Carnosol prevents cardiac remodeling and ventricular arrhythmias in pressure overload-induced heart failure mice.

Cardiac remodeling is a commonly observed pathophysiological phenomenon associated with the progression of heart failure in various cardiovascular disorders. Carnosol, a phenolic compound extracted from rosemary, possesses noteworthy pharmacological properties including anti-inflammatory, antioxidant, and anti-apoptotic activities. Considering the pivotal involvement of inflammation, oxidative stress, and apoptosis in cardiac remodeling, the present study aims to assess the effects of carnosol on cardiac remodeling and elucidate the underlying mechanisms. In an in vivo model, cardiac remodeling was induced by performing transverse aortic constriction (TAC) surgery on mice, while an in vitro model was established by treating neonatal rat cardiomyocytes (NRCMs) with Ang II. Our results revealed that carnosol treatment effectively ameliorated TAC-induced myocardial hypertrophy and fibrosis, thereby attenuating cardiac dysfunction in mice. Moreover, carnosol improved cardiac electrical remodeling and restored connexin 43 expression, thereby reducing the vulnerability to ventricular fibrillation (VF). Furthermore, carnosol significantly reduced Ang II-induced cardiomyocyte hypertrophy in NRCMs and alleviated the upregulation of hypertrophy and fibrosis markers. Both in vivo and in vitro models of cardiac remodeling exhibited the anti-inflammatory, anti-oxidative, and anti-apoptotic effects of carnosol. Mechanistically, these effects were mediated through the Sirt1/PI3K/AKT pathway, as the protective effects of carnosol were abrogated upon inhibition of Sirt1 or activation of the PI3K/AKT pathway. In summary, our study suggests that carnosol prevents cardiac structural and electrical remodeling by regulating the anti-inflammatory, anti-oxidative, and anti-apoptotic effects mediated by Sirt1/PI3K/AKT signaling pathways, thereby alleviating heart failure and VF.

Correction: Effect of the HXBM408 bacteria on rat intestinal bacterial diversity and the metabolism of soybean isoflavones.

[This corrects the article DOI: 10.1371/journal.pone.0253728.].

Ferrocene-Based Antioxidant Self-Healing Hydrogel via the Biginelli Reaction for Wound Healing.

The development of antioxidant wound dressings to remove excessive free radicals around wounds is essential for wound healing. In this study, we developed an efficient strategy to prepare antioxidant self-healing hydrogels as wound dressings by combining multicomponent reactions (MCRs) and postpolymerization modification. A polymer containing ferrocene and phenylboronic acid groups was developed via the Biginelli reaction, followed by efficient modification. This polymer is antioxidant due to its ferrocene moieties and can rapidly cross-link poly(vinyl alcohol) to realize an antioxidant self-healing hydrogel through dynamic borate ester linkages. This hydrogel has low cytotoxicity and is biocompatible. In in vivo experiments, this hydrogel is superior to existing clinical dressings in promoting wound healing. This study demonstrates the value of the Biginelli reaction in exploring biomaterials, potentially offering insights into the design of other multifunctional polymers and related materials using different MCRs.

Effect and Safety of Herbal Medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy: A Multicenter Double-Blind Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).

A comprehensive overview of graph neural network-based approaches to clustering for spatial transcriptomics.

Spatial transcriptomics technologies enable researchers to accurately quantify and localize messenger ribonucleic acid (mRNA) transcripts at a high resolution while preserving their spatial context. The identification of spatial domains, or the task of spatial clustering, plays a crucial role in investigating data on spatial transcriptomes. One promising approach for classifying spatial domains involves the use of graph neural networks (GNNs) by leveraging gene expressions, spatial locations, and histological images. This study provided a comprehensive overview of the most recent GNN-based methods of spatial clustering methods for the analysis of data on spatial transcriptomics. We extensively evaluated the performance of current methods on prevalent datasets of spatial transcriptomics by considering their accuracy of clustering, robustness, data stabilization, relevant requirements, computational efficiency, and memory use. To this end, we explored 60 clustering scenarios by extending the essential frameworks of spatial clustering for the selection of the GNNs, algorithms of downstream clustering, principal component analysis (PCA)-based reduction, and refined methods of correction. We comparatively analyzed the performance of the methods in terms of spatial clustering to identify their limitations and outline future directions of research in the field. Our survey yielded novel insights, and provided motivation for further investigating spatial transcriptomics.

Astilbin protects from sepsis-induced cardiac injury through the NRF2/HO-1 and TLR4/NF-κB pathway.

Cardiac dysfunction and arrhythmia are severe complications of sepsis-induced cardiomyopathy and are associated with an increased risk of morbidity and mortality. Currently, the precise mechanism for sepsis-induced myocardial damage remains unclear. Astilbin, a flavonoid, is reported to have anti-inflammatory, antioxidative, and antiapoptotic properties. However, the effects of astilbin on sepsis-induced cardiomyopathy have not been studied so far. This study aims to investigate the effect of astilbin in sepsis-induced myocardial injury and elucidate the underlying mechanism. In vivo and in vitro sepsis models were created using lipopolysaccharide (LPS) as an inducer in H9C2 cardiomyocytes and C57BL/6 mice, respectively. Our results demonstrated that astilbin reduced myocardial injury and improved cardiac function. Moreover, astilbin prolonged the QT and corrected QT intervals, attenuated myocardial electrical remodeling, and promoted gap junction protein (Cx43) and ion channels expression, thereby reducing the susceptibility of ventricular fibrillation. In addition, astilbin alleviated LPS-induced inflammation, oxidative stress, and apoptosis. Astilbin suppressed the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway in vivo and in vitro models. Astilbin remarkedly upregulated the nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase 1 (HO-1) expression. The in vitro treatment with an NRF2 inhibitor reversed the inhibition of the TLR4/NF-κB pathway and antioxidant properties of astilbin. Astilbin attenuated LPS-induced myocardial injury, cardiac dysfunction, susceptibility to VF, inflammation, oxidative stress, and apoptosis by activating the NRF2/HO-1 pathway and inhibiting TLR4/ NF-κB pathway. These results suggest that astilbin could be an effective and promising therapeutics target for the treatment of sepsis-induced cardiomyopathy.

The Impact of Parent-child Sports Games on Children's Psychological Development / El impacto de los juegos deportivos entre padres e hijos en el desarrollo psicológico de los niños

Childhood is a stage of rapid psychological development, movement and psychological development are inseparable. At this stage, games are the main form of activity for children which play a dominant role in promoting children's psychological development. By implementing parent-child sports game intervention activities, children can prevent psychological disorders or behavioural problems, help them better adapt to social life, and make more effective contributions to society and humanity. Therefore, current research aimed to check the impact of parent-child sports games on children's psychological development. For this purpose, survey subjects were 50 students from large class of kindergarten A and 50 students from the large class of kindergarten B. An experimental research design was applied by using control and experimental group. The findings that the experimental group showed significant improvements in cognitive ability, emotional stability, willpower, and personality shaping compared to the control group. Moreover, their social adaptability was notably higher, fostering smoother communication and harmonious interpersonal relationships. The findings highlight the importance of early engagement in sports game activities to promote psychological health and resilience in preschool children, emphasizing the need for integrating such activities into early childhood education and parental involvement programs. The research also explored a new research area for further research.(AU)

Identification of Phenolic Acid Derivatives in Danshen Using MS3 and MS2 Spectra Matching Strategy / 分析化学

"MS/MS spectrum to structure"plays a critical role in the confirmative identification of complicated matrices and is currently regarded as an extremely challenging endeavor.MS/MS information provides vital clues to structural identification.In this study,a strategy was proposed to facilitate unambiguous identification through matching MS3 with MS2 spectra.Initially,MS3 spectra of the featured ions(c-and y-type ions)generated by the decomposition of ester functional group in esters and the MS2 spectrum of the structural unit([M-H]-)were all captured on the Qtrap-MS platform equipped with two tandem-in-space collision cells,including the second quadrupole cell(q2)and linear ion trap(LIT)chambers(actually the third quadrupole unit).Subsequently,the MS/MS spectrum matching between MS3 spectra of the ester compound and MS2 spectra of the structural unit(s)were achieved.As a result,the findings corresponding to MS3 and MS2 spectra matching were summarized.Finally,based on HR-MS/MS information of total salvianolic acid derivatives(TSA),36 kinds of compounds were preliminarily identified through matching with literature information and database retrieval.The applicability of MS3 and MS2 spectra matching strategy was further justified by the confirmative identification of phenolic acid compounds(Rosmarinic acid and salvianolic acid B)in TSA.Above all,MS3 and MS2 spectra matching strategy was quite meaningful towards advancing"MS/MS spectrum to structure"analysis through recognizing and identifying featured fragment ions,and also provided inspiration and new insights for the structural characterization.

Application of nursing intervention based on information-knowledge-attitude-practice model in preventing radiodermatitis in tumor radiotherapy patients / 中国实用护理杂志

Objective:To explore the effect of nursing intervention based on information-knowledge-attitude-practice model (IKAP) in preventing radiodermatitis in tumor radiotherapy patients.Methods:This was a quasi-experimental study. A total of 72 patients who received radiotherapy in the Department of Oncology, the Second Hospital of Shanxi Medical University from August to October 2022 were selected and divided into the experimental group and the control group with 36 patients in each group by randomized digits table method. The control group received routine nursing, while the experimental group received nursing based on the IKAP. The self-management efficacy, radiodermatitis, self-perceived burden and quality of life of patients in the two groups were evaluated one day before and at the end of radiotherapy.Results:Thirty-five patients from each group completed the study. There were 11 males and 24 females in the control group, aged (58.09 ± 7.33) years old. There were 13 males and 22 females in the experimental group, aged (58.06 ± 7.28) years old.There was no statistically significant difference in self-management efficacy, self-perceived burden, and quality of life scores between the two groups of patients before intervention (all P>0.05). After intervention, the self-management efficacy,self-perceived burden, and quality of life scores of the experimental group were (106.89 ± 3.78), (18.69 ± 2.21), and (8.09 ± 1.27) points, respectively, the control group was (80.69 ± 5.76), (29.97 ± 2.48), and (15.91 ± 2.37) points, respectively. The differences between the two groups were statistically significant ( t=2.50, 1.12, 7.24, all P<0.01). The incidence of radiodermatitis above grade 2 in the experimental group was 31.4%(12/35), which was lower than 60.0%(21/35) in the control group, the difference was statistically significant ( χ2=4.64, P<0.01). Conclusions:Nursing intervention based on IKAP can improve the self-management efficacy, reduce the self-perceived burden and the incidence of radiodermatitis, and further improve the quality of life of tumor radiotherapy patients.

Summary of the best evidence for screening and management of patients with post-stroke fatigue / 中国实用护理杂志

Objective:To search, screen and summarize the best evidence of screening and management of patients with post-stroke fatigue, and to provide basis for early identification of clinical staff.Methods:According to the "6S" pyramid model, the system searches for relevant evidence on post stroke fatigue screening and management from UpToDate, BMJ Best Practice, International Guidelines Collaboration Network, New Zealand Guidelines Collaboration Group, Ontario Registered Nurses Association website, Scottish Interhospital Guidelines Network, Joanna Briggs Institute Evidence Based Health Care Center database, and Yimaitong, National Stroke Foundation, Stroke Association, National Stroke Center, Cochrane Library, PubMed, Embase, CINAHL, CNKI, WanFang Datebase, VIP and CBM from January 2013 to March 2023 regarding screening and management of post stroke fatigue patients. Researchers screen literature, evaluate quality, and summarize evidence.Results:Fifteen articles were selected, including 1 clinical decision, 3 guidelines, 3 expert consensus, 2 evidence summary, 5 systematic review and 1 randomized controlled trial. A total of 22 best evidence items were summarized from seven aspects of screening assessment, risk factors, psychosocial intervention, activity and rest, health education, complementary therapy, and follow-up.Conclusions:The study summarized the best evidence for the screening and management of patients with post-stroke fatigue, so as to provide a more scientific and systematic approach to the management of post-stroke fatigue and provide a reference for improving the long-term quality of life of stroke patients.

Mechanism by which lycium barbarum polysaccharides inhibit keratinocyte apoptosis in burn wounds via autophagy / 中国组织工程研究

BACKGROUND:Lycium barbarum polysaccharide has many biological activities and has been found to have potential effects on promoting wound healing. OBJECTIVE:To investigate the mechanism of lycium barbarum polysaccharide in tumor necrosis factor-α-mediated keratinocyte apoptosis and its effect on the healing of burn wounds. METHODS:(1)In vitro experiment:Keratinocytes were divided into four groups:cells were cultured in the α-MEM medium(complete medium)containing 15%fetal bovine serum and 1%glutamine in normal group,cultured in the complete medium containing lycium barbarum polysaccharide in positive control group,cultured in the complete medium containing tumor necrosis factor-α in model group,and cultured in the complete medium containing lycium barbarum polysaccharide and tumor necrosis factor-α in experimental group.After 24 hours of culture,cell proliferation was detected using cell counting kit-8 assay;Cleaved caspase-8,TNF R1,FADD,and LC3 were detected using western blot.Then an autophagy inhibitor group(the complete medium containing 3-methyladenine)and an autophagy inhibitor+lycium barbarum polysaccharide group(the complete medium containing lycium barbarum polysaccharide,tumor necrosis factor-α,and 3-methyladenine)were set up.After 24 hours of culture,keratinocyte apoptosis was detected by flow cytometry.(2)In vivo experiment:Six Sprague-Dawley rats were randomly divided into a control group and an experimental group,with three rats in each group.Four deep Ⅱ degree burn wounds with a diameter of 2 cm were made on the back of each rat.At 24 hours after modeling,mice in the control and experimental groups were coated with normal saline and lycium barbarum polysaccharide solution,respectively,once a day.Wound healing was observed regularly after treatment.Samples were taken 28 days after treatment and the pathologic pattern of the wound was observed. RESULTS AND CONCLUSION:(1)In vitro experiment:Addition of lycium barbarum polysaccharide alone did not affect cell proliferation and apoptosis and the expression of apoptotic and autophagic proteins in keratinocytes.After the addition of tumor necrosis factor α,the proliferation of keratinocytes was inhibited,the apoptotic rate increased,and the expression of apoptotic and autophagic proteins was elevated,while lycium barbarum polysaccharide could antagonize the above effects of tumor necrosis factor-α.Lycium barbarum polysaccharide combined with autophagy inhibitors further reduced the apoptotic rate of keratinocytes.(2)In vivo experiment:The wound healing rate of rats in the experimental group was higher than that of the control group at 12,16,20,24,and 28 days after treatment(P＜0.05,P＜0.01).Hematoxylin-eosin staining results at 28 days after treatment showed an intact and well-defined epidermis of the wound in the experimental group compared with the control group.To conclude,lycium barbarum polysaccharide protects the integrity of skin epidermal tissue and promotes wound healing by inhibiting autophagy and apoptosis of keratinocytes.

HIV antiretroviral therapy among blood donors: the impact on blood safety / 中国输血杂志

【Objective】 To explore the the potential risks of antiretroviral therapy(ART) drugs on blood safety among blood donors in Shenzhen. 【Methods】 High pressure liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was used to measure ART drugs concentrations in the plasma of regular blood donors (negative control group, n=86) and anti-HIV positive individuals (experimental group, n=98, detected from approximately 440 000 blood donors during 2019—2023). The baseline plasma concentrations of ART drugs in the negative control group were clarified, and the impact of ART drugs on blood safety was analyzed. 【Results】 The baseline concentrations of ART drugs were not detected in 86 samples of negative control group. Four positive ART drugs samples were detected in 1∶2 pooled plasma samples of 98 anti-HIV positive blood donors plasma in the resolution test. The ART positive rate of anti-HIV positive donors was 4.08%, with tenofovir, lamivudine and efavirenz detected in three blood donors and lamivudine, lopinavir, ritonavir and zidovudine detected in one blood donor. 【Conclusion】 ART drugs were found among anti-HIV positive blood donors in Shenzhen. Additional research is needed to investigate the motivation of these specific donors, so as to ascertain the groups most susceptible to potential risks, and guarantee blood safety.

Comparison of Direct and Extraction Immunoassay Methods With Liquid Chromatography-Tandem Mass Spectrometry Measurement of Urinary Free Cortisol for the Diagnosis of Cushing’s Syndrome

Background@#Twenty-four-hour urinary free cortisol (UFC) measurement is the initial diagnostic test for Cushing’s syndrome (CS). We compared UFC determination by both direct and extraction immunoassays using Abbott Architect, Siemens Atellica Solution, and Beckman DxI800 with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, we evaluated the value of 24-hr UFC measured by six methods for diagnosing CS. @*Methods@#Residual 24-hr urine samples of 94 CS and 246 non-CS patients were collected.A laboratory-developed LC-MS/MS method was used as reference. UFC was measured by direct assays (D) using Abbott, Siemens, and Beckman platforms and by extraction assays (E) using Siemens and Beckman platforms. Method was compared using Passing–Bablok regression and Bland–Altman plot analyses. Cut-off values for the six assays and corresponding sensitivities and specificities were calculated by ROC analysis. @*Results@#Abbott-D, Beckman-E, Siemens-E, and Siemens-D showed strong correlations with LC-MS/MS (Spearman coefficient r = 0.965, 0.922, 0.922, and 0.897, respectively), while Beckman-D showed weaker correlation (r = 0.755). All immunoassays showed proportionally positive bias. The areas under the curve were 0.975 for Abbott-D, 0.972 for LCMS/MS, 0.966 for Siemens-E, 0.948 for Siemens-D, 0.955 for Beckman-E, and 0.877 for Beckman-D. The cut-off values varied significantly (154.8–1,321.5 nmol/24 hrs). Assay sensitivity and specificity ranged from 76.1% to 93.2% and from 93.0% to 97.1%, respectively. @*Conclusions@#Commercially available immunoassays for measuring UFC show different levels of analytical consistency compared to LC-MS/MS. Abbott-D, Siemens-E, and Beckman-E have high diagnostic accuracy for CS.

[Prescription and medication rules of traditional Chinese medicine for prevention and treatment of diabetic microangiopathy based on literature mining].

This study explored the prescription and medication rules of traditional Chinese medicine(TCM) in the prevention and treatment of diabetic microangiopathy based on literature mining. Relevant literature on TCM against diabetic microangiopathy was searched and prescriptions were collected. Microsoft Excel 2021 software was used to establish a prescription database, and an analysis was conducted on the frequency, properties, flavors, meridian tropism, and efficacy classifications of drugs. Association rule analysis, cluster analysis, and factor analysis were performed using SPSS Modeler 18.0 and SPSS Statistics 26.0 software. The characteristic active components and mechanisms of action of medium-high frequency drugs in the analysis of medication rules were explored through li-terature mining. A total of 1 327 prescriptions were included in this study, involving 411 drugs, with a total frequency reaching 19 154 times. The top five high-frequency drugs were Astragali Radix, Angelicae Sinensis Radix, Poria, Salviae Miltiorrhizae Radix et Rhizoma, and Rehmanniae Radix. The cold and warm drugs were used in combination. Drugs were mainly sweet, followed by bitter and pungent, and acted on the liver meridian. The majority of drugs were effective in tonifying deficiency, clearing heat, activating blood, and resolving stasis. Association rule analysis identified the highly supported drug pair of Astragali Radix-Angelicae Sinensis Radix and the highly confident drug combination of Poria-Alismatis Rhizoma-Corni Fructus. The strongest correlation was found among Astragali Radix, Angelicae Sinensis Radix, Poria, and Salviae Miltiorrhizae Radix et Rhizoma through the complex network analysis. Cluster analysis identified nine categories of drug combinations, while factor analysis identified 16 common factors. The analysis of active components in high-frequency drugs for the treatment of diabetic microangiopathy revealed that these effective components mainly exerted their effects by inhibiting oxidative stress and suppressing inflammatory reactions. The study found that the pathogenesis of diabetic microangiopathy was primarily characterized by deficiency in origin, with a combination of deficiency and excess. Deficiency was manifested as Qi deficiency and blood deficiency, while excess as phlegm-heat and blood stasis. The key organ involved in the pathological changes was the liver. The treatment mainly focused on supplementing Qi and nourishing blood, supplemented by clearing heat, coo-ling blood, activating blood, and dredging collaterals. Commonly used formulas included Danggui Buxue Decoction, Liuwei Dihuang Pills, Erzhi Pills, and Buyang Huanwu Decoction. The mechanisms of action of high-frequency drugs in the treatment of diabetic microangiopathy were often related to the inhibition of oxidative stress and suppression of inflammatory reactions. These findings can provide references for the clinical treatment of diabetic microangiopathy and the development of targeted drugs.

Germacrone mitigates cardiac remodeling by regulating PI3K/AKT-mediated oxidative stress, inflammation, and apoptosis.

Cardiac remodeling is a common consequence of cardiovascular diseases and is closely associated with oxidative stress, inflammation, and apoptosis. Germacrone, a bioactive compound present in Rhizoma curcuma, has been shown to possess anti-oxidative, anti-inflammatory, and anti-apoptotic properties. The aim of this study was to investigate the protective effect of germacrone against cardiac remodeling. Here, C57BL/6 mice were subcutaneous injection with isoproterenol (ISO) once daily for two weeks and were concurrent intragastric injection of germacrone. In vitro, neonatal rat cardiomyocytes (NRCMs) were used to verify the protective effect of germacrone on ISO-induced cardiac injury. Our findings indicated that ISO induce oxidative stress, inflammation, and apoptosis in vivo and in vitro, while germacrone treatment significantly attenuates these effects, thereby attenuating myocardium remodeling and cardiac dysfunction. Mechanistically, germacrone reduced cardiac remodeling-induced activation of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, and the cardioprotective effects of germacrone were abrogated by a PI3K agonist. In conclusion, our results suggest that germacrone attenuates oxidative stress, inflammation, and apoptosis in cardiac remodeling by inhibiting the PI3K/AKT pathway, and may therefore represent a promising therapeutic approach for the treatment of cardiac remodeling.

UGCG modulates heart hypertrophy through B4GalT5-mediated mitochondrial oxidative stress and the ERK signaling pathway.

Mechanical pressure overload and other stimuli often contribute to heart hypertrophy, a significant factor in the induction of heart failure. The UDP-glucose ceramide glycosyltransferase (UGCG) enzyme plays a crucial role in the metabolism of sphingolipids through the production of glucosylceramide. However, its role in heart hypertrophy remains unknown. In this study, UGCG was induced in response to pressure overload in vivo and phenylephrine stimulation in vitro. Additionally, UGCG downregulation ameliorated cardiomyocyte hypertrophy, improved cardiomyocyte mitochondrial oxidative stress, and reduced the ERK signaling pathway. Conversely, UGCG overexpression in cardiomyocytes promoted heart hypertrophy development, aggravated mitochondrial oxidative stress, and stimulated ERK signaling. Furthermore, the interaction between beta-1,4-galactosyltransferase 5 (B4GalT5), which catalyses the synthesis of lactosylceramide, and UGCG was identified, which also functions as a synergistic molecule of UGCG. Notably, limiting the expression of B4GalT5 impaired the capacity of UGCG to promote myocardial hypertrophy, suggesting that B4GalT5 acts as an intermediary for UGCG. Overall, this study highlights the potential of UGCG as a modulator of heart hypertrophy, rendering it a potential target for combating heart hypertrophy.

[Activation of Hippo Pathway Proteins in Thrombin-Stimulated Platelets and Regutates Platelets Activation in Vitro].

OBJECTIVE: To investigate the phosphorylation levels of Hippo pathway proteins in thrombin stimulated platelets and to explore its effects on platelet activation. METHODS: The phosphorylation levels of Hippo pathway proteins - Mammalian STE20-like kinase 1/2 (MST1/2), Nuclear Dbf2 related kinase 1/2 (NDR1/2) and Mps one binder 1(MOB1) in human thrombin stimulated platelets was detected by Western blot. The effect of MST1/2 inhibitor XMU-MP-1 on platelet aggregation was detected by Platelet Aggregometer. The effect of XMU-MP-1 on platelet integrin αIIbß3 activation and CD62p expression was detected by flow cytometry. The effect of XMU-MP-1 on the "outside-in" signal of platelet integrin was detected by blood clot retraction test. The effects of XMU-MP-1 on platelet Hippo pathway proteins and p38 phosphorylation levels was detected by Western blot. RESULTS: The phosphorylation levels of MST1/2, NDR1/2 and MOB1 were significantly increased in thrombin activated platelets; XMU-MP-1 inhibited thrombin-induced platelet aggregation and αIIbß3 activation, but did not affect α-granules release and clot retraction. In addition, thrombin induced phosphorylation of the Hippo proteins were decreased in XMU-MP-1 treated platelets, while the phosphorylation of p38 was not affected. CONCLUSION: In thrombin stimulated platelets, Hippo pathway proteins were activated and contributed to platelets activation.

Effect of C7-T1 Extensional Posterior Transpedicle Osteotomy on Mobility and Quality of Life in Patients with Ankylosing Spondylitis Complicated with Lumbar Kyphosis and Related Factors.

Objective: To analyze the effect of C7-T1 extensional posterior transpedicular vertebral osteotomy (PSO) on mobility and quality of life in patients with ankylosing spondylitis (AS) and lumbar kyphosis. Methods: This study was conducted from February 2019 to February 2021 and a total of 38 patients with AS combined with kyphosis from Tianjin Union Medical Center, Tianjin, China, were selected for the study. After performing all preoperative examinations, all patients were treated with C7-T1 extensional posterior PSO osteotomy. The patients' operation and follow-up, pain degree as a Visual analogue scale (VAS) score and sagittal balance index changes before and after surgery, spinal function measured as; Bath Ankylosing Spondylitis Functional Index (BASFI) score and quality of life by Scoliosis Research Society-22 (SRS-22) score, were observed before and after surgery. Pearson correlation coefficient was used to analyze the correlation between patients' quality of life and BASFI score. Results: After surgery, the pain of the patients' back was significantly relieved, the patients' appearance and trunk balance function were significantly improved, and the symptoms related to nerve function were not significantly aggravated. No complications such as infection, internal fixation failure or spinal decompensation occurred in all patients. VAS score, kyphosis Cobb Angle and Sagittal Vertical Axis (SVA) of all patients showed P < .05 before and 1 year after surgery. BASFI score 1 year after surgery decreased significantly than that before surgery (P < .05). 1 year after surgery, body function, pain symptoms, self-image and psychological state of the patients were significantly improved, and the SRS-22 total score of the patients 1 year after surgery increased significantly than before surgery (P < 0.05). BASFI score was negatively correlated with SRS-22 score by Pearson correlation coefficient analysis (P < .05). Conclusion: C7-T1 extensional posterior PSO osteotomy has a good effect in the treatment of AS patients with lumbar kyphosis. The sagittal balance was well-restored with improvement in patients' quality of life after surgery, which makes C7-T1 osteotomy worthy of clinical application to treat patients suffering from AS combined with lumbar kyphosis.

Curcumol alleviates cardiac remodeling via the AKT/NF-κB pathway.

Cardiac remodeling is the final stage of almost all cardiovascular diseases, leading to heart failure and arrhythmias. However, the pathogenesis of cardiac remodeling is not fully understood, and specific treatment schemes are currently unavailable. Curcumol is a bioactive sesquiterpenoid that has anti-inflammatory, anti-apoptotic, and anti-fibrotic properties. This study aimed to investigate the protective effect of curcumol on cardiac remodeling and elucidate its relevant underlying mechanism. Curcumol significantly attenuated cardiac dysfunction, myocardial fibrosis, and hypertrophy in the animal model of isoproterenol (ISO)-induced cardiac remodeling. Curcumol also alleviated cardiac electrical remodeling, thereby reducing the risk of ventricular fibrillation (VF) after heart failure. Inflammation and apoptosis are critical pathological processes involved in cardiac remodeling. Curcumol inhibited the inflammation and apoptosis induced by ISO and TGF-ß1 in mouse myocardium and neonatal rat cardiomyocytes (NRCMs). Furthermore, the protective effects of curcumol were found to be mediated through the inhibition of the protein kinase B (AKT)/nuclear factor-kappa B (NF-κB) pathway. The administration of an AKT agonist reversed the anti-fibrotic, anti-inflammatory, and anti-apoptotic effects of curcumol and restored the inhibition of NF-κB nuclear translocation in TGF-ß1-induced NRCMs. Our study suggests that curcumol is a potential therapeutic agent for the treatment of cardiac remodeling.

The in vivo drug delivery pattern of the organelle-targeting small molecules.

Eukaryotic cell organelles sustain the life of cells. Their structural changes and dysfunctions can cause abnormal physiological activities and lead to various diseases. Molecular imaging technology enables the visualization of subcellular structures, cells, organs, and the whole living body's structure and metabolism dynamic changes. This could help to reveal the pharmacology mechanisms and drug delivery pathway in vivo. This article discusses the relationship between organelles and human disease, reviews recent probes targeting organelles and their behavior in vivo. We found that mitochondria-targeting probes prefer accumulation in the intestine, heart, and tumor. The lysosome-targeting probe accumulates in the intestine and tumor. Few studies on endoplasmic reticulum- or Golgi apparatus-targeting probes have been reported for in vivo imaging. We hope this review could provide new insights for developing and applying organelle-targeting probes.