Comprehensive analysis of the laccase gene family in tea plant highlights its roles in development and stress responses.

BACKGROUND: Laccase (LAC) is the pivotal enzyme responsible for the polymerization of monolignols and stress responses in plants. However, the roles of LAC genes in plant development and tolerance to diverse stresses are still largely unknown, especially in tea plant (Camellia sinensis), one of the most economically important crops worldwide. RESULTS: In total, 51 CsLAC genes were identified, they were unevenly distributed on different chromosomes and classified into six groups based on phylogenetic analysis. The CsLAC gene family had diverse intron-exon patterns and a highly conserved motif distribution. Cis-acting elements in the promoter demonstrated that promoter regions of CsLACs encode various elements associated with light, phytohormones, development and stresses. Collinearity analysis identified some orthologous gene pairs in C. sinensis and many paralogous gene pairs among C. sinensis, Arabidopsis and Populus. Tissue-specific expression profiles revealed that the majority of CsLACs had high expression in roots and stems and some members had specific expression patterns in other tissues, and the expression patterns of six genes by qRT‒PCR were highly consistent with the transcriptome data. Most CsLACs showed significant variation in their expression level under abiotic (cold and drought) and biotic (insect and fungus) stresses via transcriptome data. Among them, CsLAC3 was localized in the plasma membrane and its expression level increased significantly at 13 d under gray blight treatment. We found that 12 CsLACs were predicted to be targets of cs-miR397a, and most CsLACs showed opposite expression patterns compared to cs-miR397a under gray blight infection. Additionally, 18 highly polymorphic SSR markers were developed, these markers can be widely used for diverse genetic studies of tea plants. CONCLUSIONS: This study provides a comprehensive understanding of the classification, evolution, structure, tissue-specific profiles, and (a)biotic stress responses of CsLAC genes. It also provides valuable genetic resources for functional characterization towards enhancing tea plant tolerance to multiple (a)biotic stresses.

The molecular mechanism underlying GABAergic dysfunction in nucleus accumbens of depression-like behaviours in mice.

Depression is the most frequent psychiatric disorder in the world. Recent evidence has shown that stress-induced GABAergic dysfunction in the nucleus accumbens (NAc) contributed to the pathophysiology of depression. However, the molecular mechanisms underlying these pathological changes remain unclear. In this study, mice were constantly treated with the chronic unpredictable mild stress (CUMS) till showing depression-like behaviours expression. GABA synthesis, release and uptake in the NAc tissue were assessed by analysing the expression level of genes and proteins of Gad-1, VGAT and GAT-3 by qRT-PCR and Western blotting. The miRNA/mRNA network regulating GABA was constructed based on the bioinformatics prediction software and further validated by dual-luciferase reporter assay in vitro and qRT-PCR in vivo, respectively. Our results showed that the expression level of GAT-3, Gad-1 and VGAT mRNA and protein significantly decreased in the NAc tissue from CUMS-induced depression-like mice than that of control mice. However, miRNA-144-3p, miRNA-879-5p, miR-15b-5p and miRNA-582-5p that directly down-regulated the expression of Gad-1, VGAT and GAT-3 were increased. In the mRNA/miRNA regulatory GABA network, Gad-1 and VGAT were directly regulated by binding seed sequence of miR-144-3p, and miR-15b-5p, miR-879-5p could be served negative post-regulators by binding to the different sites of VGAT 3'-UTR. Chronic stress causes the impaired GABA synthesis, release and uptake by up-regulating miRNAs and down-regulating mRNAs and proteins, which may reveal the molecular mechanisms for the decreased GABA concentrations in the NAc tissue of CUMS-induced depression.

Ursolic acid derivative FZU-03,010 inhibits STAT3 and induces cell cycle arrest and apoptosis in renal and breast cancer cells.

Advanced renal cell carcinoma and triple negative breast cancer (TNBC) are malignancies without effective therapeutics currently. Ursolic acid (UA) has been previously reported to have anti-cancer effects in multiple solid tumors. In order to develop more potent anti-cancer reagents, FZU-03,010 based on the chemical structure of UA were synthesized. The results demonstrated that, compared with UA, FZU-03,010 could suppress renal cancer cell 786-0 and TNBC cell HCC1806 cell viability more potently.  Furthermore, FZU-03,010 could induce G1 cell cycle arrest and cell apoptosis more efficiently than UA. FZU-03,010 could also inhibit signal transducer and activator of transcription 3 activation, induce the expression of cell cycle-dependent kinase inhibitors (p21 and p27) and promote cell apoptosis. In conclusion, our results suggest that the UA derivative FZU-03,010 is more potent in inhibiting cancer cell survival, and FZU-03,010 has the potential to be developed as a therapeutic for renal cell cancers and TNBCs.

MiR-214 Attenuates Osteogenic Differentiation of Mesenchymal Stem Cells via Targeting FGFR1.

BACKGROUND/AIMS: Postmenopausal osteoporosis is closely associated with reduction in the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. Previous studies have demonstrated that miR-214 plays an important role in the genesis and development of postmenopausal osteoporosis. Here, we performed this study to investigate the potential mechanism by which miR-214 regulates osteoblast differentiation of MSCs. METHODS: First, we explored the expression of miR-214 in MSCs of osteoporotic mice. Next, we examined the change of miR-214 during osteoblast differentiation of MSCs. Then, MSCs were infected with lentiviral vectors expressing miR-214 or miR-214 sponge to investigate the effect of miR-214 on osteoblast differentiation of MSCs. Further, bioinformatics analysis and luciferase reporter assay were performed to identify and validate the target gene of miR-214. RESULTS: MiR-214 was up-regulated in MSCs of osteoporotic mice and down-regulated during osteoblast differentiation of MSCs. Furthermore, overexpression of miR-214 inhibited osteoblast differentiation of MSCs in vitro, whereas inhibition of miR-214 function promoted this process, evidenced by increased expression of osteoblast-specific genes, alkaline phosphatase (ALP) activity, and matrix mineralization. Bioinformatics, Western blot analysis and luciferase reporter assay demonstrated that FGFR1 is a direct target of miR-214. CONCLUSIONS: MiR-214 attenuates osteogenesis by inhibiting the FGFR1/FGF signaling pathway. Our findings suggest that targeting miR-214 promises to be a potential therapy in treatment of postmenopausal osteoporosis.

Pathogenetic and Therapeutic Applications of Tumor Necrosis Factor-α (TNF-α) in Major Depressive Disorder: A Systematic Review.

Major depressive disorder (MDD) is characterized by mood, vegetative, cognitive, and even psychotic symptoms and signs that can cause substantial impairments in quality of life and functioning. Up to now, the exact pathogenesis of MDD remains poorly understood. Recent research has begun to reveal that the pro-inflammatory cytokines, particularly, tumor necrosis factor-α (TNF-α), play an integral role in the pathophysiology of depressive disorders and the mechanism of antidepressant treatment. On the base of several observations: it is found that subsets of MDD patients have enhanced plasma levels TNF-α; antidepressant treatments had linked with the decline of TNF-α; central administration of TNF-α gives rise to sickness behavior which shares features with depression; and a blockade of it can ameliorate depressive symptomatology in animal models and clinical trials. In this review article, we focus on recent evidence linking TNF-α and MDD looking at data from animal and clinical studies, illustrating the pathophysiological role, susceptibility and its therapeutic application in depression. We conclude by discussing future directions for research, in particular the opportunities for the development of novel therapeutics that target TNF-α. This will be very important for designing preventative strategies and for the identification of new drug targets and preventative strategies.

Hierarchical NiCo2 O4 Hollow Microcuboids as Bifunctional Electrocatalysts for Overall Water-Splitting.

Bifunctional electrocatalysts for the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) in alkaline electrolyte may improve the efficiency of overall water splitting. Nickel cobaltite (NiCo2 O4 ) has been considered a promising electrode material for the OER. However, NiCo2 O4 that can be used as an electrocatalyst in HER has not been studied yet. Herein, we report self-assembled hierarchical NiCo2 O4 hollow microcuboids for overall water splitting including both the HER and OER reactions. The NiCo2 O4 electrode shows excellent activity toward overall water splitting, with 10 mA cm(-2) water-splitting current reached by applying just 1.65 V and 20 mA cm(-2) by applying just 1.74 V across the two electrodes. The synthesis of NiCo2 O4 microflowers confirms the importance of structural features for high-performance overall water splitting.

Schwann Cells Transplantation Improves Locomotor Recovery in Rat Models with Spinal Cord Injury: a Systematic Review and Meta-Analysis.

BACKGROUND/AIMS: Schwann cells (SCs) which were demonstrated to be responsible for axonal myelination and ensheathing are widely studied and commonly used for cell transplantation to treat spinal cord injury (SCI). We performed this meta-analysis to summarize the effects of SCs versus controls for locomotor recovery in rat models of traumatic SCI. METHODS: Studies of the BBB scores after transplantation of SCs were searched out from Pubmed, Cochrane Library Medline databases and analyzed by Review Manager 5.2.5. RESULTS: Thirteen randomized controlled animal trials were selected with 283 rats enrolled. The studies were divided to different subgroups by different models of SCI, different cell doses for transplantation, different sources of SCs and different transplantation ways. The pooled results of this meta-analysis suggested that SCs transplantation cannot significantly improve the locomotor recovery at a short time after intervention (1 week after transplantation) in both impacted and hemi-sected SCI models. However, at a longer time after intervention (3, 5-7 and over 8 weeks after transplantation), significant improvement of BBB score emerged in SCs groups compared with control groups. Subgroup analyses revealed that SCs transplantation can significantly promote locomotor recovery regardless of in high or low doses of cells, from different sources (isolated from sciatic nerves or differentiated from bone marrow stromal cells(BMSCs)) and with or without scaffolding. CONCLUSION: SCs seem to demonstrate substantial beneficial effects on locomotor recovery in a widely-used animal models of SCI.

Association of calcitonin receptor gene polymorphism with bone mineral density in postmenopausal Chinese women: a meta-analysis.

BACKGROUND: The relationship between Calcitonin receptor (CTR) gene polymorphism C1377T and bone mineral density (BMD) in postmenopausal women has been studied to some degree in Western countries, but the reports remain inconclusive and have not been generalized to other populations. PURPOSE: To evaluate the association of CTR gene polymorphism C1377T with BMD in the Han Chinese population. METHODS: We searched for all published articles indexed in MEDLINE (1950-2014), EMBASE (1974-2014), China National Knowledge Infrastructure (CNKI, 1994-2014), and the Wanfang Database, using the key words "polymorphism," "CTR," "osteoporosis," and "bone density." The data were extracted independently by two reviewers. The heterogeneity between studies was determined using the Chi-square-based Q test. Potential publication bias was estimated using a funnel plot and Egger's linear regression test. Odds ratios and 95 % confidence intervals (CI) were used to evaluate the results. RESULTS: Six eligible studies were selected for the meta-analysis. Our analysis suggested that the C1377T polymorphism of the CTR gene was associated with BMD at the lumbar spine (95 % CI -0.57 to -0.05; P = 0.02), but not associated with BMD at the femoral neck (95 % CI -0.27 to 0.24; P = 0.90) in the postmenopausal Han Chinese population. CONCLUSION: The C1377T polymorphism in the CTR gene is associated with BMD at the lumbar spine in a postmenopausal Han Chinese population and the CTR gene may become a useful genetic marker for predicting the risk of developing osteoporosis in postmenopausal Chinese women.

Association of homocysteine, vitamin B12, and folate with bone mineral density in postmenopausal women: a meta-analysis.

BACKGROUND: The relationship of homocysteine (Hcy), folate, and vitamin B12 with bone mineral density (BMD) has been investigated in postmenopausal women. However, the relationship is still controversial. PURPOSE: To evaluate the association of Hcy, folate, vitamin B12 and BMD in postmenopausal women with a meta-analysis. METHODS: We searched for all published articles indexed in Medline (1950-2012), Embase (1974-2012), and China National Knowledge Infrastructure (1994-2012). Any case-control or cohort study relating to Hcy, vitamin B12, folate, and BMD was included, and the data were extracted independently by two reviewers. Criteria for inclusion were the assessment of Hcy, vitamin B12, folate, and BMD in postmenopausal women as outcomes. We performed this meta-analysis with Review Manager 5.1 software. Odds ratios and 95 % confidence intervals (CI) were used to evaluate the results. RESULTS: Six eligible studies were selected for meta-analysis. Our analysis suggested that vitamin B12 and Hcy levels were significantly higher in postmenopausal osteoporosis (PMOP) group than that in controls (P = 0.007, <0.05; 95 % CI 3.06-19.38 and P = 0.0003, <0.05; 95 % CI 0.75-2.52, respectively). Folate level was lower in PMOP group than that in controls, but this difference was not statistically significant (P = 0.09, 95 % CI -3.33 to 0.25). CONCLUSIONS: Hcy and vitamin B12, but not folate, were related to BMD in PMOP. Extra vitamin B12 may not play a protective role for osteoporosis in postmenopausal women. Future studies are needed to confirm them, especially the relationship between increased vitamin B12 and BMD.

The Laccase Family Gene CsLAC37 Participates in Resistance to Colletotrichum gloeosporioides Infection in Tea Plants.

Fungal attacks have become a major obstacle in tea plantations. Colletotrichum gloeosporioides is one of the most devastating fungal pathogens in tea plantations that can severely affect tea yield and quality. However, the molecular mechanism of resistance genes involved in anthracnose is still largely unknown in tea plants. Here, we found that the laccase gene CsLAC37 was involved in the response to fungal infection based on a transcriptome analysis. The full-length CDS of CsLAC37 was cloned, and its protein sequence had the closest relationship with the Arabidopsis AtLAC15 protein compared to other AtLACs. Tissue-specific expression analysis showed that CsLAC37 had higher expression levels in mature leaves and stems than in the other tissues. Subcellular localization showed that the CsLAC37 protein was predominantly localized in the cell membrane. The expression levels of CsLAC37 were upregulated at different time points under cold, salt, SA, and ABA treatments. qRT-PCR confirmed that CsLAC37 responded to both Pestalotiopsis-like species and C. gloeosporioides infections. Functional validation showed that the hydrogen peroxide (H2O2) content increased significantly, and POD activity decreased in leaves after antisense oligonucleotide (AsODN) treatment compared to the controls. The results demonstrated that CsLAC37 may play an important role in resistance to anthracnose, and the findings provide a theoretical foundation for molecular breeding of tea varieties with resistance to fungal diseases.

Co-decoction of Lilii bulbus and Radix Rehmannia Recens and its key bioactive ingredient verbascoside inhibit neuroinflammation and intestinal permeability associated with chronic stress-induced depression via the gut microbiota-brain axis.

BACKGROUND: Gut microbiota plays a critical role in the pathogenesis of depression and are a therapeutic target via maintaining the homeostasis of the host through the gut microbiota-brain axis (GMBA). A co-decoction of Lilii bulbus and Radix Rehmannia Recens (LBRD), in which verbascoside is the key active ingredient, improves brain and gastrointestinal function in patients with depression. However, in depression treatment using verbascoside or LBRD, mechanisms underlying the bidirectional communication between the intestine and brain via the GMBA are still unclear. PURPOSE: This study aimed to examine the role of verbascoside in alleviating depression via gut-brain bidirectional communication and to study the possible pathways involved in the GMBA. METHODS: Key molecules and compounds involved in antidepressant action were identified using HPLC and transcriptomic analyses. The antidepressant effects of LBRD and verbascoside were observed in chronic stress induced depression model by behavioural test, neuronal morphology, and synaptic dendrite ultrastructure, and their neuroprotective function was measured in corticosterone (CORT)-stimulated nerve cell injury model. The causal link between the gut microbiota and the LBRD and verbascoside antidepressant efficacy was evaluate via gut microbiota composition analysis and faecal microbiota transplantation (FMT). RESULTS: LBRD and Verbascoside administration ameliorated depression-like behaviours and synaptic damage by reversing gut microbiota disturbance and inhibiting inflammatory responses as the result of impaired intestinal permeability or blood-brain barrier leakiness. Furthermore, verbascoside exerted neuroprotective effects against CORT-induced cytotoxicity in an in vitro depression model. FMT therapy indicated that verbascoside treatment attenuated gut inflammation and central nervous system inflammatory responses, as well as eliminated neurotransmitter and brain-gut peptide deficiencies in the prefrontal cortex by modulating the composition of gut microbiota. Lactobacillus, Parabacteroides, Bifidobacterium, and Ruminococcus might play key roles in the antidepressant effects of LBRD via the GMBA. CONCLUSION: The current study elucidates the multi-component, multi-target, and multi-pathway therapeutic effects of LBRD on depression by remodeling GMBA homeostasis and further verifies the causality between gut microbiota and the antidepressant effects of verbascoside and LBRD.

Integrated physiological, metabolite and proteomic analysis reveal the glyphosate stress response mechanism in tea plant (Camellia sinensis).

Glyphosate residues can tremendously impact the physiological mechanisms of tea plants, thus threatening tea security and human health. Herein, integrated physiological, metabolite, and proteomic analyses were performed to reveal the glyphosate stress response mechanism in tea plant. After exposure to glyphosate (≥1.25 kg ae/ha), the leaf ultrastructure was damaged, and chlorophyll content and relative fluorescence intensity decreased significantly. The characteristic metabolites catechins and theanine decreased significantly, and the 18 volatile compounds content varied significantly under glyphosate treatments. Subsequently, tandem mass tags (TMT)-based quantitative proteomics was employed to identify the differentially expressed proteins (DEPs) and to validate their biological functions at the proteome level. A total of 6287 proteins were identified and 326 DEPs were screened. These DEPs were mainly catalytic, binding, transporter and antioxidant active proteins, involved in photosynthesis and chlorophyll biosynthesis, phenylpropanoid and flavonoid biosynthesis, sugar and energy metabolism, amino acid metabolism, and stress/defense/detoxification pathway, etc. A total of 22 DEPs were validated by parallel reaction monitoring (PRM), demonstrating that the protein abundances were consistent between TMT and PRM data. These findings contribute to our understanding of the damage of glyphosate to tea leaves and molecular mechanism underlying the response of tea plants to glyphosate.

Common variants of transcription factor 7-like 2 (TCF7L2) are associated with reduced insulin secretion in women with polycystic ovary syndrome.

Common variants of the transcription factor 7-like 2 (TCF7L2) gene were identified as one of the few genetic polymorphisms with powerful effects on the risk of type 2 diabetes (T2D). Given the genetic overlap between polycystic ovary syndrome (PCOS) and T2D, the present study was undertaken to investigate whether the TCF7L2 variants are also associated with PCOS. We analyzed single nucleotide polymorphisms (SNPs) rs11196218 and rs290487 of the TCF7L2 gene, which showed robust associations with T2D in Chinese population, in 430 PCOS patients and 360 control subjects by pyrosequencing, and also assessed the effect of genotype on clinical and biochemical traits in the PCOS group. We found no evidence for association between SNP rs11196218 and PCOS. The SNP rs290487 showed marginal differences in genotype frequencies between the PCOS and control group, with the minor C allele being the at-risk allele for PCOS. In PCOS women, the C allele carriers of rs290487 had higher levels of 2h blood glucose but lower insulinogenic index than noncarriers, suggesting impaired insulin secretion. Our data suggested that the TCF7L2 variants may confer an increased risk for early impairment of glucose homeostasis in PCOS.

CBR3-AS1 Accelerates the Malignant Proliferation of Gestational Choriocarcinoma Cells by Stabilizing SETD4.

Background: Gestational choriocarcinoma (GC) is a rare malignant gestational trophoblastic tumor. Long noncoding RNA (lncRNA) CBR3 antisense RNA 1 (CBR3-AS1) has been reported to serve as a critical oncogene and facilitate tumor progression. Besides, we found that CBR3-AS1 is implicated in GC progression. Materials and Methods: Gene and protein expression was detected via quantitative reverse transcription PCR (RT-qPCR) and western blot analyses, respectively. CCK-8 assay and colony formation assay were performed to assess cell proliferative abilities while flow cytometry analysis was applied for cell cycle and apoptosis. To analyze the specific mechanism among CBR3-AS1, SET domain containing 4 (SETD4), and polypyrimidine tract binding protein 1 (PTBP1), RNA binding protein immunoprecipitation (RIP), RNA pulldown, and mRNA stability assays were conducted. Results: CBR3-AS1 was markedly upregulated in GC cells, and its downregulation suppressed cell proliferation, induced cell cycle arrest, but promoted cell apoptosis in GC. SETD4 was determined as the downstream mRNA of CBR3-AS1 and positively regulated by CBR3-AS1 in GC cells. Furthermore, CBR3-AS1 could interact with its RNA binding protein (RBP) PTBP1, thereby stabilizing SETD4 mRNA. Rescue assays verified that CBR3-AS1 facilitates GC cell malignant proliferation via SETD4. Conclusion: CBR3-AS1 accelerates the malignant proliferation of GC cells via stabilizing SETD4.

Baihe Dihuang (Lilium Henryi Baker and Rehmannia Glutinosa) decoction attenuates somatostatin interneurons deficits in prefrontal cortex of depression via miRNA-144-3p mediated GABA synthesis and release.

ETHNOPHARMACOLOGICAL RELEVANCE: Baihe Dihuang Decoction is a well-known traditional Chinese medicine prescription (Also known as Lilium Henryi Baker and Rehmannia Glutinosa Decoction, LBRD) composed of Lilium Henryi Baker bulb and raw juice from Rehmannia Glutinosa (Gaertn) DC with the curative efficacy of nourishing yin and clearing heat based on the Chinese herbal medicine theory. It has been used as routine medication in treating depression combined with conventional western medicine in China for years. AIM OF THE STUDY: LBRD can attenuates GABAergic deficits in the medial prefrontal cortex (mPFC) of depression. This study aimed to investigate the mechanism of antidepressive properties of LBRD in the prefrontal GABAergic interneuron subtypes, including parvalbumin (PV), somatostatin (SST), vasoactive intestinal peptide (VIP)-positive neuron. MATERIALS AND METHODS: In this project, chronic unpredicted mild stress paradigm was adopted to construct depression model. After treated with LBRD standard decoction and behaviors test, the level of GABA associated miRNA/mRNA and GABAergic subtype-specific markers were detected by qRT-PCR and Western blot. The lncRNAs/miRNAs/GABA regulatory axis was verified by luciferase reporter assay, RNA immunoprecipitation, RNA pull-down assay, and theses changes were measured in LBRD administration with the use of immunofluorescence staining and RNA-fluorescence in situ hybridization. RESULTS: In the current study, we found that LBRD exhibited high efficacy based on the results of behavioral tests. Meanwhile, LBRD also improved the reduced GABA levels in depression by increasing the expression of lncRNA Neat1 and Malat1, as well as decreasing miRNA-144-3p and miRNA-15b-5p. Moreover, the level of Sst mRNA and protein that were harvested from the mPFC tissues of depression group was significantly lower than those in the control mice. While, these changes can be reverted by LBRD standard decoction administration. Whereas, neither chronic stress nor treatment can change the level of PV and VIP mRNAs and protein expression. In the SST-positive neuron of mPFC tissues, treatment with LBRD standard decoction resulted in the elevation of Gad-67, VGAT, GAT-3 and a reduction of miRNA-144-3p expression. CONCLUSIONS: These findings suggested that LBRD antidepressant activities may be related to ameliorating the SST-positive neuron deficits via regulating the miRNA-144-3p mediated GABA synthesis and release.

Integrated analysis of the chemical-material basis and molecular mechanisms for the classic herbal formula of Lily Bulb and Rehmannia Decoction in alleviating depression.

BACKGROUND: Lily Bulb and Rehmannia Decoction (LBRD), is a traditional Chinese formula that has been shown to be safe and effective against depression; however, its material basis and pharmacological mechanisms remain unknown. METHODS: Here, ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) and high-performance liquid chromatography (HPLC) were used to identify the chemical spectrum and qualitatively identify the major active ingredients in the LBRD standard decoction, respectively. Subsequently, we assessed the behavior, neuronal function and morphology, neurotransmitter levels, hypothalamic-pituitary-adrenal (HPA)-axis associated hormones, inflammatory cytokine levels, and miRNA/mRNA expression alterations in an in vitro/vivo depression model treated by the LBRD standard decoction. Finally, miRNA/mRNA regulatory networks were created through bioinformatics analysis, followed by functional experiments to verify its role in LBRD standard decoction treatment. RESULTS: A total of 32 prototype compounds were identified in the LBRD standard decoction, and the average quality of verbascoside in the fresh lily bulb decoction, fresh raw Rehmannia juice, and the LBRD standard decoction were 0.001264%, 0.002767%, and 0.009046% (w/w), respectively. Administration of the LBRD standard decoction ameliorated chronic unpredictable mild stress (CUMS)-induced depression-like phenotypes and protected PC12 cells against chronic corticosterone (CORT)-induced injury. The levels of neurotransmitter, cytokine, stress hormones and neuronal morphology were disrupted in the depression model, while LBRD standard decoction could work on these alterations. After LBRD standard decoction administration, four differentially expressed miRNAs, rno-miR-144-3p, rno-miR-495, rno-miR-34c-5p, and rno-miR-24-3p, and six differentially expressed mRNAs, Calml4, Ntrk2, VGAT, Gad1, Nr1d1, and Bdnf overlapped in the in vivo/vitro depression model. Among them, miR-144-3p directly mediated GABA synthesis and release by targeting Gad1 and VGAT, and miR-495 negatively regulated BDNF expression. The LBRD standard decoction can reverse the above miRNA/mRNA network-mediated GABA and BDNF expression in the in vivo/vitro depression model. CONCLUSION: Collectively, the multi-components of the LBRD standard decoction altered a series of miRNAs in depression through mediating GABAergic synapse, circadian rhythm, and neurotrophic signaling pathway etc., thereby abolishing inhibitory/excitatory neurotransmitter deficits, recovering the pro-/anti-inflammatory cytokine levels and regulating the HPA-axis hormone secretion to achieve balance of the physiological function of the whole body.

Chinese herbal medicine for gout: a review of the clinical evidence and pharmacological mechanisms.

Gout is a common arthritis condition due to disorders of purine metabolism and decreased uric acid excretion. Although researchers have carried out various studies on this disease, there are no effective drugs for patients with gout. In traditional Chinese medicine (TCM), gout pertains the category of Bi pattern due to qi stagnation in the meridians and collaterals. Chinese herbal medicinals has been employed to treat Bi patterns since the ancient China. In recent decades, classical TCM formulas and agents isolated from some Chinese herbal medicinals have been applied to treat gout and have achieved satisfactory effect. In this review, we focus on recent studies of gout in which TCM formulas were applied to treat animal models or to treat patients, and summarize the mechanism of gout from TCM perspective, the clinical application, pharmacological mechanism and the chemical compounds of TCM formulas in treating gout. In conclusion, through this study, we summarized the application principle of TCM formulas in gout treatment and some key issues of current research, and we hope this study will provide some references for applying TCM formulas to treat gout and will lay a foundation for the development of novel formulas for gout treatments.

A novel theranostic nano-platform (PB@FePt-HA-g-PEG) for tumor chemodynamic-photothermal co-therapy and triple-modal imaging (MR/CT/PI) diagnosis.

The construction of multi-functional oncotherapy nano-platforms combining diagnosis and therapy remains a tough challenge. Prussian blue nano-cubes with optimized particle size were applied as photothermal agents and loaded with FePt NPs, effective ferroptosis agents, on the surface via an in situ reduction strategy. To attain the goal of precise medicine, hyaluronic acid was wrapped around the surface of the nanocomposites (PB@FePt NCs) for highly specific recognition of tumor cells. Finally, we successfully designed and fabricated a nano-agent (PB@FePt-HA-g-PEG NCs) to serve as a versatile nano-platform with both highly specific targeting ability for chemodynamic-photothermal co-therapy and triple-modal imaging (magnetic resonance/computed tomography/photothermal imaging) capability. Via intravenous injection, the as-constructed oncotherapy nano-platform could effectively ablate 4T1 tumor xenografts with excellent biocompatibility for chemodynamic-photothermal co-therapy. In this study we conducted a reasonable exploration to design multi-functional oncotherapy nano-platforms combining multiplexed imaging diagnosis and high therapeutic performance, which provides an innovative paradigm for precision cancer treatment.

Triage human papillomavirus testing for cytology-based cervical screening in women of different ages in primary hospitals: A retrospective clinical study.

Cervical cancer is a serious global health problem. The objective of this study was to provide a suitable cytology-based cervical screening method in women of different ages in primary hospitals.This study was a retrospective cohort study that included 9765 women who underwent primary cytology-based cervical screening and were grouped by age (35-44, 45-54, and 55-64 years old). Patients with abnormal cytology on the primary cervical thin-prep cytologic test (TCT) were advised to undergo triage human papillomavirus (HPV) test. Furthermore, patients with positive outcomes of the 2 indices underwent cervical tissue biopsy. The positive rate of TCT and HPV was compared among the 3 defined age groups. The sensitivity, specificity, and positive predictive value of TCT and HPV were assessed.In total, 2.5% (241/9765) of women had atypical squamous cells of undetermined significance or worse by TCT. High-risk (HR)-HPV infection was found in 70 triage participants. Neoplastic changes were confirmed in 95 patients (95/437, 21.7%) by biopsies. Among the different age groups, the positive rate of abnormal cytology was significantly different (P = .003), and the positive rate of HR-HPV was similar (P = .299). The sensitivity of initial TCT testing to detect intraepithelial neoplasia was higher than that of triage HPV testing, whereas the specificity, the positive predictive value of triage HPV testing was higher than that of TCT. The Youden index of HPV testing was higher than that of TCT detection in the 3 age groups, namely 0.582 versus 0.432, 0.553 versus 0.228, and 0.416 versus 0.332, respectively.The results of this study indicate that TCT testing is suitable as a cervical cancer screening method for women ≥35 years old in primary hospitals. Triage testing for women with HR-HPV has a high negative predictive value, reduces the rate of misdiagnosis, seems to be an excellent triage method for repeat atypical squamous cells of undetermined significance, and reduces the number of referral colposcopies preventing unnecessary overtreatment. The results of this study provide a crucial foundation for a unified guideline cervical cancer screening for primary health care institutions.