Fluorescent multichannel sensor array based on three carbon dots derived from Tibetan medicine waste for the quantification and discrimination of multiple heavy metal ions in water.

A fluorescent multichannel sensor array has been established based on three carbon dots derived from Tibetan medicine waste for rapid quantification and discrimination of six heavy metal ions. Due to the chelation between metal ions and carbon dots (CDs), this fluorescence "turn off" mode sensing array can quantify six metal ions as low as "µM" level. Moreover, the six heavy metal ions display varying quenching effects on these three CDs owing to diverse chelating abilities between each other, producing differential fluorescent signals for three sensing channels, which can be plotted as specific fingerprints and converted into intuitive identification profiles via principal component analysis (PCA) and hierarchical cluster analysis (HCA) technologies to accurately distinguish Cu2+, Fe3+, Mn2+, Ag+, Ce4+, and Ni2+ with the minimum differentiated concentration of 5 µM. Valuably, this sensing array unveils good sensitivity, exceptional selectivity, ideal stability, and excellent anti-interference ability for both mixed standards and actual samples. Our contribution provides a novel approach for simultaneous determination of multiple heavy metal ions in environmental samples, and it will inspire the development of other advanced optical sensing array for simultaneous quantification and discrimination of multiple targets.

Identification and preparation of selenium-containing peptides from selenium-enriched Pleurotus eryngii and their protective effect on lead-induced oxidative damage in NCTC1469 hepatocytes.

BACKGROUND: Lead (Pb) is a highly toxic and persistent substance that easily accumulates in living organisms, eliciting cellular toxicity and oxidative stress. Some selenium-containing proteins and peptides prepared from plant extracts are beneficial for protecting the body's health and resisting external disturbances. In the present study, selenium-containing peptide species were prepared from selenium-enriched Pleurotus eryngii protein hydrolysates and to evaluate the benefits of selenium-containing peptides on Pb-induced oxidative stress in NCTC1469 hepatocytes. RESULTS: Trypsin was selected as primary enzyme to hydrolyze the selenium-enriched protein (SPH). The optimal hydrolysis conditions were: hydrolysis time, 1.5 h; initial pH 8.0. The SPH was digested by trypsin and then purified by ultrafiltration, gel filtration chromatography and reversed-phase HPLC to obtain the selenium-containing peptides SPH-I-2. Furthermore, SPH-I-2 was analyzed and a number of total 12 selenium-containing peptides were identified by liquid chromatography-tandem mass spectroscopy. The NCTC1469 cell culture study showed that selenium-containing peptides were capable of reducing reactive oxygen species levels and regulating the Keap1/Nrf2 pathway by upregulating Nrf2, HO-1, GCLC, GCLM and NQO1 genes and downregulating Keap1 genes. Moreover, selenium-containing peptides were also able to suppress Pb-induced elevated levels of nitric oxide (NO), lactate dehydrogenase (LDH), malondialdehyde (MDA), increase antioxidant enzyme activity and alleviate cell apoptosis. CONCLUSION: The present study indicated that the selenium-containing peptides could protect cells from Pb2+ -induced oxidative stress. © 2023 Society of Chemical Industry.

Manual Reduction and Plaster External Fixation for the Treatment of Closed Total Talus Dislocation: Case Report and Literature Review.

BACKGROUND: Total dislocation of the talus from all its surrounding joints (talonavicular, tibiotalar, subtalar) is one kind of serious injury of the lower extremity with rare occurrence. It is usually accompanied by fractures of the talus and its periphery, as well as severe soft tissue injury, which is difficult to reset. Complications such as skin necrosis and infection are prone to occur in the early stage, and talus necrosis are prone to occur in the late stage, all of which aggravate disease severity and increase difficulties for its treatment. CASE PRESENTATION: Herein, we reported a case of right talus total dislocation accompanied by medial malleolus fracture and posterior tubercle fracture caused by traffic accident. One hour after injury, the doctor tried to perform manual reduction but failed. Then, we successfully performed manual reduction and plaster external fixation on this patient under anesthesia 6 h after injury, followed by the oral administration of Chinese medicine for 3 months. Twenty months of follow-up investigations revealed that no skin necrosis, talus dislocation, talus necrosis, or other complications occurred; no obvious joint degeneration was observed and the fractures of medial malleolus and talus healed well. MRI of ankle joint indicated the disappearance of ankle effusion caused by injury, and the bone marrow edema had also subsided at talus, medial malleolus, and lateral malleolus and calcaneus. Patient presented with no ligament relaxation, ankle instability, pain, swelling, or functional limitation of the injured limb. AOFAS score reached 100. Daily functions and recreation activities were recovered back to the normal level. CONCLUSION: For patients with closed total dislocation of the talus, fine therapeutic effects can be achieved by early closed manual reduction and plaster external fixation under anesthesia, in combination with oral Chinese herbal medicine afterwards. It is worthy of reference for clinicians.

Hydrothermal carbonization of kitchen waste: An analysis of solid and aqueous products and the application of hydrochar to paddy soil.

Hydrothermal carbonization (HTC) technology can potentially be used to safely and sustainably utilize kitchen waste (KW). However, the characteristics of HTC solid products (hydrochar) and aqueous products (HAP) based on different types of KW have not yet been clarified. Here, four types of KW, cellulose-based (CL), skeleton-based (SK), protein-based (PT), and starch-based (ST) KW, were used for HTC at 180 °C, 220 °C, and 260 °C. The basic physicochemical properties and structures of hydrochars and HAP were analyzed, and the effects of different hydrochars on rice growth were characterized. HTC decreased the H/C and O/C of KW. All hydrochars were acidic (3.12 to 6.78) and the pH values increased with the HTC temperature, while high HTC temperature reduced the porosity of hydrochars. HTC promoted the enrichment of total carbon (up to 78.1 %), total nitrogen (up to 62.6 %), and total phosphorus (up to 171.6 %) in KW. More carbon (60.7-88.0 %) and nitrogen (up to 87.4 %) were present in the hydrochars than in the HAP. The relative content of C1s increased and O1s decreased in CL and ST hydrochars as the HTC temperature increased, while the opposite pattern was observed for SK and PT hydrochars. The dissolved organic matter (DOM) of different hydrochars and HAP were mainly humus-like substances. The biodegradability of the DOM in HAP was often higher than the corresponding hydrochar, and their DOM biodegradability increased with the HTC temperature. The content of heavy metals from different hydrochars did not exceed the relevant thresholds of fertilizer standards. Rice grain yield increased by 3.7-11.1 % in the hydrochar treatments without phosphate fertilizer addition compared with the control treatment. The results of this study provide new theoretical and empirical insights into the potential for HTC technology to be used for the recycling of KW and its products in the agricultural environment.

Selenium biofortification in Pleurotus eryngii and its effect on lead adsorption of gut microbiota via in vitro fermentation.

It is of great significance to develop safe and efficient dietary selenium sources to improve lead toxicity. In this study, selenate, selenite, SeMet and Se-yeast were supplied to investigate the Se biofortification and bioaccessibility in Pleurotus eryngii. The effects of Se-enriched P. eryngii on lead binding bacteria were investigated via in vitro fermentation. With 40 mg/kg Se in the substrate, the total Se contents of P. eryngii treated with selenite and Se-yeast were 145.22 ± 8.00 mg/kg and 90.01 ± 7.01 mg/kg, respectively. Compared with selenite, Se-yeast treatment significantly increased the organic Se proportion in P. eryngii (SeCys2 2.85 ± 0.17%, MeSeCys 2.33 ± 0.21% and SeMet 78.19 ± 1.58%), which led to higher bioaccessibility. With 1 mg/L lead treatment during in vitro fermentation, Se-enriched P. eryngii promoted the growth of Desulfovibrio, which contributed to the increase of gut microbiota lead adsorption. Se-enriched P. eryngii cultivated with Se-yeast could be used as dietary Se sources for lead toxicity improvement.

Phlorizin alleviates cholinergic memory impairment and regulates gut microbiota in d-galactose induced mice.

We explored the effect of phlorizin against cholinergic memory impairment and dysbacteriosis in D-galactose induced ICR mice. The control (CON) group, D-galactose model (DGM) group, and three groups (DG-PL, DG-PM, DG-PH) treated with phlorizin at 0.01%, 0.02%, and 0.04% (w/w) in diets were raised for 12 weeks. Supplementing with phlorizin reversed the loss of organ coefficient and body weight caused by D-galactose. The functional abilities of phlorizin on hippocampal-dependent spatial learning and memory, anti-oxidation, anti-inflammation were also observed. Meanwhile, phlorizin intervention upregulated the gene expression of Nrf2, GSH-PX, SOD1, decreased the gene expression of NF-κB, TLR-4, TNF-α, and IL-1ß in the hippocampus, while enhanced the gene expression of JAM-A, Mucin2, Occludin in the caecum. Furthermore, a neurotransmitter of acetylcholine (ACh) was enhanced, while acetylcholinesterase (AChE) activity was inhibited by phlorizin administration. Moreover, phlorizin administration increased short-chain fatty acids (SCFAs) content, and reduced lipopolysaccharides (LPS) levels, which may relate to the rebuilding of gut microbiota homeostasis. Treatment with phlorizin may be an effective intervention for alleviating cognitive decline and gut microbiota dysbiosis.

Xuebijing Injection Ameliorates H / 中国结合医学杂志

OBJECTIVE@#To investigate the protective effects and underlying mechanisms of Xuebijing Injection (XBJ) on the lung endothelial barrier in hydrogen sulfide (H@*METHODS@#Sprague-Dawley rats were exposed to H@*RESULTS@#The morphological investigation showed that XBJ attenuated H@*CONCLUSIONS@#XBJ ameliorated H

Calcitriol ameliorates damage in high-salt diet-induced hypertension: Evidence of communication with the gut-kidney axis.

Several studies have established a link between high-salt diet, inflammation, and hypertension. Vitamin D supplementation has shown anti-inflammatory effects in many diseases; gut microbiota is also associated with a wide variety of cardiovascular diseases, but potential role of vitamin D and gut microbiota in high-salt diet-induced hypertension remains unclear. Therefore, we used rats with hypertension induced by a high-salt diet as the research object and analyzed the transcriptome of their tissues (kidney and colon) and gut microbiome to conduct an overall analysis of the gut-kidney axis. We aimed to confirm the effects of high salt and calcitriol on the gut-kidney immune system and the composition of the intestinal flora. We demonstrate that consumption of a high-salt diet results in hypertension and inflammation in the colon and kidney and alteration of gut microbiota composition and function. High-salt diet-induced hypertension was found to be associated with seven microbial taxa and mainly associated with reduced production of the protective short-chain fatty acid butyrate. Calcitriol can reduce colon and kidney inflammation, and there are gene expression changes consistent with restored intestinal barrier function. The protective effect of calcitriol may be mediated indirectly by immunological properties. Additionally, the molecular pathways of the gut microbiota-mediated blood pressure regulation may be related to circadian rhythm signals, which needs to be further investigated. An innovative association analysis of the microbiota may be a key strategy to understanding the association between gene patterns and host.

Xuebijing Injection Ameliorates H2S-Induced Acute Respiratory Distress Syndrome by Promoting Claudin-5 Expression.

OBJECTIVE: To investigate the protective effects and underlying mechanisms of Xuebijing Injection (XBJ) on the lung endothelial barrier in hydrogen sulfide (H2S)-induced acute respiratory distress syndrome (ARDS). METHODS: Sprague-Dawley rats were exposed to H2S (300 ppm) to establish ARDS model, while human pulmonary microvascular endothelial cells (HPMECs) were incubated with NaHS (a H2S donor, 500 µmol/L) to establish cell model. H2S and XBJ were concurrently administered to the rat and cell models. Lung hematoxylin and eosin staining, immunohistochemistry, transmission electron microscopy and wet/dry ratio measurement were used to confirm ARDS induced by H2S in vivo. The expression levels of claudin-5, phosphorylated protein kinase B (p-AKT)/t-AKT and p-forkhead box transcription factor O1 (FoxO1)/t-FoxO1 in vivo and in vitro were also assessed. Paracellular permeability and transepithelial electrical resistance (TEER) were measured to evaluate endothelial barrier function in the cell model. RESULTS: The morphological investigation showed that XBJ attenuated H2S-induced ARDS in rats. XBJ significantly ameliorated both the reduction in TEER and the increased paracellular permeability observed in NaHS-treated HPMECs (P<0.05). The protective effects of XBJ were blocked by LY294002, a phosphatidylinositol 3-kinase (PI3K)/AKT/FoxO1 pathway antagonist (P<0.05). Furthermore, XBJ promoted the expression of claudin-5 and increased the levels of p-AKT and p-FoxO1 in vivo and in vitro (P<0.05). CONCLUSIONS: XBJ ameliorated H2S-induced ARDS by promoting claudin-5 expression via the PI3K/AKT/FoxO1 signaling pathway.

Comparison of effects on colitis-associated tumorigenesis and gut microbiota in mice between Ophiocordyceps sinensis and Cordyceps militaris.

BACKGROUND: Gut microbiota plays an indispensable role in the treatment of inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). As traditional medicinal fungi, previous studies have shown that Ophiocordyceps sinensis could better maintain intestinal health via promoting the growth of probiotics in vitro compared with Cordyceps militaris. However, the detailed pharmacological activities and clinical efficacy of O. sinensis and C. militaris are still elusive. PURPOSE: We aimed to evaluate the different actions of O. sinensis and C. militaris on colitis-associated tumorigenesis in Azoxymethane (AOM)/Dextran Sulfate Sodium (DSS)-treated mice and explore the potential gut microbiota-dependent mechanisms. METHODS: C57BL/6 mice (Male, 4 weeks old) were used to construct the AOM/DSS-induced CAC mice model. The mice were administered with 0.6 mg/g/d O. sinensis or C. militaris for 12 weeks. It's worth noting that fecal microbiota transplantation (FMT) and antibiotic treatment were used to investigated the complex interactions between the medicinal fungi, gut microbiota and colonic tumorigenesis. RESULTS: O. sinensis treatment significantly increased the body weight and survival rate, reduced the number of colon tumors, improved the damage of colon epithelial tissue, restored the crypt structure and alleviate the colonic inflammation in AOM/DSS-treated mice. RT-qPCR results indicated that O. sinensis partly regulated the Wnt/ß-catenin signaling via alleviating the overexpression of ß-catenin, TCF4 and c-Myc genes in adjacent noncancerous tissues. Compared with C. militaris, O. sinensis showed better anti-tumor activity. Gut microbiota analysis revealed that O. sinensis reversed the decline of gut microbiota diversity and the structural disorder induced by AOM/DSS. Spearman's correlation analysis showed that O. sinensis promoted the growth of Parabacteroides goldsteinii and Bifidobacterium pseudolongum PV8-2, which were positively correlated with the anti-tumor activity and the production of SCFAs. FMT combined with antibiotic treatment showed that horizontal fecal transfer derived from O. sinensis-treated mice improved the intestinal inflammation and alleviated the colitis-associated tumorigenesis, which was consistent with the direct ingestion of O. sinensis. CONCLUSION: O. sinensis could better attenuate colitis-associated tumorigenesis compared with C. militaris. These effects might be at least partially due to the increased abundance of probiotics, especially P. goldsteinii and B. pseudolongum PV8-2.

Polysaccharide from Flammulina velutipes attenuates markers of metabolic syndrome by modulating the gut microbiota and lipid metabolism in high fat diet-fed mice.

Natural biological macromolecules with putative functions of gut microbiota regulation possess the advantage of improving metabolic syndrome (MS). In this research, we aimed to determine the effects of Flammulina velutipes polysaccharide (FVP) (Expt. 1) and fecal microbiota transplantation (FMT) (Expt. 2) on MS-related disorders, gut microbiota structure changes and their underlying mechanisms in a murine model fed with high-fat diet (HFD). In Expt. 1, six-week-old male C57BL/6J mice were fed with a control diet (10% calories from fat) or a high fat diet (45% calories from fat), administered with saline or FVP (0.4 mg per g b.w.) by gavage over a 12-week period. In Expt. 2, mice were fed with a HFD, administered with fecal supernatants from healthy and FVP-fed donor mice for 12 weeks simultaneously. The body mass, blood lipid levels and blood glucose homeostasis of mice were analyzed, and total RNA from mouse liver and adipose tissue were extracted by TRIzol and the lipid metabolism-related gene expressions were calculated by qRT-PCR. Gut microbiota changes were evaluated by high-throughput sequencing. Results indicated that FVP and FMT supplementations showed an attenuation effect on mouse obesity, hyperlipidemia and insulin resistance. Up-regulated expressions of Ampkα1 and Ppara were found both in FVP and FMT treatment groups. Different changes were found in the gut microbiota caused by FVP and FMT, respectively. PICRUSt analysis indicated that compared with FVP supplementation, FMT showed a significant effect on regulating lipid metabolism in HFD-fed mice. The findings from this study indicated that oral administrations of FVP or FMT could significantly attenuate MS-related obesity, hyperlipidemia and insulin resistance in HFD-fed mice, and the beneficial effects may be mediated through lipid metabolism and gut microbiota regulation in different ways. These results improve the understanding of the functional activity of FVP as prebiotics.

Polyphenols from Securidaca inappendiculata alleviated acute lung injury in rats by inhibiting oxidative stress sensitive pathways.

Objective: Securidaca inappendiculata is a medicinal plant frequently used in the treatment of inflammatory diseases in south China. In this study, we aimed to explore its bioactive constituent which contributes to the anti-inflammatory activity. Methods: Polyphenol-enriched and polyphenol-deprived fractions (PRF and PDF, respectively) were separated from the ethanolic extract by HPD300 macroporous resin-based method, and their anti-inflammatory activities were investigated on a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model in rats. The possible mechanism of action in alleviating acute inflammation was studied using RAW264.7 cells. Results: Both Folin-Ciocalteu and 1H nuclear magnetic resonance (NMR) analyses showed that polyphenolic content in PRF was approximately 10 times higher than that of PDF, and this observation reflected in their antioxidative capacities. PRF but not PDF significantly decreased the level of malondialdehyde, suppressed the expression of nicotinamide phosphoribosyltransferase (NAMPT) protein, and improved the severity of ALI in rats. PRF at 10 µg/mL effectively downregulated the expression of proteins NAMPT, HMGB1, TLR4, and p-p65, and scavenged the intracellular reactive oxygen species (ROS) in LPS-primed RAW264.7 cells. N-acetyl-L-cysteine exhibited similar inhibitory effects on ROS production and NAMPT-mediated TLR4/NF-κB activation in vitro, whereas nicotinamide mononucleotide antagonized all the changes induced by PRF during cotreatments. Conclusion: As an antioxidant, PRF exhibited potent anti-inflammatory activity under both in vivo and in vitro conditions by downregulating NAMPT and TLR4/NF-κB. Accordingly, polyphenols were identified as important bioactive constituents in S. inappendiculata targeting oxidative stress-sensitive pro-inflammatory pathways.

Qing-Luo-Yin Alleviated Experimental Arthritis in Rats by Disrupting Immune Feedback Between Inflammatory T Cells and Monocytes: Key Evidences from Its Effects on Immune Cell Phenotypes.

BACKGROUND: Qing-Luo-Yin (QLY) is an anti-rheumatic herbal formula. Despite the well-investigated therapeutic efficacy of QLY, its immune regulatory properties are largely unknown. CD4+ T cells and monocytes are two key parameters in rheumatoid arthritis (RA). This study investigated the changes in these cells in QLY-treated RA animal models. MATERIALS AND METHODS: RA models were induced in male SD rats and were orally treated with QLY. Dynamic metabolic changes in collagen-induced arthritis (CIA) rats were monitored by 1H NMR approach. The immunity profiles of CIA and adjuvant-induced arthritis (AIA) rats were evaluated using immunohistochemical, PCR, ELISA, cytokine chip, flow cytometry, and immunofluorescence experiments. The bioactive components in QLY were identified by bioinformatic-guided LC-MS analyses. The compounds with high abundance in QLY decoction and easily absorbed were taken as key anti-rheumatic components and used to treat blood-derived immune cells using in vitro experiments. RESULTS: The results indicated that QLY decreased Th17 cells frequency and T cells-released IL-6, IL-17 and GM-CSF in CIA rats, which was attributed to the impaired lymphocyte maturation and altered differentiation. QLY inhibited lactic acid production and inflammatory polarization in the monocytes during the peak period of AIA and CIA. AIA monocytes elicited significant increase in Th17 cells counts, IL-6 and IL-1ß secretion in co-cultured splenocytes, which was abrogated by QLY. QLY-containing serum suppressed the phosphorylation of JNK and p65 in AIA lymphocyte-stimulated normal monocytes and consequently inhibited iNOS and IL-1ß expression as well as IL-6 and IL-1ß production. Matrine, sinomenine and sophocarpine were identified as major bioactive compounds in QLY. These identified compounds effectively inhibited the development of inflammatory T cells using concentrations detected in QLY-treated rats. At higher concentrations (20-fold increase), the chemical stimuli significantly suppressed the production of IL-1ß in AIA monocytes by inhibiting JNK and p65 pathways. CONCLUSION: By targeting inflammatory T cells and monocytes as well as disrupting their interplay, QLY improved immune environment in RA models especially during the active stages of disease.

Research progress of Traditional Chinese Medicine on treating primary bronchial lung cancer / 国际中医中药杂志

The clinical effect of Traditional Chinese Medicine (TCM) in the treatment of primary bronchial lung cancer is good. To a certain extent, TCM can control the progress of the disease and improve quality of life by the treatment of syndrome differentiation, disease-modified prescription, experience prescription, Chinese patent medicine, TCM injection, acupuncture and acupoint application, which have been combined with chemotherapy. The mechanism of TCM in the treatment of primary bronchial lung cancer mainly includes inhibition of lung cancer cell proliferation, induction of lung cancer cell apoptosis, improvement of body immunity and overcoming chemotherapy resistance.

Polyphenols from Securidaca inappendiculata alleviated acute lung injury in rats by inhibiting oxidative stress sensitive pathways / 中草药·英文版

Objective: Securidaca inappendiculata is a medicinal plant frequently used in the treatment of inflammatory diseases in south China. In this study, we aimed to explore its bioactive constituent which contributes to the anti-inflammatory activity. Methods: Polyphenol-enriched and polyphenol-deprived fractions (PRF and PDF, respectively) were separated from the ethanolic extract by HPD300 macroporous resin-based method, and their anti-inflammatory activities were investigated on a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model in rats. The possible mechanism of action in alleviating acute inflammation was studied using RAW264.7 cells. Results: Both Folin-Ciocalteu and

Effects of a ß-type glycosidic polysaccharide from Flammulina velutipes on anti-inflammation and gut microbiota modulation in colitis mice.

Using the Flammulina velutipes polysaccharide (FVP) extracted from our previous study, herein, we investigated the improvement of this starch-free ß-type glycosidic polysaccharide in alleviating dextran sodium sulfate-induced ulcerative colitis (UC) in mice. The absolute and relative abundance of intestinal microbes in the mouse feces were both determined by 16s RNA gene sequencing. The results from the histological analysis indicate that FVP treatment reduced the symptoms of UC, up- or down-regulated the relative gene expression levels in the colon tissue, and enhanced the capacity of metabolic and biogenesis in the UC mice, as predicted by PICRUSt. 11 species of gut microbes including Lactobacillus, Bifidobacterium, and Clostridium associated with UC symptoms were analyzed by correlation analysis. Our findings suggest that FVP can alleviate the UC symptoms in mice by regulating specific gut microbes, improving the understanding of the functional activity of FVPs as prebiotics.

High-dose omega-3 polyunsaturated fatty acid supplementation might be more superior than low-dose for major depressive disorder in early therapy period: a network meta-analysis.

BACKGROUND: The application of n-3 Polyunsaturated Fatty Acids (n-3 PUFAs) supplementation for major depressive disorder (MDD) has been widely discussed in recent years, but its efficacy and application are still controversial. This network meta-analysis was conducted to compare the efficacy of different dosages of n-3 PUFAs on MDD patients in the early period of treatment. METHODS: Randomized controlled trials (RCTs) exploring the efficacy of n-3 PUFA supplementation for patients with MDD were retrieved from the databases of Pubmed, Embase and the Cochrane Library. RCTs comparing the efficacy of n-3 PUFA for adult (≥18 years) MDD patients without comorbidity were eligible for our study. The score of depressive symptoms in early therapy period of the treatment (≤9 weeks) was extracted. Standardized mean deviations (SMDs) of all the sores from the eligible RCTs were synthesized in a pairwise meta-analysis in frequentist framework and a random-effects network meta-analysis in Bayesian framework for the overall and subgroups (high- and low-dose) efficacy of n-3 PUFAs. RESULTS: A total of 910 MDD patients in 10 trials with 3 adjuvant therapy strategies (high-dose n-3 PUFAs, low-dose n-3 PUFAs and placebo) were included. Results of pairwise meta-analysis showed that n-3 PUFAs were superior to placebo (SMD: 1.243 ± 0.596; 95% CI: 0.060 ~ 2.414). Results of the network meta-analysis showed that both the high (SMD: 0.908 ± 0.331; 95% CI: 0.262 ~ 1.581) and the low-dose (SMD: 0.601 ± 0.286; 95% CI: 0.034 ~ 1.18) n-3 PUFAs were superior to placebo, and the efficacy of high-dose n-3 PUFAs is superior to that of low-dose. CONCLUSIONS: High-dose n-3 PUFAs supplementation might be more superior than low-dose in the early therapy period for MDD. More head-to-head clinical trials need to be carried out to provide more direct comparison and enhance the evidence of the efficacy of n-3PUFAs for MDD.

1,7-Dihydroxy-3,4-Dimethoxyxanthone Inhibits Lipopolysaccharide-Induced Inflammation in RAW264.7 Macrophages by Suppressing TLR4/NF-κB Signaling Cascades.

Securidaca inappendiculata Hassk. is a traditional Chinese anti-rheumatic herbal medicine native to southern China. In this study, we identified a possible TLR4 inhibitor from this plant. General effects of its xanthone-rich fraction (XRF) on inflammation in vitro were investigated by immunoblotting experiments performed on lipopolysaccharides (LPS)-treated RAW264.7 cells, and the possible ligand of TLR4 within was screened out by analyzing chemical composition differences of the XRF containing cell culture medium under different inflammatory circumstances. The interaction between ligand and TLR4 was validated by cellular thermal shift assay (CETSA) and molecular docking simulation, and TLR4/NF-κB pathway status was investigated by immunoprecipitation, ELISA, immunofluorescence, dual-luciferase reporter, and immunoblotting experiments. Treatment with XRF resulted in significant decrease in p-p65 and p-JNK, and the signal accounting for 1,7-dihydroxy-3,4-dimethoxyxanthone (XAN) at 12.5 min with mass of 289.29 was greatly decreased in XRF containing medium after LPS stimulus because of enhanced interaction with increased TLR4. CETSA and molecular docking simulation demonstrated that XAN could bind to TLR4 directly on a smooth region adjacent to its contact interface with MD-2. XAN treatment inhibited the dimerization of TLR4 and transcriptional activity of NF-κB in HEK293T cells and decreased p65 accumulation in nucleus and pro-inflammatory cytokines production in RAW264.7 cells receiving LPS treatment. Overall evidences suggest that XAN could be a selective TLR4 inhibitor with potent anti-inflammatory effects. Also, it indicated that xanthone derivatives could have promising clinical application in many immune-mediated inflammations by acting as TLR4 inhibitors.

[Effect of different fluence rates applied in curcumin-photodynamic therapy on Candida albicans biofilms].

PURPOSE: In this study, the inactivation effect of different fluence rates on Candida albicans biofilms during curcumin-photodynamic therapy was investigated in vitro. METHODS: The standard Candida albicans and clinical isolated Candida albicans were selected as model fungus and different fluence rates (12, 22, 42, 62, 82, 102 mW/cm2) during curcumin-photodynamic therapy were applied to inactivate Candida albicans biofilm. To evaluate the inactivation effect, XTT assay and Live/Dead kit were employed to quantify and visualize the activities of Candida albicans biofilms. The data were analyzed with SPSS 19.0 software package. RESULTS: When 40 µmol/L of curcumin was applied followed by 4 min illumination, both standard Candida albicans and clinical isolated Candida albicans biofilms were greatly inactivated along with the increase of fluence rates. When fluence rate increased to 102 mW/cm2, there was no significant difference between the experimental group and the previous experimental group(P>0.05). CONCLUSIONS: Fluence rate plays an important role in inactivation of Candida albicans biofilms during curcumin-photodynamic therapy, with optimized value of fluence rate of 82 mW/cm2 in this study.