Purified Phlorizin from DocynIa Indica (Wall.) Decne by HSCCC, Compared with Whole Extract, Phlorizin and Non-Phlorizin Fragment Ameliorate Obesity, Insulin Resistance, and Improves Intestinal Barrier Function in High-Fat-Diet-Fed Mice.

Natural products generally contain complex and multiple bioactive compounds that are responsible for the effects on health through complicated synergistic and/or suppressive actions. As an important raw material of local ethnic minority tea, ethnomedicines and food supplements in southwestern areas of China, Docynia indica (Wall.) Decne (DID) mainly consists of phlorizin (PHZ), which is the main active component. In this study, the holistic activities and the interactions of components of PHZ, non-phlorizin (NP) in the DID extract (DIDE) were evaluated. A rapid and effective high-speed counter-current chromatography (HSCCC) was performed to knock out PHZ from DIDE and the purity of PHZ was 96.01% determined by HPLC, with a recovery rate of 96.76%. After 13 weeks of treatment course in a high-fat diet (HFD)-induced obese mice model, the results revealed that the DIDE and PHZ significantly decreased weight gain, blood lipid levels, hyperplasia of adipocytes and alleviated inflammation (p < 0.05). Both DIDE and PHZ improves insulin resistance (p < 0.001). Meanwhile, the intestinal barrier function was improved compared to HFD group, through the determination of serum lipopolysaccharides (LPS), glucagon-likepeptide-2 (GLP-2) and hematoxylin-eosin staining of jejunum. Interestingly, after NP treatment, the metabolic syndrome of the HFD-induced obesity appeared to have a similar improvement. All the experiments showed that there is a synergistic weakening phenomenon when PHZ and NP interact with each other in the mixed state. In conclusion, for the PHZ and NP showing a good effect on anti-obesity, anti-inflammation, and intestinal barrier function, DIDE could be a good source of functional food to prevent obesity.

14,15-EET Suppresses Neuronal Apoptosis in Ischemia-Reperfusion Through the Mitochondrial Pathway.

Neuronal apoptosis mediated by the mitochondrial apoptosis pathway is an important pathological process in cerebral ischemia-reperfusion injury. 14,15-EET, an intermediate metabolite of arachidonic acid, can promote cell survival during ischemia/reperfusion. However, whether the mitochondrial apoptotic pathway is involved this survival mechanism is not fully understood. In this study, we observed that infarct size in ischemia-reperfusion injury was reduced in sEH gene knockout mice. In addition, Caspase 3 activation, cytochrome C release and AIF nuclear translocation were also inhibited. In this study, 14,15-EET pretreatment reduced neuronal apoptosis in the oxygen-glucose deprivation and re-oxygenation group in vitro. The mitochondrial apoptosis pathway was also inhibited, as evidenced by AIF translocation from the mitochondria to nucleus and the reduction in the expressions of cleaved-caspase 3 and cytochrome C in the cytoplasm. 14,15-EET could reduce neuronal apoptosis through upregulation of the ratio of Bcl-2 (anti-apoptotic protein) to Bax (apoptosis protein) and inhibition of Bax aggregation onto mitochondria. PI3K/AKT pathway is also probably involved in the reduction of neuronal apoptosis by EET. Our study suggests that 14,15-EET could suppress neuronal apoptosis and reduce infarct volume through the mitochondrial apoptotic pathway. Furthermore, the PI3K/AKT pathway also appears to be involved in the neuroprotection against ischemia-reperfusion by 14,15-EET.

Combined morphine and limb remote ischemic perconditioning provides an enhanced protection against myocardial ischemia/reperfusion injury by antiapoptosis.

BACKGROUND: Both morphine and limb remote ischemic perconditioning (RIPer) can protect against myocardial ischemia/reperfusion injury (IRI). This experiment was designed to assess whether combined morphine and limb RIPer could provide and enhanced protection against myocardial IRI in an in vivo rat model. METHODS: One hundred male Sprague-Dawley rats were randomly allocated to six groups: sham, ischemia/reperfusion (IR), ischemic preconditioning, RIPer, morphine (M), and combined morphine and remote ischemic perconditioning (M + RIPer). Ventricular arrhythmias that occurred during ischemia and early reperfusion were scored, and serum creatine kinase isoenzyme and cardiac troponin I levels were assayed. The infarct size was determined by Evans blue and triphenyl tetrazolium chloride staining. The apoptosis in the myocardial ischemic core, ischemic border, and nonischemic areas was assessed through real-time polymerase chain reaction for Bax and Bcl-2 and with the transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay. RESULTS: The infarct size, serum cardiac troponin I level, incidence, and score of the arrhythmias during the initial reperfusion were significantly reduced in the M + RIPer group compared with the IR group but did not differ significantly between the ischemic preconditioning and M + RIPer groups. Transferase-mediated deoxyuridine triphosphate-biotin nick end labeling-positive cells were significantly decreased, and the Bcl-2/Bax ratio was significantly increased in the M + RIPer group compared with the IR group. CONCLUSIONS: This experiment demonstrates that combined morphine and limb RIPer provides an enhanced protection against myocardial IRI by the Bcl-2-linked apoptotic signaling pathway.

[Discussion on relevant theories of "Qi-Blood-Shen" and formula implication of Guan-Xin-Jing capsule].

In the field of traditional Chinese medicine（TCM）,the definition of "Shen" contains a broad concept and a narrow concept. Broad "Shen" is the dominator and administrator of human vital movement,while narrow "Shen" means spirit, consciousness, thinking and emotions of human. "Shen" originates from innate essence of parents, and survives on acquired essence of water and food as well as the nutrition of its metaplastic Qi-Blood-Body fluid. Qi-Blood,the most precious asset of human body, is a quite important section of one person and the central material basis of "Shen-Zhi". Coronary heart disease(CHD) is classified as thoracic obstruction category in TCM. However, in the progress of CHD, the mental factors and physical factors interplay each other. Thus, CHD is defined as a kind of psychosomatic disorder. So, the concept of psycho-cardiology generally corresponds to the cognition of TCM. Disorder of Qi and Blood, Qi deficiency and Blood stasis and lack of spirit and "Shen" preservation, are the main causes of coronary heart disease(CHD). Guan-Xin-Jing capsule possesses multiple therapeutical effects including supplementing qi and activating blood circulation, tranquilizing "Shen" and sedating "Zhi" and balancing psychosomatic status. It will be of vital importance and promotional value in the prophylaxis and treatment of CHD.

κ-Opioid receptors are involved in enhanced cardioprotection by combined fentanyl and limb remote ischemic postconditioning.

BACKGROUND: The combination of various interventions to obtain enhanced cardioprotection is always an important area of research focus. This randomized experiment was designed to assess whether combined fentanyl and limb remote ischemic postconditioning produced enhanced protection against myocardial ischemia/reperfusion injury in an in vivo rat model, and to determine if κ-opioid receptors were implicated in the cardioprotection of these interventions. METHODS: Seventy-two rats were exposed to a 30-min myocardial ischemia followed by a 180-min reperfusion. Half of the rats (36) were randomized into four different groups receiving control treatment, fentanyl postconditioning, limb remote ischemic postconditioning, and combined fentanyl and limb remote ischemic postconditioning. The remaining 36 rats were also randomized into four groups receiving the same interventions as the above groups following the intravenous administration of a κ-opioid receptor antagonist, nor-binaltorphimine, before myocardial ischemia. At the end of reperfusion, both serum cardiac troponin I and infarct size were determined. RESULTS: Both fentanyl postconditioning and limb remote ischemic postconditioning significantly decreased the infarct size and serum cardiac troponin I level, and combined fentanyl and limb remote ischemic postconditioning produced enhanced cardioprotection on the infarct size-sparing effect. The use of nor-binaltorphimin to block κ-opioid receptors eliminated cardioprotection by fentanyl postconditioning and enhanced cardioprotection by combined fentanyl and limb remote ischemic postconditioning, but did not change cardioprotection by limb remote ischemic postconditioning. CONCLUSIONS: Combined fentanyl and limb remote ischemic postconditioning produced enhanced protection against myocardial ischemia/reperfusion injury. κ-Opioid receptors are essential for cardioprotection by fentanyl postconditioning and enhanced cardioprotection by combined fentanyl and limb remote ischemic postconditioning; however, they do not play a pivotal role in cardioprotection by limb remote ischemic postconditioning.

Optimal intervention time of vagal stimulation attenuating myocardial ischemia/reperfusion injury in rats.

OBJECTIVE: To determine the optimal intervention time of the vagal stimulation (VS) attenuating myocardial ischemia/reperfusion injury (IRI). METHODS: One hundred and twenty male SD rats were randomly allocated into six groups: sham group, IRI group, the VS performed at 15 min of ischemia (VSI15) group, the VS performed immediately before reperfusion (VSR0) group, the VS performed at 30 min of reperfusion (VSR30) group, and the VS performed at 60 min of reperfusion (VSR60) group. Rats in each group were further allocated into subgroups A and B. In each group, the hemodynamics and ventricular arrhythmias were continuously observed. In the subgroup A, serum inflammatory cytokine levels were tested, and infarct size was assessed. In the subgroup B, myocardial inflammatory cytokine levels in both ischemic and non-ischemic regions were assayed. RESULTS: As compared to the IRI, VSR0, VSR30 and VSR60 groups, infarct size, serum HMGB-1 and ICAM-1 levels at 120 min of reperfusion, myocardial HMGB-1, IL-1 and IL-6 levels in non-ischemic region, myocardial ICAM-1 level in ischemic region were all significantly decreased in the VSI15 group. Compared with the IRI group, myocardial IL-10 levels in both ischemic and non-ischemic regions were significantly increased in the VSI15 group. Compared to the IRI, VSR0, VSR30 and VSR60 groups, incidence and score of ventricular arrhythmia during initial reperfusion were significantly decreased in the VSI15 group. CONCLUSIONS: The VS performed at 15 min of ischemia provides the best protection against myocardial IRI. Also, early modulation on inflammatory responses caused by myocardial IRI may contribute to this best cardioprotection.

[Effect of Qufeng Tongluo Recipe on expression of desmin and CD2AP proteins in adriamycin-induced nephropathy rats: an experimental research].

OBJECTIVE: To investigate the effect of Qufeng Tongluo Recipe (QTR) on the expression of desmin and CD2-associated protein (CD2AP) in adriamycin-induced nephropathy rats. METHODS: The adriamycin-induced nephropathy rat model was induced by a disposable intravenous injection of adriamycin. The model was successfully established after 3 weeks. Rats were then randomly divided into the blank control group (Group A, n =12), the model control group (Group B, n = 8), the small, medium, large dose QTR group (Group C, n = 8; Group D, n = 8; Group E, n = 8), and the positive control group (Group F, n = 8). From the fourth week normal saline was given to rats in Group A and Group B, QTR 1.0 g/mL, 2.1 g/mL, and 4.2 g/mL was respectively administered to those in Group C, D, and E. Prednisone 25 mg/kg was given to rats in Group F. All medication was performed by gastrogavage at 10 mL/kg, once daily, for 28 successive days. 24-h urinary protein excretion and sera biochemical indices were determined during medication. At the end of the experiment, ultrastructure was observed, mRNA expression of desmin, mRNA and protein of CD2AP were detected by Real-time PCR and Western blot. RESULTS: (1) Compared with Group B, 24-h urinary protein excretion significantly decreased in Group C, D, E, and F (P < 0.05). (2) Compared with Group B, Alb in Group C, D, and E increased (P < 0.05) and TC significantly decreased (P < 0.05). TG significantly increased in Group F (P < 0.05). (3) Results of electron microscope showed, compared with Group B, the morphology of foot cells was improved to various degrees in Groups D, E, and F, especially the foot process structure and the number of foot processes were significantly improved, which was more obviously shown in Group D and Group E. (4) mRNA expression of desmin, mRNA and protein of CD2AP increased in adriamycin-induced nephropathy rats (P < 0.05). After intervention, when compared with Group B, mRNA expression of desmin and CD2AP were significantly lower in Group C, D, E, and F (P < 0.05). (5) Compared with Group A, expression of desmin and CD2AP significantly increased (P < 0.05). Compared with Group B, the expression of desmin protein were obviously lower in Group C, D, E, and F, and the protein expression of desmin obviously decreased in Group D, E, and F (P < 0.05). The protein expression of desmin and CD2AP gradually decreased in Group C, D, and E (P < 0.05). Compared with Group F, the expression of CD2AP protein obviously increased in Group C and D (P < 0.05); the expression of CD2AP protein obviously decreased in Group E (P < 0.05); the expression of desmin protein was higher in Group C, D, and E (P < 0.05). CONCLUSION: QTR's therapeutic effect on adriamycin-induced nephropathy rats might be achieved through altered expression of desmin and CD2AP.

Effects of long-term tillage practices on the stability of soil aggregates and organic carbon in black soil farmland.

We examined the effects of different tillage practices on plough layer soil structure and organic carbon stabilization in black soil farmland with a long-term positioning platform. The wet-sieving method and infrared spectroscopy method were used to investigate the impacts of conventional tillage (CT), no-tillage (NT), sub-soiling tillage (ST), and moldboard plowing tillage (MP) on soil aggregates distribution and organic carbon characteristics in 0-40 cm soil layers. Compared to CT, both NT and ST treatments significantly increased the proportion of large macroaggregates (>2 mm) in the topsoil layer (0-20 cm)and that of small macroaggregates (0.25-2 mm) in the subsoil layer (20-40 cm) for NT, ST, and MP. NT, ST, and MP treatments resulted in higher mean weight dia-meter (MWD) and mean geometric diameter (GMD) of soil aggregates in both the topsoil and subsoil layers. NT treatment improved organic carbon contents in bulk soil and large macroaggregates in the topsoil layer, while ST and MP enhanced organic carbon contents in bulk soil and large macroaggregates in the subsoil layer. The contribution rate of small macroaggregates organic carbon content to the total was between 68.9% and 83.4%. Furthermore, the organic carbon chemical stabilization of soil body and aggregates increased in the topsoil and subsoil layers under NT treatment compared to others. The MWD had a positive correlation with the organic carbon content and chemical stability of soil body and small macroaggregates. These findings offered a theoretical basis for understanding the impacts of different tillage practices on the stability of soil aggregate and organic carbon in black soil region.

[Short-term effect of different returning methods of maize straw on the temperature of black soil plough layer]. / 玉米秸秆不同还田方式对黑土耕层温度影响的短期效应.

Clarifying the effect of different maize straw returning methods on soil temperature is crucial for optimizing the management of farmland straw and the efficient utilization of heat resources in the black soil region of Northeast China. To investigate the impacts of straw returning methods on soil temperature, we conducted a field experiment with four treatments during 2018 and 2020, including plough tillage with straw returning (PTSR), rotary tillage with straw returning (RTSR), no-tillage with straw returning (NTSR), and a control treatment of conventional ridge tillage without straw returning (CT). We measured soil temperature and water content at the 5 cm, 15 cm and 30 cm soil layer, and the straw coverage rate during the 3-year maize growth period. We further analyzed the differences of soil temperature in different soil layer under different treatments, accumulated soil temperature and growing degree-days (GDD) above 10 ℃, daily dynamics of soil temperature, the production efficiency of air accumulated temperature among different treatments, and explored factors causing the difference of soil temperature and the production efficiency of air accumulated temperature. Our results showed that different treatments mainly affected soil temperature from the sowing to emergence stage (S-VE) of maize. The daily average soil temperature showed a trend of CT>PTSR>RTSR>NTSR. The differences of soil temperature under different treatments showed a decreasing trend as growth process advanced and soil depth increased. Compared with the CT treatment, soil temperature at 5 cm depth was decreased by 0.86, 1.84 and 3.50 ℃ for PTSR, RTSR, and NTSR treatments, respectively. NTSR significantly reduced the accumulated temperature of ≥10 ℃ in different soil layers and GDD. The accumulated temperature ≥ 10 ℃ at the 5, 15, and 30 cm soil layers decreased by 216.2, 222.7, and 165.1 ℃·d, and the GDD decreased by 201.9, 138.7 and 123.9 ℃·d, respectively. In addition, production efficiency of air accumulated temperature decreased by 9.7% to 15.6% for NTSR. Conclusively, PTSR and RTSR had significant impacts on topsoil temperature during the maize growing period from sowing to emergence, but did not affect the accumulated soil temperature and the production efficiency of air accumulated temperature. However, NTSR significantly reduced topsoil temperature and production efficiency of air accumulated temperature.

Postconditioning with vagal stimulation attenuates local and systemic inflammatory responses to myocardial ischemia reperfusion injury in rats.

OBJECTIVE: To assess effects of postconditioning with the vagal stimulation (VS) on the local and systematic inflammatory responses to acute myocardial ischemia reperfusion injury (IRI). METHODS: Sixty male Sprague-Dawley rats were randomly allocated into three groups: sham group, ischemia reperfusion group (IR group), and postconditioning with the VS group (POVS group). Serum levels of inflammatory cytokines during reperfusion and myocardial levels of inflammatory cytokines in both ischemic and non-ischemic regions at the end of the experiment were assayed. The infarct size was assessed by Evans blue and triphenyltetrazolium chloride staining. RESULTS: The infarct size was significantly reduced in the POVS group compared to the IR group. Serum levels of TNF-α at 30, 60, and 120 min of reperfusion and serum levels of HMGB-1, ICAM-1, IL-1, and IL-6 at 120 min of reperfusion were significantly lower in the POVS group than in the IR group. Myocardial levels of TNF-α, HMGB-1, ICAM-1, IL-1, and IL-6 in both ischemic and non-ischemic regions were also significantly reduced in the POVS group compared with the IR group. CONCLUSIONS: Postconditioning with the VS can significantly attenuate the local and systemic inflammatory responses to myocardial IRI, and provide an obvious cardioprotection.