Endoscopic grading of gastric atrophy and histological gastritis staging on risk assessment for early gastric cancer: A case-control study.

OBJECTIVES: To assess the predictive value of endoscopic grading of gastric atrophy using Kimura-Takemoto classification, histological grading systems of operative link on gastritis assessment (OLGA) and operative link on gastric intestinal metaplasia (OLGIM) on risk stratification for early gastric cancer (EGC) and other potential risk factors of EGC. METHODS: A single-center, case-control study was retrospectively conducted including 68 patients with EGC treated with endoscopic submucosal dissection and 68 age- and sex-matched control subjects. Kimura-Takemoto classification, OLGA and OLGIM systems, and other potential risk factors were evaluated between the two groups. RESULTS: Of the 68 EGC lesions, 22 (32.4%) were well differentiated, 38 (55.9%) were moderately differentiated, and 8 (11.8%) were poorly differentiated, respectively. Multivariate analysis revealed O-type Kimura-Takemoto classification (adjusted odds ratio [AOR] 3.282, 95% confidence interval [CI] 1.106-9.744, P = 0.032) and OLGIM stage III/IV (AOR 17.939, 95% CI 1.874-171.722, P = 0.012) were significantly related to a higher risk of EGC. Especially, O-type Kimura-Takemoto classification within 6-12 months before EGC diagnosis (AOR 4.780, 95% CI 1.650-13.845, P = 0.004) was independently associated with EGC risk. Areas under the receiver operating characteristic curve of the three systems for EGC were comparable. CONCLUSIONS: Endoscopic Kimura-Takemoto classification and histological OLGIM stage III/IV are independent risk factors for EGC, which may reduce the need for biopsies in risk stratification of EGC. Further multicenter prospective studies of large sizes are needed.

Elongases of Long-Chain Fatty Acids ELO2 and ELO9 Are Involved in Cuticle Formation and Function in Fecundity in the Yellow Fever Mosquito, Aedes aegypti.

Long-chain fatty acid elongases (ELOs) play important roles in the metabolism of fatty acids in insects. In this study, the genes for two elongases from Aedes aegypti were identified, AeELO2 and AeELO9. Quantitative real time PCR showed that AeELO2 and AeELO9 are expressed at all developmental stages and some body parts, but with different expression patterns. RNAi-mediated knockdown of AeELO2 and AeELO9 was performed to investigate their roles in the development, growth, osmotic balance, and cold tolerance of Ae. aegypti. Knockdown of AeELO2 slowed larval growth and development by causing molting abnormalities. Additionally, 33% ± 3.3% of adults died during oviposition, accompanied by an abnormal extension of cuticles in AeELO2-dsRNA knockdown mosquitos. Knockdown of AeEL09 resulted in abnormal balance of cuticular osmotic pressure and a reduction in egg production. The maximal mRNAs of AeELO2 and AeELO9 were detected in eggs at 72 h after oviposition. Moreover, AeELO2 knockdown reduced the egg hatching rates and AeELO9 knockdown larvae did not develop well. In summary, AeELO2 is involved in larval molting and growth, and its knockdown affects the flexibility and elasticity of adult mosquito cuticles. AeELO9 regulates cold tolerance, osmotic balance, and egg development in Ae. aegypti.

Ectopic invasive ACTH-secreting pituitary adenoma mimicking chordoma: a case report and literature review.

BACKGROUND: Ectopic pituitary adenoma (EPA) is defined as a special type of pituitary adenoma that originates outside of the sellar region, is extra- or intra-cranially located, and without connection to normal pituitary tissue. EPA is extremely rare, with most cases presented as case reports or small case series. Due to nonspecific symptoms and laboratory indicators, the preoperative diagnosis, treatment and management for EPA remain challenging. CASE PRESENTATION: Here, we report the imaging phenotype and pathological findings of a case of invasive EPA in a 47-year-old woman. A preoperative non-contrast CT scan revealed a 5.8 × 3.6 × 3.7 cm soft tissue mass located in the sphenoid sinus and clivus. MRI showed an ill-defined solid mass with heterogeneous signals on T1-weighted and T2-weighted images. The mass displayed infiltrative growth pattern, destroying bone of the skull base, invading adjacent muscles and encasing vessels. The patient underwent partial tumor resection via transsphenoidal endoscopic surgery. Pathological examination led to diagnosis of ectopic ACTH-secreting pituitary adenoma. Post-surgery, the patient received external beam radiotherapy. CONCLUSION: EPA with invasive growth pattern has rarely been reported. The imaging phenotype displays its relationship to the pituitary tissue and surrounding structures. Immunohistochemical examination acts as a crucial role in differentiating EPA from other skull base tumors. This case report adds to the literature on EPA by summarizing its characteristics alongside a review of the literature.

Ufl1 deficiency causes skin pigmentation by up-regulation of Endothelin-1.

Ufmylation (UFM1 modification) is a newly identified ubiquitin-like modification system involved in numerous cellular processes. However, the regulatory mechanisms and biological functions of this modification remain mostly unknown. We have recently reported that Ufmylation family genes have frequent somatic copy number alterations in human cancer including melanoma, suggesting involvement of Ufmylation in skin function and disease. UFL1 is the only known Ufmylation E3-like ligase. In this study, we generated the skin-specific Ufl1 knockout mice and show that ablation of Ufl1 caused epidermal thickening, pigmentation and shortened life span. RNA-Seq analysis indicated that Ufl1 deletion resulted in upregulation of the genes involved in melanin biosynthesis. Mechanistically, we found that Endothelin-1 (ET-1) is a novel substrate of Ufmylation and this modification regulates ET-1 stability, and thereby deletion of Ufl1 upregulates the expression and secretion of ET-1, which in turn results in up-regulation of genes in melanin biosynthesis and skin pigmentation. Our findings establish the role of Ufl1 in skin pigmentation through Ufmylation modification of ET-1 and provide opportunities for therapeutic intervention of skin diseases.

SECISBP2L-Mediated Selenoprotein Synthesis Is Essential for Autonomous Regulation of Oligodendrocyte Differentiation.

Thyroid hormone (TH) controls the timely differentiation of oligodendrocytes (OLs), and its deficiency can delay myelin development and cause mental retardation. Previous studies showed that the active TH T3 is converted from its prohormone T4 by the selenoprotein DIO2, whose mRNA is primarily expressed in astrocytes in the CNS. In the present study, we discovered that SECISBP2L is highly expressed in differentiating OLs and is required for DIO2 translation. Conditional knock-out (CKO) of Secisbp2l in OL lineage resulted in a decreased level of DIO2 and T3, accompanied by impaired OL differentiation, hypomyelination and motor deficits in both sexes of mice. Moreover, the defective differentiation of OLs in Secisbp2l mutants can be alleviated by T3 or its analog, but not the prohormone T4. The present study has provided strong evidence for the autonomous regulation of OL differentiation by its intrinsic T3 production mediated by the novel SECISBP2L-DIO2-T3 pathway during myelin development.SIGNIFICANCE STATEMENT Secisbp2l is specifically expressed in differentiating oligodendrocytes (OLs) and is essential for selenoprotein translation in OLs. Secisbp2l regulates Dio2 translation for active thyroid hormone (TH) T3 production in the CNS. Autonomous regulation of OLs differentiation via SECISBP2L-DIO2-T3 pathway.

Molecular Epidemiology and Pathogenic Characterization of Novel Chicken Infectious Anemia Viruses in Henan Province of China.

Chicken infectious anemia (CIA) is an immunosuppressive disease caused by the chicken infectious anemia virus (CIAV) resulting in heavy economic losses once an outbreak is established. This study conducted a systematic analysis of the epidemiology and pathology of CIA in Henan province, China. A total of 437 clinical tissue samples and 120 poultry disease-related live attenuated vaccines were collected during 2017-2020; of which 45 were positive for CIAV nucleic acid, with a positive rate of 8.08%. Our results showed that genome sequence similarity among a total of 12 CIAV isolates was high, and ranged from 97.1 to 99.3%, and their similarity to the vaccine strains Cux-1 and Del-Ros ranged from 97.8 to 98.6%. However, There were mutations in the locus of the major capsid proteins VP1, VP2, and VP3 among all isolates. The subsequent sequence analysis indicated that the isolates of HN-4 and HN-8 showed genetic recombination and follow up animal experiments revealed that HN-4 might be a pathogenic strain. Our results reveal that both field infection and non-CIAV vaccines contamination promote the epidemiology of CIAV in China and some dominant epidemic viruses have undergone recombination and evolution. This study provides important information to help with the prevention and control of CIAV in the poultry industry.

Essential role of Msx1 in regulating anterior-posterior patterning of the secondary palate in mice.

Development of the secondary palate displays molecular heterogeneity along the anterior-posterior axis; however, the underlying molecular mechanism remains largely unknown. MSX1 is an anteriorly expressed transcription repressor required for palate development. Here, we investigate the role of Msx1 in regional patterning of the secondary palate. The Wnt1-Cre-mediated expression of Msx1 (RosaMsx1Wnt1-Cre) throughout the palatal mesenchyme leads to cleft palate in mice, associated with aberrant cell proliferation and cell death. Osteogenic patterning of the hard palate in RosaMsx1Wnt1-Cre mice is severely impaired, as revealed by a marked reduction in palatine bone formation and decreased expression of the osteogenic regulator Sp7. Overexpression and knockout of Msx1 in mice show that the transcription repressor promotes the expression of the anterior palate-specific Alx1 but represses the expression of the medial-posterior palate genes Barx1, Meox2, and Tbx22. Furthermore, Tbx22 constitutes a direct Msx1 target gene in the secondary palate, suggesting that Msx1 can directly repress the expression of medial-posterior specific genes. Finally, we determine that Sp7 is downstream of Tbx22 in palatal mesenchymal cells, suggesting that a Msx1/Tbx22/Sp7 axis participates in the regulation of palate development. Our findings unveil a novel role for Msx1 in regulating the anterior-posterior growth and patterning of the secondary palate.

Traditional uses, phytochemistry, pharmacology and clinical applications of Cortex Juglandis Mandshuricae: A comprehensive review.

ETHNOPHARMALOGICAL RELEVANCE: Cortex Juglandis Mandshuricae (CJM) is the dry branch or stem bark of the Juglans mandshurica Maxim. and is widely used as a traditional Chinese medicine in Asia and Africa. Its use was first recorded in Kaibao Bencao. AIM OF THE STUDY: The present review provides a deeper insight, better awareness and detailed knowledge of phytochemistry, pharmacology, quality control, along with clinical applications of Cortex Juglandis Mandshuricae. METHODS: The relevant information of Cortex Juglandis Mandshuricae was obtained from several databases including Web of Science, PubMed, and CNKI. The medical books, PhD and MSc dissertations in Chinese were also used to perform this work. RESULTS: CJM has been traditionally used against a wide range of diseases, including dysentery, acute conjunctivitis, bacterial infections, and cancer. A total of 249 compounds have been isolated from CJM; they mainly include quinones and their derivatives, flavonoids, tannins, diarylheptanoids, triterpenoids, coumarins, phenylpropanoids, and volatile oils. These compounds exert anti-tumor, anti-oxidant, anti-inflammatory, bacteriostatic, anti-complement, immunomodulatory, anti-parasitic activities. Specifically, the effects of juglone, alkaloids and unsaturated fatty acid CJM components against hepatic cancer occur through exertion of apoptosis through a mitochondria-dependent pathway. In addition, taxifolin and several tannins have been found to have anti-HIV activity, and (±)-juglanaloid A and (±)-juglanaloid B target Alzheimer disease. Quality control is monitored through identification of juglone, quercetin, and volatile oils. A clinical preparation of CJM, Compound Muji Granules, is used in the treatment of various liver diseases with good therapeutic effect. CONCLUSION: While CJM has been used extensively as a folk medicine, the relationships between structure and activity remain unclear. More in vivo models are needed to study the pharmacological mechanisms of action and to assess potential toxic components, in addition to which the evidence used to demonstrate the quality standards of medicinal materials is clearly inadequate. Therefore, more in-depth research is needed to provide a reasonable scientific basis improve its clinical utilization.

[Relationship Between the Changes of Regulatory T Cells and Th17 Cells and the Prognosis of Children with Aplastic Anemia].

OBJECTIVE: To explore the correlation between the of regulatory T cells, Th17 cells and the prognosis of children with aplastic anemia. METHODS: The clinical data 13 children with aplastic anemia (AA) treated by antithymocyte globulin (ATG) combined with Cyclosporine in Beijing Children's Hospital, Capital Medical University from January 2017 to January 2018 were analyized retrospectively. The changes of T cell and Th17 cell expression level in peripheral blood of AA children before and after IST for 6 and 12 month were compared and analyzed. The SPSS 19.0 statistical package was used for data analysis. RESULTS: Compared with the pre-IST, the expression level of Treg cells decreased at 6 months of IST, the difference was statistically significant (P＜0.05); however the expression level of Th17 cells did not show significant difference as compared with that pre-IST. The expression level of Treg and Th17 cells at 12 months of IST was lower than that pre-IST (P＜0.01), compared with the level pre-IST, the ratio of Treg cells/Th17 cell at 6 months and 12 months of IST did not show a singificand difference. CONCLUSION: Treg cells and Th17 cells in peripheral blood of AA children decrease after IST, which suggests that the change of regulatory T cells and Th17 cells correlate with the clinical outcome of children with aplastic anemia.

An improved overlap extension PCR for simultaneous multiple sites large fragments insertion, deletion and substitution.

The existing molecular cloning methods are often limited by the availability of suitable restriction sites. It is still a challenge for simultaneous cloning of multiple fragments into different sites of a single vector. Here we developed a novel method named improved overlap extension PCR (IOEP) for restriction enzyme independent cloning of large fragments. The addition of primers enables IOEP to exponentially amplify the overlap extension product, thus greatly improves the amplification efficiency of large fragments. Moreover, coupled with the benefit of T4 DNA polymerase to improve cloning efficiency, our method can be used to simultaneously insert, delete and replace multiple DNA fragments at different sites.

Plasma levels and expression of interleukin-37 in patients with immune thrombocytopenia.

Interleukin (IL)-37 has an important role in autoimmune diseases by suppressing immunity and inflammation; however, the role of IL-37 in immune thrombocytopenia (ITP) has remained largely elusive. The present study aimed to investigate the expression of IL-37 and its potential role in the pathogenesis of ITP. The plasma levels and expression of IL-37 in the peripheral blood mononuclear cells of patients with active ITP, ITP patients in remission and healthy controls were measured by ELISA and reverse transcription-quantitative PCR, respectively. The levels of IL-37 in patients with ITP treated with and without glucocorticoids were also determined by ELISA. Specific anti-platelet glycoprotein (GP)IIb/IIIa and/or GPIb/IX autoantibodies were assayed by modified monoclonal antibody-specific immobilization of platelet antigens. The mean value of plasma IL-37 in ITP patients was slightly higher than that in healthy controls, but this was not statistically significant. There was no correlation between IL-37 and anti-platelet autoantibodies, and no significant difference in the IL-37 concentration was identified between patients treated with and without glucocorticoids. In addition, the correlation between IL-37 and the platelet count was analyzed, with no statistical significance observed. It was therefore concluded that IL-37 may not have a pivotal role in the development of ITP. However, the lack of significant differences may be due to the limited number of patients in different groups. A larger number of ITP patients should be enrolled in the future work and achieve more accurate results.

WNT signaling represses astrogliogenesis via Ngn2-dependent direct suppression of astrocyte gene expression.

Neural progenitor cells (NPCs) are sequentially specified into neurons and glia during the development of central nervous system. WNT/ß-catenin signaling is known to regulate the balance between the proliferation and differentiation of NPCs during neurogenesis. However, the function of WNT/ß-catenin signaling during gliogenesis remains poorly defined. Here, we report that activation of WNT/ß-catenin signaling disrupts astrogliogenesis in the developing spinal cord. Conversely, inhibition of WNT/ß-catenin signaling leads to precocious astrogliogenesis. Further analysis reveals that activation of WNT/ß-catenin pathway results in a dramatic increase of neurogenin 2 (Ngn2) expression in transgenic mice, and knockdown of Ngn2 expression in neural precursor cells can reverse the inhibitory effect of WNT/ß-catenin on astrocytic differentiation. Moreover, Ngn2 can directly bind to the promoters of several astrocyte specific genes and suppress their expression independent of STATs activity. Together, our studies provide the first in vivo evidence that WNT/ß-catenin signaling inhibits early astrogliogenesis via an Ngn2-dependent transcriptional repression mechanism.

Involvement of tetraspanin 8 in the innate immune response of the giant prawn, Macrobrachium rosenbergii.

The tetraspanins, representing a conserved superfamily of four-span membrane proteins, are highly involved in viral and bacterial infections. Thus far, the function of the tetraspanins in crustaceans remains largely unknown. In this study, we report the cloning and expression analysis of a tetraspanin 8 from the giant freshwater prawn, Macrobrachium rosenbergii (named as MrTspan8). MrTspan8 contains a 720-bp open reading frame encoding a 239-amino acids protein, which exhibits four transmembrane domains and two extracellular loops that are typical for tetraspanins. MrTspan8 was found to be widely expressed in a variety of prawn tissues including heart, gill, muscle, gut, and hepatopancreas. Additionally, MrTspan8 expression was significantly increased in the hepatopancreas and gill of the prawns challenged by the bacterial pathogen Aeromonas hydrophila. Moreover, we show that pre-incubation of the peptides from the large extracellular loop of MrTSPAN8 protein reduced the cell death caused by A. hydrophila infection in prawn tissue, suggesting that MrTSPAN8 could be a mediator for bacterial infection to prawn.

Wntless, a conserved Wnt-transport protein, is involved in the innate immune response of Macrobrachium rosenbergii.

Wnt signaling plays important roles in a variety of developmental and pathological processes. Here we show that Wntless, the main regulator for Wnt secretion, is involved in the innate immune response of the giant freshwater prawn, Macrobrachium rosenbergii. The full-length cDNA of the prawn Wntless (named MrWntless) is 2173 bp in length and contains a 1602-bp open reading frame (ORF), which is conceptually translated into a 533-amino acids sequence. MrWntless protein contains a highly conserved Wnt-binding domain which is required for secretion of Wnt ligands, and exhibits 57-67% identity with known Wntless proteins of other animals. MrWntless was found to be expressed in a variety of prawn tissues including heart, gill, muscle, gut, hepatopancreas and ovary. Moreover, MrWntless expression was significantly increased in the hepatopancreas and gill of the prawns challenged by the bacterial pathogen Aeromonas hydrophila and Vibrio parahaemolyticus. Knockdown of MrWntless by RNA interference in prawns led to dramatically decreased MrWntless expression of approximately 70%. Furthermore, the cumulative mortality rate of the prawn injected with MrWntless dsRNA was greatly increased in response to A. hydrophila challenge compared with the control prawns. Taken together, we provide evidence that prawn Wntless is important for their innate immune response against bacterial pathogens.

Molecular cloning and expression analysis of a prawn (Macrobrachium rosenbergii) juvenile hormone esterase-like carboxylesterase following immune challenge.

Methyl farnesoate (MF), the crustacean juvenile hormone (JH), plays critical roles in various physiological processes in crustaceans. The titer of MF is precisely regulated by specific carboxylesterase. Here, we report for the first time that the cloning and expression analysis of a JH esterase-like carboxylesterase from the prawn Macrobrachium rosenbergii (named as MrCXE). MrCXE contained a 1935-bp open reading frame (ORF) conceptually translated into a 644-amino acids protein. MrCXE protein shared the highest identity (36%) with JH esterase-like carboxylesterase from the swimming crab, Portunus trituberculatus and exhibited the typical motifs of JH esterase-like carboxylesterases. MrCXE was most abundantly expressed in hepatopancreas, the major tissue for MF metabolism. MrCXE was expressed at a low level in gut and was not detected in other tissues. Additionally, MrCXE expression was upregulated in hepatopancreas by eyestalk ablation to increase MF level. Furthermore, the mRNA level of MrCXE was significantly increased in the hepatopancreas when challenged by the bacterial pathogens Aeromonas hydrophila and Vibrio parahaemolyticus. To our knowledge, this is the first report that the JH esterase-like carboxylesterase is involved in the innate immune response of the crustaceans.

TT(N)mGCCTC inhibits archaeal family B DNA polymerases.

The proofreading activity of the archaeal family B DNA polymerases enables PCR with high fidelity. However, thermostable proofreading DNA polymerases occasionally failed to amplify target fragment that could be amplified by Taq DNA polymerase. We have previously showed that G-rich sequences, which form G-quadruplex, can bind to and inhibit proofreading DNA polymerases. Here we showed that single-stranded oligonucleotides containing sequences of TT(N)mGCCTC can bind and inhibit archaeal family B DNA polymerases but not Taq DNA polymerase. It is very likely that TT(N)mGCCTC inhibits thermostable DNA polymerases during PCR in a single-stranded form. To the best of our knowledge, this is the first example of DNA sequence that could inhibit DNA polymerase in its single-stranded form.

Disruption of Wnt production in Shh lineage causes bone malformation in mice, mimicking human Malik-Percin-type syndactyly.

Here, we show that Shh-Cre-mediated deletion of Wntless, the Wnt cargo protein, in mouse posterior limb mesenchyme causes bone syndactyly of the 3rd and 4th digits, resembling the human Malik-Percin type. The Shh descendants gradiently distributed from digit 5 to posterior half of digit 3 in wild-type limbs, however, they abnormally increased in posterior digit 3 in WntlessShh-Cre . WntlessShh-Cre limbs displayed altered expression of hedgehog pathway genes and impaired noncanonical Wnt signaling activity. We further showed that the anterior limb mesenchymal cells in the WlsShh-Cre served as a source of Wnt5a to reorientate the adjacent Wls-lacking Shh lineage cells to move anteriorly and subsequently led to syndactyly, suggesting that aberrant mesenchymal cell movement/condensation may underlie the pathogenesis of syndactyly.

Long non-coding RNA DGCR5 is involved in the regulation of proliferation, migration and invasion of lung cancer by targeting miR-1180.

Accumulating studies have demonstrated that non-coding RNAs (ncRNAs), including small non-coding RNAs (small ncRNAs) and long non-coding RNAs (lncRNAs), are involved in tumor growth in lung cancer (LC). However, the specific role of DGCR5 in LC progression is not yet clear. In the present study, we found that DGCR5 was downregulated and miR-1180 was upregulated in the sera and tissues of LC patients and was correlated with poor prognosis. We also found that DGCR5 suppressed proliferation, migration and invasion of LC cell lines H520 and H1299. In addition, a luciferase reporter gene assay was used to investigate the regulatory relationship between DGCR5 and miR-1180. Furthermore, we suggested that DGCR5 inhibited the expression of AKT, GSK-3ß, and ß-catenin by targeting miR-1180. Based on these findings, DGCR5 might serve as a potential target for the development of effective anti-neoplastic therapies in lung cancer.