. METHODS: Anemia was induced by intravenous injection of 5-FU and 80 female Kunming mice were randomly, assigned to oral administration of SWD, SJZD, or BZD daily for 10 days. Peripheral blood cells count and bone marrow cell cycle were monitored to evaluate anti-anemia effects. Serum cytokines, interferon-γ (IFN-γ), interleukin-3 (IL-3), erythropoietin (EPO), granulocyte-macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α) were assayed. EPO mRNA expression was assayed in kidney and liver tissue homogenates. RESULTS: BZD and SWD significantly increased the number of red blood cells, hemoglobin concentration, and hematocrit, promoted bone marrow cells to enter the cell cycle, proliferate and differentiate, significantly increased IL-3 secretion, and significantly inhibited IFN-γ secretion. BZD stimulated transcription of EPO mRNA in the kidney and liver and enhanced serum EPO expression. A therapeutic effect of SJZD was not observed. CONCLUSION: BZD and SWD treatment specifically enhanced hematopoietic function and mediated myelopoiesis by altering serum cytokines levels and accelerating entry of bone marrow cells into the cell cycle. Better curative effects were achieved via nourishing both Qi and blood (BZD) than by enriching the blood (SWD) or invigorating Qi (SWZD) alone.

Xinfeng capsule for the treatment of rheumatoid arthritis patients with decreased pulmonary function--a randomized controlled clinical trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To determine the effectiveness and safety of Xinfeng Capsules (XFC) for the treatment of rheumatoid arthritis (RA) patients with decreased pulmonary function.</p><p><b>METHODS</b>This was a randomized controlled clinical trial of 80 RA patients. Participants were assigned to the trial group (40 cases) and the control group (40 cases) by block randomization. The trial group was treated with XFC, three pills each time three times daily for 2 months. The control group was treated with tripterygium glycoside (TPT), two pills each time three times daily for 2 months. Both groups were followed up after 2 months. The clinical effects, changes in joint and pulmonary function, and quality of life before and after treatment were observed; safety indices were also evaluated.</p><p><b>RESULTS</b>Pain, swelling, tenderness, and duration of morning stiffness of joints were obviously decreased after treatment in both the trial and the control groups compared with baseline (P<0.01). Compared with before treatment, hand grip strength increased significantly after treatment in the trial group (P=0.0000); pulmonary function parameters such as forced expiratory volume in the first second of expiration/forced vital capacity (FEV1/FVC), 50% of the expiratory flow of forced vital capacity (FEF50), carbon monoxide diffusing capacity (DLco) were increased (P<0.01 or P<0.05); measures of quality of life such as role-physical, body pain, vitality and mental health were also improved after treatment in the trial group (all P<0.05). Joint swelling in the trial group decreased compared with the control group (P=0.0043), while hand grip strength was increased after treatment (P=0.0000). The increase in FEF50, DLco, and the dimensions of quality of life such as vitality and mental health were all significantly greater in the trial group than the control group (P<0.05 or P<0.01).</p><p><b>CONCLUSIONS</b>XFC not only relieved joint pain in RA patients, but also significantly improved the ventilation and diffusion function of the lungs. Therefore, XFC could improve the whole body function and enhance the quality of life of RA patients.</p>

[Effect of triptolide on expressions of Notch receptors and ligands in rats with adjuvant- induced arthritis and reduced pulmonary function].

OBJECTIVE: To investigate the effects of triptolide on Notch receptor and ligand expressions in rats with adjuvant-induced arthritis (AA). METHODS: Forty rats were randomly divided into normal control (NC) group, model (MC) group, methotrexate group and triptolide groups. Rat models of AA were established by an intradermal injection of 0.1 mL Freund's complete adjuvant into the right paw. Twelve days after the injection, the rats were treated with corresponding drugs for 30 days; the rats in NC group and MC group were given saline only. Paw edema volume (E), arthritis index (AI), pulmonary function, histomorphologies, and Notch receptor/ ligand expression in the lung tissue were analyzed after the treatments. RESULTS: Compared with the NC group, E, AI, Notch3, Notch4, and Delta1 expressions in the lung tissues significantly increased while pulmonary function and pulmonary expressions of Notch1, Jagged1, and Jagged2 significantly decreased the model rats (P<0.01). Compared with the MC group, triptolide-treated rats showed significantly improved pulmonary functions, increased expressions of Notch1, Jagged1, and Jagged2 and decreased expressions of Notch3, Notch4, and Delta1 in the lungs (P<0.05, P<0.01); the therapeutic effect of triptolide was better than that of methotrexate. CONCLUSION: Triptolide can reduce inflammatory reaction and immune complex deposition to improve joint and pulmonary symptoms in rats with AA possibly by up-regulating the expressions of Notch3, Notch4, and Delta1 and down-regulating the expressions of Jagged1, Jagged2, and Notch1.

Effect of triptolide on expressions of Notch receptors and ligands in rats with adjuvant- induced arthritis and reduced pulmonary function / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of triptolide on Notch receptor and ligand expressions in rats with adjuvant-induced arthritis (AA).</p><p><b>METHODS</b>Forty rats were randomly divided into normal control (NC) group, model (MC) group, methotrexate group and triptolide groups. Rat models of AA were established by an intradermal injection of 0.1 mL Freund's complete adjuvant into the right paw. Twelve days after the injection, the rats were treated with corresponding drugs for 30 days; the rats in NC group and MC group were given saline only. Paw edema volume (E), arthritis index (AI), pulmonary function, histomorphologies, and Notch receptor/ ligand expression in the lung tissue were analyzed after the treatments.</p><p><b>RESULTS</b>Compared with the NC group, E, AI, Notch3, Notch4, and Delta1 expressions in the lung tissues significantly increased while pulmonary function and pulmonary expressions of Notch1, Jagged1, and Jagged2 significantly decreased the model rats (P<0.01). Compared with the MC group, triptolide-treated rats showed significantly improved pulmonary functions, increased expressions of Notch1, Jagged1, and Jagged2 and decreased expressions of Notch3, Notch4, and Delta1 in the lungs (P<0.05, P<0.01); the therapeutic effect of triptolide was better than that of methotrexate.</p><p><b>CONCLUSION</b>Triptolide can reduce inflammatory reaction and immune complex deposition to improve joint and pulmonary symptoms in rats with AA possibly by up-regulating the expressions of Notch3, Notch4, and Delta1 and down-regulating the expressions of Jagged1, Jagged2, and Notch1.</p>