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Background We assess the effects of standard decompressive craniectomy with stepwise decompression of the intracranial compartment on the postoperative neurologic function, hemodynamics, and Glasgow Outcome Scale (GOS) score of patients with severe traumatic brain injury (sTBI). Methods One hundred sTBI patients admitted from July 2017 to February 2019 were enrolled and randomly divided into step and standard groups (n = 50) using a random number table. The standard group received traditional standard decompression during surgery, while the step group underwent multistep decompression during surgery. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured immediately after surgery (T0), 3 hours after surgery (T1), 6 hours after surgery (T2), and 12 hours after surgery (T3). The postoperative Glasgow Coma Scale (GCS) score, neurologic function deficit score, and GOS score were evaluated. Results After treatment, the excellent/good rate of neurologic function improvement and GCS and GOS scores of the step group significantly exceeded those of the standard group (p Conclusion Standard decompressive craniectomy under multistep decompression can markedly improve the neurologic function, hemodynamics, and prognosis of patients.

In this study, three multiplex PCR panels involving twelve microsatellite loci were developed for cross‐species amplification in bighead carp (Hypophthalmichthys nobilis) and silver carp (H. molitrix). The panels were verified using population genetic analyses, and species and simulated hybrid discriminations based on the genotype data of all individuals from two populations for each species. The number of alleles (Na), the observed and expected heterozygosity (Ho and He), and the polymorphic information content (PIC) of twelve loci were ranged from 5 to 20, 0.189 to 0.956, 0.177 to 901, and 0.169 to 0.887, respectively. Overall, almost all the microsatellite loci were detected as highly polymorphic across the two species. The populations of same species showed close genetic distances and similar genetic structures. Significant genetic differentiations were only detected between populations from different species, with a higher variation between species (21.17%) compared with that between populations within species (0.18%). In the species and simulated hybrid discrimination analyses, the individuals from different species were separated distinctly, and the simulated hybrids could almost be separated with the true individuals. In brief, the results indicated the high efficiency of the microsatellite multiplex panels developed in this study, which provide a practicable tool for further genetic analyses of H. nobilis and H. molitrix.

The bighead carp (Hypophthalmichthys nobilis) is a native freshwater fish species in China. However, the wild fishery resources of H. nobilis have recently suffered a drastic decline. In this study, a total of 106,657 putative SNP loci were identified from the assembled transcripts of H. nobilis. Thirty-seven polymorphic loci were characterized from 60 SNP loci randomly selected for validation by using 36 fin clips of H. nobilis from the Yangtze River. The observed heterozygosity, expected heterozygosity, and polymorphic information content of the 37 SNP loci ranged from 0.171 to 1.000, 0.159 to 0.509, and 0.144 to 0.375, respectively, and 13 SNP loci significantly deviated from the Hardy–Weinberg equilibrium (P

The skin color differentiation and variation are the main problems limiting the development of red tilapia commercial culture. The specific function and regulation mechanism of mc1r gene in fish pigmentation are still poorly understood. In this study, we investigated the mc1r sequence characteristics, expression profiles, localization and melanocortins (MSH)-mc1r role on melanogenesis pathway of red tilapia. The mc1r ORF of red tilapia is1056 bp, corresponding to 351 amino acid, which belongs to a family of G-protein-coupled receptors. Quantitative real-time PCR demonstrated that mc1r mRNA was mainly expressed in the brain and dorsal skin tissues of PB (pink with scattered black spots) fish. The mc1r gene was found to be expressed during early development stages of red tilapia. The mc1r mRNA expressions were high in the 48 h post-hatching (48hph), 24hph and cleavage stages. Immunofluorescence analysis revealed that Mc1r was concentrated mainly in the cytoplasm and intercellular substance of skin epidermis. Injection with caudal vein of ɑ-MSH at 2.5 mg g−1 resulted in significantly higher tyrosinase activity and melanin level in the dorsal and ventral skin of red tilapia. The expression of mc1r and tyr mRNA in the skin of red tilapia increased after ɑ-MSH injection. These results suggested that mc1r plays an important role in fish melanogenesis pathway through binding to α-MSH.

In vertebrates, the microphthalmia-associated transcription factor (mitf) is at the hub of the melanin synthesis regulation network. However, little information is known about its molecular characterization, expression, location, or function in skin color differentiation and variation of red tilapia. The full-length cDNA sequences (1977 bp and 1999 bp) of mitfa and mitfb, encoding polypeptides of 491 and 514 amino acids, were effectively identified from red tilapia in this study. The Mitfa and Mitfb sequences of red tilapia clustered first with O. aureus, then with other teleost fish, according to phylogenetic analysis. Mitfa and mitfb mRNA were highly expressed in the brain, dorsal skin and eye tissues using quantitative real-time PCR. The mRNA expressions of mitfa and mitfb were the highest in the cleavage stage during the early development of red tilapia. Among three different colors of red tilapia, the expression levels of mitfa and mitfb were highest in the PB (pink with scattered black spots) dorsal skin. After overwintering, the mitfa and mitfb mRNA expressions were high in the dorsal skin of PB (color changed from pink to black). Mitfa and mitfb were mostly found in the epidermal layer of the dorsal skin, according to in situ hybridization (ISH) analysis. After injecting mitf-dsRNA duplicates along the tail vein of red tilapia, the activity of tyrosinase and the level of melanin in the dorsal skin both decreased significantly. The mRNA expressions of mitfa and its downstream genes (tyrb, tyrp1a and dct) decreased, whereas the mRNA expression of mitfb increased after mitfa-dsRNA injection. The mRNA expressions of mitfb, tyrb, tyrp1a and dct decreased, whereas the mRNA expression of mitfa increased after injecting mitfb-dsRNA. These findings suggest that mitf gene duplicates may play an important role in red tilapia skin color differentiation and variation via the melanogenesis pathway.

The commercial value of red tilapia is hampered by variations in skin color during overwintering. In this study, three types skin of red tilapia, including the skin remained pink color during and after overwintering (WP), the skin changed from pink color to black color during overwintering and remained black color after overwintering (PB), and the skin changed from pink color to black color during overwintering but recovered to pink color when the temperature rose after overwintering (BP), were used to analyze their molecular mechanisms of color variation. The transcriptome results revealed that the PB, WP, and BP libraries had 42, 43, and 43 million clean reads, respectively. The top 10 abundance mRNAs and specific mRNAs (specificity measure SPM > 0.9) were screened. After comparing intergroup gene expression levels, there were 2528, 1924 and 1939 differentially expressed genes (DEGs) between BP and PB, BP and WP, and PB and WP, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of color-related mRNAs showed that a number of DEGs, including tyrp1, tyr, pmel, mitf, mc1r, asip, tat, hpdb and foxd3, might play a potential role in pigmentation. Additionally, the co-expression patterns of genes were detected within the pigment-related pathways by PPI network from PB_WP group. Furthermore, DEGs from the apoptosis and autophagy pathways, such as baxα, beclin1, and atg7, might be involved in the fading of red tilapia melanocytes. The findings will aid in understanding the molecular mechanism underlying skin color variation in red tilapia during and after overwintering, as well as lay a foundation for future research aimed at improving red tilapia skin color characteristics.

The commercial value of red tilapia is hampered by variations in skin color during overwintering. In this study, three types of skin of red tilapia, including the skin remained pink color during and after overwintering (P), the skin changed from pink color to black color during overwintering and remained black color after overwintering (P-B), and the skin changed from pink color to black color during overwintering but recovered to pink color when the temperature rose after overwintering (P-B-P), were used to analyze their molecular mechanisms of color variation. The transcriptome results revealed that the P, P-B, and P-B-P libraries had 43, 42, and 43 million clean reads, respectively. The top 10 abundance mRNAs and specific mRNAs (specificity measure SPM 0.9) were screened. After comparing intergroup gene expression levels, there were 2528, 1924, and 1939 differentially expressed genes (DEGs) between P-B-P and P-B, P-B-P and P, and P-B and P, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of color-related mRNAs showed that a number of DEGs, including tyrp1, tyr, pmel, mitf, mc1r, asip, tat, hpdb, and foxd3, might play a potential role in pigmentation. Additionally, the co-expression patterns of genes were detected within the pigment-related pathways by the PPI network from P-B vs. P group. Furthermore, DEGs from the apoptosis and autophagy pathways, such as baxα, beclin1, and atg7, might be involved in the fading of red tilapia melanocytes. The findings will aid in understanding the molecular mechanism underlying skin color variation in red tilapia during and after overwintering as well as lay a foundation for future research aimed at improving red tilapia skin color characteristics.

Background. Peritumoral fibroblasts are key components of the tumor microenvironment. Through remodeling of the extracellular matrix (ECM) and secretion of pro-tumorigenic cytokines, peritumoral fibroblasts foster an immunosuppressive milieu conducive to tumor cell proliferation. In this study, we investigated if peritumoral fibroblasts could be therapeutically engineered to elicit an anti-cancer response by abolishing the proteolytic activities of membrane-bound metalloproteinases involved in ECM modulation. Methods. A high affinity, glycosylphosphatidylinositol (GPI)-anchored Tissue Inhibitor of Metalloproteinase (TIMP) named “T1PrαTACE” was created for dual inhibition of MT1-MMP and TACE. T1PrαTACE was expressed in fibroblasts and its effects on cancer cell proliferation investigated in 3D co-culture models. Results. T1PrαTACE abrogated the activities of MT1-MMP and TACE in host fibroblasts. As a GPI protein, T1PrαTACE could spontaneously detach from the plasma membrane of the fibroblast to co-localize with MT1-MMP and TACE on neighboring cancer cells. In a 3D co-culture model, T1PrαTACE promoted adherence between the cancer cells and surrounding fibroblasts, which led to an attenuation in tumor development. Conclusion. Peritumoral fibroblasts can be modulated with the TIMP for the elimination of cancer cells. As a novel anti-tumor strategy, our approach could potentially be used in combination with conventional chemo- and immunotherapies for a more effective cancer therapy.

Ulcerative colitis (UC) is a chronic inflammatory disease. Here, the potential effects of Capparis spinosa water extract (CSWE) on colonic histopathology, inflammation, and gut microbiota composition in dextran sulfate sodium (DSS) induced UC mice were evaluated. Our results showed that CSWE treatment improved the colonic histopathology of UC mice, increased the levels of tight junction protein gene ZO-1 and Occludin in intestinal epithelial cells, and inhibited the expression of proinflammatory cytokines (IL-1β, IL-6, and TNF-α). Furthermore, CSWE administration alleviated oxidative stress in the colon of UC mice. The effects of CSWE on the compositions and metabolomic profiles of the gut microbiota in UC mice were investigated. It was found that CSWE could enhance the diversity of gut microbes and the abundance of probiotics and metabonomics had the strongest association with Firmicutes. Our results indicated that CSWE might be an ideal candidate as a potential therapeutic natural product for the treatment of UC.

Stromal fibroblasts surrounding cancer cells are a major and important constituent of the tumor microenvironment not least because they contain cancer-associated fibroblasts, a unique fibroblastic cell type that promotes tumorigenicity through extracellular matrix remodeling and secretion of soluble factors that stimulate cell differentiation and invasion. Despite much progress made in understanding the molecular mechanisms that underpin fibroblast&ndash, tumor cross-talk, relatively little is known about the way the two cell types interact from a physical contact perspective. In this study, we report a novel three-dimensional dumbbell model that would allow the physical interaction between the fibroblasts and cancer cells to be visualized and monitored by microscopy. To achieve the effect, the fibroblasts and cancer cells in 50% Matrigel suspension were seeded as independent droplets in separation from each other. To allow for cell migration and interaction, a narrow passage of Matrigel causeway was constructed in between the droplets, effectively molding the gel into the shape of a dumbbell. Under time-lapse microscopy, we were able to visualize and image the entire process of fibroblast-guided cancer cell migration event, from initial vessel-like structure formation by the fibroblasts to their subsequent invasion across the causeway, attracting and trapping the cancer cells in the process. Upon prolonged culture, the entire population of fibroblasts eventually infiltrated across the passage and condensed into a spheroid-like cell mass, encapsulating the bulk of the cancer cell population within. Suitable for almost every cell type, our model has the potential for a wider application as it can be adapted for use in drug screening and the study of cellular factors involved in cell&ndash, cell attraction.

The Shunaoxin dropping pill (SNX) is derived from a traditional recipe. It has been used to treat cerebrovascular diseases in China since 2005 (approval number Z20050041). In this study, we used an in vitro H2O2-induced PC12 cell oxidative damage model and an in vivo D-gal-induced mouse memory impairment model to investigate whether SNX had neuroprotective effects. In vitro, prior to exposure to 100 μM H2O2 for 2 h, PC12 cells were pre-treated with SNX 50 μg mL−1 for 24 h. Hoechst 33258 staining was used to confirm the effect of SNX on apoptosis in the PC12 cells. Our results demonstrate that H2O2 suppresses the proliferation of PC12 cells and induces cell death. Pretreatment with SNX attenuates H2O2-induced apoptosis in PC12 cells. In vivo, D-gal was administered (100 mg kg−1, subcutaneously (s.c.)) once daily for 8 weeks to induce memory deficit and neurotoxicity in the brain of an aging mouse. Then, SNX (320 mg kg−1) was simultaneously administered orally. The present study demonstrates that SNX can alleviate aging in the mouse brain induced by D-gal via improving behavioral performance, alleviating oxidative stress, inhibiting neuroinflammation, and reducing brain cell damage in the hippocampus. Overall, these data clearly demonstrate the neuroprotective effect of SNX from the in vitro and in vivo results. SNX may be considered a novel agent for easing aging and/or age-related neurodegenerative diseases.

Doxorubicin (DOX) is one of the most effective antineoplastic drugs, however, its organ toxicity inhibits the clinical utility. This study was aimed at investigating the protective effects of Yiqi Fumai lyophilized injection (YQFM) against DOX-induced tissue injury and exploring the mechanisms which mediated reactive oxygen species (ROS), inflammation and apoptosis. The experiment was as follows: rats were subjected to an intraperitoneal injection (i.p.) of YQFM (0.481 g kg−1, i.p.) for 12 days; DOX (5 mg kg−1, i.p.) was administered on the 4th, 8th and 12th days to achieve a cumulative dose of 15 mg kg−1. Pretreatment of YQFM significantly ameliorated intracellular damage and dysfunction of the heart, liver and kidneys via decreasing activities of injury indexes. The levels of lipid peroxidation and glutathione depletion were clearly reduced following YQFM pretreatment, meanwhile the activities of glutathione peroxidase, superoxide dismutase, and catalase were elevated. Additionally administering YQFM could mitigate the cardiotoxicity, hepatotoxicity and nephrotoxicity via reducing levels of inflammatory factors and decreasing apoptosis. Accordingly, this study indicated that YQFM attenuated DOX-induced toxicity by ameliorating organ function, decreasing ROS production, and preventing excessive inflammation and apoptosis.

M embrane t ype 1 - m atrix m etallo p roteinase (MT1-MMP) and t umor necrosis factor α (TNF-α)- c onverting e nzyme (TACE) are prominent membrane-anchored metalloproteinases that regulate the turnover of extracellular matrix (ECM) components and bioactive molecules required for cancer proliferation. In this study, we describe a novel approach that would allow tissue inhibitor of metalloproteinase 1 (TIMP-1), the endogenous inhibitor of the matrix metalloproteinases (MMPs), to be translocated to the cell membrane for simultaneous MT1-MMP/TACE inhibition. We achieve this by fusing T1TACE, a designer TIMP-1 with superb affinities for MT1-MMP and TACE, to the glycosyl-phosphatidyl inositol anchor of prions to create a membrane-tethered, broad-spectrum inhibitor, named T1Pr αTACE, that colocalizes with MT1-MMP and TACE on the cell surface. Transduction of T1Pr αTACE in human fibrosarcoma cells results not only in a substantial reduction in gelatinolytic and TNF-α/heparin binding epithelial growth factor shedding activities but also in a loss of tubulogenic capability in three-dimensional matrices. In renal carcinoma, T1Pr αTACE triggers cellular senescence and disrupts MMP-mediated proteolysis of ECM components such as fibronectin and collagen I, leading to an impairment in cell motility and survival under both in vitro and in vivo conditions. Taken together, our findings may provide a new perspective in TIMP targeting that could be exploited to halt metastatic renal carcinoma progression.

Background Many tilapia species or varieties have been widely introduced and have become an economically important food fish in China. Information on the genetic backgrounds of these populations is deficient and requires more research, especially for red tilapia strains. Methods In the present study, displacement loop (D-loop) sequences were used to evaluate the genetic relationship and diversity of seven tilapia populations that are widely cultured in China; this was done specifically to speculate on the maternal ancestry of red tilapia strains. Three red tilapia varieties of Oreochromis ssp., Taiwan (TW), Israel (IL), and Malaysia (MY) strains and other populations, including O. aureus (AR), O. niloticus (NL), O. mossambicus (MS), and the GIFT strain of O. niloticus, were collected and analyzed in this study. Results A total of 146 polymorphic sites and 32 haplotypes of D-loop sequences were detected among 332 fish and four major haplotypes were shared among the populations. The TW and NL populations had a greater number of haplotypes (20 and 8, respectively). The haplotype diversity (Hd) and nucleotide diversity (π) of each population ranged from 0.234 to 0.826, and 0 to 0.060, respectively. The significant positive Tajima’s D value of neutral test were detected in the NL, IL, and MY populations (P F-statistics, highly significant genetic differentiations were detected among populations (P P > 0.05). The nearest K2P genetic distance (D = 0.014) was detected between the MS and TW populations, whereas, the farthest (D = 0.101) was found between the GIFT and AR populations. The results from the molecular variance analysis (AMOVA) showed that there was an extremely significant genetic variation observed among the populations (P

Uterine leiomyoma is the most common benign neoplasm of female reproductive system, found in about 50% of women in reproductive age. The mechanisms of leiomyoma growth include cell proliferation, which is modulated by growth factors, and deposition of extracellular matrix (ECM). Activin A and myostatin are growth factors that play a role in proliferation of leiomyoma cells. Matrix metalloproteinases (MMPs) are known for their ability to remodel the ECM in different biological systems. The aim of this study was to evaluate the expression levels of activin βA-subunit, myostatin, and MMP14 messenger RNAs (mRNAs) in uterine leiomyomas and the possible correlation of these factors with clinical features of the disease. Matrix metalloproteinase 14 was highly expressed in uterine leiomyoma and correlated with myostatin and activin A mRNA expression. Moreover, MMP14 and myostatin mRNA expression correlated significantly and directly with the intensity of dysmenorrhea. Overall, the present findings showed that MMP14 mRNA is highly expressed in uterine leiomyoma, where it correlates with the molecular expression of growth factors and is further increased in cases of intense dysmenorrhea.

JinQi-JiangTang tablet (JQ), a traditional Chinese patent medicine, have been commonly applied to clinical therapy in type 2 diabetic patients. The present study was undertaken to investigate the renoprotective effect of JQ on type 2 diabetic rats. The type 2 diabetic rat model was successfully induced by a high-fat and high-sugar diet combined with a single low-dose of streptozotocin. Intervention with JQ could significantly diminish the body weight loss, reduce the levels of fasting blood glucose, 24 hour urinary protein, blood urea nitrogen and serum creatinine in STZ-induced diabetic rats. JQ improved the creatinine clearance in diabetic rats. What's more, the levels of total cholesterol, triglyceride and low-density lipoprotein cholesterol were markedly reduced following JQ treatment, while the level of high-density lipoprotein cholesterol was elevated. Moreover, JQ significantly improved the activity of superoxide dismutase, catalase and glutathione peroxidase, whereas decreased the level of lipid peroxidation malondialdehyde in renal tissue of diabetic rats. Furthermore, immunohistochemical analysis showed that JQ significantly downregulated the expression of Bax, Caspase-3 and Cytochrome c and upregulated Bcl-2 protein expression in the renal tissue of diabetic rats, which was considered as the major pathogeneses of apoptosis. These data demonstrated that JQ exhibited a renoprotective effect through blood glucose control, alleviating lipid metabolism, anti-oxidative stress and anti-apoptosis activities.

// Bingjie Jiang 1 , Yan Zhang 1 , Jian Liu 1 , Anastasia Tsigkou 1 , Magdalini Rapti 2 , Meng Huee Lee 1 1 Department of Biological Sciences, Xian Jiaotong Liverpool University, Suzhou 215123, China 2 Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge CB2 0RE, United Kingdom Correspondence to: Meng Huee Lee, email: Meng.lee@xjtlu.edu.cn Keywords: MT1-MMP, TIMP, cancer, haemopexin, protein engineering Received: November 16, 2016 Accepted: January 24, 2017 Published: February 07, 2017 ABSTRACT Metastatic cancer cells express Membrane Type 1-Matrix Metalloproteinase (MT1-MMP) to degrade the extracellular matrix in order to facilitate migration and proliferation. Tissue Inhibitor of Metalloproteinase (TIMP)-2 is the endogenous inhibitor of the MMP. Here, we describe a novel and highly effective fusion strategy to enhance the delivery of TIMP-2 to MT1-MMP. We can reveal that TIMP-2 fused to the haemopexin +/– transmembrane domains of MT1-MMP (two chimeras named T2 PEX+TM and T2 PEX ) are able to interact with MT1-MMP on the cell surface as well as intracellularly. In the case of T2 PEX+TM , there is even a clear sign of MT1-MMP:T2 PEX+TM aggregation by the side of the nucleus to form aggresomes. In vitro , T2 PEX+TM and T2 PEX suppress the gelatinolytic and invasive abilities of cervical carcinoma (HeLa) and HT1080 fibrosarcoma cancer cells significantly better than wild type TIMP-2. In mouse xenograft, we further demonstrate that T2 PEX diminishes cervical carcinoma growth by 85% relative to the control. Collectively, our findings indicate the effectiveness of the fusion strategy as a potential targeted approach in cancer inhibition.

To provide comprehensive evaluation of interactive image segmentation algorithms, we propose an automatic scribble simulation approach. We first analyze the variety of scribbles labelled by different users and its influence on segmentation result. Then, we describe the consistency and inconsistency of scribbles with normal distribution on superpixel level and superpixel group level, and analyze the effect of connection in scribble for interactive segmentation evaluation. Based on the above analysis, we simulate scribbles on foreground and background respectively by randomly selecting superpixel groups and superpixels with the previously determined coverage values. The experimental results show that the scribbles simulated by the proposed approach can obtain similar evaluation results to manually labelled scribbles and avoid serious deviation in precision and recall evaluation.

Objective To investigate the possible correlation between progesterone receptor (PR) expression in uterine leiomyoma or adjacent myometrium and patient's age, size/number of leiomyomas, or clinical symptoms such as dysmenorrhea, acyclic pelvic pain, or menstrual and intermenstrual uterine bleeding. Design Cross-sectional study. Setting Referral center. Patient(s) Sixty-two Chinese women undergoing elective hysterectomy for uterine leiomyomata. Intervention(s) None. Main Outcome Measure(s) Evaluation of PR-total and PR-B mRNA with real-time polymerase chain reaction; PR-A and PR-B proteins quantified by Western blot in leiomyoma tissue and myometrium; symptoms rated by the patients using visual analog scores. Result(s) The PR-B mRNA and PR-A and PR-B proteins were more concentrated in leiomyomas than in matched myometrium. A direct correlation between PR-B mRNA levels in leiomyoma and age (r = 0.347) and number of tumors (r = 0.295) was found. Conversely, there was an inverse correlation between PR-B mRNA levels in leiomyoma and dysmenorrhea (r = −0.260) and intermenstrual bleeding (r = −0.266). Multiple regression analysis indicated that age (β = 0.363) and the number of myomas (β = 0.296) were independently associated with PR-B mRNA levels in leiomyoma tissue. Conclusion(s) The levels of PR-B mRNA in leiomyoma tissue are directly associated with the number of tumors and inversely correlated with the intensity of intermenstrual bleeding and dysmenorrhea, suggesting that PR signaling may favor leiomyoma growth while attenuating clinical symptoms. This duality should be taken into account in the clinical management of patients with symptomatic uterine leiomyoma.