Identification of potential therapeutic targets for plaque vulnerability based on an integrated analysis.

BACKGROUND AND AIMS: This study aimed to explore potential hub genes and pathways of plaque vulnerability and to investigate possible therapeutic targets for acute coronary syndrome (ACS). METHODS AND RESULTS: Four microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs), weighted gene coexpression networks (WGCNA) and immune cell infiltration analysis (IIA) were used to identify the genes for plaque vulnerability. Then, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, Disease Ontology, Gene Ontology annotation and protein-protein interaction (PPI) network analyses were performed to explore the hub genes. Random forest and artificial neural networks were constructed for validation. Furthermore, the CMap and Herb databases were employed to explore possible therapeutic targets. A total of 168 DEGs with an adjusted P < 0.05 and approximately 1974 IIA genes were identified in GSE62646. Three modules were detected and associated with CAD-Class, including 891 genes that can be found in GSE90074. After removing duplicates, 114 hub genes were used for functional analysis. GO functions identified 157 items, and 6 pathways were enriched for the KEGG pathway at adjusted P < 0.05 (false discovery rate, FDR set at < 0.05). Random forest and artificial neural network models were built based on the GSE48060 and GSE34822 datasets, respectively, to validate the previous hub genes. Five genes (GZMA, GZMB, KLRB1, KLRD1 and TRPM6) were selected, and only two of them (GZMA and GZMB) were screened as therapeutic targets in the CMap and Herb databases. CONCLUSION: We performed a comprehensive analysis and validated GZMA and GZMB as a target for plaque vulnerability, which provides a therapeutic strategy for the prevention of ACS. However, whether it can be used as a predictor in blood samples requires further experimental verification.

A causal analysis of the relationship between exposure to sunlight and colorectal cancer risk: A Mendelian randomization study.

Several observational studies have found that exposure to sunlight reduces the risk of colorectal cancer (CRC). However, sun exposure remains ambiguous in its relationship to CRC. We carried out a Mendelian randomization (MR) study to explore the potential associations between them. We examined the exposure to sunlight summary statistics of the UK Biobank Consortium using a 2-sample MR analysis. Using data from the FinnGen consortium, we derived summary statistics for CRC. We conducted our analysis with various methods, incorporating inverse variance weighted (IVW) along with 4 other approaches. A Cochran Q statistic was used to measure the heterogeneity of instrumental variables (IVs). We screened 133 single nucleotide polymorphisms (SNPs) (time spent outdoors in summer), 41 SNPs (time spent outdoors in winter), and 35 SNPs (frequency of solarium/sunlamp use) representing sunlight exposure for MR analysis. All selected SNPs had an F-statistic >20, indicating that IVs did not weakly bias the results. The summer outdoor activity trait exhibited significant heterogeneity (Cochran Q statistic = 183.795, P = .002 < 0.05), but we found no horizontal polymorphisms or significant heterogeneity for the other exposure traits. According to IVW estimates, no causal association exists between time spent outdoors in summer and CRC (Odds Ratio, OR = 0.735, 95% confidence interval, CI = 0.494-1.017, P = .128 > 0.017). No causal relationship existed between time spent outdoors in winter and CRC, as indicated by Bonferroni-corrected adjusted p-values. The OR was 0.877 with a 95% CI of 0.334-2.299, and the P value was .789, more significant than the significance threshold of 0.017. The solarium/sunlamp use frequency was not associated with CRC (OR = 1.567, 95%CI = 0.243-10.119, P = .637 > .017). Also, an IVW with random effects was applied to determine the causal relationship between summer outdoor time and CRC. No causal association between summer outdoor time and CRC was found (OR = 0.735, 95% CI = 0.494-1.017, P = .128 > .017). Additionally, 4 additional analyses yielded similar results. The findings of our study suggest that exposure to sunlight may reduce CRC risk, but the causal relationship remains unsolved. There is no evidence to suggest that exposure to sunlight prevents CRC. Randomized, controlled trials are needed to determine whether sunlight exposure protects against CRC.

Osteoarthritis and hypertension: observational and Mendelian randomization analyses.

BACKGROUND: The association between osteoarthritis (OA) and hypertension is a subject of ongoing debate in observational research, and the underlying causal relationship between them remains elusive. METHODS: This study retrospectively included 24,871 participants in the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2020. Weighted logistic regression was performed to investigate the connection between OA and hypertension. Additionally, Mendelian randomization (MR) analysis was conducted to explore the potential causal relationship between OA and hypertension. RESULTS: In the NHANES data, after adjusting for multiple confounding factors, there was no significant relationship between OA and hypertension (OR 1.30, 95% CI, 0.97-1.73, P = 0.089). However, among males, OA appeared to be associated with a higher risk of hypertension (OR 2.25, 95% CI, 1.17-4.32, P = 0.019). Furthermore, MR results indicate no relationship between multiple OA phenotypes and hypertension: knee OA (IVW, OR 1.024, 95% CI: 0.931-1.126, P = 0.626), hip OA (IVW, OR 0.990, 95% CI: 0.941-1.042, P = 0.704), knee or hip OA (IVW, OR 1.005, 95% CI: 0.915-1.105, P = 0.911), and OA from UK Biobank (IVW, OR 0.796, 95% CI: 0.233-2.714, P = 0.715). Importantly, these findings remained consistent across different genders and in reverse MR. CONCLUSIONS: Our study found that OA patients had a higher risk of hypertension only among males in the observational study. However, MR analysis did not uncover any causal relationship between OA and hypertension.

Associations of body roundness index with cardiovascular and all-cause mortality: NHANES 2001-2018.

Body roundness index (BRI) was associated with cardiovascular diseases. But the relationship between BRI with cardiovascular disease (CVD) mortality and all-cause mortality remains largely unknown in hypertensive patients. This prospective cohort study included patients with hypertension who participated in the National Health and Nutrition Examination Survey (NHANES) from 2001 through 2018, and aimed to evaluate the association between BRI with CVD mortality and all-cause mortality. A total of 15570 patients were included. Over a median follow-up of 8.0 years (interquartile range, 4.3-12.6 years), 3445 individuals died, including 1166 CVD deaths. Weighted restricted cubic spline regression results showed a nonlinear association between BRI and CVD mortality and all-cause mortality (both P for nonlinear trend <0.001). The weighted multivariate Cox proportional hazards regression showed the hazard ratio (HRs) for CVD mortality were 0.93 (95% CI: 0.84-1.03, P = 0.160) in the low levels of BRI (≤5.9) and 1.11 (95% CI: 1.05-1.19, P < 0.001) in the high levels of BRI (>5.9). Similar associations were observed for all-cause mortality, the HRs were 0.91 (95% CI: 0.87-0.96, P < 0.001) in the low levels of BRI (≤6.3) and 1.09 (95% CI: 1.05-1.13, P < 0.001) in the high levels of BRI (>6.3). This cohort study supported that BRI was nonlinearly associated with CVD mortality and all-cause mortality among patients with hypertension. The thresholds of 5.9 and 6.3 for CVD mortality and all-cause mortality, respectively, may represent intervention targets for lowering the risk of premature death, but this needs to be confirmed in large clinical trials.

Anemoside B4, a new pyruvate carboxylase inhibitor, alleviates colitis by reprogramming macrophage function.

OBJECTIVES: Colitis is a global disease usually accompanied by intestinal epithelial damage and intestinal inflammation, and an increasing number of studies have found natural products to be highly effective in treating colitis. Anemoside B4 (AB4), an abundant saponin isolated from Pulsatilla chinensis (Bunge), which was found to have strong anti-inflammatory activity. However, the exact molecular mechanisms and direct targets of AB4 in the treatment of colitis remain to be discovered. METHODS: The anti-inflammatory activities of AB4 were verified in LPS-induced cell models and 2, 4, 6-trinitrobenzene sulfonic (TNBS) or dextran sulfate sodium (DSS)-induced colitis mice and rat models. The molecular target of AB4 was identified by affinity chromatography analysis using chemical probes derived from AB4. Experiments including proteomics, molecular docking, biotin pull-down, surface plasmon resonance (SPR), and cellular thermal shift assay (CETSA) were used to confirm the binding of AB4 to its molecular target. Overexpression of pyruvate carboxylase (PC) and PC agonist were used to study the effects of PC on the anti-inflammatory and metabolic regulation of AB4 in vitro and in vivo. RESULTS: AB4 not only significantly inhibited LPS-induced NF-κB activation and increased ROS levels in THP-1 cells, but also suppressed TNBS/DSS-induced colonic inflammation in mice and rats. The molecular target of AB4 was identified as PC, a key enzyme related to fatty acid, amino acid and tricarboxylic acid (TCA) cycle. We next demonstrated that AB4 specifically bound to the His879 site of PC and altered the protein's spatial conformation, thereby affecting the enzymatic activity of PC. LPS activated NF-κB pathway and increased PC activity, which caused metabolic reprogramming, while AB4 reversed this phenomenon by inhibiting the PC activity. In vivo studies showed that diisopropylamine dichloroacetate (DADA), a PC agonist, eliminated the therapeutic effects of AB4 by changing the metabolic rearrangement of intestinal tissues in colitis mice. CONCLUSION: We identified PC as a direct cellular target of AB4 in the modulation of inflammation, especially colitis. Moreover, PC/pyruvate metabolism/NF-κB is crucial for LPS-driven inflammation and oxidative stress. These findings shed more light on the possibilities of PC as a potential new target for treating colitis.

The effect of the CPP size on the nonlinear optical properties of the new necklace-type molecules formed by carborane and [n]Cycloparaphenylenes(n = 8-11).

The new necklace-type molecules were formed by [8-13]CPP and carborane, which further manipulated the size of the macroring, revealing the effect of size on its luminescence behavior. In this work, the effects of ring size on the absorption spectrum, electron excitation and nonlinear optical properties of the compounds were investigated in detail, aiming to reveal an effective way to improve the optical properties of these necklace-type compounds. The absorption spectra of the compounds showed that the size of the CPP ring had little effect on the spectral shape and position, but the electron transition information showed that there were the significant charge transfer within the CPP ring and a gradual enhancement of interfragment charge transfer from the CPP ring to carborane. The increasing order of polarizability, first and second hyperpolarizability values of these compounds with the increase of CPP size indicated that increasing the size of the CPP ring was an effective way to increase the nonlinear optical properties of necklace-type molecules. Among the frequency dependent hyperpolarizability values, the γ(-ω;ω,0,0) value increased by a factor of 4 from complex 1 to 6 with the increase of CPP ring size, which indicated that increasing the size of the CPP ring was an effective way to increase the optical Kerr effect of necklace-type molecules. Therefore, these the new necklace-type nolecules formed by carborane and [n]Cycloparaphenylenes would be excellent nonlinear optical materials in the field of the all-optical switch.

Mechanism of salidroside against coronary artery disease by network pharmacology analysis.

BACKGROUND: Rosenroot (Rhodiola rosea) is a traditional Chinese herbal medicine. It has been used to treat patients with coronary artery disease (CAD). Salidroside is the main active constituent of rosenroot. This study was designed to explore the mechanism of salidroside in treating CAD and its role in angiogenesis in CAD systematically. METHODS: In this study, potential targets related to salidroside and CAD were obtained from public databases. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO) and CellMarker enrichment analyses were performed. The binding of salidroside to angiogenesis-related targets was assessed by PyMOL and Ligplot. Furthermore, the effects of salidroside on collateral circulation were evaluated by correlation analysis of these angiogenesis-related targets with the coronary flow index (CFI), and the influence of salidroside on human umbilical vein endothelial cell (HUVEC) proliferation and migration was assessed. RESULTS: Eighty-three targets intersected between targets of salidroside and CAD. GO and KEGG analyses indicated that salidroside mainly treated CAD through angiogenesis and anti-inflammatory action. There were 12 angiogenesis-related targets of salidroside in coronary heart disease, among which FGF1 (r = 0.237, P = 2.597E-3), KDR (r = 0.172, P = 3.007E-2) and HIF1A (r = -0.211, P = 7.437E-3) were correlated with the coronary flow index (CFI), and salidroside docked well with them. Finally, cell experiments confirmed that salidroside promoted the proliferation and migration of HUVECs. CONCLUSIONS: This study revealed the potential molecular mechanism of salidroside on angiogenesis in CAD and provided new ideas for the clinical application of salidroside in the treatment of CAD.

Effect of intermolecular interaction of the charge-transfer complex between molecular "tweezers" and C60/C70 on second-order nonlinear optical properties.

To enhance understanding of the correlation between the intermolecular interaction and second-order nonlinear optical (NLO) properties, we studied a "molecular tweezer" with two corannulene substituents linked by a tetrahydro[5]helicene imide, which enabled highly sensitive and selective complexation of C60/C70 through convex-concave π-π interactions. The geometric structure, molecular orbitals, intermolecular interactions, electron absorption spectra and second-order NLO properties of the charge-transfer (CT) complexes formed by molecular tweezers and C60/C70 were studied by density functional theory. Larger fullerenes helped to increase the intermolecular interaction and CT, thereby increasing the first hyperpolarizabilities of CT complexes. Embedding of lithium ions helped to enhance the electron-absorption ability of fullerenes, thereby increasing the intermolecular interaction and intermolecular CT and, thus, enhancing their first hyperpolarizability significantly. Our data indicated that, through structure adjustment (including increasing the volume of fullerene and embedding alkali metal ions), we could enhance intermolecular interactions and improve intermolecular CT significantly. These actions could improve the second-order NLO properties of CT complexes.

Correlation between the Human Development Index and the Incidence and Mortality of Non-Hodgkin Lymphoma.

OBJECTIVE: This study was to examine the relationship between socioeconomic status and the incidence and mortality of non-Hodgkin lymphoma (NHL). METHODS: We compared the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and the ASMR to ASIR ratio (MIR) at national and regional levels and studied the correlation between the MIR and the human development index (HDI) in 2012 and 2018. RESULTS: The highest ASIR was in North America in 2012 and in Australia in 2018, and the lowest ASIR was in Central and South Asia in both 2012 and 2018. The highest ASMR was in North Africa in both 2012 and 2018, and the lowest ASMR was in Eastern Asia and South-Central Asia in 2012 and in South-Central Asia in 2018. The lowest MIR was in Australia in both 2012 and 2018, and the highest MIR was in Western Africa in both 2012 and 2018. HDI was strongly negatively correlated with MIR (r: -0.8810, P<0.0001, 2012; r: -0.8895, P<0.0001, 2018). Compared to the 2012 data, the MIR in the intermediate HDI countries significantly deceased and the HDI in low and high HDI countries significantly increased in 2018. CONCLUSION: The MIR is negatively correlated with HDI. Increasing the HDI in low and intermediate HDI countries may reduce the MIR and increase the survival of patients with NHL.

Rescuing "hopeless" avulsed teeth using autologous platelet-rich fibrin following delayed reimplantation: Two case reports.

BACKGROUND: Tooth avulsion is one of the most severe types of dental trauma. Most avulsed teeth undergo long-term ankylosis and replacement resorption after delayed reimplantation and exhibit a poor prognosis. The aim of this work was to improve the success rate of avulsed teeth after delayed reimplantation using autologous platelet-rich fibrin (PRF). CASE SUMMARY: Case 1 was a 14-year-old boy who fell and knocked out his left upper central incisor 18 h prior to his arrival at the department. The diagnoses were avulsion of tooth 21, lateral luxation of tooth 11 and alveolar fracture of teeth 11 and 21. In case 2, a 17-year-old boy fell 2 h prior to his presentation to the hospital, and his left upper lateral incisor was completely knocked out of the alveolar socket. The diagnoses included avulsion of tooth 22, complicated crown fracture of tooth 11 and complicated crown-root fracture of tooth 21. The avulsed teeth were reimplanted along with autologous PRF granules and splinted using a semiflexible titanium preshaped labial arch. The root canals of the avulsed teeth were filled with calcium hydroxide paste, and root canal filling was performed 4 wk after reimplantation. The reimplanted teeth showed no symptoms of inflammatory root resorption or ankylosis at the 3-, 6-, and 12-mo follow-up examinations after reimplantation with autologous PRF. In addition to the avulsed teeth, the other injured teeth were treated using corresponding conventional treatment methods. CONCLUSION: These cases provide examples of the successful use of PRF to reduce pathological root resorption of the avulsed teeth, and the application of PRF may provide new healing opportunities for traditionally "hopeless" avulsed teeth.

Hederacoside C ameliorates colitis via restoring impaired intestinal barrier through moderating S100A9/MAPK and neutrophil recruitment inactivation.

Hederacoside C (HSC) has attracted much attention as a novel modulator of inflammation, but its anti-inflammatory mechanism remains elusive. In the present study, we investigated how HSC attenuated intestinal inflammation in vivo and in vitro. HSC injection significantly alleviated TNBS-induced colitis by inhibiting pro-inflammatory cytokine production and colonic epithelial cell apoptosis, and partially restored colonic epithelial cell proliferation. The therapeutic effect of HSC injection was comparable to that of oral administration of mesalazine (200 mg·kg-1·d-1, i.g.). In LPS-stimulated human intestinal epithelial Caco-2 cells, pretreatment with HSC (0.1, 1, 10 µM) significantly inhibited activation of MAPK/NF-κB and its downstream signaling pathways. Pretreatment with HSC prevented LPS-induced TLR4 dimerization and MyD88 recruitment in vitro. Quantitative proteomic analysis revealed that HSC injection regulated 18 proteins in the colon samples, mainly clustered in neutrophil degranulation. Among them, S100A9 involved in the degranulation of neutrophils was one of the most significantly down-regulated proteins. HSC suppressed the expression of S100A9 and its downstream genes including TLR4, MAPK, and NF-κB axes in colon. In Caco-2 cells, recombinant S100A9 protein activated the MAPK/NF-κB signaling pathway and induced inflammation, which were ameliorated by pretreatment with HSC. Notably, HSC attenuated neutrophil recruitment and degranulation as well as S100A9 release in vitro and in vivo. In addition, HSC promoted the expression of tight junction proteins and repaired the epithelial barrier via inhibiting S100A9. Our results verify that HSC ameliorates colitis via restoring impaired intestinal barrier through moderating S100A9/MAPK and neutrophil recruitment inactivation, suggesting that HSC is a promising therapeutic candidate for colitis.

Effects of Atypical Hydrogen Bonds and π-π Interactions on Nonlinear Optical Properties: Dimers of Triangular Structures Based on Perylene, Naphthalene, and Pyromellitic Diimides.

Nonlinear optical (NLO) materials have become important materials in the field of high-speed optical devices due to the changes in light absorption and refraction caused by the photoelectric field. Compounds tend to exist as aggregates rather than single molecules, so intermolecular interactions are crucial to the nature of aggregates. Therefore, to study the effects of intermolecular interactions on nonlinear optical properties, we use a dimer simplified model and adopt the methods of controlling variables, which are the different intermolecular interactions resulting from the different stacking patterns of dimers based on the same monomer structures (2PMDI-1NDI and 2NDI-1PDI). It is found that compared with dimers involving π-π interactions, dimers involving C-H···O interactions have shorter intermolecular distances, larger intermolecular interaction energies, and smaller highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy gaps. Moreover, the C-H···O interactions are more conducive to the intermolecular charge transfers and more beneficial for increasing the nonlinear optical response values of aggregates with respect to π-π interactions. This work provides an important basis for the influence of intermolecular interactions on nonlinear optical properties.

The Enhancement of Hepatic Parenchyma and Portal Vein in different CLD Groups: A Comparative Study of Gadoxetic Acid and Gadopentetate Dimeglumine.

BACKGROUND: Chronic liver disease (CLD) will affect the enhancement of hepatic parenchyma and portal vein on abdominal-enhanced MRI. OBJECTIVE: To investigate the difference in liver parenchyma and portal vein enhancement in patients with CLD of different liver function grades between Gd- EOB-DTPA and Gd-DPTA in the portal venous phase (PVP). METHODS: This retrospective study included 218 patients with CLD who had undergone abdominal enhanced MRI from January 2019 to June 2020. Patients with various degrees of liver dysfunction were identified with Child-Turcotte-Pugh and albumin-bilirubin grade. Two readers measured the precontrast and PVP signal intensities of liver parenchyma, portal vein, spleen, and psoas muscle. Relative liver enhancement, liver-to-spleen contrast index, portal vein image contrast, and portal vein-to-liver contrast were calculated. RESULTS: The relative enhancement of liver parenchyma was significantly lower for the Gd-EOB-DTPA group in any degree of liver function than the Gd- DTPA group in the PVP. The Gd-EOB-DTPA group showed significantly lower portal vein-to-liver contrast in the overall study population, CTP class B, and ALBI grade 2 patients compared to the group of Gd-DTPA at PVP. No significant difference was noted in the portal vein image contrast between the two contrast agents, regardless of CTP and ALBI grading. CONCLUSION: In CLD patients, Gd-EOB-DTPA yielded lower liver parenchymal enhancement and similar portal vein image contrast compared to Gd-DTPA in the PVP. Portal vein-to-liver contrast in the Gd-EOB-DTPA group was lower in the CTP class B and ALBI grade 2 subgroups compared to the Gd- DTPA group.

The organic co-crystals formed using naphthalenediimide-based triangular macrocycles and coronene: intermolecular charge transfers and nonlinear optical properties.

Formation of organic co-crystals is an effective strategy to synthesize near infrared emission and nonlinear optical (NLO) materials, which often show "1 + 1 > 2" performance. Moreover, the crystallization process can be effectively regulated through supramolecular interactions; thus the properties of co-crystal materials can also be flexibly regulated. Here, in order to further understand the nature and formation mechanism of co-crystals from the perspective of theoretical research, we studied the structures, intermolecular interactions, absorption spectra, charge transfer (CT) characteristics and nonlinear optical (NLO) properties of the newly synthesized organic co-crystals formed between naphthalenediimide based triangles (NDI, acceptor) and coronene (COR, donor). According to the analysis of decomposition of intermolecular interaction energy, dispersion energy played a major role, so the co-crystal properties can be regulated by regulating the intermolecular dispersion energy. More importantly, the formation of co-crystals NDI-COR and NDI-2COR reduced the Egap values with respect to those of their components. And there was significant intermolecular CT from COR to NDI and the degree of CT in NDI-COR was larger than that in NDI-2COR, so that the αtot and γtot values of NDI-COR and NDI-2COR were significantly greater than those of their components. Thus, the NLO properties of organic co-crystals can be further improved by enhancing the electron-donating ability of the donor and the electron-withdrawing ability of the acceptor to enhance the degree of intermolecular interaction energy and CT.

Metformin's Mechanisms in Attenuating Hallmarks of Aging and Age-Related Disease.

Aging is a major global challenge, and there is growing demand for new strategies to address the burden of aging. The intensive search for antiaging agents has led to the discovery of a variety of drugs that promote the extension of healthspan and/or life. Metformin is a safe, effective, and globally affordable antihyperglycemic agent that has gained much attention in recent years as a potential antiaging treatment. Metformin has been shown to significantly delay the onset of age-related diseases and increase lifespan in several model organisms. In this paper, we reviewed aging hallmarks and the role of metformin in countering these hallmarks. We examined the beneficial effects of metformin on several age-related diseases and the feasibility of metformin as an agent to extend lifespan and healthspan. Finally, we discussed new research directions to better understand the translational potential of metformin in humans.

A validated LC-MS/MS method for the determination of hederasaponin C: Application to pharmacokinetics-pharmacodynamics studies in the therapeutic area of acetic acid-induced ulcerative colitis in rats.

Hederasaponin C (HSC), one of the main components of Pulsatilla chinensis, is considered as a potential drug for the treatment of inflammatory bowel disease. In the present research, we developed a pharmacokinetics-pharmacodynamics model to describe the concentration-effect course of drug action following the intraperitoneal injection of HSC in colitis rats. A sensitive UPLC-MS/MS method was established for the the determination of HSC in rat plasma to explore the pharmacokinetics properties. The separation was performed on an Accucore C18 column (2.1 × 100 mm, 2.6 µm) with a flow phase consisting of acetonitrile and 0.1% formic acid water. The assay method was validated and demonstrated good adaptability for application in the pharmacokinetics study. Then the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in colon tissues were measured using an ELISA assay. The levels of TNF-α, IL-1ß and IL-6 were decreased after HSC administration, suggesting that HSC can significantly improve the level of inflammatory syndrome factor. The pharmacokinetics study showed that the time to peak concentration of HSC was 1 h. The concentration-effect curves showed a hysteresis loop. There was also a hysteresis between the peaked concentration and the maximum effect of HSC. The present study established in vivo pharmacokinetics-pharmacodynamics models and the results showed a great potential of HSC for treating ulcerative colitis.

Therapeutic effects of menstrual blood-derived endometrial stem cells on mouse models of streptozotocin-induced type 1 diabetes.

BACKGROUND: Type 1 diabetes (T1D), a chronic metabolic and autoimmune disease, seriously endangers human health. In recent years, mesenchymal stem cell (MSC) transplantation has become an effective treatment for diabetes. Menstrual blood-derived endometrial stem cells (MenSC), a novel MSC type derived from the decidual endometrium during menstruation, are expected to become promising seeding cells for diabetes treatment because of their noninvasive collection procedure, high proliferation rate and high immunomodulation capacity. AIM: To comprehensively compare the effects of MenSC and umbilical cord-derived MSC (UcMSC) transplantation on T1D treatment, to further explore the potential mechanism of MSC-based therapies in T1D, and to provide support for the clinical application of MSC in diabetes treatment. METHODS: A conventional streptozotocin-induced T1D mouse model was established, and the effects of MenSC and UcMSC transplantation on their blood glucose and serum insulin levels were detected. The morphological and functional changes in the pancreas, liver, kidney, and spleen were analyzed by routine histological and immunohistochemical examinations. Changes in the serum cytokine levels in the model mice were assessed by protein arrays. The expression of target proteins related to pancreatic regeneration and apoptosis was examined by western blot. RESULTS: MenSC and UcMSC transplantation significantly improved the blood glucose and serum insulin levels in T1D model mice. Immunofluorescence analysis revealed that the numbers of insulin+ and CD31+ cells in the pancreas were significantly increased in MSC-treated mice compared with control mice. Subsequent western blot analysis also showed that vascular endothelial growth factor (VEGF), Bcl2, Bcl-xL and Proliferating cell nuclear antigen in pancreatic tissue was significantly upregulated in MSC-treated mice compared with control mice. Additionally, protein arrays indicated that MenSC and UcMSC transplantation significantly downregulated the serum levels of interferon γ and tumor necrosis factor α and upregulated the serum levels of interleukin-6 and VEGF in the model mice. Additionally, histological and immunohistochemical analyses revealed that MSC transplantation systematically improved the morphologies and functions of the liver, kidney, and spleen in T1D model mice. CONCLUSION: MenSC transplantation significantly improves the symptoms in T1D model mice and exerts protective effects on their main organs. Moreover, MSC-mediated angiogenesis, antiapoptotic effects and immunomodulation likely contribute to the above improvements. Thus, MenSC are expected to become promising seeding cells for clinical diabetes treatment due to their advantages mentioned above.

Assembling of Perylene, Naphthalene, and Pyromellitic Diimide-Based Materials and Their Third-Order Nonlinear Optical Properties.

π-conjugated aromatic diimides with chemical stability, heat resistance, and redox activity have attracted more attention due to their excellent fluorescence quantum yield in solution. The planar perylene diimide (PDI) derivatives generally have aggregation-induced emission quenching in the solid state, while the cyclic trimers based on pyromellitic diimides (PMDIs), naphthalene diimides (NDIs), and PDIs can increase the fluorescence quantum yield in the solid state and have large two-photon absorption cross section, which can be used as excellent nonlinear optical (NLO) materials. Therefore, this paper will study the effects of multiple assembly modes of the three monomers on the NLO responses of materials. It was found that the assembly modes of 2PMDI-1NDI and 2NDI-1PDI exhibit larger third-order NLO response (γ) values, which was due to the larger conjugate surface of PDI effectively reducing the energy gap between the HOMO and LUMO. Compared with other assembly methods, 2PMDI-1NDI and 2NDI-1PDI were conducive to causing redshifts (150 nm) in the absorption spectrum. Therefore, the larger conjugate surface of PDI and the assembly mode of the isosceles triangle were more favorable for intramolecular charge transfer, thus improving its NLO properties.

Perinatal outcomes of singleton live births after preimplantation genetic testing during single frozen-thawed blastocyst transfer cycles: a propensity score-matched study.

OBJECTIVE: To determine whether singleton pregnancy achieved after preimplantation genetic testing (PGT) is associated with a higher risk of adverse perinatal outcomes than in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) singleton pregnancy. DESIGN: A retrospective cohort study. SETTING: A university-affiliated fertility center. PATIENT(S): This cohort study included singleton live births resulting from PGT (n = 232) and IVF/ICSI singleton pregnancies (n = 2,829) with single frozen-thawed blastocyst transfer. Multiple baseline covariates were used for propensity score matching, yielding 214 PGT singleton pregnancies matched to 617 IVF/ICSI singleton pregnancies. INTERVENTION(S): Trophectoderm biopsy. MAIN OUTCOME MEASURE(S): The primary outcome was gestational hypertension, and various clinical perinatal secondary outcomes related to maternal and neonatal health were measured. RESULT(S): Compared with IVF/ICSI singleton pregnancy, PGT singleton pregnancy was associated with a significantly higher risk of gestational hypertension (adjusted odds ratio, 2.58; 95% confidence interval, 1.32, 5.05). In the matched sample, the risk of gestational hypertension remained higher with PGT singleton pregnancy (odds ratio, 2.33; 95% confidence interval, 1.04, 5.22) than with IVF/ICSI singleton pregnancy. No statistical differences were noted in any other measured outcomes between the groups. CONCLUSION(S): The perinatal outcomes of PGT and IVF/ICSI singleton pregnancies were similar except for the observed potentially higher risk of gestational hypertension with PGT singleton pregnancy. However, because the data on PGT singleton pregnancies are limited, this conclusion warrants further investigation.