Targeting circ-0034880-enriched tumor extracellular vesicles to impede SPP1highCD206+ pro-tumor macrophages mediated pre-metastatic niche formation in colorectal cancer liver metastasis.

BACKGROUND: Information transmission between primary tumor cells and immunocytes or stromal cells in distal organs is a critical factor in the formation of pre-metastatic niche (PMN). Understanding this mechanism is essential for developing effective therapeutic strategy against tumor metastasis. Our study aims to prove the hypothesis that circ-0034880-enriched tumor-derived extracellular vesicles (TEVs) mediate the formation of PMN and colorectal cancer liver metastasis (CRLM), and targeting circ-0034880-enriched TEVs might be an effective therapeutic strategy against PMN formation and CRLM. METHODS: We utilized qPCR and FISH to measure circRNAs expression levels in human CRC plasma, primary CRC tissues, and liver metastatic tissues. Additionally, we employed immunofluorescence, RNA sequencing, and in vivo experiments to assess the effect mechanism of circ-0034880-enriched TEVs on PMN formation and CRC metastasis. DARTS, CETSA and computational docking modeling were applied to explore the pharmacological effects of Ginsenoside Rb1 in impeding PMN formation. RESULTS: We found that circ-0034880 was highly enriched in plasma extracellular vesicles (EVs) derived from CRC patients and closely associated with CRLM. Functionally, circ-0034880-enriched TEVs entered the liver tissues and were absorbed by macrophages in the liver through bloodstream. Mechanically, TEVs-released circ-0034880 enhanced the activation of SPP1highCD206+ pro-tumor macrophages, reshaping the metastasis-supportive host stromal microenvironment and promoting overt metastasis. Importantly, our mechanistic findings led us to discover that the natural product Ginsenoside Rb1 impeded the activation of SPP1highCD206+ pro-tumor macrophages by reducing circ-0034880 biogenesis, thereby suppressing PMN formation and inhibiting CRLM. CONCLUSIONS: Circ-0034880-enriched TEVs facilitate strong interaction between primary tumor cells and SPP1highCD206+ pro-tumor macrophages, promoting PMN formation and CRLM. These findings suggest the potential of using Ginsenoside Rb1 as an alternative therapeutic agent to reshape PMN formation and prevent CRLM.

Astaxanthin alleviates fibromyalgia pain and depression via NLRP3 inflammasome inhibition.

Fibromyalgia is characterised by widespread chronic pain and is often accompanied by comorbidities such as sleep disorders, anxiety, and depression. Because it is often accompanied by many adverse symptoms and lack of effective treatment, it is important to search for the pathogenesis and treatment of fibromyalgia. Astaxanthin, a carotenoid pigment known for its anti-inflammatory and antioxidant properties, has demonstrated effective analgesic effects in neuropathic pain. However, its impact on fibromyalgia remains unclear. Therefore, in this study, we constructed a mouse model of fibromyalgia and investigated the effect of astaxanthin on chronic pain and associated symptoms through multiple intragastrical injections. We conducted behavioural assessments to detect pain and depression-like states in mice, recorded electroencephalograms to monitor sleep stages, examined c-Fos activation in the anterior cingulate cortex, measured activation of spinal glial cells, and assessed levels of inflammatory factors in the brain and spinal cord, including interleukin (IL)-1ß, IL-6, and tumour necrosis factor- α(TNF-α).Additionally, we analysed the expression levels of IL-6, IL-10, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Apoptosis-associated speck-like protein containing CARD, and Caspase-1 proteins. The findings revealed that astaxanthin significantly ameliorated mechanical and thermal pain in mice with fibromyalgia and mitigated sleep disorders and depressive-like symptoms induced by pain. A potential mechanism underlying these effects is the anti-inflammatory action of astaxanthin, likely mediated through the inhibition of the NLRP3 inflammasome, which could be one of the pathways through which astaxanthin alleviates fibromyalgia. In conclusion, our study suggests that astaxanthin holds promise as a potential analgesic medication for managing fibromyalgia and its associated symptoms.

Clinical outcomes of radioactive seed brachytherapy and microwave ablation in inoperable stage I non-small cell lung cancer.

This study assessed the efficacy and safety of radioactive iodine-125 seed ablation brachytherapy (RSABT) in comparison to microwave ablation therapy (MWAT) for treating inoperable stage I non-small cell lung cancer (NSCLC). We conducted a retrospective analysis of data from stage I NSCLC patients who underwent CT-guided RSABT or MWAT. The primary outcomes measured were progression-free survival (PFS), overall survival (OS), and the occurrence of adverse events. Of the patients included in the study, 71 underwent RSABT and 105 received MWAT. The median follow-up time for these groups was 47.4 months and 60 months, respectively. The PFS rates at 1-year, 3-year, and 5-year for the RSABT group were 87.3%, 72.6%, and 65.8%, while for the MWAT group, they were 89.5%, 69.3%, and 43.7%, respectively (P = 0.011). The OS rates at 1-year, 3-year, and 5-year for the RSABT group were 97.2%, 78.1%, and 66.1%, and for the MWAT group, they were 99%, 75.8%, and 55%, respectively (P = 0.112). Upon multivariate analysis, the treatment modality was identified as an independent predictor of PFS (P = 0.008). Additionally, both sex and T stage were found to be independent predictors of both PFS and OS (P < 0.05). Adverse events, such as pneumothorax, occurred in 50% of the MWAT group and 39% of the RSABT group (P = 0.313). The incidence of pleural effusion was 44% in the MWAT group compared to 14% in the RSABT group (P < 0.001). Needle bleeding was observed in 32% of the RSABT group and 5% of the MWAT group (P < 0.001). We conclude RSABT demonstrates promising efficacy and safety in the treatment of stage I NSCLC. However, further studies are essential to validate these preliminary findings.

Enhancing tylosin production by combinatorial overexpression of efflux, SAM biosynthesis, and regulatory genes in hyperproducing Streptomyces xinghaiensis strain.

Tylosin is a 16-membered macrolide antibiotic widely used in veterinary medicine to control infections caused by Gram-positive pathogens and mycoplasmas. To improve the fermentation titer of tylosin in the hyperproducing Streptomyces xinghaiensis strain TL01, we sequenced its whole genome and identified the biosynthetic gene cluster therein. Overexpression of the tylosin efflux gene tlrC, the cluster-situated S-adenosyl methionine (SAM) synthetase gene metKcs, the SAM biosynthetic genes adoKcs-metFcs, or the pathway-specific activator gene tylR enhanced tylosin production by 18%, 12%, 11%, and 11% in the respective engineered strains TLPH08-2, TLPH09, TLPH10, and TLPH12. Co-overexpression of metKcs and adoKcs-metFcs as two transcripts increased tylosin production by 22% in the resultant strain TLPH11 compared to that in TL01. Furthermore, combinational overexpression of tlrC, metKcs, adoKcs-metFcs, and tylR as four transcripts increased tylosin production by 23% (10.93g/L) in the resultant strain TLPH17 compared to that in TL01. However, a negligible additive effect was displayed upon combinational overexpression in TLPH17 as suggested by the limited increment of fermentation titer compared to that in TLPH08-2. Transcription analyses indicated that the expression of tlrC and three SAM biosynthetic genes in TLPH17 was considerably lower than that of TLPH08-2 and TLPH11. Based on this observation, the five genes were rearranged into one or two operons to coordinate their overexpression, yielding two engineered strains TLPH23 and TLPH24, and leading to further enhancement of tylosin production over TLPH17. In particular, the production of TLPH23 reached 11.35 g/L. These findings indicated that the combinatorial strategy is a promising approach for enhancing tylosin production in high-yielding industrial strains.

Rational Construction of a Novel Bioluminescent Substrate for Sensing the Tumor-Associated Hydrolase Notum.

Notum, one of the key serine hydrolases in mammals, hydrolyzes the palmitoleoyl moieties of many important proteins and modulates multiple signaling pathways including Wnt/ß-catenin signaling. Notum is tightly associated with multiple human diseases, but the reliable and practical tools for sensing Notum activities in complex biological systems are rarely reported. Herein, an efficient strategy was used to rationally construct a specific bioluminescent substrate for Notum. Following computer-aided molecular design and experimental verification, octanoyl luciferin (OL) was selected as the optimum substrate for human Notum, with excellent specificity, high detection sensitivity and high signal-to-noise ratio. Under physiological conditions, OL was readily hydrolyzed by Notum or Notum-containing biological specimens to release d-luciferin that could be easily detected by various fluorescence devices in the presence of luciferase. The applicability of OL for real-time sensing native Notum was examined in living cells, extracellular matrix, and tissue preparations. OL was also used for constructing a high-throughput assay for screening of Notum inhibitors, while a natural compound (bergapten) was newly identified as a potent Notum inhibitor. Collectively, this study devises a reliable and easy-to-use tool for sensing Notum activities in biological systems, which will strongly facilitate hNotum-associated fundamental studies, disease diagnosis, and drug discovery.

A water-soluble fluorescent probe for the determination of γ-glutamyltransferase activity and its application in tumor imaging.

γ-glutamyltransferase (GGT), an important tumor marker, is highly expressed in tumor tissues, and precise detection of its activity provides a vital indicator for the diagnosis and treatment. In this work, a "lighting-on" probe (TCF-GGT) was elaborated to detect endogenous GGT with high selectivity and sensitivity. Dicyanomethyldifuranyl (TCF-OH) was employed as the fluorescence reporter and short peptide glutathione (GSH) worked as the GGT-active trigger, the introduction of which prevented the initial proton transfer of TCF-OH contributing to a blank sensing background. A bright red fluorescence could be switched on upon GGT catalytic hydrolysis, avoiding the potential interference from background. There displayed an excellent water-solubility, and little organic solvent was required during the exploration, which otherwise avoided the potential damage to enzyme and organism. TCF-GGT has been proved to be workable at cellular and organism level with highly effective imaging and a short metabolic cycle, which is expected to offer an alternative solution or reference to the early diagnosis and treatment of tumor.

Stereotactic ablative brachytherapy with or without assistance of 3D-printing templates for inoperable locally recurrent or oligometastatic soft-tissue sarcoma: a multicenter real-world study.

The management of inoperable locally recurrent or oligometastatic soft-tissue sarcoma (STS) remains a clinical challenge. This study aimed to explore the long-term outcomes of stereotactic ablative brachytherapy (SABT) for these patients. Patients diagnosed with inoperable locally recurrent or oligometastatic STS from eight hospitals between 2006 and 2021 underwent iodine-125 (I-125) seed SABT, either with or without the assistance of three-dimensional (3D)-printing templates. The analysis concentrated on several key parameters, including objective response rate (ORR), disease control rate (DCR), local control time (LCT), overall survival (OS), adverse events (AEs), pain relief rate, and performance improvement rate. The ORR and DCR reached 78.3% and 95.0%, respectively. The results of multivariate logistic regression analysis indicated that a smaller tumor volume and a higher treatment dose were significantly associated with complete response (P < 0.001; P=0.036). The 1-, 3-, and 5-year LCT rates were 73.2%, 40.6%, and 37.9%, respectively. The 1-, 3-, and 5-year OS rates reached 83.1%, 50.5%, and 36.1%, respectively. Multivariate analysis revealed that a higher dose, a smaller tumor volume, and utilization of 3D-printing templates were significantly positive prognostic factors of LCT (P=0.006; P=0.007; P=0.034). Moreover, the tumor locations of trunk wall and extremities and lower tumor grade (G1/2) were significantly positive prognostic factors of survival (P=0.008; P=0.002). Pain relief rate was 88.0%, and the performance improvement rate was 46.7%. The AEs were predominantly of grade ≤ 2 and were well-tolerated. SABT seems to be an efficacious and safe alternative therapy for inoperable locally recurrent or oligometastatic STS.

Comparison of Electrocardiogram and QT Interval between Viral Hepatitis Cirrhosis and Alcoholic Cirrhosis.

Objective: This study aims to compare the electrocardiogram (ECG) abnormalities and QT interval prolongation in 2,886 patients with viral hepatitis cirrhosis and 643 patients with alcoholic cirrhosis in order to understand the characteristics of ECG in patients with cirrhosis and provide information and evidence for clinical diagnosis and treatment. Methods: The ECG data of patients with viral hepatitis cirrhosis and alcoholic liver cirrhosis in the outpatients and inpatients of our hospital from August 2012 to July 2018 were reviewed. The ECG data were recorded, and the ECG report was issued by ECG experts to analyze the abnormal ECG and QT interval of patients in these two groups. Results: In the present study, 1,132 (39.22%) of the 2,886 patients with viral liver cirrhosis and 322 (50.08%) of the 643 patients with alcoholic liver cirrhosis had an abnormal ECG (P < 0.001). Among patients with QT prolongation, 388 patients had viral liver cirrhosis (13.44%) and 170 patients had alcoholic liver cirrhosis (26.44%, P < 0.001). Conclusion: The hemodynamics and electrophysiology of the myocardium are often changed in patients with cirrhosis, and ECG changes may also occur. QT interval prolongation is one of the most common electrophysiological abnormalities in patients with cirrhosis, and QT prolongation is more common in patients with alcoholic liver cirrhosis. Prolonged QT is associated with severe arrhythmia and sudden death and can warn of malignant arrhythmia and sudden death. Therefore, the routine detection of abnormal ECG and QT interval in patients with liver cirrhosis is of significant importance for preventing malignant events.

Cholesterol Metabolic Markers for Differential Evaluation of Patients with Hyperlipidemia and Familial Hypercholesterolemia.

The cholesterol metabolism in humans can be indirectly reflected by measuring cholesterol metabolism marker levels. We aimed to investigate the association of cholesterol homeostasis markers on standard lipid profiling components in familial hypercholesteremia and hyperlipidemia patients. A total of 69 hyperlipidemia patients, 25 familial hypercholesteremia (FHC) patients, and 64 healthy controls were enrolled in this study. We performed routine testing of blood lipid water. Gas chromatography was used to determine the changes in the concentration of cholesterol synthesis (squalene, desmosterol, and lathosterol) and absorption markers (campesterol, sitosterol, and stigmasterol) in the blood. Baseline hyperlipidemia patients displayed significantly higher total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels in comparison to the control group, which was reflected in the increased levels of squalene, desmosterol, campesterol, and sitosterol observed (P < 0.05) in the hyperlipidemia patients. The desmosterol, lathosterol, campesterol, stigmasterol, and sitosterol were statistically different in the FHC group than the hyperlipidemic group (P < 0.05). The proportions of squalene/cholesterol, lathosterol/cholesterol, stigmasterol/cholesterol, and sitosterol/cholesterol in the FHC group were lower than those in the hyperlipidemic group; only desmosterol/cholesterol was higher than that in the hyperlipidemic group. Correlation studies between lipid metabolic factors showed that the proportion of moderate and strong correlations was much higher in the FHC group than in the other two groups (76.92% vs. 32.50% and 31.25%). Logistic regression analysis showed that the concentrations of glucose, LDL-C, lactosterol, and sitosterol were all independent risk factors for developing hyperlipidemia. This result was further confirmed by the ROC curve. These results indicated that the study of cholesterol synthesis and decomposition markers can serve as a reference index for related diseases caused by changes in its concentration.

Clinical Outcome of CT-Guided Iodine-125 Radioactive Seed Implantation for Intrahepatic Recurrent Hepatocellular Carcinoma: A Retrospective, Multicenter Study.

The efficacy and safety of CT-Guided Iodine-125 Radioactive Seed Implantation (RSI) for the treatment of intrahepatic recurrent hepatocellular carcinoma (rHCC) were analyzed in this multicenter retrospective study. We reviewed the medical records of patients with rHCC treated with I-125 seed implantation at four different hospitals in China from December 2011 and January 2021. The local progression-free survival (LPFS),liver PFS, and overall survival (OS) were calculated, and the short-term efficacy and treatment-related toxicities were evaluated. A total of 82 patients were enrolled; the median follow-up time was 46 months (range, 3-80 months). The 1-, 3- and 5-year LPFS rates were 63.8%, 27.1%, and 7.9%, respectively, and the corresponding OS rates were 74.8%, 32.9%, and 12.6%, respectively. Univariate analysis showed that factors influencing LPFS included the maximum lesion diameter, Barcelona Clinic Liver Cancer (BCLC) stage, interval between treatment and recurrence, and D90. Multivariate analyses revealed that the BCLC stage, interval between treatment and recurrence, and D90 were independent factors influencing LPFS, whereas BCLC stage, D90, and short-term efficacy were independent factors influencing OS. In summary, I-125 seed implantation is a safe and effective treatment for rHCC. The BCLC stage, interval, and D90 were found to influence the local control. A larger, prospective study is required to confirm the dose-response curve for Iodine-125 RSI of rHCC.

Safety and efficacy of stereotactic ablative brachytherapy as a salvage therapy for recurrent chest wall cancer: A retrospective, multicenter study.

Purpose: To evaluate the safety and efficacy of stereotactic ablative brachytherapy (SABT) as a salvage therapy for patients with recurrent chest wall cancer (rCWC) who have previously received external beam radiotherapy (EBRT) or surgery. Materials and methods: Between November 2013 and October 2020, a total of 130 patients (including 75 men with a median age of 63 years) with rCWC treated with SABT were enrolled in this multicenter retrospective study. There were 97 cases of non-small-cell lung carcinoma, 24 cases of breast cancer, and 9 cases of thymic cancer. Of the patients included, 102 patients previously received surgery and 58 patients received EBRT, with systemic treatment progressing after recurrence. None of them were suitable or refused to undergo salvage EBRT or surgery again. Results: During the 22 (4-70)-month median patient follow-up, 59 patients died. The local control (LC) rates at 6, 12, 24, and 36 months were 88.3%, 74.3%, 50.4%, and 36.7%, respectively. The 1-, 2- and 3-year survival rates were 85%, 56%, and 42%, respectively. The median overall survival was 26 months (95% CI, 18.9-33.1 months). The pain relief rate was 81%, and the median to remission time was 10 days. Univariate and multivariate analyses showed that independent prognostic factors for LC included tumor size and postoperative D90. On the other hand, independent prognostic factors for survival include the Karnofsky performance status (KPS) score, tumor size, and D90 19 patients (14.6%) developed grade I/II skin reaction complications. No grade III or severer complications occurred. Conclusion: SABT is safe and effective as a salvage therapy for rCWC following EBRT/surgery. For patients with a KPS score greater than 80, prescribed dose greater than 130 Gy, and tumor size less than 4 cm may bring better results.

A Dual-Control Strategy by Phosphate Ions and Local Microviscosity for Tracking Adenosine Triphosphate Metabolism in Mitochondria and Cellular Activity Dynamically.

Adenosine triphosphate (ATP) acts as the main energy source for growth and development in organisms, and the disorder reflects the mitochondrial damage to a large extent. Therefore, an efficient tool for the evaluation of the ATP metabolic level is important to track mitochondrial health, providing an additional perspective for an in-depth long-term study on living activities. Herein, a twisted intramolecular charge transfer (TICT) framework is utilized to build up a sensitive receptor, Mito-VP, with a negligible background to target mitochondrial ATP metabolism by monitoring the phosphate ion (Pi) level upon ATP hydrolysis under the overall consideration of the structural and functional features of mitochondria. The responsive fluorescence could be lighted on under the dual control of Pi and local microviscosity, and the two steps of ATP hydrolysis could be captured through fluorescence. In addition to the well-behaved mitochondrial targeting, the energy metabolism at cellular and organism levels has been clarified via mitosis and zebrafish development, respectively.

Multi-Resolution Image Segmentation Based on a Cascaded U-ADenseNet for the Liver and Tumors.

The liver is an irreplaceable organ in the human body, maintaining life activities and metabolism. Malignant tumors of the liver have a high mortality rate at present. Computer-aided segmentation of the liver and tumors has significant effects on clinical diagnosis and treatment. There are still many challenges in the segmentation of the liver and liver tumors simultaneously, such as, on the one hand, that convolutional kernels with fixed geometric structures do not match complex, irregularly shaped targets; on the other, pooling during convolution results in a loss of spatial contextual information of images. In this work, we designed a cascaded U-ADenseNet with coarse-to-fine processing for addressing the above issues of fully automatic segmentation. This work contributes multi-resolution input images and multi-layered channel attention combined with atrous spatial pyramid pooling densely connected in the fine segmentation. The proposed model was evaluated by a public dataset of the Liver Tumor Segmentation Challenge (LiTS). Our approach attained competitive liver and tumor segmentation scores that exceeded other methods across a wide range of metrics.

Clinical Outcome of CT-Guided Stereotactic Ablative Brachytherapy for Unresectable Early Non-Small Cell Lung Cancer: A Retrospective, Multicenter Study.

OBJECTIVE: To analyze the efficacy and safety of low dose rate stereotactic ablative brachytherapy (L-SABT) for treatment of unresectable early-stage non-small cell lung cancer (NSCLC). METHODS: Data of patients with early-stage NSCLC who received CT-guided L-SABT (radioactive I-125 seeds implantation) at eight different centers from December 2010 to August 2020 were retrospectively analyzed. Treatment efficacy and complications were evaluated. RESULTS: A total of 99 patients were included in this study. Median follow-up duration was 46.3 months (6.1-119.3 months). The 1-year, 3-year, and 5-year local control rates were 89.1%, 77.5%, and 75.7%, respectively. The 1-year, 3-year, and 5-year overall survival rates were 96.7%, 70.1%, and 54.4%, respectively. Treatment failure occurred in 38.4% of patients. Local/regional recurrence, distant metastasis, and recurrence combined with metastasis accounted for 15.1%, 12.1%, and 11.1%, respectively. Pneumothorax occurred in 47 patients (47.5%) with 19 cases (19.2%) needing closed drainage. The only radiation-related adverse reaction was two cases of grade 2 radiation pneumonia. KPS 80-100, T1, the lesion was located in the left lobe, GTV D90 ≥150 Gy and the distance between the lesion and chest wall was < 1 cm, were associated with better local control (all P < 0.05); on multivariate analysis KPS, GTV D90, and the distance between the lesion and chest wall were independent prognostic factors for local control (all P < 0.05). KPS 80-100, T1, GTV D90 ≥150 Gy, and the distance between the lesion and chest wall was < 1 cm were also associated with better survival (all P < 0.05); on multivariate analysis KPS, T stage, and GTV D90 were independent prognostic factors for survival (all P < 0.05). The incidence of pneumothorax in patients with lesions <1 cm and ≥1cm from the chest wall was 33.3% and 56.7%, respectively, and the differences were statistically significant (P = 0.026). CONCLUSION: L-SABT showed acceptable efficacy in the treatment of unresectable early-stage NSCLC. But the incidence of pneumothorax is high. For patients with T1 stage and lesions <1 cm from the chest wall, it may have better efficacy. Prescription dose greater than 150 Gy may bring better results.

Sarcopenia associated with 90-day readmission and overall survival after abdominal trauma.

BACKGROUND AND OBJECTIVES: It is widely recognized that sarcopenia increases postoperative complications in trauma patients. However, the effects on prognosis remain unclear. This study aimed to evaluate the impact of sarcopenia on 90-day readmission and overall survival (OS) in abdominal trauma patients. METHODS AND STUDY DESIGN: 485 consecutive patients who underwent abdominal surgery after trauma in our institution were enrolled. Sarcopenia was diagnosed with low muscle mass and low muscle strength-handgrip. Multivariate logistic regression analysis was performed to identify factors that contributed to 90-day readmission and OS. Cox logistic regression analysis was used to assess the relationship between sarcopenia and OS. RESULTS: Sarcopenia was present in 120 of 485 patients (24.7%) with abdominal trauma within one week after admission based on the diagnostic cut-off values (40.9 cm2/m2 for men and 36.8 cm2/m2 for women). 90-day readmission was significantly higher in the sarcopenia group (p=0.019), and OS lower in the sarcopenia group (p=0.025). Sarcopenia was an independent predictor of 90-day readmission [odds ratio (OR): 5.34, 95% confidence interval (CI): 2.52-11.3]. CONCLUSIONS: Sarcopenia was associated with high 90-day readmission and low OS in abdominal trauma patients, and it was an independent risk factor for 90-day readmission.

Effect of procyanidins on lipid metabolism and inflammation in rats exposed to alcohol and iron.

BACKGROUND: Lifestyle involving uncontrolled alcohol consumption coupled regularly with red meat and other iron sources has detrimental effects on the liver, which in the long term, results in Alcoholic Liver Disease (ALD). Procyanidin has lately garnered increasing attention and has become the focus of research owing to its antioxidant properties. This study explores the anti-inflammatory effects of procyanidins, in preventing ALD, by analyzing the biological activities of the compound on liver injury caused by excessive alcohol and iron. METHOD: Male SPF Wistar rats were placed in 4 groups; the control Group A (basic diet); the model Group B (excess alcohol 8-12 mL/kg/d and iron 1000 mg/kg diet); the low dose procyanidin Group C (model group diet plus 60 mg/kg/d of procyanidin); and the high dose procyanidin Group D (model group diet plus 120 mg/kg/d of procyanidin). Serum biochemical markers for liver damage were measured spectrophotometrically. The NFκB and IκB mRNA expression levels were determined using RT-PCR; the NFκB p65 and IκB protein expression levels were assessed via western blotting, while ELISA was used to detect serum inflammatory factors. RESULTS: The pathological score of the model Group B, low and high dose procyanidin Groups C and D were 6.58 ± 0.90,4.69 ± 0.70 and 2.00 ± 0.73, respectively (P < 0.05). The results showed that high alcohol and iron contents in the model group led to significant damage of liver structure, increased low-density lipoproteins (LDLs), steatosis, and increased levels of inflammatory cytokines. High amounts of procyanidins led to the preservation of the liver structure, production of high-density lipoproteins, and reduction in serum inflammatory cytokines while also significantly decreasing the expression levels of NFκB p65. CONCLUSION: The results prove that procyanidins have hepatoprotective potential and could be effective in reversing histopathology, possibly by alleviating inflammation and improving lipid metabolism.

Antibacterial Fusion Protein BPI21/LL-37 Modification Enhances the Therapeutic Efficacy of hUC-MSCs in Sepsis.

Sepsis, which is characterized by multiple organ dysfunctions as a result of an unbalanced host-inflammatory response to pathogens, is potentially a life-threatening condition and a major cause of death in the intensive care units (ICUs). However, effective treatment or intervention to prevent sepsis-associated lethality is still lacking. Human umbilical cord mesenchymal stem cell (hUC-MSC) transplantation has been shown to have potent immunomodulatory properties and improve tissue repair yet lacks direct antibacterial and endotoxin clearance activities. In this study, we engineered hUC-MSCs to express a broad-spectrum antibacterial fusion peptide containing BPI21 and LL-37 (named BPI21/LL-37) and confirmed that the BPI21/LL-37 modification did not affect the stemness and immunoregulatory capacities of hUC-MSCs but remarkably, enhanced its antibacterial and toxin-neutralizing activities in vitro. Furthermore, we showed that administration of BPI21/LL-37-engineered hUC-MSCs significantly reduces serum levels of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and IL-6, whereas increases that of IL-10 in cecal ligation and puncture (CLP)-induced sepsis mouse model. Administration of BPI21/LL-37-engineered hUC-MSCs significantly reduced systemic endotoxin (lipopolysaccharide [LPS]) levels and organ bacterial load, ameliorated damage to multiple organs, and improved survival. Taken together, our study demonstrates that BPI21/LL-37-engineered hUC-MSCs might offer a novel therapeutic strategy to prevent or treat sepsis via enhanced antimicrobial and anti-inflammatory properties to preserve organ functions better.

Enzyme-assisted Aqueous Extraction of Oil from Rice Germ and its Physicochemical Properties and Antioxidant Activity.

Enzyme-assisted aqueous extraction of rice germ oil (RGO) was performed in this study. The physicochemical properties, fatty acid composition, bioactive substances and antioxidant activity of RGO were analyzed. An enzyme composed of alcalase and cellulase (1:1, w/w) was found to be the most effective in the extraction yield of oil. The optimal oil yield of 22.27% was achieved under the conditions of an enzyme concentration of 2% (w/w), incubation time of 5 h, incubation temperature of 50°C, water to seed ratio of 5:1, and pH 6.0. The predominant fatty acids of RGO were oleic acid (39.60%), linoleic acid (34.20%) and palmitic acid (20.10%). The total saturated fatty acid (SFA), monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) composition of RGO were 22.50%, 39.60% and 36.00%, respectively. RGO yielded a high content of γ-oryzanol (530 mg/100 g oil), tocotrienol (62.96 mg/100 g oil), tocopherol (23.24 mg/100 g oil) and a significant amount of phytosterol (372.14 mg/100 g oil). It exhibited notable antioxidant activities with IC50 values of 32.37 and 41.13 mg/mL, according to the DPPH radical scavenging assay and ß-carotene/linoleic acid bleaching test, respectively.