Grazing is one of the main grassland disturbances in China, and it is essential to quantitatively evaluate the effects of different grazing intensities on grassland production for grassland carbon budget and sustainable use.
A meta-analysis was conducted to reveal general response patterns of grassland production to grazing in China. We used weighted log response ratio to assess the effect size, and 95% confidence intervals to give a sense of the precision of the estimate. Grazing effects were estimated as a percentage change relative to control (%).
A total of 48 studies, including 251 data sets, were included in the meta-analysis. Grazing significantly decreased total biomass by 58.34% (95% CI: −72.04%∼−37.94%, CI: Confidence Interval), increased root/shoot ratio by 30.58% and decreased litter by 51.41% (95% CI: −63.31%∼−35.64%). Aboveground biomass and belowground biomass decreased significantly by 42.77% (95% CI: −48.88%∼−35.93%) and 23.13% (95% CI: −39.61%∼−2.17%), respectively. However, biomass responses were dependent on grazing intensity and environmental conditions. Percentage changes in aboveground biomass to grazing showed a quadratic relationship with precipitation in light grazing intensity treatment and a linear relationship in moderate and heavy grazing intensity treatment, but did not change with temperature. Grazing effects on belowground biomass did not change with precipitation or temperature. Compared to the global average value, grazing had greater negative effects on grassland production in China.
Grazing has negative effects on grassland biomass and the grazing effects change with environmental conditions and grazing intensity, therefore flexible rangeland management tactics that suit local circumstances are necessary to take into consideration for balancing the demand of grassland utilization and conservation.
Testicular germ cell tumor (TGCT) is the most common cancer in young men and is notable for its high familial risks1,2. To date, six loci associated with TGCT have been reported3-7. From GWAS analysis of 307,291 SNPs in 986 cases and 4,946 controls, we selected for follow-up 694 SNPs, which we genotyped in a further 1,064 TGCT cases and 10,082 controls from the UK. We identified SNPs at nine new loci showing association with TGCT (P<5×10−8), at 1q22, 1q24.1, 3p24.3, 4q24, 5q31.1, 8q13.3, 16q12.1, 17q22 and 21q22.3, which together account for an additional 4-6% of the familial risk of TGCT. The loci include genes plausibly related to TGCT development. PRDM14, at 8q13.3, is essential for early germ cell specification8 whilst DAZL, at 3p24.3, is required for regulation of germ cell development9. Furthermore, PITX1, at 5q31.1 regulates TERT expression, and is the third TGCT locus implicated in telomerase regulation10.
Persistent colonization of the human stomach with Helicobacter pylori is a risk factor for gastric adenocarcinoma, and H. pylori-induced carcinogenesis is dependent on the actions of a bacterial oncoprotein known as CagA. Epidemiological studies have shown that high dietary salt intake is also a risk factor for gastric cancer. To investigate the effects of a high-salt diet, we infected Mongolian gerbils with a wild-type (WT) cagA+
H. pylori strain or an isogenic cagA mutant strain and maintained the animals on a regular diet or a high-salt diet. At 4 months postinfection, gastric adenocarcinoma was detected in 100% of the WT-infected/high-salt-diet animals, 58% of WT-infected/regular-diet animals, and none of the animals infected with the cagA mutant strain (P < 0.0001). Among animals infected with the WT strain, those fed a high-salt diet had more severe gastric inflammation, higher gastric pH, increased parietal cell loss, increased gastric expression of interleukin 1β (IL-1β), and decreased gastric expression of hepcidin and hydrogen potassium ATPase (H,K-ATPase) compared to those on a regular diet. Previous studies have detected upregulation of CagA synthesis in response to increased salt concentrations in the bacterial culture medium, and, concordant with the in vitro results, we detected increased cagA transcription in vivo in animals fed a high-salt diet compared to those on a regular diet. Animals infected with the cagA mutant strain had low levels of gastric inflammation and did not develop hypochlorhydria. These results indicate that a high-salt diet potentiates the carcinogenic effects of cagA+
H. pylori strains.
To investigate the effect of the stellate ganglion (SG) and its left-right asymmetry on atrial fibrillation (AF) inducibility, AF duration and atrial electrophysiological properties.
Sixteen adult mongrel dogs were randomly assigned to three groups. The control group (n=4) underwent 6 h rapid atrial pacing (RAP) only; the right SG (RSG) group (n=6) underwent 6 h RSG stimulation plus RAP; and the left SG (LSG) group (n=6) underwent 6 h LSG stimulation plus RAP. AF induction rate, AF duration, effective refractory period (ERP) and dispersion of ERP (dERP) were measured.
In the RSG group, the induction rate of AF was significantly increased in sites in the right atrium (RA) compared with baseline (P<0.05). In the LSG group, the induction rate of AF was significantly increased (P<0.05) compared with baseline in the left atrium (LA), left superior pulmonary vein and left inferior pulmonary vein, respectively. Compared with RSG stimulation, right stellate ganglionectomy markedly decreased the AF induction rate of the RA (P<0.05). Compared with LSG stimulation, left stellate ganglionectomy markedly decreased the AF induction rate of the LA, the left superior pulmonary vein and the left inferior pulmonary vein (P<0.05). In the RSG group, the ERP was significantly shortened (P<0.05) and the dERP was significantly increased (P<0.05) in RA sites (P<0.05). The ERP was significantly shortened in the LSG group (P<0.05). The dERP was significantly increased (P<0.05) in LA and pulmonary vein sites (P<0.05).
Unilateral electrical stimulation of the SG in combination with RAP can successfully establish a canine model of acute AF mediated by excessive sympathetic activity. SG stimulation facilitates AF induction and aggravates electrical remodelling in sites in the atrium and pulmonary vein. Inhibiting sympathetic nerve activation through unilateral stellate ganglionectomy can reduce AF initiation.
Atrial fibrillation; Stellate ganglion; Sympathetic nerve
Peripheral selective mu opioid receptor (MOR) antagonists could alleviate the symptoms of opioid-induced constipation (OIC) without compromising the analgesic effect of opioids. However, a variety of adverse effects were associated with them, partially due to their relatively low MOR selectivity. NAP, a 6β-N-4'-pyridyl substituted naltrexamine derivative, was identified previously as a potent and highly selective MOR antagonist mainly acting within the peripheral nervous system. The noticeable diarrhea associated with it prompted the design and synthesis of its analogues in order to study its structure activity relationship. Among them, compound 8 showed improved pharmacological profiles compared to the original lead, acting mainly at peripheral while increasing the intestinal motility in morphine-pelleted mice (ED50=0.03 mg/kg). The slight decrease of the ED50 compared to the original lead was well compensated by the unobserved adverse effect. Hence, this compound seems to be a more promising lead to develop novel therapeutic agents toward OIC.
peripheral selective MOR antagonist; GI transit; NAP; NMP
Gliomas, the most malignant form of brain tumors, contain a small subpopulation of glioma stem cells (GSCs) that are implicated in therapeutic resistance and tumor recurrence. Topoisomerase I inhibitors, shikonin and topotecan, play a crucial role in anti-cancer therapies. After isolated and identified the GSCs from glioma cells successfully, U251, U87, GSCs-U251 and GSCs-U87 cells were administrated with various concentrations of shikonin or topotecan at different time points to seek for the optimal administration concentration and time point. The cell viability, cell cycle and apoptosis were detected using cell counting kit-8 and flow cytometer to observe the inhibitory effects on glioma cells and GSCs. We demonstrated that shikonin and topotecan obviously inhibited proliferation of not only human glioma cells but also GSCs in a dose- and time-dependent manner. According to the IC50 values at 24 h, 2 μmol/L of shikonin and 3 μmol/L of topotecan were selected as the optimal administration concentration. In addition, shikonin and topotecan induced cell cycle arrest in G0/G1 and S phases and promoted apoptosis. The down-regulation of Bcl-2 expression with the activation of caspase 9/3-dependent pathway was involved in the apoptosis process. Therefore, the above results showed that topoisomerase I inhibitors, shikonin and topotecan, inhibited growth and induced apoptosis of GSCs as well as glioma cells, which suggested that they might be the potential anticancer agents targeting gliomas to provide a novel therapeutic strategy.
Neuroinflammation is closely implicated in the pathogenesis of neurological diseases. The hallmark of neuroinflammation is the microglia activation. Upon activation, microglia are capable of producing various proinflammatory factors and the accumulation of these factors contribute to the neuronal damage. Therefore, inhibition of microglia-mediated neuroinflammation might hold potential therapy for neurological disorders. 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG), an active component extracted from Polygonum multiflorum, is reported to be beneficial for human health with a great number of pharmacological properties including antioxidant, free radical-scavenging, anti-inflammation, antilipemia, and cardioprotective effects. Recently, TSG-mediated neuroprotective effects have been well demonstrated. However, the neuroprotective actions of TSG on microglia-induced neuroinflammation are not known. In the present study, microglia BV2 cell lines were applied to investigate the anti-neuroinflammatory effects of TSG. Results showed that TSG reduced LPS-induced microglia-derived release of proinflammatory factors such as TNFα, IL-1β, and NO. Moreover, TSG attenuated LPS-induced NADPH oxidase activation and subsequent reactive oxygen species (ROS) production. Further studies indicated that TSG inhibited LPS-induced NF-κB signaling pathway activation. Together, TSG exerted neuroprotection against microglia-mediated neuroinflammation, suggesting that TSG might present a promising benefit for neurological disorders treatment.
Sympathetic activity involves the pathogenesis of atrial fibrillation (AF). Renal sympathetic denervation (RSD) decreases sympathetic renal afferent nerve activity, leading to decreased central sympathetic drive. The aim of this study was to identify the effects of RSD on AF inducibility induced by hyper-sympathetic activity in a canine model.
To establish a hyper-sympathetic tone canine model of AF, sixteen dogs were subjected to stimulation of left stellate ganglion (LSG) and rapid atrial pacing (RAP) for 3 hours. Then animals in the RSD group (n = 8) underwent radiofrequency ablation of the renal sympathetic nerve. The control group (n = 8) underwent the same procedure except for ablation. AF inducibility, effective refractory period (ERP), ERP dispersion, heart rate variability and plasma norepinephrine levels were measured at baseline, after stimulation and after ablation.
LSG stimulation combined RAP significantly induced higher AF induction rate, shorter ERP, larger ERP dispersion at all sites examined and higher plasma norepinephrine levels (P<0.05 in all values), compared to baseline. The increased AF induction rate, shortened ERP, increased ERP dispersion and elevated plasma norepinephrine levels can be almost reversed by RSD, compared to the control group (P<0.05). LSG stimulation combined RAP markedly shortened RR-interval and standard deviation of all RR-intervals (SDNN), Low-frequency (LF), high-frequency (HF) and LF/HF ratio (P<0.05). These changes can be reversed by RSD, compared to the control group (P<0.05).
RSD significantly reduced AF inducibility and reversed the atrial electrophysiological changes induced by hyper-sympathetic activity.
The purpose of this study was to describe the epidemiology of cervical spine injury in the patients with cervical trauma and analyze its associated risk factors during the special heating season in North China.
This cross-sectional study investigated predictors for cervical spine injury in cervical trauma patients using retrospectively collected data of Hebei Provincial Orthopaedic Hospital from 11/2011 to 02/2012, and 11/2012 to 02/2013. Binary logistic regression analysis was used to determine risk factors for cervical fractures/dislocations or cord injury.
A total of 106 patients were admitted into this study. Of all, 34 patients (32.1%) were treated from 11/2011 to 02/2012 and 72 patients (67.9%) from 11/2012 to 02/2013. The mean age was 41.9±13.3 years old; 85 patients (80.2%) were male and 82 (77.4%) from rural areas. Eighty patients (75.5%) were caused by fall including 45 (42.5%) by severe fall (>2 m). Sixty-five patients (61.3%) of all suffered injuries to other body regions and 32 (30.2%) got head injury. Thirty-one patients (29.2%) sustained cervical cord injury with cervical fractures/dislocations. Twenty-six (83.9%) of cervical cord injury patients were from rural areas and 24 (77.4%) of those resulted from fall including 15 (48.4%) from severe fall (>2 m). Logistic regression displayed that age (OR, 1.47; 95% CI, 1.05–2.07), head injury (OR, 5.63; 95% CI, 2.23–14.26), were risk factors for cervical cord injury and snowing (OR, 8.25; 95% CI, 2.26–30.15) was a risk factor for cervical spine injury due to severe fall (>2 m).
The elder male patients and patients with head trauma are high-risk population for cervical cord injury. As a seasonal factor, snowing during heating season is of note a risk factor for cervical spine injury resulting from severe fall (>2 m) in the patients with cervical trauma in North China.
Background and Purpose
Erythropoietin (EPO) confers potent neuroprotection against ischemic injury. However, treatment for stroke requires high doses and multiple administrations of EPO, which may cause deleterious side effects due to its erythropoietic activity. This study identifies a novel non-erythropoietic mutant EPO (MEPO) and investigates its potential neuroprotective effects and underlying mechanism in animal model of cerebral ischemia.
We constructed a series of MEPOs, each containing a single amino acid mutation within the erythropoietic motif, and tested their erythropoietic activity. Using cortical neuronal cultures exposed to NMDA neurotoxicity and a murine model of transient middle cerebral artery occlusion (MCAO), neuroprotection and neurofunctional outcomes were assessed as well as activation of intracellular signaling pathways.
The serine to isoleucine mutation at position 104 (S104I-EPO) completely abolished the erythropoietic and platelet-stimulating activity of EPO. Administration of S104I-EPO significantly inhibited NMDA-induced neuronal death in primary cultures, and protected against cerebral infarction and neurological deficits with an efficacy similar to that of wild-type EPO. Both S104I-EPO and wild-type EPO activated similar pro-survival signaling pathways, such as PI3K/AKT, MAPK/ERK1/2 and STAT5. Inhibition of PI3K/AKT or MAPK/ERK1/2 signaling pathways significantly attenuated the neuroprotective effects of S104I-EPO, indicating that activation of these pathways underlies the neuroprotective mechanism of MEPO against cerebral ischemia.
S104I-EPO confers neuroprotective effects comparable to those of wild-type EPO against ischemic brain injury, with the added benefit of lacking erythropoietic and platelet-stimulating side effects. Our novel findings suggest that the non-erythropoietic mutant EPO is a legitimate candidate for ischemic stroke intervention.
erythropoietin; erythropoietin mutant; cerebral ischemia; neuroprotection; neurotoxicity; AKT; ERK1/2
We explore the clinical character of cystitis glandularis accompanied with upper urinary tract obstruction.
We compared 70 cases of cystitis glandularis accompanied with upper urinary tract obstruction with 60 cases of cystitis glandularis without upper urinary tract obstruction. The difference of clinical manifestation and surgical efficacy was observed between the 2 groups.
The incidence of cystitis glandularis in women was higher than in men and the age of patients with cystitis glandularis and upper urinary tract obstruction was younger than the age of patients without upper urinary tract obstruction. The main symptom of cystitis glandularis accompanied with upper urinary tract obstruction were renal colic and abdominal pain; a few patients with a shorter course of the disease also had nausea, vomiting, frequency, urgency, dysuria, hematuria and fever. The distribution and morphological characteristics of lesions on the bladder and in the urine culture were not different between the 2 groups. There was no second operation on patients with upper urinary tract obstruction, but at least a second operation was performed on 9.3% patients without upper urinary tract obstruction.
In patients with upper urinary tract obstruction, we found that it was the main clinical symptom of their cystitis glandularis. Identifying and removing the causes of upper urinary tract obstruction is the most important management method. For the cystitis glandularis, active treatment or close follow-up should be made.
Functional elucidation of causal genetic variants and elements requires precise genome editing technologies. The type II prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)/Cas adaptive immune system has been shown to facilitate RNA-guided site-specific DNA cleavage. We engineered two different type II CRISPR/Cas systems and demonstrate that Cas9 nucleases can be directed by short RNAs to induce precise cleavage at endogenous genomic loci in human and mouse cells. Cas9 can also be converted into a nicking enzyme to facilitate homology-directed repair with minimal mutagenic activity. Lastly, multiple guide sequences can be encoded into a single CRISPR array to enable simultaneous editing of several sites within the mammalian genome, demonstrating easy programmability and wide applicability of the RNA-guided nuclease technology.
Congenital cataract is a Mendelian disorder that frequently causes blindness in infants. To date, various cataract-associated loci have been mapped; more than 30 genes have been identified by linkage analysis. However, the pathogenic loci in some affected families are still unknown, and new research strategies are needed. In this study, we used linkage-exome combinational analysis to further investigate the pedigree of a four-generation Chinese family with autosomal dominant coralliform cataract.
We combined whole exome sequencing and linkage analysis to identify the causative mutation. The exome capture and next-generation sequencing were used to sequence the protein-coding regions in the genome of the proband to identify rare mutations, which were further screened for candidate mutations in linkage regions. Candidate mutations were independently verified for co-segregation in the whole pedigree using Sanger sequencing.
We identified a C to A transversion at nucleotide position c.70 in exon 2 of CRYGD, a cataract-associated gene. This mutation resulted in a threonine substitution for proline at amino acid residue 24.
We identified a missense P24T mutation in CRYGD that was responsible for coralliform cataract in our studied family. Our findings suggest that the combination of exome sequencing and linkage analysis is a powerful tool for identifying Mendelian disease mutations that might be missed by the classic linkage analysis strategy.
Autosomal dominant congenital cataract; Whole exome sequencing; Linkage analysis; CRYGD; Coralliform cataract
Tandemly arrayed genes (TAGs) or gene clusters are prevalent in higher eukaryotic genomes. For example, approximately 17% of genes are organized in tandem in the model plant Arabidopsis thaliana. The genetic redundancy created by TAGs presents a challenge for reverse genetics. As molecular scissors, engineered zinc finger nucleases (ZFNs) make DNA double-strand breaks in a sequence-specific manner. ZFNs thus provide a means to delete TAGs by creating two double-strand breaks in the gene cluster. Using engineered ZFNs, we successfully targeted seven genes from three TAGs on two Arabidopsis chromosomes, including the well-known RPP4 gene cluster, which contains eight resistance (R) genes. The resulting gene cluster deletions ranged from a few kb to 55 kb with frequencies approximating 1% in somatic cells. We also obtained large chromosomal deletions of ~9 Mb at approximately one tenth the frequency, and gene cluster inversions and duplications also were achieved. This study demonstrates the ability to use sequence-specific nucleases in plants to make targeted chromosome rearrangements and create novel chimeric genes for reverse genetics and biotechnology.
zinc finger nuclease (ZFN); tandemly arrayed genes (TAGs); deletion; inversion; Arabidopsis
Human serum albumin (HSA) is widely utilized for medical purposes and biochemical research. Transgenic rice has proved to be an attractive bioreactor for mass production of recombinant HSA (rHSA). However, transgene spread is a major environmental and food safety concern for transgenic rice expressing proteins of medical value. This study aimed to develop a selectively terminable transgenic rice line expressing HSA in rice seeds, and a simple process for recovery and purification of rHSA for economical manufacture. An HSA expression cassette was inserted into a T-DNA vector encoding an RNA interference (RNAi) cassette suppressing the CYP81A6 gene. This gene detoxifies the herbicide bentazon and is linked to the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) cassette which confers glyphosate tolerance. ANX Sepharose Fast Flow (ANX FF) anion exchange chromatography coupled with Butyl Sepharose High Performance (Butyl HP) hydrophobic interaction chromatography was used to purify rHSA. A transgenic rice line, HSA-84, was obtained with stable expression of rHSA of up to 0.72% of the total dry weight of the dehusked rice seeds. This line also demonstrated high sensitivity to bentazon, and thus could be killed selectively by a spray of bentazon. A two-step chromatography purification scheme was established to purify the rHSA from rice seeds to a purity of 99% with a recovery of 62.4%. Results from mass spectrometry and N-terminus sequencing suggested that the purified rHSA was identical to natural plasma-derived HSA. This study provides an alternative strategy for large-scale production of HSA with a built-in transgene safety control mechanism.
Recombinant human serum albumin (rHSA); Selectively terminable transgenic rice; Purification
The objective of this study was to investigate the tempo-spatial distribution of paddy rice in Northeast China using moderate resolution imaging spectroradiometer (MODIS) data. We developed an algorithm for detection and estimation of the transplanting and flooding periods of paddy rice with a combination of enhanced vegetation index (EVI) and land surface water index with a central wavelength at 2 130 nm (LSWI2130). In two intensive sites in Northeast China, fine resolution satellite imagery was used to validate the performance of the algorithm at pixel and 3×3 pixel window levels, respectively. The commission and omission errors in both of the intensive sites were approximately less than 20%. Based on the algorithm, annual distribution of paddy rice in Northeast China from 2001 to 2009 was mapped and analyzed. The results demonstrated that the MODIS-derived area was highly correlated with published agricultural statistical data with a coefficient of determination (R
2) value of 0.847. It also revealed a sharp decline in 2003, especially in the Sanjiang Plain located in the northeast of Heilongjiang Province, due to the oversupply and price decline of rice in 2002. These results suggest that the approaches are available for accurate and reliable monitoring of rice cultivated areas and variation on a large scale.
Paddy rice; Moderate resolution imaging spectroradiometer (MODIS); Northeast China; Enhanced vegetation index; Land surface water index
AIM: To investigate whether transforming growth factor-β1 (TGF-β1) signaling pathway is involved in the pathogenesis of primary biliary cirrhosis (PBC).
METHODS: A murine model of PBC was developed by injection of polyinosinic polycytidylic acids (poly I: C) in C57BL/6 mice, and the liver expressions of TGF β1, TGF-β receptor I (TβRI), TGF-β receptor II (TβRII), p-Smad2/3, monoclonal α-smooth muscle actin antibody (α-SMA) and α1 (I) collagen in the mouse model and control mice were evaluated by immunohistochemistry, immunoblotting and real-time polymerase chain reaction (RT-PCR). Lymphocyte subsets in liver were analyzed using flow cytometry.
RESULTS: The mouse model had several key phenotypic features of human PBC, including elevated levels of alkaline phosphatase, antimitochondrial antibodies, portal bile ducts inflammation, and progressive collagen deposition. Compared with control mice, protein and mRNA levels of TGF β1, TβRI, TβRII, p-Smad2/3, α-SMA and α1 (I) collagen in liver (1.7 ± 0.4 vs 8.9 ± 1.8, 0.8 ± 0.2 vs 5.1 ± 1.5, 0.6 ± 0.01 vs 5.1 ± 0.1, 0.6 ± 0.3 vs 2.0 ± 0.3, 0.9 ± 0.4 vs 3.4 ± 0.6, 0.8 ± 0.4 vs 1.7 ± 0.3, 1.1 ± 1.2 vs 11.8 ± 0.6, P < 0.05), and the total number and percentage of CD4+ CD25+ FOXP3+ and CD8+ lymphocytes (0.01 ± 0.001 vs 0.004 ± 0.00, 0.12 ± 0.04 vs 0.52 ± 0.23, P < 0.01) were higher in the mouse model.
CONCLUSION: TGFβ1 might play a dual role in the development of PBC: it suppresses inflammatory response but operates to enhance fibrogenesis. The aberrant activity of TGF-β1 signaling contributes to the development of PBC.
Primary biliary cirrhosis; Transforming growth factor-β1; Regulatory T cell; Liver
The basolateral amygdala (BLA) plays a crucial role in emotional learning irrespective of valence1–5. While the BLA projection to the nucleus accumbens (NAc) is hypothesized to modulate cue-triggered motivated behaviors4, 6, 7,, our understanding of the interaction between these two brain regions has been limited by the inability to manipulate neural circuit elements of this pathway selectively during behavior. To circumvent this limitation, we used in vivo optogenetic stimulation or inhibition of glutamatergic fibers from the BLA to the NAc, coupled with intracranial pharmacology and ex vivo electrophysiology. We show that optical stimulation of the BLA-to-NAc pathway in mice reinforces behavioral responding to earn additional optical stimulations of these synaptic inputs. Optical stimulation of BLA-to-NAc glutamatergic fibers required intra-NAc dopamine D1-type, but not D2-type, receptor signaling. Brief optical inhibition of BLA-to-NAc fibers reduced cue-evoked intake of sucrose, demonstrating an important role of this specific pathway in controlling naturally occurring reward-related behavior. Moreover, while optical stimulation of medial prefrontal cortex (mPFC) to NAc glutamatergic fibers also elicited reliable excitatory synaptic responses, optical self-stimulation behavior was not observed by activation of this pathway. These data suggest that while the BLA is important for processing both positive and negative affect, the BLA-to-NAc glutamatergic pathway in conjunction with dopamine signaling in the NAc promotes motivated behavioral responding.
Treatment of chronic skin wounds is difficult and largely ineffective. Little improvement has been shown in promoting the healing of these wounds in the past few decades. Innovative treatments to enhance chronic wound healing process are therefore needed.
In this study, we examined the efficacy of angiopoietin-1 gene-modified bone marrow mesenchymal stem cells (Ang1-MSCs) on the promotion of cutaneous wound healing in rats. Excisional full-thickness wounds were treated with Ang1-MSCs, a recombinant adenovirus encoding angiopoietin-1 (Ad-Ang1), unmodified bone marrow mesenchymal stem cells (MSCs), or vehicle medium (sham).
The results showed that Ang1-MSCs significantly promoted wound healing with increased epidermal and dermal regeneration, and enhanced angiogenesis compared with MSCs, Ad-Ang1 or sham treatment. Moreover, Ang1-MSCs expressed CD31 in the wound, suggesting a direct contribution of Ang1-MSCs to angiogenesis.
Here we show that Ang1-MSCs accelerate wound healing by promoting skin regeneration and angiogenesis, compared with MSCs or Ad-Ang1 alone.
Gallstone ileus (GI) is characterized by occlusion of the intestinal lumen as a result of one or more gallstones. GI is a rare complication of gallstones that occurs in 1%-4% of all cases of bowel obstruction. The mortality associated with GI ranges between 12% and 27%. Classical findings on plain abdominal radiography include: (1) pneumobilia; (2) intestinal obstruction; (3) an aberrantly located gallstone; and (4) change of location of a previously observed stone. The optimal management of acute GI is controversial and can be: (1) enterotomy with stone extraction alone; (2) enterotomy, stone extraction, cholecystectomy and fistula closure; (3) bowel resection alone; and (4) bowel resection with fistula closure. We describe a case to highlight some of the pertinent issues involved in GI management, and propose a scheme to minimize recurrent disease and postoperative complications. We conclude that GI is a rare condition affecting mainly the older population with a female predominance. The advent of computed tomography and magnetic resonance imaging has made it easier to diagnose GI. Enterotomy with stone extraction alone remains the most common surgical method because of its low incidence of complications.
Gallstone ileus; Fistula closure; Intestinal obstruction; Bowel obstruction; Enterolithotomy
The association between polymorphisms on 5p12 and breast cancer (BC) has been widely evaluated since it was first identified through genome-wide association approach; however, the studies have yielded contradictory results. We sought to investigate this inconsistency by performing a comprehensive meta-analysis on two wildly studied polymorphisms (rs10941679 and rs4415084) on 5p12.
Databases including Pubmed, EMBASE, Web of Science, EBSCO, and Cochrane Library databases were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. The random-effects model was applied, addressing heterogeneity and publication bias.
A total of 19 articles involving 100,083 cases and 163,894 controls were included. An overall random-effects per-allele OR of 1.09 (95% CI: 1.06–1.12; P = 4.5×10−8) and 1.09 (95% CI: 1.05–1.12; P = 4.2×10−7) was found for the rs10941679 and rs4415084 polymorphism respectively. Significant results were found in Asians and Caucasians when stratified by ethnicity; whereas no significant associations were found among Africans/African-Americans. Similar results were also observed using dominant or recessive genetic models. In addition, we find both rs4415084 and rs10941679 conferred significantly greater risks of ER-positive breast cancer than of ER-negative tumors.
Our findings demonstrated that rs10941679-G allele and rs4415084-T allele might be risk-conferring factors for the development of breast cancer, especially in Caucasians and East-Asians.
Hawthorn (Crataegus spp.) is an important pome with a long history as a fruit, an ornamental, and a source of medicine. Fruits of hawthorn are marked by hard stony endocarps, but a hawthorn germplasm with soft and thin endocarp was found in Liaoning province of China. To elucidate the molecular mechanism underlying the soft endocarp of hawthorn, we conducted a de novo assembly of the fruit transcriptome of Crataegus pinnatifida and compared gene expression profiles between the soft-endocarp and the hard-endocarp hawthorn varieties. De novo assembly yielded 52,673 putative unigenes, 20.4% of which are longer than 1,000 bp. Among the high-quality unique sequences, 35,979 (68.3%) had at least one significant match to an existing gene model. A total of 1,218 genes, represented 2.31% total putative unigenes, were differentially expressed between the soft-endocarp hawthorn and the hard-endocarp hawthorn. Among these differentially expressed genes, a number of lignin biosynthetic pathway genes were down-regulated while almost all the flavonoid biosynthetic pathway genes were strongly up-regulated, concomitant with the formation of soft endocarp. In addition, we have identified some MYB and NAC transcription factors that could potentially control lignin and flavonoid biosynthesis. The altered expression levels of the genes encoding lignin biosynthetic enzymes, MYB and NAC transcription factors were confirmed by quantitative RT-PCR. This is the first transcriptome analysis of Crataegus genus. The high quality ESTs generated in this study will aid future gene cloning from hawthorn. Our study provides important insights into the molecular mechanisms underlying soft endocarp formation in hawthorn.
Curcuminoids are well known for their capabilities to combat risk factors that are associated with ageing and cellular senescence. Recent reports have demonstrated that curcuminoids can extend the lifespan of model organisms. However, the underlying mechanisms by which these polyphenic compounds exert these beneficial effects remain unknown. In this study, t-BHP-induced premature senescence model in human fibroblasts was chosen to explore the protective effects of a curcuminoid, bisdemethoxycurcumin (BDMC), on cellular senescence. The results demonstrated that BDMC attenuated oxidative stress-induced senescence-like features which include the induction of an enlarged cellular appearance, higher frequency of senescence-associated β-galactosidase staining activity, appearance of senescence-associated heterochromatic foci in nuclei, decrease in proliferation capability, and alteration in related molecules such as p16 and retinoblastoma protein. Notably, we found that BDMC treatment activated Sirt1/AMPK signaling pathway. Moreover, downregulating Sirt1 by the pharmacological inhibitor nicotianamine or small interfering RNA blocked BDMC-mediated protection against t-BHP-mediated decrease in proliferation. These results suggested that BDMC prevented t-BHP-induced cellular senescence, and BDMC-induced Sirt1 may be a mechanism mediating its beneficial effects.
Preconditioning has been considered promising for the treatment of ischemic flaps. In this study, the therapeutic effect of postconditioning was compared with that of preconditioning during ischemia/reperfusion (I/R) injury, and a role of inducible nitric oxide synthase (iNOS) in postconditioning treatment was also explored.
Sixty rats were randomly divided into four groups with 15 rats in each group. Ischemic injury was induced in a rat’s gracilis muscle flap model. Preconditioning and postconditioning were performed respectively on the flaps in the pre-con group and the post-con group. No treatment was given to the flaps in the control group, and flaps without I/R injury were used as a sham control. Muscle viability ratio, histology, and gene expression of iNOS were examined at different time intervals (3, 12, and 18 h).
A significantly higher survival ratio was observed in both the pre-con group (78.98 ± 3.39, 62.74 ± 3.7, and 54.42 ± 4.45 %) and the post-con group (77.42 ± 4.14, 59.74 ± 6.67, and 49.52 ± 4.13 %) than the control group (45.22 ± 3.69, 42.44 ± 3.76, and 33.2 ± 3.29 %) at 3, 12, and 18 h postoperatively (P < 0.05). There was no statistical difference between the pre-con group and the post-con group (P > 0.05). Histological examination showed delayed and attenuated tissue damage in both the pre-con group and the post-con group when compared to that of the control group. A higher expression of iNOS was observed in both the pre-con group and the post-con group than the control group and the sham group (P < 0.05).
Significant improvement of flap survival could be achieved by both preconditioning and postconditioning treatments; however, better protection could be provided by preconditioning. The higher expression of iNOS may play an important role in the therapeutic effect of postconditioning during I/R injury.
Ischemic postconditioning; Ischemic preconditioning; Ischemia/reperfusion (I/R) injury; Inducible nitric oxide synthase