Bidirectional effects of the tryptophan metabolite indole-3-acetaldehyde on colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) has a high incidence and mortality. Recent studies have shown that indole derivatives involved in gut microbiota metabolism can impact the tumorigenesis, progression, and metastasis of CRC. AIM: To investigate the effect of indole-3-acetaldehyde (IAAD) on CRC. METHODS: The effect of IAAD was evaluated in a syngeneic mouse model of CRC and CRC cell lines (HCT116 and DLD-1). Cell proliferation was assessed by Ki-67 fluorescence staining and cytotoxicity tests. Cell apoptosis was analysed by flow cytometry after staining with Annexin V-fluorescein isothiocyanate and propidium iodide. Invasiveness was investigated using the transwell assay. Western blotting and real-time fluorescence quantitative polymerase chain reaction were performed to evaluate the expression of epithelial-mesenchymal transition related genes and aryl hydrocarbon receptor (AhR) downstream genes. The PharmMapper, SEA, and SWISS databases were used to screen for potential target proteins of IAAD, and the core proteins were identified through the String database. RESULTS: IAAD reduced tumorigenesis in a syngeneic mouse model. In CRC cell lines HCT116 and DLD1, IAAD exhibited cytotoxicity starting at 24 h of treatment, while it reduced Ki67 expression in the nucleus. The results of flow cytometry showed that IAAD induced apoptosis in HCT116 cells but had no effect on DLD1 cells, which may be related to the activation of AhR. IAAD can also increase the invasiveness and epithelial-mesenchymal transition of HCT116 and DLD1 cells. At low concentrations (< 12.5 µmol/L), IAAD only exhibited cytotoxic effects without promoting cell invasion. In addition, predictions based on online databases, protein-protein interaction analysis, and molecular docking showed that IAAD can bind to matrix metalloproteinase-9 (MMP9), angiotensin converting enzyme (ACE), poly(ADP-ribose) polymerase-1 (PARP1), matrix metalloproteinase-2 (MMP2), and myeloperoxidase (MPO). CONCLUSION: Indole-3-aldehyde can induce cell apoptosis and inhibit cell proliferation to prevent the occurrence of CRC; however, at high concentrations (≥ 25 µmol/L), it can also promote epithelial-mesenchymal transition and invasion in CRC cells. IAAD activates AhR and directly binds MMP9, ACE, PARP1, MMP2, and MPO, which partly reveals why it has a bidirectional effect.

Microplastic-mediated new mechanism of liver damage: From the perspective of the gut-liver axis.

Microplastics (MPs) are environmental contaminants that are present in all environments and can enter the human body, accumulate in various organs, and cause harm through the ingestion of food, inhalation, and dermal contact. The connection between bowel and liver disease and the interplay between gut, liver, and flora has been conceptualized as the "gut-liver axis". Microplastics can alter the structure of microbial communities in the gut and the liver can also be a target for microplastic invasion. Numerous studies have found that when MPs impair human health, they not only promote dysbiosis of the gut microbiota and disruption of the gut barrier but also cause liver damage. For this reason, the gut-liver axis provides a new perspective in understanding this toxic response. The cross-talk between MPs and the gut-liver axis has attracted the attention of the scientific community, but knowledge about whether MPs cause gut-liver interactions through the gut-liver axis is still very limited, and the effect of MPs on liver injury is not well understood. MPs can directly induce microbiota disorders and gut barrier dysfunction. As a result, harmful bacteria and metabolites in the gut enter the blood through the weak intestinal barrier (portal vein channel along the gut-liver axis) and reach the liver, causing liver damage (inflammatory damage, metabolic disorders, oxidative stress, etc.). This review provides an integrated perspective of the gut-liver axis to help conceptualize the mechanisms by which MP exposure induces gut microbiota dysbiosis and hepatic injury and highlights the connection between MPs and the gut-liver axis. Therefore, from the perspective of the gut-liver axis, targeting intestinal flora is an important way to eliminate microplastic liver damage.

Chemo-photothermal nanoplatform with diselenide as the key for ferroptosis in colorectal cancer.

Colorectal cancer (CRC) is a prevalent clinical malignancy of the gastrointestinal system, and its clinical drug resistance is the leading cause of poor prognosis. Mechanistically, CRC cells possess a specific oxidative stress defense mechanism composed of a significant number of endogenous antioxidants, such as glutathione, to combat the damage produced by drug-induced excessive reactive oxygen species (ROS). We report on a new anti-CRC nanoplatform, a multifunctional chemo-photothermal nanoplatform based on Camptothecin (CPT) and IR820, an indocyanine dye. The implementation of a GSH-triggered ferroptosis-integrated tumor chemo-photothermal nanoplatform successfully addressed the poor targeting ability of CPT and IR820 while exhibiting significant growth inhibitory effects on CRC cells. Mechanistically, to offset the oxidative stress created by the broken SeSe bonds, endogenous GSH was continuously depleted, which inactivated GPX4 to accumulate lipid peroxides and induce ferroptosis. Concurrently, exogenously administered linoleic acid was oxidized under photothermal conditions, resulting in an increase in LPO accumulation. With the breakdown of the oxidative stress defense system, chemotherapeutic efficacy could be effectively enhanced. In combination with photoacoustic imaging, the nanoplatform could eradicate solid tumors by means of ferroptosis-sensitized chemotherapy. This study indicates that chemotherapy involving a ferroptosis mechanism is a viable method for the treatment of CRC.

Function of macrophage-derived exosomes in chronic liver disease: From pathogenesis to treatment.

Chronic liver disease (CLD) imposes a heavy burden on millions of people worldwide. Despite substantial research on the pathogenesis of CLD disorders, no optimal treatment is currently available for some diseases, such as liver cancer. Exosomes, which are extracellular vesicles, are composed of various cellular components. Exosomes have unique functions in maintaining cellular homeostasis and regulating cell communication, which are associated with the occurrence of disease. Furthermore, they have application potential in diagnosis and treatment by carrying diverse curative payloads. Hepatic macrophages, which are key innate immune cells, show extraordinary heterogeneity and polarization. Hence, macrophage-derived exosomes may play a pivotal role in the initiation and progression of various liver diseases. This review focuses on the effects of macrophage-derived exosomes on liver disease etiology and their therapeutic potential, which will provide new insights into alleviating the global pressure of CLD.

Eight Zhes Decoction ameliorates the lipid dysfunction of nonalcoholic fatty liver disease using integrated lipidomics, network pharmacology and pharmacokinetics.

Nonalcoholic fatty liver disease (NAFLD) has developed into the most common chronic liver disease and can lead to liver cancer. Our laboratory previously developed a novel prescription for NAFLD, "Eight Zhes Decoction" (EZD), which has shown good curative effects in clinical practice. However, the pharmacodynamic material basis and mechanism have not yet been revealed. A strategy integrating lipidomics, network pharmacology and pharmacokinetics was used to reveal the active components and mechanisms of EZD against NAFLD. The histopathological results showed that EZD attenuated the degrees of collagen deposition and steatosis in the livers of nonalcoholic steatofibrosis model mice. Furthermore, glycerophospholipid metabolism, arachidonic acid metabolism, glycerolipid metabolism and linoleic acid metabolism with phospholipase A2 group IVA (PLA2G4A) and cytochrome P450 as the core targets and 12,13-cis-epoxyoctadecenoic acid, 12(S)-hydroxyeicosatetraenoic acid, leukotriene B4, prostaglandin E2, phosphatidylcholines (PCs) and triacylglycerols (TGs) as the main lipids were found to be involved in the treatment of NAFLD by EZD. Importantly, naringenin, artemetin, canadine, and bicuculline were identified as the active ingredients of EZD against NAFLD; in particular, naringenin reduces PC consumption by inhibiting the expression of PLA2G4A and thus promotes sufficient synthesis of very-low-density lipoprotein to transport excess TGs in the liver. This research provides valuable data and theoretical support for the application of EZD against NAFLD.

Analysis of the correlation between BMI and respiratory tract microbiota in acute exacerbation of COPD.

Objective: To investigate the distribution differences in the respiratory tract microbiota of AECOPD patients in different BMI groups and explore its guiding value for treatment. Methods: Sputum samples of thirty-eight AECOPD patients were collected. The patients were divided into low, normal and high BMI group. The sputum microbiota was sequenced by 16S rRNA detection technology, and the distribution of sputum microbiota was compared. Rarefaction curve, α-diversity, principal coordinate analysis (PCoA) and measurement of sputum microbiota abundance in each group were performed and analyzed by bioinformatics methods. Results: 1. The rarefaction curve in each BMI group reached a plateau. No significant differences were observed in the OTU total number or α-diversity index of microbiota in each group. PCoA showed significant differences in the distance matrix of sputum microbiota between the three groups, which was calculated by the Binary Jaccard and the Bray Curtis algorithm. 2. At the phylum level, most of the microbiota were Proteobacteria, Bacteroidetes Firmicutes, Actinobacteria, and Fusobacteria. At the genus level, most were Streptococcus, Prevotella, Haemophilus, Neisseria and Bacteroides. 3. At the phylum level, the abundance of Proteobacteria in the low group was significantly higher than that in normal and high BMI groups, the abundances of Firmicutes in the low and normal groups were significantly lower than that in high BMI groups. At the genus level, the abundance of Haemophilus in the low group was significantly higher than that in high BMI group, and the abundances of Streptococcus in the low and normal BMI groups were significantly lower than that in the high BMI group. Conclusions: 1. The sputum microbiota of AECOPD patients in different BMI groups covered almost all microbiota, and BMI had no significant association with total number of respiratory tract microbiota or α-diversity in AECOPD patients. However, there was a significant difference in the PCoA between different BMI groups. 2. The microbiota structure of AECOPD patients differed in different BMI groups. Gram-negative bacteria (G-) in the respiratory tract of patients predominated in the low BMI group, while gram-positive bacteria (G+) predominated in the high BMI group.

LPS-induced macrophage exosomes promote the activation of hepatic stellate cells and the intervention study of total astragalus saponins combined with glycyrrhizic acid.

Huangqi decoction, also known as Huangqi Liuyi decoction, was first recorded in the prescriptions of the Bureau of Taiping People's Welfare Pharmacy. It comprises astragalus and licorice, which is a commonly used prescription in traditional Chinese medicine for the clinical treatment of chronic liver disease, especially liver cirrhosis. Total astragalus saponins (AST) is the main component of astragalus, and glycyrrhizic acid (GA) is the main component of licorice. In this study, normal macrophage exosomes were extracted, and the exosomes incubated with lipopolysaccharides (LPS) and those incubated with LPS + AST + GA were co-cultured with JS1 cells (hepatic stellate cell line). The survival rate and the activation of key signaling pathways of JS1 cells in each group were detected and compared. We found that the co-culture of LPS-induced macrophage exosomes with JS1 cells could significantly increase the expression levels of Collagen-1 (Col-1) and Alpha smooth muscle actin (α-SMA)in JS1 cells. However, a significant reversal effect was observed after pretreatment with AST combined with GA. Further evaluation found that the expression levels of phospho (p)-Smad2 and p-Smad3 in the JS1 cells were significantly increased after macrophages were induced with LPS, whereas pretreatment with AST + GA could significantly decrease the expression levels of p-Smad2 and p-Smad3. Preliminary results of this study indicated that LPS-induced macrophage exosomes can promote the activation of hepatic stellate cells, and the pretreatment of AST combined with GA can exert a significant intervention effect. In this study, the new mechanism of anti-hepatic fibrosis effect of traditional Chinese medicine components of Huangqi Decoction was analyzed from the perspective of exosomes.

Associations between Dietary Antioxidant Vitamin Intake and the Changes in Bone Mass in Chinese Adolescents: A 2.5-Year Longitudinal Study.

(1) Background: Optimal bone mass accumulation during adolescence is crucial for maximising peak bone mass during adulthood. Dietary antioxidant vitamins may contribute to bone mass accumulation. This 2.5-year-long longitudinal study aimed to evaluate the relationships between dietary vitamin A, C, and E intakes and the annual changes in bone parameters among Chinese adolescents. (2) Method: Subjects aged 10-18 years (n = 1418) were recruited from a secondary school in Jiangmen, China. Dietary vitamin A, C, and E intakes were assessed using 24 h dietary records over 3 consecutive days. The Sahara Clinical Bone Sonometer was used to measure the broadband ultrasound attenuation (BUA) and the speed of sound (SOS). Their annual changes were then calculated (i.e., BUA%/year, SOS%/year). The associations were detected after adjusting for the baseline bone phenotype; age; sex; weight; height; pubertal stage; physical activity; and dietary intakes of vitamin D, calcium and energy. (3) Results: A curvilinear relationship was found between the dietary intake of vitamin C and BUA%/year (p = 0.026); further analyses in the subgroups revealed that this relationship was observed in male adolescents (p = 0.012). A positive association was observed only in boys with a dietary vitamin C intake of ≥159.01 mg/day (ß = 0.395, p = 0.036). Moreover, a linear positive association was shown between the dietary intake of vitamin E and BUA%/year in female adolescents (ß = 0.082, p = 0.033). (4) Conclusion: Our findings indicated that dietary vitamin C intake has a threshold effect on bone mass gain in male adolescents and that dietary vitamin E intake could be a positive predictor of bone mass gain in female adolescents.

Nanotechnology-Based siRNA Delivery Systems to Overcome Tumor Immune Evasion in Cancer Immunotherapy.

Immune evasion is a common reason causing the failure of anticancer immune therapy. Small interfering RNA (siRNA), which can activate the innate and adaptive immune system responses by silencing immune-relevant genes, have been demonstrated to be a powerful tool for preventing or reversing immune evasion. However, siRNAs show poor stability in biological fluids and cannot efficiently cross cell membranes. Nanotechnology has shown great potential for intracellular siRNA delivery in recent years. Nano-immunotherapy can efficiently penetrate the tumor microenvironment (TME) and deliver multiple immunomodulatory agents simultaneously, which appears to be a promising method for combination therapy. Therefore, it provides a new perspective for siRNA delivery in immunomodulation and cancer immunotherapy. The current advances and challenges in nanotechnology-based siRNA delivery strategies for overcoming immune evasion will be discussed in this review. In addition, we also offer insights into therapeutic options, which may expand its applications in clinical cancer treatment.

One-year follow-up study after patients with severe COVID-19 received human umbilical cord mesenchymal stem cells treatment.

BACKGROUND: The novel coronavirus is still mutating, and the pandemic continues. Meanwhile, many COVID-19 survivors have residual postinfection clinical manifestations. Human umbilical cord mesenchymal stem cells (hUC-MSCs) have been shown to be effective in the early stages of COVID-19. OBJECTIVES: The aim of this study was to investigate long-term safety and efficacy of treatment in patients with severe COVID-19 patients who had received hUC-MSCs therapy. METHODS: Twenty-five discharged patients who had severe COVID-19 (including the standard treatment group and the standard treatment plus hUC-MSCs group) were enrolled in a 1-year follow-up. The assessment considered adverse effects (including effects on liver and kidney function, coagulation, ECG, tumor marker, and so on), pulmonary function, St George's Respiratory Questionnaire (SGRQ), postinfection sequelae and serum concentration of Krebs von den Lungen-6 (KL-6), malondialdehyde (MDA), H2S, carnitine, and N-6 long-chain polyunsaturated fatty acids (N-6 LC-PUFAs). MEASUREMENTS AND MAIN RESULTS: Pulmonary ventilation function had significantly improved at the 1-year follow-up in both the hUC-MSCs group and the control group compared with the 3-month follow-up (P < 0.01). Fatigue (60% [15/25]) remained the most common symptom at the 1-year follow-up. The rate of fatigue relief was significantly reduced in the hUC-MSCs group (25% [2/8]) compared to the control group (76.5% [13/17]) (P = 0.028). The level of KL-6 was significantly lower in the hUC-MSCs group (2585.5 ± 186.5 U/ml) than in the control group (3120.7 ± 158.3 U/ml) (P < 0.001). Compared with the control group, the hUC-MSCs group had a lower level of MDA (9.27 ± 0.54 vs. 9.91 ± 0.72 nmol/ml, P = 0.036). No obvious adverse effects were observed in the hUC-MSCs treatment group at 1 year after discharge. CONCLUSIONS: Intravenous transplantation of hUC-MSCs was a safe approach in the long term in the treatment of patients with severe COVID-19. In addition, hUC-MSCs had a positive effect on postinfection sequelae in COVID-19 survivors. TRIAL REGISTRATION: Chinese Clinical Trial Registration; ChiCTR2000031494; Registered 02 April 2020-Retrospectively registered, http://www.medresman.org.

Relationships of sex hormones with muscle mass and muscle strength in male adolescents at different stages of puberty.

This study analysed the associations of sex steroids with fat-free mass (FFM) and handgrip strength in 641 Chinese boys. Serum total testosterone (TT) and oestradiol were measured by chemiluminescence immunoassay. Free testosterone (FT) and oestradiol were calculated. FFM and handgrip strength were measured by bioelectrical impedance analysis and a hand dynamometer, respectively. Generalised additive models and multiple linear regression were used to explore the relationships. A subgroup analysis was conducted in early-mid pubertal and late-post pubertal groups. Age, height, weight, physical activity, intake of dietary protein and/or stage of puberty were adjusted. TT and FT were positively related to FFM and handgrip strength, with a curvilinear relationship being detected for handgrip strength (p<0.050). This curvilinear relationship was only observed in the late-post pubertal group, suggesting a potential threshold effect (FT>11.99ng/dL, ß = 1.275, p = 0.039). In the early-mid pubertal group, TT and/or FT were linearly or near-linearly related to FFM or handgrip strength (ß = 0.003-0.271, p<0.050). The association between FT and FFM was stronger than that in the late-post pubertal group. This study found that serum T had different associations with muscle parameters in Chinese early-mid pubertal and late-post pubertal boys. In the late-post pubertal boys, serum T was curvilinearly related to muscle strength with a threshold effect and its link with muscle mass was weaker.

Association between Body Composition and Bone Mineral Density in Children and Adolescents: A Systematic Review and Meta-Analysis.

BACKGROUND: Bone mass acquisition during growth is a major determinant of the risk of developing osteoporosis later in life. Body composition is an anthropometric determinant of bone mineral density (BMD) and significantly influences its development during childhood and adolescence. OBJECTIVE: This study aimed to systematically examine the association between body composition and bone mineral density in children and adolescents. METHODS: Observational studies addressing this association were identified from PubMed (MEDLINE), Embase, Scopus and the Cochrane Library (up to January 2021). The study populations consisted of healthy children and adolescents. The DerSimonian and Laird method was used to compute pooled estimates of effect size and the respective 95% confidence intervals for upper limbs, femoral neck (FN), lumbar spine (LS) and total body, respectively. Subgroup analyses were further performed based on age, sex and ethnicity. RESULTS: Thirty-one published studies were eligible for inclusion in this systematic review and meta-analysis, including three longitudinal studies. The combined population from all the studies amounted to 21,393 (11,205 males and 10,188 females). The pooled estimates of the correlation coefficients for lean mass (LM) and BMD ranged from 0.53 to 0.74 (p < 0.050), and the pooled regression coefficients ranged from 0.23 to 0.79 for FN, LS and total body (p < 0.050). For fat mass (FM), the pooled correlation coefficients ranged from 0.10 to 0.50 (p < 0.050) and the pooled regression coefficient was only significant for FN BMD with a weak strength (pooled ß = 0.07, p < 0.050). The pooled regression coefficients for body fat percentage (BF%) were between -0.54 and -0.04 (p < 0.050). The subgroup analysis revealed a stronger association in Asians than in Caucasians for LM and in males compared to females for BF% (p < 0.050). CONCLUSIONS: This systematic review and meta-analysis supports a positive association between LM and BMD. BF% appears to have a deleterious effect on bone acquisition in children and adolescents.

Analysis of the Association between Fat Mass Distribution and Bone Mass in Chinese Male Adolescents at Different Stages of Puberty.

BACKGROUND: Bone mineral acquisition during adolescence is crucial for maximizing peak bone mass. Fat mass (FM) and bone mass are closely related. This study investigated the association of FM distribution with bone mass in Chinese male adolescents. METHOD: A total of 693 male adolescents aged 10-18 years were recruited from a secondary school in Jiangmen, China. Their bone mass and body composition were measured by quantitative ultrasound and bioelectrical impedance analysis, respectively. The associations of the measures of fat distribution with bone parameters, i.e., broadband ultrasound attenuation, speed of sound (SOS), and stiffness index (SI), were analyzed using multiple linear regression. Age, height, body mass index, stage of puberty, physical activity, sedentary behavior, dietary energy intake, and dietary calcium and vitamin D intake were adjusted in the model. Further subgroup analyses of prepubertal and pubertal participants were conducted. RESULTS: The measures of fat distribution showed negative associations with SOS and SI in total subjects (p < 0.010). In prepubertal boys, the measures of fat distribution were only associated with SOS (ß = -0.377 to -0.393, p < 0.050). In pubertal boys, the measures of fat distribution had associations with all bone parameters (ß = -0.205 to -0.584, p < 0.050). The strongest association was between trunk FM and SOS (ß = -0.584, p < 0.001). CONCLUSION: This study supported that the measures of fat distribution were negatively associated with bone parameters in Chinese male adolescents. Trunk FM had the strongest association with bone parameter. These associations appear to be stronger in pubertal boys than in prepubertal boys.

Human Umbilical Cord Mesenchymal Stromal Cell Treatment of Severe COVID-19 Patients: A 3-Month Follow-Up Study Following Hospital Discharge.

Previously, we demonstrated the therapeutic effects of human umbilical cord mesenchymal stromal cells (hUC-MSCs) in severe coronavirus disease 2019 (COVID-19) patients. In this 3-month follow-up study, we examined discharged patients who had received hUC-MSC therapy to assess the safety of this therapy and the health-related quality of life (HRQL) of these patients. The follow-up cohort consisted of 28 discharged severe COVID-19 patients who received either the standard treatment (the control group) or the standard treatment plus hUC-MSC therapy. We examined liver function, kidney function, pulmonary function, coagulation, tumor markers, and vision. We also conducted electrocardiography (ECG) analysis, let the patients answer the St. George's Respiratory Questionnaire (SGRQ), and performed computed tomography (CT) imaging for assessing the lung changes. No obvious adverse effects were observed in the hUC-MSC group after 3 months. Measurements of blood routine index, C-reactive protein and procalcitonin, liver and kidney function, coagulation, ECG, tumor markers, and vision were almost within the normal ranges in both the treatment and control groups. Forced expiratory volumes in 1 s (FEV1) (% of predicted) were 71.88% ± 8.46% and 59.45% ± 27.45% in the hUC-MSC and control groups (P < 0.01), respectively, and FEV1/forced vital capacity (FEV1/FVC) ratios were 79.95% ± 8.00% and 58.97% ± 19.16% in the hUC-MSC and control groups, respectively (P < 0.05). SGRQ scores were lower in the hUC-MSC group than in the control group (15.25 ± 3.69 vs. 31.9 ± 8.78, P < 0.05). The rate of wheezing in the hUC-MSC group was also significantly lower than that in the control group (37.5% vs. 75%, P < 0.05). There were no significant differences in CT scores between the two groups (0.60 ± 0.88 vs. 1.00 ± 1.31, P = 0.917). Overall, the intravenous transplantation of hUC-MSCs accelerated partial pulmonary function recovery and improved HRQL, indicating relative safety and preliminary efficacy of this treatment for patients with severe COVID-19.

A Multiepitope Peptide, rOmp22, Encapsulated in Chitosan-PLGA Nanoparticles as a Candidate Vaccine Against Acinetobacter baumannii Infection.

BACKGROUND: The development of vaccines is a promising and cost-effective strategy to prevent emerging multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections. The purpose of this study was to prepare a multiepitope peptide nanovaccine and evaluate its immunogenicity and protective effect in BALB/c mice. METHODS: The B-cell and T-cell epitopes of Omp22 from A. baumannii were predicted using bioinformatics methods and identified by immunological experiments. The optimal epitopes were conjugated in series by 6-aminocaproic acid and chemically synthesized multiepitope polypeptide rOmp22. Then, rOmp22 was encapsulated by chitosan (CS) and poly (lactic-co-glycolic) acid (PLGA) to prepare CS-PLGA-rOmp22 nanoparticles (NPs). The immunogenicity and immunoprotective efficacy of the vaccine were evaluated in BALB/c mice. RESULTS: CS-PLGA-rOmp22 NPs were small (mean size of 272.83 nm) with apparently spherical structures, positively charged (4.39 mV) and nontoxic to A549 cells. A high encapsulation efficiency (54.94%) and a continuous slow release pattern were achieved. Compared with nonencapsulated rOmp22, CS-PLGA-rOmp22 immunized BALB/c mice induced higher levels of rOmp22-specific IgG in serum and IFN-γ in splenocyte supernatant. Additionally, lung injury and bacterial burdens in the lung and blood were suppressed, and potent protection (57.14%-83.3%) against acute lethal intratracheal A. baumannii challenge was observed in BALB/c mice vaccinated with CS-PLGA-rOmp22. CONCLUSION: CS-PLGA-rOmp22 NPs elicited specific IgG antibodies, Th1 cellular immunity and protection against acute lethal intratracheal A. baumannii challenge. Our results indicate that this nanovaccine is a desirable candidate for preventing A. baumannii infection.

Clinical characteristics of moderate COVID-19 patients aggravation in Wuhan Stadium Cabin Hospital: A 571 cases of retrospective cohort study.

To report the clinical characteristics and potential risk factors of patients with coronavirus disease 2019 (COVID-19) in Wuhan Stadium Cabin Hospital in Hubei Province. A total of 571 patients of COVID-19 treated in the Wuhan Stadium Cabin Hospital were selected for analysis, univariable and multivariable logistic regression methods were used to explore the risk factors associated with disease aggravation. The main clinical symptoms of moderate COVID-19 were fever, cough and dyspnea, hypertension, diabetes, and coronary heart diseases were the main comorbidities both in transferred and stable patients. Twenty-six patients (4.55%) of mild and moderate patients had disease aggravation, and most of which occurred between 36 and 48 hours after admission. Multiple regression analysis showed increasing odds of disease aggravation associated with former smoker history, diabetes, dyspnea, consolidation, and interstitial abnormalities of computed tomography scanning, lymphopenia and elevated of C-reactive protein, the time points of transferred patients mainly between 36 and 48 hours (65.38%), and the average hospital stay for stable patients was 15 days.It could help clinicians to identify patients with poor prognosis at an early stage, and provide early warning role for timely intervention.

Population and Age-Based Cardiorespiratory Fitness Level Investigation and Automatic Prediction.

Maximal oxygen consumption (VO2max) reflects aerobic capacity and is crucial for assessing cardiorespiratory fitness and physical activity level. The purpose of this study was to classify and predict the population-based cardiorespiratory fitness based on anthropometric parameters, workload, and steady-state heart rate (HR) of the submaximal exercise test. Five hundred and seventeen participants were recruited into this study. This study initially classified aerobic capacity followed by VO2max predicted using an ordinary least squares regression model with measured VO2max from a submaximal cycle test as ground truth. Furthermore, we predicted VO2max in the age ranges 21-40 and above 40. For the support vector classification model, the test accuracy was 75%. The ordinary least squares regression model showed the coefficient of determination (R 2) between measured and predicted VO2max was 0.83, mean absolute error (MAE) and root mean square error (RMSE) were 3.12 and 4.24 ml/kg/min, respectively. R 2 in the age 21-40 and above 40 groups were 0.85 and 0.75, respectively. In conclusion, this study provides a practical protocol for estimating cardiorespiratory fitness of an individual in large populations. An applicable submaximal test for population-based cohorts could evaluate physical activity levels and provide exercise recommendations.

The Pseudomonas aeruginosa Secreted Protein PA3611 Promotes Bronchial Epithelial Cell Epithelial-Mesenchymal Transition via Integrin αvß6-Mediated TGF-ß1-Induced p38/NF-κB Pathway Activation.

Pseudomonas aeruginosa (PA) is an important pathogen that has been proven to colonize and cause infection in the respiratory tract of patients with structural lung diseases and to lead to bronchial fibrosis. The development of pulmonary fibrosis is a complication of PA colonization of the airway, resulting from repeated infection, damage and repair of the epithelium. Bronchial epithelial cell epithelial-mesenchymal transition (EMT) plays a vital role in bronchial fibrosis. To date, research on bronchial epithelial cell EMT caused by PA-secreted virulence factors has not been reported. Here, we found that PA3611 protein stimulation induced bronchial epithelial cell EMT with mesenchymal cell marker upregulation and epithelial cell marker downregulation. Moreover, integrin αvß6 expression and TGF-ß1 secretion were markedly increased, and p38 MAPK phosphorylation and NF-κB p65 subunit phosphorylation were markedly enhanced. Further research revealed that PA3611 promoted EMT via integrin αvß6-mediated TGF-ß1-induced p38/NF-κB pathway activation. The function of PA3611 was also verified in PA-infected rats, and the results showed that ΔPA3611 reduced lung inflammation and EMT. Overall, our results revealed that PA3611 promoted EMT via integrin αvß6-mediated TGF-ß1-induced p38/NF-κB pathway activation, suggesting that PA3611 acts as a crucial virulence factor in bronchial epithelial cell EMT and is a potential target for the clinical treatment of bronchial EMT and fibrosis caused by chronic PA infection.

Treatment of severe COVID-19 with human umbilical cord mesenchymal stem cells.

BACKGROUND: COVID-19 is a highly infectious respiratory disease. No therapeutics have yet been proven effective for treating severe COVID-19. OBJECTIVES: To determine whether human umbilical cord mesenchymal stem cell infusion may be effective and safe for the treatment of severe COVID-19. METHODS: Patients with severe COVID-19 were randomly divided into 2 groups: the standard treatment group and the standard treatment plus hUC-MSC infusion group. The incidence of progression from severe to critical illness, 28-day mortality, clinical symptom improvement, time to clinical symptom improvement, hematologic indicators including C-reactive protein, lymphocyte number, and interleukin 6, and imaging changes were observed and compared between the two groups. MEASUREMENTS AND MAIN RESULTS: The incidence of progression from severe to critical illness and the 28-day mortality rate were 0 in the hUC-MSC treatment group, while 4 patients in the control group deteriorated to critical condition and received invasive ventilation; 3 of them died, and the 28-day mortality rate was 10.34%. In the hUC-MSC treatment group, the time to clinical improvement was shorter than that in the control group. Clinical symptoms of weakness and fatigue, shortness of breath, and low oxygen saturation obviously improved beginning on the third day of stem cell infusion and reached a significant difference on day 7. CRP and IL-6 levels were significantly lower from day 3 of infusion, the time for the lymphocyte count to return to the normal range was significantly faster, and lung inflammation absorption was significantly shorter on CT imaging in the hUC-MSC group than in the control group. CONCLUSIONS: Intravenous transplantation of hUC-MSCs is a safe and effective method that can be considered a salvage and priority treatment option for severe COVID-19. TRIAL REGISTRATION: Chinese Clinical Trial Registration; ChiCTR2000031494; Registered on 2 April 2020; http:// www.medresman.org.

Effect of hormone therapy on muscle strength in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This study aimed to evaluate the overall effects of hormone therapy (HT) on muscle strength in postmenopausal women through a systematic review and meta-analysis. METHODS: PubMed, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials were systematically searched from the inception dates to August 2019. Randomized controlled trials (RCTs) that compared the effects of HT with either no therapy or placebo on muscle strength in postmenopausal women were eligible. The quality of studies was assessed using the Cochrane risk of bias tool. Measurements of changes in muscle strength compared to baseline were extracted for pooled analysis. The effect size was calculated as standardized mean differences using a random effects model. RESULTS: We identified nine studies with a combined population of 2,476 postmenopausal women. The studies included were assessed to be of good quality overall. The results showed that HT was not associated with muscle strength gain in postmenopausal women (standardized mean difference = 0.352; 95% confidence interval, -0.098 to 0.803; P = 0.125; I = 95.3%). The changes in muscle strength in women receiving HT were not significant. The results were unchanged when stratified by treatment type, muscle group, and treatment duration. CONCLUSIONS: The use of HT was not associated with the improvement of muscle strength in postmenopausal women. This finding suggested that HT might not improve muscle strength or that the effect size was too small to identify significant therapeutic efficacy.