Myrrh Essential Oil Improves DSS-Induced Colitis by Modulating the MAPK Signaling Pathway: In vitro and in vivo Studies.

Objective: To explore the mechanism and active components of the anti-colitis effects of myrrh essential oil (MEO). Methods: In this study, we investigated the anti-inflammatory effects and molecular mechanisms of MEO on dextran sulfate sodium (DSS)-induced colitis with in vitro cell experiments, RNA-seq (RNA Sequencing), Weighted gene co-expression network analysis (WGCNA), combined with "weighting coefficient" network pharmacology, as and in vivo pharmacodynamic experiments. A 3% DSS solution was used to induce colitis in BALB/c mice and MEO was administered orally. We performed gas chromatography-mass spectrometry (GC-MS) analysis of the MEO components. The disease activity index (DAI) was evaluated by observing body weight, fecal characteristics, and blood in the stool of mice. The levels of inflammatory cytokines (TNF-α and IL-1ß) in mouse serum were measured using ELISA (Enzyme-linked immunosorbent assay) kits. Additionally, the expression of MAPK-related proteins (JNK, p-JNK, ERK, and p-ERK) in mouse colonic tissues was detected by Western blotting and immunohistochemistry. Results: MEO (0.0625-0.125µg/g, p.o). significantly inhibited the expression of the inflammatory mediator Nitric oxide (NO) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. After treatment, there was a significant increase in body weight and alleviation of diarrhea and bloody stools in colitis mice. It also reduced inflammatory cell infiltration. Furthermore, it decreased the serum levels of TNF-α and IL-1ß, and reduced the activity of p-JNK and p-ERK in the MAPK pathway. Conclusion: MEO relieved DSS-induced colitis by modulating the MAPK pathway. The experimental results indicate that the MAPK pathway might be inhibited by the synergistic effect of gamma-Muurolene, Curzerene, beta-Elemene, and Furanoeudesma 1.3-diene in MEO, which provides a novel idea for subsequent research and development of new anti-colitis drugs.

Morphological variation and expressed sequence tags-simple sequence repeats-based genetic diversity of Aspergillus cristatus in Chinese dark tea.

Introduction: Aspergillus cristatus is a homothallic fungus that is used in the natural fermentation process of Chinese Fuzhuan tea and has been linked to the production of bioactive components. However, not much is known about the variations present in the fungus. To understand the variation of the dominant microorganism, A. cristatus, within dark tea, the present study investigated the genetic and morphological diversity of 70 A. cristatus collected across six provinces of China. Methods: Expressed sequence tags-simple sequence repeats (EST-SSR) loci for A. cristatus were identified and corresponding primers were developed. Subsequently, 15 specimens were selected for PCR amplification. Results: The phylogenetic tree obtained revealed four distinct clusters with a genetic similarity coefficient of 0.983, corresponding to previously identified morphological groups. Five strains (A1, A11, B1, D1, and JH1805) with considerable differences in EST-SSR results were selected for further physiological variation investigation. Microstructural examinations revealed no apparent differentiation among the representative strains. However, colony morphology under a range of culture media varied substantially between strains, as did the extracellular enzymatic activity (cellulase, pectinase, protease, and polyphenol oxidase); the data indicate that there are differences in physiological metabolic capacity among A. cristatus strains. Discussion: Notably, JH1805, B1, and A11 exhibited higher enzymatic activity, indicating their potential application in the production of genetically improved strains. The findings provide valuable insights into species identification, genetic diversity determination, and marker-assisted breeding strategies for A. cristatus.

Deciphering the antidepressant effects of Rosa damascena essential oil mediated through the serotonergic synapse signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Rosa damascena is an ancient plant with significance in both medicine and perfumery that have a variety of therapeutic properties, including antidepressant, anti-anxiety, and anti-stress effects. Rose damascena essential oil (REO) has been used to treat depression, anxiety and other neurological related disorders in Iranian traditional medicine. However, its precise mechanism of action remains elusive. AIM OF THE STUDY: The aim of this study was to investigate the impact and mechanism underlying the influence of REO on chronic unpredictable mild stress (CUMS) rats. MATERIALS AND METHODS: Gas chromatography-mass spectrometry (GC-MS) technique coupling was used to analyze of the components of REO. A CUMS rat model was replicated to assess the antidepressant effects of varying doses of REO. This assessment encompassed behavioral evaluations, biochemical index measurements, and hematoxylin-eosin staining. For a comprehensive analysis of hippocampal tissues, we employed transcriptomics and incorporated weighting coefficients by means of network pharmacology. These measures allowed us to explore differentially expressed genes and biofunctional pathways affected by REO in the context of depression treatment. Furthermore, GC-MS metabolomics was employed to assess metabolic profiles, while a joint analysis in Metscape facilitated the construction of a network elucidating the links between differentially expressed genes and metabolites, thereby elucidating potential relationships and clarifying key pathways regulated by REO. Finally, the expression of relevant proteins in the key pathways was determined through immunohistochemistry and Western blot analysis. Molecular docking was utilized to investigate the interactions between active components and key targets, thereby validating the experimental results. RESULTS: REO alleviated depressive-like behavior, significantly elevated levels of the neurotransmitter 5-hydroxytryptamine (5-HT), and reduced hippocampal neuronal damage in CUMS rats. This therapeutic effect may be associated with the modulation of the serotonergic synapse signaling pathway. Furthermore, REO rectified metabolic disturbances, primarily through the regulation of amino acid metabolic pathways. Joint analysis revealed five differentially expressed genes (EEF1A1, LOC729197, ATP8A2, NDST4, and GAD2), suggesting their potential in alleviating depressive symptoms by modulating the serotonergic synapse signaling pathway and tryptophan metabolism. REO also modulated the 5-HT2A-mediated extracellular regulated protein kinases-cAMP-response element binding protein-brain-derived neurotrophic factor (ERK-CREB-BDNF) pathway. In addition, molecular docking results indicated that citronellol, geraniol and (E,E)-farnesol in REO may serve as key active ingredients responsible for its antidepressant effects. CONCLUSIONS: This study is the first to report that REO can effectively alleviate CUMS-induced depression-like effects in rats. Additionally, the study offers a comprehensive understanding of its intricate antidepressant mechanism from a multi-omics and multi-level perspective. Our findings hold promise for the clinical application and further development of this essential oil.

Predictive value of machine learning models for lymph node metastasis in gastric cancer: A two-center study.

BACKGROUND: Gastric cancer is one of the most common malignant tumors in the digestive system, ranking sixth in incidence and fourth in mortality worldwide. Since 42.5% of metastatic lymph nodes in gastric cancer belong to nodule type and peripheral type, the application of imaging diagnosis is restricted. AIM: To establish models for predicting the risk of lymph node metastasis in gastric cancer patients using machine learning (ML) algorithms and to evaluate their predictive performance in clinical practice. METHODS: Data of a total of 369 patients who underwent radical gastrectomy at the Department of General Surgery of Affiliated Hospital of Xuzhou Medical University (Xuzhou, China) from March 2016 to November 2019 were collected and retrospectively analyzed as the training group. In addition, data of 123 patients who underwent radical gastrectomy at the Department of General Surgery of Jining First People's Hospital (Jining, China) were collected and analyzed as the verification group. Seven ML models, including decision tree, random forest, support vector machine (SVM), gradient boosting machine, naive Bayes, neural network, and logistic regression, were developed to evaluate the occurrence of lymph node metastasis in patients with gastric cancer. The ML models were established following ten cross-validation iterations using the training dataset, and subsequently, each model was assessed using the test dataset. The models' performance was evaluated by comparing the area under the receiver operating characteristic curve of each model. RESULTS: Among the seven ML models, except for SVM, the other ones exhibited higher accuracy and reliability, and the influences of various risk factors on the models are intuitive. CONCLUSION: The ML models developed exhibit strong predictive capabilities for lymph node metastasis in gastric cancer, which can aid in personalized clinical diagnosis and treatment.

ATP homeostasis and signaling in plants.

ATP is the primary form of energy for plants, and a shortage of cellular ATP is generally acknowledged to pose a threat to plant growth and development, stress resistance, and crop quality. The overall metabolic processes that contribute to the ATP pool, from production, dissipation, and transport to elimination, have been studied extensively. Considerable evidence has revealed that in addition to its role in energy supply, ATP also acts as a regulatory signaling molecule to activate global metabolic responses. Identification of the eATP receptor DORN1 contributed to a better understanding of how plants cope with disruption of ATP homeostasis and of the key points at which ATP signaling pathways intersect in cells or whole organisms. The functions of SnRK1α, the master regulator of the energy management network, in restoring the equilibrium of the ATP pool have been demonstrated, and the vast and complex metabolic network mediated by SnRK1α to adapt to fluctuating environments has been characterized. This paper reviews recent advances in understanding the regulatory control of the cellular ATP pool and discusses possible interactions among key regulators of ATP-pool homeostasis and crosstalk between iATP/eATP signaling pathways. Perception of ATP deficit and modulation of cellular ATP homeostasis mediated by SnRK1α in plants are discussed at the physiological and molecular levels. Finally, we suggest future research directions for modulation of plant cellular ATP homeostasis.

Comparison of Machine Learning and Logic Regression Algorithms for Predicting Lymph Node Metastasis in Patients with Gastric Cancer: A two-Center Study.

OBJECTIVES: This two-center study aimed to establish a model for predicting the risk of lymph node metastasis in gastric cancer patients using machine learning (ML) and logistic regression (LR) algorithms, and to evaluate its predictive performance in clinical practice. METHODS: Data of a total of 369 patients who underwent radical gastrectomy in the Department of General Surgery of Affiliated Hospital of Xuzhou Medical University (Xuzhou, China) from March 2016 to November 2019 were collected and retrospectively analyzed as the training group. In addition, data of 123 patients who underwent radical gastrectomy in the Department of General Surgery of Jining First People's Hospital (Jining, China) were collected and analyzed as the verification group. Besides, 7 ML and logistic models were developed, including decision tree, random forest, support vector machine (SVM), gradient boosting machine (GBM), naive Bayes, neural network, and LR, in order to evaluate the occurrence of lymph node metastasis in patients with gastric cancer. The ML model was established following 10 cross-validation iterations within the training dataset, and subsequently, each model was assessed using the test dataset. The model's performance was evaluated by comparing the area under the receiver operating characteristic curve of each model. RESULTS: Compared with the traditional logistic model, among the 7 ML algorithms, except for SVM, the other models exhibited higher accuracy and reliability, and the influences of various risk factors on the model were more intuitive. CONCLUSION: For the prediction of lymph node metastasis in gastric cancer patients, the ML algorithm outperformed traditional LR, and the GBM algorithm exhibited the most robust predictive capability.

Basis with RNA-Seq and WGCNA to explore the effect of Frankincense essential oil on dextran sodium sulfate-induced ulcerative colitis through MAPK/NF-κB signaling.

PURPOSE: Frankincense has been shown in studies to have healing benefits for people with ulcerative colitis (UC). However, its underlying mechanisms have not been fully investigated. The objective of this study was to explore the potential molecular mechanisms of Frankincense essential oil (FREO) in improving dextran sodium sulfate (DSS)-induced UC from multiple perspectives. METHODS: The FREO components were analyzed by GC-MS, and the interactions between the key active components and the mechanism of FREO were determined based on RNA-seq, "quantity-effect" weighting coefficient network pharmacology, WGCNA and pharmacodynamic experiments. The protection of FREO against DSS-induced UC mice was assessed by behavioral and pathological changes through mice. The expression of pro-inflammatory cytokines was measured using enzyme-linked immunosorbent assay. The expression of MAPK and NF-κB-related proteins by the Western Blotting and immunohistochemistry method. RESULTS: Treatment with FREO significantly improved the symptoms of weight loss, diarrhea, stool blood, and colon shortening in UC mice. Reduced intestinal mucosal damage and the degree of inflammatory cell infiltration in the colon. Decreased TNF-α and IL-6 levels in mice's serum and inhibited phosphorylation of ERK, p65 in MAPK and NF-κB signaling. CONCLUSION: FREO may decrease the inflammatory response to reduce the symptoms of UC by modulating the MAPK/ NF-κB pathway. This may be due to the synergistic interaction of the effective ingredient Hepten-2-yl tiglate, 6-methyl-5-, Isoneocembrene A and P-Cymene. This study provides a promising drug candidate and a new concept for the treatment of UC.

Effects of insecticidal proteins of Enterobacter cloacae NK on cellular immunity of Galleria mellonella larvae.

Enterobacter cloacae produces insecticidal proteins capable of causing toxicity in pests, but the insecticidal mechanisms of these proteins for insect control remain unclear. To elucidate the mechanisms, the purified insecticidal protein from E. cloacae NK was administered to Galleria mellonella larvae either by intraperitoneal injection or by feeding. The number of hemocytes, apoptosis in immune cells, and polyphenol oxidase (PO) activity of G. mellonella larvae were detected by hemocytometer, Annexin V-FITC/PI, and UV-vis spectrophotometer, respectively. With the extension of the invasion time of NK insecticidal protein, the number of hemocytes in G. mellonella larvae decreased significantly (p < 0.05), whereas the apoptosis rate of hemocytes increased. The activity of PO showed a trend of rising-peak-sharp decline and the melanization reaction was deepened simultaneously. Moreover, the phagocytosis and coating capabilities of hemocytes decreased, and the intraperitoneal injection method was more effective than the feeding method. Taking together, the insecticidal protein of E. cloacae NK inhibits and destroys the cellular immune response of G. mellonella larvae, which suggests an important role in killing the host insect.

CXCL16 Promotes Ly6Chigh Monocyte Infiltration and Impairs Heart Function after Acute Myocardial Infarction.

High CXCL16 levels during acute cardiovascular events increase long-term mortality. However, the mechanistic role of CXCL16 in myocardial infarction (MI) is unknown. Here we investigated the role of CXCL16 in mice with MI injury. CXCL16 deficiency increased the survival of mice after MI injury, and inactivation of CXCL16 resulted in improved cardiac function and decreased infarct size. Hearts from CXCL16 inactive mice exhibited decreased infiltration of Ly6Chigh monocytes. In addition, CXCL16 promoted the macrophage expression of CCL4 and CCL5. Both CCL4 and CCL5 stimulated Ly6Chigh monocyte migration, and CXCL16 inactive mice had a reduced expression of CCL4 and CCL5 in the heart after MI. Mechanistically, CXCL16 promoted CCL4 and CCL5 expression by activating the NF-κB and p38 MAPK signaling pathways. Anti-CXCL16 neutralizing Ab administration inhibited Ly6Chigh monocyte infiltration and improved cardiac function after MI. Additionally, anti-CCL4 and anti-CCL5 neutralizing Ab administration inhibited Ly6Chigh monocyte infiltration and improved cardiac function after MI. Thus, CXCL16 aggravated cardiac injury in MI mice by facilitating Ly6Chigh monocyte infiltration.

Comparative Efficacy of Secukinumab Versus Tumor Necrosis Factor Inhibitors for the Treatment of Takayasu Arteritis.

OBJECTIVE: Tumor necrosis factor (TNF) alpha and interleukin-17 (IL-17) are thought to be involved in the pathogenesis of Takayasu arteritis (TAK), and TNF inhibitors (TNFi) are recommended for the treatment of TAK. The present study was undertaken to investigate the efficacy of secukinumab, an IL-17A monoclonal antibody, compared to treatment with TNFi. METHODS: This was a prospective, single-center, open-label cohort study. Patients with active TAK who did not respond to treatment with glucocorticoids combined with 2 immunosuppressive agents were treated with either secukinumab or TNFi as an add-on therapy without an increased dosage of glucocorticoids. A complete response was defined as complete resolution of signs and symptoms of active disease, normal values of inflammatory markers, no progression on imaging of involved arteries, and dose of glucocorticoid <15 mg/day. A partial response was similarly defined as a complete response except with an erythrocyte sedimentation rate <40 mm/hour and C-reactive protein level of <20 mg/liter. RESULTS: Nineteen patients in the secukinumab group and 34 patients in the TNFi group were enrolled. The demographic data and inflammatory markers of the 2 groups were comparable at baseline. Complete response and partial response for patients treated with secukinumab and TNFi were 31.6% and 58.8% (P = 0.057), respectively, at 3 months and 52.6% and 64.7%, respectively, at 6 months (P = 0.389). CONCLUSION: Our findings suggest that secukinumab and TNFi are effective for patients with TAK who do not respond to oral glucocorticoids and conventional immunosuppressive agents, with similar response rates at 3 and 6 months.

Pathogenic antibody response to glucose-6-phosphate isomerase targets a modified epitope uniquely exposed on joint cartilage.

OBJECTIVES: To identify the arthritogenic B cell epitopes of glucose-6-phosphate isomerase (GPI) and their association with rheumatoid arthritis (RA). METHODS: IgG response towards a library of GPI peptides in patients with early RA, pre-symptomatic individuals and population controls, as well as in mice, were tested by bead-based multiplex immunoassays and ELISA. Monoclonal IgG were generated, and the binding specificity and affinity were determined by ELISA, gel size exclusion chromatography, surface plasma resonance and X-ray crystallography. Arthritogenicity was investigated by passive transfer experiments. Antigen-specific B cells were identified by peptide tetramer staining. RESULTS: Peptide GPI293-307 was the dominant B cell epitope in K/BxN and GPI-immunised mice. We could detect B cells and low levels of IgM antibodies binding the GPI293-307 epitopes, and high affinity anti-GPI293-307 IgG antibodies already 7 days after GPI immunisation, immediately before arthritis onset. Transfer of anti-GPI293-307 IgG antibodies induced arthritis in mice. Moreover, anti-GPI293-307 IgG antibodies were more frequent in individuals prior to RA onset (19%) than in controls (7.5%). GPI293-307-specific antibodies were associated with radiographic joint damage. Crystal structures of the Fab-peptide complex revealed that this epitope is not exposed in native GPI but requires conformational change of the protein in inflamed joint for effective recognition by anti-GPI293-307 antibodies. CONCLUSIONS: We have identified the major pathogenic B cell epitope of the RA-associated autoantigen GPI, at position 293-307, exposed only on structurally modified GPI on the cartilage surface. B cells to this neo-epitope escape tolerance and could potentially play a role in the pathogenesis of RA.

The trace that is valuable: serum copper and copper to zinc ratio for survival prediction in younger patients with newly diagnosed acute myeloid leukaemia.

PURPOSE: No data on predicting the survival of AML patients based on the level of trace elements in the serum have been presented to date. The aims of this prospective cohort study were as follows: (i) to evaluate the serum Cu and Zn levels in people from Northeast China, (ii) to assess the association between the serum Cu level (SCL) and Cu to Zn ratio (SCZR) and clinical and nutrition data, and (iii) to investigate the predictive values of the SCL and SCZR in newly diagnosed de novo AML patients. METHODS: A total of 105 newly diagnosed AML patients and 82 healthy controls were recruited. The serum Cu and Zn levels were determined by inductively coupled plasma spectrometry. The associations of SCL and SCZR with the survival of these AML patients were assessed by Cox proportional hazards models. RESULTS: Both SCL and SCZR were positively related to the blast percentage of bone marrow and C-reactive protein, negatively related to albumin level and CEBPA double mutation and were significantly associated with worse overall survival and disease-free survival. Meanwhile, patients with higher SCL had worse CTCAE levels, and patients with higher SCZR showed less complete remission during the first course of induction chemotherapy. Moreover, higher SCZR was positively associated with ELN risk stratification, and was negatively associated with haemoglobin level and prognostic nutritional index (PNI). CONCLUSION: The SCL and SCZR are associated with long-term survival in patients with newly diagnosed AML undergoing intensive induction and may serve as important predictive biomarkers.

Anaemia can be improved by controlling the disease activity of Takayasu's arteritis without iron administration.

BACKGROUND: Anaemia is a common clinical manifestation observed in Takayasu's arteritis (TAK), but few studies have been conducted. This study investigated whether improvement of inflammatory indicators was associated with improvement of anaemia in TAK. We also investigated whether iron supplement treatment could benefit in addition to immunosuppressant therapy in the anaemia patients with TAK. METHODS: This was a retrospective cohort study of 160 patients diagnosed with TAK. All patients were further assigned into anaemia group (67 cases) or non-anaemia group (93 cases) according to their haemoglobin levels. Fifty two anaemia patients completed follow-up (median 5.2 months). RESULTS: There were 67 (41.88%) anaemia patients among all 160 TAK patients. Compared to TAK patients without anaemia, the average age [32 (24, 45) vs. 40 (31, 48), p = 0.002], disease duration [36 (7, 120) vs. 72 (14, 162), p = 0.017] and BMI [21.43 (18.96, 23.81) vs. 22.86 (20.09, 25.81), p = 0.008] were significantly lower in TAK patients with anaemia. The levels of ESR [23 (15, 51) vs. 11 (5.5, 22), p = 0.0001] and CRP [9.33 (1.99, 27.8) vs. 1.99 (0.45, 6.68), p = 0.0001] were significantly increased in TAK patients who complicated with anaemia. After follow-up, decrease of ESR, CRP and disease activity score (NIH and ITAS) were significantly associated with improvement of anaemia. One unit decrease of ESR and CRP, the hazard ratio of the improvement rate of anaemia was 1.02 [95% CI (1.00, 1.03); p = 0.027] and 1.04 [95% CI (1.02, 1.07); p < 0.001] respectively. One point decrease of NIH and ITAS-A was associated with a higher probability of anaemia improvement [HR 95% CI: 1.25 (1.02, 1.41), p = 0.022, HR 95% CI: 1.62 (1.21, 2.17), p = 0.001]. These relationships were consistent between iron supplement treatment group and without iron supplement treatment group. We found no significant difference in cumulative hazard between the two groups (p = 0.692). CONCLUSION: Anaemia was a common complication in TAK. Decrease of ESR, CRP and disease activity score (NIH and ITAS) were significantly associated with improvement of anaemia, even after adjusting for various covariates. Moreover, these relationships were consistent between iron supplement treatment group and without iron supplement treatment group. There was no significant difference in the improvement of anaemia in patients receiving immunosuppressant therapy with or without iron supplement treatment.

Differential tissue expression of sex steroid-synthesizing enzyme CYP11A1 in male Tibetan sheep (Ovis aries).

Steroid metabolism is a fundament to testicular development and function. The cytochrome P450, family 11, subfamily A, polypeptide 1 (CYP11A1) is a key rate-limiting enzyme for catalyzing the conversion of cholesterol to pregnenolone. However, despite its importance, what expression and roles of CYP11A1 possesses and how it regulates the testicular development and spermatogenesis in Tibetan sheep remains largely unknown. Based on this, we evaluated the expression and localization patterns of CYP11A1 in testes and epididymides of Tibetan sheep at three developmental stages (three-month-old, pre-puberty; one-year-old, sexual maturity and three-year-old, adult) by quantitative real-time PCR (qPCR), western blot and immunofluorescence. The results showed that CYP11A1 mRNA and protein were expressed in testes and epididymides throughout the development stages and obviously more intense in one- and three-year-old groups than three-month-old group (except for the caput epididymidis). Immunofluorescence assay showed that the CYP11A1 protein was mainly located in Leydig cells and epididymal epithelial cells. In addition, positive signals of CYP11A1 protein were observed in germ cells, epididymal connective tissue and sperms stored in the epididymal lumen. Collectively, these results suggested that the CYP11A1 gene might be mainly involved in regulating spermatogenesis and androgen synthesis in developmental Tibetan sheep testis and epididymis.

Involvement of miRNAs-mediated senescence and salicylic acid defense in postharvest litchi downy blight.

Litchi downy blight, caused by Peronophythora litchii, results in decline of market value of litchi fruit. In this study, roles of microRNAs (miRNAs) in regulating litchi fruit response to P. litchii infection was investigated. Results showed that P. litchii infection decreased anthocyanin content while accelerating fruit senescence. Salicylic acid (SA) content was also altered by P. litchii infection. Meanwhile, expression levels of LcmiR159, LcmiR828, LcmiR160 and LcmiR167 were investigated using stem-loop real-time quantitative PCR (RT-qPCR). Then, we identified LcGAMYB, LcTT2, LcARF18 and LcARF8 as their target genes, respectively, based on RNA Ligase-Mediated (RLM)-5'-RACE, transient co-expression assay in Nicotiana benthamiana as well as expression change of target genes. Our results suggested that LcmiR159-LcGAMYB and LcmiR828-LcTT2 modules participated in litchi downy blight possibly through regulating fruit senescence while LcmiR160-LcARF18 and LcmiR167-LcARF8 through SA-mediated defense response. This study provides new knowledge on deployment of miRNAs to increase litchi fruit resistance against fungal disease.

Transcriptome analysis provides insights into light condition effect on paclitaxel biosynthesis in yew saplings.

BACKGROUND: Taxus is a rare gymnosperm plant that is the sole producer of the anticancer drug paclitaxel. The growth and development of Taxus is affected by environmental factors such as light. However, little is known about how light conditions affect growth and metabolic processes, especially paclitaxel biosynthesis. RESULTS: In this study, we applied three different light conditions to Taxus chinensis young saplings and investigated the physiological response and gene expression. Our observations showed that exposure to high light led to oxidative stress, caused photoinhibition, and damaged the photosynthetic systems in T. chinensis. The paclitaxel content in T. chinensis leaves was significantly decreased after the light intensity increased. Transcriptomic analysis revealed that numerous genes involved in paclitaxel biosynthesis and phenylpropanoid metabolic pathways were downregulated under high light. We also analyzed the expression of JA signaling genes, bHLH, MYB, AP2/ERF transcription factors, and the CYP450 families that are potentially related to paclitaxel biosynthesis. We found that several CYP450s, MYB and AP2/ERF genes were induced by high light. These genes may play an important role in tolerance to excessive light or heat stress in T. chinensis. CONCLUSIONS: Our study elucidates the molecular mechanism of the effects of light conditions on the growth and development of T. chinensis and paclitaxel biosynthesis, thus facilitating the artificial regeneration of Taxus and enhancing paclitaxel production.

The 8p11 myeloproliferative syndrome: Genotypic and phenotypic classification and targeted therapy.

EMS(8p11 myeloproliferative syndrome, EMS) is an aggressive hematological neoplasm with/without eosinophilia caused by a rearrangement of the FGFR1 gene at 8p11-12. It was found that all cases carry chromosome abnormalities at the molecular level, not only the previously reported chromosome translocation and insertion but also a chromosome inversion. These abnormalities produced 17 FGFR1 fusion genes, of which the most common partner genes are ZNF198 on 13q11-12 and BCR of 22q11.2. The clinical manifestations can develop into AML (acute myeloid leukemia), T-LBL (T-cell lymphoblastic lymphoma), CML (chronic myeloid leukemia), CMML (chronic monomyelocytic leukemia), or mixed phenotype acute leukemia (MPAL). Most patients are resistant to traditional chemotherapy, and a minority of patients achieve long-term clinical remission after stem cell transplantation. Recently, the therapeutic effect of targeted tyrosine kinase inhibitors (such as pemigatinib and infigratinib) in 8p11 has been confirmed in vitro and clinical trials. The TKIs may become an 8p11 treatment option as an alternative to hematopoietic stem cell transplantation, which is worthy of further study.

Fermentation of rose residue by Lactiplantibacillus plantarum B7 and Bacillus subtilis natto promotes polyphenol content and beneficial bioactivity.

The present study evaluated the effect of fermentation with Lactiplantibacillus plantarum B7 and Bacillus subtilis natto on phenolic compound levels and enzyme activity, as well as antioxidant capacity of the rose residue. Results showed that the polyphenol content of rose residue was significantly increased from 16.37 ± 1.51 mg/100 mL to 41.02 ± 1.68 mg/100 mL by fermentation at 37 °C and 2.0% (v/v) inoculum size for 40 h. The flavone, soluble dietary, and protein contents were also enhanced by almost 1-fold, 3-fold, and 1-fold, respectively. Fifteen phenolic compounds were quantified in the fermented broth, among which the concentration of gallic acid, quercetin, and p-coumaric acid increased by 5-fold, 4-fold, and almost 8-fold, respectively. Chlorogenic acid was a new phenolic compound produced during fermentation. Moreover, the fermented rose residue presented higher superoxide dismutase, α-amylase, and protease activity. ABTS•+, hydroxylradical, and DPPH• scavenging activity increased by 60.93%, 57.70%, and 37.00%, respectively. This provides an effective means of transforming rose residue into a highly bioactive value-added substance.

Valerian essential oil for treating insomnia via the serotonergic synapse pathway.

Valerian volatile oil can be used in the treatment of insomnia; however, the active components and mechanisms of action are currently unclear. Therefore, we used transcriptome sequencing and weight coefficient network pharmacology to predict the effective components and mechanism of action of valerian volatile oil in an insomnia model induced by intraperitoneal injection of para-Chlorophenylalanine (PCPA) in SD rats. Valerian essential oil was given orally for treatment and the contents of 5-hydroxytryptamine receptor 1 A (5-HT1AR), γ-aminobutyric acid (GABA), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA) in the hippocampus of rats in each group were detected by enzyme-linked immunosorbent assay (ELISA), western blot, Polymerase Chain Reaction (PCR), and immunohistochemistry. The results showed that after treatment with valerian essential oil, insomnia rats showed significantly prolonged sleep duration and alleviated insomnia-induced tension and anxiety. Regarding the mechanism of action, we believe that caryophyllene in valerian essential oil upregulates the 5-HT1AR receptor to improve the activity or affinity of the central transmitter 5-HT, increase the release of 5-HT, couple 5-HT with a G protein coupled receptor, convert adenosine triphosphate (ATP) into cAMP (catalyzed by ADCY5), and then directly regulate the downstream pathway. Following pathway activation, we propose that the core gene protein kinase PKA activates the serotonergic synapse signal pathway to increase the expression of 5-HT and GABA, thus improving insomnia symptoms and alleviating anxiety. This study provides a theoretical basis for the application of valerian volatile oil in health food.

Study of the Mechanism of Antiemetic Effect of Lavandula angustifolia Mill. Essential Oil Based on Ca2+/CaMKII/ERK1/2 Pathway.

Purpose: To investigate the effective components and possible mechanism of action of Lavandula angustifolia Mill. essential oil (LEO) in preventing vomiting through the olfactory pathway. Materials and Methods: A new network pharmacology-based method was established to analyze main components and pathways of LEO involved in antiemetic effects by introducing component content; biological activities of key proteins of the olfactory pathway and their corresponding compounds were verified by molecular docking technique; and finally pica in a rat model was established to verify the molecular mechanism of antiemetic effects of LEO by enzyme-linked immunosorbent assay (ELISA) to determine the serum 5-HT, substance P, and DA levels in each group and by immunohistochemistry to determine the contents of 5-HT3R, CaMKII and ERK1/2 proteins in the medulla oblongata tissue. Results: Network pharmacology combined with molecular docking analysis showed that the mechanism of the antiemetic effect of LEO may be related to (2Z)-3,7-dimethyl-2,6-octadienyl acetate, linalyl acetate, butanoic acid, hexyl ester, 4-hexen-1-ol, 5-methyl-2-(1-methylethenyl)-, acetate, .tau.-cadinol and other active ingredients, which regulate the cyclic adenosine monophosphate (cAMP) signaling pathway and the expression of BRAF, PDE and other targets on the pathway. An ELISA revealed that LEO reduced the levels of 5-hydroxytryptamine (5-HT), substance P, and dopamine in serum compared with the model group (P <0.05). Immunohistochemical analysis showed that LEO decreased the expression of 5-HT3R, CaMKII, and ERK1/2 proteins in the medulla oblongata of rats compared with the model group (P <0.01). Conclusion: LEO may achieve the antiemetic effect by reducing the content of 5-HT and inhibiting its related receptors, thereby regulating downstream Ca2+/CaMKII/ERK1/2 pathway of the cAMP signaling pathway.