Molecular basis for heat desensitization of TRPV1 ion channels.

The transient receptor potential vanilloid 1 (TRPV1) ion channel is a prototypical molecular sensor for noxious heat in mammals. Its role in sustained heat response remains poorly understood, because rapid heat-induced desensitization (Dh) follows tightly heat-induced activation (Ah). To understand the physiological role and structural basis of Dh, we carried out a comparative study of TRPV1 channels in mouse (mV1) and those in platypus (pV1), which naturally lacks Dh. Here we show that a temperature-sensitive interaction between the N- and C-terminal domains of mV1 but not pV1 drives a conformational rearrangement in the pore leading to Dh. We further show that knock-in mice expressing pV1 sensed heat normally but suffered scald damages in a hot environment. Our findings suggest that Dh evolved late during evolution as a protective mechanism and a delicate balance between Ah and Dh is crucial for mammals to sense and respond to noxious heat

Effectiveness and safety of transcatheter aortic valve replacement in elderly people with severe aortic stenosis with different types of heart failure.

Impaired left ventricular function is an independent predictor of adverse clinical outcomes in patients with aortic stenosis. The aim of this study is to evaluate the short-term changes of echocardiographic parameters, New York Heart Association (NYHA) class and B-type natriuretic peptide (BNP) level and adverse events amongst patients with heart failure (HF) after transcatheter aortic valve replacement (TAVR) procedure. This was a retrospective cohort study conducted at affiliated Yantai Yuhuangding Hospital of Qingdao University between September 2017 and September 2022. TAVR cases were stratified into three groups [heart failure with reduced ejection fraction (HFrEF), heart failure with mildly reduced ejection fraction (HFmrEF), heart failure with preserved ejection fraction (HFpEF)] by left ventricular ejection fraction (LVEF). Baseline characteristics, changes in echocardiographic parameters (1 week and 1 month), BNP (1 month), and NYHA class (6 months) post-TAVR were compared across the three groups. Meanwhile, we observed the adverse events of the patients after TAVR. A total of 96 patients were included, of whom 15 (15.6%) had HFrEF, 15 (15.6%) had HFmrEF, and 66 (68.8%) had HFpEF. Compared to the HFpEF subgroup, patients in the HFrEF subgroup were younger (p < 0.05), and with a higher BNP (p < 0.05). The left ventricular end-diastolic dimension (LVEDD) in HFrEF group decreased significantly after TAVR. HFmrEF and HFrEF patients showed significant improvements in LVEF after TAVR. The pulmonary artery systolic pressure (PASP), aortic valve peak gradient (AVPG) and aortic valve peak gradient (V ) decreased significantly 1 month after TAVR in all three groups compared to the baseline (all p < 0.05). BNP significantly reduced in HFrEF group compared to HFpEF patients after TAVR (p < 0.05). The majority of patients experienced an improvement at least one NYHA class in all three groups 6 months post-TAVR. There is no significant increase in the risk of adverse events in the HFrEF group. Patients who underwent TAVR achieved significant improvements in BNP, NYHA class, LVEDD, LVEF, and PASP across the three HF classes, with a more rapid and pronounced improvement in the HFrEF and HFmrEF groups. Complication rates were low in the different HF groups. There is no significant increase in the risk of periprocedural complications in the HFrEF and HFmrEF groups. [Abstract copyright: © 2023. The Author(s).

Memory-enhancing effect of Rhodiola rosea L extract on aged mice

Purpose: The memory-enhancing effects of Rhodiola rosea L. extract (RRLE) on normal aged mice were assessed.Methods: In the open-field test, the effect of RRLE (150 and 300 mg/kg) on mouse locomotive activities was evaluated by investigating the extract’s influence on CAT and AchE activities in the brain tissue of mice.Results: Compared with aged group, high dose of RRLE reduced the total distance (3212.4 ± 123.1 cm, p &lt; 0.05) significantly, increased catalase (CAT) activity (101.4 ± 12.2 U/mg pro, p &lt; 0.05), and inhibited acetyl cholinesterase (AChE) activity (0.94 ± 0.12 U/mg pro, p &lt; 0.05) in the brain tissue of aged mice.Conclusion: The results show that RRLE improves the memory functions of aged mice probably by increasing CAT activity while decreasing AChE activity.Keywords: Rhodiola rosea, Memory function, Catalase, Acetyl cholinesterase, Open-field tes

Effectiveness and safety of transcatheter aortic valve replacement in elderly people with severe aortic stenosis with different types of heart failure

Background: Impaired left ventricular function is an independent predictor of adverse clinical outcomes in patients with aortic stenosis. The aim of this study is to evaluate the short-term changes of echocardiographic parameters, New York Heart Association (NYHA) class and B-type natriuretic peptide (BNP) level and adverse events amongst patients with heart failure (HF) after transcatheter aortic valve replacement (TAVR) procedure. Methods: This was a retrospective cohort study conducted at affiliated Yantai Yuhuangding Hospital of Qingdao University between September 2017 and September 2022. TAVR cases were stratified into three groups [heart failure with reduced ejection fraction (HFrEF), heart failure with mildly reduced ejection fraction (HFmrEF), heart failure with preserved ejection fraction (HFpEF)] by left ventricular ejection fraction (LVEF). Baseline characteristics, changes in echocardiographic parameters (1 week and 1 month), BNP (1 month), and NYHA class (6 months) post-TAVR were compared across the three groups. Meanwhile, we observed the adverse events of the patients after TAVR. Results: A total of 96 patients were included, of whom 15 (15.6%) had HFrEF, 15 (15.6%) had HFmrEF, and 66 (68.8%) had HFpEF. Compared to the HFpEF subgroup, patients in the HFrEF subgroup were younger (p < 0.05), and with a higher BNP (p < 0.05). The left ventricular end-diastolic dimension (LVEDD) in HFrEF group decreased significantly after TAVR. HFmrEF and HFrEF patients showed significant improvements in LVEF after TAVR. The pulmonary artery systolic pressure (PASP), aortic valve peak gradient (AVPG) and aortic valve peak gradient (Vmax) decreased significantly 1 month after TAVR in all three groups compared to the baseline (all p < 0.05). BNP significantly reduced in HFrEF group compared to HFpEF patients after TAVR (p < 0.05). The majority of patients experienced an improvement at least one NYHA class in all three groups 6 months post-TAVR. There is no significant increase in the risk of adverse events in the HFrEF group. Conclusions: Patients who underwent TAVR achieved significant improvements in BNP, NYHA class, LVEDD, LVEF, and PASP across the three HF classes, with a more rapid and pronounced improvement in the HFrEF and HFmrEF groups. Complication rates were low in the different HF groups. There is no significant increase in the risk of periprocedural complications in the HFrEF and HFmrEF groups

Complement Expression in the Retina is not Influenced by Short-term Pressure Elevation

Purpose: To determine whether short-term pressure elevation affects complement gene expression in the retina in vitro and in vivo. Methods: Muller cell (TR-MUL5) cultures and organotypic retinal cultures from adult mice and monkeys were sub- jected to either 24-h or 72-h of pressure at 0, 15, 30, and 45 mmHg above ambient. C57BL/6 mice were subjected to microbead-induced intraocular pressure (IOP) elevation for 7 days. RNA and protein were extracted and used for analysis of expression levels of complement component genes and complement component 1, q subcomponent (C1q) and comple- ment factor H (CFH) immunoblotting. Results: mRNA levels of complement genes and C1q protein levels in Muller cell cultures remained the same for all pressure levels after exposure for either 24 or 72 h. In primate and murine organotypic cultures, pressure elevation did not produce changes in complement gene expression or C1q and CFH protein levels at either the 24-h or 72-h time points. Pressure-related glial fibrillary acidic protein (GFAP) mRNA expression changes were detected in primate retinal organotypic cultures (analysis of variance [ANOVA]; p0.05 for both) with contralateral control and naïve control eyes. Conclusions: Short-term elevation of pressure in vitro as well as short-term (1 week) IOP elevation in vivo does not seem to dramatically alter complement system gene expression in the retina. Prolonged expression to elevated pressure may be necessary to affect the complement system expression

Transcriptome profiling of genes regulated by phosphate-solubilizing bacteria Bacillus megaterium P68 in potato (Solanum tuberosum L.)

The insoluble phosphorus in the soil is extremely difficult to be absorbed and used directly through the potato root system. Although many studies have reported that phosphorus-solubilizing bacteria (PSB) can promote plant growth and uptake of phosphorus, the molecular mechanism of phosphorus uptake and growth by PSB has not been investigated yet. In the present study, PSB were isolated from rhizosphere soil in soybean. The data of potato yield and quality revealed that the strain P68 was the most effective In the present study, PSB identification, potato field experiment, pot experiment and transcriptome profiling to explored the role of PSB on potato growth and related molecular mechanisms. The results showed that the P68 strain (P68) was identified as Bacillus megaterium by sequencing, with a P-solubilizing ability of 461.86 mg·L−1 after 7-day incubation in National Botanical Research Institute’s Phosphate (NBRIP) medium. Compared with the control group (CK), P68 significantly increased the yield of potato commercial tubers by 17.02% and P accumulation by 27.31% in the field. Similarly, pot trials showed that the application of P68 significantly increased the biomass, total phosphorus content of the potato plants, and available phosphorus of the soil up by 32.33, 37.50, and 29.15%, respectively. Furthermore, the transcriptome profiling results of the pot potato roots revealed that the total number of bases was about 6G, and Q30 (%) was 92.35–94.8%. Compared with the CK, there were a total of 784 differential genes (DEGs) regulated when treated with P68, which 439 genes were upregulated and 345 genes were downregulated. Interestingly, most of the DEGs were mainly related to cellular carbohydrate metabolic process, photosynthesis, and cellular carbohydrate biosynthesis process. According to the KEGG pathway analysis, a total of 46 categorical metabolic pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were annotated to 101 DEGs found in potato roots. Compared with the CK, most of the DEGs were mainly enriched in glyoxylate and dicarboxylate metabolism (sot00630), nitrogen metabolism (sot00910), tryptophan metabolism (sot00380), and plant hormone signal transduction (sot04075), and these DEGs might be involved in the interactions between Bacillus megaterium P68 and potato growth. The qRT-PCR analysis of differentially expressed genes showed that inoculated treatments P68 significantly upregulated expression of the phosphate transport, nitrate transport, glutamine synthesis, and abscisic acid regulatory pathways, respectively, and the data from qRT-PCR were consistent with that obtained from RNA-seq. In summary, PSB may be involved in the regulation of nitrogen and phosphorus nutrition, glutaminase synthesis, and abscisic acid-related metabolic pathways. This research would provide a new perspective for studying the molecular mechanism of potato growth promotion by PSB in the level of gene expression and related metabolic pathways in potato roots under the application of Bacillus megaterium P68

CCND1 as a Predictive Biomarker of Neoadjuvant Chemotherapy in Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma

BACKGROUND: Cyclin D1 (CCND1) has been associated with chemotherapy resistance and poor prognosis. In this study, we tested the hypothesis that CCND1 expression determines response and clinical outcomes in locally advanced head and neck squamous cell carcinoma (HNSCC) patients treated with neoadjuvant chemotherapy followed by surgery and radiotherapy. METHODOLOGY AND FINDINGS: 224 patients with HNSCC were treated with either cisplatin-based chemotherapy followed by surgery and radiotherapy (neoadjuvant group, n = 100) or surgery and radiotherapy (non-neoadjuvant group, n = 124). CCND1 expression was assessed by immunohistochemistry. CCND1 levels were analyzed with chemotherapy response, disease-free survival (DFS) and overall survival (OS). There was no significant difference between the neoadjuvant group and non-neoadjuvant group in DFS and OS (p = 0.929 and p = 0.760) when patients treated with the indiscriminate administration of cisplatin-based chemotherapy. However, in the neoadjuvant group, patients whose tumors showed a low CCND1 expression more likely respond to chemotherapy (p<0.001) and had a significantly better OS and DFS than those whose tumors showed a high CCND1 expression (73% vs 8%, p<0.001; 63% vs 6%, p<0.001). Importantly, patients with a low CCND1 expression in neoadjuvant group received more survival benefits than those in non-neoadjuvant group (p = 0.016), however patients with a high CCND1 expression and treated with neoadjuvant chemotherapy had a significantly poor OS compared to those treated with surgery and radiotherapy (p = 0.032). A multivariate survival analysis also showed CCND1 expression was an independent predictive factor (p<0.001). CONCLUSIONS: This study suggests that some but not all patients with HNSCC may benefit from neoadjuvant chemotherapy with cisplatin-based regimen and CCND1 expression may serve as a predictive biomarker in selecting patients undergo less than two cycles of neoadjuvant chemotherapy

Individual or mixing extrusion of Tartary buckwheat and adzuki bean: Effect on quality properties and starch digestibility of instant powder

IntroductionTartary buckwheat and adzuki bean, which are classified as coarse grain, has attracted increasing attention as potential functional ingredient or food source because of their high levels of bioactive components and various health benefits.MethodsThis work investigated the effect of two different extrusion modes including individual extrusion and mixing extrusion on the phytochemical compositions, physicochemical properties and in vitro starch digestibility of instant powder which consists mainly of Tartary buckwheat and adzuki bean flour.ResultsCompared to mixing extrusion, instant powder obtained with individual extrusion retained higher levels of protein, resistant starch, polyphenols, flavonoids and lower gelatinization degree and estimated glycemic index. The α-glucosidase inhibitory activity (35.45%) of the instant powder obtained with individual extrusion was stronger than that obtained with mixing extrusion (26.58%). Lower levels of digestibility (39.65%) and slower digestion rate coefficient (0.25 min−1) were observed in the instant powder obtained with individual extrusion than in mixing extrusion (50.40%, 0.40 min−1) by logarithm-of-slope analysis. Moreover, two extrusion modes had no significant impact on the sensory quality of instant powder. Correlation analysis showed that the flavonoids were significantly correlated with physicochemical properties and starch digestibility of the instant powder.DiscussionThese findings suggest that the instant powder obtained with individual extrusion could be used as an ideal functional food resource with anti-diabetic potential