The role of uterus mitochondrial function in high-fat diet-related adverse pregnancy outcomes and protection by resveratrol.

This study elucidates the mechanism of obesity-related adverse pregnancy outcomes and further investigates the effect of resveratrol on reproductive performance in a short- or long-term HFD-induced obese mouse model. Results show that maternal weight had a significant positive correlation with litter mortality in mice. A long-term HFD increased body weight and litter mortality with decreased expression of uterine cytochrome oxidase 4 (COX4), which was recovered by resveratrol in mice. Moreover, HFD decreased the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factors-1 (Nrf-1), and phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase (p-AMPK) and increased the expression of phosphorylated extracellular regulated protein kinases (p-ERK) in the uterus. Resveratrol, a polyphenol that can directly bind to the ERK protein, suppressed the phosphorylation of ERK, increased the expression of p-AMPK, PGC-1α and Nrf-1, and decreased litter mortality in mice.

Development and validation of serological dynamic risk score to predict outcome in gastric cancer with adjuvant chemotherapy: a multicentre, longitudinal, cohort study.

Background: Baseline serological biomarkers have the potential to predict the benefits of adjuvant chemotherapy in patients with gastric cancer. However, the fluctuating nature of postoperative recurrence risk makes precise treatment challenging. We aimed to develop a risk score in real-time predicting outcomes for postoperative GC patients using blood chemistry tests. Materials and methods: This was a retrospective, multicentre, longitudinal cohort study from three cancer centres in China, with a total of 2737 GC patients in the pTNM stage Ib to III. Among them, 1651 patients with at least two serological records were assigned to the training cohort. Model validation was carried out using separate testing data with area under curve (AUC). The least absolute shrinkage and selection operator (LASSO) and random forest-recursive feature elimination (RF-RFE) algorithm were used to select the parameters. Results: The Cox regression model derived six risk factors to construct a composite score (low-risk: 0-2 score; high risk: 3-6 score), including CEA, CA125, CA199, haemoglobin, albumin, and neutrophil to lymphocyte ratio. The risk score accurately predicted mortality in 1000-time bootstrap (AUROCs:0.658; 95% CI: 0.645, 0.670), with the highest AUROC (0.767; 95% CI: 0.743, 0.791) after 1 year since the gastrectomy. In validation dataset, the risk score had an AUROC of 0.586 (95% CI 0.544, 0.628). Furthermore, patients with high risk at 1 month derived significant clinical benefits from adjuvant chemotherapy (P for interaction <0.0001). Compared with the low-low-low risk group, the low-low-high risk group of the long-term state chain (risk state at baseline, 6 months, 1 year) had the worse OS (HR, 6.91; 95%CI: 4.27, 11.19) and DFS (HR, 7.27; 95%CI: 4.55, 11.63). Conclusion: The dynamic risk score is an accurate and user-friendly serological risk assessment tool for predicting outcomes and assisting clinical decisions after gastrectomy.

Acupuncture combined with mifepristone improves sex hormones and inflammatory factors in patients with uterine fibroids.

OBJECTIVE: To analyze the therapeutic effect of acupuncture combined with mifepristone on uterine fibroids and its influence on sex hormones and inflammatory factors. METHODS: Data of 102 patients with uterine fibroids admitted to Shanxi Provincial Hospital of Chinese Medicine from January 2019 to January 2022 were retrospectively analyzed. Among them, there were 50 patients treated with mifepristone alone (control group) and 52 patients undergoing combined treatment of acupuncture and mifepristone (observation group). After 2 months of continuous treatment, the therapeutic efficacy, volume of uterine fibroids and uterus, levels of inflammatory factors (C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α)), as well as levels of estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), along with hemodynamic levels and incidence of adverse reactions were recorded and compared between the two groups. Logistic analysis was employed to identify the independent risk factors for the recurrence of uterine fibroids in patients. RESULTS: Compared with the control group, the observation group was identified with significantly higher overall response rate (P < 0.05). The uterine fibroid volume and uterine volume significantly improved in both groups after treatment, and the improvements were more prominent in the observation group than in the control group (P < 0.05). After treatment, the serum CRP and TNF-α were both evidently decreased in the two groups, while levels of E2, FSH, LH and peak blood flow velocity were significantly ameliorated, and the improvements in the observation group were more significant than those in the control group (P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P > 0.05). Alcohol intake and treatment regime were independent risk factors for the recurrence of uterine fibroids in patients. CONCLUSION: Combining acupuncture with mifepristone can significantly improve uterine fibroids, estrogen and progesterone levels, as well as reduce inflammation, with a high level of safety, making it a promising treatment for clinical use.

Study on bioactive compounds of microalgae as antioxidants in a bibliometric analysis and visualization perspective.

Natural antioxidants are more attractive than synthetic chemical oxidants because of their non-toxic and non-harmful properties. Microalgal bioactive components such as carotenoids, polysaccharides, and phenolic compounds are gaining popularity as very effective and long-lasting natural antioxidants. Few articles currently exist that analyze microalgae from a bibliometric and visualization point of view. This study used a bibliometric method based on the Web of Science Core Collection database to analyze antioxidant research on bioactive compounds in microalgae from 1996 to 2022. According to cluster analysis, the most studied areas are the effectiveness, the antioxidant mechanism, and use of bioactive substances in microalgae, such as carotene, astaxanthin, and tocopherols, in the fields of food, cosmetics, and medicine. Using keyword co-occurrence and keyword mutation analysis, future trends are predicted to improve extraction rates and stability by altering the environment of microalgae cultures or mixing extracts with chemicals such as nanoparticles for commercial and industrial applications. These findings can help researchers identify trends and resources to build impactful investigations and expand scientific frontiers.

Combination of switchable hydrophilic solvent liquid-liquid microextraction with QuEChERS for trace determination of triazole fungicide pesticides by GC-MS.

This work first proposed a novel green and efficient method based on Quick, Easy, Cheap, Efficient, Rugged, and Safe pretreatment (QuEChERS) combined with switchable hydrophilic solvent homogeneous liquid-liquid microextraction (SHS-HLLME) for trace determination of triazole fungicides (TFs) in agricultural products such as vegetables and fruits by gas chromatography-mass spectrometry (GC-MS). N,N-Dimethyl benzylamine was used for the synthesis of SHS. Box-Behnken design was applied for the optimization of extraction conditions and a mathematical model was obtained. Ultimately, 0.50 mL SHS, 1.0 mL 10 mol L-1 sodium hydroxide, and 45 s ultrasonic time were determined as optimal conditions for the SHS-HLLME method. The limit of detection and limit of quantification determined using the optimal method (SHS-HLLME/GC-MS) were 0.13-0.27 ng mL-1 and 0.43-0.90 ng mL-1, respectively. In addition, the SHS-HLLME method under optimal conditions was combined with the traditional QuEChERS method to realize the advancement of the SHS-HLLME method from simple to complex matrix analysis, and the QuEChERS-SHS-HLLME method was successfully applied to the analysis of TFs in cucumbers, tomatoes, watermelon and grapes in agricultural products. Matrix-matched calibration standards were used to improve the accuracy of TFs in spiked cucumber samples to obtain recovery results close to 100%. It was shown that the new method is green and rapid, enabling fast and inexpensive sample pretreatment with up to 100-fold enrichment factor and low detection limit compared with the original QuEChERS method.

A male germ-cell-specific ribosome controls male fertility.

Ribosomes are highly sophisticated translation machines that have been demonstrated to be heterogeneous in the regulation of protein synthesis1,2. Male germ cell development involves complex translational regulation during sperm formation3. However, it remains unclear whether translation during sperm formation is performed by a specific ribosome. Here we report a ribosome with a specialized nascent polypeptide exit tunnel, RibosomeST, that is assembled with the male germ-cell-specific protein RPL39L, the paralogue of core ribosome (RibosomeCore) protein RPL39. Deletion of RibosomeST in mice causes defective sperm formation, resulting in substantially reduced fertility. Our comparison of single-particle cryo-electron microscopy structures of ribosomes from mouse kidneys and testes indicates that RibosomeST features a ribosomal polypeptide exit tunnel of distinct size and charge states compared with RibosomeCore. RibosomeST predominantly cotranslationally regulates the folding of a subset of male germ-cell-specific proteins that are essential for the formation of sperm. Moreover, we found that specialized functions of RibosomeST were not replaceable by RibosomeCore. Taken together, identification of this sperm-specific ribosome should greatly expand our understanding of ribosome function and tissue-specific regulation of protein expression pattern in mammals.

Comparative study on sex hormone secretion in peripheral blood of women with common hematological tumors before and after chemotherapy.

This study aimed to explore the secretion of sex hormones in peripheral blood of women with common hematological tumors before and after chemotherapy. From January 2019 to April 2021, 100 female patients with common hematological tumors in our hospital were selected as the observation group, and 50 healthy women in our hospital during the same period were selected as the control group. The serum levels of follicle-stimulating hormone (FSH), estradiol (E2) and luteinizing hormone (LH) were detected and compared between the observation group and the control group before chemotherapy, patients with different disease types in the observation group, postmenopausal patients in the observation group, and postmenopausal patients in the observation group. Results showed that the serum FSH, E2 and LH levels of the observation group had no significant changes before chemotherapy (P > 0.05). Compared with before chemotherapy, the levels of serum FSH and LH in patients with different disease types in the observation group after chemotherapy were significantly higher, while E2 was significantly lower (P < 0.05), and the serum FSH, E2 and LH levels of postmenopausal patients in the observation group did not change significantly after chemotherapy (P > 0.05). The levels of FSH and LH in the observation group after chemotherapy were significantly higher, and E2 was significantly lower (P < 0.05). In general, the levels of sex hormone secretion in peripheral blood of women with common hematological tumors before and after chemotherapy can change significantly, especially in postmenopausal patients, but not in postmenopausal patients, which has a certain reference value for clinical practice.

Emergency Removal of Ingested Foreign Bodies in 586 Adults at a Single Hospital in China According to the European Society of Gastrointestinal Endoscopy (ESGE) Recommendations: A 10-Year Retrospective Study.

BACKGROUND The 2016 European Society of Gastrointestinal Endoscopy (ESGE) guidelines recommend that ingested foreign bodies in the upper gastrointestinal (GI) tract are removed as an emergency within 6 hours, with an endoscopic approach that is individualized according to the type of foreign body identified. This retrospective study evaluated the 10-year experience of a single hospital in China performing emergency removal of ingested foreign bodies in 586 adults. MATERIAL AND METHODS Between 2011 and 2020, medical records of 642 adults with a diagnosis of foreign bodies ingestion were retrospectively screened. The timing of endoscopic intervention was classified according to ESGE recommendations. Uni- and multivariate analyses were performed. RESULTS We included 586 patients. The median (range) diameter of foreign bodies was 2.5 (1-24) cm: for sharp ones it was 2.5 (1.5-4.0) cm and for long ones it was 16.9 (10-24) cm. The most common site of foreign body lodgment was the esophagus (n=481; 82.1%); 45.6% (n=252) received emergent removal within 6 hours, while 32.2% (n=178) underwent urgent removal within 24 hours. There were 583 (99.5%) foreign bodies removed successfully and the complication rate was 17.9%. Major complications occurred in 45 patients (7.7%). Female sex and non-emergent endoscopy after 6 hours were significantly associated with a higher overall complications rate. For major complications, older age, time interval >24 hours, and sharper objects were associated with major complications. CONCLUSIONS The findings from this retrospective study support the ESGE statement that endoscopic removal of ingested foreign bodies from the upper GI tract within 6 hours reduces complication rates for adults in the emergency setting.

Risk stratification in patients with upper gastrointestinal submucosal tumors undergoing submucosal tunnel endoscopic resection.

Background: A substantial heterogeneity exists in patients with upper gastrointestinal submucosal tumors (SMTs). This study aimed to identify predictors of long procedure time (≥60 min), occurrence of procedure-related complications, and long hospital stay (≥6 days) in patients with SMTs undergoing submucosal tunnel endoscopic resection (STER) and stratify risk based on the predictors. Methods: Sixty-six consecutive patients with upper gastrointestinal SMTs undergoing STER between January 2013 and December 2018 were retrospectively included. Binary logistic regression models were developed to identify predictors of outcomes. Receiver operating characteristic (ROC) curves were constructed to evaluate the discrimination of tumor size. Results: Complete resection and en bloc resection of tumor were achieved in 66 (100%) and 64 patients (97%), respectively. Twenty-seven patients (41%) had a long procedure time, 10 (15%) developed STER-related complications, and 17 (26%) had a long hospital stay. On multivariable analysis, tumor size was an independent predictor of long procedure time (OR 1.37, 95% CI 1.13-1.67; p = 0.001), occurrence of complications (OR 1.06, 95% CI 1.01-1.10; p = 0.012), and long hospital stay (OR 1.05, 95% CI 1.01-1.09; p = 0.035). ROC curves identified a tumor of size 25 mm as the best cutoff; those who had a tumor above this value had a 76-fold risk of long procedure time, 8.56-fold risk of occurrence of complications, and 6.35-fold risk of long hospital stay. Conclusion: Patients with a tumor size ≥25 mm had longer procedure time, higher risk of STER-related complications, and longer hospital stay; therefore, they should be classified as a high-risk group.

Application and practice of trimodal prehabilitation model in preoperative management of patients with lung cancer undergoing video-assisted thoracoscopic surgery.

Lung cancer is one of the malignant tumors with high mortality worldwide. To date, the most effective treatment of non-small cell lung cancer (NSCLC) is still surgical resection. Video-assisted thoracoscopic surgery has become the main surgical approach. Tumor patients are the high-risk perioperative population. At present, how to optimize perioperative management measures to improve the patient's body function and promote the rehabilitation after video-assisted thoracoscopic surgery is a hot research topic for medical staff. In this study, 148 patients with lung cancer were selected as the research object, to analyze and discuss the application value of trimodal prehabilitation model in preoperative management of patients with lung cancer undergoing video-assisted thoracoscopic surgery.

68Ga-Labeled GX1 Dimer: A Novel Probe for PET/Cerenkov Imaging Targeting Gastric Cancer.

PURPOSE: To synthesize the dimer of GX1 and identify whether its affinity and targeting are better than those of GX1. To prepare 68Ga-DOTA-KEK-(GX1)2 and to apply it to PET and Cerenkov imaging of gastric cancer. METHODS: 68Ga-DOTA-KEK-(GX1)2 was prepared, and the labeling yield and stability were determined. Its specificity and affinity were verified using an in vitro cell binding assay and competitive inhibition test, cell immunofluorescence, and cell uptake and efflux study. Its tumor-targeting ability was determined by nano PET/CT and Cerenkov imaging, standardized uptake value (SUV), signal-to-background ratio (SBR) quantification, and a biodistribution study in tumor-bearing nude mice. RESULTS: 68Ga-DOTA-KEK-(GX1)2 was successfully prepared, and the labeling yield was more than 97%. It existed stably for 90 min in serum. The binding of 68Ga-DOTA-KEK-(GX1)2 to cocultured HUVECs (Co-HUVECs) was higher than that to human umbilical vein endothelial cells (HUVECs), BGC823 cells, and GES cells. It was also higher than that of 68Ga-DOTA-GX1, indicating that the dimer did improve the specificity and affinity of GX1. The binding of KEK-(GX1)2 to Co-HUVECs was significantly higher than that of GX1. Additionally, the uptake of 68Ga-DOTA-KEK-(GX1)2 by Co-HUVECs was higher than that of 68Ga-DOTA-GX1 and reached a maximum at 60 min. Nano PET/CT and Cerenkov imaging showed that the tumor imaging of the nude mice injected with 68Ga-DOTA-KEK-(GX1)2 was clear, and the SUV and SBR value of the tumor sites were significantly higher than those of the nude mice injected with 68Ga-DOTA-GX1, indicating that the probe had better targeting in vivo. Finally, the biodistribution showed quantitatively that when organs such as the kidney and liver metabolized rapidly, the radioactivity of the tumor site of the nude mice injected with 68Ga-DOTA-KEK-(GX1)2 decreased relatively slowly. At the same time, the percentage of injected dose per gram (%ID/g) of the tumor site was higher than that of other normal organs except the liver and kidney at 60 min, which indicated that the tumor had good absorption of the probe. CONCLUSION: GX1 was modified successfully, and the in vivo and in vitro properties of the GX1 dimer were significantly better than those of GX1. The imaging probe, 68Ga-DOTA-KEK-(GX1)2, was successfully prepared, which provides a candidate probe for PET and Cerenkov diagnosis of gastric cancer.

Evaluation of acupuncture treatments of postpartum female pelvic floor dysfunction by four-dimensional transperineal pelvic floor ultrasound.

INTRODUCTION: In the present investigation, a systematic evaluation of the clinical treatment performance of diagnosed with pelvic floor dysfunction is explored. By comparing the 4Dtransperineal pelvic floor ultrasound images with the acupuncture treatment performance of the patients, an evaluation system with various parameters is established to provide critical information to guide the clinical treatment fpostpartum female pelvic floor dysfunction (FPFD). METHODS: Eighty patients diagnosed with FPFD are divided into 2 groups. After the designated treatment to the patients, they are carefully examined using transperineal pelvic floor ultrasound. The shape and activity of bladder neck, cervix and rectum anal canal under resting, anal sphincter and Valsalva movements are observed and recorded. The morphology and continuous shape of levator ani muscle in different states after 4D image reconstruction are obtained. RESULTS: After the acupuncture treatment, the bladder neck descent is decreased by 3.8 cm and the anal levator muscle area is decreased by 3.4 cm2 comparing with the control group. The anal levator muscle hole diameter is decreased by 0.3 cm, while the anterior and posterior diameter is reduced by 0.5 cm. Reduced possibility of cystocele and uterine prolapse is demonstrated by X2 test. These changes upon acupuncture therapy are in line with the improved conditions of the patients, indicating these parameters can help evaluate the therapy performance. CONCLUSION: 4D pelvic floor ultrasound imaging provides objective and quantified information for the clinical diagnosis and treatment of FPFD and the assessment of therapy efficacy, making it a promising novel method in practical applications.

Non-invasive high-frequency oscillatory ventilation in preterm infants after extubation: a randomized, controlled trial.

OBJECTIVE: To investigate the effectiveness and safety of non-invasive high-frequency oscillatory ventilation (NHFOV) in post-extubation preterm infants. METHODS: This was a randomized, controlled trial. A total of 149 preterm infants aged between 25 to 34 weeks' gestational age with a birth weight of <1500 g who required invasive mechanical ventilation on admission were included. After extubation, they were randomized to the NHFOV group (n = 47), nasal intermittent positive pressure ventilation (NIPPV) group (n = 51), or nasal continuous positive airway pressure (NCPAP) group (n = 51). We compared the effectiveness and safety among these three groups. RESULTS: A total of 139 preterm infants finally completed the study. The reintubation rate was significantly lower in the NHFOV group than in the other groups. The duration of non-invasive ventilation and the length of hospital stay in the NHFOV and NIPPV groups were significantly shorter than those in the NCPAP group. The incidence of bronchopulmonary dysplasia in the NHFOV and NIPPV groups was significantly lower than that in the NCPAP group. The NHFOV group had significantly less nasal injury than the NCPAP group. CONCLUSION: As post-extubation respiratory support in preterm infants, NHFOV has a lower reintubation rate compared with NCPAP and NIPPV, without increasing the rate of complications.

Association of systemic inflammation and body mass index with survival in patients with resectable gastric or gastroesophageal junction adenocarcinomas.

Objective: The systemic inflammation index and body mass index (BMI) are easily accessible markers that can predict mortality. However, the prognostic value of the combined use of these two markers remains unclear. The goal of this study was therefore to evaluate the association of these markers with outcomes based on a large cohort of patients with gastric cancer. Methods: A total of 2,542 consecutive patients undergoing radical surgery for gastric or gastroesophageal junction adenocarcinoma between 2009 and 2014 were included. Systemic inflammation was quantified by the preoperative neutrophil-to-lymphocyte ratio (NLR). High systemic inflammation was defined as NLR ≥ 3, and underweight was defined as BMI < 18.5 kg/m2. Results: Among 2,542 patients, NLR ≥ 3 and underweight were common [627 (25%) and 349 (14%), respectively]. In the entire cohort, NLR ≥ 3 or underweight independently predicted overall survival (OS) [hazard ratio (HR): 1.236, 95% confidence interval (95% CI): 1.069-1.430; and HR: 1.600, 95% CI: 1.350-1.897, respectively] and recurrence-free survival (RFS) (HR: 1.230, 95% CI: 1.054-1.434; and HR: 1.658, 95% CI: 1.389-1.979, respectively). Patients with both NLR ≥ 3 and underweight (vs. neither) had much worse OS (HR: 2.445, 95% CI: 1.853-3.225) and RFS (HR: 2.405, 95% CI: 1.802-3.209). Furthermore, we observed similar results in subgroup analyses according to pathological stage, age, and postoperative chemotherapy. Conclusions: Our results showed that preoperative elevated NLR and decreased BMI had a significant negative effect on survival. Underweight combined with severe inflammation could enhance prognostication. Taking active therapeutic measures to reduce inflammation and increase nutrition may help improve outcomes.

[Comparison of the effect and safety of Er:YAG laser combined with fluoride and methylene blue-photodynamic therapy on caries prevention].

OBJECTIVE: To compare the anti-caries effect and safety of Er:YAG laser combined with fluoride and methylene blue-photodynamic therapy (MB-PDT). METHODS: A total of 28 rat dental caries models were established and randomly divided into seven groups: photodynamic therapy (PDT) group, laser combined with fluoride group, laser group, sodium fluoride group, and 0.9% saline control group. Spectrophotometric optical density was used to reflect the growth of Streptococcus mutans. Laser-induced fluorescence diagnostic (LF) instrument was utilized to detect the demineralization degree of dental caries. Histopathological sections were employed to observe the damage of dental pulp and buccal mucosa. RESULTS: The optical density (OD) value of the PDT and combination groups was significantly lower than that of other treatment groups (P<0.05). An increase in LF value and demineralization occurred in varying degrees with different treatment methods. Histopathological observation showed that pulp and buccal mucosa injury was more obvious in the combination group of 70 mw·cm⁻² and Er:YAG laser group compared with other groups. CONCLUSIONS: Under the same parameters, the combined group and PDT have good germicidal efficacy, but PDT has fewer adverse reactions and less damage. It is an effective and safe method for caries prevention.

The Tumor-Associated Macrophage-M2-Cancer Cell Complex and the Observation of Heterogeneous Modification of the Morphological Structure of Lung Adenocarcinoma.

OBJECTIVE: The aim of this study was to investigate the effect of the tumor-associated macrophage-m2-cancer cell complex (TAM-M2-CC) on the heterostructural modification of lung adenocarcinoma. METHODS: The expression of CD163+/CD68+ in macrophages in the microenvironment of 161 cases of lung adenocarcinoma was identified by dual immunohistochemistry, and the association between a TAM-M2-CC and its growth, as well as the histological changes in lung adenocarcinoma cells, was assessed. RESULTS: The morphological change of lung adenocarcinoma was related to the number of m2 phenotypes of the macrophages in the microenvironment of lung adenocarcinoma. TAM-M2-CCs were involved in the process of cancer cell recognition, association, and reconstruction. CONCLUSION: The microenvironment of lung adenocarcinoma can affect the phenotypic distinction of macrophages, and the polarization recruitment, zombification, and formation of a TAM-M2-CC, which can also affect the local differentiation of lung adenocarcinoma to a certain extent. The applicable pathogenesis needs to be verified and studied further.

188Re-labeled GX1 dimer as a novel dual-functional probe targeting TGM2 for imaging and antiangiogenic therapy of gastric cancer.

PURPOSE: The GX1 peptide (CGNSNPKSC) can specifically bind to TGM2 and possesses the ability to target the blood vessels of gastric cancer. This study intends to develop an integrated dual-functional probe with higher affinity, specificity and targeting and to characterize it in vivo and in vitro. METHODS: The dimer and tetramer of GX1 were prepared using cross-linked PEG and labeled with 99mTc. The best targeting probe [PEG-(GX1)2] was selected by gamma camera imaging in nude mouse models of gastric cancer. 188Re-PEG-(GX1)2 was prepared and characterized through cell binding analysis and competitive inhibition experiments, gamma camera imaging, MTT analysis and flow cytometry, BLI, immunohistochemistry, HE staining and biochemical analysis. RESULTS: PEG-(GX1)2 bound specifically to Co-HUVEC with higher affinity than GX1. 188Re-PEG-(GX1)2 had better ability to target gastric cancer in tumor-bearing nude mice and higher T/H ratios than 188Re-GX1. 188Re-PEG-(GX1)2 inhibited the growth of Co-HUVEC and induced apoptosis, and its effects were more robust than those of 188Re-GX1. BLI showed that 188Re-PEG-(GX1)2 inhibited tumor proliferation in vivo with a stronger effect than 188Re-GX1. Compared with 188Re-GX1, 188Re-PEG-(GX1)2 suppressed tumor angiogenesis and tumor cell proliferation and induced tumor cell apoptosis in vivo. The 188Re-PEG-(GX1)2 group did not cause visible changes in liver and kidney morphology and function in vivo. CONCLUSION: The dimer of GX1 was synthesized by using cross-linked PEG, and then 188Re-PEG-(GX1)2 was prepared. This radiopharmaceutical played both diagnostic and therapeutic functions, and gamma camera imaging could be utilized to detect the distribution of drugs in vivo during treatment. Through a series of experiments in vitro and in vivo, the feasibility of the drug was confirmed, and these results laid the foundation for the subsequent development and application of GX1.

TNF­α treatment increases DKK1 protein levels in primary osteoblasts via upregulation of DKK1 mRNA levels and downregulation of miR­335­5p.

Elucidation of the underlying mechanisms governing osteogenic differentiation is of significant importance to the improvement of therapeutics for bone­related inflammatory diseases. Tumor necrosis factor­α (TNF­α) is regarded as one of the major agents during osteogenic differentiation in an inflammatory environment. miR­335­5p post­transcriptionally downregulates the Dickkopf WNT signaling pathway inhibitor 1 (DKK1) protein level by specifically binding to the DKK1 3'UTR and activating Wnt signaling. The role of miR­335­5p in TNF­α­induced post­transcriptional regulation of DKK1 remains to be elucidated. In the present study, the mRNA and protein levels of DKK1 and the level of miR­335­5p were determined in MC3T3­E1 cells and the primary calvarial osteoblasts treated with or without TNF­α. The role of NF­κB signaling in TNF­α­induced post­transcriptional regulation of DKK1 was also evaluated. The present study determined that although TNF­α treatment exhibited cell­specific effects on DKK1 mRNA expression, the stimulation of TNF­α time­ and concentration­dependently upregulated the protein levels of DKK1. In primary calvarial osteoblasts, the decreased miR­335­5p level induced by TNF­α­activated NF­κB signaling served an important role in mediating the post­transcriptional regulation of DKK1 by TNF­α treatment. In MC3T3­E1 cells, the post­transcriptional regulation of DKK1 by TNF­α treatment was more complicated and involved other molecular signaling pathways in addition to the NF­κB signaling. In conclusion, TNF­α treatment served an important role in the post­transcriptional regulation of DKK1 expression, which requires further investigation. The results of the present study not only provided new insights into the regulatory effects of miR­335­5p on osteogenic differentiation in an inflammatory microenvironment, but may also promote the development of potential therapeutic strategies for the treatment of bone­related inflammatory diseases.

Pinolenic acid ameliorates oleic acid-induced lipogenesis and oxidative stress via AMPK/SIRT1 signaling pathway in HepG2 cells.

Pinolenic acid (PLA), a natural compound isolated from pine nut oil, has been reported to exert bioactivity against lipid anabolism. Nonetheless, the underlying mechanisms still poorly elucidated. The aim of this study is to comprehensively demonstrate the effects of PLA on oleic acid (OA)-induced non-alcoholic fatty liver disease (NAFLD) and their relationship with the lipid metabolic regulation. The results demonstrated that treatment with PLA dramatically inhibited lipid accumulation, oxidative stress as well as inflammatory responses induced by oleic acid in HepG2 cells. PLA also obviously decreased the levels of cellular triglyceride (TG), total cholesterol (TC), malondialdehyde (MDA), reactive oxygen species (ROS) and nitric oxide (NO). As well as PLA stilled promoted the antioxidant enzymes activity including superoxide dismutase (SOD) and glutathione peroxidase (GPX). Furthermore, PLA could increase the expressions of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase1 (HO-1) to alleviate oxidative damage. It also could reduce lipogenesis-related transcription factors expression, such as sterol regulatory element-binding protein 1 (SREBP1c), fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1). PLA treatment resulted in increasing phosphorylation of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-α (PPARα) expression. However, pretreatment with compound C (inhibitor of AMPK) inhibited the effect of PLA on promoting the expression of p-AMPK, SIRT1 and PPARα for lipolysis. Taken together, these results demonstrated that PLA possessed the potential to prevent lipid accumulation in OA-induced HepG2 cells via upregulating the AMPK/SIRT1 signaling pathway, which supported the development of new drug candidate against non-alcoholic steatohepatitis.