Integrative physiology and transcriptome reveal salt-tolerance differences between two licorice species: Ion transport, Casparian strip formation and flavonoids biosynthesis.

BACKGROUND: Glycyrrhiza inflata Bat. and Glycyrrhiza uralensis Fisch. are both original plants of 'Gan Cao' in the Chinese Pharmacopoeia, and G. uralensis is currently the mainstream variety of licorice and has a long history of use in traditional Chinese medicine. Both of these species have shown some degree of tolerance to salinity, G. inflata exhibits higher salt tolerance than G. uralensis and can grow on saline meadow soils and crusty saline soils. However, the regulatory mechanism responsible for the differences in salt tolerance between different licorice species is unclear. Due to land area-related limitations, the excavation and cultivation of licorice varieties in saline-alkaline areas that both exhibit tolerance to salt and contain highly efficient active substances are needed. The systematic identification of the key genes and pathways associated with the differences in salt tolerance between these two licorice species will be beneficial for cultivating high-quality salt-tolerant licorice G. uralensis plant varieties and for the long-term development of the licorice industry. In this research, the differences in growth response indicators, ion accumulation, and transcription expression between the two licorice species were analyzed. RESULTS: This research included a comprehensive comparison of growth response indicators, including biomass, malondialdehyde (MDA) levels, and total flavonoids content, between two distinct licorice species and an analysis of their ion content and transcriptome expression. In contrast to the result found for G. uralensis, the salt treatment of G. inflata ensured the stable accumulation of biomass and total flavonoids at 0.5 d, 15 d, and 30 d and the restriction of Na+ to the roots while allowing for more K+ and Ca2+ accumulation. Notably, despite the increase in the Na+ concentration in the roots, the MDA concentration remained low. Transcriptome analysis revealed that the regulatory effects of growth and ion transport on the two licorice species were strongly correlated with the following pathways and relevant DEGs: the TCA cycle, the pentose phosphate pathway, and the photosynthetic carbon fixation pathway involved in carbon metabolism; Casparian strip formation (lignin oxidation and translocation, suberin formation) in response to Na+; K+ and Ca2+ translocation, organic solute synthesis (arginine, polyamines, GABA) in response to osmotic stresses; and the biosynthesis of the nonenzymatic antioxidants carotenoids and flavonoids in response to antioxidant stress. Furthermore, the differential expression of the DEGs related to ABA signaling in hormone transduction and the regulation of transcription factors such as the HSF and GRAS families may be associated with the remarkable salt tolerance of G. inflata. CONCLUSION: Compared with G. uralensis, G. inflata exhibits greater salt tolerance, which is primarily attributable to factors related to carbon metabolism, endodermal barrier formation and development, K+ and Ca2+ transport, biosynthesis of carotenoids and flavonoids, and regulation of signal transduction pathways and salt-responsive transcription factors. The formation of the Casparian strip, especially the transport and oxidation of lignin precursors, is likely the primary reason for the markedly higher amount of Na+ in the roots of G. inflata than in those of G. uralensis. The tendency of G. inflata to maintain low MDA levels in its roots under such conditions is closely related to the biosynthesis of flavonoids and carotenoids and the maintenance of the osmotic balance in roots by the absorption of more K+ and Ca2+ to meet growth needs. These findings may provide new insights for developing and cultivating G. uralensis plant species selected for cultivation in saline environments or soils managed through agronomic practices that involve the use of water with a high salt content.

Cyaonoside A-loaded composite hydrogel microspheres to treat osteoarthritis by relieving chondrocyte inflammation.

Cyaonoside A (CyA), derived from the natural Chinese medicine, Cyathula officinalis Kuan, which was for a long time used to treat knee injuries and relieve joint pain in traditional Chinese medicine, showed an unclear mechanism for protecting cartilage. In addition, CyA was poorly hydrosoluble and incapable of being injected directly into the joint cavity, which limited its clinical application. This study reveals that CyA resisted IL-1ß-mediated chondrogenic inflammation and apoptosis. Next, transcriptome sequencing is used to explore the potential mechanisms underlying CyA regulation of MSC chondrogenic differentiation. Based on these findings, CyA-loaded composite hydrogel microspheres (HLC) were developed and they possessed satisfactory loading efficiency, a suitable degradation rate and good biocompatibility. HLC increased chondrogenic anabolic gene (Acan, COL2A, and SOX9) expression, while downregulating the expression of the catabolic marker MMP13 in vitro. In the osteoarthritis mouse model, HLC demonstrated promising therapeutic capabilities by protecting the integrity of articular cartilage. In conclusion, this study provides insights into the regulatory mechanisms of CyA for chondrocytes and proposes a composite hydrogel microsphere-based advanced therapeutic strategy for osteoarthritis.

Enhanced Knowledge Distillation for Advanced Recognition of Chinese Herbal Medicine.

The identification and classification of traditional Chinese herbal medicines demand significant time and expertise. We propose the dual-teacher supervised decay (DTSD) approach, an enhancement for Chinese herbal medicine recognition utilizing a refined knowledge distillation model. The DTSD method refines output soft labels, adapts attenuation parameters, and employs a dynamic combination loss in the teacher model. Implemented on the lightweight MobileNet_v3 network, the methodology is deployed successfully in a mobile application. Experimental results reveal that incorporating the exponential warmup learning rate reduction strategy during training optimizes the knowledge distillation model, achieving an average classification accuracy of 98.60% for 10 types of Chinese herbal medicine images. The model boasts an average detection time of 0.0172 s per image, with a compressed size of 10 MB. Comparative experiments demonstrate the superior performance of our refined model over DenseNet121, ResNet50_vd, Xception65, and EfficientNetB1. This refined model not only introduces an approach to Chinese herbal medicine image recognition but also provides a practical solution for lightweight models in mobile applications.

Green Starch-Based Hydrogels with Excellent Injectability, Self-Healing, Adhesion, Photothermal Effect, and Antibacterial Activity for Promoting Wound Healing.

Hydrogel materials have proven valuable in wound healing, but improving the safety of these hydrogels is still challenging. Therefore, designing multifunctional natural polymeric-based hydrogels with excellent mechanical properties to replace toxic or potentially risky, refractory chemical polymer-based hydrogels such as polyacrylamide and polyethylene glycol is of particular significance. Here, a green starch-based hydrogel (Starch@Ca/CGC hydrogel) with injectability, self-healing, and instant adhesion was constructed by coordination interaction, electrostatic interaction, and intramolecular and intermolecular hydrogen bonds. Therein, natural bioactive small molecules gallic acid (GA) and carvacrol (CA) were coordinated with metal ions by the ultrasonic-triggered self-assembly and ionic cross-linking codriven strategy to prepare Cu-gallic acid-carvacrol nanospheres (CGC NPs), which conferred the hydrogel with near-infrared light (NIR)-controlled CA release and photothermal synergistic sterilization properties, as well as antioxidant and anti-infection capabilities. More importantly, the multifunctional hydrogel platforms could completely cover an irregular wound shape to prevent secondary injury and significantly accelerate wound healing under NIR with more skin appendages like hair follicles and blood vessels appearing. Therefore, it is expected that this starch-based hydrogel could serve as a competitive multifunctional dressing in the biomedical field, including bacteria-derived wound infection and other tissue repair.

A Bilayer Microneedle for Modulated Sequential Release of Adrenaline and Lidocaine for Prolonged Local Anesthesia.

Chronic pain emerges as a major global health issue, significantly impacting individuals' health and quality of life. In this study, we designed a bilayer microneedle loaded with lidocaine nanocomposites in the inner layer and adrenaline (Adr) in the outer layer (HCP MNs) for modulated sequential release to achieve prolonged local anesthesia. The obtained HCP MNs featured an intact structure with adequate mechanical strength for efficient skin penetration. The bilayer structure of MNs was evidenced by loading two fluorescent dyes in each layer. Furthermore, these HCP MNs were capable of inducing rapid as well as prolonged local anesthetic effects in guinea pigs. Hence, the bilayer MN coloaded with Adr and lidocaine nanocomposite serves as a promising transdermal delivery platform for chronic pain management.

The Causal Association between Alcohol, Smoking, Coffee Consumption, and the Risk of Arthritis: A Meta-Analysis of Mendelian Randomization Studies.

Objective: To evaluate the genetic causality between alcohol intake, smoking, coffee consumption, and arthritis. Methods: Mendelian randomization (MR) studies with alcohol, smoking, and coffee consumption behaviors as exposures, and osteoarthritis (OA) and rheumatoid arthritis (RA) as outcomes were retrieved from up to July 2023. Two researchers with relevant professional backgrounds independently assessed the quality and extracted data from the included studies. Meanwhile, we applied MR analyses of four lifestyle exposures and five arthritis outcomes (two for OA and three for RA) with gene-wide association study (GWAS) data that were different from the included studies, and the results were also included in the meta-analysis. Statistical analyses were performed using Stata 16.0 and R software version 4.3.1. Results: A total of 84 studies were assessed. Of these, 11 were selected for meta-analysis. As a whole, the included studies were considered to be at a low risk of bias and were of high quality. Results of the meta-analysis showed no significant genetic causality between alcohol intake and arthritis (odds ratio (OR): 1.02 (0.94-1.11)). Smoking and arthritis had a positive genetic causal association (OR: 1.44 (1.27-1.64)) with both OA (1.44 (1.22-1.71)) and RA (1.37 (1.26-1.50)). Coffee consumption and arthritis also had a positive genetic causal association (OR: 1.02 (1.01-1.03)). Results from the subgroup analysis showed a positive genetic causality between coffee consumption and both OA (OR: 1.02 (1.00-1.03)) and RA (OR: 1.56 (1.19-2.05)). Conclusion: There is positive genetic causality between smoking and coffee consumption and arthritis (OA and RA), while there is insufficient evidence for genetic causality between alcohol intake and arthritis.

Therapeutic effects of low-color-temperature light-emitting diodes on dry eye.

BACKGROUND: As a new technology for treating dry eye diseases, phototherapy has attracted great attention, but the research on its safety and effectiveness is limited. In this study, the therapeutic effects of low-color-temperature light-emitting diodes on dry eye in humans, rabbits, and rats were investigated. METHODS: In clinical experiments, subjects in both groups read the same paper for 3 h under light sources of two color temperatures: 1900 K (low-color-temperature light-emitting diodes) or 4000 K (artificial fluorescent white light-emitting diodes). The differences in the non-invasive tear film breakup time, tear meniscus height, and conjunctival congestion scores before and after the experiment were compared between the two groups. In animal experiments, corneal epithelial barrier function and tear production of Sprague-Dawley rats and New Zealand white rabbits with dry eye were compared before and after low-color-temperature light-emitting diodes treatment. TUNEL staining and Western blotting were used to detect the apoptosis of corneal and conjunctival cells and the expression of inflammatory factor IL-1ß. RESULTS: Low-color-temperature light-emitting diodes prolonged tear film breakup time in patients with dry eye. Moreover, it increased tear secretion, decreased fluorescein sodium staining scores, corneal and conjunctival cell apoptosis, and inflammatory factor expression in rabbits and rats with dry eye. CONCLUSIONS: Low-color-temperature light-emitting diodes phototherapy can be used as an effective treatment for dry eye, reducing its symptoms and related ocular surface damage in humans, rabbits, and rats.

Lycium ruthenicum Murr. anthocyanins inhibit hyperproliferation of synovial fibroblasts from rheumatoid patients and the mechanism study powered by network pharmacology.

BACKGROUND: Rheumatoid arthritis (RA), is a typical autoimmune disease affecting nearly 1% of the world's population. The dysfunctional hyperproliferation of synovial fibroblast (SF) in articular cartilage of RA patients is considered as the essential etiology. Traditional chemotherapeutic agents for RA treatment are imperfect for their high cost and unpredictable side-effects. L. ruthenicum anthocyanins (LRAC) is a natural product that of potential for therapeutic application against RA. METHODS: LRAC was characterized by UPLC-MS/MS. Bioinformatics analyses based on network pharmacology were applied to predict the potential targets of LRAC, and to select DEGs (differentially expressed genes) caused by RA pathogenesis from GSE77298. Interactions between LRAC and the predicted targets were evaluated by molecular docking. Effects of LRAC on SFs from RA patients were examined by in vitro assays, which were analyzed by flow cytometry and western blotting (WB). RESULTS: LRAC was able to inhibit the abnormal proliferation and aggressive invasion of SFs from RA patients. LRAC was mainly constituted by petunidin (82.7%), with small amount of delphinidin (12.9%) and malvidin (4.4%) in terms of anthocyanidin. Bioinformatics analyses showed that in 3738 RA-related DEGs, 58 of them were collectively targeted by delphinidin, malvidin and delphinidin. AR, CDK2, CHEK1, HIF1A, CXCR4, MMP2 and MMP9, the seven hub genes constructed a central network mediating the signal transduction. Molecular docking confirmed the high affinities between the LRAC ligands and the protein receptors encoded by the hub genes. The in vitro assays validated that LRAC repressed the growth of RASF by cell cycle arresting and cell invasion paralyzing (c-Myc/p21/CDK2), initiating cell apoptosis (HIF-1α/CXCR4/Bax/Bcl-2), and inducing pyroptosis via ROS-dependent pathway (NOX4/ROS/NLRP3/IL-1ß/Caspase-1). CONCLUSION: LRAC can selectively inhibit the proliferation of RASFs, without side-effecting immunosuppression that usually occurred for RA treatment using MTX (methotrexate). These findings demonstrate the potential application of LRAC as a phytomedicine for RA treatment, and provide a valid approach for exploring natural remedies against autoimmune diseases.

Alleviation of D-gal-induced senile liver injury by Rg3, a signature component of red ginseng.

To investigate the mechanism by which ginsenoside Rg3 regulates oxidative stress (OS) and inflammation through NF/KB pathway to delay mouse liver injury. This work randomized Balbc mice as four groups: Normal, D-gal, Rg3-L, Rg3-H. Paraffin-embedded liver tissue sections were prepared, later, BAX/BCL-2 protein expression was observed by HE, Sirius red, TUNEL and immunofluorescence to detect apoptotic injury and α-SMA/TGF-ß protein expression to detect fibrosis, and liver inflammation-related protein NF-KB was detected. HE and TUNEL staining showed that Rg3 reduced necrotic cells and fibrosis in liver-injured mice, Rg3 increased anti-inflammatory cytokine IL-18 and reduced TNF-α, IL-1ß and IL-6 expression. Conclusion: Ginsenoside Rg3 can effectively antagonize D-gal's role in mouse liver injury, and its mechanism may be associated with regulating inflammatory pathway by Rg.

A Multicentre Randomized Controlled Clinical Study of Cross Electro-Nape-Acupuncture (CENA) for the Treatment of Pseudobulbar Palsy in Patients with Tracheotomy Intubation for Severe Cerebral Haemorrhage.

Objective: The objective is to evaluate the clinical efficacy of cross electro-nape-acupuncture (CENA) in the treatment of pseudobulbar palsy in patients with tracheotomy intubation for severe cerebral haemorrhage and to provide an innovative acupuncture method for the treatment of such patients. Methods: A total of 126 patients from six trial centres who met the inclusion criteria were randomly divided into three groups according to the random number table method in the ratio of 1 : 1 : 1, with 42 patients in each group, and the three groups were divided into CENA group, electro-acupuncture group, and acupuncture group. Each group's acupuncture treatment lasted for 30 minutes, and the needles were removed at the end of the treatment. Acupuncture was performed once a week on Sunday only and twice a day from Monday to Saturday, a total of 4 weeks of treatment. The SWT, FDA, ChSWAL-QOL, and TCRGS scores of the three groups of patients before and after treatment were compared to evaluate the effect of CENA on remodelling the function of swallowing reflex and cough reflex and promoting the recovery of dysarthria and swallowing quality of life in pseudobulbar palsy in patients with tracheotomy intubation for severe cerebral haemorrhage. Results: After treatment, the WST and TCRGS grade scores decreased and the FDA and ChSWAL-QOL scores increased significantly in all three groups compared with the pretreatment scores and were statistically significant. There was a significant difference between the three groups for these four indicators after treatment; the comparison between groups showed significant differences in the CENA group compared to the electro-acupuncture and acupuncture groups. The efficiency of the CENA group was significantly better than that of the electro-acupuncture and acupuncture groups. Conclusion: Compared with the acupuncture and electro-acupuncture groups, the CENA could better promote the remodelling of swallowing function and cough reflex function, promote the recovery of dysarthria, and better improve the quality of life of patients with pseudobulbar palsy from tracheotomy intubation in severe cerebral haemorrhage.

Genetic variation in the glycine-rich protein gene BnGRP1 contributes to low phosphorus tolerance in Brassica napus.

Lack of phosphorus (P) is a major environmental factor affecting rapeseed (Brassica napus. L) root growth and development. For breeding purposes, it is crucial to identify the molecular mechanisms underlying root system architecture traits that confer low-P tolerance in rapeseed. Natural variations in the glycine-rich protein gene BnGRP1 were analysed in the natural population of 400 rapeseed cultivars under low-P stress through genome-wide association study and transcriptome analysis. Based on 11 single nucleotide polymorphism mutations in the BnGRP1 sequence, 10 haplotypes (Hap) were formed. Compared with the other types, the cultivar BnGRP1Hap1 in the panel demonstrated the longest root length and heaviest root weight. BnGRP1Hap1 overexpression in rapeseed led to enhanced low-P tolerance. CRISPR/Cas9-derived BnGRP1Hap4 knockout mutations in rapeseed can lead to sensitivity to low-P stress. Furthermore, BnGRP1Hap1 influences the expression of the phosphate transporter 1 gene (PHT1) associated with P absorption. Overall, the findings of this study highlight new insights into the mechanisms of GRP1 enhancement of low-P tolerance in rapeseed.

Compositions analysis and insecticidal activity of Aconitum polycarpum Chang ex W.T.Wang petroleum ether fractions and essential oils.

ETHNOPHARMACOLOGICAL RELEVANCE: The Aconitum genus plants as a natural pesticide for insecticide and rodent control has been recorded in Chinese folk. However, the insecticide effect, mechanism, and active composition of Aconitum polycarpum Chang ex W.T.Wang have not been studied further. AIM OF THE STUDY: This study was designed to analyze the chemical composition, evaluate contact toxicity of petroleum ether extracts (PEEs) and essential oils (EOs) of A. polycarpum, and further explore their possible insecticidal mechanism. MATERIALS AND METHODS: The roots of A. polycarpum were extracted with 90% methanol, and then extracted with petroleum ether to obtain PEEs; the EOs was extracted by distillation. The chemical compositions of PEEs and EOs were analyzed by GC-MS. Contact toxicity was evaluated by the immersion method. Exploring insecticidal mechanisms through in vitro enzyme inhibitory activity. RESULTS: 12 compounds were identified from PEEs by GC-MS, mainly including aliphatic (94.8%), the main compositions were Octadecadienol (ODO) (aliphatic, 53.2%) and L-Ascorbyl dipalmitate (LADP) (aliphatic, 36.1%). 24 compounds were identified in EOs. About 44.6% of the identified components were terpenoids and their derivatives, and the rest were mainly aliphatic (34.7%) and phenols (3.0%). The main chemical components were L (-)-Borneol (LB) (terpenoid, 28.3%), LADP (aliphatic, 19.1%), and Isoborneol (terpenoid, 9.1%). The contact toxicity indicated that the PEEs showed great contact toxicity against Spodoptera exigua (LC50 = 126.2 mg/L). Meanwhile, LADP (LC50 = 128.1 mg/L) and ODO (LC50 = 121.3 mg/L) was similar to that of Cyhalothrin (LC50 = 124.2 mg/L) in contact toxicity. In addition, we found that LADP and ODO exhibited excellent inhibitory activity against CarE (IC50 = 58.0, 56.1 mg/L, respectively) by measuring in vitro enzyme inhibitory activity, which was superior than Cyhalothrin (IC50 = 68.1 mg/L). CONCLUSIONS: The chemical compositions and contact toxicity of EOs and PEEs of A. polycarpum were analyzed and evaluated, and their insecticidal mechanisms were preliminarily discussed for the first time. It proved PEEs of A. polycarpum and its main components (LADP and ODO) exhibited excellent contact toxicity against S. exigua, and CarE was identified as a potential target for contact toxicity. This study indicated that the insecticidal activity of petroleum ether extracts from A. polycarpum is quite promising, and provides a practical and scientific basis for the development and application of botanical pesticides.

Effects of Buyang Huanwu Decoction on Intestinal Barrier, Intestinal Flora, and Trimethylamine Oxide in Rats with Heart Failure.

OBJECTIVE: To explore the mechanisms of Buyang Huanwu Decoction (BYHWD) modulating the gut microbiome and trimethylamine oxide (TAMO) to exert cardioprotective effects. METHODS: Ligation of the left anterior descending coronary artery was performed in rats to induce heart failure (HF). Except for the sham-operation group (n=10), 36 operation-induced models were randomized into 3 groups using a random number table (n=12 in each group): the model group, the BYHWD group (15.02 g/kg BYHWD), and the positive group (4.99 g/kg metoprolol succinate). After 4-week treatment (once daily by gavage), echocardiography was applied to evaluate the cardiac function and the Tei index (the ratio of ventricular isovolumic contraction time (IVCT) and isovolumic diastolic time (IVRT) to ejection time (ET)) was calculated; hematoxylin-eosin (HE) staining was observed to characterize the pathology of the myocardium and small intestinal villi. D-lactic acid was detected by an enzyme-linked immunosorbent assay (ELISA). Expressions of occludin, claudin-1, and zonula occludens (ZO-1) were detected by Western blot. 16S ribosomal ribonucleic acid (16S rRNA) sequencing was used to explore the changes in the intestinal flora. TMAO was detected via liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: In the echocardiography, the Tei index was considerably lower in the positive and BYHWD groups compared with the model group (P<0.05). Besides, BYHWD improved the pathology of myocardium and small intestine of HF rats and lowered the D-lactic acid content in the serum, when compared with the model group (P<0.05). BYHWD also improved the expression of occludin and claudin-1 (P<0.05); in the gut microbiota analysis, BYHWD slowed down modifications in the structure distribution of gut microbiota and regulated the diversity of intestinal flora in HF rats. The content of TMAO in the serum was significantly lowered by BYWHT compared with the model group (P<0.05). CONCLUSION: BYHWD may delay progression of HF by enhancing the intestinal barrier structure, and regulating intestinal flora and TAMO.

Massage of Bladder Meridian Relieved Anxiety Induced by Chronic Stress in Rats.

The aim of this paper was to explore the mechanism of bladder meridian massage (BMM) on anxiety in rats with chronic stress. Chronic stress induced rats to establish rat anxiety model. The sugar water preference (SPF), tail suspension time (TST), and forced swimming time (FST) of rats were measured. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and inflammatory cytokines in serum and hippocampus of rats were detected. Brain neurotransmitters (dopamine (DA), 5- hydroxytryptamine (5-HT), and norepinephrine (NE)) were detected by enzyme-linked immunosorbent assay (ELISA) kits. Immunohistochemistry and western blotting were used to detect autophagy protein expression in hippocampus of rats. BMM significantly increased SPF, decreased TST and FST, increased SOD level in serum and hippocampus, and decreased MDA level and cytokine level. BMM reversed the changes of neurotransmitters. At the same time, BMM significantly decreased autophagy protein expression in hippocampus of rats. The above results show that BMM significantly relieve anxiety induced by chronic stress in rats.

Synergism Between Multi-Pseudomonas and Cutinase for Biodegradation of Crude Oil-Based Derivatives.

Polyethylene terephthalate (PET) as one of the main crude oil-based derivatives, produces a significant amount of waste that is difficult to degrade. Currently, microbial degradation of PET is an eco-friendly, efficient, and economical method. This study was conducted to propose a novel screening strategy for PET-degrading bacteria, and evaluate their degradation efficiency of PET. Two strains, Pseudomonas nitroreducens S8 and Pseudomonas monteilii S17, were isolated and could utilize PET as a carbon source by co-culture. The combined use of both bacteria gave a synergistic effect on the disruption of the PET surface through colonization behavior, which could enhance the subsequent degradation of PET. Its time of reaching a peak value of PET degradation rate (94.5% at 6 d) was 2 days earlier than these of single bacteria. A similar synergistic effect was also observed in the metabolization of PET monomers, and the metabolic rate was expressed as 82.4% of bis (2-hydroxyethyl) terephthalate (BHET), 64.0% of mono (2-hydroxyethyl) terephthalate (MHET), and 20.0% of terephthalic acid (TPA), respectively. This study is novel in showing the degradation of PET waste by combinations of bacterial pretreatment and enzymatic treatment, which can be a promising method.

HDAC2 Induces DNA Methyltransferase DNMT3B Expression to Regulate the Wnt Signaling Pathway and Thus Promotes Glioma Development and Progression.

Purpose: To investigate the role and molecular mechanism of HDAC2 in glioma. Methods: GSE16011, GSE31262, and GSE90598 datasets were used to identify co-expressed genes, GO analysis, and KEGG analysis to identify gene enrichment pathways, and PPI networks were constructed to identify gene interrelationships. HDAC2 enrichment on DNMT3B promoter and DNMT3B enrichment on Bcl2 CpG island was detected by a ChIP assay. The expression, prognosis, and hierarchical distribution of HDAC2, DNMT3B, and Bcl2 were examined in the CGGA database, and the correlation between HDAC2 and DNMT3B, Bcl2, and DNMT3B and Bcl2 was assessed. Results: The HDAC2-DNMT3B-Bcl2 axis is differentially expressed and interacts in gliomas. HDAC2 activates the transcriptional activity of DNMT3B, and DNMT3B inhibits the expression of Bcl2. HDAC2 and DNMT3B are highly expressed in gliomas and have a poor prognosis, while Bcl2 is lowly expressed in gliomas and has a good prognosis. Conclusion: HDAC2 promotes DNMT3B transcriptional repression of Bcl2 expression and Wnt pathway activity, thereby activating glioma cell activity in vitro and in vivo.

Function and therapeutic potential of transient receptor potential ankyrin 1 in fibrosis.

The transient receptor potential (TRP) protein superfamily is a special group of cation channels expressed in different cell types and signaling pathways. In this review, we focus on TRPA1 (transient receptor potential ankyrin 1), an ion channel in this family that exists in the cell membrane and shows a different function from other TRP channels. TRPA1 usually has a special activation effect that can induce cation ions, especially calcium ions, to flow into activated cells. In this paper, we review the role of TRPA1 in fibroblasts. To clarify the relationship between fibroblasts and TRPA1, we have also paid special attention to the interactions between TRPA1 and inflammatory factors leading to fibroblast activation. TRPA1 has different functions in the fibrosis process in different organs, and there have also been interesting discussions of the mechanism of TRPA1 in fibroblasts. Therefore, this review aims to describe the function of TRP channels in controlling fibrosis through fibroblasts in different organ inflammatory and immune-mediated diseases. We attempt to prove that TRPA1 is a target for fibrosis. In fact, some clinical trials have already proven that TRPA1 is a potential adjuvant therapy for treating fibrosis.

Effect of Moxibustion Treatment on Degree Centrality in Patients With Mild Cognitive Impairment: A Resting-State Functional Magnetic Resonance Imaging Study.

Background: Mild cognitive impairment (MCI) is a common neurological disorder. Moxibustion has been shown to be effective in treating MCI, but its therapeutic mechanisms still remain unclear. This study mainly aimed to investigate the modulation effect of moxibustion treatment for patients with MCI by functional magnetic resonance imaging (fMRI). Methods: A total of 47 patients with MCI and 30 healthy controls (HCs) participated in resting-state fMRI imaging (rs-fMRI) scans. Patients with MCI were randomly divided into true moxibustion group (TRUE, n = 30) and sham moxibustion group (SHAM, n = 17). The degree centrality (DC) approach was applied to distinguish altered brain functions. Correlation analysis was then performed to examine the relationships between the neuroimaging findings and clinical symptoms. Results: Compared with HCs, patients with MCI mainly showed decreased DC in the left middle frontal cortex (MFC) and bilateral middle cingulate cortex (MCC). After moxibustion treatment, the SHAM group had no significant DC findings, while TRUE group mainly showed significant increased DC in the bilateral MFC and MCC, as well as decreased DC in the left middle occipital cortex (MOC). Repeated measures analysis of variance (ANOVA) showed significant interactions between the two groups of patients with MCI. In addition, the higher Mini-Mental State Examination (MMSE) score was significantly positively correlated with increased DC in the right MFC and left MCC after moxibustion treatment. Conclusion: Our findings demonstrate that the potential value of moxibustion treatment on MCI, which adds new insights into the popular view that moxibustion treatment may slow cognitive decline in patients with MCI.

Tangeretin Synergizes with 5-Fluorouracil to Induce Autophagy through MicroRNA-21 in Colorectal Cancer Cells.

Combining innocuous natural products with cytotoxic agents may enhance the effectiveness of chemotherapy. Tangeretin is a citrus flavonoid that has antineoplastic properties, but its mechanism of action is still unknown. Here, we used a high throughput-screening (HTS) platform to screen for drugs that may synergize with tangeretin and confirmed the top hits against colorectal cancer (CRC) cells in vitro and in vivo. 5-Fluorouracil (5-FU) and PI3K/Akt inhibitors have come out as top hits that show a strong synergy effect with tangeretin by HTS. We further confirmed the synergistic effect of tangeretin with 5-FU against CRC cells in vitro and in vivo. Since 5-FU can increase microRNA-21 (miR-21) expression and activate PI3K/Akt signaling, we addressed if tangeretin acted at this level. In 5-FU treated cells, tangeretin inhibited miR-21 induction, rescued the expression of the target PTEN, reduced Akt activation, and induced autophagy. Together, our data indicated that a natural product, such as tangeretin, can modulate miR-21 expression and that this pathway might be a potential therapeutic target for CRC. Combining tangeretin with 5-FU may be useful in the clinic, since 5-FU is the current first line drug for treating CRC.

Hypothalamic-related neural mechanism in lifelong premature ejaculation and trends following selective serotonin reuptake inhibitor administration.

Lifelong premature ejaculation patients had altered structural and functional parameters of the hypothalamus compared with healthy controls. The patients showed increased hypothalamus-related functional connectivity in several regions one hour after dapoxetine administration. The changing trends of the brain functional connectivity after dapoxetine administration possibly provided important information about the selective serotonin reuptake inhibitor effects on the functional neural system.