Corn stigma ameliorates hyperglycemia in zebrafish and GK rats of type 2 diabetes.

ETHNOPHARMACOLOGICAL RELEVANCE: Cornstigma (CS), derived from the stigma and style of gramineous plant Zeamays. The medicinal use of CS can be traced back to DianNanMateriaMedica. LingnanMedicinalPlantsCompendium records its effectiveness in ameliorating diabetes. Diabetes is a metabolic disorder characterized by hyperglycemia and the consequent chronic complications of kidney, heart, brain and other organs, which pose a significant threat to human health. CS has shown great potential in relieving hyperglycemia associated with diabetes. However, the mechanism of CS in treating diabetes remains unclear. AIM OF THE STUDY: To explore the pathogenesis of diabetes and the mechanism of CS improving hyperglycemia in diabetes. MATERIALS AND METHODS: We measured apigenin and luteolin contents in CS by UPLC/MS/MS method. Selecting Wistar rats as normal group, and GK rats as model group. For rats, we detected glucose and lipid metabolism indicators, including GHb, AST, ALT, U-Glu, UA, U-TP, U-ALB, and ACR after treatment. For zebrafish, we utilized alloxan and sucrose to establish the diabetes model. Measuring zebrafish blood glucose is employed to evaluate the hypoglycemic capability of CS. In order to explore the mechanism of CS in treating diabetes, we sequenced the transcriptome of zebrafish, compared differentially expressed genes of normal, diabetic, and CS-treated group, and validated multiple enrichment pathways by PCR. RESULTS: CS can improve blood glucose levels in both GK rats and diabetic zebrafish. For rats, CS partially restored glucose and lipid metabolism indicators. Transcriptome data from zebrafish showed a close correlation with steroid biosynthesis. The RNA-Sequencing was consistent with PCR results, indicating that CS downregulated gene (fdft1,lss,cyp51) expression concerned with steroid biosynthesis pathway in the diabetes model. CONCLUSION: CS effectively improved blood glucose levels, regulated glucose and lipid metabolism by suppressing gene expression in steroid biosynthesis pathway, and ameliorated hyperglycemia. Our research provides valuable insights for CS in the treatment of diabetes, and proposes a new strategy for selecting clinical medications for diabetes.

Contrasting effects of MgAl- and MgFe-based layered double hydroxides on phosphorus mobilization and microbial communities in sediment.

The effects of two types of layered double hydroxides (LDH) in-situ treatment on sediment phosphorus (P) mobilization and microbial community's structure were studied comparatively. The results presented that magnesium/aluminum-based (MA) and magnesium/iron (MF)-based LDH displayed great phosphate uptake ability in aqueous solution in a broad pH range of 3-8. The maximum phosphate sorption capacity of MA was 64.89 mg/g, around four times greater than that of MF (14.32 mg/g). Most of phosphate bound by MA and MF is hard to re-liberate under reduction and ordinary pH (5-9) conditions. In the in-situ remediation, the MA and MF capping/amendment both prevented P migration from the sediment to the overlying water (OL-water) under long-term anaerobic conditions, and MA had a better interception efficiency compared to MF in the same application mode. MA amendment significantly reduced mobile P (Mob-P) content in sediment and could remain its stable Mob-P inactivation capacity over a wide pH range. On the contrary, MF amendment increased Mob-P content in sediment and exhibited a variable ability to inactivate Mob-P under elevated pH conditions. MF can decrease Mob-P content at pH of 7 and 11 but increase Mob-P content at pH of 8-10. Under resuspension conditions, MA and MF capping groups still maintained low P levels in OL-water, while MA capping simultaneously showed a certain degree of resistance to sediment resuspension, but it had a weaker stabilizing effect for sediment than MF. Microbial community analysis manifested neither MA nor MF addition observably altered the sediment microbial diversity, but impacted the functional microorganisms' abundance and reshaped the microbial community's structure, intervening the sediment-P stabilization. Viewed from environmental friendliness, control efficiency, stability of P fixation capacity, and application convenience, MA capping wrapped by fabric is more suitable for addressing internal P loading in eutrophic lakes and holds great potential application.

Danhong injection improves neurological function in rats with ischemic stroke by enhancing neurogenesis and activating BDNF/AKT/CREB signaling pathway.

Danhong injection (DHI) is a traditional Chinese medicine injection that promotes blood circulation and removes blood stasis and has been widely used in the treatment of stroke. Many studies have focused on the mechanism of DHI in acute ischemic stroke (IS); however, few studies have thoroughly explored its role during recovery. In this study, we aimed to determine the effect of DHI on long-term neurological function recovery after cerebral ischemia and explored the related mechanisms. Middle cerebral artery occlusion (MCAO) was used to establish an IS model in rats. The efficacy of DHI was assessed using neurological severity scores, behaviors, cerebral infarction volume and histopathology. Immunofluorescence staining was performed to assess hippocampal neurogenesis. An in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) cell model was constructed and western-blot analyses were performed to verify the underlying mechanisms. Our results showed that DHI treatment greatly reduced the infarct volume, promoted neurological recovery and reversed brain pathological changes. Furthermore, DHI promoted neurogenesis by increasing the migration and proliferation of neural stem cells, and enhancing synaptic plasticity. Moreover, we found that the pro-neurogenic effects of DHI were related to an increase in brain-derived neurotrophic factor (BDNF) expression and the activation of AKT/CREB, which were attenuated by ANA-12 and LY294002, the inhibitors of the BDNF receptor and PI3K. These results suggest that DHI improves neurological function by enhancing neurogenesis and activating the BDNF/AKT/CREB signaling pathways.

KDM4C Contributes to Trophoblast-like Stem Cell Conversion from Porcine-Induced Pluripotent Stem Cells (piPSCs) via Regulating CDX2.

Studies on ESRRB-regulating porcine-induced pluripotent stem cells (piPSCs) converted to trophoblast-like stem cells (TLSCs) contribute to the understanding of early embryo development. However, the epigenetic modification regulation network during the conversion is poorly understood. Here, the global change in histone H3 Lysine 4, 9, 27, 36 methylation and Lysine 27 acetylation was investigated in piPSCs and TLSCs. We found a high modification profile of H3K36me2 in TLSCs compared to that of piPSCs, whereas the profiles of other modifications remained constant. KDM4C, a H3K36me3/2 demethylase, whose gene body region was combined with ESRRB, was upregulated in TLSCs. Moreover, KDM4 inhibitor supplementation rescued the AP-negative phenotype observed in TLSCs, confirming that KDM4C could regulate the pluripotency of TLSCs. Subsequently, KDM4C replenishment results show the significantly repressed proliferation and AP-positive staining of TLSCs. The expressions of CDX2 and KRT8 were also upregulated after KDM4C overexpression. In summary, these results show that KDM4C replaced the function of ESRRB. These findings reveal the unique and crucial role of KDM4C-mediated epigenetic chromatin modifications in determination of piPSCs' fate and expand the understanding of the connection between piPSCs and TSCs.

Tractography of the stria terminalis in the human brain.

The aim of this study was to investigate the trajectory of the stria terminalis and develop a protocol for mapping the stria terminalis using multi-shell diffusion images based tractography. The stria terminalis was reconstructed by combining one region of interest at the amygdala with another region of interest at the bed nucleus of stria terminalis. In addition, one region of avoidance was placed on the fornix at the interventricular foramen and another was set at the anterior perforated substance. The fiber-tracking protocol was tested in a Human Connectome Project-842 template, 35 healthy subjects from Massachusetts General Hospital, and 20 healthy subjects from the Human Connectome Project using generalized q-sampling imaging based tractography. The stria terminalis was reconstructed in the Human Connectome Project-842 template, 35 Massachusetts General Hospital healthy subjects, and 20 Human Connectome Project healthy subjects with our protocol. The stria terminalis originated from the amygdala and traveled parallel to the fornix. Then, the stria terminalis followed a C-shaped trajectory around the inferior, posterior, and dorsal surfaces of the thalamus before projecting to the bed nucleus of stria terminalis between the thalamus and caudate nucleus. There were no significant differences in the quantitative anisotropy and fractional anisotropy values between the left and right stria terminalis. The stria terminalis was accurately visualized across subjects using multi-shell diffusion images through generalized q-sampling imaging based tractography. This method could be an important tool for the reconstruction and evaluation of the stria terminalis in various neurological disorders. One Sentence Summary The visualization of the stria terminalis through the multi-shell diffusion images using generalized q-sampling imaging based tractography.

Treatment of Chronic Aplastic Anemia with Chinese Patent Medicine Pai-Neng-Da Capsule () for Replacing Androgen Partially: A Clinical Multi-Center Study.

OBJECTIVE: To evaluate the efficacy and safety of Pai-Neng-Da Capsule (, panaxadiol saponins component, PNDC) in combination with the cyclosporine and androgen for patients with chronic aplastic anemia (CAA). METHODS: A total of 79 CAA patients was randomly divided into 2 groups by a random number table, including PCA group [43 cases, orally PNDC 320 mg/d plus cyclosporine 5 mg/(kg·d) plus andriol 80 mg/d] and CA group [36 cases, orally cyclosporine 5 mg/(kg·d) plus andriol 160 mg/d]. All patients were treated and followed-up for 6 treatment courses over 24 weeks. The complete blood counts, score of Chinese medical (CM) symptoms were assessed and urine routine, electrocardiogram, hepatic and renal function were observed for safety evaluation. Female masculinization rating scale was established according to the actual clinical manifestations to evaluate the accurate degree of masculinization in female CAA patients treated by andriol. RESULTS: The effective rates were 88.1% (37/42) in the PCA group and 77.8% (28/36) in the CA group based on the standard for the therapeutic efficacy evaluation of hematopathy. There was no significant difference in the white blood cell (WBC) counts, platelet counts and hemoglobin concentration of peripheral blood between two groups after 6 months treatment. The masculinization score of female patient in the PCA group was significantly lower than the CA group (P<0.05). The mild abdominal distention was observed in 1 cases in the PCA group. In CA group, the abnormalities in the hepatic function developed in 2 cases and the renal disfunction was found in 1 case. CONCLUSION: The PNDC possesses certain curative effects in the treatment of CAA without obvious side-effects and can partially replace andriol thereby to reduce the degree of masculinization [Registried at Chinese Clinical Trial Registry (ChicTR1900028153)].

Tractography of the ansa lenticularis in the human brain.

The aim of this study was to make a thorough investigation of the trajectory of the ansa lenticularis (AL) and its subcomponents using high-resolution fiber-tracking tractography. The subcomponents of the AL were reconstructed from one region of interest (ROI) in the area of the globus pallidus combined with another ROI in the red nucleus, substantia nigra, subthalamic nucleus, or thalamus. This fiber-tracking protocol was tested in an HCP-1065 template, 35 healthy subjects from Massachusetts General Hospital (MGH), and 20 healthy subjects from the human connectome project (HCP) using generalized q-sampling imaging (GQI)-based tractography. Quantitative anisotropy and fractional anisotropy were also computed for the AL subcomponents. The subcomponents of the AL could be reconstructed in the HCP-1065 template, 35 MGH healthy subjects, and 20 HCP healthy subjects. The AL descends from the globus pallidus and joins the ansa peduncularis for a short distance, subdividing later into fibers that continue separately to the red nucleus, substantia nigra, subthalamic nucleus, and thalamus. The study demonstrated the trajectory of the ansa lenticularis and its subcomponents using GQI-based tractography, improving our understanding of the anatomical connectivity between the globus pallidus and the thalamo-subthalamic region in the human brain. One Sentence Summary The investigation of the ansa lenticularis and its subcomponents using high-resolution diffusion images based tractography.

Chinese Medicine Regulates DNA Methylation to Treat Haematological Malignancies: A New Paradigm of "State-Target Medicine".

Aberrant regulation of DNA methylation plays a crucial causative role in haematological malignancies (HMs). Targeted therapy, aiming for DNA methylation, is an effective mainstay of modern medicine; however, many issues remain to be addressed. The progress of epigenetic studies and the proposed theory of "state-target medicine" have provided conditions to form a new treatment paradigm that combines the "body state adjustment" of CM with targeted therapy. We discussed the correlation between Chinese medicine (CM) syndromes/states and DNA methylation in this paper. Additionally, the latest research findings on the intervention and regulation of DNA methylation in HMs, including the core targets, therapy status, CM compounds and active components of the Chinese materia medica were concisely summarized to establish a theoretical foundation of "state-target synchronous conditioning" pattern of integrative medicine for HMs, simultaneously leading a new perspective in clinical diagnosis and therapy.

Integrative analysis of key candidate genes and signaling pathways in autoimmune thyroid dysfunction related to anti-CTLA-4 therapy by bioinformatics.

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), the first immune checkpoint to be targeted clinically, has provided an effective treatment option for various malignancies. However, the clinical advantages associated with CTLA-4 inhibitors can be offset by the potentially severe immune-related adverse events (IRAEs), including autoimmune thyroid dysfunction. To investigate the candidate genes and signaling pathways involving in autoimmune thyroid dysfunction related to anti-CTLA-4 therapy, integrated differentially expressed genes (DEGs) were extracted from the intersection of genes from Gene Expression Omnibus (GEO) datasets and text mining. The functional enrichment was performed by gene ontology (GO) annotation and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. Protein-protein interaction (PPI) network, module enrichment, and hub gene identification were constructed and visualized by the online Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software. A total of 22 and 17 integrated human DEGs in hypothyroidism and hyperthyroidism group related to anti-CTLA-4 therapy were identified, respectively. Functional enrichment analysis revealed 24 GO terms and 1 KEGG pathways in the hypothyroid group and 21 GO terms and 2 KEGG pathways in the hyperthyroid group. After PPI network construction, the top five hub genes associated with hypothyroidism were extracted, including ALB, MAPK1, SPP1, PPARG, and MIF, whereas those associated with hyperthyroidism were ALB, FCGR2B, CD44, LCN2, and CD74. The identification of the candidate key genes and enriched signaling pathways provides potential biomarkers for autoimmune thyroid dysfunction related to anti-CTLA-4 therapy and might contribute to the future diagnosis and management of IRAEs for cancer patients.

Chinese Medicine Treatment on Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

Graft-versus-host disease (GVHD) is the most common complication after allogeneic hematopoietic stem cell transplantation, and also an important factor affecting the survival and quality of life in patients after transplantation. Currently, immunosuppressive therapy is commonly used for GVHD, but the curative effect is not ideal. How to effectively prevent and treat GVHD is one of the difficulties to be solved urgently in the field of transplantation. In this paper, we summarize the latest progress in pathogenesis, prevention and treatment of GVHD with Chinese medicine (CM). We hope it will provide ideas and methods for exploring the mechanism and establishing a new comprehensive therapy for GVHD with CM.

Combined use of calcium nitrate, zeolite, and anion exchange resin for controlling phosphorus and nitrogen release from sediment and for overcoming disadvantage of calcium nitrate addition technology.

Ca(NO3)2 addition has proved to have a high potential to immobilize internal phosphorus (P) in sediments; however, it cannot effectively stop the release of ammonium-nitrogen (NH4+-N) from sediments into overlying waters (OL-waters). Additionally, the addition of Ca(NO3)2 alone has high risk of nitrate-nitrogen (NO3--N) releasing into OL-waters. To overcome the shortcoming of the Ca(NO3)2 addition method, we reported an integrated method, i.e., a combined method based on Ca(NO3)2 injection, zeolite capping, and anion exchange resin (AERN)-contained floating system suspending (Ca(NO3)2/zeolite/AERN). The effectiveness and mechanism of the Ca(NO3)2/zeolite/AERN method for simultaneously controlling the release of soluble reactive P (SRP) and NH4+-N were investigated, and the NO3--N releasing risk of this method was evaluated. It was found that the joint use of Ca(NO3)2 injection, zeolite capping, and AERN-contained floating system suspending not only could effectively suppress the release of SRP and NH4+-N from sediments into OL-waters simultaneously, but also had much less risk of NO3--N releasing into OL-waters as compared to the single Ca(NO3)2 injection method and the combined Ca(NO3)2/zeolite method. The inhibition of the reductive dissolution of the P-bound Fe(III) oxides/hydroxides by the presence of nitrate and the adsorption of ammonium on the zeolite played very important roles in the interception of SRP and NH4+-N releasing into OL-waters by the Ca(NO3)2/zeolite/AERN method. After the sediment remediation using the Ca(NO3)2/zeolite/AERN approach, the increase in the content of residual P in the sediment layer of 0-50 mm, the decrease of mobile P in the sediment layer of 0-10 mm, and the increased NH4+-N adsorption capacity for the sediment layer of 0-10 mm would be conductive to the interception of SRP and NH4+-N liberation in the long run. Results of this research suggest a promising application potential of the Ca(NO3)2/zeolite/AERN method in the simultaneous control of the release of SRP and NH4+-N from sediments.

Assessment of iron-modified calcite/zeolite mixture as a capping material to control sedimentary phosphorus and nitrogen liberation.

Calcite/zeolite mixture (CZ) can be used to construct a capping layer for the simultaneous management of phosphorus (P) and nitrogen (N) liberation from sediments into the overlying water (OVER-water). However, its control efficiency of sedimentary P release still needs to be improved. To address this issue, an iron-modified CZ (Fe-CZ) was synthesized, characterized, and employed as a capping material to simultaneously prevent P and N release from sediments into OVER-water. Batch and microcosm incubation experiments were performed to study the efficiency and mechanism for the control of P and N release from sediments by capping Fe-CZ. Results showed that sediment capping with Fe-CZ resulted in the significant reduction of soluble reactive P (SRP) and ammonium-N (NH3-N) in OVER-water, with reduction rates of 77.8-99.7% and 54.0-96.7%, respectively. Furthermore, the Fe-CZ capping layer decreased the SRP concentration in the pore water (PORE-water) at depth of 0-30 mm and reduced the concentration of PORE-water NH3-N at depth of 0-50 mm. Moreover, the Fe-CZ capping layer gave rise to the great decrement of the concentration of the labile P measured by DGT (diffusive gradient in thin films) technology (P-DGT) in the profile of OVER-water and sediment. Additionally, the Fe-CZ capping resulted in the reduction of redox-sensitive P (P-BD) in the 0-50 mm sediment and caused the transformation of P-BD to calcium-bound P (P-HCl) and residual P (P-RES) in the 0-10 mm sediment as well as to P-RES in the 10-20 mm sediment. Results of this work indicate that the Fe-CZ capping has a high potential for the simultaneous management of P and N release from sediments, and the decrease of the contents of sediment P-DGT, sediment P-BD, PORE-water SRP and PORE-water NH3-N as well as the conversion of mobile P to more stable P in the top sediment should have a significant role in the simultaneous interception of sedimentary P and N liberation into OVER-water by the Fe-CZ capping.

Simultaneous control of nitrogen and phosphorus release from sediments using iron-modified zeolite as capping and amendment materials.

The use of zeolite as a geo-engineering tool has a high potential to control nitrogen (N) release from sediments, but its efficiency for controlling sedimentary phosphorus (P) release still need to be further increased. To address this issue, this work synthesized an iron-modified zeolite (IM-Z) by coating iron onto the surface of natural zeolite (NAT-Z) and then the as-obtained IM-Z was utilized as a geo-engineering material to block the upward mobilization of N and P from sediments to the overlying water. The efficiencies of IM-Z covering and amendment to prevent the liberation of N and P from sediments were evaluated, and the controlling mechanism was explored. Capping and amendment with IM-Z not only resulted in the tremendous reduction of the levels of ammonium-N (NH4+-N) and reactive soluble P (RSP) in the overlying water, but also led to the decrease of the contents of NH4+-N and RSP in the pore water. More importantly, sediment capping and amendment with IM-Z resulted in the formation of a static layer in the upper sediment directly below the sediment-water interface, with very low concentration of RSP in the pore water. In addition, IM-Z capping and addition effectively immobilized the diffusive gradients in thin films (DGT)-labile P in the overlying water and sediment. Furthermore, the decrease of the DGT-labile Fe concentrations in the overlying water as well as the top sediment were also observed after IM-Z capping and addition. Nearly 70% of P bound by IM-Z is stable and difficult to be released back into the overlying water under common pH and anoxic conditions. The adsorption of pore water NH4+-N on IM-Z, the immobilization of pore water RSP and DGT-labile P by IM-Z and the uptake of DGT-labile Fe on IM-Z played a significant role in the simultaneous control of NH4+-N and RSP liberation. Compared to NAT-Z, the efficiency of IM-Z to block the liberation of sedimentary P was higher. Results of this study demonstrate that IM-Z is suitable for use in the simultaneous interception of the upward transportation of NH4+-N and RSP from sediments into the overlying water.

Assessment of sediment capping with zirconium-modified bentonite to intercept phosphorus release from sediments.

Three different types of zirconium-modified bentonites (ZrMBs) including zirconium-modified original bentonite (ZrMOB), zirconium-modified magnesium-pretreated bentonite (ZrMMgB), and zirconium-modified calcium-pretreated bentonite (ZrMCaB) were synthesized and used as active covering materials to suppress the release of phosphorus (P) from sediments. To assess the covering efficiency of ZrMBs to inhibit P release from sediments, we examined the impact of ZrMB covering layer on P mobilization in sediments at different depths as well as the release of P through the interface between sediment and overlying water (SWI) by use of simulating P release control experiments and diffusive gradients in thin films (DGT) technology. The results showed that the amount of soluble reactive P (SRP) in the overlying water greatly decreased after covering with ZrMBs. Moreover, both pore water SRP and DGT-liable P (DGT-P) in the top sediments decreased after capping with ZrMBs. An obvious stratification of DGT-P was observed along the vertical direction after covering with ZrMBs, and static and active layers were found in the top sediment and in the lower sediment directly below the static layer, respectively. Furthermore, ZrMB covering led to the change of P species from easily released P to relatively or very stable P, making P in the top sediment more stable compared to that without ZrMB covering. Besides, an overwhelming majority of P immobilized by ZrMBs is hard to be re-released into the water column in a common environment. Overall, the above results demonstrate that sediment covering with ZrMBs could effectively prevent the transport of SRP from sediments into the overlying water through the SWI, and the control of P transport into the overlying water by ZrMB covering could be mostly due to the immobilization of pore water SRP, DGT-P, and mobile P in the top sediment by ZrMBs.