PSMC6 induces immune cell infiltration and inflammatory response to aggravate primary Sjögren's syndrome.

Increasing evidence suggests that immune cell infiltration is involved in primary Sjögren's syndrome (pSS), while the underlying molecular mechanisms remain elusive. Herein, this study aims to explore the key molecular mechanism in immune cell infiltration in pSS based on Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were obtained, followed by weighted gene co-expression network analysis to acquire the pSS-related module genes. Moreover, pSS-related DEGs and module genes were intersected. Additionally, the correlation between key genes and immune cell infiltration was analyzed by CIBERSORT algorithm. Furthermore, pSS mouse models were established to explore the effects of PSMC6 on immune cell infiltration and inflammatory responses in pSS. A total of 51 DEGs and 334 key module genes were involved in the occurrence of pSS. The immune cell infiltration was correlated with pSS, and PSMC6, highly expressed in pSS samples, may be the key immune gene. In vivo animal experiments demonstrated that PSMC6 was upregulated in pSS, and PSMC6 knockdown could reduce lymphocytic infiltration in salivary glands and lacrimal glands and the levels of related inflammatory factors in the pSS and increase the proportion of Treg cells. Collectively, PSMC6 could induce immune cell infiltration and inflammatory responses to promote the occurrence of pSS, providing us with a potential therapeutic target for treating pSS.

Performance-enhanced fiber optic humidity sensors based on SiO2/porous PMMA coatings.

Employing functional and structured thin films on fiber optic sensors has tremendously improved capabilities in humidity sensing applications. In this paper, we demonstrate fabrication of a fiber optic evanescent wave humidity sensor based on S i O 2/porous polymethyl methacrylate (PMMA) thin films. With the exposure to moisture, S i O 2/porous PMMA thin films absorb water molecules. The refractive index and absorption coefficient of thin films change with ambient humidity, resulting in modulation of the light intensity transmitted in fiber. A good linearity is determined between the logarithm of output light intensity and relative humidity (RH). An optimal average sensitivity of 188.3 lux/%RH is achieved with an increase of 11.7 fold in the RH range of 5% to 95%. The response and recovery times are 8 s and 23 s, respectively. Furthermore, the sensor exhibits low hysteresis, and excellent stability and repeatability.

[Optimization of extraction process of Chuanxiong Rhizoma-Gastrodiae Rhizoma based on network pharmacology and multi-index orthogonal test].

To optimize the extraction process of Chuanxiong Rhizoma-Gastrodiae Rhizoma herb pair by network pharmacology combined with analytic hierarchy process(AHP)-entropy weight method and multi-index orthogonal test. The potential active components and targets of Chuanxiong Rhizoma-Gastrodiae Rhizoma were screened by network pharmacology and molecular docking, and the process evaluation indexes were determined with reference to the Chinese Pharmacopoeia(2020 edition). The core components of Chuanxiong Rhizoma-Gastrodiae Rhizoma were determined as gastrodin, parishin B, parishin C, parishin E, ferulic acid, and 3-butylphthalide. With the extraction volume of each indicator and yield of dry extract as comprehensive evaluation indicators, the extraction conditions were optimized by the AHP-entropy weight method and orthogonal test as the ethanol volume of 50%, the solid-liquid ratio of 1∶8(g·mL~(-1)), extraction for three times, and 1.5 h each time. Through network pharmacology and molecular docking, the process evaluation index was determined, and the optimized process was stable and reproducible for the extraction of Chuanxiong Rhizoma-Gastrodiae Rhizoma herb pair, which could provide reference for in-depth research.

Phytochemicals from the flowers of Prunus persica (L.) Batsch: Anti-adipogenic effect of mandelamide on 3T3-L1 preadipocytes.

Flowers of Prunus persica (L.) Batsch (Rosaceae), known as peach blossoms, have been reported to exert anti-obesity effects by improving hepatic lipid metabolism in obese mice. However, little is known regarding the anti-adipogenic effects of the phenolic compounds isolated from P. persica flowers. This study investigated the inhibitory effects of compounds extracted from P. persica flowers (PPF) on adipogenesis in 3T3-L1 murine preadipocytes using adipogenic differentiation assays. Additionally, we compared the anti-adipogenic effects of the phenolic compounds isolated from PPF, such as prunasin amide (1), amygdalin amide (2), prunasin acid (3), mandelamide (4), methyl caffeate (5), ferulic acid (6), chlorogenic acid (7), benzyl α-l-xylpyranosyl-(1 â†’ 6)-ß-d-glucopyranoside (8), prunin (9), naringenin (10), nicotiflorin (11), astragalin (12), afzelin (13), and uridine (14), on adipogenesis in 3T3-L1 murine preadipocytes. PPF and compounds 4-7 and 10 significantly inhibited adipogenesis. Among them, mandelamide (4) exhibited the maximum inhibitory activity with an IC50 of 36.04 ± 1.82 µM. Additionally, mandelamide downregulated the expression of key adipogenic markers, such as extracellular signal-regulated kinase, c-Jun-N-terminal kinase, P38, CCAAT/enhancer-binding protein α, CCAAT/enhancer-binding protein ß, peroxisome proliferator activated receptor γ, and glucocorticoid receptor. These results indicate that mandelamide is an active ingredient of PPF possessing anti-obesity properties.

(1'S)-1'-Acetoxyeugenol Acetate Enhances Glucose-Stimulated Insulin Secretion.

Alpinia galanga have been widely used as spice or traditional medicine in East Asia, commonly known as Thai ginger. In the present study, seven major phenylpropanoids, (±)-1'-hydoxychavicol acetate (1; HCA), (1'S)-1'-acetoxychavicol acetate (2; ACA), (1'S)-1'-acetoxyeugenol acetate (3; AEA), eugenyl acetate (4), trans-p-coumaraldehyde (5), trans-p-acetoxycinnamyl alcohol (6), and trans-p-coumaryl diacetate (7), were isolated from the 95% EtOH and hot water extracts of the rhizomes of A. galanga by chromatographic method. Phenylpropanoids 1-7 were evaluated for glucose-stimulated insulin secretion (GSIS) effect and α-glucosidase inhibitory activity. Phenylpropanoids 1-4 increase GSIS effect without cytotoxicity in rat INS-1 pancreatic ß-cells. In addition, INS-1 cells were treated with AEA (3) to determine a plausible mechanism of ß-cell function and insulin secretion through determining the activation of insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), Akt, and pancreatic and duodenal homeobox-1 (PDX-1). Upon treatment with AEA (3), INS-1 cells showed an increase in these protein expressions. Meanwhile, AEA (3) exhibited α-glucosidase inhibitory activity. On the basis of the above findings, we suggest AEA (3) as a potential antidiabetic agent.

Huoxin Pill Reduces Myocardial Ischemia Reperfusion Injury in Rats via TLR4/NFκB/NLRP3 Signaling Pathway.

OBJECTIVE: To explore the protective effect of Huoxin Pill (HXP) on acute myocardial ischemia-reperfusion (MIRI) injury in rats. METHODS: Seventy-five adult SD rats were divided into the sham-operated group, model group, positive drug group (diltiazem hydrochloride, DH), high dose group (24 mg/kg, HXP-H) and low dose group (12 mg/kg, HXP-L) of Huoxin Pill (n=15 for every group) according to the complete randomization method. After 1 week of intragastric administration, the left anterior descending coronary artery of the rat's heart was ligated for 45 min and reperfused for 3 h. Serum was separated and the levels of creatine kinase (CK), creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA), hypersensitive C-reactive protein (hs-CRP) and interleukin-1ß (IL-1ß) were measured. Myocardial ischemia rate, myocardial infarction rate and myocardial no-reflow rate were determined by staining with Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC). Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN) databases were used to screen for possible active compounds of HXP and their potential therapeutic targets; the results of anti-inflammatory genes associated with MIRI were obtained from GeneCards, Drugbank, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Datebase (TTD) databases was performed; Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to analyze the intersected targets; molecular docking was performed using AutoDock Tools. Western blot was used to detect the protein expression of Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NFκB)/NOD-like receptor protein 3 (NLRP3). RESULTS: Compared with the model group, all doses of HXP significantly reduced the levels of LDH, CK and CK-MB (P<0.05, P<0.01); HXP significantly increased serum activity of SOD (P<0.05, P<0.01); all doses of HXP significantly reduced the levels of hs-CRP and IL-1ß (P<0.05, P<0.01) and the myocardial infarction rate and myocardial no-reflow rate (P<0.01). GO enrichment analysis mainly involved positive regulation of gene expression, extracellular space and identical protein binding, KEGG pathway enrichment mainly involved PI3K-Akt signaling pathway and lipid and atherosclerosis. Molecular docking results showed that kaempferol and luteolin had a better affinity with TLR4, NFκB and NLRP3 molecules. The protein expressions of TLR4, NFκB and NLRP3 were reduced in the HXP group (P<0.01). CONCLUSIONS: HXP has a significant protective effect on myocardial ischemia-reperfusion injury in rats, and its effect may be related to the inhibition of redox response and reduction of the inflammatory response by inhibiting the TLR4NFκB/NLRP3 signaling pathway.

Methyl Caffeate Isolated from the Flowers of Prunus persica (L.) Batsch Enhances Glucose-Stimulated Insulin Secretion.

Phenolic compounds from natural products are considered effective enhancers of insulin secretion to prevent and treat type 2 diabetes (T2DM). The flowers of Prunus persica (L.) Batsch also contain many phenolic compounds. In this study, the extract of flowers of P. persica (PRPE) exhibited an insulin secretion effect in a glucose-stimulated insulin secretion (GSIS) assay, which led us to isolate and identify the bioactive compound(s) responsible for these effects. Compounds isolated from PRPE were screened for their efficacy in INS-1 rat pancreatic ß-cells. Among them, caffeic acid (5), methyl caffeate (6), ferulic acid (7), chlorogenic acid (8), naringenin (11), nicotiflorin (12), and astragalin (13) isolated from PRPE increased GSIS without inducing cytotoxicity. Interestingly, the GSIS effect of methyl caffeate (6) as a phenolic compound was similar to gliclazide, an antidiabetic sulfonylurea drug. Western blot assay showed that methyl caffeate (6) enhanced the related signaling proteins of the activated pancreatic and duodenal homeobox-1 (PDX-1) and peroxisome proliferator-activated receptor-γ (PPAR-γ), but also the phosphorylation of the total insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), and Akt, which influence ß-cell function and insulin secretion. This study provides evidence that methyl caffeate (6) isolated from PRPE may aid in the management of T2DM.

Chemical Constituents of the Leaves of Campanula takesimana (Korean Bellflower) and Their Inhibitory Effects on LPS-induced PGE2 Production.

Campanula takesimana Nakai (Campanulaceae; Korean bellflower) is one of the endemic herbs of Korea. The plant has been used as traditional medicines for treating asthma, tonsillitis, and sore throat in Korea. A hot water extract of the leaves of C. takesimana exhibited a significant inhibitory effect on lipopolysaccharide (LPS)-stimulated prostaglandin E2 (PGE2) production. Repetitive chromatographic separation of the hot water extract led to the isolation of three new neolignan glucosides, campanulalignans A-C (1-3), with 15 known compounds (4-18). The structures of new compounds 1-3 were elucidated by analyzing nuclear magnetic resonance (NMR) spectroscopic data, along with high resolution quadrupole time of flight mass (HR-Q-TOF-MS) spectrometric data. Among the isolates, simplidin (7), 5-hydroxyconiferaldehyde (11), icariside F2 (12), benzyl-α-l-arabinopyranosyl-(1″→6')-ß-d-glucopyranoside (13), and kaempferol 3-O-ß-d-apiosyl (1→2)-ß-d-glucopyranoside (15) were isolated from the Campanulaceae family for the first time. The isolates (1, 2, and 4-18) were assessed for their anti-inflammatory effects on LPS-stimulated PGE2 production on RAW 264.7 cells. 7R,8S-Dihydrodehydrodiconiferyl alcohol (5), 3',4-O-dimethylcedrusin 9-O-ß-glucopyranoside (6), pinoresinol di-O-ß-d-glucoside (8), ferulic acid (10), 5-hydroxyconiferaldehyde (11), and quercetin (18) showed significant inhibitory effects on LPS-stimulated PGE2 production.

Effects of Dislocation Density Evolution on Mechanical Behavior of OFHC Copper during High-Speed Machining.

This paper aims at investigating the change in material behavior induced by microstructure evolution during high-speed machining processes. Recently, high-speed machining has attracted quite a lot of interest from researchers due to its high efficiency and surface quality in machining large-scale components. However, the material behavior could change significantly at high-cutting speeds compared to the conventional cutting conditions, including their microstructure and t mechanical response. This is due to the basic physics of material at microscopic levels with high strain, high strain rates, and high temperatures. In this study, the dislocation density-related microstructure evolution process and mechanical behavior of OFHC (Oxygen-free high-conductivity) copper in high-speed machining with speeds ranging from 750 m/min to 3000 m/min are investigated. SEM (Scanning Electron Microscope) and advanced EBSD (Electron Backscattered Diffraction) techniques are used to obtain high-quality images of the microstructures and analyze the dislocation density and grain size evolution with different cutting speeds. Moreover, as material plasticity is induced by the motion of dislocations at micro-scales, a dislocation-density based (DDB) model is applied to predict strain-stress and microstructure information during the cutting process. The distributions of dislocation densities, both statistically stored dislocations (SSDs) and geometrically necessary dislocations (GNDs), are obtained through simulation and experimentation, respectively. The results show that the fluctuation in the cutting forces at high cutting speeds is induced by the specific evolution and distribution of the dislocation density under high strain-rates, and the periodical distribution of sub-surface and fracture behavior during chip separation, which are also found to be influenced by the evolution of the dislocation density.

New Depsides and Neuroactive Phenolic Glucosides from the Flower Buds of Rugosa Rose ( Rosa rugosa).

The flower buds of Rosa rugosa Thunb. have been commonly used as a source of rose oil and as an ingredient in tea in eastern Asia, including China, Japan, and Korea. Repeated chromatography of a hot water extract from the flower buds of R. rugosa led to the isolation and characterization of three new depside glucosides, rosarugosides A-C (1-3), along with three phenolic compounds, one ionone glucoside, four flavonoids, and two tannins having known chemical structures. Linarionoside A and 2-phenylethyl-(6- O-galloyl)-ß-d-glucopyranoside were isolated from R. rugosa for the first time in this study. The structures of the new compounds 1-3 were elucidated by interpreting one- and two-dimensional nuclear magnetic resonance spectroscopic and mass spectrometric data. Among the isolates, a new depside glucoside (1) and two major phenolic glucosides (4 and 5) improved MK-801-induced sensorimotor gating deficits, which were measured via an acoustic startle response test in mice.