Systematically explore the potential hepatotoxic material basis and molecular mechanism of Radix Aconiti Lateralis based on the concept of toxicological evidence chain (TEC).

Radix aconiti lateralis (Fuzi) is widely used in China as a traditional Chinese medicine for the treatment of asthenia, pain and inflammation. However, its toxic alkaloids often lead to adverse reactions. Currently, most of the toxicity studies on Fuzi are focused on the heart and nervous system, and more comprehensive toxicity studies are needed. In this study, based on the previous reports of Fuzi hepatotoxicity, serum pharmacochemistry and network toxicology were used to screen the potential toxic components of Heishunpian(HSP), a processed product of Fuzi, and to explore the possible mechanism of HSP-induced hepatotoxicity. The results obtained are expressed based on the toxicological evidence chain (TEC). It was found that 22 potential toxic components screened can affect Th17 cell differentiation, Jak-STAT signaling pathway, glutathione metabolism, and other related pathways by regulating AKT1, IL2, F2, GSR, EGFR and other related targets, which induces oxidative stress, metabolic disorders, cell apoptosis, immune response, and excessive release of inflammatory factors, eventually inducing liver damage in rats. This is the first study on HSP-induced hepatotoxicity based on the TEC concept, providing references for further studies on the toxicity mechanism of Fuzi.

[Evaluation of taste changes of Scutellariae Radix before and after wine-frying based on electronic ongue technology and its application in identification of Scutellariae Radix pieces].

Scutellariae Radix(Huangqin) is a well-known traditional Chinese medicine(TCM) used for the treatment of clearing heat in clinical application. It is bitter-cold by using directly, but the bitter-cold property can be relieved after wine-frying. The study of taste changes before and after wine-frying of Scutellariae Radix is of great significance in identifying Scutellariae Radix and wine-processed Scutellariae Radix and clarifying the traditional theory of wine-processing. In this experiment, 10 batches of Scutellariae Radix and wine-processed Scutellariae Radix were prepared. The contents of 5 flavonoids were determined by high performance liquid chromatography(HPLC), and principal component analysis(PCA) was performed with 5 flavonoids as variables. As a result, the contents were different in different batches of Scutellariae Radix, but Scutellariae Radix and wine-processed Scutellariae Radix could not be distinguished. Five sensory attributes(sour, salty, fresh, sweet, and bitter) were evaluated by artificial tasting, and the response values of 7 sensors(AHS, AHS, PKS, CTS, NMS, CPS, ANS, SCS) representing the taste of pieces were detected by electronic tongue. The correlation between sensory evaluation and response values of the electronic tongue were analyzed, and the results showed that the sensory evaluation of sour, salty, fresh, sweet, bitter and AHS, CTS, NMS, ANS, SCS sensors had different degrees of correlation, indicating that the electronic tongue technology can be used as an alternative to artificial taste and can serve as a means for quantifying the taste, and it can be used to evaluate the taste of TCM pieces. The taste method was used to analyze the response values of the electronic tongue, and the results showed that the bitterness of wine-processed Scutellariae Radix decreased and the salty taste increased. PCA was used to analyze taste changes before and after wine-processed Scutellariae Radix, and the results showed that taste differences between 2 pieces were divided into 2 categories. PCA loading scattering plots showed that response of saltiness and bitterness were the major factors to affect overall taste in Scutellariae Radix and wine-processed Scutellariae Radix. Based on electronic tongue response values, the Fisher discriminant model for Scutellariae Radix and wine-processed Scutellariae Radix was established, which showed that it could effectively discriminate them with a recognition rate of 100%. The experimental results showed that the electronic tongue combined with multivariate statistical analysis can be used to evaluate taste of TCM, at the same time, it could provide a fast and simple method for identifying different processed products.

The Impact of Traditional Chinese Herbal Decoctions Combined with Rehabilitation Therapy on Pulmonary Function and Respiratory Muscle Strength in COVID-19 Recovery Patients.

Objective: This study aims to evaluate the clinical efficacy of integrated traditional Chinese and Western medicine rehabilitation treatment during the recovery period of COVID-19, providing a scientific basis for developing more effective rehabilitation protocols. Methods: The study included 120 COVID-19 (novel coronavirus) recovery patients treated at our hospital from November 2021 to April 2022. After registration, patients were randomly divided into two groups, namely the study group and the control group. The control group received conventional rehabilitation treatment, while the study group underwent integrated traditional Chinese and Western medicine rehabilitation treatment, with 60 cases in each group. The clinical observation indicators in this study include the results of the 6-minute walk test (6MWT), respiratory and circulatory parameters, pulmonary function, changes in respiratory muscle strength, and quality of life in both groups of patients. Results: The 6MWT distance increased significantly in both groups, with the study group showing a larger improvement (P < 0.05). SpO2 and PaO2 values improved significantly in both groups, with greater increases in the study group (P < 0.05). Lung function parameters (FEV1 and FEV1/FVC) improved significantly in the study group compared to the control group (P < 0.05). Diaphragmatic thickness and mobility were also significantly higher in the study group (P < 0.05). The SF-36 quality of life scores were significantly better in the study group (P < 0.05). Conclusion: Integrated traditional Chinese and Western medicine rehabilitation treatment has achieved significant efficacy during the recovery period of COVID-19. The complementary use of traditional Chinese medicine's differential diagnosis and treatment and modern medical approaches from Western medicine provides patients with comprehensive and personalized rehabilitation services, offering new ideas and methods to improve the quality of patient recovery.

Dry Ball-Milled Quinoa Starch as a Pickering Emulsifier: Preparation, Microstructures, Hydrophobic Properties and Emulsifying Properties.

This research supplied a "cleaner-production" way to produce "clean-label" quinoa starch-based Pickering emulsifier with excellent emulsifying properties. The effects of dry ball-milling time and speed on the multi-scale structures and emulsifying properties of quinoa starch were studied. With increasing ball-milling time and speed, particle size first decreased and then increased, the crystallinity, lamellar structure and short-range ordered structure gradually decreased, and contact angle gradually increased. The increased contact angle might be related to the increased oil absorption properties and the decreased water content. The emulsification properties of ball-milled quinoa starch (BMQS)-based Pickering emulsions increased with the increase in ball-milling time and speed, and the emulsions of BMQS-4 h, 6 h, 8 h, and 600 r reached the full emulsification state. After 120 days' storage, the oil droplets of BMQS-2 h (BMQS-400 r) deformed, the oil droplets increased, and the emulsification index decreased. The emulsification index and the oil droplets of BMQS-4 h, 6 h, 8 h and 600 r-based emulsions did not show obvious changes after storage, indicating the good emulsifying stability of these BMQS-based emulsions, which might be because that the relatively larger amount of starch particles that dispersed in the voids among the oil droplets could act as stronger network skeletons for the emulsion gel. This Pickering emulsifier was easily and highly efficiently produced and low-cost, having great potential to be used in the food, cosmetic and pharmaceutical industries.

The impact of 25-hydroxyvitamin D and calcium on risk of age-related macular degeneration: a Mendelian randomization study.

BACKGROUND: The relationships between 25-hydroxyvitamin D [25(OH)D] and calcium and age-related macular degeneration (AMD) are unclear. OBJECTIVES: This study aimed to investigate the causal role of 25(OH)D concentrations, calcium concentrations, and dietary supplements use of vitamin D and calcium on risk of AMD and its subtypes. METHODS: Independent genetic variants associated with 25(OH)D and calcium concentrations were used as instrumental variables in published genome-wide association studies (GWASs) of European ancestry. The bidirectional 2-sample Mendelian randomization (MR) analyses were performed using summary-level data from the UK Biobank and FinnGen datasets. Sensitivity analyses were conducted to ensure the robustness of the MR results. The meta-analyses were conducted using both fixed-effect and random-effect models to provide comprehensive and reliable estimates. RESULTS: A standard deviation increase in calcium concentrations was linked to a 14%, 17%, and 13% reduction in the likelihood of developing AMD (95% confidence interval [CI]: 0.77, 0.97), wet AMD (95% CI: 0.73, 0.95), and dry AMD (95% CI: 0.75, 1.00), respectively. No significant causal relationships were detected between genetically predicted 25(OH)D concentrations and AMD and its subtypes (all P > 0.05). The combined analyses showed that higher calcium concentrations were associated with a reduced risk of overall AMD, with an odds ratio of 0.89 (95% CI: 0.81, 0.98). CONCLUSIONS: This study provides evidence supporting the causal relationship between calcium concentrations and risk of AMD and its subtypes, which may have important implications for the prevention, monitoring, and treatment of AMD.

A prediction model for 30-day deaths of cirrhotic patients in intensive care unit hospitalization.

ABSTRACT: The aim of this study was to establish a prediction model for 30-day deaths of cirrhotic patients in intensive care unit.A case-control study involving 1840 patients was conducted in the Medical Information Mart of the Intensive Care Database III version 1.4. The logistic regression with L1 regularization was used to screen out the variables. The 30-day in-hospital death was used as the dependent variable and the selected variables were used as the independent variable to build a random forest model. The performance of the model was validated by the internal validation.The variables screened by logistic regression analysis were the age, heart rate, respiratory rate, systolic blood pressure, diastolic blood pressure, Oxygen saturation, white blood cells, platelets, red cell distribution width, glucose, blood urea nitrogen, bicarbonate, total bilirubin, hematocrit, alanine transaminase, aspartate transaminase, bilirubin, Simplified Acute Physiology Score II and Sequential Organ Failure Assessment. The areas under the curve of the random forest model based on these variables was 0.908, and the performance of this model were internally validated with an areas under the curve of 0.801. The random forest model displayed that Simplified Acute Physiology Score, Sequential Organ Failure Assessment, blood urea nitrogen, total bilirubin and bilirubin were more important predictors for the 30-day death of cirrhotic patients in intensive care unit.A prediction model for death of cirrhotic patients was developed based on a random forest analysis, providing a tool to evaluate the patients with a high risk of 30-day in-hospital deaths to help clinician make preventive intervention to decrease the mortality.

Enzymatically modified quinoa starch-based Pickering emulsion: Effect of enzymolysis and emulsifying conditions.

Both the effects of enzymolysis condition on the microstructures and emulsifying property of enzymatic modified quinoa starch (EMQS) and the effects of emulsion formulation on the EMQS based emulsions were investigated. The emulsifying capacity (EC) and stability (ES) of EMQS were positive correlated with enzyme amount (0-2.4 % w/wstarch). The particle sizes of EMQS decreased and its hydrophobicity increased with increasing enzyme amount (0-2.4 % w/wstarch), which were the main reasons for the increasing emulsifying performance of EMQS. With the increasing starch concentration, the EC of the EMQS increased, the oil droplet size of the emulsion decreased. With the oil/water ratios ranging from 1:9 to 6:4, the emulsification index (EI) and oil droplet size of the emulsion increased. EMQS based emulsion had a relatively good stability in the pH range of 2-10. This study lays the foundation for the application of EMQS as a stable clean-label Pickering emulsifier.

Study on the Mechanism of Mesaconitine-Induced Hepatotoxicity in Rats Based on Metabonomics and Toxicology Network.

Mesaconitine (MA), one of the main diterpenoid alkaloids in Aconitum, has a variety of pharmacological effects, such as analgesia, anti-inflammation and relaxation of rat aorta. However, MA is a highly toxic ingredient. At present, studies on its toxicity are mainly focused on the heart and central nervous system, and there are few reports on the hepatotoxic mechanism of MA. Therefore, we evaluated the effects of MA administration on liver. SD rats were randomly divided into a normal saline (NS) group, a low-dose MA group (0.8 mg/kg/day) and a high-dose MA group (1.2 mg/kg/day). After 6 days of administration, the toxicity of MA on the liver was observed. Metabolomic and network toxicology methods were combined to explore the effect of MA on the liver of SD rats and the mechanism of hepatotoxicity in this study. Through metabonomics study, the differential metabolites of MA, such as L-phenylalanine, retinyl ester, L-proline and 5-hydroxyindole acetaldehyde, were obtained, which involved amino acid metabolism, vitamin metabolism, glucose metabolism and lipid metabolism. Based on network toxicological analysis, MA can affect HIF-1 signal pathway, MAPK signal pathway, PI3K-Akt signal pathway and FoxO signal pathway by regulating ALB, AKT1, CASP3, IL2 and other targets. Western blot results showed that protein expression of HMOX1, IL2 and caspase-3 in liver significantly increased after MA administration (p < 0.05). Combined with the results of metabonomics and network toxicology, it is suggested that MA may induce hepatotoxicity by activating oxidative stress, initiating inflammatory reaction and inducing apoptosis.

1,2-Bis(2-meth-oxy-6-formyl-phen-oxy)ethane.

IN THE TITLE COMPOUND [SYSTEMATIC NAME: 3,3'-dimethoxy-2,2'-(ethane-1,2-diyldioxy)dibenzaldehyde], C(18)H(18)O(6), prepared from 1,2-dibromo-ethane and ortho-vanillin in the presence of sodium carbonate, the two vanillin units are linked via a CH(2)-CH(2) bridge. The two benzene rings are inclined at a dihedral angle of 41.6 (5)°.

The Molecular Mechanism of Antioxidation of Huolisu Oral Liquid Based on Serum Analysis and Network Analysis.

Huolisu Oral Liquid (HLS), a well-known traditional Chinese medicine (TCM) prescription, is an over-the-counter drug that is registered and approved by the State Food and Drug Administration (Approval No. Z51020381). HLS has been widely applied in the clinical treatment of cognitive disorders and has effects on delaying aging. The antioxidant effects of HLS are closely related to its antiaging activities, but the underlying mechanisms are unclear. In this study, the potential antioxidant ingredients of HLS were screened based on serum pharmacochemistry and network pharmacology, and the potential mechanisms involved in HLS antioxidant effects were preliminarily explored. Further, the antioxidant effects of HLS were verified by in vivo and in vitro experiments. The results showed that potential antioxidant ingredients could affect the toxic advanced glycation end products-receptor for advanced glycation end products (TAGE-RAGE) signaling, mitogen-activated protein kinase (MAPK) signaling, interleukin (IL)-17 signaling, tumor necrosis factor (TNF) signaling, toll-like receptors (TLRs), cyclic adenosine monophosphate (cAMP) signaling, hypoxia-inducible factor (HIF)-1 signaling, and other related pathways by regulating GAPDH, AKT1, TP53, MAPK1, JUN, and other associated targets. Thus, HLS may reduce inflammation, control the release of inflammatory cytokines, and regulate mitochondrial autophagy and metabolic abnormalities to ultimately play an antioxidant role. This is the first study attempting to construct a multilevel network of "HLS-antioxidant targets" based on serum pharmacochemistry and network pharmacology to explore the relationship between HLS and antioxidation and the molecular mechanisms of antioxidation combined with bioinformatics functional analysis and lays a foundation for further elucidating the antioxidant mechanisms of HLS.

Pickering emulsifiers based on enzymatically modified quinoa starches: Preparation, microstructures, hydrophilic property and emulsifying property.

Quinoa starch was developed as a new kind of Pickering emulsifier by enzymatic modification. The morphological structure, crystalline structure, lamellar structure, fractal structure, particle size distribution, contact angle, emulsion index (EI), and emulsion micromorphology were studied to explore the relationship between structure characteristics, hydrophilic property, and emulsifying properties of enzymatically modified (EM) quinoa starches. With the increasing enzymatic hydrolysis time in the test range of 0-9 h, particle size of EM quinoa starch decreased, and the broken starch and contact angle of EM quinoa starch increased; the EI value of emulsions with EM quinoa starch increased, and the oil droplet size of emulsions with EM quinoa starch decreased. It suggested that both the smallest particle size and the closest extent of the contact angle to 90° derived the best emulsifying property of EM-9. The EM quinoa starch had higher emulsifying capacity at higher oil volume fraction (Φ) (50%) than at lower Φ (20%), proving that the EM starch has potential to be used as Pickering emulsifiers in higher oil products, such as salad dressing.

Microbiome Analysis Investigating the Impacts of Fermented Spent Mushroom Substrates on the Composition of Microbiota in Weaned Piglets Hindgut.

The purpose of this study was to investigate the effects of fermented spent mushroom substrates (FSMS) on growth performance, serum biochemical, gut digestive enzyme activity, microbial community, genes expression of tight junction proteins, and volatile fatty acids in the hindgut (colon and cecum) of weaned piglets. A total of 100 weaned Yihao native pigs (native × Duroc, 50 males and 50 females) were allocated to two groups with five replicates and 10 pigs per replicate. Pigs in the control group were fed a basal diet (BD group), and the others were fed basal diets supplemented with 3% FSMS (FSMS group). Relative to the BD group, it had better results for final weight, average daily gain, and feed conversion ratio in the FSMS group but not significant (p > 0.05), which was accompanied by improved serum triiodothyronine, immunoglobulin G, and immunoglobulin A (p < 0.05) but lower serum total protein, albumin, total cholesterol, and total triglyceride during the overall period (p < 0.05). Similarly, FSMS significantly upregulated (p < 0.05) the messenger RNA expression of duodenal tight junction proteins such as tight junction protein 1, tight junction protein 2, and occludin. Meanwhile, isobutyric acid, valeric acid, and isovaleric acid levels were increased, whereas propanoic acid was decreased (p < 0.05) in the FSMS group than the BD group. In addition, the piglets in the FSMS group changed the microbial diversity in the colon and cecum. 16S rRNA gene sequencing-based compositional analysis of the colonic and cecal microbiota showed differences in the relative abundance of bacterial phyla (Firmicutes, Bacteroidetes, etc.), genus (Lactobacillus, Streptococcus, Roseburia, etc.), and species (Lactobacillus gasseri, Clostridium disporicum, etc.) between the BD and FSMS fed piglets. In conclusion, dietary supplementation with FSMS benefited to the intestinal mucosal barrier, immunity, and composition of the microbiota.

A new meroterpenoid functions as an anti-tumor agent in hepatoma cells by downregulating mTOR activation and inhibiting EMT.

Liver cancer, also known as primary liver cancer, is cancer that starts in the liver. JNU-144, a new meroterpenoid purified from Lithospermum erythrorhizon, has exhibited promising anticancer activity; however, the molecular mechanisms of action of JNU-144 on malignant cells remain unclear. Our studies revealed that JNU-144 suppressed cell viability and proliferation in hepatoma cells by downregulating mTOR activation. Meanwhile, JNU-144 activated the intrinsic apoptosis pathway and subsequently triggered apoptotic cell death in SMMC-7721 cells. We also found that JNU-144 inhibited the epithelial-mesenchymal transition in both SMMC-7721 and HepG2 cells through reprogramming of epithelial-mesenchymal transition (EMT)-related gene expression or regulating protein instability. These findings indicate that JNU-144 exerts potent anticancer activity in hepatoma cells and may be developed as a potential therapeutic drug.

The breeding of two polyploid rice lines with the characteristic of polyploid meiosis stability.

Polyploidization is a basic feature of plant evolution. Nearly all of the main food, cotton and oil crops are polyploid. When ploidy levels increase, yields double; this phenomenon suggested a new strategy of rice breeding that utilizes wide crosses and polyploidization dual advantages to breed super rice. Because low seed set rates in polyploid rice usually makes it difficult to breed, the selection of Ph-liked gene lines was emphasized. After progenies of indica-japonica were identified and selected, two polyploid lines, PMeS-1 and PMeS-2 with Polyploid Meiosis Stability (PMeS) genes were bred. The procedure included seven steps: selecting parents, crossing or multiple crossing, back-crossing, doubling chromosomes, identifying the polyploid, and choosing plants with high seed set rates that can breed themselves into stable lines. The characteristics of PMeS were determined by observing meiotic behaviors and by cross-identification of seed sets. PMeS-1 and PMeS-2, (japonica rice), have several characteristics different from other polyploid rice lines, including a higher rate of seed set (more than 65%, increasing to more than 70% in their F1 offspring); and stable meiotic behaviors (pairing with bivalents and quarivalents nearly without over-quarivalent in prophase, nearly without lagging chromosomes in metaphase and without micronuclei in anaphase and telophase). The latter was obviously different from control polyploid line Dure-4X, which displayed abnormal meiotic behaviors including a higher rate of multivalents, univalents and trivalents in prophase, lagging chromosomes in metaphase and micronuclei in anaphase and telophase. There were also three differences of the breeding method between PMeS lines and normal diploid lines: chromosomes doubling, polyploidism identifying and higher seed set testing. The selection of PMeS lines is the first step in polyploid rice breeding; their use will advance the progress of polyploid rice breeding, which will in turn offer a new way to breed super rice.

EFFECT OF INTRAPERITONEAL RESUSCITATION WITH DIFFERENT CONCENTRATIONS OF SODIUM PYRUVATE ON INTESTINAL ISCHEMIA REPERFUSION INJURY IN HEMORRHAGIC SHOCK RAT.

OBJECTIVE: To determine the effects of intraperitoneal resuscitation (PR) with different concentrations of sodium pyruvate (PY) on intestinal ischemia reperfusion injury in rats hemorrhagic shock (HS). METHODS: Sixty rats were randomly assigned to six groups. These included: group SHAM, intravenous resuscitation only (VR) group, and four PR groups based on resuscitation fluid: glucose-lactate-based peritoneal dialysis solution (LA), and PY-1.1%, PY-1.6%, and PY-2.2% (concentrations in grams/dL). Mean arterial pressure (MAP) was monitored continuously. Blood pH, base excess (BE), lactate, intestinal myeloperoxidase (MPO), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), activated caspase-3, and zonula occludens-1 (ZO-1) were measured; intestinal mucosal damage index (IMDI) and subcellular changes were observed; apoptotic index (AI) was calculated. RESULTS: Three hours after resuscitation, in PY groups, MPO, MDA, IMDI, AI, TNF-alpha, and IL-6 were significantly lower than VR and LA groups, while pH and BE were higher. PY groups showed less expression of activated caspase-3 but elevated ZO-1. Among PY groups, group PY-1.1% had the lowest MPO, MDA and TNF-alpha, and had less pathological damage and subcellular changes than other experimental groups. CONCLUSIONS: PR using PY solution combined with VR provided protection against intestinal ischemia-reperfusion injury following HS and resuscitation. Under the same hypertonic condition, 1.1% PY solution showed significant advantages compared with 2.2% and 1.6% solutions. The underlying mechanisms may include the maintenance of hemodynamic stability, regulation of homeostasis, inhibition of oxidative stress and inflammation, and protection of intestinal epithelial tight junction barrier function.

HO-1 Protects against Hypoxia/Reoxygenation-Induced Mitochondrial Dysfunction in H9c2 Cardiomyocytes.

BACKGROUND: Mitochondrial dysfunction would ultimately lead to myocardial cell apoptosis and death during ischemia-reperfusion injuries. Autophagy could ameliorate mitochondrial dysfunction by autophagosome forming, which is a catabolic process to preserve the mitochondrial's structural and functional integrity. HO-1 induction and expression are important protective mechanisms. This study in order to investigate the role of HO-1 during mitochondrial damage and its mechanism. METHODS AND RESULTS: The H9c2 cardiomyocyte cell line were incubated by hypoxic and then reoxygenated for the indicated time (2, 6, 12, 18, and 24 h). Cell viability was tested with CCK-8 kit. The expression of endogenous HO-1(RT-PCR and Western blot) increased with the duration of reoxygenation and reached maximum levels after 2 hours of H/R; thereafter, the expression gradually decreased to a stable level. Mitochondrial dysfunction (Flow cytometry quantified the ROS generation and JC-1 staining) and autophagy (The Confocal microscopy measured the autophagy. RFP-GFP-LC3 double-labeled adenovirus was used for testing.) were induced after 6 hours of H/R. Then, genetic engineering technology was employed to construct an Lv-HO1-H9c2 cell line. When HO-1 was overexpressed, the LC3II levels were significantly increased after reoxygenation, p62 protein expression was significantly decreased, the level of autophagy was unchanged, the mitochondrial membrane potential was significantly increased, and the mitochondrial ROS level was significantly decreased. Furthermore, when the HO-1 inhibitor ZnPP was applied the level of autophagy after reoxygenation was significantly inhibited, and no significant improvement in mitochondrial dysfunction was observed. CONCLUSIONS: During myocardial hypoxia-reoxygenation injury, HO-1 overexpression induces autophagy to protect the stability of the mitochondrial membrane and reduce the amount of mitochondrial oxidation products, thereby exerting a protective effect.

Effects of bone marrow-derived mesenchymal stem cells transfected with survivin on pulmonary fibrosis in mice.

The aim of the present study was to investigate the effects of bone marrow-derived mesenchymal stem cells (BMSCs) transfected with survivin on lung fibrosis in mice. Mice with bleomycin-induced pulmonary fibrosis were allocated at random to group A, B or C, and injected with 1×106 survivin gene-expressing BMSCs, 1×106 BMSCs or normal saline, respectively. A total of 6 mice were sacrificed from each group on days 7, 14 and 28 after treatment. The extent of alveolitis and pulmonary fibrosis was assessed and the apoptotic rates of the BMSCs and survivin-expressing BMSCs were detected. The content of surfactant protein A (SP-A) in the lung and hydroxyproline (Hyp) in the serum was measured. The mRNA expression levels of transforming growth factor (TGF)-ß1 and matrix metalloproteinase (MMP)-9 in the lung tissue of the mice was detected. Furthermore, the protein expression levels of caspase-3 and -9 were detected. The apoptotic rates of the BMSCs (group B) and survivin-expressing BMSCs (group A) were 14.466±1.953 and 7.718±0.493%, respectively. The degree of lung fibrosis in groups A and B was reduced compared with that in group C. The hydroxyproline content in groups A and B was reduced compared with that in group C, and the SP-A content in groups A and B was increased compared with that in group C. The mRNA expression levels of TGF-ß1 in group A were reduced compared with those in group B, and the levels in group B were reduced compared with those in group C. By contrast, the mRNA expression levels of MMP-9 in group A were increased compared with those in groups B and C, and the levels in group B were increased compared with those in group A. The expression levels of caspase-3 and -9 in group A were elevated compared with those in groups B and C. In conclusion, BMSCs are effective in preventing bleomycin-induced lung fibrosis, and survivin may enhance the protective effects of BMSCs.

Protection against intestinal injury from hemorrhagic shock by direct peritoneal resuscitation with pyruvate in rats.

OBJECTIVE: We explored the effects of direct peritoneal resuscitation with pyruvate-peritoneal dialysis solution (PDS) following intravenous resuscitation (VR) on intestinal ischemia-reperfusion injury in rats with hemorrhagic shock (HS). METHODS: Fifty rats were randomly assigned equally to five groups. In group sham, a surgical operation was performed on rats without shock or resuscitation. In group VR, rats were subjected only to VR. In groups NS, LA, and PY, direct peritoneal resuscitation was performed with normal saline (NS), lactate-based PDS (Lac-PDS), and pyruvate-based PDS (Pyr-PDS), respectively, after VR. Mean arterial pressure was monitored in the right common carotid artery. Two hours after resuscitation, the lactate level in arterial blood and the wet weight/dry weight ratio of the intestine were determined. The intestinal mucosal damage index was estimated, and ultrastructural changes in the intestinal mucosa were observed. Malondialdehyde, myeloperoxidase, nitric oxide, and tumor necrosis factor α levels were also measured. RESULTS: Two hours after HS and resuscitation, the increase in arterial blood lactate and intestinal wet weight/dry weight ratio declined significantly in rats from Groups LA and PY compared with groups VR and NS, whereas group PY was more advantageous in the changes of these parameters. The intestinal mucosal damage index and ultrastructural changes were also improved in groups LA and PY when compared with groups VR and NS. Protection was more apparent with Pyr-PDS than Lac-PDS. Hemorrhagic shock resulted in a significant increase in malondialdehyde levels and myeloperoxidase activity and was accompanied by overexpression of tumor necrosis factor α and a reduction in nitric oxide levels. These changes were significantly attenuated by Lac-PDS and Pyr-PDS at 2 h after resuscitation, and Pyr-PDS showed more effective protection for the intestine than Lac-PDS. CONCLUSIONS: Direct peritoneal resuscitation with Lac-PDS and Pyr-PDS after VR alleviated intestinal injury from HS in rats, and Pyr-PDS was superior to Lac-PDS in its protective effect. Mechanisms of action might include the elimination of free oxygen radicals, reduction of neutrophil infiltration, inhibition of the inflammatory response, and regulation of intestinal mucosal blood flow and barrier function.

[Monoclonal antibody against laminin receptor 1 inhibits the pulmonary fibrosis induced by bleomycin in rats].

OBJECTIVE: To investigate the effect of the anti-laminin receptor 1 (anti-LAMR1) monoclonal antibody (mAb) on rat pulmonary fibrosis induced by bleomycin. METHODS: Seventy-two male Wistar rats were randomly divided into 3 groups: LAMR1 mAb group (group L), control group (group C) and model group (group M). All rats were injected with bleomycin via tracheal instillation (5 mg/kg body mass) to induce pulmonary fibrosis. Then, the rats were treated with anti-LAMR1 mAb (group L), dexamethasone (group C), normal saline (group M), three times each week via intraperitoneal injection. Eight rats in each group were sacrificed at the 7, 14, 28 days. Histological changes of the lungs were evaluated by HE staining. The expression of surfactant protein A (SP-A) in the lung tissue was measured by immunohistochemistry. The expression of hydroxyproline (Hyp) in serum was measured by ELISA. The expressions of MMP-9 and TGF-ß1 mRNA were evaluated by PCR. RESULTS: Compared with the other two groups, group M presented more apparent alveolitis and the higher expression of hydroxyproline in serum, the lower expression of SP-A, and the higher expressions of MMP-9 and TGF-ß1 mRNA in the lung tissue. CONCLUSION: LAMR1 mAb can evidently alleviate pulmonary fibrosis induced by bleomycin in rats.