Multiple organs injury and myocardial energy metabolism disorders induced by isoproterenol.

The study sought to assess the detrimental effects of isoproterenol (ISO) on major organs and investigate the potential reversibility of these adverse reactions in mice. Male mice were divided into normal control, 0.2 mg/kg.d and 3.0 mg/kg.d ISO groups, and were subcutaneously administered of the respective doses for 14 consecutive days. Subsequently, a recovery period experiment was conducted, replicating the aforementioned procedure, followed by an additional 2-week recovery period for the mice. Following 14 consecutive days of administration, mice treated with ISO exhibited notable cardiac damage manifested by abnormal ECG patterns, dysregulated energy metabolism, elevated cardiac hypertrophy, and increased heart pathological score. Additionally, the administration of ISO resulted in liver and kidney damage, as evidenced by increased pathological score, serum albumin level, and urea level. Lung damage was also observed, indicated by an increase in lung pathological score. Furthermore, the administration of ISO at a dosage of 3.0 mg/kg.d resulted in a decrease in liver mass index, serum iron content, and an increase in lung mass index. After a 2-week recovery period, mice treated with ISO showed abnormalities in ECG patterns and dysregulated myocardial energy metabolism, accompanied by a decrease in serum iron content. Histopathological examinations revealed continued pathological changes in the heart and lung, as well as significant hemosiderin deposition in the spleen. Furthermore, the group treated with ISO at a dosage of 3.0 mg/kg.d showed an increase in serum AST and TP levels. In summary, the study demonstrates that both 0.2 mg/kg.d and 3.0 mg/kg.d doses of ISO can induce damage to the heart, liver, lung, kidney, and spleen, with the higher dose causing more severe injuries. After a 2-week withdrawal period, the liver, kidney, and thymus injuries caused by 0.2 mg/kg ISO shows signs of recovery, while damage to the heart, lung, and spleen persists. The thymus injury mostly recovers, with minimal kidney pathology, but significant damage to the heart, liver, and lung remains even after the withdrawal period for the 3.0 mg/kg ISO dose.

[Screening and expression analysis of transcription factors involved in genuineness of Codonopsis pilosula in Shanxi].

This study aims to mine the transcription factors that affect the genuineness of Codonopsis pilosula in Shanxi based on the transcriptome data of C. pilosula samples collected from Shanxi and Gansu, and then analyze the gene expression patterns, which will provide a theoretical basis for the molecular assisted breeding of C. pilosula. Gene ontology(GO) functional annotation, conserved motif prediction, and gene expression pattern analysis were performed for the differential transcription factors predicted based on the transcriptome data of C. pilosula from different habitats. A total of 61 differentially expressed genes(DEGs) were screened out from the transcriptome data. Most of the DEGs belonged to AP2/ERF-ERF family, with the conserved motif of [2X]-[LG]-[3X]-T-[3X]-[AARAYDRAA]-[3X]-[RG]-[2X]-A-[2X]-[NFP]. Forty-three of the DEGs showed significantly higher gene expression in C. pilosula samples from Shanxi than in the samples from Gansu, including 11 genes in the AP2/ERF-ERF family, 5 genes in the NAC fa-mily, 1 gene in the bHLH family, and 2 genes in the RWP-RK family, while 18 transcription factors showed higher expression levels in the samples from Gansu. GO annotation predicted that most of the DEGs were enriched in GO terms related to transcriptional binding activity(103), metabolic process(26), and stress response(23). The expression of transcription factor genes, CpNAC92, CpNAC100, CpbHLH128, and CpRAP2-7 was higher in the samples from Shanxi and in the roots of C. pilosula. CpNAC92, CpbHLH128, and CpRAP2-7 responded to the low temperature, temperature difference, and iron stresses, while CpNAC100 only responded to low temperature and iron stresses. The screening and expression analysis of the specific transcription factors CpNAC92, CpNAC100, CpbHLH128, and CpRAP2-7 in C. pilosula in Shanxi laid a theoretical foundation for further research on the mechanism of genuineness formation of C. pilosula.

Determination of total phenol and six polyphenolic components in the polyphenol extract of Cinnamomi cortex by quantitative nuclear magnetic resonance spectroscopy.

A quantitative nuclear magnetic resonance spectroscopy (qNMR) method was established for determining the total phenol and six polyphenolic components in the polyphenol extract of Cinnamomi cortex. The qNMR approach utilized DMSO-d6 as the deuterated solvent and potassium hydrogen phthalate as the internal standard for quantifying the total phenolic content, expressed as epicatechin equivalence in the sample. Two complementary qNMR methods with DMSO-d6 or D2O as solvent were established to simultaneously determine 6 polyphenol components in the cinnamon polyphenol extract, including epigallocatechin gallate (EGCG), epicatechingallate (ECG), epicatechin (EC), epigallocatechin (EGC), gallocatechin gallate (GCG) and gallic acid (GA). Method validation demonstrated excellent precision with intraday relative standard deviation (RSD) below 1.08% and interday RSD below 1.48%. The linear correlation coefficient (r) exceeded 0.999, and the limits of detection (LOD) were from 0.01 to 0.14 mg mL-1, while the limits of quantification (LOQ) were from 0.07 to 0.69 mg mL-1. Recovery rates for this method fell within the range of 98.2% to 101.7%. Furthermore, the method has been successfully applied for determining the polyphenolic content in authentic cinnamon polyphenol extracts obtained from different sources.

Acute liver failure: A systematic review and network meta-analysis of optimal type of stem cells in animal models.

BACKGROUND: The therapeutic effects of various stem cells in acute liver failure (ALF) have been demonstrated in preclinical studies. However, the specific type of stem cells with the highest therapeutic potential has not been determined. AIM: To validate the efficacy of stem cells in ALF model and to identify the most promising stem cells. METHODS: A search was conducted on the PubMed, Web of Science, Embase, Scopus, and Cochrane databases from inception to May 3, 2022, and updated on November 16, 2022 to identify relevant studies. Two independent reviewers performed the literature search, identification, screening, quality assessment, and data extraction. RESULTS: A total of 89 animal studies were included in the analysis. The results of traditional meta-analysis showed that stem cell therapy could significantly reduce the serum levels of alanine aminotransferase [weighted mean difference (WMD) = -181.05 (-191.71, -170.39)], aspartate aminotransferase [WMD = -309.04 (-328.45, -289.63)], tumor necrosis factor-alpha [WMD = -8.75 (-9.93, -7.56)], and interleukin-6 [WMD = -10.43 (-12.11, -8.76)] in animal models of ALF. Further subgroup analysis and network meta-analysis showed that although mesenchymal stem cells are the current research hotspot, the effect of liver stem cells (LSCs) on improving liver function is significantly better than that of the other five types of stem cells. In addition, the ranking results showed that the possibility of LSCs improving liver function ranked first. This fully proves the great therapeutic potential of LSCs, which needs to be paid more attention in the future. CONCLUSION: LSCs may have a higher therapeutic potential. Further high-quality animal experiments are needed to explore the most effective stem cells for ALF.

Establishment of a genetic transformation system for Codonopsis pilosula callus.

Codonopsis pilosula, a traditional Chinese medicinal and edible plant, contains several bioactive components. However, the biosynthetic mechanism is unclear because of the difficulties associated with functional gene analysis. Therefore, it is important to establish an efficient genetic transformation system for gene function analysis. In this study, we established a highly efficient Agrobacterium-mediated callus genetic transformation system for C. pilosula using stems as explants. After being pre-cultured for 3 days, the explants were infected with Agrobacterium tumefaciens strain GV3101 harboring pCAMBIA1381-35S::GUS at an OD600 value of 0.3 for 15 min, followed by co-cultivation on MS induction medium for 1 day and delayed cultivation on medium supplemented with 250 mg l-1 cefotaxime sodium for 12 days. The transformed calli were selected on screening medium supplemented with 250 mg l-1 cefotaxime sodium and 2.0 mg l-1 hygromycin and further confirmed by PCR amplification of the GUS gene and histochemical GUS assay. Based on the optimal protocol, the induction and transformation efficiency of calli reached a maximum of 91.07%. The establishment of a genetic transformation system for C. pilosula calli lays the foundation for the functional analysis of genes related to bioactive components through genetic engineering technology.

Sodium houttuyfonate protects against cardiac injury by regulating cardiac energy metabolism in diabetic rats.

Diabetic cardiomyopathy is a diabetic complication with complicated pathophysiological changes and pathogenesis and difficult treatment. Sodium houttuyfonate is the adduct of sodium bisulfite and houttuynin, the main volatile component in Houttuynia cordata Thunb, possesses a variety of activities including multiple interventions on inhibiting ventricular remodeling. The study aims to explore effect of sodium houttuyfonate on diabetic myocardial injury and its underlying mechanisms. The diabetes model was established by intraperitoneal injection of streptozotocin at a dose of 85 mg/kg. By intragastric administration for 26 days, sodium houttuyfonate (50 and 100 mg/kg/d) reversed the abnormal serum levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol and low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio, improved the abnormal levels of serum aspartate aminotransferase and brain natriuretic peptide, reduced electrocardiogram P-R and QRS interval extension, accelerated the heart rate, decreased serum malondialdehyde content, up-regulated the myocardial energy metabolism including elevated the contents of ATP, ADP, total adenine nucleotides and phosphocreatine in myocardium, decreased AMP/ATP ratio, elevated myocardial Ca2+-Mg2+-ATPase activity, and down-regulated the mRNA expressions of AMP protein activation kinase α2 (AMPK-α2) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). In a conclusion, these results suggest that sodium houttuyfonate can improve cardiac energy metabolism disorder caused by diabetes by increasing cardiac Ca2+-Mg2+-ATPase activity and regulating AMPK signaling pathway, and then attenuates cardiac injury caused by hyperglycemia. In addition, sodium houttuyfonate also has the effects of anti-oxidation and improving abnormal levels of blood lipid.

Antinociceptive activities and mechanism of action of Cepharanthine.

Cepharanthine is an alkaloid that isolated from Stephania cepharantha Hayata, however，its analgesic properties are unclear and the molecular targets that mediating Cepharanthine-induced analgesia are not explored yet. In the current study, mice pain models including hot plate, acetic acid-induced writhing and formalin tests were conducted to evaluate the antinociceptive actions of Cepharanthine. [3H]-ligand competitive binding assay was applied to determine the binding affinity and selectivity of Cepharanthine at κ, µ and δ opioid receptors. Cepharanthine-induced constipation was investigated using the small intestinal transit test. The results showed that intraperitoneal injection of Cepharanthine produced potent antinociception with an ED50 value of 24.5 mg/kg in the acetic acid-induced writhing test. In the formalin test, Cepharanthine produced moderate antinociception with the maximum analgesic activity of 42.6 ± 11.3% in phase I and 60.1 ± 7.7% in phase Ⅱ, respectively. Cepharanthine had no effects in the hot plate test. In vitro radioligand binding assay, Cepharanthine exhibited a high affinity for µ opioid receptors with a Ki value of 80 nM, without binding to κ and δ opioid receptors. Correspondingly, Cepharanthine-mediated antinociceptive effects were antagonized by pretreatment with opioid receptor antagonist naloxone. Cepharanthine also decreased the small intestine propulsion rates in the small intestinal transit test. Together, this study firstly demonstrates that Cepharanthine produces potent antinociception in acetic acid-induced visceral pain and moderate antinociception in formalin-induced inflammatory pain, and its mechanism of action may be through activation of µ opioid receptors.

NFAM1 Promotes Pro-Inflammatory Cytokine Production in Mouse and Human Monocytes.

NFAT activating protein with ITAM motif 1 (NFAM1) is an ITAM bearing-transmembrane receptor that has been reported to play a role in B cell signaling and development. We performed expression analysis of NFAM1 using publicly available gene expression data sets and found that NFAM1 expression is significantly induced in intestinal biopsies from Crohn's disease (CD) and ulcerative colitis (UC) patients. At the cellular level, we further observed high expression of NFAM1 in monocytes and neutrophils, and low expression in B and T cells. To explore the role of NFAM1 in multiple immune cells and its potential role in IBD, we generated NFAM1-/- mice. In contrast with previous reports using NFAM1-transgenic mice, NFAM1-/- mice have no obvious defects in immune cell development, or B cell responses. Interestingly, NFAM1-/- monocytes produce reduced levels of TNF-α in response to activation by multiple IBD-relevant stimuli, including CD40L, TLR ligands and MDP. Additional cytokines and chemokines such as IL-6, IL-12, CCL3 and CCL4 are also reduced in CD40L stimulated NFAM1-/- monocytes. Collectively, these findings indicate that NFAM1 promotes monocyte activation, thereby amplifying the response to diverse stimuli. Similarly, we observed that deletion of NFAM1 in human monocytes reduces expression of CD40L-induced CCL4. Lastly, to assess the role of NFAM1 in IBD, we compared development of anti-CD40 induced colitis in NFAM1+/+ and NFAM1-/- mice. We found that although NFAM1 deletion had no impact on development of gut pathology, we did observe a decrease in serum TNF-α, confirming that NFAM1 promotes pro-inflammatory cytokine production in vivo. Taken together, we conclude that NFAM1 functions to amplify cytokine production and should be further evaluated as a therapeutic target for treatment of autoimmune disease.

Oridonin Attenuates TNBS-induced Post-inflammatory Irritable Bowel Syndrome via PXR/NF-κB Signaling.

To investigate the beneficial effects of oridonin, a diterpenoid compound isolated from Rabdosia rubescens, on the inflammatory response in TNBS-induced post-inflammatory irritable bowel syndrome (PI-IBS) model and the underlying mechanism. Using the PI-IBS rat model and Caco-2 cell lines, we found that intestinal barrier function reflected by lactulose/mannitol (L/M) ratio and tight junction protein level was significantly ameliorated by oridonin. We also demonstrated that oridonin abrogated inflammation through inhibiting the phosphorylation of NF-κBp65 as well as its downstream gene (iNOS, COX-2, IL-1ß, and IL-6) level. Molecular docking studies confirmed the good binding activity between oridonin and PXR. In Caco-2 cell lines, oridonin markedly inhibited LPS-induced NF-κB activation in a PXR-dependent manner. Meanwhile, PXR and its target genes CYP3A4 and P-gp were induced by oridonin, which was associated with the decreased expression of NF-κB and the recovery of intestinal barrier. This study indicated that the therapeutic effect of oridonin on experimental PI-IBS through repairing intestinal barrier function may be closely associated with the regulatory role of PXR/NF-κB signaling pathway. Oridonin may serve as a PXR ligand for the development of drugs in the therapy for PI-IBS.

Shaoyao-Gancao Decoction Relieves Visceral Hyperalgesia in TNBS-Induced Postinflammatory Irritable Bowel Syndrome via Inactivating Transient Receptor Potential Vanilloid Type 1 and Reducing Serotonin Synthesis.

Postinflammatory irritable bowel syndrome (PI-IBS) is a common functional gastrointestinal disorder, which is characterized by abdominal pain, low-grade inflammation, and visceral hypersensitivity. Shaoyao-Gancao decoction (SGD) has been used to improve the clinical symptoms of abdominal spasmodic pain accompanying acute gastroenteritis, but the underlying therapeutic mechanism has not been fully elucidated. In the present study, a rat model of PI-IBS was established via rectal administration of TNBS. Rats were scored daily for 28 days using disease activity index (DAI). Abdominal withdrawal reflex (AWR) was used to measure the pain threshold. After SGD (6.25, 12.5, and 25 g/kg/d) treatment for 14 days, rat colonic tissue was collected for histopathological grading, enterochromaffin (EC) cell count, and 5-HT content measurement. RT-qPCR and western blot analyses were employed to detect the gene and protein level of tryptophan hydroxylase (TPH), serotonin reuptake transporter (SERT), and transient receptor potential vanilloid 1 (TRPV1). To further validate the effect of SGD on TRPV1, another experiment was performed in cells. The results revealed that visceral hyperalgesia, reflected by increased DAI, AWR, pathological injury score, 5-HT content, and EC cell count in PI-IBS rats, was significantly ameliorated by SGD. In cells, SGD markedly inhibited the expression and function of TRPV1. Moreover, the expression levels of TPH were also repressed by SGD. The findings of the present study indicated that the therapeutic effect of SGD on visceral hyperalgesia may be closely associated with the regulatory role of TRPV1 and 5-HT signaling pathways.

Determination of adenosine phosphates in mouse myocardium tissue by HPLC with UV detection and using porous graphite carbon column.

A high-performance liquid chromatography (HPLC) method with UV detection was established and validated for the simultaneous determination of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) in mouse myocardial tissues. After protein precipitation and compound extraction with pre-cooled perchloric acid and the supernatant was centrifuged with the pH value adjusted to 6.5-7.5, the analytes were separated on a porous graphitic carbon LC column (4.6 mm × 100 mm, 5 µm) using gradient elution with a mobile phase of 10 mmol/L borax solution, pH 9.18(A) and acetonitrile-tetrahydrofuran (1:1, v/v) (B). The LC flow rate was 0.8 mL/min; the UV detection wavelength was 254 nm and the column temperature was maintained at 35 °C. ATP, ADP, and AMP were separated and the intra-day relative standard deviations (RSDs) of peak area repeatability were 1.3-2.5% (n = 6). The correlation coefficients of the linearity between UV responses and adenosine phosphate concentrations were larger than 0.9998 in all cases, within concentration ranges of 0.71-91.6 µg/mL for ATP, 1.3-81.5 µg/mL for ADP and 1.69-108.1 µg/mL for AMP. The limits of detection were within 0.17-0.21 µg/mL. The average standard substance spiked-in recoveries were 93.6-104.7% (n = 3). The established HPLC method was successfully applied to quantitate ATP, ADP, and AMP in mouse myocardial tissues.

Response of Bioactive Metabolite and Biosynthesis Related Genes to Methyl Jasmonate Elicitation in Codonopsis pilosula.

Bioactive metabolites in Codonopsis pilosula are of particular interest as an immunostimulant. Methyl jasmonate (MeJA) plays an important role in the elicitation of metabolite biosynthesis. Here, we explored the response of metabolites to MeJA elicitation in C. pilosula adventitious roots and multiple shoots. The results showed that the biomass, polysaccharide, and lobetyolin content of adventitious roots exhibited the highest increases with 100 µmol·L-1 MeJA at the 16th day of subculture, whereas the atractylenolide III (a terpenoid) content increased extremely with 50 µmol·L-1 MeJA treatment at the 7th day of subculture. In addition, the biomass and lobetyolin content significantly increased at the 4th day after treatment. Similarly, the polysaccharide and lobetyolin content increased in multiple shoots. Further identification of different metabolites responding to MeJA by ¹H-NMR showed an extremely significant increase of the lobetyolinin level, which coincided with lobetyolin. Accordingly, the precursor, fatty acids, showed a highly significant decrease in their levels. Furthermore, a significant increase in ß-d-fructose-butanol glycoside was detected, which was accompanied by a decrease in the sucrose level. Accordingly, the enzyme genes responsible for terpenoid and carbohydrate biosynthesis, CpUGPase, and CpPMK, were up regulated. In conclusion, MeJA promoted culture growth and accelerated bioactive metabolite accumulation by regulating the expression of the metabolite biosynthesis related genes, CpUGPase and CpPMK in C. pilosula.

Effect of fermented Cordyceps sinensis on doxorubicin­induced cardiotoxicity in rats.

Cordyceps sinensis (CS) is a prominent medicinal herb in traditional Chinese medicine, and fermented CS is frequently used as a substitute for natural CS. Doxorubicin (DOX), an antitumor drug used in chemotherapy, is limited by its poor cardiotoxicity. The aim of the present study was to evaluate the protective effect of fermented CS against DOX­induced cardiotoxicity and the potential underlying mechanisms. Male Sprague­Dawley rats (180­200 g) were randomly assigned to seven different treatment groups: Normal control, DOX control, DOX+captopril (0.05 g/kg), 0.75, 1.5 and 3 g/kg DOX+CS, and the CS (1.5 g/kg) control. Histopathological changes, cardiac energy metabolism, cyclic adenosine monophosphate (cAMP) signaling and the associated mRNA expression of AMP­activated protein kinase (AMPK) were then evaluated. Fermented CS decreased the left ventricular weight index, heart weight index and mortality; however, it increased diastolic blood pressure and mean arterial pressure. In addition, it shortened the duration of the QRS complex and Sα­T segment, decreased serum creatine kinase (CK) and aspartate aminotransferase activity, inhibited histopathological changes and reduced brain natriuretic peptide content. Treatment with fermented CS also increased the activities of superoxide dismutase and glutathione peroxidase, reduced malondialdehyde content, increased the mitochondrial activities of Na+K+­adenosine 5'­triphosphate (ATP) ase, Ca2+Mg2+­ATPase and CK, and increased the creatine phosphate/ATP ratio and AMP/ATP ratio. Furthermore, it decreased the ATP/adenosine 5'­diphosphate (ADP) ratio, upregulated AMPKα2 expression, reduced the activity of serum phosphodiesterases (PDEs) and increased myocardial cAMP content. The results of the present study demonstrated that fermented CS attenuated DOX­induced cardiotoxicity by inhibiting myocardial hypertrophy and myocardial damage, ameliorating systolic function and the antioxidant enzyme system, improving cardiac energy metabolism, depressing the activities of PDEs, and by upregulating the cAMP and AMPK signaling pathways. Thus, fermented CS may be a candidate for the prevention of DOX­induced cardiotoxicity, cardiac energy impairment and against a number of cardiac diseases.

[Clone and expression of CpGAPDH gene in Codonopsis pilosula].

GAPDH(glyceraldehyde-3-phosphate dehydrogenase) gene is a key enzyme gene in carbohydrate metabolism and always used as reference gene. To clarify and complete the biosynthetic pathway of polysaccharide, the GAPDH gene in Codonopsis pilosula, named CpGAPDH, was cloned according to the transcriptome of pilosula, using the GAPDH gene in potato as query. The CpGAPDH contained a 1 014 bp open reading frame(ORF) and encoded a protein with 337 amino acids. Bioinformatic analysis clearly suggested that CpGAPDH shared high similarity with GAPDH among other plants, and had the closest relatives to potato and danshen. The predicted protein did not have signal peptide, which indicated that it might be located in the cytoplasm. According to the existing of several phosphorylation sites and the conserved domains analysis, we predicted that it belonged to Gp_dh_N superfamily. Prokaryotic expression showed that the recombinant expressed a 44.3 kDa protein, which was corresponding to the theoretical relative molecular mass. However, the relative transcript level of the CpGAPDH did not have significant differences in different tissues and roots at different developmental stages of pilosula. Moreover, the stability of the CpGAPDH was analyzed by BestKeeper, geNorm, and NormFinder and RefFinder software, which showed that the CpGAPDH was more stable and could be used as a new reference gene. All these lay a foundation for the expression analysis of the gene relative to the polysaccharide synthesis.

[Study on antioxidant activity of flavonoids from leaves of Psidium guajava].

The present study is to study the chemical constituents from ethanol extract of Psidium guajava leaves. The constituents were separated and purified by silica gel column chromaiographios over, macroporous resin D-101, Sephadex LH-20, and ODS. Six flavonoids compounds were isolated and identified as quercetin(1), quercetin-3-O-α-D-arabinopyranoside(2), quercetin-3-O-α-D-ribopyranoside(3), quercetin-3-O-ß-D-galactopyranoside(4), quercetin-3-O-α-D-glucopyranoside(5), and quercetin-3-O-α-D-xylpyranoside(6). The antioxidant effects of six flavonoids was evaluated by scavenging ability of DPPH, superoxide anion, ABTS·âº, and reducing effect of Fe³âº as well as total antioxidant capacity(FRAP). Vitamin C was used as positive control. The results indicated that six flavonoids exhibited significant antioxidant effects.

Effect of Atractylodes macrocephala rhizoma on isoproterenol­induced ventricular remodeling in rats.

Myocardial infarction (MI) is the primary cause of ventricular remodeling (VR). The aim of the present study was to determine the effect of Atractylodis macrocephalae rhizoma (AMR) on VR induced by isoproterenol (ISO) in rats. Male Sprague Dawley rats were randomly divided into the normal control, ISO­induced and AMR groups. Rats in the ISO­induced and AMR groups were subcutaneously injected with 85 mg/kg/day ISO for two consecutive days. Compared with the ISO­induced group, AMR normalized the levels of hemodynamic parameters, markedly attenuated myocardial pathological damage, decreased the level of N­terminal prohormone of brain natriuretic peptide, and inhibited cardiac hypertrophy and myocardial fibrosis. In addition, AMR inhibited oxidative stress and activation of the rennin­angiotensin­aldosterone system (RAAS) when compared with the ISO­induced group. The results of the present study suggest that AMR may reverse VR via its antioxidative effect and inhibition of RAAS activation.

Intensive blood pressure control in patients with acute type B aortic dissection (RAID): study protocol for randomized controlled trial.

BACKGROUND: Blood pressure control is an essential therapy for patients with acute type B aortic dissection (ABAD) and should be maintained throughout the entire treatment. Thus, vast majority current guidelines recommend control the blood pressure to lower than 140/90 mmHg. Theoretically, a much lower target may further decrease the risk of propagation of dissection. However, some argued that too lower blood pressure would compromise the organ perfusion. Thus, there is no unanimous optimal target for blood pressure in patients with ABAD so far. The present study aimed to investigate the optimal blood pressure target for patients with ABAD, in the hope that the result would optimize the treatment of aortic dissection (AD). METHODS: The study is a multi-center randomized controlled clinical trial. Study population will include patients with new diagnosed ABAD and hypertension. Blocked randomization was performed where intensive blood pressure control (<120 mmHg) with conventional blood pressure control (<140 mmHg) were allocated at random in a ratio of 1:1 in blocks of sizes 4, 6, 8, and 10 to 360 subjects. Interim analysis will be performed. The primary outcome is a composite in-hospital adverse outcome, including death, permanent paraplegia or semi- paralysis during the hospitalization, and renal failure requiring hemodialysis at discharge. While the secondary outcomes include the aortic size, lower extremity or visceral ischemia, retrograde propagation into aortic arch or ascending aorta, mortality in 6 months and 1 year, intensive care unit (ICU) length of stay, total length of hospital stay, creatinine level, and surgical or endovascular intervention. ETHICS AND DISSEMINATION: The study was approved by the institutional review board of Sir Run Run Shaw Hospital (approval number: 20160920-9). Informed consent will be obtained from participants or their next-of-kin. The results will be published in a peer-reviewed journal and shared with the worldwide medical community. TRIAL REGISTRATION: NCT03001739 (https://register.clinicaltrials.gov/).

Synergistic effects of polydatin and vitamin C in inhibiting cardiotoxicity induced by doxorubicin in rats.

The purpose of this study was to assess the synergistic effect of polydatin and vitamin C on attenuating cardiotoxicity induced by doxorubicin (DOX) in rats. Polydatin could significantly increase the activity of superoxide dismutase (SOD) and the heart rate, attenuate myocardial pathological damage, decrease malondialdehyde (MDA) content, slightly increase arterial pressure and glutathione peroxidase (GSH-Px) activity, reduce intervals of QRS, QT, and ST, and lower free fatty acid (FFA) content. The combination of polydatin and vitamin C could significantly increase arterial pressure and heart rate, decrease QRS interval and slightly reduce ST and QT intervals, significantly attenuate myocardial pathological damage, increase the activities of GSH-Px,T-SOD, Na+ K+ -ATPase, and Ca2+ Mg2+ -ATPase, elevate phosphocreatine (PCr) and adenosine triphosphate (ATP) contents, slightly increase adenosine diphosphate (ADP) and total adenine nucleotide (TAN) contents and PCr/ATP, and significantly decrease the contents of MDA and FFA, when compared with those in the DOX group. Meanwhile, the improvement effects on FFA content, the activities of ATPase and SOD, and contents of ATP and TAN in combination group were more obvious than those in polydatin group, and the improvement effects on arterial pressure, heart rate, interval of QRS, GSH-Px activity, and MDA, ADP, and PCr contents in combination group were slightly obvious when compared with those in polydatin group. In addition, the mRNA expression levels of AMPK-α2 and PPAR-α were slightly improved in combination group. The results illustrate that the combination of polydatin and vitamin C has the ability to enhance the myocardial protective effects by its antioxidative effect and improve energy metabolism.

Nanogold-functionalized g-C3N4 nanohybrids for sensitive impedimetric immunoassay of prostate-specific antigen using enzymatic biocatalytic precipitation.

This work reports on a new impedimetric immunosensing strategy for sensitive detection of prostate-specific antigen (PSA) in biological fluids. The assay was carried out on monoclonal anti-PSA capture antibody-modified glassy carbon electrode with a sandwich-type detection format. Gold nanoparticles-decorated g-C3N4 nanosheets (AuNP/g-C3N4), synthesized by the wet-chemistry method, were utilized for the labeling of polyclonal anti-PSA detection antibody and horseradish peroxidase (HRP). Upon target PSA introduction, the sandwiched immunocomplex could be formed between capture antibody and detection antibody. Followed by the AuNP/g-C3N4, the labeled HRP could catalyze 4-choloro-1-naphthol into benzo-4-chlorohexadienone. The as-generated insoluble product was coated on the electrode surface, thus increasing the Faradaic impedance of Fe(CN)6(4-/3)(-) indicator between the solution and the base electrode. Under the optimal conditions, the impedance increased with the increasing target PSA in the sample, and exhibited a wide linear range from 10pgmL(-1) and 30ngmL(-1) with a detection limit of 5.2pgmL(-1). A repeatability and intermediate precision of <14% was accomplished. The specificity and method accuracy in comparison with commercial PSA ELISA kit for analysis of human serum specimens were relatively satisfactory.

Doxorubicin toxicity changes myocardial energy metabolism in rats.

BACKGROUND: Doxorubicin (DOX) is an antitumor antibiotics used against malignancies. But its toxicity limits the therapy of DOX. OBJECTIVE: The purpose of this study was to evaluate DOX toxicity and the alteration of energy metabolism after short term and long term treatment. METHODS: Male Sprague-Dawley rats were randomly assigned to four groups: Short term control group, short term DOX treatment group, long term control group and long term DOX treatment group. In short term treated group, rats were injected with DOX i.p. at a dose of 2.5 mg/kg every 48 h for six equal injections. In long term, treated group, rats were tail-intravenously injected with DOX at a dose of 3 mg/kg once a week for four weeks. At the end of the experiment, histopathological changes, general blood biomarkers, endogenous antioxidant enzymes, cardiac energy metabolism and related mRNA expression of AMPK signal pathway were determined. RESULTS: DOX induced prominent oxidative stress, a higher mortality rate, histological and ECG changes, obvious cardiac hypertrophy, acute cardiac damage and cardiac energy impairment in short term treatment rats. In long term treatment rats, DOX caused serious nephropathy and systolic dysfunction, terrible cardiac energy impairment, clear alteration of substrate utilization and AMPK signal pathway. CONCLUSION: DOX treatment can induce different damages after short term and long term treatment. In short term treatment group, rats experienced a terrible mortality rate about 40%, the acute cardiac damage, cardiac energy impairment and an early heart failure which are potential connected with reduction of glucose utilization. In the long term treatment group, serious nephropathy and obvious changes of mRNA expressions of AMPK signal pathway were observed. Meanwhile, the serious cardiac energy impairment and substrate utilization alteration denote an obviously heart failure. This study could be helpful to develop therapy strategies of DOX complications for clinical application.