Anti-psoriasis effect of 18ß-glycyrrhetinic acid by breaking CCL20/CCR6 axis through its vital active group targeting GUSB/ATF2 signaling.

BACKGROUND: Psoriasis is an immune-mediated chronic inflammatory skin disease. Current research suggests that the long-term persistence and recurrence of psoriasis are closely related to the feedback loop formed between keratinocytes and immune cells, especially in Th 17 or DC cells expressing CCR6. CCL20 is the ligand of CCR6. Therefore, drugs that block the expression of CCL20 or CCR6 may have a certain therapeutic effect on psoriasis. Glycyrrhetinic acid (GA) is the main active ingredient of the plant drug licorice and is often used to treat autoimmune diseases, including psoriasis. However, its mechanism of action is still unclear. METHODS: Psoriasis like skin lesion model was established by continuously applying imiquimod on the back skin of normal mice and CCR6-/- mice for 7 days. The therapeutic and preventive effects of glycyrrhetinic acid (GA) on the model were observed and compared. The severity of skin injury is estimated through clinical PASI scores and histopathological examination. qRT-PCR and multiple cytoline assay were explored to detect the expression levels of cytokines in animal dorsal skin lesions and keratinocyte line HaCaT cells, respectively. The dermis and epidermis of the mouse back were separated for the detection of CCL20 expression. Transcription factor assay was applied to screen, and luciferase activity assay to validate transcription factors regulated by GA. Technology of surface plasmon laser resonance with LC-MS (SPR-MS), molecular docking, and enzyme activity assay were used to identified the target proteins for GA. Finally, we synthesized different derivatives of 18beta-GA and compared their effects, as well as glycyrrhetinic acid (GL), on the skin lesion of imiquimod-induced mice to evaluate the active groups of 18beta-GA. RESULTS: 18ß-glycyrrhetinic acid (GA) improved IMQ-induced psoriatic lesions, and could specifically reduce the chemokine CCL20 level of the epidermis in lesion area, especially in therapeutic administration manner. The process was mainly regulated by transcription factor ATF2 in the keratinocytes. In addition, GUSB was identified as the primary target of 18ßGA. Our findings indicated that the subject on molecular target research of glycyrrhizin should be glycyrrhetinic acid (GA) instead of glycyrrhizic acid (GL), because GL showed little activity in vitro or in vivo. Apart from that, α, ß, -unsaturated carbonyl in C11/12 positions was crucial or unchangeable to its activity of 18ßGA, while proper modification of C3 or C30 position of 18ßGA may vastly increase its activity. CONCLUSION: Our research indicates that 18ßGA exerted its anti-psoriasis effect mainly by suppressing ATF2 and downstream molecule CCL20 predominately through α, ß, -unsaturated carbonyl at C11/12 position binding to GUSB in the keratinocytes, and then broke the feedback loop between keratinocytes and CCR6-expressing immune cells. GA has more advantages than GL in the external treatment of psoriasis. A highlight of this study is to investigate the influence of special active groups on the pharmacological action of a natural product, inspired by the molecular docking result.

The characterization of the pectin/alginate nanoparticle for encapsulation of hydroxypropyl-ß-cyclodextrin-complexed naringin and its effects on cellular uptake and oxidative stress in Caco-2 cells.

Naringin (NR) and hydroxypropyl-ß-cyclodextrin (HPCD) can form a water-soluble complex, but it is unstable. This study aimed to investigate the characterization of the pectin/alginate hydrogel nanoparticles (HNPs) loading HPCD-complexed naringin. The encapsulation efficiency and loading capacity of the HNPs for NR were found to be 79.23 % ± 1.31 % and 23.79 % ± 0.67 %, respectively. HNPs had an average diameter of 409.5 ± 8.5 nm, a PDI of 0.237 ± 0.014, and a zeta-potential of -33.5 ± 0.2. FTIR, XRD, and DSC analysis confirmed that the NR-HPCD complex was embedded into the HNPs. In simulated gastrointestinal digestion, the HNPs exhibited a lower cumulative release rate compared to free NR. In Caco-2 cells, the HNPs were more efficiently transported into the cells. Consequently, the HNPs resulted in a greater decrease in ROS levels, more recovery of mitochondrial membrane potential and higher content of glutathione. This study provided a carrier for encapsulating NR, making it possible for use in food or functional food.

Systems Pharmacology Strategy for the Investigation of Action Mechanisms of Qin Herb Libanotis Buchtormensis (Fisch.) DC. in Bone Diseases.

INTRODUCTION: Qin medicines are medicinal plants growing in habitat around the peak of Qinling Mountain. Their unique curative effects on bone metabolic diseases and pain diseases have been favoured by the local people in clinical trials for thousands of years. Libanotis buchtormensis (Fisch.) DC. (LBD), is one of the popular Qin herbs, which has been widely used for the treatment of various diseases, such as osteoporosis, rheumatic, and cardiovascular diseases. However, due to the multiple compounds in LBD, the underlying molecular mechanisms of LBD remain unclear. OBJECTIVE: This study aimed to systemically investigate the underlying mechanisms of LBD against bone diseases. METHODS: In this study, a systems pharmacology platform included the potential active compound screening, target fishing, and network pharmacological analysis was employed to decipher the action mechanisms of LBD. RESULTS: As a result, 12 potential active compounds and 108 targets were obtained. Furthermore, compound-target network and target-pathway network analysis showed that multi-components interacted with multi-targets and multi-pathways, i.e., MARK signalling pathway, mTORC1 signalling pathway, etc., involved in the regulation of the immune system and circulatory system. These results suggested the mechanisms of the therapeutic effects of LBD on various diseases through most compounds targeted by multiple targets. CONCLUSION: In conclusion, we successfully predicted the LBD bioactive compounds and potential targets, implying that LBD could be applied as a novel therapeutic herb in osteoporosis, rheumatic, and cardiovascular diseases. This work provides insight into the therapeutic mechanisms of LBD for treating various diseases.

Ellagic acid inhibits CDK12 to increase osteoblast differentiation and alleviate osteoporosis in hindlimb-unloaded and ovariectomized mice.

BACKGROUND: Osteoporosis is a highly prevalent bone disease occurred commonly in astronauts and postmenopausal women due to mechanical unloading and estrogen deficiency, respectively. At present, there are some traditional Chinese medicine compounds for preventing and treating osteoporosis induced by simulated microgravity, but the detailed components of the traditional Chinese medicines still need to be confirmed and osteoporosis is still untreatable due to a lack of effective small-molecule natural medicine. PURPOSE: To explore the role of cyclin-dependent kinase 12 (CDK12) in osteoporosis induced by simulated microgravity and the therapeutic effect of CDK12-targeted Ellagic Acid (EA) on osteoporosis. METHODS: Our previous study has suggested that CDK12 as a potential target for treating and preventing osteoporosis. In this study, the role of CDK12 in osteoblasts and mice bone tissues was further studied under simulated microgravity. And by targeting CDK12, natural small-molecule product EA was screened out based on a large scale through the weighted set similarity (WES) method and the therapeutic effects of EA on osteoporosis was investigated in hindlimb-unloaded (HU) mouse model and ovariectomized (OVX) model. RESULTS: The results demonstrated that simulated microgravity inhibited bone formation and up-regulated the expression of CDK12. Furthermore, CDK12-siRNA or THZ531 (an inhibitor of CDK 12) promoted osteoblast differentiation, while the overexpression of CDK12 inhibited osteoblasts differentiation. And we further proved that CDK12-targeted EA showed a rescue effect on osteoblast differentiation inhibition caused by simulated microgravity. EA (50 mg·kg-1·day-1) daily intragastric administration alleviated the symptoms of osteoporosis and accompanied with the improvement of trabecular bone and cortical bone parameters with significantly overexpression of CDK12. CONCLUSION: EA efficiently improves osteoporosis by targeting CDK12, which is a suppresser of osteoblast differentiation and a novel therapeutic target for treating osteoporosis.

Antibacterial and antibiofilm potential of Lacticaseibacillus rhamnosus YT and its cell-surface extract.

BACKGROUND: Foodborne pathogens and spoilage bacteria survived in the biofilm pose a serious threat to food safety and human health. It is urgent to find safe and effective methods to control the planktonic bacteria as well as the biofilm formation. Substances with antibacterial and antibiofilm activity found in lactic acid bacteria were mainly metabolites secreted in the cell-free supernatant. Previously, Lacticaseibacillus rhamnosus YT was isolated because its cell pellets displayed distinguished antibacterial activity under neutral conditions. This study aimed to investigate the antibacterial and antibiofilm properties of the L. rhamnosus YT cells and its crude cell-surface extract. RESULTS: The antibacterial activity of the L. rhamnosus YT cells constantly increased with cells growth and reached the peak value after the cells grew into stationary phase. After cocultivation with the L. rhamnosus YT cells, the biofilm formation of B. subtilis and S. enterica was reduced. The antibacterial activity of the L. rhamnosus YT cells was varied along with various culture conditions (carbon sources, nitrogen sources, medium pH and cultural temperatures) and the antibacterial intensity (antibacterial activity per cell) was disproportional to the biomass. Furthermore, the cell-surface extract was isolated and displayed broad antimicrobial spectrum with a bacteriostatic mode of action. The antibiofilm activity of the extract was concentration-dependent. In addition, the extract was stable to physicochemical treatments (heat, pH and protease). The extract performed favorable emulsifying property which could reduce the water surface tension from 72.708 mN/m to 51.011 mN/m and the critical micelle concentration (CMC) value was 6.88 mg/mL. Besides, the extract was also able to emulsify hydrocarbon substrates with the emulsification, index (E24) ranged from 38.55% (for n-hexane) to 53.78% (for xylene). The E24 for xylene/extract emulsion was merely decreased by 5.77% after standing for 120 h. The main components of the extract were polysaccharide (684.63 µg/mL) and protein (120.79 µg/mL). CONCLUSION: The properties of the extract indicated that it might be a kind of biosurfactant. These data suggested that L. rhamnosus YT and the cell-surface extract could be used as an alternative antimicrobial and antibiofilm agent against foodborne pathogens and spoilage bacteria in food industry.

Hypoglycemic effect of the Phellinus baumii extract with α-glucosidase-inhibited activity and its modulation to gut microbiota in diabetic patients.

Phellinus baumii extract (PBE) possesses considerable α-glucosidase-inhibited activity. This study investigated the hypoglycemic effect in vitro and in vivo using a glucose consumption assay in HepG2 cells, intragastric administration for ten weeks in STZ-induced mice, and intestinal flora fermentation in patients with type 2 diabetes to reveal the possible underlying mechanisms. PBE was prepared, including α-glucosidase-inhibited ethanol extract (EE) and aqueous extract (AE). In vitro, PBE promoted glucose consumption and enhanced glycogen content and hexokinase activity but lowered phosphoenolpyruvate carboxylase kinase activity in HepG2 cells. In vivo, PBE treatment significantly reduced the body weight (p < 0.05) and fasting blood glucose levels of diabetic mice (p < 0.01), with the lowest blood glucose level observed in the EE+AE group. Furthermore, the serum insulin levels and insulin resistance index (HOMA) of PBE-treated groups decreased significantly (p < 0.01). Moreover, gene expression levels of the IRS-1/PI3K/AKT pathway were significantly upregulated by PBE treatment (p < 0.01). In vitro fermentation demonstrated that EE significantly inhibited the production of H2S and NH3 in the intestinal flora fermentation model in diabetic patients (p < 0.05). In addition, the ratio of Firmicutes to Bacteroidetes was reduced, the growth of Lactobacillus and Prevotella 9 was promoted, and Pseudomonas aeruginosa was inhibited. This study provides new insights and clues for using PBE as a functional food and clinical drug for glycemic control.

Characterization of the Fungal Community in Fritillariae Cirrhosae Bulbus through DNA Metabarcoding.

Fritillariae Cirrhosae Bulbus (FCB) is a well-known and precious traditional Chinese medicine with a medicinal history spanning thousands of years. In recent years, it has been reported that fungal and mycotoxin contamination influenced the safety and quality of FCB. It is essential to systematically study the fungal community for the early warning of fungal and mycotoxin contamination in this herb. A total of 15 FCB samples were collected from five provinces in China, and the fungal communities in the FCB samples were analyzed via amplifying the internal transcribed spacer 2 region through the Illumina Miseq PE300 platform. Furthermore, we compared the differences in fungal community in five groups based on collection areas. Results showed that Ascomycota (41.58-99.66%) and Mucoromycota (0-57.42%) were dominant at the phylum level. Eurotiomycetes (8.49-63.93%), Eurotiales (8.49-63.53%), and Aspergillaceae (8.49-63.51%) were the most abundant at the class, order, and family levels. Aspergillus (8.49-63.41%), Rhizopus (0-57.42%), Fusarium (0-22.81%), Cladosporium (0.16-9.14%), and Alternaria (0.06-17.95%) were the main genera in FCB samples. A total of 34 fungal taxa were identified at the species level, including five potentially toxigenic fungi namely Penicillium brevicompactum, P. citrinum, P. oxalicum, Trichothecium roseum, and Aspergillus restrictus. The differences in fungal community between the five groups were observed. Our findings provide references for the safe utilization and quality improvement of FCB.

Protective Effect and Mechanism of Plant-Based Monoterpenoids in Non-alcoholic Fatty Liver Diseases.

The protective effect of plant active ingredients against non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prominent, and the terpenoids have always been the main active compounds in Chinese herbal medicine exerting hepatoprotective effects. However, the related pharmacological effects, especially for monoterpenoids or iridoid glycosides, which have obvious effects on improvement of NAFLD, have not been systematically analyzed. The objective of this review is to systematically examine the molecular mechanisms of monoterpenoids in NAFLD. The signaling pathways of peroxisome proliferator-activated receptor, insulin, nuclear factor κB, toll-like receptor, adipocytokine, RAC-α serine/threonine protein kinase, mammalian target of rapamycin, 5'-AMP-activated protein kinase, and autophagy have been proven to mediate this protective effect. We further compared the experimental data from animal models, including the dosage of these monoterpenoids in detail, and demonstrated that they are effective and safe candidate drugs for NAFLD. This review provides a reference for the development of NAFLD drugs as well as a research guideline for the potential uses of plant monoterpenoids.

Biological activities and gene expression of detoxifying enzymes in Tribolium castaneum induced by Moutan cortex essential oil.

Tribolium castaneum is one of the most harmful storage pests in the world. The aim of this study was to determine the chemical composition, repellent, and contact activities of Moutan cortex essential oil against this insect pest. In addition, the effects of Moutan cortex were examined on the expressions of three major detoxifying enzyme genes in T. castaneum. Four components were identified in this essential oil by gas chromatography-mass spectrometry (GC-MS), which was predominantly paeonol (99.13%). Paeonol exerted significant repellent activity against T. castaneum, which was more potent than the positive control N.N-diethyl-meta-toluamide (DEET). The most significant contact toxicity was observed at 24 h after exposure to paeonol. Further, quantitative real-time PCR (qRT-PCR) was used to assess expression changes in three detoxification enzyme genes in T. castaneum, including carboxylesterase (CarE), glutathione S-transferase (Gst) and cytochrome P4506BQ8 (Cyp6bq8). Among these, Gst was most highly up-regulated after treatment with paeonol with the highest expression level of 4.9-fold (Rps18 as internal reference gene) greater than control at 24 h following treatment. Data indicated that Gst might play a critical role in metabolic detoxification of toxic xenobiotics. Taken together, our findings might lay a foundation for development of paeonol as a potential natural repellent or pesticide to control storage pests.

The efficacy of mindfulness-based stress reduction intervention 3 for post-traumatic stress disorder (PTSD) symptoms in patients with PTSD: A meta-analysis of four randomized controlled trials.

As one of the most widely used mindfulness-based psychotherapeutic intervention techniques, mindfulness-based stress reduction (MBSR) has emerged as an auxiliary or alternative technique for the treatment of post-traumatic stress disorder (PTSD). This study conducted a meta-analysis of the effect of MBSR on the changes in symptoms in PTSD patients. The final search was conducted on 10 December 2021, and 10 eligible randomized controlled trials were identified, including 768 participants. A quality assessment was conducted. Proportional sensitivity analysis and random effects meta-analysis were performed, and the 95% confidence interval was calculated. Subgroup analyses were also conducted to identify moderators (e.g., features of population and intervention). Compared with the control condition, MBSR significantly reduced the symptoms of PTSD patients and had a moderately positive effect (g = 0.46, 95% CI: 0.31-0.62, p < 0.001). This was the case in people who suffer from PTSD for different reasons, indicating that MBSR is an effective treatment for PTSD symptoms in PTSD patients. It was feasible to implement MBSR interventions for PTSD patients caused by different reasons.

Long-term porosity and retreatability of oval-shaped canals obturated using two different methods with a novel tricalcium silicate sealer.

OBJECTIVE: To evaluate the percentage volume of voids and gaps in oval-shaped canals obturated using two different methods with a tricalcium silicate-based sealer after short- or long-term storage. The long-term effect of storage on the efficiency of removing filling material was also investigated. MATERIALS AND METHODS: Forty premolar teeth with oval-shaped canals were instrumented to Reciproc R25 and obturated using single cone obturation (SCO) or warm vertical compaction (WVC) techniques with gutta-percha and HiFlow sealer. The specimens were stored at 100% humidity and 37°C for 2 weeks or 6 months and scanned using micro-computed tomography. Initial retreatment was performed up to a Reciproc R40, and the operating time was recorded. The residual material in the canal received a supplementary procedure using XP-endo Finisher R (XPFR) files. After each retreatment procedure, the specimens were rescanned. RESULTS: The percentage volume of voids and gaps in the SCO group was higher than that of the WVC group at both 2 weeks and 6 months (P < 0.05). The percentage volume of the filling material removed after initial retreatment and XPFR cleaning was significantly higher in the 6-month group than in the 2-week groups (P < 0.05). The proportion of the residual material decreased significantly when XPFR files were used, compared to the initial retreatment group (P < 0.05) in both storage times. CONCLUSION: The efficiency of retreatment in the oval-shaped canal was closely related to the storage time rather than the filling technique using a tricalcium silicate sealer. The XPFR instrument proved effective in the removal of the remaining materials from the oval-shaped canal. CLINICAL RELEVANCE: Obturation of the oval-shaped canal with TSBS using the SCO technique in the coronal area needs to be optimized. The retreatment was less efficacious in freshly filled canals than aged filled canals.

Cytotoxic Flavonoids from the Leaves and Twigs of Murraya Tetramera.

Cytotoxic flavonoids of Murraya tetramera were investigated in this study. A novel flavonoid and twelve known flavonoids, including seven flavones (1-7), three flavanones (8-10), and three chalcones (11-13) were isolated from the leaves and twigs of Murraya tetramera. Chemical structures were elucidated by NMR combined with MS spectral analysis, and the new compound (6) was confirmed as 3',5'-dihydroxy-5,6,7,4'-tetramethoxyflavone. Furthermore, all the isolated flavonoids were evaluated for their cytotoxicities against murine melanoma cells (B16), and human breast cancer cells (MDA-MB-231) by CCK-8 assay. Among them, compounds 7, 13, and 5 exhibited potent cytotoxic activities against B16 cell lines (IC50 = 3.87, 7.00 and 8.66 µg/mL, respectively). Compounds 5, 13, and 12 displayed potent cytotoxicities against MDA-MB-231 cell lines (IC50 = 3.80, 5.95 and 7.89 µg/mL, respectively). According to the correlation of the structure and activity analysis, 5-hydroxyl and 8-methoxyl substituents of the flavone, 8-methoxyl substituent of the flavanone, and 3',5'-methoxyl substituents of the chalcone could be critical factors of the high cytotoxicity. The results indicated that the active flavonoids have potential to be developed as leading compounds for treating cancers.

Gene therapy via canalostomy approach preserves auditory and vestibular functions in a mouse model of Jervell and Lange-Nielsen syndrome type 2.

Mutations in voltage-gated potassium channel KCNE1 cause Jervell and Lange-Nielsen syndrome type 2 (JLNS2), resulting in congenital deafness and vestibular dysfunction. We conducted gene therapy by injecting viral vectors using the canalostomy approach in Kcne1-/- mice to treat both the hearing and vestibular symptoms. Results showed early treatment prevented collapse of the Reissner's membrane and vestibular wall, retained the normal size of the semicircular canals, and prevented the degeneration of inner ear cells. In a dose-dependent manner, the treatment preserved auditory (16 out of 20 mice) and vestibular (20/20) functions in mice treated with the high-dosage for at least five months. In the low-dosage group, a subgroup of mice (13/20) showed improvements only in the vestibular functions. Results supported that highly efficient transduction is one of the key factors for achieving the efficacy and maintaining the long-term therapeutic effect. Secondary outcomes of treatment included improved birth and litter survival rates. Our results demonstrated that gene therapy via the canalostomy approach, which has been considered to be one of the more feasible delivery methods for human inner ear gene therapy, preserved auditory and vestibular functions in a dose-dependent manner in a mouse model of JLNS2.

Brd4 participates in epigenetic regulation of the extinction of remote auditory fear memory.

BACKGROUND: Inaccurate fear memories can be maladaptive and potentially portrait a core symptomatic dimension of fear adaptive disorders such as post-traumatic stress disorder (PTSD), which is generally characterized by an intense and enduring memory for the traumatic events. Evidence exists in support of epigenetic regulation of fear behavior. Brd4, a member of the bromodomain and extra-terminal domain (BET) protein family, serves as a chromatin "reader" by binding to histones in acetylated lysine residues, and hence promotes transcriptional activities. However, less is known whether Brd4 participates in modulating cognitive activities especially memory formation and extinction. Here we provide evidence for a role of Brd4 in modulation of auditory fear memory. Auditory fear conditioning resulted in a biphasic Brd4 activation in the anterior cingulate cortex (ACC) and hippocampus of adult mice. Thus, Brd4 phosphorylation occurred 6 h and 3-14 days, respectively, after auditory fear conditioning. Systemic inhibition of Brd4 with a BET inhibitor, JQ1, impaired the extinction of remote (i.e., 14 days after conditioning) fear memory. Further, conditional Brd4 knockout in excitatory neurons of the forebrain impaired remote fear extinction as observed in the JQ1-treated mice. Herein, we identified that Brd4 is essential for extinction of remote fear in rodents. These results thus indicate that Brd4 potentially plays a role in the pathogenesis of PTSD.

Systems pharmacology dissection of action mechanisms for herbs in osteoporosis treatment.

Objective: Osteoporosis has become the biggest cause of non-fatal health issue. Currently, the limitations of traditional anti-osteoporosis drugs such as long-term ill-effects and drug resistance, have raised concerns toward complementary and alternative therapies, particularly herbal medicines and their natural active compounds. Thus, this study aimed to provide an integrative analysis of active chemicals, drug targets and interacting pathways of the herbs for osteoporosis treatment. Methods: Here, we introduced a systematic pharmacology model, combining the absorption, distribution, metabolism, and excretion (ADME) screening model, drug targeting and network pharmacology, to probe into the therapeutic mechanisms of herbs in osteoporosis. Results: We obtained 86 natural compounds with favorable pharmacokinetic profiles and their 58 targets from seven osteoporosis-related herbs. Network analysis revealed that they probably synergistically work through multiple mechanisms, such as suppressing inflammatory response, maintaining bone metabolism or improving organism immunity, to benefit patients with osteoporosis. Furthermore, experimental results showed that all the five compounds (calycosin, asperosaponin VI, hederagenin, betulinic acid and luteolin) enhanced osteoblast proliferation and differentiation in vitro, which corroborated the validity of this system pharmacology approach. Notably, gentisin and aureusidin among the identified compounds were first predicted to be associated with osteoporosis. Conclusion: Herbs and their natural compounds, being characterized as the classical combination therapies, might be engaged in multiple mechanisms to coordinately improve the osteoporosis symptoms. This work may contribute to offer novel strategies and clues for the therapy and drug discovery of osteoporosis and other complex diseases.

Essential oil from Artemisia annua aerial parts: composition and repellent activity against two storage pests.

As a medicinal plant, Artemisia annua is widely distributed in China. The purpose of this work was to analyze the chemical composition of essential oil from A. annua aerial portions, as well as to assess its repellent activity against Lasioderma serricorne and Tribolium castaneum adults. GC-FID and GC-MS analyses enabled the identification of 15 components representing 90.1% of the essential oil. The main components included artemisia ketone (70.6%), α-caryophyllene (5.1%) and germacrene D (3.8%). The essential oil was found to possess considerable ability to repel the two storage pests. This paper provided some evidence for the exploitation and utilization of A. annua resources as a natural repellent.

Kaempferol promotes proliferation and osteogenic differentiation of periodontal ligament stem cells via Wnt/ß-catenin signaling pathway.

AIMS: Kaempferol, a type of flavonoid, is widely present in fruits, vegetables and medicinal herbs. This study was designed to investigate the effects of kaempferol on proliferation and osteogenesis of periodontal ligament stem cells (PDLSCs) and to identify the related pathway. MATERIALS AND METHODS: PDLSCs were isolated from extracted premolars and cultured in vitro. Cell-counting kit-8 (CCK-8) and colony formation assays were performed to determine the effect of kaempferol, at various concentrations, on the proliferation of PDLSCs. Alkaline phosphatase (ALP) activity was analyzed both quantitatively and qualitatively, and extracellular matrix mineralization was examined by alizarin red-S staining. In addition, the mRNA and protein expression levels of ALP, RUNX Family Transcription Factor 2 (RUNX2), Sp7 Transcription Factor (SP7; Osterix), Bone Gamma-Carboxyglutamate Protein (BGLAP; osteocalcin) and catenin beta 1 (CTNNB1; ß-catenin) were monitored by qPCR and Western blot analysis. Additionally, the tankyrase inhibitor, XAV939, was used to determine the role of the Wnt/ß-catenin pathway. KEY FINDINGS: The results illustrated that 10-6 M kaempferol markedly promoted the proliferation, ALP activity and mineral deposition of PDLSCs (P < 0.05). The expression levels of ALP, RUNX2, SP7, BGLAP and ß-catenin were all upregulated (P < 0.05). After blocking the Wnt/ß-catenin pathway with XAV939, the effects of kaempferol were apparently reversed. SIGNIFICANCE: kaempferol enhanced proliferation and osteogenesis of PDLSCs by activating the Wnt/ß-catenin signaling, which suggests the potential application of kaempferol for periodontal tissue regeneration.

Do halophytes and glycophytes differ in their interactions with arbuscular mycorrhizal fungi under salt stress? A meta-analysis.

BACKGROUND: Halophytes are better than glycophytes at employing mechanisms to avoid salt injury, but both types of plants can undergo damage due to high soil salinity. Arbuscular mycorrhizal fungi (AMF) can mitigate the damage from salt stress in both halophytes and glycophytes by enhancing salt tolerance and improving energy efficiency. However, variations in mycorrhizal symbiotic efficiency between halophytes and glycophytes were still poorly understood. Therefore, we evaluated the magnitude of AMF effects on plant growth and determined the mechanisms that regulate the growth response of halophytes and glycophytes by performing a meta-analysis of 916 studies (from 182 publications). RESULTS: Arbuscular mycorrhizal fungi significantly enhance biomass accumulation, osmolytes synthesis (soluble sugar and soluble protein), nutrients acquisition (nitrogen, phosphorus, and potassium ion), antioxidant enzyme activities (superoxide dismutase and catalase), and photosynthetic capacity (chlorophyll and carotenoid contents, photosynthetic rate, stomatal conductance, and transpiration rate). AMF also substantially decreased sodium ion acquisition and malondialdehyde levels in both halophytes and glycophytes under salt stress conditions. Mycorrhizal halophytes deploy inorganic ions (potassium and calcium ions) and limited organic osmolytes (proline and soluble sugar) to achieve energy-efficient osmotic adjustment and further promote biomass accumulation. Mycorrhizal glycophytes depend on the combined actions of soluble sugar accumulation, nutrients acquisition, sodium ion exclusion, superoxide dismutase elevation, and chlorophyll synthesis to achieve biomass accumulation. CONCLUSIONS: Arbuscular mycorrhizal fungi inoculation is complementary to plant function under salt stress conditions, not only facilitating energy acquisition but also redistributing energy from stress defence to growth. Glycophytes are more dependent on AMF symbiosis than halophytes under salt stress conditions.

Antrodan Alleviates High-Fat and High-Fructose Diet-Induced Fatty Liver Disease in C57BL/6 Mice Model via AMPK/Sirt1/SREBP-1c/PPARγ Pathway.

Non-alcoholic fatty liver disease (NAFLD) and -steatohepatitis (NASH) imply a state of excessive fat built-up in livers with/or without inflammation and have led to serious medical concerns in recent years. Antrodan (Ant), a purified ß-glucan from A. cinnamomea has been shown to exhibit tremendous bioactivity, including hepatoprotective, antihyperlipidemic, antiliver cancer, and anti-inflammatory effects. Considering the already well-known alleviating bioactivity of A. cinnamomea for the alcoholic steatohepatitis (ASH), we propose that Ant can be beneficial to NAFLD, and that the AMPK/Sirt1/PPARγ/SREBP-1c pathways may be involved in such alleviations. To uncover this, we carried out this study with 60 male C57BL/6 mice fed high-fat high-fructose diet (HFD) for 60 days, in order to induce NAFLD/NASH. Mice were then grouped and treated (by oral administration) as: G1: control; G2: HFD (HFD control); G3: Ant, 40 mgkg (Ant control); G4: HFD+Orlistat (10 mg/kg) (as Orlistat control); G5: HFD+Ant L (20 mg/kg); and G6: HFD+Ant H (40 mg/kg) for 45 days. The results indicated Ant at 40 mg/kg effectively suppressed the plasma levels of malondialdehyde, total cholesterol, triglycerides, GOT, GPT, uric acid, glucose, and insulin; upregulated leptin, adiponectin, pAMPK, Sirt1, and down-regulated PPARγ and SREBP-1c. Conclusively, Ant effectively alleviates NAFLD via AMPK/Sirt1/CREBP-1c/PPARγ pathway.

Combination of Traditional Chinese Medicine and Low-Molecular-Weight Heparin Prevents Deep Vein Thrombosis After Surgery: A Meta-Analysis.

At present, there is no consistent understanding of the effect of traditional Chinese medicine (TCM) prescription in the prevention of the deep vein thrombosis (DVT), though TCM has been widely used in China. To evaluate the efficacy of TCM prescription combined with low-molecular-weight heparin (LMWH) for preventing DVT after major orthopedics surgery. All the retrieved articles were evaluated using specific inclusion and exclusion criteria. Then, data were extracted and evaluated for inclusion in a randomized controlled trial. In this study, variables included relative risk (RR), mean difference (MD), and their corresponding 95% confidence intervals (95% CIs). Overall, 16 articles were included with 1538 patients, 768 in the combination group (combination of TCM prescription and LMWH) and 770 in the LMWH group. The results indicated that in the combination group, the incidence of DVT (RR: 0.34, 95% CI: 0.23-0.50, P < .00001) and d-dimer levels (standardized mean difference: -1.19, 95% CI: -1.80 to -0.58, P = .0001) was significantly lower than that in the LMWH group. Furthermore, the combination treatment obviously decreased the concentration of fibrinogen (MD: -1.19, 95% CI: -2.13 to -0.25, P = .01). The combination of TCM prescription and LMWH could significantly reduce the incidence of DVT, suggesting that it may be a more effective prophylaxis measure for DVT after major orthopedics surgery.