Effect of Acupuncture on Endometrial Blood Flow in Women Undergoing in vitro Fertilization Embryo Transfer: A Single Blind, Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of manual acupuncture on endometrial blood flow parameters by three-dimensional (3D) power Doppler ultrasound in women undergoing in vitro fertilization embryo transfer (IVF-ET). METHODS: Seventy patients undergoing IVF-ET were equally randomized into traditional or sham acupuncture treatment group for totally 4 days (from the day of oocyte aspiration to the day of embryo transfer) of treatment by random envelope method at the Reproductive Medicine Center and Outpatient Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology from January 2013 to December 2015. Patients in the traditional acupuncture group accepted traditional acupuncture methods with manual acupuncture, and Zhongji (CV3), Qihai (CV 6), Sanyinjiao (SP6), Taichong (LR 3), Tianshu (ST 25), Guilai (ST 29) and Zusanli (ST 36) were chosen. Patients at the sham acupuncture group accepted shallow acupuncture methods at 4 non-meridian points at each shoulder and upper arm. Outcome measures included endometrial ultrasonic indices such as vascularization index (VI), flow index (FI) and vascularization flow index (VFI), endometrial thickness and volume, subendometrial VI (sVI), subendometrial FI (sFI), subendometrial VFI (sVFI), implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births. RESULTS: Finally, 34 patients in the traditional acupuncture group and 35 in the sham acupuncture group completed this trial. VI, FI and VFI of the traditional acupuncture group were significantly higher than those in the sham acupuncture group (P<0.05). No significant differences were found in endometrial thickness, endometrial volume, sVI, sFI, sVFI, implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births (P>0.05). CONCLUSIONS: Manual acupuncture performed after oocyte aspiration and before transplantation improved the endometrial blood flow parameters VI, RI and VFI in women who underwent IVF-ET, instead of sVI, sFI and sVFI. Therefore, acupuncture might be beneficial in women undergoing IVF-ET by increasing endometrial blood flow and endometrial receptivity. (Registration No. ChiCTR2100053354).

Phenolamide extract of apricot bee pollen alleviates glucolipid metabolic disorders and modulates the gut microbiota and metabolites in high-fat diet-induced obese mice.

Obesity is a serious health problem, and it is important to discover natural active ingredients for alleviating it. In this study, we investigated the effect of phenolamide extract (PAE) from apricot bee pollen on obese mice fed a high-fat diet (HFD). The main compounds in PAE were identified by HPLC-ESI-QTOF-MS/MS, and HFD-fed mice were treated with PAE for 12 weeks. The results demonstrated that the content of phenolamides in PAE was 87.75 ± 5.37%, with tri-p-coumaroyl spermidine as the dominant compound. PAE intervention in HFD-fed mice effectively reduced weight gain and lipid accumulation in the liver and epididymal fat, increased glucose tolerance, reduced insulin resistance and improved lipid metabolism. In terms of the gut microbiota, PAE could reverse the increase in the Firmicutes/Bacteroidetes ratio in HFD-fed mice. In addition, PAE could increase beneficial bacteria such as Muribaculaceae and Parabacteroides, and reduce harmful bacteria such as Peptostreptococcaceae and Romboutsia. Metabolomic analysis revealed that PAE could regulate the levels of metabolites, including bile acids, phosphatidyl choline (PC), lysophosphatidylcholine (lysoPC), lysophosphatidylethanolamine (lysoPE) and tyrosine. This is the first study finding that PAE can regulate glucolipid metabolism and modulate the gut microbiota and metabolites in HFD-induced obese mice, and the results indicate that PAE can be used as a functional dietary supplement to alleviate HFD-induced obesity.

The Dynamic Changes in the Main Substances in Codonopsis pilosula Root Provide Insights into the Carbon Flux between Primary and Secondary Metabolism during Different Growth Stages.

The dried root of Codonopsis pilosula (Franch.) Nannf., referred to as Dangshen in Chinese, is a famous traditional Chinese medicine. Polysaccharides, lobetyolin, and atractylenolide III are the major bioactive components contributing to its medicinal properties. Here, we investigated the dynamic changes of the main substances in annual Dangshen harvested at 12 time points from 20 May to 20 November 2020 (from early summer to early winter). Although the root biomass increased continuously, the crude polysaccharides content increased and then declined as the temperature fell, and so did the content of soluble proteins. However, the content of total phenolics and flavonoids showed an opposite trend, indicating that the carbon flux was changed between primary metabolism and secondary metabolism as the temperature and growth stages changed. The changes in the contents of lobetyolin and atractylenolide III indicated that autumn might be a suitable harvest time for Dangshen. The antioxidant capacity in Dangshen might be correlated with vitamin C. Furthermore, we analyzed the expression profiles of a few enzyme genes involved in the polysaccharide biosynthesis pathways at different growth stages, showing that CpUGpase and CPPs exhibited a highly positive correlation. These results might lay a foundation for choosing cultivars using gene expression levels as markers.

Characteristics analysis of water pollutants in Cihu Lake, China, based on a multivariate statistical analysis method.

In order to understand the sources of pollutants and the temporal and spatial distribution characteristics of the water quality in Cihu Lake, China, the monitoring data of seven water quality indicators from 12 sampling sites from 2015 to 2019 were selected, and the temporal and spatial variation laws of the water quality and pollution sources were analyzed by the use of the multivariate statistical analysis method. The results show that nitrogen and phosphorus pollution in the lake is dominant. The average concentrations of total nitrogen (TN) and total phosphorus (TP) exceed the surface water quality Class III standards by 1.6 and 2.2 times, respectively. Spatially, the results of the cluster analysis showed that the water quality in Cihu Lake can be categorized into three regions: the northern half of the lake, the southern half of the lake, and the canal entering the lake. Temporally, the water quality in these three regions can be classified into three categories: March to May (the northern half of Cihu Lake), September to November (the southern half of Cihu Lake), and September (the canal entering Cihu Lake). The discriminant analysis results showed that NH3-N, TN, CODCr, and BOD5 are the main factors that affect the uneven spatial distribution of the water quality of Cihu Lake, while TN, DO, and CODMn are the main factors that affect the temporal difference in the northern half of Cihu Lake, and NH3-N, TP, CODCr, DO, CODMn, TN, and TP are the main factors affecting the temporal difference in the southern half of Cihu Lake and the canal entering Cihu Lake. It was found that the water pollution in the study area can be mainly attributed to the incoming water and urban domestic pollution. The main pollution sources for the canal entering Cihu Lake and the southern half of Cihu Lake are the water from the sewage treatment plant and the domestic sewage that has not been intercepted, while the northern half of Cihu Lake is mainly affected by surface runoff, mixed rainwater and sewage, and internal pollution.

Iridoid Glycosides and Flavonoids Isolated from the Twigs and Leaves of Callicarpa nudiflora and Their Anti-Inflammatory Activities.

A new iridoid glycoside, named 6'-O-trans-feruloyl-8-epiloganic acid, together with fifteen known compounds were isolated from the twigs and leaves of Callicarpa nudiflora, a traditional Chinese medicine to treat inflammatory-related diseases. Their structures were identified by comprehensive spectroscopic analysis and comparison with reported data. Bioassay results revealed that twelve of the isolates could obviously inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cell lines with IC50 values from 0.64 to 38.72 µM. Among them, compounds 1 (3.27 µM), 6 (5.23 µM), 13 (1.56 µM) and 14 (0.64 µM) exhibited significantly higher activities than that of the positive control (27.13 µM). Additionally, it was supposed that the presence of the carboxy group at the C-4 position of iridoid glycosides and glycosylation at C-3 position of flavonoids might impact their inhibitory activities against NO production.

Edge-enhanced dual discriminator generative adversarial network for fast MRI with parallel imaging using multi-view information.

In clinical medicine, magnetic resonance imaging (MRI) is one of the most important tools for diagnosis, triage, prognosis, and treatment planning. However, MRI suffers from an inherent slow data acquisition process because data is collected sequentially in k-space. In recent years, most MRI reconstruction methods proposed in the literature focus on holistic image reconstruction rather than enhancing the edge information. This work steps aside this general trend by elaborating on the enhancement of edge information. Specifically, we introduce a novel parallel imaging coupled dual discriminator generative adversarial network (PIDD-GAN) for fast multi-channel MRI reconstruction by incorporating multi-view information. The dual discriminator design aims to improve the edge information in MRI reconstruction. One discriminator is used for holistic image reconstruction, whereas the other one is responsible for enhancing edge information. An improved U-Net with local and global residual learning is proposed for the generator. Frequency channel attention blocks (FCA Blocks) are embedded in the generator for incorporating attention mechanisms. Content loss is introduced to train the generator for better reconstruction quality. We performed comprehensive experiments on Calgary-Campinas public brain MR dataset and compared our method with state-of-the-art MRI reconstruction methods. Ablation studies of residual learning were conducted on the MICCAI13 dataset to validate the proposed modules. Results show that our PIDD-GAN provides high-quality reconstructed MR images, with well-preserved edge information. The time of single-image reconstruction is below 5ms, which meets the demand of faster processing.

Overexpression of SmLAC25 promotes lignin accumulation and decreases salvianolic acid content in Salvia miltiorrhiza.

Laccase (LAC) is a blue multicopper oxidase that contains four copper ions, which is involved in lignin polymerization and flavonoid biosynthesis in plants. Although dozens of LAC genes have been identified in Salvia miltiorrhiza Bunge (a model medicinal plant), most have not been functionally characterized. Here, we explored the expression patterns and the functionality of SmLAC25 in S. miltiorrhiza. SmLAC25 has a higher expression level in roots and responds to methyl jasmonate, auxin, abscisic acid, and gibberellin stimuli. The SmLAC25 protein is localized in the cytoplasm and chloroplasts. Recombinant SmLAC25 protein could oxidize coniferyl alcohol and sinapyl alcohol, two monomers of G-lignin and S-lignin. To investigate its function, we generated SmLAC25-overexpressed S. miltiorrhiza plantlets and hairy roots. The lignin content increased significantly in all SmLAC25-overexpressed plantlets and hairy roots, compared with the controls. However, the concentrations of rosmarinic acid and salvianolic acid B decreased significantly in all the SmLAC25-overexpressed lines. Further studies revealed that the transcription levels of some key enzyme genes in the lignin synthesis pathway (e.g., SmCCR and SmCOMT) were significantly improved in the SmLAC25-overexpressed lines, while the expression levels of multiple enzyme genes in the salvianolic acid biosynthesis pathway were inhibited. We speculated that the overexpression of SmLAC25 promoted the metabolic flux of lignin synthesis, which resulted in a decreased metabolic flux to the salvianolic acid biosynthesis pathway.

Network pharmacology combined with pharmacodynamics revealed the anti-inflammatory mechanism of Tanreqing capsule against acute-exacerbation chronic obstructive pulmonary disease.

Acute-exacerbation chronic obstructive pulmonary disease (AECOPD) is mainly associated with acute respiratory tract infection. In recent years, a growing number of studies have found that Tanreqing capsule (TRQ) has a favorable anti-inflammatory effect. In this study, we used network pharmacology and pharmacodynamics to explore the molecular mechanism and effects of TRQ in AECOPD treatment. To further understand the molecular mechanism of TRQ in AECOPD treatment, we used the network pharmacology to predict components of TRQ, TRQ-related targets, AECOPD-related targets, and pathways. In addition, we used the cigarette-smoke/lipopolysaccharide -induced AECOPD experimental model in Sprague-Dawley rats (72 rats randomly divided into six groups [n = 12 each]: control, model, high-TRQ [TRQ-H], medium-TRQ [TRQ-M], low-TRQ, and dexamethasone [Dex]) to evaluate the therapeutic effects of TRQ and to verify the network pharmacology. We found that 59 overlapping targets based on component-and AECOPD-related targets were frequently involved in the advanced glycation end product-receptor for advanced glycation end product signaling pathway in diabetic complications, the phosphatidylinositol-3-kinase-protein kinase B signaling pathway, and the hypoxia-inducible factor 1 signaling pathway, which might play important roles in the anti-inflammatory mechanism of TRQ in AECOPD treatment. Moreover, TRQ groups exerted protective effects against AECOPD by reducing the infiltration of inflammatory cells. Meanwhile, TRQ-M and TRQ-H groups significantly downregulated or upregulated the expression of tumor necrosis factor, interleukin (IL) 6, C-reactive protein, IL10, and serum amyloid A, as key targets in network pharmacology, in the serum and bronchoalveolar lavage fluid to achieve anti-inflammatory efficacy. Our study showed that TRQ had better anti-inflammatory efficacy against AECOPD, and initially elucidated its molecular mechanism. Moreover, our study also provides a new strategy to explore effective mechanism of TRQ against AECOPD; and further studies are needed to validate the biological processes and pathways of TRQ against AECOPD.

Culture-dependent and culture-independent methods reveal microbe-clay mineral interactions by dissimilatory iron-reducing bacteria in an integral oilfield.

Fe(III) may be reasonably considered as one of the most important electron acceptors in petroleum reservoir ecosystems. The microbial mineralization of clay minerals, especially montmorillonite, is also of great significance to the exploration of petroleum and gas reservoirs. The bioreduction mechanisms of iron-poor minerals in petroleum reservoirs have been poorly investigated. This study investigated the bioreduction of montmorillonite by dissimilatory iron-reducing bacteria (DIRB) in petroleum reservoirs based on culture-independent and culture-dependent methods. Microbial diversity analysis revealed that Halolactibacillus, Bacillus, Alkaliphilus, Shewanella, Clostridium, and Pseudomonas were the key genera involved in the bioreduction of Fe(III). Through the traditional culture-dependent method, most of the key genera were isolated from the samples collected from petroleum reservoirs. Traditional culture-dependent methods can be used to reveal the metabolic characteristics of microorganisms (such as iron-reduction efficiency) to further elucidate the roles of different species (B. subtilis and B. alkalitelluris) in the environment. Moreover, many species with high iron-reduction efficiencies and relatively low abundances in the samples, such as Tessaracoccus and Flaviflexus, were isolated from petroleum reservoirs for the first time. The combination of culture-dependent and culture-independent methods can be used to further the understanding of the microbial communities and the metabolic characteristics of DIRB in petroleum reservoirs. Structural alterations that occurred during the interactions of microorganisms and montmorillonite were revealed through scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and X-ray powder diffraction (XRD). The physical and chemical analysis results demonstrated that microorganisms from petroleum reservoirs can dissolve iron-poor montmorillonite and promote the release of interlayer water. The secondary minerals illite and clinoptilolite were observed in bioreduced smectite. The formation of secondary minerals was closely related to the dissolution degrees of minerals based on iron reduction.

Identification of polyphenols from Rosa roxburghii Tratt pomace and evaluation of in vitro and in vivo antioxidant activity.

Rosa roxburghii Tratt pomace (RRTP) has increasingly attracted attention due to its various nutritional ingredients and health benefits. In this study, the free phenolic fraction (RRTP-FPF) and bound phenolic fraction (RRTP-BPF) were extracted from RRTP by solvent extraction method and alkaline hydrolysis method, respectively. The composition of polyphenols in RRTP-FPF and RRTP-BPF were identified by ultra-high performance liquid chromatography equipped with an electrospray ionization and quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS/MS). In vitro antioxidant assays indicated that RRTP-FPF and RRTP-BPF could scavenge radicals in a dose-dependent manner, and RRTP-BPF exhibited better scavenging activity than RRTP-FPF. In addition, RRTP-FPF and RRTP-BPF (20 âˆ¼ 100 µg/mL) treatment for 24 h could significantly increase the survival rate and decrease reactive oxygen species (ROS) level of paraquat-exposed nematodes through improving the activities of superoxide dismutase (SOD) and catalase (CAT). These results suggest that RRTP could be as a good and cheap source of natural antioxidants.

The pharmacokinetic study of Tanreqing and the interaction with cefixime in rat model of pneumonia by validated UPLC-MS/MS.

Combining traditional Chinese medicine and chemical drugs with antimicrobial activities has become more popular, but there is insufficient relevant research on such combinations. The Tanreqing injection (TRQI), a Chinese compound medicine, exhibits therapeutic effects in treating upper respiratory tract infections, severe influenza, and pneumonia. This research investigates the pharmacokinetics of TRQI in pneumonia model rats and explores the effect of the antibiotic cefixime on its metabolism. The pneumonia model rats were randomly divided into six groups: low, medium, and high (3, 6, and 12 mL kg-1) dose TRQI group, and a medium dose TRQI combined with cefixime (14.4 mg kg-1) group, with the remainder two groups were control group. Blood samples were collected from the tail vein at different time points between 0 and 24 h after injection. A sensitive and quick method based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established for the simultaneous determination of the 13 TRQI components in the blood samples. The analytes were separated on an XBridge™C18 column (2.1 mm × 150 mm, 5 µm), with the flow phase consisting of methanol and 0.1% formic acid water at a flow rate of 0.3 mL/min. The assay method met the biological sample determination requirements, demonstrating good adaptability and practicability for application in the pharmacokinetic study of TRQI in pneumonia model rats. Moreover, the method was used successfully in the interaction study of TRQI with cefixime. The results indicated that co-administration results in a significant change in the pharmacokinetic parameters of the main TRQI components. However, the changes in the pharmacokinetic characteristics of multiple TRQI components were inconsistent. Thus, the results of this drug combination under different pathological conditions in clinical applications were unpredictable. Therefore, more attention should be paid to the combined use of cefixime and TRQI in clinical applications to avoid the risk of adverse drug reactions in future studies.

SmSPL6 Induces Phenolic Acid Biosynthesis and Affects Root Development in Salvia miltiorrhiza.

Salvia miltiorrhiza is a renowned model medicinal plant species for which 15 SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) family genes have been identified; however, the specific functions of SmSPLs have not been well characterized as of yet. For this study, the expression patterns of SmSPL6 were determined through its responses to treatments of exogenous hormones, including indole acetic acid (IAA), gibberellic acid (GA3), methyl jasmonic acid (MeJA), and abscisic acid (ABA). To characterize its functionality, we obtained SmSPL6-ovexpressed transgenic S. miltiorrhiza plants and found that overexpressed SmSPL6 promoted the accumulation of phenolic acids and repressed the biosynthesis of anthocyanin. Meanwhile, the root lengths of the SmSPL6-overexpressed lines were significantly longer than the control; however, both the fresh weights and lateral root numbers decreased. Further investigations indicated that SmSPL6 regulated the biosynthesis of phenolic acid by directly binding to the promoter regions of the enzyme genes Sm4CL9 and SmCYP98A14 and activated their expression. We concluded that SmSPL6 regulates not only the biosynthesis of phenolic acids, but also the development of roots in S. miltiorrhiza.

Impact of Low Frequency Electro-acupuncture on Glucose and Lipid Metabolism in Unmarried PCOS Women: A Randomized Controlled Trial.

OBJECTIVE: To explore the effect of electro-acupuncture (EA) on glucose and lipid metabolism in unmarried patients with polycystic ovary syndrome (PCOS). METHODS: Fifty-four PCOS patients were equally randomized into true acupuncture group and sham acupuncture group (control) for totally 16 weeks of treatment by random method with a computerized randomization program. Patients in true acupuncture group accepted traditional acupuncture methods with EA and two sets of acupoint groups were used alternatively. The first set consisted of Zhongji (CV 3), Qihai (CV 6), Guilai (ST 29), Sanyinjiao (SP 6), Yinlingquan (SP 9), Hegu (LI4) and Baihui (GV 20), and the second set consisted of Tianshu (ST 25), ST 29, CV 3, CV 6, SP 6, Taichong (LR 3), Neiguan (PC) 6 and GV 20. Patients in the sham acupuncture group accepted shallow acupuncture methods through EA without electricity at 4 non-meridian points in each shoulder and upper arm. Outcome measures included body mass index (BMI), waist-hip-ratio (WHR), oral glucose tolerance test (OGTT), insulin release test, glucose and lipid metabolism indicators such as total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, adiponectin, leptin, visfatin, resistin, and interleukin (IL-6). RESULTS: Twenty-six subjects in the true acupuncture group and 20 subjects in the sham group completed the clinical trial. After 16 weeks of treatment, no significant difference in the outcome measures were observed between the two groups (P>0.05). However, as compared with baseline data, a reduction in weight, BMI, hipline, WHR, fasting glucose, homeostatic model assessment of insulin sensitivity, visfatin and HDL-C, and an increase in resistin and IL-6 were observed in the true acupuncture group (P<0.05). In addition, a reduction in visfatin and an increase in TC were also observed in the sham group (P<0.05). CONCLUSIONS: Acupuncture may have a beneficial effect in the treatment of PCOS by improving glucose and lipid metabolism. Moreover, the sham acupuncture may be not completely ineffective. Sham acupuncture may improve some of the aspects of the glucose and lipid metabolism of PCOS patients through a placebo effect. (Registration Nos. ChiCTR-TRC-12002529 and NCT01812161).

Tiaobu Feishen therapy inhibits inflammation induced by cigarette smoke extracts in a human monocyte/macrophage cell line.

OBJECTIVE: To study the mechanistic effects of Tiaobu Feishen therapy (TBFS) on inflammation induced by cigarette smoke extract (CSE) in a human monocyte/macrophage cell line. METHODS: The human monocyte/macrophage cell line THP-1 was stimulated with 10 % CSE in the presence or absence of Bufei Yishen formula (BYF), Bufei Jianpi formula (BJF) and Yiqi Zishen formula (YZF). All formulations contained serum. Pro-inflammatory cytokines were measured in the supernatants using enzyme-linked immunosorbent assay. The activity of STAT3 DNA binding was detected using electrophoretic mobility shift assay and janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway activation was assessed using Western blotting. RESULTS: The results showed that BYF, BJF and YZF treatment strongly decreased the CSE-induced secretion of interleukin (IL)-6, IL-8, tumor necrosis factor-α and matrix metalloproteinase-9 by THP-1 cells. Furthermore, BYF, BJF and YZF treatment attenuated STAT3 DNA binding capacity and JAK2 and STAT3 were shown to be phosphorylated. CONCLUSION: The data revealed that BYF, BJF and YZF effectively inhibited a CSE-induced inflammatory response in THP-1 cells by limiting activation of the JAK2/STAT3 pathway.

Icariin, Formononetin and Caffeic Acid Phenethyl Ester Inhibit Feline Calicivirus Replication In Vitro.

Cats infected with feline calicivirus (FCV) often display oral ulcers and inflammation of the upper respiratory tract, which can lead to death in severe cases. Antiviral therapy is one of the most effective ways to control FCV infection. Natural compounds in Chinese herbal medicines and medicinal plants provide abundant resources for research on antiviral drugs. In this study, we found that icariin (ICA), formononetin (FMN) and caffeic acid phenethyl ester (CPAE) show low cytotoxicity towards F81 cells, that the three natural compounds have apparent antiviral effects on FCV in vitro, and that they can inhibit different FCV strains. Then, we found that ICA and FMN mainly function in the early stage of FCV infection, while CAPE can function in both the early and late stages of FCV infection. Finally, we found that ICA has an antagonistic effect on FMN and CAPE in FCV infection, and FMN has a synergistic effect with CAPE against FCV infection. Our results showed that ICA, FMN and CAPE may be potential drug candidates for FCV-induced diseases.

The microbiome affects liver sphingolipids and plasma fatty acids in a murine model of the Western diet based on soybean oil.

Studies in mice using germfree animals as controls for microbial colonization have shown that the gut microbiome mediates diet-induced obesity. Such studies use diets rich in saturated fat, however, Western diets in the United States America are enriched in soybean oil, composed of unsaturated fatty acids, either linoleic or oleic acid. Here, we addressed whether the microbiome is a variable in fat metabolism in mice on a soybean oil diet. We used conventionally-raised, low-germ, and germfree mice fed for 10 weeks diets either high or low in high-linoleic-acid soybean oil as the sole source of fat. Conventional and germfree mice gained relative fat weight and all mice consumed more calories on the high fat vs. low fat soybean oil diet. Plasma fatty acid levels were generally dependent on diet, with microbial colonization status affecting iso-C18:0, C20:3n-6, C14:0, and C15:0 levels. Colonization status, but not diet, impacted levels of liver sphingolipids including ceramides, sphingomyelins, and sphinganine. Our results confirm that absorbed fatty acids are mainly a reflection of the diet and that microbial colonization influences liver sphingolipid pools regardless of diet.

Synergistic effects of α-Mangostin and sorafenib in hepatocellular carcinoma: New insights into α-mangostin cytotoxicity.

Sorafenib remains the standard first-line treatment for advanced hepatocellular carcinoma (HCC), although other clinical trials are currently underway for treatments that show better curative effects. However, some patients are not sensitive to sorafenib. α-Mangostin, extracted from the pericarp of the mangosteen, which is widely used as a traditional medicine, has anticancer and anti-proliferative properties in various types of cancers, including HCC. In the present study, we found that combining sorafenib and α-Mangostin could be synergistically toxic to HCC both in vitro and in vivo. We then demonstrated that the combination of sorafenib and α-Mangostin enhances the inhibition of cell proliferation in HCC cell lines. Combination therapy leads directly to apoptosis. In xenograft mouse models, the in vivo safety and effectivity was confirmed by a reduction in tumor size after combination treatment. RNA sequencing and protein testing showed that the expression of LRRC8A and RNF181 genes and mTOR and MAPK pathways may be associated with the synergistic effect of the two drugs. In conclusion, our results highlight the synergistic effect of the combination of sorafenib and α-Mangostin, which indicates a potential treatment for advanced HCC for patients that are not sensitive to sorafenib therapy.

Electroacupuncture Ameliorates Depressive-Like Behaviors in Poststroke Rats via Activating the tPA/BDNF/TrkB Pathway.

BACKGROUND: Electroacupuncture (EA) is a form of physical therapy that has been widely used in clinical practice in China. Post-stroke depression (PSD) is the most common neuropsychiatric complication after stroke. EA has been shown to have beneficial effects on PSD patients. However, the potential mechanism underlying the protective effects of EA on PSD remains unclear. Here, we investigated whether tissue plasminogen activator (tPA)/brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling pathway participates in the therapeutic effects of EA in a rat PSD model. METHODS: Experimental PSD was induced by combining middle cerebral artery occlusion (MCAO) with chronic unpredictable mild stimulation (CUMS) in adult male rats. Bodyweight gain, neurological score, sucrose preference, and open field test were determined at 0, 7, 14, and 35 days after completing MCAO. The protein expressions of tPA, precursor BDNF (proBDNF), mature BDNF (mBDNF), and TrkB were measured by immunofluorescence and Western blot analysis. The tPA inhibitor plasminogen inhibitor-1 (PAI-1) was used to explore whether tPA plays a crucial role in the protective effects of EA on PSD. RESULTS: Compared with the sham rats, the PSD rats showed decreased bodyweight, deteriorated neurological score, and significant depressive-like behaviors. EA remarkably reversed bodyweight loss, neurological deficit, and depressive-like behaviors in PSD rats. Immunofluorescence staining and Western blot analysis showed that PSD-induced decreased expression of tPA, mBDNF, and TrkB were prevented by EA. Furthermore, we found that the effects of EA against PSD-induced depressive-like behaviors were abolished by PAI-1, the specific inhibitor of tPA. CONCLUSION: Our results suggest that the improvement in depressive-like behaviors induced by EA is likely achieved via activation of the tPA/BDNF/TrkB pathway.

Very Long-Chain Branched-Chain Fatty Acids in Chia Seeds: Implications for Human Use.

Dairy and fermented foods are common sources of dietary branched-chain fatty acids (BCFA) of chain lengths C13-C18 serving a putative prebiotic role and a component of human integument. Few studies have reported on nonfermented plant-derived BCFA in human diets or cosmetics. A three-ion monitoring method was adapted to confirm branch position of ultratrace (<0.01%, w/w) BCFA. We identified chia as a new source of BCFA with C15-C35 chain lengths. Surprisingly, even-numbered very long-chain BCFA (VLC BCFA), anteiso-22:0, anteiso-24:0, and anteiso-26:0 were unequivocally identified in natural products for the first time. Plant-derived BCFA are predominantly anteiso, in contrast with similar iso and anteiso levels in ruminant and fermented foods. Chia seeds contain 0.4% BCFA, w/w of total fatty acids, or 32 mg BCFA in a food serving, surpassing other plant oils. Topical administration of chia seed oil containing VLC BCFA may have a role in skin and hair functionality.

Effective-constituent compatibility-based analysis of Bufei Yishen formula, a traditional herbal compound as an effective treatment for chronic obstructive pulmonary disease.

OBJECTIVE: Critical effective constituents were identified from Bufei Yishen formula (BYF), a traditional herbal compound and combined as effective-constituent compatibility (ECC) of BYF I, which may have potential bioactive equivalence to BYF. METHODS: The active constituents of BYF were identified using four cellular models and categorised into Groups 1 (Bufeiqi), 2 (Bushen), 3 (Huatan) and 4 (Huoxue) according to Chinese medicinal theory. An orthogonal design and a combination method were used to determine the optimal ratios of effective constituents in each group and the ratios of "Groups 1 to 4" according to their pharmacological activity. We also comprehensively assessed bioactive equivalence between the BYF and the ECC of BYF I in a rat model of chronic obstructive pulmonary disease (COPD). RESULTS: We identified 12 active constituents in BYF. The numbers of constituents in Groups 1 to 4 were 3, 2, 5 and 2, respectively. We identified the optimal ratios of effective constituents within each group. In Group 1, total ginsenosides:Astragalus polysaccharide:astragaloside IV ratio was 9:5:2. In Group 2, icariin:schisandrin B ratio was 100:12.5. In Group 3, nobiletin:hesperidin:peimine:peiminine:kaempferol ratio was 4:30:6.25:0:0. In Group 4, paeoniflorin:paeonol ratio was 4:1. An orthogonal design was then used to establish the optimal ratios of Group 1, Group 2, Group 3 and Group 4 in ECC of BYF I. The ratio for total ginsenosides:Astragalus polysaccharide:astragaloside IV:icariin:schisandrin B:nobiletin:hesperidin:peimine:paeoniflorin:paeonol was determined to be 22.5:12.5:5:100:12.5:4:30:6.25:25:6.25. A comprehensive evaluation confirmed that ECC of BYF I presented with bioactive equivalence to the original BYF. CONCLUSION: Based on the ECC of traditional Chinese medicine formula method, the effective constituents of BYF were identified and combined in a fixed ratio as ECC of BYF I that was as effective as BYF itself in treating rats with COPD.