Recent progress in mesenchymal stem cell-based therapy for acute lung injury.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening diseases in critically ill patients. Although pathophysiology of ALI/ARDS has been investigated in many studies, effective therapeutic strategies are still limited. Mesenchymal stem cell (MSC)-based therapy is emerging as a promising therapeutic intervention for patients with ALI. During the last two decades, researchers have focused on the efficacy and mechanism of MSC application in ALI animal models. MSC derived from variant resources exhibited therapeutic effects in preclinical studies of ALI with different mechanisms. Based on this, clinical studies on MSC treatment in ALI/ARDS has been tried recently, especially in COVID-19 caused lung injury. Emerging clinical trials of MSCs in treating COVID-19-related conditions have been registered in past two years. The advantages and potential of MSCs in the defense against COVID-19-related ALI or ARDS have been confirmed. This review provides a brief overview of recent research progress in MSC-based therapies in preclinical study and clinical trials in ALI treatment, as well as the underlying mechanisms.

A repeat-dose toxicity study of human umbilical cord mesenchymal stem cells in NOG mice by intravenous injection.

BACKGROUND: Stem cell-based therapies have demonstrated great potential in several clinical trials. However, safety data on stem cell application remain inadequate. This study evaluated the toxicity of human umbilical cord mesenchymal stem cells (hUC-MSCs) in NOD/Shi-scid/IL-2 Rγnull (NOG) mice. RESEARCH DESIGN AND METHODS: Mice were administered hUC-MSCs intravenously at doses of 3.5 × 106 cells/kg and 3.5 × 107 cells/kg. Toxicity was assessed by clinical observation, behavioral evaluation, pathology, organ weight, and histopathology. We determined the distribution of hUC-MSCs using a validated qPCR method and colonization using immunohistochemistry. RESULTS: No significant abnormal effects on clinical responses, body weight, or food intake were observed in the mice, except for two in the high-dose group that died during the last administration. Mouse activity in the high-dose group decreased 6 h after the first administration. Terminal examination revealed dose-dependent changes in hematology. The mice in the high-dose group displayed pulmonary artery wall plaques and mild alveolar wall microthrombi. hUC-MSCs colonized primarily the lung tissues and were largely distributed there 24 h after the final administration. CONCLUSIONS: The no observed adverse effect level for intravenous administration of hUC-MSCs in NOG mice over a period of 3 w was 3.5 × 106 cells/kg.

Lipid metabolism reprogramming in head and neck cancer.

Lipid metabolism reprogramming is one of the most prominent metabolic anomalies in cancer, wherein cancer cells undergo dysregulation of lipid metabolism to acquire adequate energy, cell membrane building blocks, as well as signaling molecules essential for cell proliferation, survival, invasion, and metastasis. These adaptations enable cancer cells to effectively respond to challenges posed by the tumor microenvironment, leading to cancer therapy resistance and poor cancer prognosis. Head and neck cancer, ranking as the seventh most prevalent cancer, exhibits numerous abnormalities in lipid metabolism. Nevertheless, the precise role of lipid metabolic rewiring in head and neck cancer remains unclear. In line with the LIPID MAPS Lipid Classification System and cancer risk factors, the present review delves into the dysregulated molecules and pathways participating in the process of lipid uptake, biosynthesis, transportation, and catabolism. We also present an overview of the latest advancements in understanding alterations in lipid metabolism and how they intersect with the carcinogenesis, development, treatment, and prognosis of head and neck cancer. By shedding light on the significance of metabolic therapy, we aspire to improve the overall prognosis and treatment outcomes of head and neck cancer patients.

Repeat-dose toxicity study of human umbilical cord mesenchymal stem cells in cynomolgus monkeys by intravenous and subcutaneous injection.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) are proposed for the treatment of acute lung injury and atopic dermatitis. To advance hUC-MSC entry into clinical trials, the effects of hUC-MSCs on the general toxicity, immune perturbation and toxicokinetic study of hUC-MSCs in cynomolgus monkeys were assessed. hUC-MSCs were administered to cynomolgus monkeys by intravenous infusion of 3.0 × 106 or 3.0 × 107cells/kg or by subcutaneous injection of 3.0 × 107cells/kg twice a week for 3 weeks followed by withdrawal and observation for 6 weeks. Toxicity was assessed by clinical observation, clinical pathology, ophthalmology, immunotoxicology and histopathology. Moreover, toxicokinetic study was performed using a validated qPCR method after the first and last dose. After 3rd or 4th dosing, one or three the monkeys in the intravenous high-dose group exhibited transient coma, which was eliminated by slow-speed infusion after 5th or 6th dosing. In all dose groups, hUC-MSCs significantly increased NEUT levels and decreased LYMPH and CD3+ levels, which are related to the immunosuppressive effect of hUC-MSCs. Subcutaneous nodules and granulomatous foci were found at the site of administration in all monkeys in the subcutaneous injection group. Other than above abnormalities, no obvious systemic toxicity was observed in any group. The hUC-MSCs was detectable in blood only within 1 h after intravenous and subcutaneous administration. The present study declared the preliminary safety of hUC-MSCs, but close monitoring of hUC-MSCs for adverse effects, such as coma induced by intravenous infusion, is warranted in future clinical trials.

Umbilical cord mesenchymal stem cells relieve osteoarthritis in rats through immunoregulation and inhibition of chondrocyte apoptosis.

This study aims to investigate the effectiveness of umbilical cord mesenchymal stem cells (UCMSCs) in treating osteoarthritis (OA). Sprague-Dawley rats were used in in vivo experiments and divided into four groups: normal, OA model, saline, and UCMSC-treated groups (n = 6). An OA model was established by injecting iodoacetic acid into the joint cavity. The results indicate that UCMSC transplantation significantly reduced joint surface and articular cartilage damage, and the levels of IL-1ß, TNF-α, and MMP13 in the joint fluid were significantly reduced after UCMSC treatment. In vitro experiments showed that co-culturing UCMSCs and chondrocytes promoted the expression of aggrecan, COL2, SOX9, and BCL-2; downregulated the expression of BAX and BAD in chondrocytes; and promoted the expression of IL-10 and TGF-ß1 in UCMSCs. Additionally, the supernatant of UCMSCs inhibited the expression of IL-1ß and TNF-α in the articular cavity and promoted the expression of COL2 and aggrecan in vivo. These effects were impaired when IL-10 and TGF-ß1 were removed. Collectively, UCMSC transplantation appears to improve joint pathology, reduce inflammatory factors, and decrease chondrocyte apoptosis, likely through the involvement of IL-10 and TGF-ß1, thus providing a potential therapeutic option for patients with OA.

Investigating material basis and molecular mechanism of Qing Cuo formula in the treatment of acne based on animal experiments, UPLC-LTQ-Orbitrap-MS and network pharmacology.

CONTEXT: Qing Cuo Formula (QCF) is a traditional Chinese medicine for treating acne, but its active compounds and molecular mechanisms are unclear. OBJECTIVE: To investigate the material basis and molecular mechanism of QCF. MATERIALS AND METHODS: In vivo experiments were conducted on 60 male golden hamsters with damp-heat acne, with a blank group, a spironolactone group and 3 QCF administration groups (given high, medium and low doses) over a 30-day period. Serum androgen and inflammatory cytokine levels were tested by ELISA. In vitro, chemical compositions of QCF were investigated by UPLC-LTQ-Orbitrap-MS. Network pharmacology approaches were used to analyse the protein-protein interaction (PPI) network and QCF active compounds-intersection targets-acne network. GO enrichment and KEGG pathway analysis was conducted subsequently. RESULTS: Low-dose QCF group (11.4 g/kg/day) showed significantly reduced levels of serum T (4.94 ± 0.36; 5.51 ± 0.36 ng/mL), DHT (6.67 ± 0.61; 8.09 ± 0.59 nmol/L), E2 (209.01 ± 20.92; 237.08 ± 13.94 pg/mL), IL-1α (36.84 ± 3.23; 44.07 ± 4.00 pg/mL) and FFA (128.32 ± 10.94; 148.00 ± 12.12 µmol/L) compared to the blank group (p < 0.05). In vitro experiments identified 75 compounds in QCF decoction, with 27 active compounds absorbed in serum. Network pharmacology identified 6 active components connecting 17 targets. GO enrichment and KEGG pathway analysis indicated that QCF's anti-acne targets mainly regulate extracellular matrix function, inflammatory processes, immune response and endocrine function. CONCLUSIONS: This study provides evidence of the molecular mechanism and material basis of QCF in treating androgen-related damp-heat acne, paving the way for further research on its potential in treating other conditions related to damp-heat constitution.

Cancer risk following surgical removal of tonsils and adenoids - a population-based, sibling-controlled cohort study in Sweden.

BACKGROUND: Removal of tonsils and adenoids is among the most common surgical procedures worldwide. Evidence of increased risk of cancer following such surgery is, however, inconclusive. METHODS: We conducted a population-based, sibling-controlled cohort study of 4,953,583 individuals in Sweden with a follow-up during 1980-2016. History of tonsillectomy, adenotonsillectomy, and adenoidectomy was identified from the Swedish Patient Register whereas incident cases of cancer during follow-up were identified from the Swedish Cancer Register. We used Cox models to calculate hazard ratios (HR) with 95% confidence intervals (CI) of cancer in both a population and a sibling comparison. The sibling comparison was used to assess the potential impact of familial confounding, due to shared genetic or non-genetic factors within a family. RESULTS: We found a modestly increased risk for any cancer following tonsillectomy, adenoidectomy, or adenotonsillectomy in both the population (HR 1.10; 95%CI 1.07-1.12) and sibling (HR 1.15; 95%CI 1.10-1.20) comparisons. The association did not differ greatly by type of surgery, age at surgery, or potential indication for surgery, and persisted more than two decades after surgery. An excess risk was consistently observed for cancer of the breast, prostate, thyroid, and for lymphoma in both population and sibling comparisons. A positive association was observed for pancreatic cancer, kidney cancer, and leukemia in the population comparison whereas a positive association was observed for esophageal cancer in the sibling comparison. CONCLUSIONS: Surgical removal of tonsils and adenoids is associated with a modestly increased risk of cancer during the decades following the surgery. The association is unlikely attributed to confounding due to shared genetic or non-genetic factors with a family.

Novel Matrine Derivatives as Potential Larvicidal Agents against Aedes albopictus: Synthesis, Biological Evaluation, and Mechanistic Analysis.

A large number of studies have shown that matrine (MA) possesses various pharmacological activities and is one of the few natural, plant-derived pesticides with the highest prospects for promotion and application. Fifty-eight MA derivatives were prepared, including 10 intermediates and 48 target compounds in 3 series, to develop novel mosquitocidal agents. Compounds 4b, 4e, 4f, 4m, 4n, 6e, 6k, 6m, and 6o showed good larvicidal activity against Aedes albopictus, which is both a highly aggressive mosquito and an important viral vector that can transmit a wide range of pathogens. Dipping methods and a bottle bioassay were used for insecticidal activity evaluation. The LC50 values of 4e, 4m, and 6m reached 147.65, 140.08, and 205.79 µg/mL, respectively, whereas the LC50 value of MA was 659.34 µg/mL. Structure-activity relationship analysis demonstrated that larvicidal activity could be improved by the unsaturated heterocyclic groups introduced into the carboxyl group after opening the D ring. The MA derivatives with oxidized N-1 lost their mosquitocidal activities, indicating that the bareness of N-1 is crucial to maintain their anti-mosquito activity. However, the activity was not greatly influenced by introducing a cyan group at C-6 or a benzene sulfonyl group at N-16. Additionally, compounds 4e and 4m exhibited good inhibitory activities against acetylcholinesterase with inhibitory rates of 59.12% and 54.30%, respectively, at a concentration of 250 µg/mL, whereas the inhibitory rate of MA was 9.88%. Therefore, the structural modification and mosquitocidal activity of MA and its derivatives obtained here pave the way for those seeking strong mosquitocidal agents of plant origin.

Identification of adolescent patients with depression via assessment of the niacin skin flushing response.

BACKGROUND: Depressive disorder (DD) affects approximately 20 % of adolescents worldwide, but it is underdiagnosed due to the lack of objective biomarkers. Niacin skin flushing response (NSFR) is an objective and noninvasive biomarker of adult depression; however, its effectiveness has not been assessed in adolescents. METHODS: This study included 198 adolescents with 50 % healthy controls (HC). Linear mixed-effects model and multiple linear regression analyses were performed to assess differences in NSFR between the DD and HC groups. Logistic regression models based on NSFR were constructed, and the area under curve (AUC) was calculated to evaluate the performance of models. Spearman correlations were calculated to assess the relationships between NSFR and disease duration and hormone levels associated with puberty. RESULTS: Adolescents with DD displayed significantly attenuated and delayed NSFR compared to HC. NSFR effectively distinguished DD patients from HC with AUC values of 0.719 (sensitivity = 0.844) and 0.721 (sensitivity = 0.829) determined in the discovery and validation sets, respectively. Within the DD group, the maximum degree of NSFR was negatively correlated with the disease duration (r = -0.28, p = 0.011), and the overall degree of NSFR was positively associated with prolactin (r = 0.29, p = 0.039) and thyroxine (r = 0.29, p = 0.027) levels. LIMITATIONS: Future investigations will be necessary to confirm our results in an independent sample set. CONCLUSIONS: This study provides the first evidence of the utility of NSFR as an objective auxiliary diagnostic biomarker for adolescent depression. It provides new clues to understand the pathophysiology of the disease, and helps promote precise diagnosis, treatment, and prognostic evaluation of adolescent depression.

Rutaecarpin reduces lipids by DGKθ-dependent activation of PPARα.

OBJECTIVE: Lipid metabolic disorders pose a serious threat to human health, and currently no good treatments exist. In earlier studies by the authors, HepG2 cells with diacylglycerol kinase theta (DGKθ) knockout were found to cause significant lipid accumulation, suggesting that DGKθ may be a potential target for treating lipid metabolic disorders. METHODS: A high-throughput screening of natural products targeting the potential signaling pathway of lipid metabolism was carried out in the DGKθ-T2A-luciferase knock-in HepG2 cell. RNA-sequencing and bioinformatic approaches were used to analyze the potential pathway by which rutaecarpin decreases lipids. Western blot and quantitative polymerase chain reaction were performed to investigate the mechanisms of rutaecarpin's reduction in lipid levels. RESULTS: Rutaecarpin was found to significantly enhance DGKθ expression, and the potential mechanisms by which rutaecarpin accelerates lipid metabolism by targeting DGKθ was explored in vitro and in vivo. The results indicated that rutaecarpin could markedly reduce lipid accumulation in oleic acid-induced HepG2 cells and in high-fat diet-induced obese C57BL/6J mice by targeting the hepatocyte nuclear factor 1-beta (HNF1B)-DGKθ-peroxisome proliferator-activated receptor alpha (PPARα)-apolipoprotein C3 (APOC3) pathway. CONCLUSION: Rutaecarpin is effective in reducing lipid accumulation, and the development of a high-throughput screening platform based on a reporter knock-in cell line may facilitate the discovery of effective drugs for lipid metabolic disorders based on the DGKθ target.

RNA-Sequencing approach for exploring the therapeutic effect of umbilical cord mesenchymal stem/stromal cells on lipopolysaccharide-induced acute lung injury.

Acute lung injury (ALI) is significantly associated with morbidity and mortality in patients with critical diseases. In recent years, studies have identified that mesenchymal stem/stromal cells (MSCs) ameliorate ALI and pulmonary fibrosis. However, the mechanism underlying this outcome in ALI has not yet been investigated. In this study, RNA sequencing technology was used to analyze the gene expression profile of lung tissue in lipopolysaccharide (LPS)-induced ALI rats following treatment with human umbilical cord MSC (HUCMSC). Differential expression analyses, gene ontology annotation, Kyoto Encyclopedia of Genes and Genomes enrichment, protein-protein interaction network identification, and hub gene analysis were also performed. HUCMSC treatment decreased inflammatory factor production and alveolar exudates, and attenuated lung damage in LPS-induced ALI rats. The RNA-Seq data indicated that HUCMSC treatment activated the IL-17, JAK-STAT, NF-κB, and TNF-α signaling pathways, increased oxygen transport, and decreased extracellular matrix organization. HUCMSC exert beneficial effects on ALI via these signaling pathways by reducing inflammation, inhibiting pulmonary fibrosis, and improving lung ventilation. Moreover, our study further revealed the hub genes (Tbx2, Nkx2-1, and Atf5) and signaling pathways involved in HUCMSC treatment, thus providing novel perspectives for future research into the molecular mechanisms underlying cell treatment of ALI. HUCMSC can regulate multiple genes and signaling pathways, which can prevent LPS-induced lung damage in an ALI rat model.

Attenuated niacin skin flushing response in children and adolescents with mental disorders: A transdiagnostic early warning marker.

Mental disorders are the leading cause of disability in children and adolescents worldwide, but among the difficulties that pediatric mental health faces is a lack of objective biomarkers used for early identification or diagnosis. Studies to date indicate that niacin skin flushing response (NSFR) could be a biomarker for adult patients with schizophrenia and affective disorders. However, there are limited data on NSFR in pediatric patients with mental disorders. This study provides the first evidence of NSFR as a potential transdiagnostic marker in pediatric patients with schizophrenia (SZ), bipolar disorder (BD), depressive disorder (DD) and autism spectrum disorder (ASD). We conducted 10-min niacin skin flush tests on 227 pediatric participants, including 59 SZ patients, 23 BD patients, 57 DD patients, 40 ASD patients and 48 healthy controls (HCs). Group, time and the concentrations of aqueous methyl nicotinate had significant effects on the flush scores. Pediatric patients with BD, DD, and SZ clustered together, while ASD patients appeared to be more similar with HCs. SZ, BD and DD groups had lower flush scores than HCs, while ASD group had higher scores than BD and DD groups. These findings suggested NSFR was blunted in pediatric SZ, BD and DD and was distinct in ASD from the other disease groups. Our data demonstrate NSFR could be a transdiagnostic marker for pediatric SZ, BD and DD, which would help to identify a subgroup of patients sharing dysfunctions of membrane phospholipids. Besides, NSFR might have potential for early identification of affective disorders from ASD.

Integration Profiling Between Plasma Lipidomics, Epstein-Barr Virus and Clinical Phenomes in Nasopharyngeal Carcinoma Patients.

Plasma lipidomics has been commonly used for biomarker discovery. Studies in cancer have suggested a significant alteration of circulating metabolite profiles which is correlated with cancer characteristics and treatment outcome. However, the lipidomics characteristics of nasopharyngeal carcinoma (NPC) have rarely been studied. We previously described the phenomenon of lipid droplet accumulation in NPC cells and showed that such accumulation could be regulated by latent infection of Epstein-Barr virus (EBV). Here, we compared the plasma lipidome of NPC patients to that of healthy controls by liquid chromatography-tandem mass spectrometry (LC-MS/MS). We found 19 lipids (e.g., phosphatidylinositols 18:0/20:4 and 18:0/18:2 and free fatty acid 22:6) to be remarkably decreased, whereas 2 lipids (i.e., diacylglycerols 16:0/16:1 and 16:0/20:3) to be increased, in the plasma of NPC patients, compared with controls. Different lipid profiles were also observed between patients with different titers of EBV antibodies (e.g., EA-IgA and VCA-IgA) as well as between patients with and without lymph node or distant organ metastasis. In conclusion, plasma lipidomics might help to differentiate NPC cases from controls, whereas EBV infection might influence the risk and prognosis of NPC through modulating lipid metabolism in both tumor cells and peripheral blood.

Traditional Chinese Medicine Constitution Identification Based on Objective Facial and Tongue Features: A Delphi Study and a Diagnostic Nomogram for Blood Stasis Constitution.

Objective: The aim of this study was to systematically summarize and form an expert consensus on the theoretical experience of tongue and facial features for the identification of nine types of traditional Chinese medicine (TCM) constitution. Additionally, we sought to explore the feasibility of TCM constitution identification through objective tongue and facial features. Methods: We used Delphi method to investigate the opinions of experts on facial and tongue feature items for identifying TCM constitution. We developed and validated a diagnostic nomogram for blood stasis constitution (BSC) based on objective facial and tongue features to demonstrate the reliability of expert consultation. Results: Eleven experts participated in two rounds of expert consultation. The recovery rates of the two rounds of expert consultation were 100.0% and 90.9%. After the first round, 39 items were screened out from 147 initial items, and 2 items were supplemented by experts. In the second round, 7 items were eliminated, leaving 34 items for 8 types of TCM constitution. The coefficient of variation in the first round was 0.11-0.49 for the 147 items and 0.11-0.29 for the included items. The coefficient of variation in the second round was 0.10-0.27 for the 41 items and 0.10-0.20 for the included items. The W value was 0.548 (P < 0.001) in the first round and 0.240 (P < 0.001) in the second round. Based on expert consultation, we selected BSC as an example and developed and validated a diagnostic nomogram consisting of six indicators: sex, hair volume, lip color-dark purple, susceptibility-facial pigmentation/chloasma/ecchymosis, zygomatic texture-red blood streaks, and sublingual vein-varicose and dark purple. The nomogram showed good discrimination (AUC: 0.917 [95% confidence interval [CI], 0.877-0.956] for the primary dataset, 0.902 [95% CI, 0.828-0.976] for the validation dataset) and good calibration. Decision curve analysis demonstrated that the nomogram was clinically useful. Conclusion: This is the first study to systematically summarize the existing knowledge and clinical experience to form an expert consensus on the tongue and facial features of nine types of TCM constitution. Our results will provide important prior knowledge and expert experience for future constitution identification research. Based on expert consultation, this study presents a nomogram for BSC that incorporates objective facial and tongue features, which can be conveniently used to facilitate the individualized identification of BSC.

Novel 18ß-glycyrrhetinic acid derivatives as a Two-in-One agent with potent antimicrobial and anti-inflammatory activity.

18ß-glycyrrhetinic acid (GA) is a well-known natural compound of oleanane-type triterpene and is found possessing antimicrobial and anti-inflammatory properties. Nonetheless, its relatively low bioactivity restricts its potential in pharmaceutical applications. To maximize the potential use of this natural herbal compound as antimicrobial and anti-inflammatory agents, the rational modification of GA to enhance its pharmacological activity with low toxicity and to understand the mechanism of action is critically essential. We reported herein the design and synthesis of a series of new GA derivatives. The antimicrobial activities of these new compounds were evaluated by inhibition zone test and minimum inhibitory concentration (MIC) assay. In addition, the anti-inflammatory activity was evaluated by LPS induced BV2 cells inflammation model and 12-O-tetradecanoyl phorbol-13-acetate (TPA) induced ear inflammation mice model. It was found that the derivatives functionalized with a di-substituted phenyl group at the 2-position of GA generally displayed high antimicrobial activity against Gram-positive bacteria (MIC down to 2.5 µM) and potent anti-inflammatory effects (inhibition of NO production up to 55%, comparable to dexamethasone). The in vitro and in vivo results also showed that GA-O-02 and GA-O-06 exert their anti-inflammatory activities through downregulation of NO, pro-inflammatory cytokines and chemokines (IL-1ß, IL-6, IL-12, TNF-α, MCP-1 and MIP-1α) and upregulation of anti-inflammatory cytokines (IL-10). The anti-inflammatory mechanism may involve the inhibition of NF-κB, MAPKs and PI3K/Akt related inflammatory signaling pathways and activation of Nrf2/HO-1 signaling pathway. The results demonstrated that GA-O-02 and GA-O-06 possess great application potential as potent antimicrobial and anti-inflammatory agents.

Tranexamic acid usage in hip fracture surgery: a meta-analysis and meta-regression analysis of current practice.

INTRODUCTION: The use of tranexamic acid (TXA) in hip fracture surgery remains inconclusive. The aim of the present meta-analysis was to assess the role of TXA use in hip fracture surgery, and attempt to disclose possible factors which might influence TXA efficacy and safety. MATERIALS AND METHODS: A systematic computerized literature search was conducted to retrieve all randomized controlled trials (RCTs) and cohort studies regarding TXA use in hip fracture surgery. Overall efficacy and safety were evaluated. Then, subgroup and meta-regression analyses were conducted to disclose the influence of geographic area, fracture type, administration route, frequency and dosage of TXA, blood transfusion threshold, and follow-up duration on the overall effect. RESULTS: Thirty-four RCTs and 11 cohort studies were included. Patients receiving TXA had a significant decrease in the need for blood transfusion, reduced total, intra-operative and post-operative blood loss, a decrease in pre- and postoperative hemoglobin difference, without increasing thromboembolic events risk. Subgroup analysis showed that topical TXA had a lower transfusion rate compared with controls, yet the result did not reach statistical significance. Also, TXA had similar efficacy and safety profiles in patients with different frequency and dosage of TXA. CONCLUSION: Current evidence indicated that intravenous administration of TXA could significantly reduce blood transfusion and blood loss without increasing risk of thromboembolic events. The frequency and dosage of TXA might not alter the beneficial effect. The application of topical TXA should be cautious.

The relationship of CCL4, BCL2A1, and NFKBIA genes with premature aging in women of Yin deficiency constitution.

BACKGROUND: Traditional Chinese Medicine (TCM) defined constitution as a health statue or physical fitness that determines individual susceptibility to diseases. Yin deficiency constitution (YinDC) is a type of constitution closely related to aging. Previous studies found that the characteristic genes of YinDC are part of the inflammatory aging signaling pathways (e.g., NF-kappa B). Therefore, the aim of the study was to further reveal the dysregulation of genes associated with inflammatory aging in YinDC women. METHODS: This study adopted the industrial standard of constitutional judgment, and screened YinDC (n = 30) and Balanced constitution (BC) (n = 30) from women between the ages of 35 to 49, a range categorized as the degenerating period by TCM. Five genes CCL4, BCL2A1, NFKBIA, TAK1, and IL-8 were analyzed by qRT-PCR. RESULTS: Logistical regression revealed the correlation between body constitution and the expression of the five genes: the expression of NFKBIA and CCL4 mRNA was significantly up-regulated, whereas the expression of BCL2A1 mRNA was significantly down-regulated in YinDC (P < 0.05). Age or weight, when included in the model, did not affected the correlations. CONCLUSION: Increased mRNA expression of CCL4 and NFKBIA and decreased mRNA expression of BCL2A1 may be the molecular basis of premature aging of YinDC women. These results provide a mechanistic basis for early conditioning of YinDC, anti-aging, and the prevention of aging-related diseases.

Synthesis and biological evaluation of pentacyclic triterpenoid derivatives as potential novel antibacterial agents.

A series of ursolic acid (UA), oleanolic acid (OA) and 18ß-glycyrrhetinic acid (GA) derivatives were synthesized by introducing a range of substituted aromatic side-chains at the C-2 position after the hydroxyl group at C-3 position was oxidized. Their antibacterial activities were evaluated in vitro against a panel of four Staphylococcus spp. The results revealed that the introduction of aromatic side-chains at the C-2 position of GA led to the discovery of potent triterpenoid derivatives for inhibition of both drug sensitive and resistant S. aureus, while the other two series derivatives of UA and OA showed no significant antibacterial activity even at high concentrations. In particular, GA derivative 33 showed good potency against all four Staphylococcus spp. (MIC = 1.25-5 µmol/L) with acceptable pharmacokinetics properties and low cytotoxicity in vitro. Molecular docking was also performed using S. aureus DNA gyrase to rationalize the observed antibacterial activity. This series of GA derivatives has strong potential for the development of a new type of triterpenoid antibacterial agent.

Biochar addition affects root morphology and nitrogen uptake capacity in common reed (Phragmites australis).

Nitrogen (N) is a key factor that limits plant growth in most terrestrial ecosystems, and biochar reportedly improves soil characteristics and grain yields. However, the effects of biochar on plant N uptake in wetland ecosystems and the underlying mechanisms of these effects remain unclear. Therefore, our study sought to characterise the effects of biochar addition on Phragmites australis N absorption rates at two different N deposition conditions [30 and 60 kg N hm-2 yr-1; i.e., "low" and "high" N treatments, respectively]. Our results demonstrated that biochar significantly promoted root biomass growth in P. australis in the high N treatment group. In contrast, the low N treatment group exhibited an increased proportion of fine roots and a decrease in the average P. australis root diameter. The N absorption rate of P. australis in the low N treatment group significantly increased with biochar addition and ammonium N became the preferred N source. The absorption rates of both ammonium and nitrate N were negatively correlated with the average P. australis root diameter. Therefore, our findings indicate that biochar may affect the N uptake strategy of P. australis by altering root morphogenesis, thereby providing new insights into potential restoration strategies for wetland vegetation.

Biochar-compost addition benefits Phragmites australis growth and soil property in coastal wetlands.

Salinity stress is common for plants growing in coastal wetlands. The addition of biochar in the soil may alleviate the negative effect of salinity through its unique physicochemical properties. To test this, we conducted a greenhouse experiment where the cosmopolitan wetland plant Phragmites australis was subjected to four salinity treatments (0, 5, 10 and 15‰) and three biochar treatments (no biochar addition, with biochar addition and with biochar-compost addition, both biochar and compost were made from P. australis) in a factorial design. Both biochar addition and biochar-compost addition to the substrate enhanced belowground mass of P. australis, application of biochar-compost significantly increased total mass by 35.5% and net photosynthesis rate of P. australis by 51.4%. Both biochar addition and biochar-compost addition significantly increased soil organic carbon content by 62.9% and 31.7%, respectively, but decreased soil ammonium nitrogen content. In the saline soil, application of the mixture of biochar-compost had a strong, and positive effect on the growth of P. australis, compared to biochar alone. Therefore, incorporation of biochar and compost might be an appropriate approach to improve the productivity of P. australis growing in coastal wetlands, where soil salinity is a common environmental stress.