Journal of Physiology and Pharmacology最新文献

The potential of plant bioactives for the prevention and therapy of diabetes is increasingly being recognized. In the present study we investigated the antidiabetic properties of an aqueous Bistorta officinalis Delarbre extract (BODE) by employing both in-vitro assays and in-vivo models. Multiple targets in glucose homeostasis which are involved in the regulation of the blood glucose level were affected by BODE in-vitro. The extract exhibited inhibitory activities towards the intestinal carbohydrate-hydrolysing enzymes α-amylase and α-glucosidase with IC₅₀ values of 81.5 μg/mL and 8.4 μg/mL, respectively. Furthermore, moderate reduction of the dipeptidyl peptidase-4 (DPP4) enzyme activity was evident when tested in the presence of 1.0 mg/mL BODE. A significant inhibition of the intestinal glucose transporter sodium-dependent glucose transporter 1 (SGLT1) in response to 1.0 mg/mL BODE was shown for Caco-2 cells mounted in Ussing chambers. High performance liquid chromatography-mass spectrometry analyses of the BODE revealed several plant bioactives including gallotannins, catechins and chlorogenic acid. Although our in-vitro data were promising, BODE-supplementation in the model organism Drosophila melanogaster lacked to confirm the antidiabetic effect of the extract in-vivo. Moreover, BODE failed to reduce blood glucose levels in chicken embryos (in-ovo). Hence, BODE is probably not a suitable candidate for developing a pharmaceutical against diabetes mellitus.

Urocortin 2, an endogenous selective ligand for the corticotropin-releasing hormone receptor type 2, has been suggested to exert cardioprotective effects. We analyzed the possible relationship between the level of Ucn2 and specific indicators of cardiovascular risk factors in patients with untreated hypertension and in healthy subjects. Sixty seven subjects were recruited: 38 with newly diagnosed treatment-naive hypertension (with no pharmacological treatment - HT group) and 29 healthy subjects without hypertension (nHT group). We evaluated ambulatory blood pressure monitoring, Ucn2 levels and metabolic indices. Multivariable regression analyses were performed to assess the effects of gender, age, and Ucn2 levels on metabolic indices or blood pressure (BP) level. Log of Ucn2 levels were higher in healthy subjects than in hypertensive patients (2.44±0.7 versus 2.09±0.66, p<.05) and correlated inversely with 24-hour diastolic blood pressure, and both night-time systolic and diastolic blood pressure regardless of age and gender (R2=0.06; R2=0.06; R2=0.052; respectively). Furthermore, Ucn2 levels inversely correlated with cholesterol and low-density cholesterol (LDL) concentrations in healthy subjects only. Ucn2 was independently related to total cholesterol (but not to LDL) regardless of age, gender and the presence of hypertension (R2=0.18). However, we did not find any relationship between urocortin 2, body mass index or waist-hip ratio as well as parameters of glucose metabolism. Our data indicates that higher levels of urocortin 2 are related to more favorable lipid profiles and lower blood pressure.

The formation and luteolysis of the corpus luteum (CL) is strictly controlled by many factors. Imbalance between proliferation and apoptosis processes leads to deficiency of the luteal phase and infertility. Our previous study showed resistin expression in porcine luteal cells and an inhibitory effect on progesterone synthesis. Thus, the aim of the present study was to examine the in vitro effect of resistin on the proliferation/viability, apoptosis and autophagy of porcine luteal cells as well as the involvement of mitogen-activated kinase (MAP3/1), protein kinase B (AKT) and signal transducer and activator of transcription 3 (STAT3) in these processes. Porcine luteal cells were incubated with resistin (0.1-10 ng/mL) for 24-72 h and viability was assessed using the alamarBlue or 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Then, the time-dependent effect of resistin on mRNA and protein expression of proliferating cell nuclear antigen (PCNA), caspase 3, BCL2-like protein 4 (BAX), B-cell lymphoma 2 (BCL2), beclin1, microtubule-associated protein 1A/1B-light chain 3 (LC3) and lysosomal-associated membrane protein 1 (LAMP1) was measured by real-time polymerase chain reaction (PCR) and immunoblotting, respectively. We found that resistin enhanced luteal cell viability with no effect on caspase 3 mRNA and protein, increased the BAX/BCL2 mRNA and protein ratio and significantly stimulated the initiation of autophagy, which promotes the maintenance of CL function rather than its regression. Additionally, using pharmacological inhibitors of MAP3/1 (PD98059), AKT (LY294002) and STAT3 (AG490), we observed that the effect of resistin was reversed to the control level in viability and, by influence, MAP3/1 and STAT3 in autophagy. Taken together, our results suggest that resistin, in addition to its well-known effect on granulosa cell function has direct influence on CL luteolysis and the formation and maintenance of luteal cell function.

To observe the evolution of the intestinal microbiota in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and discuss the relationship between the intestinal microbiota and graft-versus-host disease (GVHD). In this study, 11 patients who underwent allo-HSCT in the Aerospace Central Hospital from January 2021 to October 2021 were selected, along with 11 donors. Fecal specimens were collected 7 times: at admission, after pre-treatment, and every 3 weeks after transplantation from patients and once from donors. The composition of the intestinal microbiota and its association with GVHD after allogeneic hematopoietic stem cell transplantation were analyzed by 16S rRNA sequencing. Of the 11 patients, 5 developed GVHD, and 6 did not. The diversity of the intestinal microbiota among GVHD patients first increased and then decreased after transplantation, while that among non-GVHD patients first increased and then tended to be stable. The diversity of the intestinal microbiota among GVHD patients was lower than that among non-GVHD patients before pre-treatment and after transplantation. The taxa diversity of the intestinal microbiota in the non-GVHD group was better than that in the GVHD group before allo-HSCT, and the difference was statistically significant (P<0.05 for OTUs and CHAO1 index). The taxa abundance of Enterococcaceae 2.16% (2.13%, 2.22%) before allo-HSCT was significantly higher than that in the non-GVHD group 1.33% (0.27%, 1.52%), and the difference was statistically significant (P=0.004). There was no significant difference between the GVHD group and the non-GVHD group in the diversity of the intestinal microbiota of donors (P<0.05). The characteristics of the intestinal microbiota in the final sample of patients in the GVHD group were similar to the preoperative structure of the intestinal microbiota. In conclusion: The decrease in the diversity of the intestinal microbiota after HSCT may be a risk factor for the occurrence of GVHD. The presence of Enterococcaceae in the intestinal microbiota may be associated with an increased risk of developing GVHD. The intestinal microbiota reconstitute to be close to the intestinal microbiota composition of the donors in the non-GVHD group.

The aim of this study was to explore the role and pathological mechanism of microRNA-663b in interleukin-1beta (IL-1β)-induced inflammation and apoptosis of nucleus pulposus cells. First, the best concentration and time to construct the nucleus pulposus cell inflammation model was screen out. Overexpression or inhibition of miR-663b expression was performed by adding microRNA-663b mimic or microRNA-663b inhibitor. 293T cells were transfected according to experimental requirements. The luciferase activity of each group was detected to analyze the targeted regulation of microRNA-663b on interleukin-1 receptor (IL1R1). Compared with the mimic negative control (NC) group, the expression of inflammatory factors in the microRNA-663b overexpression group was inhibited (P<0.05), and the expression of type 2 collagen and polysaccharide protein increased (P<0.05), and the apoptosis of nucleus pulposus cells was inhibited (P<0.01), and the number of TUNEL-positive cells decreased significantly (P<0.01), and the microRNA and protein expression of IL1R1, the ratio of P-P65/P65 and phospho-nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (P-IκBα)/nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) protein expression were significantly decreased (P<0.05). The expression of inflammatory factors in the miR-663b inhibitor group was significantly higher than that in the inhibitor NC group (P<0.01), and the expression of type 2 collagen and polysaccharide protein was significantly decreased (P<0.01), and the number of apoptosis cells and TUNEL staining positive cells increased (p<0.01). The expression of IL1R1 gene and protein was significantly increased (P<0.01). The ratio of P-P65/P65 and P-IκBα/IκBα protein expression increased (P<0.05). IL1R1 is a downstream target gene of microRNA-663b. MicroRNA-663b may down-regulate the expression of IL1R1 at the transcriptional level by targeting IL1R1, inhibit the inflammatory response of nucleus pulposus cells, and slow down the degeneration of nucleus pulposus cells.

Adropin is a hormone which increases insulin sensitivity. It enhances the oxygenation of glucose in the muscles. The 91 obese pregnant women (BMI >30 kg/m²) with gestational diabetes mellitus (GDM) diagnosed in the first half of pregnancy has been recruited to the study group. The control group consisted of 10 age matched and homogeneous pregnant women with BMI <25 kg/m². Blood samples were collected on visit V1 - between the 28^th and 32^nd week and on visit V2 - between the 37^th and 39^th week of gestation. The ELISA test was used to measure the adropin level. The results in the study group and the control group were compared. Blood samples were collected at the same visits. The median concentration of adropin was 442.2 pg/ml on V1 and 453.1 pg/ml on V2. The increase was significant (p<0.05). Results were significantly lower in the control group's patients, i.e. 57.0 pg/ml (p<0.001) on V1 and 107.9 pg/ml on V2 (p<0.001). The higher adropin level on the V1 and V2 visits were related to patients' lower BMI and better metabolic control. The increase in the adropin level in the third trimester may have been involved in the weight gain reduction, whereas better dietary adherence might have had a compensatory effect on increasing insulin resistance. However, the small control group is a limitation of this study.

This study aimed to explore the mechanism of Qingre Huoxue Fang (QRHXF) treatment on anti-angiogenesis in rheumatoid arthritis (RA) based on network pharmacology and in vitro experiments. We used the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Therapeutic Target (TTD) database to extract the active components of QRHXF and potential targets for regulating angiogenesis. First, we used Cytoscape bioinformatics software to construct the network of QRHXF-angiogenesis and screened the potential targets. Then, we performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis on the potential core targets. In addition, enzyme-linked immune assay and Western blot were used for in vitro validation and to verify the effects of different concentrations of QRHXF on the expression levels of the vascular endothelial growth factor receptor type 1 (VEGFR-1) and VEGFR-2 cytokines and phosphoinositide 3-kinase (PI3k) and Ak strain transforming (Akt) proteins in human umbilical vein endothelial cells (HUVECs). In results, we screened 179 core QRHXF antiangiogenic targets, including vascular endothelial growth factor (VEGF) cytokines. Enrichment analysis showed that the targets were enriched in 56 core signaling pathways, including PI3k and Akt. In vitro experiments showed that the migration distance and square, adhesion optical density (OD) values, and the number of branch points in tube formation significantly decreased in the QRHXF group compared with the induced group (P<0.01). Notably, the serum levels of VEGFR-1 and VEGFR-2 were lower compared with the induced group (P<0.05 or P<0.01). In addition, the expressions of PI3K and p-Akt proteins were decreased in the middle- and high doses groups (P<0.01). This study's results suggest that the downstream mechanism of QRHXF anti-angiogenesis might inhibit the PI3K-Akt signalling pathway and downregulate VEGF-1 and VEGF-2.