Gallic Acid Inhibits Mesaconitine-Activated TRPV1-Channel-Induced Cardiotoxicity.

Aconiti Kusnezoffii Radix (Caowu) is often combined or processed with Chebulae Fructus (Hezi) to achieve attenuation purposes in Mongolian medicine. Mesaconitine (MA), a main bioactive ingredient of Caowu, is also famous for its high cardiotoxicity while exerting good anti-inflammatory and analgesic properties. Gallic acid (GA), one of the leading chemical components in Hezi, possesses cardiac protection. This study aimed to clarify the detoxification effects of GA from Hezi on MA-induced cardiotoxicity and whether the detoxification mechanism is related to the TRPV1 channel. Cell viability was determined by methyl thiazol tetrazolium (MTT), and lactate dehydrogenase (LDH) leakage rate was determined by ELISA. Hoechst 33258, JC-1, DCFH-DA, and Fluo-3 AM staining were conducted to detect apoptosis, mitochondrial membrane potential, reactive oxygen species (ROS), and Ca2+ respectively; TRPV1 channel current was recorded by whole-cell patch-clamp technology to observe the effect of GA and MA alone or in combination on TRPV1 channel. The results showed that GA exhibited pronounced detoxification effects on MA-induced cardiotoxicity. GA significantly inhibited the MA-induced decrease in cell viability; suppressed the MA-induced LDH leakage rate, apoptosis, and the release of ROS and Ca2+; and alleviated the reduction of mitochondrial membrane potential. We found that MA-induced cardiotoxicity was significantly attenuated in H9c2 cells pretreated with the TRPV1 antagonist BCTC. In the whole-cell patch-clamp experiment, the TRPV1 channel current increase was caused by the GA and MA treatment, whereas it was reduced by the cotreatment of GA and MA. Our data demonstrate that GA in Hezi can reduce MA-induced cardiotoxicity by inhibiting intracellular Ca2+ influx, restoring mitochondrial membrane potential, and reducing apoptosis. The detoxification mechanism may be related to the desensitization of the TRPV1 channel by the combined application of MA and GA.

Comparative transcriptome and DNA methylation analysis in temperature-sensitive genic male sterile wheat BS366.

BACKGROUND: Known as the prerequisite component for the heterosis breeding system, the male sterile line determines the hybrid yield and seed purity. Therefore, a deep understanding of the mechanism and gene network that leads to male sterility is crucial. BS366, a temperature-sensitive genic male sterile (TGMS) line, is male sterile under cold conditions (12 °C with 12 h of daylight) but fertile under normal temperature (20 °C with 12 h of daylight). RESULTS: During meiosis, BS366 was defective in forming tetrads and dyads due to the abnormal cell plate. During pollen development, unusual vacuolated pollen that could not accumulate starch grains at the binucleate stage was also observed. Transcriptome analysis revealed that genes involved in the meiotic process, such as sister chromatid segregation and microtubule-based movement, were repressed, while genes involved in DNA and histone methylation were induced in BS366 under cold conditions. MethylRAD was used for reduced DNA methylation sequencing of BS366 spikes under both cold and control conditions. The differentially methylated sites (DMSs) located in the gene region were mainly involved in carbohydrate and fatty acid metabolism, lipid metabolism, and transport. Differentially expressed and methylated genes were mainly involved in cell division. CONCLUSIONS: These results indicated that the methylation of genes involved in carbon metabolism or fatty acid metabolism might contribute to male sterility in BS366 spikes, providing novel insight into the molecular mechanism of wheat male sterility.

Comprehensive analysis of formin gene family highlights candidate genes related to pollen cytoskeleton and male fertility in wheat (Triticum aestivum L.).

BACKGROUND: Formin, a highly conserved multi-domain protein, interacts with microfilaments and microtubules. Although specifically expressed formin genes in anthers are potentially significant in research on male sterility and hybrid wheat breeding, similar reports in wheat, especially in thermo-sensitive genic male sterile (TGMS) wheat, remain elusive. RESULTS: Herein, we systematically characterized the formin genes in TGMS wheat line BS366 named TaFormins (TaFHs) and predicted their functions in inducing stress response. In total, 25 TaFH genes were uncovered, majorly localized in 2A, 2B, and 2D chromosomes. According to the neighbor-joining (NJ) method, all TaFH proteins from wheat and other plants clustered in 6 sub-groups (A-F). The modeled 3D structures of TaFH1-A/B, TaFH2-A/B, TaFH3-A/B and TaFH3-B/D were validated. And different numbers of stress and hormone-responsive regulatory elements in their 1500 base pair promoter regions were contained in the TaFH genes copies. TaFHs had specific temporal and spatial expression characteristics, whereby TaFH1, TaFH4, and TaFH5 were expressed highly in the stamen of BS366. Besides, the accumulation of TaFHs was remarkably lower in a low-temperature sterile condition (Nanyang) than fertile condition (Beijing), particularly at the early stamen development stage. The pollen cytoskeleton of BS366 was abnormal in the three stages under sterile and fertile environments. Furthermore, under different stress levels, TaFHs expression could be induced by drought, salt, abscisic acid (ABA), salicylic acid (SA), methyl jasmonate (MeJA), indole-3-acetic acid (IAA), polyethylene glycol (PEG), and low temperature. Some miRNAs, including miR167, miR1120, and miR172, interacts with TaFH genes; thus, we constructed an interaction network between microRNAs, TaFHs, phytohormone responses, and distribution of cytoskeleton to reveal the regulatory association between upstream genes of TaFH family members and sterile. CONCLUSIONS: Collectively, this comprehensive analysis provides novel insights into TaFHs and miRNA resources for wheat breeding. These findings are, therefore, valuable in understanding the mechanism of TGMS fertility conversion in wheat.

Effectiveness and safety of electroacupuncture in treating Parkinson disease: A protocol for systematic review and meta-analyses.

BACKGROUND: Parkinson disease (PD) is an Extrapyramidal Disease mainly characterized by static tremor, myotonia, bradykinesia and postural gait disorder. As China's population ages, the number of people suffering from PD is increasing. Since there are many side effects of western medicine for Parkinson's patients, and the high price of the drugs make it difficult for many patients to adhere to treat. At present, many clinical studies have shown that electroacupuncture is effective in treating PD. Therefore, this systematic review aims to explore the effectiveness and safety of electroacupuncture in the treatment of PD. METHODS: Comprehensive search of PubMed, Embase, Medline, Cochrane Database of Systematic Reviews, Chinese Biomedical Literatures Database, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wang Fang Database from inception to February 2021, the literature selected is not restricted by language. In addition, we will search for unpublished studies and the references that were originally included in the literature manually. There were two reviewers screened the data and cross-checked the information individually, the quality of the literature was assessed by reviewers independently. The outcomes of interest include:the scale of Unifified PD Rating Scales, the Webster scale, the Quality of Life Questionnaire, total effective rate, recurrence rate, adverse events. The laboratory inspection indicators include:the content of lipid peroxidase, Superoxide dismutase activity in plasma and erythrocyte. The relevant randomized controlled trials will be included in this study. And we will evaluate the quality of the selected literature according to the Cochrane Handbook. Meta-analysis will be performed using RevMan 5.4.0 software. The heterogeneity test will be implemented in the included literature, the tests' thresholds will be P < .1 and I2 > 50%. We will use either fixed effects model or random effects model according to the size of heterogeneity. RESULTS: The results of this systematic review will provide a comprehensive evidence for the clinical treatment of PD, and we will report this result soon. CONCLUSION: This paper will explore whether or not electroacupuncture can be used as a non-drug therapy for PD. ETHICS AND DISSEMINATION: Ethical approval is not required for this paper, our plan will be published in the journal. TRIAL REGISTRATION NUMBER: INPLASY202120031.