A novel interactive deep cascade spectral graph convolutional network with multi-relational graphs for disease prediction.

Graph neural networks (GNNs) have recently grown in popularity for disease prediction. Existing GNN-based methods primarily build the graph topological structure around a single modality and combine it with other modalities to acquire feature representations of acquisitions. The complicated relationship in each modality, however, may not be well highlighted due to its specificity. Further, relatively shallow networks restrict adequate extraction of high-level features, affecting disease prediction performance. Accordingly, this paper develops a new interactive deep cascade spectral graph convolutional network with multi-relational graphs (IDCGN) for disease prediction tasks. Its crucial points lie in constructing multiple relational graphs and dual cascade spectral graph convolution branches with interaction (DCSGBI). Specifically, the former designs a pairwise imaging-based edge generator and a pairwise non-imaging-based edge generator from different modalities by devising two learnable networks, which adaptively capture graph structures and provide various views of the same acquisition to aid in disease diagnosis. Again, DCSGBI is established to enrich high-level semantic information and low-level details of disease data. It devises a cascade spectral graph convolution operator for each branch and incorporates the interaction strategy between different branches into the network, successfully forming a deep model and capturing complementary information from diverse branches. In this manner, more favorable and sufficient features are learned for a reliable diagnosis. Experiments on several disease datasets reveal that IDCGN exceeds state-of-the-art models and achieves promising results.

Consolidating Organometallic Complex Ir-CA Empowers Mitochondria-Directed Chemotherapy against Resistant Cancer via Stemness and Metastasis Inhibition.

Cancer treatment has faced severe obstacles due to the smart biological system of cancer cells. Herein, we report a three-in-one agent Ir-CA via attenuation of cancer cell stemness with the down-regulated biomarker CD133 expression from the mitochondria-directed chemotherapy. Over 80% of Ir-CA could accumulate in mitochondria, result in severe mitochondrial dysfunctions, and subsequently initiate mitophagy and cell cycle arrest to kill cisplatin-resistant A549R cells. In vitro and in vivo antimetastatic experiments demonstrated that Ir-CA can effectively inhibit metastasis with down-regulated MMP-2/MMP-9. RNA seq analysis and Western blotting indicated that Ir-CA also suppresses the GSTP1 expression to decrease the intracellular Pt-GS adducts, resulting in the detoxification and resensitization to cisplatin of A549R cells. In vivo evaluation indicated that Ir-CA restrains the tumor growth and has minimal side effects and superior biocompatibility. This work not only provides the first three-in-one agent to attenuate cancer cell stemness and simultaneously realize anticancer, antimetastasis, and conquer metallodrug resistance but also demonstrates the effectiveness of the mitochondria-directed strategy in cancer treatment.

Prognostic value of geriatric nutritional risk index in patients with diffuse large B-cell lymphoma: a meta-analysis

Background Geriatric nutritional risk index (GNRI) on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) remains unclear. The purpose of this meta-analysis was to discuss the value of the GNRI in evaluating long-term outcomes in DLBCL. Methods We systematically and roundly retrieved PubMed, Cochrane Library, Embase, Scopus and Web of Science electronic databases from inception of the databases to March 20, 2023. At the same time, we calculated the pool hazard ratios (HRs) with their 95% confidence interval (CI) for overall survival and progression-free survival to assess the effect of GNRI on the prognosis of DLBCL patients. Results In our primary meta-analysis, 7 trials with a total of 2448 patients were enrolled. Results showed that lower level of GNRI was related to poorer overall survival (HR = 1.78, 95% CI 1.27, 2.50, p < 0.01) and worse progression-free survival (HR = 2.31, 95% CI 1.71, 3.13, p < 0.01) in DLBCL patients. Conclusion The results of our meta-analysis indicate that a lower GNRI significantly associated with poorer prognosis for DLBCL. It is believed that GNRI was a promisingly predictive indicator of survival outcomes in DLBCL patients. However, large multicenter prospective studies are necessary to verify the results (AU)

BML-111 inhibit H2O2-induced pyroptosis and osteogenic dysfunction of human periodontal ligament fibroblasts by activating the Nrf2/HO-1 pathway.

BACKGROUND: Periodontitis is a common and harmful chronic inflammatory oral disease, characterized by the destruction of periodontal soft and hard tissues. The NLRP3 inflammasome-related pyroptosis and human periodontal ligament fibroblasts (hPDLFs) osteogenic dysfunction are involved in its pathogenesis. Studies have shown that lipoxin A4 is an endogenous anti-inflammatory mediator and BML-111 is a lipoxin A4 analog, which was found to have potent and durable anti-inflammatory effects in inflammatory diseases, but the mechanism remains unclear. The purpose of this study was to investigate whether BML-111 inhibits H2O2-induced dysfunction of hPDLFs, attenuates inflammatory responses, and identifies the underlying mechanisms. METHODS: The oxidative stress model was established with H2O2, and the cell proliferation activity was measured by CCK-8. ALP staining and alizarin red staining were used to detect the osteogenic differentiation capacity of cells; flow cytometry and ELISA were used to detect cell pyroptosis; we explored the effect of BML-111 on hPDLFs under oxidative stress by analyzing the results of PCR and Western blotting. The Nrf2 inhibitor ML385 was added to further identify the target of BML-111 and clarify its mechanism. RESULTS: BML-111 can alleviate the impaired cell proliferation viability induced by H2O2. H2O2 treatment can induce NLRP3 inflammasome-related pyroptosis, impairing the osteogenic differentiation capacity of hPDLFs. BML-111 can effectively alleviate H2O2-induced cellular dysfunction by activating the Nrf2/HO-1 signaling pathway. CONCLUSION: The results of this study confirmed the beneficial effects of BML-111 on H2O2-induced NLRP3 inflammasome-related pyroptosis in hPDLFs, and BML-111 could effectively attenuate the impaired osteogenic differentiation function. This beneficial effect is achieved by activating the Nrf2/HO-1 signaling pathway, therefore, our results suggest that BML-111 is a potential drug for the treatment of periodontitis.

Prognostic value of geriatric nutritional risk index in patients with diffuse large B-cell lymphoma: a meta-analysis.

BACKGROUND: Geriatric nutritional risk index (GNRI) on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) remains unclear. The purpose of this meta-analysis was to discuss the value of the GNRI in evaluating long-term outcomes in DLBCL. METHODS: We systematically and roundly retrieved PubMed, Cochrane Library, Embase, Scopus and Web of Science electronic databases from inception of the databases to March 20, 2023. At the same time, we calculated the pool hazard ratios (HRs) with their 95% confidence interval (CI) for overall survival and progression-free survival to assess the effect of GNRI on the prognosis of DLBCL patients. RESULTS: In our primary meta-analysis, 7 trials with a total of 2448 patients were enrolled. Results showed that lower level of GNRI was related to poorer overall survival (HR = 1.78, 95% CI 1.27, 2.50, p < 0.01) and worse progression-free survival (HR = 2.31, 95% CI 1.71, 3.13, p < 0.01) in DLBCL patients. CONCLUSION: The results of our meta-analysis indicate that a lower GNRI significantly associated with poorer prognosis for DLBCL. It is believed that GNRI was a promisingly predictive indicator of survival outcomes in DLBCL patients. However, large multicenter prospective studies are necessary to verify the results.

Metal-polyphenol microgels for oral delivery of puerarin to alleviate the onset of diabetes.

Puerarin (Pue) is a naturally bioactive compound with many potential functions in regulating blood glucose and lipid metabolism. However, the low bioavailability and rapid elimination in vivo limit the application of Pue in diabetic treatment. Here, we developed a metal-polyphenol-functionalized microgel to effectively deliver Pue in vivo and eventually alleviate the onset of diabetes. Pue was initially encapsulated in alginate beads through electrospray technology, and further immersed in Fe3+ and tannic acid solution from tannic acid (TA)-iron (Fe) coatings (TF). These constructed Pue@SA-TF microgels exhibited uniform spheres with an average size of 367.89 ± 18.74 µm and high encapsulation efficiency of Pue with 61.16 ± 1.39%. In vivo experiments proved that compared with free Pue and microgels without TF coatings, the biological distribution of Pue@SA-TF microgels specifically accumulated in the small intestine, prolonged the retention time of Pue, and achieved a high effectiveness in vivo. Anti-diabetic experimental results showed that Pue@SA-TF microgels significantly improved the levels of blood glucose, blood lipid, and oxidative stress in diabetic mice. Meanwhile, histopathological observations indicated that Pue@SA-TF microgels could significantly alleviate the damage to the liver, kidney, and pancreas in diabetic mice. Our study provided an effective strategy for oral delivery of Pue and achieved high anti-diabetic efficacy.

Knockdown of FOXRED2 restrains proliferation, invasion and migration of human melanoma cells.

Objectives: This experiment investigated the role of the FAD-dependent oxidoreductase domain-containing 2 (FOXRED2) in the development of cutaneous malignant melanoma. Methods: We explored the expression and prognostic effects of FOXRED2 in cutaneous malignant melanoma by performing bioinformatics analyses and immunohistochemical staining experiments and verified the biological influence of FOXRED2 on human melanoma cells using in vitro experiments. Results: FOXRED2 expression was significantly higher in cutaneous malignant melanoma compared to normal skin and nevus tissues and closely associated with prognosis. The expression levels of FOXRED2 mRNA and protein were significantly upregulated in human melanoma cell lines, and knocking down FOXRED2 expression inhibits proliferation, invasion, and migration, promotes apoptosis, and alters tumor cell biology in A2058 and A375 cells. Conclusion: FOXRED2 may play a crucial role in the development and progression of cutaneous malignant melanoma.

Genome-Wide Identification, Characterization, and Expression Analysis of the Copper-Containing Amine Oxidase Gene Family in Mangrove Kandelia obovata.

Copper-containing amine oxidases (CuAOs) are known to have significant involvement in the process of polyamine catabolism, as well as serving crucial functions in plant development and response to abiotic stress. A genome-wide investigation of the CuAO protein family was previously carried out in sweet orange (Citrus sinensis) and sweet cherry (Prunus avium L.). Six CuAO (KoCuAO1-KoCuAO6) genes were discovered for the first time in the Kandelia obovata (Ko) genome through a genome-wide analysis conducted to better understand the key roles of the CuAO gene family in Kandelia obovata. This study encompassed an investigation into various aspects of gene analysis, including gene characterization and identification, subcellular localization, chromosomal distributions, phylogenetic tree analysis, gene structure analysis, motif analysis, duplication analysis, cis-regulatory element identification, domain and 3D structural variation analysis, as well as expression profiling in leaves under five different treatments of copper (CuCl2). Phylogenetic analysis suggests that these KoCuAOs, like sweet cherry, may be subdivided into three subgroups. Examining the chromosomal location revealed an unequal distribution of the KoCuAO genes across four out of the 18 chromosomes in Kandelia obovata. Six KoCuAO genes have coding regions with 106 and 159 amino acids and exons with 4 and 12 amino acids. Additionally, we discovered that the 2.5 kb upstream promoter region of the KoCuAOs predicted many cis elements linked to phytohormones and stress responses. According to the expression investigations, CuCl2 treatments caused up- and downregulation of all six genes. In conclusion, our work provides a comprehensive overview of the expression pattern and functional variety of the Kandelia obovata CuAO gene family, which will facilitate future functional characterization of each KoCuAO gene.

Genome-Wide Identification and Expression Analysis of the Copper Transporter (COPT/Ctr) Gene Family in Kandelia obovata, a Typical Mangrove Plant.

The copper transporter (COPT/Ctr) gene family plays a critical part in maintaining the balance of the metal, and many diverse species depend on COPT to move copper (Cu) across the cell membrane. In Arabidopsis thaliana, Oryza sativa, Medicago sativa, Zea mays, Populus trichocarpa, Vitis vinifera, and Solanum lycopersicum, a genome-wide study of the COPT protein family was performed. To understand the major roles of the COPT gene family in Kandelia obovata (Ko), a genome-wide study identified four COPT genes in the Kandelia obovata genome for the first time. The domain and 3D structural variation, phylogenetic tree, chromosomal distributions, gene structure, motif analysis, subcellular localization, cis-regulatory elements, synteny and duplication analysis, and expression profiles in leaves and Cu were all investigated in this research. Structural and sequence investigations show that most KoCOPTs have three transmembrane domains (TMDs). According to phylogenetic research, these KoCOPTs might be divided into two subgroups, just like Populus trichocarpa. KoCOPT gene segmental duplications and positive selection pressure were discovered by universal analysis. According to gene structure and motif analysis, most KoCOPT genes showed consistent exon-intron and motif organization within the same group. In addition, we found five hormones and four stress- and seven light-responsive cis-elements in the KoCOPTs promoters. The expression studies revealed that all four genes changed their expression levels in response to copper (CuCl2) treatments. In summary, our study offers a thorough overview of the Kandelia obovata COPT gene family's expression pattern and functional diversity, making it easier to characterize each KoCOPT gene's function in the future.

Phosphatidylserine-functionalized liposomes-in-microgels for delivering genistein to effectively treat ulcerative colitis.

Ulcerative colitis (UC) is an inflammatory disease involving ulcers in the colon and rectum. The conventional treatments for UC still have many limitations, such as non-specific release, adverse effects and low absorption, resulting in the poor bioavailability of therapeutic agents. To address these challenges, targeting delivery systems are required to specifically deliver drugs to the colonic site with controlled release. Herein, we present a novel microgel oral delivery system, loaded with liposome nanoparticles (Li NPs) containing a natural anti-inflammatory compound genistein (Gen) into alginate microgels, thereby achieving the targeted release of Gen in the colonic region and ameliorating UC symptoms. Initially, Gen was loaded into phosphatidylserine (PS)-functionalized Li NPs to form Gen@Li NPs with an average size of 245.9 ± 9.6 nm. In vitro assessments confirmed that Gen@Li NPs efficiently targeted macrophages and facilitated the internalization of Gen into cells. To prevent rapid degradation in the harsh gastrointestinal tract, Gen@Li NPs were further encapsulated into alginate microgels through electric spraying technology, forming Gen@Li microgels. In vivo distribution tests demonstrated that Gen@Li microgels possessed long-term retention in the colon and gradual release characteristics compared to Gen@Li NPs. Furthermore, in vivo experiments confirmed that Gen@Li microgels significantly alleviated UC symptoms in mice induced by dextran sulfate sodium salt (DSS) mainly through reducing the expression levels of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) and promoting colonic mucosal barrier repair through upregulation of mucosal protein expression. This study shed light on the potential of utilizing oral administration of natural compounds for UC treatment.

The clinical value of the monocyte to high-density lipoprotein cholesterol ratio and alkaline phosphatase-to-platelet ratio in primary biliary cholangitis.

This study aimed to evaluate the clinical value of the monocyte to high-density lipoprotein cholesterol ratio (MHR) and alkaline phosphatase-to-platelet ratio (APPR) in the diagnosis and prognosis of primary biliary cholangitis (PBC). Clinical and laboratory data were retrospectively collected and analyzed from 92 PBC patients, 92 patients with autoimmune hepatitis (AIH), 120 patients with chronic hepatitis B (CHB) and 124 healthy controls (HCs). We compared the levels of MHR and APPR among the groups with PBC, AIH, CHB and HCs, and analyzed the correlations between MHR and APPR with laboratory indices including aspartate aminotransferase platelet ratio index, fibrosis index based on 4 factors, and Mayo score in PBC. Receiver operating characteristic curves were used to analyze the diagnostic performance of MHR and APPR for PBC, AIH, and CHB, respectively. MHR and APPR were significantly increased in PBC group than that in AIH, CHB and HCs groups (each P < .05). MHR and APPR were significantly higher in Child class B|C than that in class A in PBC patients. (P < .01, P < .05, respectively). MHR and APPR were positively related to the Mayo score [R = 0.508 (P < .001), R = 0.295 (P = .008), respectively]. The area under the receiver operating characteristic curves of MHR and APPR in diagnosing PBC were 0.764 (95% confidence interval [CI]: 0.699-0.821, P < .001) and 0.952 (95% CI: 0.915-0.977, P < .001), respectively, and the area under the curve of the combination of both was 0.974 (95% CI: 0.941-0.991, P < .001). MHR and APPR may prove to be useful prognostic biomarkers for PBC, and the combination of MHR and APPR have some clinical diagnostic value of PBC.

Helical-Like Assembly of Nateglinide as Coating for Oral Delivery of Insulin and Their Synergistic Prevention of Diabetes Mellitus.

Oral delivery of antidiabetic active components promises to free millions of people from daily suffering who require routine injections. However, oral insulin (Ins) and other short-acting compounds such as nateglinide (NG) in harsh gastrointestinal tract still face great challenging, including low bioavailability, and rapid elimination. In this study, inspired by the self-assembly of phenylalanine-based peptides in nature, it is showed that NG a small phenylalanine derivative, assembles into left-handed helical nanofibers in the presence of Ca2+ . These helical NG nanofibers functioned as a coating layer on the surface of Ca2+ -linked alginate (Alg) microgels for the effective encapsulation of Ins. As expected, the sustained release and prolonged circulation of Ins and NG from the Ins-loading Alg/NG microgels (Ins@Alg/NG) in the intestinal tract synergistically maintain a relatively normal blood glucose level in streptozotocin-induced diabetic mice after oral administration of Ins@Alg/NG. This further confirms that Ins@Alg/NG ameliorated Ins resistance mainly through activating Insreceptor substrate 1 (IRS1), protein kinase B (AKT), and AMP-activated protein kinase (AMPK), as well as by repressing glycogen synthase kinase-3ß (GSK-3ß). The strategy of using the assembly of NG as a coating achieves the oral delivery of insulin and showcases a potential for the treatment of diabetes.

Effect and mechanism of pearl on ovarian function of rats with premature ovarian failure induced by tripterygium glycosides.

Background and aim: Recent studies show that combination of apoptosis and oxidative stress forms a "vicious circle" in the process of premature ovarian failure (POF). Pearl extract has a good effect for anti-oxidation and anti-aging in vitro and vivo and can be used to treat various aging diseases. However, reports about effect and mechanism of pearl on ovarian function of premature ovarian failure (POF)are limited. Experimental procedure: The effect and mechanism of pearl on ovarian function of rats with POF were evaluated using rats with premature ovarian failure induced by tripterygium glycosides. The estrous cycle, contents of serum reproductive hormones, tissue structure, oxidative stress level, autophagy and apoptotic protein expression, and MAPK signaling pathway of ovary were assessed to characterise pearl. Result and conclusion: Low, medium and high-dose pearl improved the estrous cycle in POF rats, and high-dose pearl was the best in terms of recovery effect; high-dose pearl significantly increased (P < 0.05) contents of E2, AMH and GSH, activities of SOD, CAT and GSH-PX and follicular development, while significantly decreased (P < 0.05)contents of FSH, LH and ROS and MDA in POF rats; low, medium and high-dose pearl notably reduced (P < 0.05) the apoptotic protein cleaved-caspase 3 and Bax expression, and MAPK signaling pathway of ERK1/2, p38 and JNK in POF rats, among which high-dose pearl behaved best. Medium and high-dose pearl apparently raised (P < 0.05)expressions of autophagy protein LC3II, Beclin-1 and p62 in POF rats. Therefore, pearl can effectively enhance ovarian function of POF rats. The optimal concentration was found to be 740 mg kg-1 at a high dose. The mechanism may be related with the enhanced follicular development through improving granulosa cell autophagy and inhibiting granulosa cell apoptosis by inhibition of MAPK signaling pathway after scavenging excessive ROS. Section: 1. Natural Products. Taxonomy classification by EVISE: Ovarian Cancer, Chinese Herbal Medicine, Traditional Medicine, Oxidative Stress, Antioxidant Studies, Rat, Autophagy.

MicroRNAs as promising therapeutic agents: A perspective from acupuncture.

MicroRNAs (miRNAs) are gaining recognition as potential therapeutic agents due to their small size, ability to target a wide range of genes, and significant role in disease progression. However, despite their promising potential, nearly half of the miRNA drugs developed for therapeutic purposes have been discontinued or put on hold, and none have advanced to phase III clinical trials. The development of miRNA therapeutics has faced obstacles such as difficulties in validating miRNA targets, conflicting evidence regarding competition and saturation effects, challenges in miRNA delivery, and determining appropriate dosages. These hurdles primarily arise from the intricate functional complexity of miRNAs. Acupuncture, a distinct, complementary therapy, offers a promising avenue to overcome these barriers, particularly by addressing the fundamental issue of preserving functional complexity through acupuncture regulatory networks. The acupuncture regulatory network consists of three main components: the acupoint network, the neuro-endocrine-immune (NEI) network, and the disease network. These networks represent the processes of information transformation, amplification, and conduction that occur during acupuncture. Notably, miRNAs serve as essential mediators and shared biological language within these interconnected networks. Harnessing the therapeutic potential of acupuncture-derived miRNAs can help reduce the time and economic resources required for miRNA drug development and alleviate the current developmental challenges miRNA therapeutics face. This review provides an interdisciplinary perspective by summarizing the interactions between miRNAs, their targets, and the three acupuncture regulatory networks mentioned earlier. The aim is to illuminate the challenges and opportunities in developing miRNA therapeutics. This review paper presents a comprehensive overview of miRNAs, their interactions with acupuncture regulatory networks, and their potential as therapeutic agents. By bridging the miRNA research and acupuncture fields, we aim to offer valuable insights into the obstacles and prospects of developing miRNA therapeutics.

The Value of Hematological Indexes in Evaluating the Risk of Hip Involvement in Patients with Ankylosing Spondylitis.

BACKGROUND: The goal was to explore the value of neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) in evaluating the risk of hip involvement in patients with ankylosing spondylitis (AS). METHODS: The study included 188 AS patients (Based on BASRI-hip score, patients were classified as hip involvement group (BASRI-hip ≥ 2; n = 84) and non-hip involvement group (BASRI-hip ≤ 1; n = 104), 173 patients with osteoarthritis (OA) of the hip and 181 age- and gender-matched healthy controls (HCs). The value of NLR and MLR in different groups were observed. RESULTS: The NLR and MLR in AS patients with hip involvement were significantly higher than in the non-hip involvement group (p < 0.05), and patients with moderate and severe hip involvement were significantly higher than mild hip involvement (p < 0.05). The analysis of receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) of NLR, MLR, and the combination of NLR and MLR for AS patients with hip involvement were 0.817, 0.840, and 0.863, respectively (each p < 0.001) and the AUC values for predicting AS patients with moderate and severe hip involvement in patients with AS were 0.862, 0.847, and 0.889, respectively (each p < 0.001), which showed their significance in clinical settings. Also, NLR and MLR of AS patients were positively correlated with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (each p < 0.01). CONCLUSIONS: Therefore, NLR and MLR may be diagnostic hematological indexes in evaluating AS patients with hip involvement, particularly in the patients with moderate and severe hip involvement and higher diagnostic efficiency when combined analysis is done.

Advances in the Anti-Tumor Activity of Biflavonoids in Selaginella.

Despite the many strategies employed to slow the spread of cancer, the development of new anti-tumor drugs and the minimization of side effects have been major research hotspots in the anti-tumor field. Natural drugs are a huge treasure trove of drug development, and they have been widely used in the clinic as anti-tumor drugs. Selaginella species in the family Selaginellaceae are widely distributed worldwide, and they have been well-documented in clinical practice for the prevention and treatment of cancer. Biflavonoids are the main active ingredients in Selaginella, and they have good biological and anti-tumor activities, which warrant extensive research. The promise of biflavonoids from Selaginella (SFB) in the field of cancer therapy is being realized thanks to new research that offers insights into the multi-targeting therapeutic mechanisms and key signaling pathways. The pharmacological effects of SFB against various cancers in vitro and in vivo are reviewed in this review. In addition, the types and characteristics of biflavonoid structures are described in detail; we also provide a brief summary of the efforts to develop drug delivery systems or combinations to enhance the bioavailability of SFB monomers. In conclusion, SFB species have great potential to be developed as adjuvant or even primary therapeutic agents for cancer, with promising applications.

The protective effects of electroacupuncture on intestinal barrier lesions in IBS and UC model.

Irritable bowel syndrome (IBS) and ulcerative colitis (UC) are two intestinal diseases with different pathological changes. Electroacupuncture (EA) at Zusanli (ST36) on both IBS and UC is widely used in clinic practice. But it is unclear whether acupuncture at one acupoint can treat two different intestinal diseases at different layers of intestinal barrier. To address this question, we explored three intestinal barrier lesions in IBS and UC mice with the aid of transcriptome data analysis and studied the efficacy of EA at ST36 on them. The transcriptome data analysis showed that both UC and IBS had disrupted intestinal barrier in various layers. And both UC and IBS had epithelial barrier lesions with reduction of ZO-1, Occludin and Claudin-1, while UC rather than IBS had the destruction of the mucus barrier with less MUC2 expression. As to the vascular barrier, UC showed a higher CD31 level and mesenteric blood flow reduction, while IBS showed a lower PV-1 level. EA at ST36 can significantly improve the above lesions of intestinal barrier of IBS and UC. Our results gave more details about the comprehensive protective effect of EA for UC and IBS. We guess the effect of acupuncture may be a kind of homeostasis regulation.

Performance evaluation of E-nose and E-tongue combined with machine learning for qualitative and quantitative assessment of bear bile powder.

Bear bile powder (BBP) is a valuable animal-derived product with a huge adulteration problem on market. It is a crucially important task to identify BBP and its counterfeit. Electronic sensory technologies are the inheritance and development of traditional empirical identification. Considering that each drug has its own specific odor and taste characteristics, electronic tongue (E-tongue), electronic nose (E-nose) and GC-MS were used to evaluate the aroma and taste of BBP and its common counterfeit. Two active components of BBP, namely tauroursodeoxycholic acid (TUDCA) and taurochenodeoxycholic acid (TCDCA) were measured and linked with the electronic sensory data. The results showed that bitterness was the main flavor of TUDCA in BBP, saltiness and umami were the main flavor of TCDCA. The volatiles detected by E-nose and GC-MS were mainly aldehydes, ketones, alcohols, hydrocarbons, carboxylic acids, heterocyclic, lipids, and amines, mainly earthy, musty, coffee, bitter almond, burnt, pungent odor descriptions. Four different machine learning algorithms (backpropagation neural network, support vector machine, K-nearest neighbor, and random forest) were used to identify BBP and its counterfeit, and the regression performance of these four algorithms was also evaluated. For qualitative identification, the algorithm of random forest has shown the best performance, with 100% accuracy, precision, recall and F1-score. Also, the random forest algorithm has the best R2 and the lowest RMSE in terms of quantitative prediction.

Protective effect of Nrf2 in periodontitis - A preclinical systematic review and meta-analysis.

OBJECTIVE: Periodontitis is an inflammatory disease, while Nuclear factor erythroid-2 related factor 2 (Nrf2) acts a significant part in antioxidant, anti-inflammatory and immune response. However, the evidence in preclinical studies to certify Nrf2 can slow down the progression of periodontitis or facilitate its recovery is not enough. The present report aims to investigate the functional implications of Nrf2 in animal periodontitis models by evaluating the changes of Nrf2 levels and analyzing the clinical benefits of Nrf2 activation in the same models. DESIGN: We searched PubMed, Web of Science, EBSCO, CNKI, VIP, Wan Fang databases. The random-effects model was used to evaluate the mean differences (MD) and 95 % confidence intervals (95%CI) when the units of measurements of outcome indicators were the same, in contrast, the standardized mean differences (SMD) and 95%CI were evaluated while the units were different. RESULTS: 8 studies were included for quantitative synthesis. Compared with healthy groups, the expression of Nrf2 was markedly lower in periodontitis groups (SMD: -3.69; 95%CI: -6.25, -1.12). After administration of kinds of Nrf2-activators, a significant increase in Nrf2 levels (SMD: 2.01; 95%CI: 1.27, 2.76) was accompanied by a decrease in distance between cementoenamel junction and alveolar bone crest (CEJ-ABC) (SMD: -2.14; 95%CI: -3.29, -0.99) and an improvement of bone volume/tissue volume (BV/TV) (SMD:17.51; 95%CI: 16.24, 18.77) was evaluated compared with periodontitis groups. CONCLUSIONS: Nrf2 has a certain protective effect on periodontitis, however, the specific role Nrf2 plays in the development and severity of periodontitis remains to be demonstrated. PROSPERO registration number: CRD42022328008.

Purinergic signaling: A gatekeeper of blood-brain barrier permeation.

This review outlined evidence that purinergic signaling is involved in the modulation of blood-brain barrier (BBB) permeability. The functional and structural integrity of the BBB is critical for maintaining the homeostasis of the brain microenvironment. BBB integrity is maintained primarily by endothelial cells and basement membrane but also be regulated by pericytes, neurons, astrocytes, microglia and oligodendrocytes. In this review, we summarized the purinergic receptors and nucleotidases expressed on BBB cells and focused on the regulation of BBB permeability by purinergic signaling. The permeability of BBB is regulated by a series of purinergic receptors classified as P2Y1, P2Y4, P2Y12, P2X4, P2X7, A1, A2A, A2B, and A3, which serve as targets for endogenous ATP, ADP, or adenosine. P2Y1 and P2Y4 antagonists could attenuate BBB damage. In contrast, P2Y12-mediated chemotaxis of microglial cell processes is necessary for rapid closure of the BBB after BBB breakdown. Antagonists of P2X4 and P2X7 inhibit the activation of these receptors, reduce the release of interleukin-1 beta (IL-1ß), and promote the function of BBB closure. In addition, the CD39/CD73 nucleotidase axis participates in extracellular adenosine metabolism and promotes BBB permeability through A1 and A2A on BBB cells. Furthermore, A2B and A3 receptor agonists protect BBB integrity. Thus, the regulation of the BBB by purinergic signaling is complex and affects the opening and closing of the BBB through different pathways. Appropriate selective agonists/antagonists of purinergic receptors and corresponding enzyme inhibitors could modulate the permeability of the BBB, effectively delivering therapeutic drugs/cells to the central nervous system (CNS) or limiting the entry of inflammatory immune cells into the brain and re-establishing CNS homeostasis.