AIM To observe the protective effects and mechanism of Shuli Jiangzhuo Formula on cardiac function in a rat model of uremic cardiomyopathy(UCM).METHODS The successful UCM models established by 5/6 nephrectomy were randomly allocated into the model group,the valsartan group(8.33 mg/kg),and the low-dose,medium-dose and high-dose Shuli Jiangzhuo Formula groups(7.19,14.38,28.76 g/kg),in contrast to those of the sham operation group,followed by 8 weeks respective drug administration.Upon the completion of the pharmacological intervention,the rats had the left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),ejection fraction(EF)and fractional shortening(FS)measured by echocardiography;the whole heart mass index(HMI)and left ventricular mass index(LVMI)detected;the renal function(serum creatinine,blood urea nitrogen)and the hemoglobin concentration detected;the mitochondrial morphology analyzed by observation of cardiomyocyte ultrastructure using transmission electron microscopy;the DNA damage in cardiomyocytes detected by TUNEL staining;the serum levels of IL-1β,IL-18 and BNP detected by ELISA;and the myocardial mRNA and protein expressions of NLRP3,Caspase-1 and IL-1β detected by RT-qPCR and Western blot.RESULTS Compared with the sham operated controls,the model group demonstrated significant elevation of serum creatinine and urea nitrogen(P＜0.01);decreased hemoglobin concentration(P＜0.01);disorganized myocardial collagen fiber architecture,and pronounced mitochondrial swelling with ultrastructural damage;decreased EF and FS(P＜0.05);increased LVEDD and LVESD(P＜0.01);increased HMI and LVMI(P＜0.01);increased levels of serum IL-1β,IL-18 and BNP(P＜0.01);increased cardiomyocyte pyroptosis(P＜0.01);and enhanced mRNA and protein expressions of NLRP3,Caspase-1 and IL-1 β(P＜0.01).Compared to model group controls,the high-dose Shuli Jiantuo Formula intervention exhibited decreased levels of serum creatinine and urea nitrogen(P＜0.01);increased hemoglobin concentration(P＜0.01);reduced DNA fragmentation,alleviated mitochondrial swelling and mitigated ultrastructural damage;reduced LVEDD and LVESD(P＜0.05,P＜0.01);decreased HMI and LVMI(P＜0.01);downregulated levels of serum IL-1β,IL-18 and BNP(P＜0.01);decreased cardiomyocyte pyroptosis(P＜0.01);and inhibited mRNA and protein expressions of NLRP3,Caspase-1 and IL-1β(P＜0.05,P＜0.01).CONCLUSION Shuli Jiangzhuo Formula demonstrates dual cardiorenal protective effects in UCM rats through suppression of the left ventricular hypertrophy progression and inhibition of the adverse ventricular remodeling processess.The therapeutic efficacy primarily stems from targeted suppression of NLRP3/Caspase-1 signaling pathway activation and substantial attenuation of cardiomyocyte pyroptosis cascade.

Objective To investigate the effect and mechanism of methyl oxofulnonone A(META)on high glucose(HG)-induced H9c2 cell injury.Methods H9c2 cells were divided into control group(normal culture),model group(55 mmol·L-1 glucose)and experimental-L,-M,-H groups(55 mmol·L-1 glucose+12.5,25.0,50.0 μmol·L-1 META).Cell viability was detected by cell counting kit-8;intracellular reactive oxygen species(ROS)level was detected by DCFH-DA fluorescent probe;intracellular adenosine triphosphate(ATP)content was detected by luciferase;and autophagy-related protein expression was detected by Western blotting.Results The optical density values of 72-hour cells in the control group,model group and experimental-M,-H groups were 0.91±0.03,0.61±0.01,0.69±0.02 and 0.72±0.03;the ROS levels were(40.75±1.53)％,(43.73±1.30)％,(30.87±1.27)％and(28.28±1.43)％;the ATP contents were(8.16±0.71),(4.03±0.29),(5.29±0.31)and(5.83±0.31)nmol·mg-1;the relative expression levels of autophagy-related gene 5 protein were 1.05±0.06,1.46±0.09,0.98±0.11 and 0.89±0.09;the relative expression levels of ubiquitin-binding protein were 1.05±0.10,0.55±0.13,0.89±0.04 and 0.98±0.04;the ratios of microtubule-associated protein 1 light chain 3 11/Ⅰ protein were 1.09±0.09,1.82±0.05,1.67±0.29 and 1.09±0.15,respectively.Among the above indicators,there were statistically significant differences between the model group and the control and experimental-M,-H groups(P＜0.05,P＜0.01).Conclusion META significantly ameliorates H9c2 cardiomyocyte damage caused by high glucose,ameliorates oxidative stress,protects mitochondrial respiration and inhibits autophagy.

Objective:To study the mechanism of arsenic trioxide(ATO)combined with metformin(MET)in promoting apoptosis of leukemia cells.Methods:CCK-8 method was used to detect the viability of leukemia cell line KG1a,K562,and THP1 cells treated by ATO monotherapy,MET monotherapy,and ATO combined with MET.Flow cytometry was used to detect cell cycle and apoptosis.RT-qPCR was used to detect the mRNA expression of PI3K/Akt and LKB1/AMPK pathway-related genes.Western blot was used to detect the expression of PI3K/Akt and LKB1/AMPK pathway-related proteins and autophagy-related protein LC3B and P62.Results:Compared with the ATO monotherapy group,ATO combined with MET significantly inhibited the growth of KG1a,K562 and THP1 cells,and the difference in KG1a cells was more statistically significant.The combination of the two drugs induced KG1a cell cycle arrest,promoted apoptosis,increased the expression of autophagy-related protein LC3B and P62,up-regulated the mRNA expression levels of PI3K/Akt pathway and LKB1/AMPK pathway-related genes,as well as the expression of LKB1/AMPK pathway-related proteins,and down-regulated the expression of PI3K/Akt pathway-related proteins.Conclusion:ATO combined with MET promotes apoptosis by up-regulating LKB1/AMPK and down-regulating PI3K/Akt signaling pathway to regulate the autophagy of leukemia cells.

Objective:To study the mechanism of arsenic trioxide(ATO)combined with metformin(MET)in promoting apoptosis of leukemia cells.Methods:CCK-8 method was used to detect the viability of leukemia cell line KG1a,K562,and THP1 cells treated by ATO monotherapy,MET monotherapy,and ATO combined with MET.Flow cytometry was used to detect cell cycle and apoptosis.RT-qPCR was used to detect the mRNA expression of PI3K/Akt and LKB1/AMPK pathway-related genes.Western blot was used to detect the expression of PI3K/Akt and LKB1/AMPK pathway-related proteins and autophagy-related protein LC3B and P62.Results:Compared with the ATO monotherapy group,ATO combined with MET significantly inhibited the growth of KG1a,K562 and THP1 cells,and the difference in KG1a cells was more statistically significant.The combination of the two drugs induced KG1a cell cycle arrest,promoted apoptosis,increased the expression of autophagy-related protein LC3B and P62,up-regulated the mRNA expression levels of PI3K/Akt pathway and LKB1/AMPK pathway-related genes,as well as the expression of LKB1/AMPK pathway-related proteins,and down-regulated the expression of PI3K/Akt pathway-related proteins.Conclusion:ATO combined with MET promotes apoptosis by up-regulating LKB1/AMPK and down-regulating PI3K/Akt signaling pathway to regulate the autophagy of leukemia cells.

ObjectiveIn nature, objects cast shadows due to illumination, forming the basis for stereoscopic perception. Birds need to adapt to changes in lighting (meaning they can recognize stereoscopic shapes even when shadows look different) to accurately perceive different three-dimensional forms. However, how neurons in the key visual brain area in birds handle these lighting changes remains largely unreported. In this study, pigeons (Columba livia) were used as subjects to investigate how neurons in pigeon’s ventrolateral mesopallium (MVL) represent stereoscopic shapes consistently, regardless of changes in lighting. MethodsVisual cognitive training combined with neuronal recording was employed. Pigeons were first trained to discriminate different stereoscopic shapes (concave/convex). We then tested whether and how light luminance angle and surface appearance of the stereoscopic shapes affect their recognition accuracy, and further verify whether the results rely on specify luminance color. Simultaneously, neuronal firing activity of neurons was recorded with multiple electrode array implanted from the MVL during the presentation of difference shapes. The response was finally analyzed how selectively they responded to different stereoscopic shapes and whether their selectivity was affected by the changes of luminance condition (like lighting angle) or surface look. Support vector machine (SVM) models were trained on neuronal population responses recorded under one condition (light luminance angle of 45°) and used to decode responses under other conditions (light luminance angle of 135°, 225°, 315°) to verify the invariance of responses to different luminance conditions. ResultsBehavioral results from 6 pigeons consistently showed that the pigeons could reliably identify the core 3D shape (over 80% accuracy), and this ability wasn’t affected by changes in light angle or surface appearance. Statistical analysis of 88 recorded neurons from 6 pigeons revealed that 83% (73/88) showed strong selectivity for specific 3D shapes (selectivity index>0.3), and responses to convex shapes were consistently stronger than to concave shapes. These shape-selective responses remained stable across changes in light angle and surface appearance. Neural patterns were consistent under both blue and orange lighting. The decoding accuracy achieves above 70%, suggesting stable responses under different conditions (e.g., different lighting angles or surface appearance). ConclusionNeurons in the pigeon MVL maintain a consistent neural encoding pattern for different stereoscopic shapes, unaffected by illumination or surface appearance. This ensures stable object recognition by pigeons in changing visual environments. Our findings provide new physiological evidence for understanding how birds achieve stable perception (“invariant neural representations”) while coping with variations in the visual field.

Objective To investigate the effect and mechanism of methyl oxofulnonone A(META)on high glucose(HG)-induced H9c2 cell injury.Methods H9c2 cells were divided into control group(normal culture),model group(55 mmol·L-1 glucose)and experimental-L,-M,-H groups(55 mmol·L-1 glucose+12.5,25.0,50.0 μmol·L-1 META).Cell viability was detected by cell counting kit-8;intracellular reactive oxygen species(ROS)level was detected by DCFH-DA fluorescent probe;intracellular adenosine triphosphate(ATP)content was detected by luciferase;and autophagy-related protein expression was detected by Western blotting.Results The optical density values of 72-hour cells in the control group,model group and experimental-M,-H groups were 0.91±0.03,0.61±0.01,0.69±0.02 and 0.72±0.03;the ROS levels were(40.75±1.53)％,(43.73±1.30)％,(30.87±1.27)％and(28.28±1.43)％;the ATP contents were(8.16±0.71),(4.03±0.29),(5.29±0.31)and(5.83±0.31)nmol·mg-1;the relative expression levels of autophagy-related gene 5 protein were 1.05±0.06,1.46±0.09,0.98±0.11 and 0.89±0.09;the relative expression levels of ubiquitin-binding protein were 1.05±0.10,0.55±0.13,0.89±0.04 and 0.98±0.04;the ratios of microtubule-associated protein 1 light chain 3 11/Ⅰ protein were 1.09±0.09,1.82±0.05,1.67±0.29 and 1.09±0.15,respectively.Among the above indicators,there were statistically significant differences between the model group and the control and experimental-M,-H groups(P＜0.05,P＜0.01).Conclusion META significantly ameliorates H9c2 cardiomyocyte damage caused by high glucose,ameliorates oxidative stress,protects mitochondrial respiration and inhibits autophagy.

Nigella sativa L. seeds have been traditionally utilized in Chinese folk medicine for centuries to treat vitiligo. This study revealed that the ethanolic extract of Nigella sativa L. (HZC) enhances melanogenesis and mitigates oxidative stress-induced cellular senescence and dysfunction in melanocytes. In accordance with established protocols, the ethanol fraction from Nigella sativa L. seeds was extracted, concentrated, and lyophilized to evaluate its herbal effects via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, tyrosinase activity evaluation, measurement of cellular melanin contents, scratch assays, senescence-associated β-galactosidase (SA-β-gal) staining, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis for expression profiling of experimentally relevant proteins. The results indicated that HZC significantly enhanced tyrosinase activity and melanin content while notably increasing the protein expression levels of Tyr, Mitf, and gp100 in B16F10 cells. Furthermore, HZC effectively mitigated oxidative stress-induced cellular senescence, improved melanocyte condition, and rectified various functional impairments associated with melanocyte dysfunction. These findings suggest that HZC increases melanin synthesis in melanocytes through the activation of the MAPK, PKA, and Wnt signaling pathways. In addition, HZC attenuates oxidative damage induced by H₂O₂ therapy by activating the nuclear factor E2-related factor 2-antioxidant response element (Nrf2-ARE) pathway and enhancing the activity of downstream antioxidant enzymes, thus preventing premature senescence and dysfunction in melanocytes.
Oxidative Stress/drug effects* ; Melanocytes/cytology* ; Cellular Senescence/drug effects* ; Nigella sativa/chemistry* ; Plant Extracts/pharmacology* ; Seeds/chemistry* ; Mice ; Animals ; Melanins/metabolism* ; Monophenol Monooxygenase/metabolism* ; Humans

AIM To observe the protective effects and mechanism of Shuli Jiangzhuo Formula on cardiac function in a rat model of uremic cardiomyopathy(UCM).METHODS The successful UCM models established by 5/6 nephrectomy were randomly allocated into the model group,the valsartan group(8.33 mg/kg),and the low-dose,medium-dose and high-dose Shuli Jiangzhuo Formula groups(7.19,14.38,28.76 g/kg),in contrast to those of the sham operation group,followed by 8 weeks respective drug administration.Upon the completion of the pharmacological intervention,the rats had the left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),ejection fraction(EF)and fractional shortening(FS)measured by echocardiography;the whole heart mass index(HMI)and left ventricular mass index(LVMI)detected;the renal function(serum creatinine,blood urea nitrogen)and the hemoglobin concentration detected;the mitochondrial morphology analyzed by observation of cardiomyocyte ultrastructure using transmission electron microscopy;the DNA damage in cardiomyocytes detected by TUNEL staining;the serum levels of IL-1β,IL-18 and BNP detected by ELISA;and the myocardial mRNA and protein expressions of NLRP3,Caspase-1 and IL-1β detected by RT-qPCR and Western blot.RESULTS Compared with the sham operated controls,the model group demonstrated significant elevation of serum creatinine and urea nitrogen(P＜0.01);decreased hemoglobin concentration(P＜0.01);disorganized myocardial collagen fiber architecture,and pronounced mitochondrial swelling with ultrastructural damage;decreased EF and FS(P＜0.05);increased LVEDD and LVESD(P＜0.01);increased HMI and LVMI(P＜0.01);increased levels of serum IL-1β,IL-18 and BNP(P＜0.01);increased cardiomyocyte pyroptosis(P＜0.01);and enhanced mRNA and protein expressions of NLRP3,Caspase-1 and IL-1 β(P＜0.01).Compared to model group controls,the high-dose Shuli Jiantuo Formula intervention exhibited decreased levels of serum creatinine and urea nitrogen(P＜0.01);increased hemoglobin concentration(P＜0.01);reduced DNA fragmentation,alleviated mitochondrial swelling and mitigated ultrastructural damage;reduced LVEDD and LVESD(P＜0.05,P＜0.01);decreased HMI and LVMI(P＜0.01);downregulated levels of serum IL-1β,IL-18 and BNP(P＜0.01);decreased cardiomyocyte pyroptosis(P＜0.01);and inhibited mRNA and protein expressions of NLRP3,Caspase-1 and IL-1β(P＜0.05,P＜0.01).CONCLUSION Shuli Jiangzhuo Formula demonstrates dual cardiorenal protective effects in UCM rats through suppression of the left ventricular hypertrophy progression and inhibition of the adverse ventricular remodeling processess.The therapeutic efficacy primarily stems from targeted suppression of NLRP3/Caspase-1 signaling pathway activation and substantial attenuation of cardiomyocyte pyroptosis cascade.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.