Wogonin inhibits the migration and invasion of fibroblast-like synoviocytes by targeting PI3K/AKT/NF-κB pathway in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is currently an autoimmune inflammatory disease with an unclear pathogenesis. Fibroblast-like synoviocytes (FLSs) have tumor-like properties, and their activation and secretion of pro-inflammatory factors are important factors in joint destruction. Wogonin (5,7-dihydroxy-8-methoxyflavone), a natural flavonoid isolated from Scutellaria baicalensis root, has been shown to have significant anti-inflammatory, anti-oxidative stress, and anti-tumor effects in a variety of diseases. However, the role of wogonin in RA has not yet been demonstrated. PURPOSE: To investigate the inhibitory effect of wogonin on the invasive behavior of fibroblast-like synoviocytes and to explore the mechanism of action of wogonin in RA. METHODS: CCK-8, EdU, cell migration and invasion, immunofluorescence staining, RT-qPCR, and protein blot analysis were used to study the inhibitory effects of wogonin on migration, invasion, and pro-inflammatory cytokine overexpression in the immortalized rheumatoid synovial cell line MH7A. The therapeutic effects of wogonin were validated in vivo using arthritis scores and histopathological evaluation of collagen-induced arthritis mice. RESULTS: Wogonin inhibited the migration and invasion of MH7A cells, reduced the production of TNF-α, IL-1ß, IL-6, MMP-3 and MMP-9, and increased the expression of IL-10. Moreover, wogonin also inhibited the myofibrillar differentiation of MH7A cells, increased the expression of E-cadherin (E-Cad) and decreased the expression of α-smooth muscle actin (α-SMA). In addition, wogonin treatment effectively ameliorated joint destruction in CIA mice. Further molecular mechanism studies showed that wogonin treatment significantly inhibited the activation of PI3K/AKT/NF-κB signaling pathway in TNF-α-induced arthritic FLSs. CONCLUSION: Wogonin effectively inhibits migration, invasion and pro-inflammatory cytokine production of RA fibroblast-like synoviocytes through the PI3K/AKT/NF-κB pathway, and thus wogonin, as a natural flavonoid, has great potential for treating RA.

Altered Gut Microbiota and Short-chain Fatty Acids in Chinese Children with Constipated Autism Spectrum Disorder.

Gastrointestinal symptoms are more prevalent in children with autism spectrum disorder (ASD) than in typically developing (TD) children. Constipation is a significant gastrointestinal comorbidity of ASD, but the associations among constipated autism spectrum disorder (C-ASD), microbiota and short-chain fatty acids (SCFAs) are still debated. We enrolled 80 children, divided into the C-ASD group (n = 40) and the TD group (n = 40). In this study, an integrated 16S rRNA gene sequencing and gas chromatography-mass spectrometry-based metabolomics approach was applied to explore the association of the gut microbiota and SCFAs in C-ASD children in China. The community diversity estimated by the Observe, Chao1, and ACE indices was significantly lower in the C-ASD group than in the TD group. We observed that Ruminococcaceae_UCG_002, Erysipelotrichaceae_UCG_003, Phascolarctobacterium, Megamonas, Ruminiclostridium_5, Parabacteroides, Prevotella_2, Fusobacterium, and Prevotella_9 were enriched in the C-ASD group, and Anaerostipes, Lactobacillus, Ruminococcus_gnavus_group, Lachnospiraceae_NK4A136_group, Ralstonia, Eubacterium_eligens_group, and Ruminococcus_1 were enriched in the TD group. The propionate levels, which were higher in the C-ASD group, were negatively correlated with the abundance of Lactobacillus taxa, but were positively correlated with the severity of ASD symptoms. The random forest model, based on the 16 representative discriminant genera, achieved a high accuracy (AUC = 0.924). In conclusion, we found that C-ASD is related to altered gut microbiota and SCFAs, especially decreased abundance of Lactobacillus and excessive propionate in faeces, which provide new clues to understand C-ASD and biomarkers for the diagnosis and potential strategies for treatment of the disorder. This study was registered in the Chinese Clinical Trial Registry ( www.chictr.org.cn ; trial registration number ChiCTR2100052106; date of registration: October 17, 2021).

Efficacy and safety of fecal microbiota transplantation in the treatment of ulcerative colitis: a systematic review and meta-analysis.

To explore the efficacy and safety of fecal microbiota transplantation (FMT) as a treatment approach for ulcerative colitis (UC), a comprehensive systematic review and meta-analysis of randomized controlled trials was conducted. To collect and evaluate randomized controlled trials of high quality on FMT for UC, we searched a number of databases, including PubMed, Web of Science, Cochrane, Embase, and Medline, for studies published between the establishment of the databases and March 2023. We conducted a meta-analysis of the studies using Review Manager software (version 5.4.1) to determine the differences in rates of remission and adverse reactions between the FMT group and the control group, utilizing the risk ratio (RR) and 95% confidence interval (CI) to combine our findings. A total of 13 randomized controlled trials (RCTs) on the efficacy of FMT in patients with UC were included in the study, in which 580 patients participated, including 293 patients treated with FMT and 287 control subjects. Meta-analysis revealed that clinical remission was significantly better in the FMT group than in the control group [RR = 1.73; 95% CI = (1.41, 2.12); P < 0.00001]; endoscopic remission was significantly better in the FMT group than in the control group [RR = 1.74; 95% CI = (1.24, 2.44); P = 0.001]. Additionally, there were no significant differences in the incidence of adverse reactions between the two groups [RR = 1.00; 95% CI = (0.86, 1.15); P = 0.96]. Fecal microbiota transplantation has shown potential as a therapeutic intervention for inducing clinical remission in ulcerative colitis UC; nevertheless, the attainment of endoscopic remission and the maintenance of long-term remission continue to present challenges. Safety concerns persist throughout the treatment process, necessitating the implementation of measures to augment both safety and success rates.

Hawthorn total flavonoids ameliorate ambient fine particulate matter-induced insulin resistance and metabolic abnormalities of lipids in mice.

Recent studies have shown a strong correlation between ambient fine particulate matter (PM2.5) exposure and diabetes risk, including abnormal lipid accumulation and systemic insulin resistance (IR). Hawthorn total flavonoids (HF) are the main groups of active substances in Hawthorn, which showed anti-hyperlipidemic and anti-hyperglycemic effects. Therefore, we hypothesized that HF may attenuate PM2.5-induced IR and abnormal lipid accumulation. Female C57BL/6 N mice were randomly assigned to the filtered air exposure (FA) group, concentrated PM2.5 exposure (PM) group, PM2.5 exposure maintained on a low-dose HF diet (LHF) group, and PM2.5 exposure maintained on a high-dose HF diet (HHF) group for an 8-week PM2.5 exposure using a whole-body exposure device. Body glucose homeostasis, lipid profiles in the liver and serum, and enzymes responsible for hepatic lipid metabolism were measured. We found that exposure to PM2.5 impaired glucose tolerance and insulin sensitivity. In addition, triacylglycerol (TAG) in serum elevated, whereas hepatic TAG levels were decreased after PM2.5 exposure, accompanied by inhibited fatty acid uptake, lipogenesis, and lipolysis in the liver. HF administration, on the other hand, balanced the hepatic TAG levels by increasing fatty acid uptake and decreasing lipid export, leading to alleviated systemic IR and hyperlipidemia in PM2.5-exposed mice. Therefore, HF administration may be an effective strategy to protect against PM2.5-induced IR and metabolic abnormalities of lipids.

Qianjinweijing Decoction Protects Against Fine Particulate Matter Exposure-mediated Lung Function Disorder.

Fine particulate matter (PM2.5) is well known to impair lung function. Strategies protecting against PM2.5-exerted lung dysfunction have been less investigated. Qianjinweijing decoction (QJWJ), a decoction of a herbal medicine of natural origin, has been used to treat lung disorders as it inhibits oxidation and inflammation. However, no clinical trial has yet evaluated the role of QJWJ in PM2.5-induced lung dysfunction. Therefore, we conducted a randomized, double-blind, placebo-controlled trial to assess whether QJWJ provided lung benefits against the adverse effects of PM2.5 exposure among adults. Eligible participants (n = 65) were recruited and randomized to receive QJWJ decoction (n = 32) or placebo (n = 33) for 4 weeks. The restrictive ventilatory defect (RVD), lung function parameters, and induced sputum were analyzed. The PM2.5 exposure concentration was significantly associated with the vital capacity (VC), peak expiratory flow (PEF), and forced expiratory flow at 75% of the forced vital capacity (FEF75). The negative associations between PM2.5 and the lung function parameters were eliminated in response to the QJWJ intervention. Additionally, the percentage of RVD (P = 0.018) and the proportion of eosinophils (Eo%) in induced sputum (P = 0.014) in the QJWJ group was significantly lower than that in the placebo group. This study demonstrated that QJWJ could alleviated PM2.5-induced lung dysfunction and could be a potential treatment for air pollution-related chronic respiratory disease.

Association of serum 25-hydroxyvitamin D (25(OH)D) levels with the gut microbiota and metabolites in postmenopausal women in China.

BACKGROUND: Vitamin D insufficiency or deficiency is associated with an altered microbiota in older men. However, the relationship between the gut microbiota and 25-hydroxyvitamin D (25(OH)D) levels remains unknown in postmenopausal women. In this study, fecal microbiota profiles for 88 postmenopausal women in the high 25(OH)D (HVD) group (n = 44) and the low 25(OH)D (LVD) group (n = 44) were determined. An integrated 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approach was applied to explore the association of serum 25(OH)D levels with the gut microbiota and fecal metabolic phenotype. Adjustments were made using several statistical models for potential confounding variables identified from the literature. RESULTS: The results demonstrated that the community diversity estimated by the Observe, Chao1 and ACE indexes was significantly lower in the LVD group than in the HVD group. Additionally, two kinds of characteristic differences in the microflora were analyzed in the HVD group, and ten kinds of characteristic differences in the microflora were analyzed in the LVD group. We observed that some bacteria belonging to the genera Bifidobacterium, Bacillus, F0332 and Gemella, were enriched in the LVD group, as were other genera, including Lachnoclostridium, UC5_1_2E3, Ruminococcus_gnavus_group and un_f_Lachnospiraceae. Christensenellaceae, Eggerthellaceae and Cloacibacillus were enriched in the HVD group. The L-pyroglutamic acid, inosine, and L-homocysteic acid levels were higher in the HVD group and were negatively correlated with the 1,2-benzenedicarboxylic acid and cholic acid metabolic levels. CONCLUSIONS: These observations provide a better understanding of the relationships between serum 25(OH)D levels and the fecal microbiota and metabolites in postmenopausal women.

Toward Multifunctional Electronics: Flexible NBT-Based Film with a Large Electrocaloric Effect and High Energy Storage Property.

Advances in smart and wearable devices are driving innovations in multifunctional flexible materials at a tremendous pace. Here, drawing support from the unique flexible fluorophlogopite mica platform, we present a promising all-inorganic bendable Mn-modified 0.65(0.94Na0.5Bi0.5TiO3-0.06BaTiO3)-0.35SrTiO3 (NBBST) film with dual use in electrocaloric (EC) refrigeration and energy storage via a cost-effective transfer-free process. An appreciable room-temperature EC effect with adiabatic temperature change of 12 K and isothermal entropy of 18 J K-1 kg-1 was realized in the NBBST film, which benefits from the large change in dipolar ordering near depolarization temperature. Also, the film exhibits a broad operating temperature span over 25 °C because of its relaxor feature. Most importantly, the film can maintain a high EC performance either under bending deformation at 5 mm radius or after undergoing 104 bending-unbending cycles. Meanwhile, the flexible NBBST film possesses good energy storage property with a recoverable energy density of 56 J cm-3 and an efficiency of 66%. This is the first example of a lead-free all-inorganic multifunctional film capacitor toward the flexible EC refrigeration and energy storage devices. This work shows bright prospects in the emerging flexible e-market.

Flexible, Temperature-Resistant, and Fatigue-Free Ferroelectric Memory Based on Bi(Fe0.93Mn0.05Ti0.02)O3 Thin Film.

A recent hot-spot topic for flexible and wearable devices involves high-performance nonvolatile ferroelectric memories operating under compressive or tensile mechanical deformations. This work presents the direct fabrication of a flexible (Mn,Ti)-codoped multiferroic BiFeO3 film capacitor with Pt bottom and Au top electrodes on mica substrate. The fabricated polycrystalline Bi(Fe0.93Mn0.05Ti0.02)O3 film on mica exhibits superior ferroelectric switching behavior with robust saturated polarization ( Ps ∼ 93 µC/cm2) and remanent polarization ( Pr ∼ 66 µC/cm2) and excellent frequency stability (1-50 kHz) and temperature resistance (25-200 °C), as well as reliable long-lifetime operation. More saliently, it can be safely bent to a small radius of curvature, as low as 2 mm, or go through repeated compressive/tensile mechanical flexing for 103 bending times at 4 mm radius without any obvious deterioration in polarization, retention time at 105 s, or fatigue resistance after 109 switching cycles. These findings demonstrate a novel route to designing flexible BiFeO3-based ferroelectric memories for information storage and data processing, with promising applications in next-generation smart electronics.

Lysine Stimulates Protein Synthesis by Promoting the Expression of ATB0,+ and Activating the mTOR Pathway in Bovine Mammary Epithelial Cells.

Background: l-lysine (Lys) is a critical dietary nutrient for mammary gland development and milk production. However, the specific pathways of Lys utilization and how milk protein synthesis is affected in bovine mammary epithelial cells (BMECs) are poorly understood. Objective: We aimed to investigate the effects of Lys on milk protein synthesis and the mechanism of Lys uptake and catabolism in BMECs. Methods: BMECs were cultured in 0, 0.5, 1.0, 1.5, 2.0, 5.0, and 10.0 mmol Lys/L to detect cell viability, or cultured in 0-2.0 mmol Lys/L with l-[ring-3H5] phenylalanine to study the effect of Lys on protein turnover, or cultured in Krebs buffer with [U-14C] l-Lys to quantify Lys metabolism. In some experiments, BMECs were cultured in a conditioned medium alone or including 1.0 mmol Lys/L and 2-amino-endo-bicyclo [2.2.1] heptane-2-carboxylic acid (BCH) for 24 h to analyze the expression of amino acid transporter B (0+) (ATB0,+), mammalian target of rapamycin (mTOR), and Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) pathways. Results: Including 1.0 mmol Lys/L in cultures increased cell viability by 17-47% and protein synthesis by 7-23%, whereas protein degradation was inhibited by 4-64% compared with BMECs cultured with 0, 0.5, or 2.0 mmol Lys/L (all P ≤ 0.05). Studies that used [U-14C] l-Lys showed that most Lys was incorporated into proteins (90%), whereas the remainder was either oxidized into CO2 (4%) or used as a substrate for aspartate (3%) and histidine synthesis (3%). Furthermore, Lys significantly increased expression of ATB0,+ (71% mRNA and 44% protein), STAT5 (27% mRNA and 21% phosphorylated proteins), and mTOR (51% mRNA and 22% phosphorylated proteins) compared with cells without Lys. Conclusions: Lys promoted protein synthesis, mostly through enhancing uptake by ATB0,+ and the mTOR and JAK2-STAT5 pathways. Understanding the utilization of Lys in BMECs provides insights into the role of amino acid nutrition in bovine milk production.

Study of platelet-rich fibrin combined with rat periodontal ligament stem cells in periodontal tissue regeneration.

The objective of this study was to investigate the advantages and feasibility of periodontal tissue regeneration using platelet-rich fibrin (PRF) combined with rat periodontal ligament stem cells (PDLSCs) for the first time. We first determined the effect of PRF on rat PDLSCs in vitro. We next conducted an in vivo study, in which a tissue engineering technique was performed to repair periodontal defects in five groups: a blank group, collagen group (implanted collagen membrane), collagen + cells group (implanted collagen membrane and rat PDLSCs), PRF group (implanted PRF membrane) and PRF + cells group (implanted PRF membrane and rat PDLSCs). PRF greatly enhanced cell proliferation, mRNA and protein expression levels of bone sialoprotein (BSP), osteocalcin (OC), and runt-related transcription factor 2 (RUNX2) and activity of alkaline phosphatase (ALP) in vitro. Transplantation of PRF combined with rat PDLSCs resulted in higher expression of osteopontin (Opn), collagen I (COL1A) and RUNX2 at both 12 and 24 days after surgery. Micro-computed tomography and histological analysis showed substantially more new bone formation in the PRF + cells group at 24 days after surgery. Based on these results, we discuss the role of PRF in the proliferation and differentiation of rat PDLSCs and suggest that PRF combined with rat PDLSCs provides a valuable tool for periodontal tissue engineering.

hsa-miR-485-5p reverses epithelial to mesenchymal transition and promotes cisplatin-induced cell death by targeting PAK1 in oral tongue squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is currently a highly prevalent disease worldwide. Cisplatin (CDDP) is widely used for the chemotherapy of OSCC. Yet, the molecular mechanisms responsible for cisplatin resistance have not been fully elucidated. In this study, we showed that overexpression of p21 (RAC1) activated kinase 1 (PAK1) induced epithelial to mesenchymal transition (EMT) and significantly promoted the invasion and migration of oral squamous cell carcinoma SCC25 cells. Emerging evidence indicates a strong link between resistance to therapy and the induction of EMT in cancer. We showed that overexpression of PAK1 induced cisplatin resistance in SCC25 cells. ERCC1 and YAP can promote cisplatin resistance in human OSCC. We showed that ERCC1 and YAP protein were upregulated by PAK1 in SCC25 cells. -We found that miR­485­5p inhibited PAK1 protein expression in the SCC25 cells. Contrary to PAK1, we demonstrated that overexpression of miR­485­5p reversed EMT and significantly inhibited invasion and migration. Moreover, its overexpression sensitized SCC25-CR cells (cisplatin-resistant cells) to cisplatin. Thus, we conclude that miR­485­5p reverses EMT and promotes cisplatin-induced cell death by targeting PAK1 in oral tongue squamous cell carcinoma. This study suggests that PAK1 plays an essential role in the progression of OSCC and it is a potential therapeutic target for OSCC.

The Use of "Omics" in Lactation Research in Dairy Cows.

"Omics" is the application of genomics, transcriptomics, proteomics, and metabolomics in biological research. Over the years, tremendous amounts of biological information has been gathered regarding the changes in gene, mRNA and protein expressions as well as metabolites in different physiological conditions and regulations, which has greatly advanced our understanding of the regulation of many physiological and pathophysiological processes. The aim of this review is to comprehensively describe the advances in our knowledge regarding lactation mainly in dairy cows that were obtained from the "omics" studies. The "omics" technologies have continuously been preferred as the technical tools in lactation research aiming to develop new nutritional, genetic, and management strategies to improve milk production and milk quality in dairy cows.

[Expression of vascular endothelial growth factor in dental pulp of immature and mature permanent teeth in human].

PURPOSE: To investigate the expression and distribution of vascular endothelial growth factor(VEGF) in human dental pulp of immature and mature permanent teeth, and the relationship between VEGF and root development of human permanent teeth. METHODS: The normal teeth extracted for orthodontic or impacted reason were divided into two groups: group 1 contained 10 immature permanent teeth and group 2 contained 15 apical closed mature permanent teeth. The pulps were processed with immunohistochemically staining of VEGF. Image pro-plus 5.1 software was used to evaluate the histological sections and the data was analyzed by Chi-square test, Students't test, one-way ANOVA and SNK-q test with SPSS 13.0 software package. RESULTS: The expression of VEGF was strongly positive in the cytoplasma of pulp fibroblasts and odontoblasts in immature permanent teeth,significantly higher than in mature permanent teeth (P<0.05). The expression of VEGF was demonstrated most strongly positive in fibroblasts in the top area of apical pipe socket of immature root pulp, and gradually weakly positive toward the coronal and apical direction. CONCLUSIONS: The expression of VEGF in dental pulp of immature and mature permanent teeth shows different characteristics. VEGF may play a role in permanent tooth development and maturation.

[Scanning electron microscopic study on the use of traditional Chinese medical irrigant in ultrasonic root canal instrumentation].

PURPOSE: To evaluate the cleaning ability of traditional Chinese medicine Jieeryin used as ultrasonic root canal irrigant. METHODS: A total of 20 extracted human single-rooted teeth were divided into 4 groups: normal saline, 3.33% Jieeryin, 30% Jieeryin and 2.5% sodium hypochlorite. After ultrasonic root canal preparation a 15#-K type ultrasonic file was inserted into the root canal without contacting the root canal wall and the ultrasonic irrigation was kept for 10 seconds. The cleaning of the cervical, middle and apical thirds of the root canal walls was evaluated by scanning electron microscope. The data were analyzed statistically by ANOVA and Bonferroni test. RESULTS: The cleaning ability of 30% Jieeryin was similar to that of 2.5% NaClO (P>0.05) in the cervical third, and it was significantly better than 3.33% Jieeryin (P<0.01) and normal saline (P<0.05). There was significant difference between the cervical third and the middle or apical thirds (P<0.01) of 30% Jieeryin. There was no significant difference between the four groups in the middle third (P>0.05). In the apical third, 2.5% NaClO was significantly better than normal saline (P>0.05). No significant difference was found between 3.33% Jieeryin and saline in all thirds. CONCLUSION: Cleaning by 30% Jieeryin or 2.5% NaClO with ultrasonic technique was superior compared to the cleaning by 3.33% Jieeryin or normal saline in the cervical third.