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Antidiabetic activity of perylenequinonoid-rich extract from Shiraia bambusicola in KK-Ay mice with spontaneous type 2 diabetes mellitus.

ETHNOPHARMACOLOGICAL RELEVANCE: Bitter and cold traditional Chinese medicines (TCMs) have been long used to treat diabetes mellitus (DM) based on unique medical theory system since ancient China. As one of bitter and cold TCMs, the stromatas of Shiraia bambusicola have been used for the treatment of DM and exerted clinical effects to a certain extent. However, the corresponding active principles and antidiabetic mechanism of the TCM still remain unknown. Therefore, the aim of the present investigation was to evaluate the potential antidiabetic effect of the active Shiraia bambusicola EtOAc ext

Effect of vascular endothelial growth factor on cultured endothelial cell monolayer transport properties.

Vascular endothelial growth factor (VEGF) is a potent enhancer of microvascular permeability in vivo. To date, its effects on hydraulic conductivity (L(p)) and diffusive albumin permeability (P(e)) of endothelial monolayers have not been thoroughly assessed in vitro. We hypothesized that VEGF affects endothelial transport properties differently depending on vessel location and endothelial phenotype. Using three well-established endothelial cell culture models-human umbilical vein endothelial cells (HUVECs), bovine aortic endothelial cells (BAECs), and bovine retinal microvascular cells (BRECs)

Induction of the transcription factor AP-1 in cultured human colon adenocarcinoma cells following exposure to bile acids.

We studied the effects of bile acids on inducibility of the transcription factor AP-1 in human colon carcinoma LoVo cells. Firstly, cells were treated with chenodeoxycholic acid and the nuclear extracts from those cells were processed by electrophoretic mobility shift assays to analyze nuclear AP-1 DNA-binding activity. We demonstrated that chenodeoxycholic acid induced AP-1 DNA-binding activity in a dose- and time-dependent fashion. Antibody supershift experiments clearly revealed that the majority of protein components in induced AP-1 DNA-binding activity were the products of oncogenes c-fos

Functional associations of CD38 with CD3 on the T-cell membrane.

CD38 is a multifunctional membrane surface glycoprotein expressed by different cells and tissues, including T cells at certain stages of their development. Besides its involvement in transmembrane signaling, CD38 play a role in cell adhesion processes. Structurally, membrane CD38 was reported as presenting lateral associations with molecules involved in recognition and signaling, namely with the TCR/CD3 complex in T cells. Here we report that ligation of CD38 by agonistic and non-agonistic monoclonal antibodies exerts different effects on T cells, the former inducing down-modulation of the ass

The cytoplasmic domain of P-selectin is phosphorylated on serine and threonine residues.

P-selectin is an adhesion receptor for leukocytes that is redistributed from secretory granule membranes to the surfaces of activated platelets and endothelial cells. The cytoplasmic domain of P-selectin contains two serines, two threonines, and one tyrosine that could potentially be phosphorylated. We found that P-selectin was phosphorylated in both platelets and endothelial cells and that phosphorylation rapidly increased after cell activation. Approximately 0.02, 0.05, and 0.08 mol of phosphate/mol of P-selectin were incorporated, respectively, into resting, thrombin-activated, and phorbol

[Effect of electroacupuncture on intestinal mucosal barrier in IBS-D rats via NGF/TrkA pathway mediated by mast cells].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the activation of mast cells (MCs) in the colon of rats with diarrhea-predominant irritable bowel syndrome (IBS-D) and to explore the underlying mechanisms of its protective effect on the intestinal mucosal barrier. METHODS: Of 74 offsprings from 6 pregnant SD rats, 14 offsprings were randomly collected as a normal group, and the remaining 60 offsprings underwent IBS-D model prepared by maternal separation combined with acetic acid enema and chronic restraint stress. Fifty-six successfully modeled rats were randomly divided into a

Activation of type I protein kinase A during receptor-mediated human T lymphocyte activation.

The experiments reported herein have characterized the signaling pathway leading to stimulation of type I protein kinase A isozyme (PKA-I) activity during the early events of Ag receptor-mediated T cell activation. Inhibitor studies demonstrated that receptor-initiated activation of nonreceptor protein tyrosine kinases, phosphorylation and activation of phospholipase C-gamma 1, and activation of protein kinase C occur temporally and precede PKA-I activation. Bypass of both the TCR/CD3 complex and IL-1R and direct activation of protein kinase C by a phorbol ester can also activate PKA-I. To con

Work in Progress: Drugs in Development.

Primary biliary cholangitis is an archetypal autoimmune disease that causes cholestasis, fibrosis, and liver failure. Ursodeoxycholic acid and obeticholic acid are approved for its treatment. Not all patients respond, some are intolerant, many have ongoing symptoms, and new therapies are required. Herein we describe drugs in development and potential future biological targets. We consider compounds acting on the farnesoid X receptor/fibroblast growth factor 19 pathway, fibrates and other agonists of the peroxisome proliferator-activated receptor family, transmembrane-G-protein-receptor-5 agoni

Advances in delivery methods of Arthrospira platensis (spirulina) for enhanced therapeutic outcomes.

Arthrospira platensis (A. platensis) aqueous extract has massive amounts of natural products that can be used as future drugs, such as C-phycocyanin, allophycocyanin, etc. This extract was chosen because of its high adaptability, which reflects its resolute genetic composition. The proactive roles of cyanobacteria, particularly in the medical field, have been discussed in this review, including the history, previous food and drug administration (FDA) reports, health benefits and the various dose-dependent therapeutic functions that A. platensis possesses, including its role in fighting against

[Network pharmacology and experimental validation reveal therapeutic mechanism of Yuyang Jianpi Pills for gastric ulcer with spleen-stomach deficiency-cold syndrome by inhibiting inflammation and apoptosis via IL-6/JAK2/STAT3 pathway].

This study integrated network pharmacology, molecular docking, and animal experiments to investigate the therapeutic effects and mechanisms of Yuyang Jianpi Pills for gastric ulcer(GU) in rats modeled with spleen-stomach deficiency-cold syndrome. Active ingredients and targets of Yuyang Jianpi Pills were searched against TCMSP, BATMAN-TCM, SwissTargetPrediction, and relevant literature. The targets associated with GU and spleen-stomach deficiency-cold syndrome were screened from the GeneCards database and the TCMIP platform. The common targets shared by Yuyang Jianpi Pills and GU were identifi

Role of LFB3 in cell-specific cAMP induction of the urokinase-type plasminogen activator gene.

In previous work we suggested that a kidney-specific transcription factor LFB3 cooperates with cAMP-response element (CRE)-binding proteins within a cAMP regulatory unit comprised of three protein-binding domains and located 3.4 kilobase pairs upstream of the urokinase-type plasminogen activator (uPA) gene in LLC-PK1 cells (Menoud, P.-A., Matthies, R., Hofsteenge, J., and Nagamine, Y. (1993) Nucleic Acids Res. 21, 1845-1852). The two domains contain a CRE-like sequence, and the third domain is recognized by LFB3. The absolute requirement of LFB3 as well as the cooperation among the three domai

[Effects of autophagy on myocardial injury in rats with common bile duct ligation].

OBJECTIVE: To investigate the impact of autophagy on cardiac tissue injury following common bile duct ligation (CBDL) in rats. METHODS: Twenty-four SPF grade healthy adult male Sprague-Dawley (SD) rats were randomly divided into four groups, with 6 rats in each group. The sham-operated (Sham) group underwent only dissection of the common bile duct without ligation. The CBDL group underwent CBDL to simulate jaundice-induced myocardial injury. The autophagy inhibitor 3-methyladenine (3-MA)+CBDL group was intraperitoneally injected with 15 mg/kg 3-MA 2 hours before modeling, and then injected on

The combined treatment of Copaxone and Salirasib attenuates experimental autoimmune encephalomyelitis (EAE) in mice.

EAE is a common animal model for multiple sclerosis (MS). Immunomodulatory treatments such as glatiramer acetate (GA, Copaxone) are beneficial in EAE but are not universally effective in the clinic. The Ras inhibitor farnesylthiosalycylic acid (FTS, Salirasib), efficiently ameliorate EAE as well. Here we demonstrate a synergistic beneficial effect of the combined GA and FTS treatment on EAE; 22.5% of the combined-treatment mice developed disease compared to 87.5%, 77.5% and 82.5% of mice treated with vehicle, GA and FTS, respectively, results supported by MRI, histological, immunological and b

Aberrantly expressed c-Jun and JunB are a hallmark of Hodgkin lymphoma cells, stimulate proliferation and synergize with NF-kappa B.

AP-1 family transcription factors have been implicated in the control of proliferation, apoptosis and malignant transformation. However, their role in oncogenesis is unclear and no recurrent alterations of AP-1 activities have been described in human cancers. Here, we show that constitutively activated AP-1 with robust c-Jun and JunB overexpression is found in all tumor cells of patients with classical Hodgkin's disease. A similar AP-1 activation is present in anaplastic large cell lymphoma (ALCL), but is absent in other lymphoma types. Whereas c-Jun is up-regulated by an autoregulatory proces

[Mechanism of vanillic acid against cardiac fibrosis induced by isoproterenol in mice based on Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways].

This study investigated the effects and underlying mechanisms of vanillic acid(VA) against cardiac fibrosis(CF) induced by isoproterenol(ISO) in mice. Male C57BL/6J mice were randomly divided into control group, VA group(100 mg·kg~(-1), ig), ISO group(10 mg·kg~(-1), sc), ISO + VA group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig), ISO + dynamin-related protein 1(Drp1) inhibitor(Mdivi-1) group(10 mg·kg~(-1), sc + 50 mg·kg~(-1), ip), and ISO + VA + Mdivi-1 group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig + 50 mg·kg~(-1), ip). The treatment groups received the corresponding medications once daily for 14 c

G-protein-coupled receptors act via protein kinase C and Src to regulate NMDA receptors.

The N-methyl-D-aspartate (NMDA) receptor contributes to synaptic plasticity in the central nervous system and is both serine-threonine and tyrosine phosphorylated. In CA1 pyramidal neurons of the hippocampus, activators of protein kinase C (PKC) as well as the G-protein-coupled receptor ligands muscarine and lysophosphatidic acid enhanced NMDA-evoked currents. Unexpectedly, this effect was blocked by inhibitors of tyrosine kinases, including a Src required sequence and an antibody selective for Src itself. In neurons from mice lacking c-Src, PKC-dependent upregulation was absent. Thus, G-prote

[Effect and mechanism of taurocholic acid in promoting colorectal cancer liver metastasis by regulating neutrophil extracellular trap formation].

Objective: To investigate the effect and underlying mechanism by which taurocholic acid (TCA) promotes colorectal cancer liver metastasis (CRLM) through regulation of neutrophil extracellular trap (NET) formation. Methods: A total of 20 CRLM patients and 20 non-metastatic colorectal cancer (non-mCRC) patients admitted to Qilu Hospital of Shandong University from 2021 to 2022 were retrospectively included. The age of the CRLM patients was (57±12) years, including 11 males and 9 females; the age of the non-mCRC patients was (60±9) years, including 15 males and 5 females. Non-targeted metabolomic

Short-chain fatty acids in the tumor microenvironment: from molecular mechanisms to cancer therapy.

Short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, serve as pivotal metabolites within the tumor microenvironment (TME), playing essential roles in modulating tumor progression. Although the biological functions and mechanisms of SCFAs in the TME show some overlap, each SCFA also exerts some distinct regulatory effects on tumors and TME. Notably, even a single SCFA may exhibit pleiotropic effects across different cancer types or under varying conditions within the same malignancy. Consequently, according to the different metabolic microenvironment of patients, precis

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… Acetate is then synthesized via phosphotransacetylase and acetate kinase. …

Rosmarinic Acid and Related Dietary Supplements: Potential Applications in the Prevention and Treatment of Cancer.

Cancer constitutes a severe threat to human health and quality of life and is one of the most significant causes of morbidity and mortality worldwide. Natural dietary products have drawn substantial attention in cancer treatment and prevention due to their availability and absence of toxicity. Rosmarinic acid (RA) is known for its excellent antioxidant properties and is safe and effective in preventing and inhibiting tumors. This review summarizes recent publications on culture techniques, extraction processes, and anti-tumor applications of RA-enriched dietary supplements. We discuss techniqu

The potential of dibenzazepine carboxamides in cancer therapy.

Cancer is a leading cause of mortality worldwide, with most conventional treatments lacking efficacy and having significant challenges like drug resistance. Finding new molecules is quite challenging in terms of cost, time and setbacks. Hence, drug repurposing is considered sensible for skipping the long process of drug development. Dibenzazepine carboxamides, as traditional anticonvulsants, primarily function by blocking voltage-gated sodium channels, which not only mitigate seizures but also influence mood disorders through modulation of serotonin and dopamine. Recent studies have uncovered