Rose long noncoding RNA lncWD83 promotes flowering by modulating ubiquitination of the floral repressor RcMYC2L.

Long noncoding RNAs (lncRNAs) play important roles in various signaling pathways in vascular plants. However, the crosstalk between lncRNAs and E3 ubiquitin ligases has been barely reported. In this study, we demonstrate that the lncRNA lncWD83 from rose (Rosa chinensis) 'Old blush' activates flowering by modulating the ubiquitination of the floral repressor MYC2 LIKE (RcMYC2L). Flowering was substantially delayed in rose by virus-induced gene silencing of lncWD83. In an in vitro pull-down assay, lncWD83 associated with PLANT U-BOX PROTEIN 11 (PUB11), a U-box-containing E3 ubiquitin ligase. Seedlings with knocked down RcPUB11 transcripts phenocopied the later-flowering phenotype of lncWD83-silenced seedlings. RcMYC2L physically interacted with RcPUB11 and was ubiquitinated in an RcPUB11-dependent manner in vitro. Accordingly, silencing RcMYC2L fully reversed the later-flowering phenotype resulting from RcPUB11 knockdown. Furthermore, RcMYC2L bound to G-box-related motifs in the FLOWERING LOCUS T (RcFT) promoter and repressed its transcription. However, RcPUB11 alleviated this repression of RcFT expression via proteasomal degradation of RcMYC2L, and lncWD83 enhanced this degradation by associating with RcPUB11. Therefore, lncWD83 promotes flowering by modulating the ubiquitination of the floral repressor RcMYC2L in rose plants. These findings reveal a distinct regulatory mechanism for an lncRNA in facilitating ubiquitin-mediated proteolysis to regulate rose flowering.

Screening and evaluation of quality markers from Shuangshen Pingfei formula for idiopathic pulmonary fibrosis using network pharmacology and pharmacodynamic, phytochemical, and pharmacokinetic analyses.

BACKGROUND: The Shuangshen Pingfei formula (SSPF), a classic Chinese medicine derivative formula, has been shown to exert therapeutic effects on idiopathic pulmonary fibrosis (IPF). However, the quality control compounds of SSPF remain unclear. PURPOSE: To select and confirm Q-markers of SSPF based on network pharmacology, cytobiology, animal-based pharmacodynamics, and phytochemical and pharmacokinetic analyses. METHODS: A compound-target network was constructed based on previous research. In addition, high-degree compounds of SSPF were chosen as potential Q-marker candidates. Animal and cytological experiments were performed to verify key targets of IPF. Haematoxylin-eosin and Masson's trichrome staining were used to observe lung tissue pathology. Cytokine levels in the bronchoalveolar lavage fluid (BALF) were measured using ELISA kits. Gene and protein expression levels were determined using PCR and western blotting, respectively. The contents of Q-marker candidates in different batches of SSPF were then determined for traceability research, and the quality consistency of SSPF was objectively evaluated using principal component analysis (PCA). Finally, pharmacokinetic research was performed, and candidates with desirable metabolite and bioavailability parameters were confirmed as Q-markers of SSPF. RESULTS: The compound-target network included 56 compounds and 14 therapeutic targets. Animal experiments showed that SSPF attenuates lung fibrosis. SSPF decreased CC motif chemokine 2 (CCL2) and CC chemokine receptor type 2 (CCR2) levels in the BALF and downregulated the gene and protein expression of IPF therapy-related molecules, such as 5-hydroxytryptamine receptor 2A (HTR2A), CCL2, and CCR2, in the lungs. Cell experiments showed that nine Q-marker candidates in SSPF regulated the expression of CCL2 and CCR2, as predicted. Phytochemical analysis and PCA indicated that the qualities of SSPF in the nine batches were relatively stable. Pharmacokinetic studies demonstrated that mangiferin, salvianolic acid B, tanshinone IIA, naringin, and glycyrrhizic acid could be effectively absorbed into rat plasma, which ensured desirable bioavailability and confirmed their roles as Q-markers to represent anti-pulmonary fibrotic activity. CONCLUSION: Our study is an integrated strategy, based on network pharmacology with experimental verification and phytochemical and pharmacokinetic analyses that provides a novel approach for Q-marker selection and validation of SSPF for IPF treatment.

Prescriptions with Mori Cortex in Treatment of Respiratory Diseases： A Review / 中国实验方剂学杂志

Mori Cortex is sweet and pungent in taste， cold in nature， and has the tropism to the lung meridian. It has the functions of purging the lung and relieving asthma and can treat oliguria and edema， being one of the commonly used herbal medicines in clinical practice. The prescriptions with Mori Cortex， such as Sangbaipi Tang， Qingjin Huatanfang， and Qingfei Huatantang， are widely used in clinical practice. The main active components in Mori Cortex are the material basis for its efficacy. Owing to the mature methods for the identification of pharmacodynamic substances in Chinese herbal medicines， the research on the chemical components of Mori Cortex has been in-depth and systematic. This article reviews the recent studies about the chemical components and pharmacological effects of Mori Cortex， as well as the treatment of respiratory diseases by the prescriptions with Mori Cortex. On this basis， the effect and mechanism of Mori Cortex and related prescriptions in the treatment of respiratory diseases are summarized. Furthermore， this article analyzes the formulation compatibility and commonly used dosages of Mori Cortex-related prescriptions in clinical practice. It provides reference for the clinical application of Mori Cortex and related prescriptions in the treatment of respiratory diseases.

Prescriptions with Mori Cortex in Treatment of Respiratory Diseases： A Review / 中国实验方剂学杂志

Mori Cortex is sweet and pungent in taste， cold in nature， and has the tropism to the lung meridian. It has the functions of purging the lung and relieving asthma and can treat oliguria and edema， being one of the commonly used herbal medicines in clinical practice. The prescriptions with Mori Cortex， such as Sangbaipi Tang， Qingjin Huatanfang， and Qingfei Huatantang， are widely used in clinical practice. The main active components in Mori Cortex are the material basis for its efficacy. Owing to the mature methods for the identification of pharmacodynamic substances in Chinese herbal medicines， the research on the chemical components of Mori Cortex has been in-depth and systematic. This article reviews the recent studies about the chemical components and pharmacological effects of Mori Cortex， as well as the treatment of respiratory diseases by the prescriptions with Mori Cortex. On this basis， the effect and mechanism of Mori Cortex and related prescriptions in the treatment of respiratory diseases are summarized. Furthermore， this article analyzes the formulation compatibility and commonly used dosages of Mori Cortex-related prescriptions in clinical practice. It provides reference for the clinical application of Mori Cortex and related prescriptions in the treatment of respiratory diseases.

Clinical effect of Zhizhukuanzhong capsule combined with Deanxit in the treatment of functional dyspepsia of spleen-deficiency and qi-stagnation / 中国基层医药

Objective To investigate the curative effect of Zhizhukuanzhong capsule combined with Deanxit in the treatment of functional dyspepsia ( FD) of spleen -deficiency and qi -stagnation.Methods Seventy -six patients with FD were randomly divided into three groups .A group (24 cases)_was given Zhizhukuanzhong combined with Deanxit,B group (26 cases) was given Zhizhukuanzhong ,C group (26 cases) received trimebutine dispersible tablets treatment.After treatment for 8 weeks,the symptoms of indigestion,depressive state and therapeutic effect were observed.Results Before treatment,there were no statistically significant differences in the symptoms of dyspepsia (all P>0.05).After treatment,the symptoms of dyspepsia were improved in different degree ,the effective rates of A, B,C three groups were 91.6%,65.4% and 42.3%,respectively,there was no statistically significant difference between A group and B group(χ2 =1.579,P=0.209);there was statistically significant difference between A group and C group(χ2 =13.549,P=0.000);there was no statistically significant difference between B group and C group (χ2 =2.786,P=0.09).The FD patients complicated with varying degrees of anxiety and depression ,there was no statistically significant difference among the three groups before treatment (P>0.05).After treatment,comparison of HAMA and HAMD scores among the three groups:there were statistically significant differences between A group and B group (tHAMA =6.839,tHAMD =4.607,all P<0.05),A group and C group (tHAMA =20.069,tHAMD =15.342,all P<0.01),B group and C group (tHAMA =11.951,tHAMD =12.071,all P<0.01).After treatment,the HAMA,HAMD scores of A group and B group were significantly decreased compared with before treatment ( A group tHAMA =52.758,tHAMD=49.970,B group tHAMA =30.230,tHAMD =17.151,all P<0.01).Those in C group had no statistically significant decline compared with before treatment (tHAMA =7.845,tHAMD =3.530,all P>0.05).The adverse reactions of A group were mainly weakness ,dizziness,drowsiness,which were alleviated within 2 weeks.The adverse reactions of B group were slight stomach disease and stool frequency increased ,which not affected the treatment.The adverse reactions of C group were digestive tract symptoms ,which lasted for more than 2 weeks.Conclusion Zhizhukuanzhong capsule combined with Deanxit in the treatment of FD of spleen -deficiency and qi -stagnation can obtain good curative effect,it is safe,convenient,and with minor side effects,good compliance.