Interferon-α induces differentiation of cancer stem cells and immunosuppression in hepatocellular carcinoma by upregulating CXCL8 secretion.

Interferon-alpha (IFN-α) is widely used in the clinical treatment of patients with chronic hepatitis B and hepatocellular carcinoma (HCC). However, high levels of CXCL8 are associated with resistance to IFN-α therapy and poorer prognosis in advanced cancers. In this study, we investigated whether IFN-α could directly induce the production of CXCL8 in HCC cells and whether CXCL8 could antagonize the antitumor activity of IFN-α. We found that IFN-α not only upregulated the expression of the inducible genes CXCL9, CXCL10, CXCL11 and PD-L1, but also significantly stimulated CXCL8 secretion in HCC cells. Mechanically, IFN-α induces CXCL8 expression by activating the AKT and JNK pathways. In addition, our results demonstrate that IFN-α exposure significantly increases the differentiation of HCC stem cells, but this effect is reversed by the addition of the CXCL8 receptor CXCR1/2 inhibitor Reparixin and STAT3 inhibitor Stattic. Besides, our study reveals that the cytokine CXCL8 secreted by IFN-α-induced HCC cells inhibits T-cell function. Conversely, inhibition of CXCL8 promotes TNF-α and IFN-γ secretion by T cells. Finally, liver cancer patients who received anti-PD-1/PD-L1 immunotherapy with high CXCL8 expression had a lower immunotherapy efficacy. Overall, our findings clarify that IFN-α triggers immunosuppression and cancer stem cell differentiation in hepatocellular carcinoma by upregulating CXCL8 secretion. This discovery provides a novel approach to enhance the effectiveness of HCC treatment in the future.

Extraction, Modification and Biomedical Application of Agarose Hydrogels: A Review.

Numerous compounds present in the ocean are contributing to the development of the biomedical field. Agarose, a polysaccharide derived from marine red algae, plays a vital role in biomedical applications because of its reversible temperature-sensitive gelling behavior, excellent mechanical properties, and high biological activity. Natural agarose hydrogel has a single structural composition that prevents it from adapting to complex biological environments. Therefore, agarose can be developed into different forms through physical, biological, and chemical modifications, enabling it to perform optimally in different environments. Agarose biomaterials are being increasingly used for isolation, purification, drug delivery, and tissue engineering, but most are still far from clinical approval. This review classifies and discusses the preparation, modification, and biomedical applications of agarose, focusing on its applications in isolation and purification, wound dressings, drug delivery, tissue engineering, and 3D printing. In addition, it attempts to address the opportunities and challenges associated with the future development of agarose-based biomaterials in the biomedical field. It should help to rationalize the selection of the most suitable functionalized agarose hydrogels for specific applications in the biomedical industry.

The complete chloroplast genome sequences of Hippuris vulgaris (Plantaginaceae).

Two complete chloroplast genomes of Hippuris vulgaris (H. vulgaris_A and H. vulgaris_B), representing two distinct clades in China, were sequenced and assembled in this study. The circular genomes were 152,763 and 152,713 bp in length and exhibit a typical quadripartite structure of the large single-copy (LSC, 82,983/82,949 bp) and small single-copy (SSC, 18,294/18,278 bp) regions, separated by a pair of inverted repeats (IRs, both 25,743 bp). Both two cp genomes identically contain 133 genes, including 88 protein-coding genes, 37 tRNA, and eight rRNA genes. The phylogenetic analysis within Plantaginaceae demonstrated Hippuris an independent clade included in the expanded Plantaginaceae.

Downregulated hippocampal expression of brain derived neurotrophic factor and tyrosine kinase B in a rat model of comorbid epilepsy and depression.

OBJECTIVE:  To investigate the expression of brain-derived neurotrophic factor(BDNF) and tyrosine kinase B (TrkB) protein in the hippocampus of model rats of comorbid epilepsy and depression. METHODS: A rat model of epilepsy was established using lithium chloride.pilocarpine. Among these epileptic rats, those with comorbid depression were selected by a battery of behavioral tests starting on the 14th day after establishing the epilepsy model. A depression group was established by unpredicted chronic mild stress (UCMS) and separate housing. These treatment groups were compared to an untreated control group. Thirteen rats per group were examined by immunofluorescence staining with optical density quantitation to determine the distribution of BDNF- and TrkB-positive cells in the hippocampus and by western blotting to estimate total protein expression levels during the 4th week after establishing the models. Immunofluorescence staining for NeuN was also conducted in hippocampus to evaluate neuronal survival. Depression-like behaviors were also assessed. RESULTS:  Compared to the untreated control group and the epilepsy alone group, the comorbid group exhibited lower average optical densities of BDNF- and TrkB-immunopositive cells as well as lower total BDNF and TrkB protein expression levels (all P = 0.000). The comorbid group exhibited lower behavioral scores compared to all other groups (all P=0.000). Numbers of NeuN-positive cells were lower in the hippocampus of all three experimental groups compared to the untreated control group (all P = 0.000). CONCLUSIONS:  These results suggest that hypofunctional BDNF-TrkB signaling may contribute to depression in epilepsy. ABBREVIATIONS: BDNF: Brain-derived neurotrophic factor; TrkB: tyrosine kinase B; UCMS: unpredicted chronic mild stress; PBS: phosphate-buffered saline; HS: Hippocampal sclerosis.

Application of different patella height indices in patients undergoing total knee arthroplasty.

BACKGROUND: One complication of total knee arthroplasty (TKA) is patella baja (PB). Patellar tendon shortening and joint line elevation are two main causes of PB. The purpose of this study was to determine the incidence of PB before and after TKA by measuring the patellar height and provide evidence for choosing a suitable index. METHODS: In total, 256 consecutive patients who underwent primary TKA were included in this study. Radiographic measurements were performed; the Insall-Salvati (IS) index, modified IS (MIS) index, Blackburne-Peel (BP) index, and Caton-Deschamps (CD) index were computed; and the incidence of PB was calculated before and after the operation. The consistency between the IS and MIS indices and between the BP and CD indices was analyzed. RESULTS: The preoperative incidence of true PB (TPB) and pseudo-PB (PPB) was 9.4 and 0.8%, respectively. The postoperative incidence of TPB and PPB was 10.2 and 9.0%, respectively. The consistency between the IS and MIS indices was moderate preoperatively (pre-kappa = 0.602) and postoperatively (post-kappa = 0.742). The consistency between the BP and CD indices was moderate preoperatively (pre-kappa = 0.742) and good postoperatively (post-kappa = 0.797). CONCLUSION: The incidence of PB, especially PPB, increased after TKA. The CD and BP indices are of greater importance for the diagnosis of PB after TKA. The MIS index is a better choice than the IS index to measure the length of the patellar tendon. To measure the height of the joint line, the BP index is better postoperatively and the CD index is better preoperatively.

The efficacy and safety of using a bipolar sealer to prevent blood loss in spine surgery: A meta-analysis.

OBJECTIVE: The purpose of this systematic review and meta-analysis of randomized controlled trials (RCTs) and non-RCTs was to evaluate the effect of using a bipolar sealer to prevent surgical bleeding in spine surgery. METHODS: In June 2017, the PubMed, Embase, Cochrane controlled trials register, Web of Science, Google, and Chinese Wanfang databases were used to identify RCTs and non-RCTs comparing the effects of intraoperative placement of a bipolar sealer versus standard electrocautery with regard to blood loss and blood transfusion. Stata 12.0 software was used to perform the meta-analysis. Weighted mean differences with 95% confidential intervals (CIs) were used for continuous outcomes, and relative risks with 95% CIs were used for discontinuous outcomes. After testing for publication bias and heterogeneity across studies, the data were aggregated and assessed with a random effects model when necessary. RESULTS: In total, 6 clinical trials with 560 patients were included in this meta-analysis. The pooled results indicated that the use of a bipolar sealer decreased the estimated blood loss (MD = -165.06, 95% CI -236.73 to -93.40, P < 0.001), the need for a blood transfusion (RR = 0.46, 95% CI 0.31 to 0.68, P < 0.001), the transfusion units used (MD = -0.41, 95% CI -0.60 to -0.21, P < 0.001), the operative time (MD = -12.98, 95% CI -21.82 to -4.15, P = 0.004) and the length of hospital stay (MD = -2.77, 95% CI -5.45 to -0.10, P = 0.042). No significant difference was observed for the occurrence of infection (RR = 0.52, 95% CI 0.19 to 1.39, P = 0.192). CONCLUSION: Based on the current meta-analysis, the use of a bipolar sealer is superior to standard electrocautery for reducing intraoperative blood loss and is therefore recommend for use during spine surgery.

The association of ADAM12 polymorphism with osteoarthritis susceptibility: a meta-analysis.

BACKGROUND: The pathology of osteoarthritis (OA) is partly attributed to genetic factors; however, the role of ADAM12 polymorphism is still controversial. It is necessary to perform a meta-analysis to investigate this possible correlation. METHODS: Case-control studies on the association between OA susceptibility and ADAM12 polymorphism were comprehensively collected by searching PubMed, Embase, and Web of Science. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled to evaluate OA risk that was possibly conferred by ADAM12 variant. The analyses were performed not only among general population but also in male and female groups. RESULTS: A total of 8 studies with 10 populations were finally included in this meta-analysis. In the general population, 4 comparisons were carried out (C allele vs G allele, CC vs GG, GC + CC vs GG, and CC vs GC + GG) and found that ADAM12 rs3740199 polymorphism was not associated with increased OA vulnerability. On the other hand, the analyses stratified by gender made 5 comparisons (C allele vs G allele, CC vs GG, GC vs GG, GC + CC vs GG, and CC vs GC + GG). It was shown that rs3740199 polymorphism (GC + CC vs GG) was a risk factor for OA among male patients (OR =1.45, 95% CI =1.04-2.01). Sensitivity analysis indicated that it was an unstable outcome. No correlation was identified in women. Neither heterogeneity nor publication bias was detected in the analyses mentioned above. CONCLUSION: ADAM12 rs3740199 polymorphism is likely to be associated with OA susceptibility among male patients, other than the general population. More studies are needed to confirm this observation. The mechanism by which ADAM12 variant plays a role in OA pathogenesis is also warranted and important for interpreting this possible correlation.

Multiple origins of BBCC allopolyploid species in the rice genus (Oryza).

In the rice genus (Oryza), about one half of the species are allopolyploids. These species are not only important resources for rice breeding but also provide a unique opportunity for studying evolution of polyploid species. In the present study, we sequenced four biparentally inherited nuclear loci and three maternally inherited chloroplast fragments from all diploid and tetraploid species with the B- and C-genome types in this genus. We detected at least three independent origins of three BC-genome tetraploid species. Specifically, the diploid O. punctata (B-genome) and O. officinalis (C-genome) were the parental progenitors of O. minuta and O. malampuzhaensis with O. punctata being the maternal donors, whereas the diploid O. punctata and O. eichingeri (C-genome) were the progenitors of tetraploid O. punctata with O. punctata being the paternal donor. Our relaxed clock analyses suggest that all the BBCC species originated within the last one million years, which is coincident with the severe climate oscillations occurred during the last ice age, implying the potential impact of climate change on their formations and dispersals. In addition, our results support previous taxonomic arguments that the tetraploid O. punctata might be better treated as a separate species (O. schweinfurthiana).

Comparative phylogeography of the wild-rice genus Zizania (Poaceae) in eastern Asia and North America.

PREMISE OF THE STUDY: Comparative phylogeography of intercontinental disjunct taxa allowed us not only to elucidate their diversification and evolution following geographic isolation, but also to understand the effect of climatic and geological histories on the evolutionary processes of closely related species. A phylogeographic analysis was conducted on the eastern Asian-North American disjunct genus Zizania to compare intracontinental phylogeographic patterns between different continents. METHODS: Surveys were conducted of 514 individuals using three chloroplast DNA fragments and three nuclear microsatellite loci. These individuals included 246 from 45 populations of Zizania latifolia in eastern Asia, and the following from North America: 154 individuals from 26 populations of Z. aquatica, 84 individuals from 14 populations of Z. palustris, and 30 individuals from one population of Z. texana. KEY RESULTS: The genetic diversity of North American Zizania was significantly higher than that of eastern Asian Zizania. High levels of genetic differentiation among populations and no signal of population expansion were detected in three widespread species. No phylogeographic structure was observed in Z. latifolia, and discordant patterns of cpDNA and microsatellite markers were observed in North American Zizania. CONCLUSIONS: Reduced variation in Zizania latifolia likely reflects its perennial life history, the North American origin of Zizania, and the relative homogeneity of aquatic environments. High levels of genetic differentiation suggest limited dispersal among populations in all Zizania species. The more complex patterns of diversification and evolution in North American Zizania may be driven by the greater impact of glaciation in North America relative to eastern Asia.

Development of microsatellite markers in the hexaploid aquatic macrophyte, Myriophyllum spicatum (Haloragaceae).

PREMISE OF THE STUDY: We developed microsatellite primers to investigate genetic diversity and population genetic structure of the cosmopolitan submerged plant Myriophyllum spicatum. • METHODS AND RESULTS: Twenty microsatellite loci were identified in M. spicatum using the microsatellite-enriched library method. The numbers of alleles per locus ranged from one to 13, and the expected heterozygosity varied from 0 to 0.873 with a mean of 0.504 in two Chinese populations of M. spicatum. All of the loci were also found to be amplifiable in the related species M. verticillatum and M. sibiricum. • CONCLUSIONS: The results indicate that these markers will be significant for studies of population genetic structure and evolutionary history of M. spicatum as well as some of its related species.

[Risk factors of post-renal biopsy bleeding].

OBJECTIVE: To evaluate the risk factors of post-renal biopsy bleeding (PBB). METHODS: We retrospectively analyzed the clinical data of 1 262 patients who received ultrasound-guided biopsy of native kidney at our hospital from January 2005 to December 2006. RESULTS: The overall incidence of PBB was 30.3% (383/1,262), among which the incidence of hematoma was 29.4% (371/1,262) (the percentages of less and more than 5cm were 73.9% and 26.1%, respectively) while that of gross hematuria was only 1.3% (17/1,262). The incidences of minor, intermediate, and major bleeding complications were 21.4% (270/1,262), 8.4% (106/1,262), and 0.6% (7/1,262), respectively. In seven patients with major bleeding complications, six had renal disease secondary to rheumatic disease (lupus nephritis, n = 5; scleroderma crisis, n = 1), while the other one had IgA nephropathy (Lee's classification V). The risk of PBB was relatively higher in women and younger patients. CONCLUSIONS: Patients with chronic connective tissue diseases are vulnerable to severe PBB complications. A close monitoring of these patients is necessary.

A preliminary study on population genetic structure and phylogeography of the wild and cultivated Zizania latifolia (Poaceae) based on Adh1a sequences.

Recent decades have witnessed growing interests in exploring the population genetics and phylogeography of crop plants and their wild relatives because of their important value as genetic resources. In this study, sequence variation of the nuclear Adh1a gene was used to investigate the genetic diversity and phylogeographic pattern of the wild and cultivated Zizania latifolia Turcz. Sequence data were obtained from 126 individuals representing 21 wild populations in China and 65 varieties of the cultivated Zizania latifolia. Low to medium level nucleotide diversity was found in the wild populations, with northeastern populations being the most variable. We detected significant population subdivision (F (ST) = 0.481) but no significant phylogeogaphical structure, suggesting limited gene flow and dispersal among populations. The current pattern of genetic variation in the wild populations might be explained by a fragmentation of ancient populations due to habitat destruction and degradation during recent decades. The heterogeneous levels and spatial apportionment of genetic diversity among wild populations also suggested a history of gradual colonization of Zizania latifolia populations from the northeast to the south of China. Interestingly, all 65 varieties of the cultivated Zizania latifolia possessed a single identical genotype, implying a single domestication associated with very few initial individuals.

Independent versus sequential reading in ROC studies of computer-assist modalities: analysis of components of variance.

RATIONALE AND OBJECTIVES: The authors analyzed two methods for arranging the temporal sequencing of unaided versus computer-assisted reading in multiple-reader, multiple-case receiver operating characteristic studies of detection of solitary pulmonary nodules on chest radiographs. In the "independent" mode the readings are separated by about I month; in the "sequential" mode, the computer-assisted reading immediately follows the unassisted reading. MATERIALS AND METHODS: The authors used the method of Beiden, Wagner, and Campbell (BWC) to decompose the components of variance of receiver operating characteristic accuracy measures into those that are correlated and those that are uncorrelated across reading conditions. Only the latter contribute to uncertainty in estimates of the difference in accuracy measures across reading conditions (unaided vs aided). This method was used to analyze data from two independent studies of the detection of solitary pulmonary nodules on chest radiographs. RESULTS: In the sequential reading mode the components that were correlated across reading conditions increased compared to the independent reading mode, as might be expected. What was not anticipated was the fact that the total reader variance was approximately the same for the two reading modes. The results were remarkably similar across the two independent studies analyzed. CONCLUSION: The sequential reading mode may thus be the more sensitive probe of the difference between unassisted and computer-assisted reading, if the mean effect is unperturbed (as here). It is also the least demanding on the logistics and investment of reader time.