Berberine-based self-assembly agents with enhanced synergistic antitumor efficacy.

Tumors are still a major threat to people worldwide. Nanodrug delivery and targeting systems can significantly improve the therapeutic efficacy of chemotherapeutic drugs for antitumor purposes. However, many nanocarriers are likely to exhibit drawbacks such as a complex preparation process, limited drug-loading capacity, untargeted drug release, and toxicity associated with nanocarriers. Therefore, new therapeutic alternatives are urgently needed to develop antitumor drugs. Natural products with abundant scaffold diversity and structural complexity, which are derived from medicinal plants, are important sources of new antitumor drugs. Here, two carrier-free berberine (BBR)-based nanoparticles (NPs) were established to increase the synergistic efficacy of tumor treatment. BBR can interact with glycyrrhetinic acid (GA) and artesunate (ART) to self-assemble BBR-GA and BBR-ART NPs without any nanocarriers, respectively, the formation of which is dominated by electrostatic and hydrophobic interactions. Moreover, BBR-GA NPs could lead to mitochondria-mediated cell apoptosis by regulating mitochondrial fission and dysfunction, while BBR-ART NPs induced ferroptosis in tumor cells. BBR-based NPs have been demonstrated to possess significant tumor targeting and enhanced antitumor properties compared with those of simple monomer mixes both in vitro and in vivo. These carrier-free self-assemblies based on natural products provide a strategy for synergistic drug delivery and thus offer broad prospects for developing enhanced antitumor drugs.

Target Separation and Potential Anticancer Activity of Withanolide-Based Glucose Transporter Protein 1 Inhibitors from Physalis angulata var. villosa.

The glucose transporter 1 (GLUT1) protein is involved in the basal-level absorption of glucose in tumor cells. Inhibiting GLUT1 decreases tumor cell proliferation and induces tumor cell damage. Natural GLUT1 inhibitors have been studied only to a small extent, and the structures of known natural GLUT1 inhibitors are limited to a few classes of natural products. Therefore, discovering and researching other natural GLUT1 inhibitors with novel scaffolds are essential. Physalis angulata L. var. villosa is a plant known as Mao-Ku-Zhi (MKZ). Withanolides are the main phytochemical components of MKZ. MKZ extracts and the components of MKZ exhibited antitumor activity in recent pharmacological studies. However, the antitumor-active components of MKZ and their molecular mechanisms remain unknown. A cell membrane-biomimetic nanoplatform (CM@Fe3O4/MIL-101) was used for target separation of potential GLUT1 inhibitors from MKZ. A new withanolide, physagulide Y (2), together with six known withanolides (1, 3-7), was identified as a potential GLUT1 inhibitor. Physagulide Y was the most potent GLUT1 inhibitor, and its antitumor activity and possible mechanism of action were explored in MCF-7 human cancer cells. These findings advance the development of technologies for the targeted separation of natural products and identify a new molecular framework for the investigation of natural GLUT1 inhibitors.

Historical Review of Acute Pancreatitis Research Over the Last 80 Years.

OBJECTIVES: Research on acute pancreatitis (AP) has been ongoing for a long time. It is necessary to summarize and investigate the history of AP research. METHODS: Publications related to AP research were retrieved from PubMed. Medical Subject Headings (MeSH) terms, countries, journals, and publication dates were analyzed. Co-occurrence analysis was conducted to illustrate the holistic trend in AP research. A dynamic bar graph, heat maps, and line charts were created to illustrate change trends of MeSH terms. RESULTS: In total, 28,222 publications with 8558 MeSH terms were retrieved from 1941 to 2020. Among these, 16,575 publications with 7228 MeSH terms were from 2001 to 2020. The top 10 MeSH terms showed a considerable change from 1941 to 1970 but remained stable since the 1970s. Four clusters obtained from the co-occurrence analysis were "experiments on animals," "diagnosis and treatment," "prognosis and expectation," and "protein and enzyme." From 1941 to 2020, 33 MeSH terms with increasing trends (MH-I) and 15 MeSH terms with decreasing trends (MH-D) were selected to create a heat map (every decade). Meanwhile, 16 MH-I and 41 MH-D were selected to create the heat map from 2001 to 2020 (every 2 years). CONCLUSION: Over the past 80 years, the pathogenesis, treatment, risk management, and experimental model were the main research highlights. Optimal supportive management, minimally invasive treatment, and prediction of prognosis are subjects of interest for clinical practitioners; signal transduction to identify a target for precise treatment is the focus of experimental research in AP.

Therapeutic potential and mechanism of Chinese herbal medicines in treating fibrotic liver disease.

Liver fibrosis is a pathological condition characterized by replacement of normal liver tissue with scar tissue, and also the leading cause of liver-related death worldwide. During the treatment of liver fibrosis, in addition to antiviral therapy or removal of inducers, there remains a lack of specific and effective treatment strategies. For thousands of years, Chinese herbal medicines (CHMs) have been widely used to treat liver fibrosis in clinical setting. CHMs are effective for liver fibrosis, though its mechanisms of action are unclear. In recent years, many studies have attempted to determine the possible mechanisms of action of CHMs in treating liver fibrosis. There have been substantial improvements in the experimental investigation of CHMs which have greatly promoted the understanding of anti-liver fibrosis mechanisms. In this review, the role of CHMs in the treatment of liver fibrosis is described, based on studies over the past decade, which has addressed the various mechanisms and signaling pathways that mediate therapeutic efficacy. Among them, inhibition of stellate cell activation is identified as the most common mechanism. This article provides insights into the research direction of CHMs, in order to expand its clinical application range and improve its effectiveness.

MAGT1 Deficiency Dysregulates Platelet Cation Homeostasis and Accelerates Arterial Thrombosis and Ischemic Stroke in Mice.

BACKGROUND: MAGT1 (magnesium transporter 1) is a subunit of the oligosaccharide protein complex with thiol-disulfide oxidoreductase activity, supporting the process of N-glycosylation. MAGT1 deficiency was detected in human patients with X-linked immunodeficiency with magnesium defect syndrome and congenital disorders of glycosylation, resulting in decreased cation responses in lymphocytes, thereby inhibiting the immune response against viral infections. Curative hematopoietic stem cell transplantation of patients with X-linked immunodeficiency with magnesium defect causes fatal bleeding and thrombotic complications. METHODS: We studied the role of MAGT1 deficiency in platelet function in relation to arterial thrombosis and hemostasis using several in vitro experimental settings and in vivo models of arterial thrombosis and transient middle cerebral artery occlusion model of ischemic stroke. RESULTS: MAGT1-deficient mice (Magt1-/y) displayed accelerated occlusive arterial thrombus formation in vivo, a shortened bleeding time, and profound brain damage upon focal cerebral ischemia. These defects resulted in increased calcium influx and enhanced second wave mediator release, which further reinforced platelet reactivity and aggregation responses. Supplementation of MgCl2 or pharmacological blockade of TRPC6 (transient receptor potential cation channel, subfamily C, member 6) channel, but not inhibition of store-operated calcium entry, normalized the aggregation responses of Magt1-/y platelets to the control level. GP (glycoprotein) VI activation of Magt1-/y platelets resulted in hyperphosphorylation of Syk (spleen tyrosine kinase), LAT (linker for activation of T cells), and PLC (phospholipase C) γ2, whereas the inhibitory loop regulated by PKC (protein kinase C) was impaired. A hyperaggregation response to the GPVI agonist was confirmed in human platelets isolated from a MAGT1-deficient (X-linked immunodeficiency with magnesium defect) patient. Haploinsufficiency of TRPC6 in Magt1-/y mice could normalize GPVI signaling, platelet aggregation, and thrombus formation in vivo. CONCLUSIONS: These results suggest that MAGT1 and TRPC6 are functionally linked. Therefore, deficiency or impaired functionality of MAGT1 could be a potential risk factor for arterial thrombosis and stroke.

Modelling novelty detection in the thalamocortical loop.

In complex natural environments, sensory systems are constantly exposed to a large stream of inputs. Novel or rare stimuli, which are often associated with behaviorally important events, are typically processed differently than the steady sensory background, which has less relevance. Neural signatures of such differential processing, commonly referred to as novelty detection, have been identified on the level of EEG recordings as mismatch negativity (MMN) and on the level of single neurons as stimulus-specific adaptation (SSA). Here, we propose a multi-scale recurrent network with synaptic depression to explain how novelty detection can arise in the whisker-related part of the somatosensory thalamocortical loop. The "minimalistic" architecture and dynamics of the model presume that neurons in cortical layer 6 adapt, via synaptic depression, specifically to a frequently presented stimulus, resulting in reduced population activity in the corresponding cortical column when compared with the population activity evoked by a rare stimulus. This difference in population activity is then projected from the cortex to the thalamus and amplified through the interaction between neurons of the primary and reticular nuclei of the thalamus, resulting in rhythmic oscillations. These differentially activated thalamic oscillations are forwarded to cortical layer 4 as a late secondary response that is specific to rare stimuli that violate a particular stimulus pattern. Model results show a strong analogy between this late single neuron activity and EEG-based mismatch negativity in terms of their common sensitivity to presentation context and timescales of response latency, as observed experimentally. Our results indicate that adaptation in L6 can establish the thalamocortical dynamics that produce signatures of SSA and MMN and suggest a mechanistic model of novelty detection that could generalize to other sensory modalities.

A novel purgative mechanism of multiflorin A involves changing intestinal glucose absorption and permeability.

BACKGROUND: Multiflorin A (MA) is a potential active ingredient of traditional herbal laxative, Pruni semen, with unusual purgative activity and an unclear mechanism, and inhibiting intestinal glucose absorption is a promising mechanism of novel laxatives. However, this mechanism still lacks support and a description of basic research. PURPOSE: This study aimed to determine the main contribution of MA to the purgative activity of Pruni semen and elucidate the effect intensity, characteristics, site, and mechanism of MA in mice, and determine the novel mechanism of traditional herbal laxatives from the perspective of intestinal glucose absorption. METHODS: We induced diarrhoea in mice by administering Pruni semen and MA, and the defecation behaviour, glucose tolerance, and intestinal metabolism were analysed. The effects of MA and its metabolite on peristalsis of the intestinal smooth muscle were evaluated using an intestinal motility assay in vitro. Intestinal tight junction proteins, aquaporins, and glucose transporters expression were analysed using immunofluorescence; gut microbiota and faecal metabolites were analysed using 16S rRNA and liquid chromatography-mass spectrometry. RESULTS: MA administration (20 mg/kg) induced watery diarrhoea in over half of the experimental mice. The activity of MA in lowering peak postprandial glucose levels was synchronous with purgative action, with the acetyl group being the active moiety. MA was metabolised primarily in the small intestine, where it decreased sodium-glucose cotransporter-1, occludin, and claudin1 expression, then inhibited glucose absorption, resulting in a hyperosmotic environment. MA also increased the aquaporin3 expression to promote water secretion. Unabsorbed glucose reshapes the gut microbiota and their metabolism in the large intestine and the increasing gas and organic acid promoted defecation. After recovery, the intestinal permeability and glucose absorption function returned, and the abundance of probiotics such as Bifidobacterium increased. CONCLUSION: The purgative mechanism of MA involves inhibiting glucose absorption, altering permeability and water channels to promote water secretion in the small intestine, and regulating gut microbiota metabolism in the large intestine. This study is the first systematic experimental study on the purgative effect of MA. Our findings provide new insight into the study of novel purgative mechanisms.

Astragaloside IV-mediated inhibition of oxidative stress by upregulation of ghrelin in type 2 diabetes-induced cognitive impairment.

This study is to observe the upregulation effect of astragaloside IV on ghrelin in diabetic cognitive impairment (DCI) rats and to investigate the pathway in prevention and treatment by reducing oxidative stress. The DCI model was induced with streptozotocin (STZ) in conjunction with a high-fat and high-sugar diet and divided into three groups: model, low-dose (40 mg/kg), and high-dose (80 mg/kg) astragaloside IV. After 30 days of gavage, the learning and memory abilities of rats, as well as their body weight and blood glucose levels, were tested using the Morris water maze and then detection of insulin resistance, SOD activity, and serum MDA levels. The whole brain of rats was sampled for hematoxylin-eosin and Nissl staining to observe pathological changes in the hippocampal CA1 region. Immunohistochemistry was used to detect ghrelin expression in the hippocampal CA1 region. A Western blot was used to determine changes in GHS-R1α/AMPK/PGC-1α/UCP2. RT-qPCR was used to determine the levels of ghrelin mRNA. Astragaloside IV reduced nerve damage, increased superoxide dismutase (SOD) activity, decreased MDA levels, and improved insulin resistance. Ghrelin levels and expression increased in serum and hippocampal tissues, and ghrelin mRNA levels increased in rat stomach tissues. According to Western blot, it increased the expression of the ghrelin receptor GHS-R1α and upregulated the mitochondrial function associated-protein AMPK-PGC-1α-UCP2. Astragaloside IV increases ghrelin expression in the brain to reduce oxidative stress and delay diabetes-induced cognitive impairment. It may be related to the promotion of ghrelin mRNA levels.

Bioactive Dimeric Diterpenoids from Taiwania cryptomerioides (Hayata) and Their Biological Activities.

Taiwania cryptomerioides Hayata is an endangered relict plant belonging to Taxodiaceae, and it is also an endemic plant to China. The decay-resistant of Taiwania timber can provide highly quality wood for building and furniture. Plenty of regenerative of leaves of T. cryptomerioides also has been used as a resource for the discovery of new dimeric diterpenoids. In a search for structurally diverse dimeric diterpenoids and potent bioactive isolates, ten new heterodimeric diterpenoids, taiwaniadducts K-T (1-4, 6, 8-11, and 14), along with five known ones (5, 7, 12, 13, and 15), were isolated from the leaves of T. cryptomerioides. These new compounds were defined by comprehensive spectroscopic analyses, putative biosynthetic pathways, and the values of optical. Biologically, anti-multidrug resistance (MDR) activities of compounds were evaluated. Compounds 4 and 10 exerted a 9.18-fold potentiation effect on bortezmib (BTZ) susceptibility at a tested concentration (20 µM) better than the positive control verapamil. The research of the leaves of T. cryptomerioides not only added the new data to the structural diversity and activities of dimeric diterpenoids but also could provide support for the medical and industrial application of the leaves of this endangered relict plant.

Evaluation of the distribution and mobility of labile phosphorus in sediment profiles of Lake Nansi, the largest eutrophic freshwater lake in northern China.

Understanding various biogeochemical processes, especially in eutrophic sediments, necessitates fine-scale phosphorus (P) measurements in pore waters. To the best of our knowledge, the fine-scale distributions of P across the sediment profiles of Lake Nansi have rarely been investigated. Herein we evaluated the dynamic distributions of labile P and Fe across the sediment-water interface (SWI) of Lake Nansi at two-dimensional (2D) and sub-millimeter resolution, using well-established colorimetric diffusive gradients in thin films (DGT) methodology. The concentrations of labile P in all investigated sediment profiles exhibited strong spatial variations, ranging from 0 to 1.50 mg/L with a considerable number of hotspots. Lake Nanyang (0.55 ± 0.21 mg/L) had the highest mean concentration of labile P, followed by Lake Dushan (0.38 ± 0.19 mg/L), Lake Weishan (0.28 ± 0.21 mg/L), and Lake Zhaoyang (0.18 ± 0.09 mg/L). The highest concentrations of labile P were always detected in Lake Dushan, which had been subjected to excessive exogenous P pollution. The co-distributions of labile P and Fe in the majority of the sediment of Lake Nansi confirmed highly positive correlations (P < 0.01), suggesting that the mobility of labile P throughout the SWI was likely governed by iron redox processes. The apparent diffusion fluxes of P across the SWI ranged from -7.7 to 33.6 µg/m2·d, with a mean value of 5.26 ± 7.80 µg/m2·d. Positive apparent fluxes for labile P were recorded in most sediment cores, demonstrating the strong upward mobility of P from the sediment to the overlying water. Our results provided accurate and extensive information regarding the micro-distribution and dynamic exchange of labile P across the SWI. This allows for a better understanding of eutrophication processes and the implementation of P management strategies in Lake Nansi.

Carrier-free nanoplatforms from natural plants for enhanced bioactivity.

BACKGROUND: Natural plants as well as traditional Chinese medicine have made outstanding contributions to the health and reproduction of human beings and remain the basis and major resource for drug innovation. Carrier-free nanoplatforms completely self-assembled by pure molecules or therapeutic components have attracted increasing attention due to their advantages of improved pharmacodynamics/pharmacokinetics, reduced toxicity, and high drug loading. In recent years, carrier-free nanoplatforms produced by self-assembly from natural plants have contributed to progress in a variety of therapeutic modalities. Notably, these nanoplatforms based on the interactions of components from different natural plants improve efficiency and depress toxicity. AIM OF REVIEW: In this review, different types of self-assembled nanoplatforms are first summarized, mainly including nanoassemblies of pure small molecules isolated from different plants, extracellular vesicles separated from fresh plants, charcoal nanocomponents obtained from charred plants, and nanoaggregates from plants formulae decoctions. Key Scientific Concepts of Review: We mainly focus on composition, self-assembly mechanisms, biological activity and modes of action. Finally, a future perspective of existing challenges with respect to the clinical application of plant-based carrier-free nanoplatforms is discussed, which may be instructive to further develop effective carrier-free nanoplatforms from natural plants in the future.

Providing holistic care to children with cerebral palsy treated with transnasal neural stem cell transplantation.

Objective: Holistic care is a key element in nursing care. Aiming at the heterogeneous disease of cerebral palsy, researchers focused on children with cerebral palsy who received transnasal transplantation of neural stem cells as a specific group. Based on establishing a multidisciplinary team, comprehensive care is carried out for this type of patient during the perioperative period to improve the effectiveness and safety of clinical research and increase the comfort of children. Methods: Between January 2018 and June 2023, 22 children with cerebral palsy underwent three transnasal transplants of neural stem cells. Results: No adverse reactions related to immune rejection were observed in the 22 children during hospitalization and follow-up. All children tolerated the treatment well, and the treatment was superior. One child developed nausea and vomiting after sedation; three had a small amount of bleeding of nasal mucosa after transplantation. Two children had a low fever (≤38.5°C), and one had a change in the type and frequency of complex partial seizures. Moreover, 3 children experienced patch shedding within 4 h of patch implantation into the nasal cavity. Conclusion: The project team adopted nasal stem cell transplantation technology. Based on the characteristics of transnasal transplantation of neural stem cells in the treatment of neurological diseases in children, a comprehensive and novel holistic care plan is proposed. It is of great significance to guide caregivers of children to complete proper care, further improve the safety and effectiveness of treatment, and reduce the occurrence of complications.

From macrophyte to algae: Differentiated dominant processes for internal phosphorus release induced by suspended particulate matter deposition.

In shallow lakes, eutrophication leads to a shift of the macrophyte-dominated clear state towards an algae-dominated turbid state. Phosphorus (P) is a crucial element during this shift and is usually concentrated in the suspended particulate matter (SPM) in water. However, the dominant processes controlling internal P release in the algae- (ADA) and macrophyte-dominated (MDA) areas under the influence of P-concentrated SPM remains unclear. In this study, we conducted monthly field observations of P exchange across the sediment-water interface (SWI) with the deposition of SPM in the ADA and MDA of Lake Taihu. Results revealed that both algae- and macrophyte-originated SPM led to the depletion of oxygen across the SWI during summer and autumn. Redox-sensitive P (Fe-P) and organic P (Org-P) were the dominant mobile P fractions in both areas. High fluxes of P across the SWI were observed in both areas during the summer and autumn. However, the processes controlling P release were quite different. In MDA, P release was mostly controlled by a traditional Fe-P dissolution process influenced by the coupled cycling of iron, sulfur, and P. In the ADA, Org-P control was intensified with the deterioration of algal bloom status, accompanied with the dissolution of Fe-P. Evidence from the current study revealed that the dominant process controlling the internal P release might gradually shift from Fe-P to a coupled process of Fe-P and Org-P with the shift of the macrophyte- to an algae-dominated state in shallow eutrophic lakes. The differentiated processes in the MDA and ADA should be given more attention during future research and management of internal P loadings in eutrophic lakes.

Calreticulin as an Adjuvant In Vivo to Promote Dendritic Cell Maturation and Enhance Antigen-Specific T Lymphocyte Responses against Melanoma.

An endoplasmic reticulum resident protein, calreticulin (CRT), participates in many cellular processes. CRT is a tumor-associated antigen with an important role in antitumor immunity. Previously, we reported that the recombinant CRT fragment 39-272 (CRT/39-272) exhibited superior immunobiological activity, activating macrophages to release cytokines and promoting dendritic cell (DC) maturation. However, the effect of CRT/39-272 in vivo, especially its adjuvant effect on in vivo antitumor immune responses, was not fully investigated. In this study, we constructed a fusion protein linking CRT/39-272 to an ovalbumin (OVA) peptide (residues 182-297, OVAp) and used the fusion protein (OVAp-CRT) to examine the adjuvant effect of CRT. We investigated whether CRT/39-272 could induce bone marrow-derived DC maturation and strongly promote the proliferation of OVA-specific T cells in vitro. Compared with OVAp, OVAp-CRT induced stronger antigen-specific T lymphocyte responses, including antigen-specific T cell proliferation, interferon-γ secretion, and cytotoxic T lymphocyte responses. OVAp-CRT-immunized mice generated significantly increased OVAp-specific antibody and CD4+/CD8+ memory T cells, which mediated long-term protective effects. OVAp-CRT upregulated CD40, CD80, and CD86 expressions in splenic conventional DCs. Furthermore, OVAp-CRT protected immunized mice against OVA-expressing B16 melanoma cells in vivo. Moreover, mice that were adoptively transferred with OVAp-CRT-pulsed DCs showed inhibited tumor growth and prolonged mouse survival. Our results demonstrate that CRT/39-272 can be used as a potential new adjuvant for tumor vaccines, and this finding may be useful in tumor vaccine development.

24-Epibrassinolide Promotes Fatty Acid Accumulation and the Expression of Related Genes in Styrax tonkinensis Seeds.

Styrax tonkinensis, whose seeds are rich in unsaturated fatty acids (UFAs), is a high oil value tree species, and the seed oil has perfect biodiesel properties. Therefore, the elucidation of the effect of 24-epibrassinolide (EBL) on fatty acid (FA) concentration and the expression of FA biosynthesis-related genes is critical for deeply studying the seed oil in S. tonkinensis. In this study, we aimed to investigate the changing trend of FA concentration and composition and identify candidate genes involved in FA biosynthesis under EBL treatment using transcriptome sequencing and GC-MS. The results showed that 5 µmol/L of EBL (EBL5) boosted the accumulation of FA and had the hugest effect on FA concentration at 70 days after flowering (DAF). A total of 20 FAs were identified; among them, palmitic acid, oleic acid, linoleic acid, and linolenic acid were the main components. In total, 117,904 unigenes were detected, and the average length was 1120 bp. Among them, 1205 unigenes were assigned to 'lipid translations and metabolism' in COG categories, while 290 unigenes were assigned to 'biosynthesis of unsaturated fatty acid' in KEGG categories. Twelve important genes related to FA biosynthesis were identified, and their expression levels were confirmed by quantitative real-time PCR. KAR, KASIII, and accA, encoding FA biosynthesis-related enzymes, all expressed the highest at 70 DAF, which was coincident with a rapid rise in FA concentration during seed development. FAD2 and FATB conduced to UFA and saturated fatty acids (SFA) accumulation, respectively. EBL5 induced the expression of FA biosynthesis-related genes. The concentration of FA was increased after EBL5 application, and EBL5 also enhanced the enzyme activity by promoting the expression of genes related to FA biosynthesis. Our research could provide a reference for understanding the FA biosynthesis of S. tonkinensis seeds at physiological and molecular levels.

The ethanol extract of Periplaneta Americana L. improves ulcerative colitis induced by a combination of chronic stress and TNBS in rats.

PURPOSE: To investigate the effects of Periplaneta americana L. on ulcerative colitis (UC) induced by a combination of chronic stress (CS) and 2,4,6-trinitrobenzene sulfonic acid enema (TNBS) in rats. METHODS: The experiment UC model with CS was established in rats by a combination of chronic restraint stress, excess failure, improper, and TNBS. The body weight, disease activity index (DAI), colonic mucosal injury index (CMDI), histopathological score (HS) and pro-inflammatory mediators were measured. The content of corticotropin-releasing hormone (CRH) in hypothalamus or adrenocorticotropic hormone (ACTH) and corticosteroids (CORT) in plasma were evaluated by enzyme-linked immunosorbent assay. The proportion of T lymphocyte subsets was detected by flow cytometry, and gut microbiota was detected by 16S rDNA amplicon sequencing. RESULTS: Weight loss, DAI, CMDI, HS and proinflammatory mediators were reversed in rats by P. americana L. treatment after UC with CS. Increased epidermal growth factor (EGF) was observed in P. americana L. groups. In addition, P. americana L. could reduce the content of CRH and ACTH and regulate the ratio of CD3+, CD3+CD8+ and CD3+CD4+CD25+/CD4+ in spleen. Comparably, P. americana L. changes composition of gut microbiota. CONCLUSIONS: The ethanol extract of Periplaneta Americana L. improves UC induced by a combination of CS and TNBS in rats.

Promising natural lysine specific demethylase 1 inhibitors for cancer treatment: advances and outlooks.

Lysine specific demethylase 1 (LSD1), a transcriptional corepressor or coactivator that serves as a demethylase of histone 3 lysine 4 and 9, has become a potential therapeutic target for cancer therapy. LSD1 mediates many cellular signaling pathways and regulates cancer cell proliferation, invasion, migration, and differentiation. Recent research has focused on the exploration of its pharmacological inhibitors. Natural products are a major source of compounds with abundant scaffold diversity and structural complexity, which have made a major contribution to drug discovery, particularly anticancer agents. In this review, we briefly highlight recent advances in natural LSD1 inhibitors over the past decade. We present a comprehensive review on their discovery and identification process, natural plant sources, chemical structures, anticancer effects, and structure-activity relationships, and finally provide our perspective on the development of novel natural LSD1 inhibitors for cancer therapy.

Acupuncture-related therapies for the poststroke cognitive impairment patients: A protocol for systematic review and network meta-analysis.

BACKGROUND: To compare and rank the clinical effects of different acupuncture and acupuncture-related therapies on patients with poststroke cognitive impairment. METHODS: We evaluated the direct and indirect evidence from relevant studies using network meta-analysis. Eight databases were examined in order to find randomized controlled trials of acupuncture-related therapies for individuals with poststroke cognitive impairment. After 2 researchers independently scanned the literature, extracted the data, and assessed the risk of bias in the included studies, the data were analyzed using RevMan5.4, Stata15.0, and WinBUGS1.4.3 software. RESULTS: We assess the benefits and drawbacks of various acupuncture-related therapies, rank the efficacy of various acupuncture-related therapies in the treatment of poststroke cognitive impairment, and describe the best acupuncture intervention approaches or combinations based on the available data. CONCLUSION: This study will contribute to the existence of data on the safety and efficacy of acupuncture-related therapies in the treatment of poststroke cognitive impairment, and it may aid clinical guideline makers in selecting the best acupuncture treatment for poststroke cognitive impairment. REGISTRATION NUMBER: INPLASY2021120117.

The diagnosis and management of intestinal obstruction after pediatric liver transplantation.

BACKGROUND: The aim of this study was to analyze the risk factors, causes, and management of intestinal obstruction after pediatric liver transplantation. METHODS: Retrospective analysis was performed on pediatric liver transplantation recipients from January 1st 2013 to December 31st 2019 at Organ Transplant Center, Tianjin First Central Hospital. The cases of intestinal obstruction were analyzed. RESULTS: A total of 1034 pediatric liver transplantations were performed during the study period, 66 intestinal obstructions were diagnosed in 61 recipients. Three recipients suffered intestinal obstructions twice, and one recipient suffered three times. Forty of the 66 cases were treated with non-surgical treatment, including fasting, gastrointestinal decompression, purgation, enema, and parenteral nutrition. Surgical intervention was performed in 26 cases. Diaphragmatic hernia, intestinal inflammatory stenosis, PTLD, and intestine perforation are essential causes of intestinal obstruction in pediatric liver transplant recipients. Diaphragmatic hernia was independent risk factors for intestinal obstruction. The 1-, 2- and 3-year survival rate of the recipients with or without intestinal obstruction were 98.4%, 96.5%, 96.5% and 95.3%, 94.4%, 94.0%, respectively, without significant difference. CONCLUSIONS: Most cases of intestinal obstruction after liver transplantation in children can be remitted by non-surgical treatment, but there are still some cases need to be treated by surgery. Both measures are related to ideal outcomes, intestinal obstruction does not increase the mortality rate in pediatric liver transplantation.

Characterizing the Diffusion and Rheological Properties of Aged Asphalt Binder Rejuvenated with Bio-Oil Based on Molecular Dynamic Simulations and Laboratory Experimentations.

Soybean-derived bio-oil is one of the vegetable-based oils that is gaining the most interest for potential use in the rejuvenation of aged asphalt binders. This laboratory study was conducted to characterize and quantify the diffusion and rheological properties of bio-oil-rejuvenated aged asphalt binder (BRAA) using soybean oil. In the study, the chemical structure of the soybean oil was comparatively characterized using an element analyzer (EA), gel permeation chromatography (GPC), and a Fourier infrared (FTIR) spectrometer, respectively. Based on the chemical structure of the bio-oil, BRAA molecular models were built for computing the diffusion parameters using molecular dynamic simulations. Likewise, a dynamic shear rheometer (DSR) test device was used for measuring and quantifying the rheological properties of the aged asphalt binder rejuvenated with 0%, 1%, 2%, 3%, 4%, and 5% soybean oil, respectively. The laboratory test results indicate that bio-oil could potentially improve the diffusion coefficients and phase angle of the aged asphalt binder. Similarly, the corresponding decrease in the complex shear modulus has a positive effect on the low-temperature properties of BRAA. For a bio-oil dosage 4.0%, the diffusion coefficients of the BRAA components are 1.52 × 10-8, 1.33 × 10-8, 3.47 × 10-8, 4.82 × 10-8 and 3.92 × 10-8, respectively. Similarly, the corresponding reduction in the complex shear modulus from 1.27 × 107 Pa to 4.0 × 105 Pa suggests an improvement in the low-temperature properties of BRAA. Overall, the study contributes to the literature on the potential use of soybean-derived bio-oil as a rejuvenator of aged asphalt binders.