Investigation of the Therapeutic Effect of Salbutamol on Endometriosis in a Mouse Model.

Endometriosis is an immune chronic inflammatory disease, and there are currently no more effective drugs for treating endometriosis due to its unknown etiology. Salbutamol is a ß2-adrenergic receptor (ß2AR) agonist commonly used to treat asthma by selectively activating ß2 receptors on airway smooth muscle and leukocytes, exerting bronchial dilation and synergistic anti-inflammatory effects. In recent years, ß2AR agonists have been used in endometriosis studies, and we speculate that salbutamol may have a therapeutic effect on endometriosis. The purpose of this research was to explore the therapeutic effect of salbutamol on endometriosis mice. The mouse endometriosis model was established and treated with different doses of salbutamol. Endometrial lesions were harvested for pathological diagnosis, immunohistochemistry (IHC), Masson staining, and toluidine blue analysis. We found that the number and size of endometriotic lesions were all significantly decreased after 3 weeks of treatment with different doses of salbutamol on endometriosis model mice (P < 0.05). After Salbutamol treatment, the amount of mast cells (toluidine blue) and macrophages (F4/80) in the lesions as well as the expressions of interleukin (IL)-1ß, tumor necrosis factor (TNF)-ɑ, platelet-derived growth factor subunit B (PDGFB), CD31, transforming growth factor (TGF)-ß, Masson staining, BCL2, TUBB3, substance P (SP), and nerve growth factor (NGF) were significantly reduced (P < 0.05). These results suggested that salbutamol could effectively treat endometriosis in mice by reducing immune inflammatory cells and factors, angiogenesis, and fibrosis, increasing apoptosis of endometriotic lesions, and decreasing neurogenesis.

First Report of Leaf Spot on Soybean Caused by Epicoccum sorghinum in Heilongjiang Province, China.

Soybean (Glycine max (Linn.) Merr.) is one of the important oil crops in China. In September 2022, a new soybean leaf spot disease was found in Zhaoyuan County, Suihua City, Heilongjiang Province, China. Symptoms of the initial formation of irregular brown lesions on the leaves, dark brown inside, the periphery is yellow, vein chlorotic yellow, severe leaf spots connected into pieces, late fall off, not the same as previously reported soybean leaf spot (Fig. 1A). The leaf samples of infected plants were collected, and the leaf tissue (5 × 5 mm) was cut from the edge of the lesion, and then surface sterilized with 3% sodium hypochlorite for 5 min, rinsed with sterile distilled water for 3 times, and inoculated on potato dextrose agar (PDA) at 28°C. Isolates growing around the tissues from samples were subcultured on PDA, and 3 isolates were obtained using the single-spore isolation method. The fungal hyphae were white or grayish white in early stage, and the hyphae with light green concentric ring appeared on the front of the colony after 3 days, appeared orange, pink or white convex, irregular shape, reddish brown on the front of the colony for 10 days and black spherical pycnidium can be produced in the hyphae layer for 15 days (Fig.1D, E). Conidia were oval, hyaline, unicellular, aseptate, and 2.3 to 3.7 × 4.1 to 6.8 µm (n=30, Fig. 1F). Chlamydospores were subglobose, light brown, unicellular or multicellular, and 7.2 to 14.7 × 12.2 to 43.9 µm (n=30, Fig. 1H, I). Pycnidia mostly spheroid, brown, and 47.1 to 114.4 × 72.6 to 167.4 µm (n=30, Fig. 1G). A cetyl trimethyl ammonium bromide method was used to extract DNA from 7-day-old. Internal transcribed spacer (ITS), RNA polymerase II (RPB2) and ß-tubulin (TUB) gene were amplified using ITS1/ITS4 (White et al. 1990), RPB2-5F/RPB2-7cR (Liu et al. 1999) and BT2a/Bt2b (O'Donnell et al. 1997) primers respectively. The sequences obtained by polymerase chain reaction (PCR) were sequenced and the results showed that the DNA sequences of the 3 isolates were identical. Therefore, the sequence of isolate DNES22-01, DNES22-02 and DNES22-03 was submitted to GenBank. According to BLAST search, the ITS (OP884646), RPB2 (OP910000) and TUB (OP909999) sequences showed 99.81% similarity to Epicoccum sorghinum strain LC12103 (MN215621.1), 99.07% to strain P-XW-9A (MW446946.1), and 98.85% with the strain UMS (OM048108.1), respectively. Phylogenetic analysis by maximum likelihood method (MEGA7.0) generated based on the ITS, RPB2 and TUB sequences indicated that the isolates formed a supported clade to the related E. sorghinum type sequences. Isolates was found to be most closely related to E. sorghinum and far from other species. Based on morphological and phylogenetic characteristics, isolates DNES22-01, DNES22-02 and DNES22-03 was identified as E. sorghinum (Bao et al. 2019; Chen et al. 2021; Zhang et al. 2022). At the 4-leaf-stage, 10 soybean plants were inoculated by spraying with a conidial suspension (1 × 106 spores·ml-1). Sterile water served as a control. The test was repeated 3 times. All samples were incubated in a growth chamber at 27°C. Symptoms typical developed on the leaves after 7 days, but control samples remained healthy (Fig.1B, C). The fungus was reisolated from symptomatic tissues and identified as E. sorghinum by morphology characteristics and molecular characterization. To our knowledge, this is the first report of E. sorghinum causing leaf spot on soybean in Heilongjiang, China. The results can provide the basis for future studies on the occurrence, prevention, and management of this disease.

Integrating Spatial Transcriptomics and Single-nucleus RNA Sequencing Reveals the Potential Therapeutic Strategies for Uterine Leiomyoma.

Uterine leiomyoma is the most common gynecological tumor in reproductive women. Tumor-host interface is a complex ecosystem with intimate cell-cell communications and a critical scenario for tumor pathogenesis and progression. The pseudocapsule is the main tumor-host interface of uterine leiomyoma, but its cellular spatial disposition and gene expression are poorly explored. This study mapped the cellular architecture and corresponding gene profiles of the leiomyoma and its surrounding pseudocapsule by integrating spatial transcriptomics and single-nucleus RNA-sequencing at the first time. Here, we reported that estrogen receptor alpha and progesterone receptor mediated the occurrence and development of uterine leiomyoma and that estrogen receptor beta involved in the angiogenesis, which explained the effectiveness of hormonotherapy. Therapeutic targets including ERK1/ERK2 pathway and IGF1-IGF1R were found and might be applied for non-hormonal therapy of uterine leiomyoma. Furthermore, the injection of prostaglandin E2 was initially presented for bleeding control during myomectomy, injection site should be located at the junction between pseudocapsule and leiomyoma, and surrounding pseudocapsule should not be eliminated. Collectively, a single-cell and spatially resolved atlas of human uterine leiomyoma and its surrounding pseudocapsule was established. The results revealed potentially feasible strategies for hormonotherapy, non-hormonal targeted therapy and bleeding control during myomectomy.

Comprehensive Analysis of RNA-Seq in Endometriosis Reveals Competing Endogenous RNA Network Composed of circRNA, lncRNA and mRNA.

Although long non coding RNAs (lncRNAs) and circular RNAs (circRNAs) play important roles in the pathogenesis of diseases, endometriosis related lncRNAs and circRNAs are still rarely reported. This study focused on the potential molecular mechanism of endometriosis related competitive endogenous RNA (ceRNA) composed of lncRNAs and circRNAs. We performed high-throughout sequencing of six normal endometria, six eutopic endometria and six ectopic endometria for the first time to describe and analyze the expression profile of lncRNA, circRNA and mRNA. Our results showed that 140 lncRNAs, 107 circRNAs and 1,206 mRNAs were differentially expressed in the ectopic group, compared with the normal and eutopic groups. We established an lncRNA/circRNA-mRNA co-expression network using pearson correlation test. Meanwhile, the results of Gene set enrichment analysis analysis showed that the 569 up-regulated differentially expressed mRNA (DEmRNA) were mainly related to the epithelial-mesenchymal transition, regulation of immune system process and immune effector process. Subsequently, we established a DElncRNA-miRNA and DEcircRNA-miRNA network using the starbase database, identified the common miRNAs and constructed DElncRNA/DEcircRNA-miRNA pairs. miRDB, Targetscan, miRwalk and circRNA/lncRNA-mRNA pairs jointly determined the miRNA-mRNA portion of the circRNA/lncRNA-miRNA-mRNA co-expression network. RT-qPCR results of 15 control samples and 25 ectopic samples confirmed that circGLIS2, circFN1, LINC02381, IGFL2-AS1, CD84, LYPD1 and FAM163A were significantly overexpressed in ectopic tissues. In conclusion, this is the first study to illustrate ceRNA composed of differentially expressed circRNA, lncRNA and mRNA in endometriosis. We also found that lncRNA and circRNA exerted a pivotal function on the pathogenesis of endometriosis, which can provide new insights for further exploring the pathogenesis of endometriosis and identifying new targets.

ROMA Index Is an Effective Predictor for Advanced Endometrial Cancer before Surgery.

There is a high rate of inconformity between clinical staging and surgical-pathologic staging in endometrial cancer. Many patients with advanced endometrial cancer are preoperatively understaged and thereby do not receive the optimal therapy. Here, we aimed to develop a predictive model or biomarker for preoperative diagnosis of advanced endometrial cancer via multivariate logistic regression analysis. In this study, 259 eligible patients were included, and 195 patients were assigned to the training dataset and 64 patients to validation dataset. Age, menopause status, sterilization situation, parity, body mass index, hypertension, diabetes mellitus, tumor size, and ovarian malignancy algorithm (ROMA) index were included as predictive variables, and the binary outcome was advanced endometrial cancer or not. When the P value was set as less than 0.01 in forward stepwise regression, only ROMA index was retained. The odds ratio of being positive ROMA index was 15.531 times that of negative value. The area under receiver operating characteristic curve was 0.790 in the training dataset and 0.776 in the validation dataset. The decision curve analysis curve showed that the prediction by ROMA index added more net benefits for almost all threshold probabilities. Therefore, ROMA index is an effective predictor for advanced endometrial cancer before surgery. Since ROMA index is a standard, measurable, and reliable laboratory test, it can be used as a reference tool for gynecologists to design the appropriate therapeutic schedule for patients with high-stage endometrial cancer before surgery.

Correction to: Effects of probiotics on type II diabetes mellitus: a meta-analysis.

Following publication of the original article [1], the authors reported an error in one of the author names. In this Correction the incorrect and correct author names are listed.

Effects of probiotics on type II diabetes mellitus: a meta-analysis.

OBJECTIVE: The purpose of the present study was to evaluate the effectiveness of probiotics on type II diabetes mellitus (T2DM). METHODS: We performed a comprehensive search on PubMed, Web of Science, China National Knowledge Infrastructure, Chinese Scientific Journal Databases, Wan Fang database and China biology medicine disc for relevant studies published before June 2019. Glycated hemoglobin A1c (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR) and fasting blood glucose (FBG) were used as indicators for T2DM. Inverse-variance weighted mean difference (WMD) with 95% confidence interval (CI) was calculated for the mean HbA1c, FBG and HOMA-IR changes from baseline. RESULTS: 15 randomized controlled trials (RCT) with a total of 902 participants were included into the meta-analysis. Considering the clinical heterogeneity caused by variation of dosage and duration of probiotic treatment, random-effects model was used to estimate the pooled WMD. Significantly greater reduction in HbA1c% (WMD = - 0.24, 95% CI [- 0.44, - 0.04], p = 0.02), FBG (WMD = - 0.44 mmol/L, 95% CI [- 0.74, - 0.15], p = 0.003) and HOMA-IR (WMD = - 1.07, 95% CI [- 1.58, - 0.56], p < 0.00001) were observed in probiotics treated group. Further sensitivity analysis verified the reliability and stability of our results. CONCLUSION: The results of our meta-analysis indicated that probiotics treatment may reduce HbA1c, FBG and insulin resistance level in T2DM patients. More clinical data and research into the mechanism of probiotics are needed to clarify the role of probiotics in T2DM.