Discovery of potential RIPK1 inhibitors by machine learning and molecular dynamics simulations.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) plays a crucial role in inflammation and cell death, so it is a promising candidate for the treatment of autoimmune, inflammatory, neurodegenerative, and ischemic diseases. So far, there are no approved RIPK1 inhibitors available. In this study, four machine learning algorithms were employed (random forest, extra trees, extreme gradient boosting and light gradient boosting machine) to predict small molecule inhibitors of RIPK1. The statistical metrics revealed similar performance and demonstrated outstanding predictive capabilities in all four models. Molecular docking and clustering analysis were employed to confirm six compounds that are structurally distinct from existing RIPK1 inhibitors. Subsequent molecular dynamics simulations were performed to evaluate the binding ability of these compounds. Utilizing the Shapley additive explanation (SHAP) method, the 1855 bit has been identified as the most significant molecular fingerprint fragment. The findings propose that these six small molecules exhibit promising potential for targeting RIPK1 in associated diseases. Notably, the identification of Cpd-1 small molecule (ZINC000085897746) from the Musa acuminate highlights its natural product origin, warranting further attention and investigation.

Moringa oleifera leaf attenuate osteoporosis in ovariectomized rats by modulating gut microbiota composition and MAPK signaling pathway.

Moringa oleifera leaf (MLP) contains abundant complex nutrients with anti-osteoporosis potential. However, its efficacy and mechanisms against osteoporosis remain unknown. The purpose of this research is to investigate MLP's anti-osteoporotic effects and mechanisms. Animal experiments were used in this work to validate MLP's anti-osteoporotic efficacy. We investigated the mode of action of MLP, analyzed its impact on the gut microbiota, and predicted and validated its anti-osteoporosis-related molecular targets and pathways through network pharmacology, molecular docking, and western blotting. In an ovariectomized osteoporosis rat model, MLP significantly increased bone mineral density and improved bone metabolism-related indicators, bone microstructure, and lipid profile. Moreover, it improved gut microbiota composition and increased the expression of Occludin and Claudin-1 protein in the duodenum. Network pharmacology identified a total of 97 active ingredients and 478 core anti-osteoporosis targets. Of these, MAPK1 (also known as ERK2), MAPK3 (also known as ERK1), and MAPK8 (also known as JNK) were successfully docked with the active constituents of MLP. Interestingly, MLP increased ERK and VAV3 protein expression and decreased p-ERK and JNK protein expression in the femur. These findings confirm MLP's anti-osteoporotic efficacy, which could be mediated via regulation of gut microbiota and MAPK signaling.

Analysis of DAT Combined with the VSD Technique in Wound Repair of Rats and Its Effect on Inflammatory Factors.

The clinical efficacy of decellularized adipose tissue (DAT) combined with vacuum sealing drainage (VSD) in the treatment of wound healing in rats is investigated, and the changes of inflammatory factors are analyzed. The tissue defect model of SD (Sprague-Dawley) rats is established and divided into the combined group (n = 12) and the control group (n = 12) according to different treatment methods. The control group is treated with a single VSD technique, and the combined group is treated with DAT on the basis of the control group. The wound healing time of the two groups is observed. Wound tissue is collected 1 day, 10 days, 20 days, and 30 days after treatment, and neutrophil infiltration is observed by HE (hematoxylin-eosin) staining. The expression changes of IL-6 and IL-13 at each time point before and after treatment are compared. Histological observation shows that the cell infiltration is reduced in both groups, and the wound repair in the combined group is better than that in the control group. The experimental results show that the DAT combined with the VSD technique can further speed up wound healing and reduce inflammation in rats.

Expression Patterns of Key Genes in the Photoperiod and Vernalization Flowering Pathways in Lilium longiflorum with Different Bulb Sizes.

Lilium longiflorum is a wild Lilium, and its flowering transition requires a long period of cold exposure to meet the demand of vernalization. The responses of different sized bulbs to cold exposure and photoperiod are different, and the floral transition pathways of small and large bulbs are different. In this study, small and large bulbs were placed in cold storage for different weeks and then cultured at a constant ambient temperature of 25 °C under long day (LD) and short day (SD) conditions. Then, the flowering characteristics and expression patterns of key genes related to the vernalization and photoperiod pathways in different groups were calculated and analyzed. The results showed that the floral transition of Lilium longiflorum was influenced by both vernalization and photoperiod, that vernalization and LD conditions can significantly improve the flowering rate of Lilium longiflorum, and that the time from planting to visible flowering buds' appearance was decreased. The flowering time and rate of large bulbs were greatly influenced by cold exposure, and the vernalization pathway acted more actively at the floral transition stage. The floral transition of small bulbs was affected more by the photoperiod pathway. Moreover, it was speculated that cold exposure may promote greater sensitivity of the small bulbs to LD conditions. In addition, the expression of LlVRN1, LlFKF1, LlGI, LlCO5, LlCO7, LlCO16, LlFT1, LlFT3 and LlSOC1 was high during the process of floral transition, and LlCO13, LlCO14 and LlCO15 were highly expressed in the vegetative stage. The expression of LlCO13 and LlCO14 was different under different lighting conditions, and the flowering induction function of LlCO9 and LlFT3 was related to vernalization. Moreover, LlFKF1, LlGI, LlCO5, LlCO16, LlSOC1 and LlFT2 were involved in the entire growth process of plants, while LlCO6, LlCO16 and LlFT1 are involved in the differentiation and formation of small bulblets of plants after the inflorescence stage, and this process is also closely related to LD conditions. This study has great significance for understanding the molecular mechanisms of the vernalization and photoperiod flowering pathways of Lilium longiflorum.

Comparison of samples of blister fluid and scales in the diagnosis of dermatomycosis.

BACKGROUND: The successful diagnosis of dermatomycosis depends on specimen collection. Dermatomycosis is sampled mainly for scales, but there is a lack of research on specimens of blister fluid. OBJECTIVES: To explore whether blister fluid can diagnose dermatomycosis and compare blister fluid and scale specimens for dermatomycosis diagnosis. METHODS: From April to July 2021, we prospectively gathered 34 patients who needed to meet all inclusion criteria simultaneously and collected their blister fluid and scales as specimens. The two samples were tested by fluorescent stain microscopy, fungal culture and PCR, and the diagnosis results were compared. RESULTS: The blister fluid sample's sensitivity, specificity and accuracy were 90%, 100% and 94.1%, respectively, whereas the scales sample were 60%, 100% and 76.5%, respectively. The positive likelihood ratios were >10 for both blister fluid and scales specimen, and the negative likelihood ratios were not <0.1. On the Youden's index, the blister fluid specimen was 90%, and the scales specimen was 60%. As for the diagnostic odds ratio, both of them were >1. By fungal culture, we detected 14 cases of fungi in blister fluid and eight in scales. On PCR, 22 cases of fungi in blister fluid and ten in scales were identified. CONCLUSIONS: This study demonstrated that a sample of blister fluid had better sensitivity, accuracy and Youden's index in diagnosing dermatomycosis with blister fluid. Collection of blister fluid might compensate for the inadequacy of collecting only scales specimens for mycological testing.

Naringenin regulates gut microbiota and SIRT1/ PGC-1ɑ signaling pathway in rats with letrozole-induced polycystic ovary syndrome.

PURPOSE: To evaluate the effect of naringenin on improving PCOS and explore the mechanism. METHODS: Firstly, we carried out differential gene expression analysis from transcriptome sequencing data of human oocyte to screen the KEGG pathway, then the PCOS-like rat model was induced by letrozole. They were randomly divided into four groups: Normal group (N), PCOS group (P), Diane-35 group (D), and Naringenin group (Nar). The changes of estrus cycle, body weight, ovarian function, serum hormone levels, glucose metabolism, along with the expression of SIRT1, PGC-1ɑ, claudin-1 and occludin of the ovary and colon were investigated. Furthermore, the composition of the gut microbiome of fecal was tested. RESULTS: By searching the KEGG pathway in target genes, we found that at least 15 KEGG pathways are significantly enriched in the ovarian function, such as AMPK signaling pathway, insulin secretion, and ovarian steroidogenesis. Interestingly, naringenin supplementation significantly reduced body weight, ameliorated hormone levels, improved insulin resistance, and mitigated pathological changes in ovarian tissue, up-regulated the expression of PGC-1ɑ, SIRT1, occludin and claudin-1 in colon. In addition, we also found that the abundance of Prevotella and Gemella was down-regulated, while the abundance of Butyricimonas, Lachnospira, Parabacteroides, Butyricicoccus, Streptococcus, Coprococcus was up-regulated. CONCLUSION: Our data suggest that naringenin exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota and SIRT1/PGC-1ɑ signaling pathway. Our research may provide a new perspective for the treatment of PCOS and related diseases.

The effect of magnesium sulfate on emergence agitation in children undergoing general anesthesia: A systematic review and meta-analysis.

STUDY OBJECTIVE: Emergence agitation (EA) is a common complication in pediatric patients after general anesthesia. The effectiveness of magnesium sulfate in decreasing the incidence of EA in children remains controversial. Therefore, a systematic review and meta-analysis was performed to assess the efficacy of magnesium sulfate in preventing EA in pediatric patients following general anesthesia. DESIGN: Systematic review and meta-analysis. SETTING: PubMed, Embase, Web of Science, and Cochrane Library were searched to identify eligible randomized controlled trials from their respective database inception dates to June 30, 2021. PATIENTS: Pediatric patients (< 18 years old) undergoing general anesthesia. INTERVENTIONS: Intravenous administration of magnesium sulfate. MEASUREMENTS: The primary outcome of the meta-analysis was EA incidence. The risk of bias of the included studies was evaluated using the revised Cochrane risk of bias tool for randomized trials (RoB 2.0). Grading of Recommendations, Assessment, Development, and Evaluation was applied to assess the level of certainty. MAIN RESULTS: Eight studies with 635 participants were identified. The forest plot revealed no significant difference in the incidence of EA between patients treated with magnesium sulfate and the control group (risk ratio = 0.69, 95% confidence interval [0.44, 1.07]; P = 0.10, I2 = 74%, moderate level of certainty). Additionally, magnesium sulfate did not reduce postoperative pediatric anesthesia emergence delirium scores but prolonged the emergence time. No significant differences were observed in postoperative complications (nausea, vomiting, laryngospasm, breath-holding, coughing, oxygen desaturation, and cardiac arrhythmias). CONCLUSIONS: Administration of magnesium sulfate during general anesthesia did not affect the occurrence of EA in pediatric patients. However, magnesium sulfate can prolong the emergence time without adverse effects. PROSPERO registration number: CRD42021252924.

Stomata and ROS changes during Botrytis elliptica infection in diploid and tetraploid Lilium rosthornii Diels.

Polyploid plants often show improved resistance against many diseases, but whether they show increased resistance to grey mould, a devastating disease caused by Botrytis spp. fungi, is seldom reported. Stomata and reactive oxygen species (ROS) play dual roles in defence against grey mould, and it is unclear how their roles change after polyploidization. We addressed these questions in diploid and colchicine-induced Lilium rosthornii after B. elliptica infection. Tetraploids were less susceptible to grey mould, with lower morality rates in naturally infected plants. Before the stomata closed in artificially infected leaves, tetraploids, with larger stomatal apertures, were more easily invaded by the pathogen than diploids. However, the lesion area increased more slowly in tetraploids than in diploids, which may be explained by three causes based on histological and physiological characteristics. First, the pathogen required more time to penetrate the epidermis and closed stomata in tetraploids than in diploids. Second, the pathogen penetrated the reopened stomata more easily than the epidermis, and stomatal density was lower in tetraploids than in diploids. Third, tetraploids showed faster ROS accumulation, a more effective ROS-scavenging system and less malondialdehyde (MDA) accumulation than diploids. Stomatal starch and abnormal guard cell nuclei were present in the infected leaves. This phenomenon may be caused by oxalic acid, a pathogenic factor for many pathogens that promotes stomatal starch degradation and stomatal reopening in Sclerotinia spp., a pathogen closely related to Botrytis spp. This suggestion was primarily confirmed by immersing healthy leaves in oxalic acid solution.

Effects of Salvianolic acid B on RNA expression and co-expression network of lncRNAs in brown adipose tissue of obese mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvianolic acid B (SalB) is a polyphenolic compound in Salvia miltiorrhiza Bunge ("Danshen"), which has been largely used in Traditional Chinese Medicine for the treatment of metabolic syndrome, obesity, diabetes, among others. AIM OF STUDY: This study was to investigate the effects of Salvianolic acid B (SalB) on mRNA, lncRNA and circRNA's expression profile in brown adipose tissue (BAT) of obese mice. MATERIALS AND METHODS: High-fat-diet induced obese C57BL/6J mice were treated with SalB (100 mg/kg/day) for 8 weeks. Then, BAT was harvested for RNA-Seq analysis. Differentially expressed mRNAs, lncRNAs and circRNAs were analyzed using the Illumina Hiseq 4000. Following this procedure, bioinformatic tools including Gene ontology (GO), KEGG pathway and lncRNA-mRNA co-network analysis were utilized. Finally, RT-qPCR was performed to validate the differentially expressed RNAs. RESULTS: Compared with control group, 2532 mRNAs, 774 lncRNAs and 25 circRNAs were differentially expressed in SalB group. Additionally, 40 upregulated and 109 downregulated gene-related pathways were identified in the SalB group. Among them, metabolic pathways showed the highest enrichment coefficient in upregulated genes. Moreover, 54 up-regulated and 626 down-regulated coding mRNAs associated with lncRNA-Hsd11b1 and lncRNA-Vmp1. CONCLUSIONS: SalB may play an anti-obesity role by adjusting the expression of mRNAs correlated with inflammatory response and energy metabolism through regulating the expression of lncRNA-Hsd11b1. The findings of this research provide new directions to study the mechanisms of SalB, and would open therapeutic avenues for the treatment of obesity.

OsIAA20, an Aux/IAA protein, mediates abiotic stress tolerance in rice through an ABA pathway.

In plants, auxin and ABA play significant roles in conferring tolerance to environmental abiotic stresses. Earlier studies have been shown that some Aux/IAA genes, with important signaling factors in the auxin pathway, were induced in response to drought and other abiotic stresses. However, the mechanistic links between Aux/IAA expression and general drought response remain largely unknown. In this study, OsIAA20, a rice Aux/IAA protein, shown with important roles in abiotic stress. Phenotypic analyses revealed that OsIAA20 RNAi transgenic rice reduced drought and salt tolerance; whereas, OsIAA20 overexpression plants displayed the opposite phenotype. Physiological analyses of OsIAA20 RNAi rice grown under drought or salt stress showed that proline and chlorophyll content significantly decreased, while malondialdehyde content and the ratio of Na+/ K+ significantly increased. In addition, OsIAA20down-regulation reduced stomatal closure and increased the rate of water loss, while transgenic plants overexpressing OsIAA20 exhibited the opposite physiological responses. Furthermore, an ABA-responsive gene, OsRab21, was down-regulated in OsIAA20 RNAi rice lines and upregulated in OsIAA20 overexpression plants. Those results means OsIAA20 played an important role in plant drought and salt stress responses, by an ABA dependent mechanism, and it will be a candidate target gene used to breed abiotic stress tolerance.

Functional analysis and expression patterns of members of the FLOWERING LOCUS T (FT) gene family in Lilium.

Lilium is an important commercial flowering species, and there are many varieties and more than 100 species of wild Lilium. Lilium × formolongi is usually propagated from seedlings, and the flowering of these plants is driven mainly by the photoperiodic pathway. Most of the other lily plants are propagated via bulblets and need to be vernalized; these plants can be simply divided into pretransplantation types and posttransplantation types according to the time at which the floral transition occurs. We identified three Lilium FLOWERING LOCUS T (LFT) family members in 7 Lilium varieties, and for each gene, the coding sequence of the different varieties was identical. Among these genes, the LFT1 gene of Lilium was most homologous to the AtFT gene, which promotes flowering in Arabidopsis. We analyzed the expression patterns of LFT genes in Lilium × formolongi seedlings and in different Lilium varieties, and the results showed that LFT1 and LFT3 may promote floral induction. Compared with LFT3, LFT1 may have a greater effect on floral induction in Lilium, which is photoperiod sensitive, while LFT3 may play a more important role in the floral transition of lily plants, which have a high requirement for vernalization. LFT2 may be involved in the differentiation of bulblets, which was verified by tissue culture experiments, and LFT1 may have other functions involved in promoting bulblet growth. The functions of LFT genes were verified by the use of transgenic Arabidopsis thaliana plants, which showed that both the LFT1 and LFT3 genes can promote early flowering in Arabidopsis. Compared with LFT3, LFT1 promoted flowering more obviously, and thus, this gene could be an important promoter of floral induction in Lilium.

Transcriptome Sequencing Analysis of Peripheral Blood of Type 2 Diabetes Mellitus Patients With Thirst and Fatigue.

Purpose: The purpose of this study is to explore the differences in transcriptome expression profiles between healthy subjects and type 2 diabetes mellitus patients with thirst and fatigue (D-T2DM) and, in addition, to investigate the possible role of noncoding ribonucleic acids (RNAs) in the pathogenesis of D-T2DM. Methods: We constructed the expression profiles of RNAs by RNA sequencing in the peripheral blood of D-T2DM patients and healthy subjects and analyzed differentially expressed RNAs. Results: Compared with healthy subjects, a total of 469 mRNAs, 776 long non-coding RNAs (lncRNAs), and 21 circular RNAs (circRNAs) were differentially expressed in D-T2DM patients. Furthermore, several genes associated with insulin resistance, inflammation, and mitochondrial dysfunction were identified within the differentially expressed mRNAs. Differentially expressed lncRNAs were primarily involved in biological processes associated with immune responses. In addition, differentially expressed circRNAs may target miRNAs associated with glucose metabolism and mitochondrial function. Conclusions: Our results may bring a new perspective on differential RNA expression involved in the pathogenesis of D-T2DM and promote the development of novel treatments for this disease.

Microarray analysis of aberrant microRNA expression patterns in spinal cord gliomas of different grades.

MicroRNAs (miRNAs) are involved in the development of several types of tumor; however, their role in spinal gliomas remains unknown. The present study aimed to identify potentially novel spinal cord gliomas (SCG)-associated miRNAs and to characterize their roles in the development and progression of SCG. miRNA expression levels in low-grade SCG (classed as stage I-II SCG based on the World Health Organization grading system), high-grade SCG (classed as stage IV SCG based on the World Health Organization grading system) and 5 control cases were measured using a miRNA expression microarray. Subsequently, blood samples from the spinal cord of patients with differing grades of SCG were screened for differentially expressed miRNAs (DEmiRNAs). Compared with the control group, 7 upregulated and 36 downregulated miRNAs were identified in the low-grade SCG group and a total of 70 upregulated and 20 downregulated miRNAs were identified in the high-grade SCG group (P≤0.05, fold change >2). Gene Ontology analysis revealed that the regulation of cellular metabolic processes, negative regulation of biological processes and axon guidance were primarily involved. Moreover, pathway analysis showed that the target genes of DEmiRNAs were enriched in tumor-related signaling pathways, such as the MAPK and Wnt signaling pathway. The results suggest that DEmiRNAs in peripheral blood may serve as novel target markers with high specificity and sensitivity for the diagnosis of SCG.

Aetiology of superficial fungal infections of the foot in urban outpatients in mainland China: A multicentre, prospective case study.

BACKGROUND: In China, the prevalence of superficial fungal infections of the foot is high and recurrence is common. However, a prospective, large-scale and multicentre study on the aetiology of superficial fungal infections of the foot is still lacking. OBJECTIVES: To study the epidemiology of aetiological agents of superficial fungal infections of the foot in urban outpatients in mainland China, as well as to understand the aetiology features of the pathogenic agent. METHODS: The study was designed as a multicentre, prospective epidemiological survey. A total of 1704 subjects were enrolled from seven geographical areas in mainland China. For each subject, one mycological sample and one bacterial sample were collected. KOH wet mount examination and culture were performed at local laboratories. The bacterial results were only reported in those with positive mycology. Further morphological identification and, if necessary, molecular biological identification were conducted in a central laboratory. RESULTS: Of 1704 enrolled subjects, 1327 (77.9%) subjects had positive fungal culture results. The incidence of dermatophytes, yeasts and moulds was 90.1%, 8.1% and 1.1%, respectively. The most frequently isolated aetiological agent (fungus) was Trichophyton rubrum. Moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections. The most frequently isolated bacterial genus in patients was Staphylococcus. CONCLUSION: This study prospectively investigated the clinical and mycological features of human dermatophytosis in mainland China. T rubrum was the most frequently isolated fungus, and moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections.

A comparative study of microbial community and functions of type 2 diabetes mellitus patients with obesity and healthy people.

The gut microbiota is crucial in the pathogenesis of type 2 diabetes mellitus (T2DM). However, the metabolism of T2DM patients is not well-understood. We aimed to identify the differences on composition and function of gut microbiota between T2DM patients with obesity and healthy people. In this study, 6 T2DM patients with obesity and 6 healthy volunteers were recruited, and metagenomic approach and bioinformatics analysis methods were used to understand the composition of the gut microbiota and the metabolic network. We found a decrease in the abundance of Firmicutes, Oribacterium, and Paenibacillus; this may be attributed to a possible mechanism and biological basis of T2DM; moreover, we identified three critical bacterial taxa, Bacteroides plebeius, Phascolarctobacterium sp. CAG207, and the order Acidaminococcales that can potentially be used for T2DM treatment. We also revealed the composition of the microbiota through functional annotation based on multiple databases and found that carbohydrate metabolism contributed greatly to the pathogenesis of T2DM. This study helps in elucidating the different metabolic roles of microbes in T2DM patients with obesity.

Combined analysis of whole-exon sequencing and lncRNA sequencing in type 2 diabetes mellitus patients with obesity.

This study sought to find more exon mutation sites and lncRNA candidates associated with type 2 diabetes mellitus (T2DM) patients with obesity (O-T2DM). We used O-T2DM patients and healthy individuals to detect mutations in their peripheral blood by whole-exon sequencing. And changes in lncRNA expression caused by mutation sites were studied at the RNA level. Then, we performed GO analysis and KEGG pathway analysis. We found a total of 277 377 mutation sites between O-T2DM and healthy individuals. Then, we performed a DNA-RNA joint analysis. Based on the screening of harmful sites, 30 mutant genes shared in O-T2DM patients were screened. At the RNA level, mutations of 106 differentially expressed genes were displayed. Finally, a consensus mutation site and differential expression consensus gene screening were performed. In the current study, the results revealed significant differences in exon sites in peripheral blood between O-T2DM and healthy individuals, which may play an important role in the pathogenesis of O-T2DM by affecting the expression of the corresponding lncRNA. This study provides clues to the molecular mechanisms of metabolic disorders in O-T2DM patients at the DNA and RNA levels, as well as biomarkers of the risk of these disorders.

Relationships of Non-coding RNA with diabetes and depression.

In order to study the molecular differences between type 2 diabetes mellitus (T2DM) and T2DM with depression (DD), we aimed to screen the differential expression of lncRNA, mRNA, and circRNA in the blood of patients with T2DM and DD. Based on the self-rating depression scale (SDS), patient health questionnaire 9 (PHQ9), blood glucose and HbA1c, we divided the patients into T2DM and DD group. Peripheral blood was collected from the two groups of patients to perform lncRNA, mRNA, and circRNA expression profiling and screening DD-related specific molecules. Subsequently, bioinformatics analysis was performed to investigate the functions of differentially expressed genes (DEgenes). Finally, RT-PCR and lncRNA-mRNA regulatory network was performed to verify the expressions of lncRNAs and mRNAs related to the occurrence and development of DD. 28 lncRNAs, 107 circRNAs, and 89 mRNAs were identified in DD differential expression profiles. GO and pathway analysis found that 20 biological process (BP) related entities and 20 pathways associated with DD. The analysis shows that the genes that are differentially expressed in the DD group involved in the development of the neuropsychiatric system, immunity, and inflammation. Then, we screening for the important DElncRNA and mRNA associated with DD were verified by RT-PCR experiments and the results of RT-PCR were consistent with the sequencing results. LncRNA, circRNA, and mRNA differential expression profiles exist in DD patients compared with T2DM. The lncRNA-mRNA regulatory network analysis confirmed the crosslinking and complex regulation patterns of lncRNA and mRNA expression and verified the authenticity of the regulatory network.

Salvianolic acid B plays an anti-obesity role in high fat diet-induced obese mice by regulating the expression of mRNA, circRNA, and lncRNA.

BACKGROUND: Adipose tissue plays a central role in obesity-related metabolic diseases such as type 2 diabetes. Salvianolic acid B (Sal B), a water-soluble ingredient derived from Salvia miltiorrhiza, has been shown to reduce obesity and obesity-related metabolic diseases by suppressing adipogenesis. However, the role of Sal B in white adipose tissue (WAT) is not yet clear. METHODS: Illumina Hiseq 4000 was used to study the effects of Sal B on the expression of long non-coding RNA (lncRNA) and circular RNA (circRNA) in epididymal white adipose tissue induced by a high fat diet in obese mice. RESULTS: RNA-Seq data showed that 234 lncRNAs, 19 circRNAs, and 132 mRNAs were differentially expressed in WAT under Sal B treatment. The up-regulated protein-coding genes in WAT of the Sal B-treated group were involved in the insulin resistance pathway, while the down-regulated genes mainly participated in the IL-17 signaling pathway. Other pathways may play an important role in the formation and differentiation of adipose tissue, such as B cell receptor signaling. Analysis of the lncRNA-mRNA network provides potential targets for lncRNAs in energy metabolism. We speculate that Sal B may serve as a potential therapeutic approach for obesity.

Baduanjin exerts anti-diabetic and anti-depression effects by regulating the expression of mRNA, lncRNA, and circRNA.

BACKGROUND: Baduanjin, a traditional Chinese exercise therapy, has been widely used in China to treat type 2 diabetes (T2DM) with depression (DD). However, the underlying mechanism of Baduanjin in anti-DD is unclear. This study was focused on investigating the effects of Baduanjin on symptoms of depression and blood glucose in patients with DD and the underlying mechanism. METHODS: We performed a 12-week Baduanjin intervention on patients with DD and longitudinally compared the differential expressions of lncRNAs, circRNAs, and mRNAs between pre- (BDD) and post- (ADD) Baduanjin intervention in the same group. Subsequently, Gene Ontology (GO) and pathway analysis was performed to investigate the function of differentially expressed mRNAs. Finally, Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was used to verify the sequencing result and the mRNA-lncRNA regulatory network was constructed. RESULTS: The blood glucose level, depression index scores, and PHQ9 scores of the patients with DD were significantly decreased (P < 0.05) after Baduanjin intervention. Compared to BDD, 207 lncRNAs, 266 circRNAs, and 610 differentially expressed mRNAs were identified in ADD. Kyoto Encyclopedia of Genes and Genomes (KEGG) and GO showed that the significantly dysregulated mRNAs were mainly involved in immune function and inflammatory response pathways, and various signaling pathways including IL-17 and TNF. In addition, we selected five differentially expressed lncRNAs to construct an lncRNA-mRNA regulatory network, and found a total of 1045 mRNAs associated with them. CONCLUSIONS: Our research is the first systematic profiling of mRNA, lncRNA, and circRNA in patients of ADD and BDD, and provides valuable insights in the potential mechanism of Baduanjin in anti-DD. Further, it was confirmed that Baduanjin is a safe and effective intervention for patients with DD because it can effectively ameliorate the symptoms of depression and blood glucose levels in patients with DD by regulating the dysregulated expression of lncRNA, mRNA, and circRNA.