An efficient method for decellularization of the rat liver

Background/PurposeUsing gradient ionic detergent, we optimized the preparation procedure for the decellularized liver biologic scaffold, and analyzed its immunogenicity and biocompatibility.MethodsEDTA, hypotonic alkaline solution, Triton X-100, and gradient sodium dodecyl sulfate (1%, 0.5%, and 0.1%, respectively) were prepared for continuous perfusion through the hepatic vascular system. The decellularization of the liver tissue was performed with the optimized reagent buffer and washing protocol. In addition, the preservation of the original extracellular matrix was observed. To analyze its biocompatibility, the scaffold was embedded in a heterologous animal and the inflammation features, including the surrounding cell infiltration and changes of the scaffold architecture, were detected. The cell-attachment ability was also validated by the perfusion culture of HepG2 cells with the scaffold.ResultsBy using gradient ionic detergent, we completed the decellularization process in approximately 5 h, which was shorter than >10 hours in previous experiments (p<0.001). The extracellular matrix was kept relatively intact, with no obvious inflammatory cellular infiltration or structural damage in the grafted tissue. The engraftment efficiencies of HepG2 were 86±5% (n=8). The levels of albumin and urea synthesis were significantly superior to the ones in traditional two-dimensional culture.ConclusionThe current new method can be used efficiently for the decellularization of the liver biologic scaffold with satisfying biocomparability for application both in vivo and in vitro

Oocytes Selected Using BCB Staining Enhance Nuclear Reprogramming and the In Vivo Development of SCNT Embryos in Cattle

The selection of good quality oocytes is crucial for in vitro fertilization and somatic cloning. Brilliant cresyl blue (BCB) staining has been used for selection of oocytes from several mammalian species. However, the effects of differential oocyte selection by BCB staining on nuclear reprogramming and in vivo development of SCNT embryos are not well understood. Immature compact cumulus–oocyte complexes (COCs) were divided into control (not exposed to BCB), BCB+ (blue cytoplasm) and BCB− (colorless cytoplasm) groups. We found that BCB+ oocytes yielded a significantly higher somatic cell nuclear transfer (SCNT) blastocyst rate and full term development rate of bovine SCNT embryos than the BCB− and control oocytes. BCB+ embryos (embryos developed from BCB+ oocytes) showed increased acetylation levels of histone H3 at K9 and K18 (AcH3K9, AcH3K18), and methylation levels of histone H3 at K4 (H3K4me2) than BCB− embryos (embryos developed from BCB− oocytes) at the two-cell stage. Furthermore, BCB+ embryos generated more total cells, trophectoderm (TE) cells, and inner cell mass (ICM) cells, and fewer apoptotic cells than BCB− embryos. The expression of SOX2, CDX2, and anti-apoptotic microRNA-21 were up-regulated in the BCB+ blastocysts compared with BCB− blastocysts, whereas the expression of pro-apoptotic gene Bax was down-regulated in BCB+ blastocysts. These results strongly suggest that BCB+ oocytes have a higher nuclear reprogramming capacity, and that BCB staining can be used to select developmentally competent oocytes for nuclear transfer

Early Blockade of TLRs MyD88-Dependent Pathway May Reduce Secondary Spinal Cord Injury in the Rats

To determine the role of toll-like receptors (TLRs) myeloid differentiation factor 88 (MyD88) dependent pathway in the spinal cord secondary injury, compression injury was made at T8 segment of the spinal cord in adult male Sprague-Dawley rats. Shown by RT-PCR, TLR4 mRNA in the spinal cord was quickly elevated after compression injury. Intramedullary injection of MyD88 inhibitory peptide (MIP) resulted in significant improvement in locomotor function recovery at various time points after surgery. Meanwhile, injury area, p38 phosphorylation, and proinflammation cytokines in the injured spinal cord were significantly reduced in MIP-treated animals, compared with control peptide (CP) group. These data suggest that TLRs MyD88-dependent pathway may play an important role in the development of secondary spinal cord injury, and inhibition of this pathway at early time after primary injury could effectively protect cells from inflammation and apoptosis and therefore improve the functional recovery

Scientometric trends and knowledge maps of global health systems research

Background: In the last few decades, health systems research (HSR) has garnered much attention with a rapid increase in the related literature. This study aims to review and evaluate the global progress in HSR and assess the current quantitative trends. Methods: Based on data from the Web of Science database, scientometric methods and knowledge visualization techniques were applied to evaluate global scientific production and develop trends of HSR from 1900 to 2012. Results: HSR has increased rapidly over the past 20 years. Currently, there are 28,787 research articles published in 3,674 journals that are listed in 140 Web of Science subject categories. The research in this field has mainly focused on public, environmental and occupational health (6,178, 21.46%), health care sciences and services (5,840, 20.29%), and general and internal medicine (3,783, 13.14%). The top 10 journals had published 2,969 (10.31%) articles and received 5,229 local citations and 40,271 global citations. The top 20 authors together contributed 628 papers, which accounted for a 2.18% share in the cumulative worldwide publications. The most productive author was McKee, from the London School of Hygiene \& Tropical Medicine, with 48 articles. In addition, USA and American institutions ranked the first in health system research productivity, with high citation times, followed by the UK and Canada. Conclusions: HSR is an interdisciplinary area. Organization for Economic Co-operation and Development countries showed they are the leading nations in HSR. Meanwhile, American and Canadian institutions and the World Health Organization play a dominant role in the production, collaboration, and citation of high quality articles. Moreover, health policy and analysis research, health systems and sub-systems research, healthcare and services research, health, epidemiology and economics of communicable and non-communicable diseases, primary care research, health economics and health costs, and pharmacy of hospital have been identified as the mainstream topics in HSR fields. These findings will provide evidence of the current status and trends in HSR all over the world, as well as clues to the impact of this popular topic; thus, helping scientific researchers and policy makers understand the panorama of HSR and predict the dynamic directions of research

Current and future therapeutic strategies for Alzheimer’s disease: an overview of drug development bottlenecks

Alzheimer’s disease (AD) is the most common chronic neurodegenerative disease worldwide. It causes cognitive dysfunction, such as aphasia and agnosia, and mental symptoms, such as behavioral abnormalities; all of which place a significant psychological and economic burden on the patients’ families. No specific drugs are currently available for the treatment of AD, and the current drugs for AD only delay disease onset and progression. The pathophysiological basis of AD involves abnormal deposition of beta-amyloid protein (Aβ), abnormal tau protein phosphorylation, decreased activity of acetylcholine content, glutamate toxicity, autophagy, inflammatory reactions, mitochondria-targeting, and multi-targets. The US Food and Drug Administration (FDA) has approved five drugs for clinical use: tacrine, donepezil, carbalatine, galantamine, memantine, and lecanemab. We have focused on the newer drugs that have undergone clinical trials, most of which have not been successful as a result of excessive clinical side effects or poor efficacy. Although aducanumab received rapid approval from the FDA on 7 June 2021, its long-term safety and tolerability require further monitoring and confirmation. In this literature review, we aimed to explore the possible pathophysiological mechanisms underlying the occurrence and development of AD. We focused on anti-Aβ and anti-tau drugs, mitochondria-targeting and multi-targets, commercially available drugs, bottlenecks encountered in drug development, and the possible targets and therapeutic strategies for future drug development. We hope to present new concepts and methods for future drug therapies for AD

Stray dogs as indicators of Toxoplasma gondii distributed in the environment: the first report across an urban-rural gradient in China

<p>Abstract</p> <p>Background</p> <p>Toxoplasmosis is an important parasitic zoonosis caused by the protozoan <it>Toxoplasma gondii </it>that is distributed world-wide and infects a variety of hosts. However, the prevalence of <it>T. gondii </it>in the environment (such as soil, water and food) is largely unknown. Due to the technical difficulty in oocyst counting directly, an alternative assay using the serologic status of <it>T. gondii </it>in free-living animals, such as stray or free-living dogs, as an indicator, can be used to evaluate environmental contamination indirectly, as they are exposed to the same risk of infection as humans and other animals.</p> <p>Results</p> <p>In the present study, 231 stray or free-living dogs across an urban-rural gradient were examined to assess the frequency of <it>T. gondii </it>in the environment. Specific antibodies to <it>T. gondii </it>were found in 93 dogs (40.3%) by enzyme-linked immunosorbent assay (ELISA), and no statistically significant differences were observed in seroprevalences of <it>T. gondii </it>between urban dogs (38.7%) and rural dogs (41%) (<it>p </it>> 0.05).</p> <p>Conclusions</p> <p>A high seroprevalence of <it>T. gondii </it>in stray or free-living dogs in the present study indicates that there would be a wide distribution and a constant infection pressure of <it>T. gondii </it>across an urban-rural gradient, and the oocysts of <it>T. gondii </it>in the environment would be an important source of infection for humans and other animals both in urban and rural areas in China.</p

Mechanical durability of superhydrophobic surfaces: the role of surface modification technologies

Various surface modification technologies have been used to develop superhydrophobic surface, however their durability has been recognized as the major obstacle for the real applications. Here a quantitative investigation was conducted to evaluate the effects of different surface modification methods on the surfaces’ mechanical durability. The superhydrophobic surfaces were prepared by the combination of two surface roughing methods (etching and sandblasting) with chemical modifications with four low surface energy materials: silica sol (SS), octadecanoic acid (OA), heptadecafluoro-1,1,2,2-tetrahydrodecyltrichlorosilane (HDFS) and hexadecyltriethoxysilane (HTS). XPS was used to analyze the elements composition and AFM was used to measure the roughness of the surfaces. The durability of these surfaces was tested by a sandpaper abrasion experiment. The collective results showed that the low surface energy materials had significant effects on the surface roughness, which would then play an important role in the durability of these rough surfaces. The SS modified rough surfaces possessed higher roughness and better durability than the surfaces modified by other three low surface energy materials. SS modified rough surfaces could bear 60 cycles of abrasion with 10 g weights on 1500 CW sandpaper

Molecular Identification of a Trichinella Isolate from a Naturally Infected Pig in Tibet, China

The first human case with trichinellosis was reported in 1964 in Tibet, China. However, up to the present, the etiological agent of trichinellosis has been unclear. The aim of this study was to identify a Tibet Trichinella isolate at a species level by PCR-based methods. Multiplex PCR revealed amplicon of the expected size (173 bp) for Trichinella spiralis in assays containing larval DNA from Tibet Trichinella isolate from a naturally infected pig. The Tibet Trichinella isolate was also identified by PCR amplification of the 5S ribosomal DNA intergenic spacer region (5S ISR) and mitochondrial large-subunit ribosomal RNA (mt-lsrDNA) gene sequences. The results showed that 2 DNA fragments (749 bp and 445 bp) of the Tibet Trichinella isolate were identical to that of the reference isolates of T. spiralis. The Tibet Trichinella isolate might be classifiable to T. spiralis. This is the first report on T. spiralis in southwestern China

Research Progress on PARP14 as a Drug Target

Poly-adenosine diphosphate-ribose polymerase (PARP) implements posttranslational mono- or poly-ADP-ribosylation modification of target proteins. Among the known 18 members in the enormous family of PARP enzymes, several investigations about PARP1, PARP2, and PARP5a/5b have been launched in the past few decades; more specifically, PARP14 is gradually emerging as a promising drug target. An intact PARP14 (also named ARTD8 or BAL2) is constructed by macro1, macro2, macro3, WWE, and the catalytic domain. PARP14 takes advantage of nicotinamide adenine dinucleotide (NAD+) as a metabolic substrate to conduct mono-ADP-ribosylation modification on target proteins, taking part in cellular responses and signaling pathways in the immune system. Therefore, PARP14 has been considered a fascinating target for treatment of tumors and allergic inflammation. More importantly, PARP14 could be a potential target for a chemosensitizer based on the theory of synthetic lethality and its unique role in homologous recombination DNA repair. This review first gives a brief introduction on several representative PARP members. Subsequently, current literatures are presented to reveal the molecular mechanisms of PARP14 as a novel drug target for cancers (e.g., diffuse large B-cell lymphoma, multiple myeloma, prostate cancer, and hepatocellular carcinoma) and allergic inflammatory. Finally, potential PARP inhibitor-associated adverse effects are discussed. The review could be a meaningful reference for innovative drug or chemosensitizer discovery targeting to PARP14