Mechanism of indoleamine 2, 3-dioxygenase inhibiting cardiac allograft rejection in mice.

Indoleamine 2, 3-dioxygenase (IDO)-mediated regulation of tryptophan metabolism plays an important role in immune tolerance in transplantation, but it has not been elucidated which mechanism specifically induces the occurrence of immune tolerance. Our study revealed that IDO exerts immunosuppressive effects through two pathways in mouse heart transplantation, 'tryptophan depletion' and 'tryptophan metabolite accumulation'. The synergism between IDO+ DC and TC (tryptophan catabolic products) has stronger inhibitory effects on T lymphocyte proliferation and mouse heart transplant rejection than the two intervention factors alone, and significantly prolong the survival time of donor-derived transplanted skin. This work demonstrates that the combination of IDO+ DC and TC can induce immune tolerance to a greater extent, and reduce the rejection of transplanted organs.

Genotoxicity and teratogenicity of seabuckthorn (Hippophae rhamnoides L.) berry oil.

As botanicals and dietary supplements are used increasingly in many countries, the issue of safety is particularly critical for regulation of food products containing these substances. Seabuckthorn (Hippophae rhamnoides L.) has been used for centuries as a medicine and nutritional supplement in Asia and Europe. However, data regarding to the safety assessment of the plant and its extracts is still rare. This study was to evaluate the potential toxicity of seabuckthorn berry (SB) oil conducted in three genotoxicity studies and a teratogenicity study. Results of the genotoxicity studies indicated that SB oil has no genotoxicity under the experimental conditions of this study. Specifically, SB oil did not display any mutagenic activity on histidine dependent strains of Salmonella typhimurium under exposure concentrations of 8, 40, 200, 1000, and 5000 µg/plate; SB oil did not have significant effect on sperm morphology and have no influence on micronucleus rate of polychromatic erythrocytes in mice at doses of 9.36, 4.68, and 2.34 g/kg body weight. In the teratogenicity study, pregnant rats were treated with 4.68, 2.34, and 1.17 g/kg SB oil from gestation day 7 to 16 and no treatment-related maternal toxicity or embryo toxicity was observed. Taken together, these results support the safe use of seabuckthorn berry oil for potential dietary consumption in food or as a dietary supplement.

A New Insight of Kartogenin Induced the Mesenchymal Stem Cells (MSCs) Selectively Differentiate into Chondrocytes by Activating the Bone Morphogenetic Protein 7 (BMP-7)/Smad5 Pathway.

BACKGROUND Rotator cuff injury is the most common cause of shoulder disability, and although the repair technique has improved, the rate of rotator cuff reduction after repair is still high. The fibrocartilage region, which appears to be histologically inserted, cannot be regenerated. In recent years, studies have reported that mesenchymal stem cells (MSCs) have enhanced cartilage regeneration in the tendon and bone interface after rotator cuff repair, which has become a hot topic of research. MATERIAL AND METHODS Two mesenchymal stem cell types, SMSC (synovial-derived mesenchymal stem cells) and BMSC (bone marrow-derived mesenchymal stem cells) were intervened using kartogenin (KGN). The cytotoxicity was evaluated and the proliferation of the 2 cells was observed. Four commonly used cartilage phenotype genes were detected by quantitative real-time polymerase chain reaction, and the cartilage differentiation of MSCs induced by KGN was explored. The bidirectional regulation of the expression of BMP-7 and the downstream gene Smad5 was observed by constructing a lentiviral overexpression vector containing the target gene BMP-7. To explore whether BMP-7/Smad5 pathway activation promotes differentiation of SMSCs into chondrocytes. RESULTS KGN can induce the selective differentiation of endogenous MSCs into chondrocytes by activating the BMP-7/Smad5 pathway, which promotes the regeneration of interfacial cartilage, and improves the quality of tendon healing of the tendon after rotator cuff repair. CONCLUSIONS This study found a new biological intervention method to promote the effect of tendon on bone healing after rotator cuff repair.

User testing of the psychometric properties of pictorial-based disability assessment Longshi Scale by healthcare professionals and non-professionals: a Chinese study in Shenzhen.

OBJECTIVE: The aim of this study was to validate a novel pictorial-based Longshi Scale for evaluating a patient's disability by healthcare professionals and non-professionals. DESIGN: Prospective study. SETTING: Rehabilitation departments from a grade A, class 3 public hospital, a grade B, class 2 public hospital, and a private hospital and seven community rehabilitation centers. SUBJECTS: A total of 618 patients and 251 patients with functional disabilities were recruited in a two-phase study, respectively. MAIN MEASURES: Outcome measure: pictorial scale of activities of daily living (ADLs, Longshi Scale). Reference measure: Barthel Index. The Spearman correlation coefficient was used to analyze the validity of Longshi Scale against Barthel Index. RESULTS: In phase 1 study, from March 2016 to August 2016, the results demonstrated that the Longshi Scale was both reliable and valid (intraclass correlation coefficient based on two-way random effect (ICC2,1) = 0.877-0.974 for intra-rater reliability; ICC2,1 = 0.928-0.979; κ = 0.679-1.000 for inter-rater reliability; intraclass correlation coefficient based on one-way random effect (ICC1,1) = 0.921-0.984 for test-retest reliability and Spearman correlation coefficient = 0.836-0.899). In the second phase, in March 2018, results further demonstrated that the Longshi Scale had good inter-rater and intra-rater reliability among healthcare professionals and non-professionals including therapists, interns, and personal care aids (ICC1,1 = 0.822-0.882 on Day 1; ICC1,1 = 0.842-0.899 on Day 7 for inter-rater reliability). In addition, the Longshi Scale decreased assessment time significantly, compared with the Barthel Index assessment (P < 0.01). CONCLUSION: The Longshi Scale could potentially provide an efficient way for healthcare professionals and non-professionals who may have minimal training to assess the ADLs of functionally disabled patients.

Toxicological evaluation of silver nanoparticles and silver nitrate in rats following 28 days of repeated oral exposure.

The increasing application of silver nanoparticles (AgNPs) has been raising concerns about their potential adverse effects to human and the environment. However, the knowledge on the systemic toxicity of AgNPs in mammalian systems is still limited. The present study investigated the toxicity of PVP-coated AgNPs in rats treated with repeated oral administration, and compared that with equivalent dose of AgNO3 . Specifically, one hundred male and female rats were orally administrated with particulate or ionic forms of silver (Ag) separately at doses of 0.5 and 1 mg kg-1 body weight daily for 28 days. The results reveal no significant toxic effects of AgNPs and AgNO3 up to 1 mg kg-1 body weight, with respect to the body weight, organ weight, food intake, and histopathological examination. Ag distribution pattern in organs of rats treated with AgNPs was similar to that of AgNO3 treated rats, showing liver and kidneys are the main target organs followed by testis and spleen. The total Ag contents in organs were significantly lower in the AgNPs treated rats than those in the AgNO3 treated rats. However, the comparisons between AgNPs and AgNO3 treatments further indicated more potent of AgNPs in biochemical and hematological parameters in rats, including red blood cell count (RBC), platelet count (PLT), white blood cell count (WBC) and aspartate transaminase (AST). Results of this study suggested that particulate Ag at least partially contributed to the observed toxicity of AgNPs, and both ionic and particulate Ag should be taken into consideration in toxicological evaluation of AgNPs. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 609-618, 2017.

Surgical treatment and survival analysis of primary duodenal malignant tumor: a retrospective cohort study.

Background: A primary duodenal malignant tumor (PDMT) is an extremely uncommon malignancy that originates from a gastrointestinal tract tumor. Currently, there is no unified, effective surgical treatment for PDMTs. In this retrospective study, we sought to analyze and evaluate the surgical procedure for PDMTs including pancreaticoduodenectomy (PD) and limited resection (LR), expect to inform the management of PDMT. Methods: We retrospectively reviewed patients with PDMT who underwent PD and LR in General Surgery Department of Tianjin Medical University General Hospital from January 2014 to December 2019. The clinical characteristics of the malignant tumors among the different segment of the duodenum were analyzed. We analyzed and compared the efficacy and safety of these two surgical treatments. Through survival result of the patients, we analyzed the survival factors affecting the PDMT. Results: Of the 94 patients, 60 (63.8%) were diagnosed with duodenal adenocarcinomas (DAs), 32 (34.1%) with duodenal gastrointestinal stromal tumors (d-GISTs), and 2 (2.1%) with duodenal lymphomas. Of the duodenal malignancies localized in the descending (D2) segment, 72.6% were DAs, and the initial symptom was jaundice (27.4%). Comparing with D2, d-GISTs were more common in the non-D2 segment (50.0%), and 46.9% of these patients presented with anemia as a primary symptom. PDs (87.1%) were more commonly performed for malignancies localized in the D2 segment, and LRs (59.4%) were more commonly performed for malignancies localized in the non-D2 segment (P<0.05). Conclusions: In this study, we found that PDMT is more likely to occur in the D2 segment than the other segments, and the most common pathological type is DA. Treatment decisions for PD and LR might depend on the tumor type, location, and whether invasion of the pancreas. PD might be the first choice of treatment for PDMTs located in the D2 segment; otherwise, LR would be preferred. Further studies, preferably large randomized clinical trials, are needed to confirm these results.

Reliability of shear wave elastography for the assessment of gastrocnemius fascia elasticity in healthy individual.

The mechanical properties of the deep fascia, particularly their stiffness, strongly affect the development of muscle pathologies (such as compartment syndrome) and the action of the muscles. However, the mechanical characteristics of the deep muscular fascia are still not clearly understood. The present study focuses on examining the reliability of ultrasonic shear wave elastography (USWE) devices in quantifying the shear modulus of the gastrocnemius fascia in healthy individuals, particularly their ability to measure the shear modulus of the deep fascia of the gastrocnemius during ankle dorsiflexion. Twenty-one healthy males (age: 21.48 ± 1.17 years) participated in the study. Using USWE, the shear moduli of the medial gastrocnemius fascia (MGF) and lateral gastrocnemius fascia (LGF) were quantified at different angles during passive lengthening. The two operators took turns measuring each subject's MGF and LGF over a 1-h period, and operator B took an additional measurement 2 h later. For the intra-operator test, the same subjects were measured again at the same time of day 5 days later. Both the intrarater [intraclass correlation coefficient (ICC) = 0.846-0.965)] and interrater (ICC = 0.877-0.961) reliability values for measuring the shear moduli of the MGF and LGF were rated as excellent; the standard error of the mean (SEM) was 3.49 kPa, and the minimal detectable change (MDC) was 9.68 kPa. Regardless of the ankle angle, the shear moduli of the LGF were significantly greater than that of the MGF (p < 0.001). Significant increases in the shear moduli of both the MGF and the LGF were observed in the neutral position compared to the relaxed position. These results indicate that USWE is a reliable technique to assess the shear modulus of the gastrocnemius fascia and detect its dynamic changes during ankle dorsiflexion. USWE can be used for biomechanical studies and intervention experiments concerning the deep fascia.

Toxicological evaluation of water-extract sericin from silkworm (Bombyx mori) in pregnant rats and their fetus during pregnancy.

Sericin is a natural protein produced by the silkworm Bombyx mori, which has a wide range of biological activities and has a broad application prospect in multiple areas. However, systemic toxicity and safety assessment of sericin is still rare. This study was aimed to evaluate the toxic effects of water-extract sericin from cocoons of Bombyx mori in pregnant rats and their fetuses during pregnancy. Eighty pregnant rats were randomly divided into three treatment groups, one negative and one positive control group. The treatment groups were administered water-extract sericin solutions at doses of 1,000, 500, and 250 mg/kg, while the negative and positive control groups were administered pure water and 300 mg/kg aspirin, respectively. Rats were exposed daily by oral gavage from the seventh day of gestation for 10 consecutive days and sacrificed on the 20th day of gestation. The results showed that water-extract sericin did not induce any treatment-related changes on pregnant rats (clinical signs, body weights, food consumption, ovarian and uterine weights) and fetuses (body weights, body lengths, tail lengths, visceral, and skeletal development). The no-observed-adverse-effect-level (NOAEL) of sericin was determined to be 1,000 mg/kg body weight in rats. These results indicated that water-extract sericin is of low teratogenic potential under the experimental conditions of this study.

[Contents comparision of atractylode I, II, III in rhizoma atractylodis macrocephalae and the processed with soils].

OBJECTIVE: To research the effect of processing with soils on the contents of Atractylode I, II, III of Rhizoma Atractylodis Macrocephalae. METHODS: Contents of Atractylode I, II, III were determined by HPLC. Hypersil-ODS C18 (200 mm x 4.6 mm, 5 microm) column was used; The mobile phase consisted of acetonitrile-water; The flow rate was 1.0 mL/min; The detection wavelength was 220 nm and 276 nm,the column temperature was 30 degrees C. RESULTS: All the indexes of Atractylode I, II, III peak were qualified; The result of methodological study was met the requirement of HPLC; The average contents of Atractylode I , II , II in raw Rhizoma Atractylodis Macrocephalae were 0.4365, 0.2878, 0.4140 mg/g, the soil-processed Rhizoma Atractylodis Macrocephalae were 0.5503, 0.3013, 0.8403 mg/g, the processed Rhizoma Atractylodis Macrocephalae were 0.5386, 0.2958, 0.7399 mg/g. CONCLUSION: The content of Atractylode II is no significant difference among the raw Rhizoma Atractylodis Macrocephalae and the Processed. The contents of both Atractylode I and III increased after processed. However, there is no significant difference between the soil-processed and the processed Rhizoma Atractylodis Macrocephalae with nothing.

PLLA/POSS Nanofibers Loaded with Multitargeted pANG Composite Nanoparticles for Promotion of Vascularization in Shear Flow.

In vitro prevascularization is particularly important for the clinical application of tissue engineering scaffolds that require vascularization. The principal challenge is simulating the dynamic in vivo environment to promote the continuous growth of blood vessels. In this study, two targeting polypeptides are linked to the two ends of an amphiphilic block copolymer, polyethyleneimine-b-poly(lactide-co-3(S)-methyl-morpholine-2,5-dione)-b-polyethyleneimine (PEI-PLMD-PEI), and self-assembled to form positively charged nanoparticles (NPs), which can bind to negatively charged pANG through electrostatic interactions; the polypeptides are finally loaded into PLLA/polyhedral oligomeric silsesquioxane (POSS) porous fibers to prepare untargeted nanofibers (unTFs), targeted porous nanofibers (TFBs), and targeted nanofiber bundles. The effects of the porous nanofibers on human umbilical vein endothelial cell (HUVEC) transfection, spreading, proliferation, morphology, and expression of related factors are investigated under the action of shear flow force. The results show that the PLLA/POSS nanofibers can maintain stable release of multitargeted NPs for nearly 45 days. Both the dual-targeted porous NPs and shear flow improve the pANG transfection efficiency and promote cell proliferation, and they have a good synergistic effect. These results provide a potential strategy for designing HUVEC-specific gene carriers and using shear flow to enhance endothelialization.

Evaluation of the disability assessment Longshi scale: A multicenter study.

OBJECTIVE: We investigated factors affecting the disability assessment Longshi scale, and differences between the Longshi and Barthel scales, as well as modified Rankin scale (mRS), to determine whether the Longshi scale is superior to the other scales. METHODS: This cross-sectional study included 721 participants with disability. We performed the t-test, analysis of variance, Pearson's correlation test, and multiple linear regression to analyze group differences and define explanatory variables. RESULTS: The Longshi scale had a strong positive correlation with the Barthel scale (r = 0.868) but a weak negative correlation with the mRS (r = -0.185). Scores obtained among seven study hospitals in two provinces of southeast China were significantly different (F = 8.034). Social activities of participants with disability can be positively predicted using the Longshi (ß = 0.251) and Barthel scales (ß = 0.276). However, age has a weak negative correlation with the Longshi scale (r = -0.163). CONCLUSION: Training did not cause significant variations in assessment using the Longshi scale. However, the results differed among different regions. The Longshi scale showed a strong correlation with the Barthel scale but a weak correlation with the mRS. Assessment time was shorter using the Longshi scale and the scale can be used to predict the social activities of individuals with disability.

Safety Assessment of Water-Extract Sericin from Silkworm (Bombyx mori) Cocoons Using Different Model Approaches.

Sericin is a natural protein component of silks of silkworm and has potential utility in multiple areas such as pharmacological, cosmetics, and biotechnological industries. However, the understanding of its toxicological safety is still limited. This study evaluated the safety of water-extract sericin from silkworm (Bombyx mori) cocoons using different model approaches, including three genotoxicity studies (the bacterial reverse mutation test, the mammalian erythrocyte micronucleus test, and the mouse spermatogonia chromosomal aberration test) and a 90-day subchronic toxicity study in Sprague-Dawley (SD) rats. The results of this study showed that water-extract sericin was nonmutagenic and nongenotoxic both in vitro and in vivo. Sericin did not induce significant changes in the body and organ weight, food intake, blood hematology and serum biochemistry, urine index, and histopathology in rats. The NOAEL of sericin was determined to be 1 g/kg/day for male and female rats. These results indicated that water-extract sericin was of low toxicity in the experimental conditions of the current study and had the potential for application in food-related products.

MiR-669b-3p regulates CD4+ T cell function by down-regulating indoleamine-2, 3-dioxygenase.

OBJECTIVE: Acute rejection is a major cause of morbidity and mortality after solid organ transplantation. Therefore, optimizing treatment strategies and improving curative effect is urgent and necessary. Reliable biomarkers for acute rejection and the underlying molecular mechanisms remain to be determined. METHODS: In this study, we established a mouse-to-mouse cardiac transplantation model and identified miR-669b-3p as a potential biomarker of acute rejection using a microRNA polymerase chain reaction (PCR)-based chip assay. RESULTS: Further analyses showed that miR-669b-3p negatively regulated indoleamine-2,3-dioxygenase (IDO), a rate-limiting enzyme of tryptophan catabolism inhibiting T cell function. Using mixed lymphocyte reaction assay, we showed that miR-669b-3p increased proliferation stimulation index and inhibited apoptosis in CD4+ T cells. Moreover, miR-669b-3p regulated the expression of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and Interleukin 10 (IL-10) and contributed to cytokine shift towards a Th2-dominant response. CONCLUSION: Our results advance the current understanding of the immune regulatory function of miRNA and shed light on the role of miR-669b-3p in CD4+ T cells, suggesting that miR-669b-3p is a potential target for acute allograft rejection.

C1 Titanium Cables Combined with C2 Pedicle Screw-Rod Fixation for Atlantoaxial Instability Not Suitable for Placement of C1 Screws.

OBJECTIVE: We sought to develop a new posterior fusion technique composed of bilateral C1 titanium cables and C2 pedicle screw-rods for treatment of atlantoaxial instability not suitable for C1 screw placement. METHODS: A study was conducted of 18 patients with atlantoaxial instability who had C1 broken screw trajectory or anatomic anomalies. All patients underwent posterior fixation with bilateral C1 titanium cables and C2 pedicle screws. The follow-up period was a minimum 1 year. Clinical outcomes measurements included visual analog scale score for neck pain assessment, the American Spinal Injury Association Impairment Scale and Japanese Orthopaedic Association score for neurologic status and function. According to preoperative computed tomography (CT) reconstruction and CT angiography, the patients selected in this study were not suitable for C1 screw placement. Postoperative plain radiographs and CT reconstruction were performed to evaluate the reduction, bony fusion, and implant position. All outcomes were evaluated at each follow-up. RESULTS: The average clinical follow-up period was 24 months (range 12-36 months). All patients had complete neck pain relief at postoperative 6 months. Their neurologic symptoms had improved significantly at 1-year follow-up. Radiologic outcomes indicated good bony fusion and construction stability in all patients without implant failure at the last follow-up. No neural or vascular complications related to this technique were observed. CONCLUSIONS: Posterior atlantoaxial fixation using C1 titanium cables and C2 pedicle screw-rod construct appears to be an effective and safe technique for treatment of atlantoaxial instability, which could be an alternative method for cases unsuitable for C1 screw placement when using C1-C2 screw fixation.

Developing New Oligo Probes to Distinguish Specific Chromosomal Segments and the A, B, D Genomes of Wheat (Triticum aestivum L.) Using ND-FISH.

Non-denaturing FISH (ND-FISH) technology has been widely used to study the chromosomes of Triticeae species because of its convenience. The oligo probes for ND-FISH analysis of wheat (Triticum aestivum L.) chromosomes are still limited. In this study, the whole genome shotgun assembly sequences (IWGSC WGA v0.4) and the first version of the reference sequences (IWGSC RefSeq v1.0) of Chinese Spring (T. aestivum L.) were used to find new tandem repeats. One hundred and twenty oligo probes were designed according to the new tandem repeats and used for ND-FISH analysis of chromosomes of wheat Chinese Spring. Twenty nine of the 120 oligo probes produce clear or strong signals on wheat chromosomes. Two of the 29 oligo probes can be used to conveniently distinguish wheat A-, B-, and D-genome chromosomes. Sixteen of the 29 oligo probes only produce clear or strong signals on the subtelomeric regions of 1AS, 5AS, 7AL, 4BS, 5BS, and 3DS arms, on the telomeric regions of 1AL, 5AL, 2BS, 3BL, 6DS, and 7DL arms, on the intercalary regions of 4AL and 2DL arms, and on the pericentromeric regions of 3DL and 6DS arms. Eleven of the 29 oligo probes generate distinct signal bands on several chromosomes and they are different from those previously reported. In addition, the short and long arms of 6D chromosome have been confirmed. The new oligo probes developed in this study are useful and convenient for distinguishing wheat chromosomes or specific segments of wheat chromosomes.