Rare Gingival Metastasis by Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) uncommonly metastasizes to the gingiva, which always means a poor outcome. We reported a rare HCC case with multiple metastases to gingiva, lungs, and brain. A 60-year-old man was initially diagnosed as HCC with metastases to double lungs. He was subjected to a transarterial chemoembolization (TACE) (5-fluorouracil, 750 mg) and two cycles of intravenous chemotherapy (gemcitabine 1.8 g at days 1 and 8, oxaliplatin 200 mg at day 2, every 4 weeks). However, the volume of liver tumor still increased. A bean-size gingival nodule growing with occasional bleeding was also found. TACE (5-fluorouracil 750 mg, perarubicin 40 mg, cisplatin 20 mg) was performed again and an oral sorafenib therapy (400 mg, twice per day) was adopted. The disease maintained relatively stable for about 6 months until a second obvious progress. The gingival nodule was then palliatively excised and identified as a poorly differentiated metastatic HCC by histopathological examination. Best supportive treatments were made since the performance score was too bad. Finally, cerebral metastases occurred and the patient died of systemic failure. Upon review of previous reports, we discussed risk factors, clinical and pathological characteristics, treatments, and prognosis of gingival metastasis by HCC

Insights into the Ecological Roles and Evolution of Methyl-Coenzyme M Reductase-Containing Hot Spring Archaea

Several recent studies have shown the presence of genes for the key enzyme associated with archaeal methane/alkane metabolism, methyl-coenzyme M reductase (Mcr), in metagenome-assembled genomes (MAGs) divergent to existing archaeal lineages. Here, we study the mcr-containing archaeal MAGs from several hot springs, which reveal further expansion in the diversity of archaeal organisms performing methane/alkane metabolism. Significantly, an MAG basal to organisms from the phylum Thaumarchaeota that contains mcr genes, but not those for ammonia oxidation or aerobic metabolism, is identified. Together, our phylogenetic analyses and ancestral state reconstructions suggest a mostly vertical evolution of mcrABG genes among methanogens and methanotrophs, along with frequent horizontal gene transfer of mcr genes between alkanotrophs. Analysis of all mcr-containing archaeal MAGs/genomes suggests a hydrothermal origin for these microorganisms based on optimal growth temperature predictions. These results also suggest methane/alkane oxidation or methanogenesis at high temperature likely existed in a common archaeal ancestor

Yinchen Linggui Zhugan Decoction Ameliorates Nonalcoholic Fatty Liver Disease in Rats by Regulating the Nrf2/ARE Signaling Pathway

Yinchen Linggui Zhugan Decoction (YCLGZGD) is the combination of Linggui Zhugan (LGZGD) and Yinchenhao (YCHD) decoctions, two famous traditional Chinese medicine prescriptions. In previous studies, we found that Yinchen Linggui Zhugan Decoction (YCLGZGD) could regulate lipid metabolism disorder and attenuate inflammation in pathological process of nonalcoholic fatty liver disease (NAFLD). However, the exact underlying mechanism remains unknown. The aim of this study was to explore the effect of Yinchen Linggui Zhugan Decoction on experimental NAFLD and its mechanism in rats with high-fat diet (HFD) which was established by 8-week administration of HFD. YCLGZGD, LGZGD, and YCHD were administered daily for 4 weeks, after which the rats were euthanized. The level of blood lipid, liver enzymes, H&E, and Oil Red O staining were determined to evaluate NAFLD severity. Western blotting and real-time polymerase chain reaction were, respectively, used to determine hepatic protein and gene expression of Keap1, Nrf2, NQO1, and HO-1. Oral YCLGZGD ameliorated HFD-induced NAFLD. Furthermore, YCLGZGD increased the protein and gene expression of Nrf2, NQO1, and HO-1 without changing Keap1. Overall, these results suggest that YCLGZGD ameliorates HFD-induced NAFLD in rats by upregulating the Nrf2/ARE signaling pathway

GABA, progesterone and zona pellucida activation of PLA2 and regulation by MEK-ERK1/2 during acrosomal exocytosis in guinea pig spermatozoa

AbstractWe investigated whether GABA activates phospholipase A2 (PLA2) during acrosomal exocytosis, and if the MEK-ERK1/2 pathway modulates PLA2 activation initiated by GABA, progesterone or zona pellucida (ZP). In guinea pig spermatozoa prelabelled with [14C]arachidonic acid or [14C]choline chloride, GABA stimulated a decrease in phosphatidylcholine (PC), and release of arachidonic acid and lysoPC, during exocytosis. These lipid changes are indicative of PLA2 activation and appear essential for exocytosis since inclusion of aristolochic acid (a PLA2 inhibitor) abrogated them, along with exocytosis. GABA activation of PLA2 seems to be mediated, at least in part, by diacylglycerol (DAG) and protein kinase C since inclusion of the DAG kinase inhibitor R59022 enhanced PLA2 activity and exocytosis stimulated by GABA, whereas exposure to staurosporine decreased both. GABA-, progesterone- and ZP-induced release of arachidonic acid and exocytosis were prevented by U0126 and PD98059 (MEK inhibitors). Taken together, our results suggest that PLA2 plays a fundamental role in agonist-stimulated exocytosis and that MEK-ERK1/2 are involved in PLA2 regulation during this process

Molecular dissection of Neuroligin 2 and Slitrk3 reveals an essential framework for GABAergic synapse development

In the brain, many types of interneurons make functionally diverse inhibitory synapses onto principal neurons. Although numerous molecules have been identified to function in inhibitory synapse development, it remains unknown whether there is a unifying mechanism for development of diverse inhibitory synapses. Here we report a general molecular mechanism underlying hippocampal inhibitory synapse development. In developing neurons, the establishment of GABAergic transmission depends on Neuroligin 2 (NL2), a synaptic cell adhesion molecule (CAM). During maturation, inhibitory synapse development requires both NL2 and Slitrk3 (ST3), another CAM. Importantly, NL2 and ST3 interact with nanomolar affinity through their extracellular domains to synergistically promote synapse development. Selective perturbation of the NL2-ST3 interaction impairs inhibitory synapse development with consequent disruptions in hippocampal network activity and increased seizure susceptibility. Our findings reveal how unique postsynaptic CAMs work in concert to control synaptogenesis and establish a general framework for GABAergic synapse development

Single cell epigenomic and transcriptomic analysis uncovers potential transcription factors regulating mitotic/meiotic switch

In order to reveal the complex mechanism governing the mitotic/meiotic switch in female germ cells at epigenomic and genomic levels, we examined the chromatin accessibility (scATAC-seq) and the transcriptional dynamics (scRNA-seq) in germ cells of mouse embryonic ovary between E11.5 to 13.5 at single-cell resolution. Adopting a strict transcription factors (TFs) screening framework that makes it easier to understand the single-cell chromatin signature and a TF interaction algorithm that integrates the transcript levels, chromatin accessibility, and motif scores, we identified 14 TFs potentially regulating the mitotic/meiotic switch, including TCFL5, E2F1, E2F2, E2F6, E2F8, BATF3, SP1, FOS, FOXN3, VEZF1, GBX2, CEBPG, JUND, and TFDP1. Focusing on TCFL5, we constructed Tcfl5(+/-) mice which showed significantly reduced fertility and found that decreasing TCFL5 expression in cultured E12.5 ovaries by RNAi impaired meiotic progression from leptotene to zygotene. Bioinformatics analysis of published results of the embryonic germ cell transcriptome and the finding that in these cells central meiotic genes (Stra8, Tcfl5, Sycp3, and E2f2) possess open chromatin status already at the mitotic stage together with other features of TCFL5 (potential capability to interact with core TFs and activate meiotic genes, its progressive activation after preleptotene, binding sites in the promoter region of E2f2 and Sycp3), indicated extensive amplification of transcriptional programs associated to mitotic/meiotic switch with an important contribution of TCFL5. We conclude that the identified TFs, are involved in various stages of the mitotic/meiotic switch in female germ cells, TCFL5 primarily in meiotic progression. Further investigation on these factors might give a significant contribution to unravel the molecular mechanisms of this fundamental process of oogenesis and provide clues about pathologies in women such as primary ovarian insufficiency (POI) due at least in part to meiotic defects

Core cis-element variation confers subgenome-biased expression of a transcription factor that functions in cotton fiber elongation

Cotton cultivars have evolved to produce extensive, long, seed-born fibers important for the textile industry, but we know little about the molecular mechanism underlying spinnable fiber formation. Here, we report how PACLOBUTRAZOL RESISTANCE 1 (PRE1) in cotton, which encodes a basic helix-loop-helix (bHLH) transcription factor, is a target gene of spinnable fiber evolution. Differential expression of homoeologous genes in polyploids is thought to be important to plant adaptation and novel phenotypes. PRE1 expression is specific to cotton fiber cells, upregulated during their rapid elongation stage and A-homoeologous biased in allotetraploid cultivars. Transgenic studies demonstrated that PRE1 is a positive regulator of fiber elongation. We determined that the natural variation of the canonical TATA-box, a regulatory element commonly found in many eukaryotic core promoters, is necessary for subgenome-biased PRE1 expression, representing a mechanism underlying the selection of homoeologous genes. Thus, variations in the promoter of the cell elongation regulator gene PRE1 have contributed to spinnable fiber formation in cotton. Overexpression of GhPRE1 in transgenic cotton yields longer fibers with improved quality parameters, indicating that this bHLH gene is useful for improving cotton fiber quality

TCR Repertoire as a Novel Indicator for Immune Monitoring and Prognosis Assessment of Patients With Cervical Cancer

There is increasing evidence that deep sequencing-based T cell repertoire can sever as a biomarker of immune response in cancer patients; however, the characteristics of T cell repertoire including diversity and similarity, as well as its prognostic significance in patients with cervical cancer (CC) remain unknown. In this study, we applied a high throughput T cell receptor (TCR) sequencing method to characterize the T cell repertoires of peripheral blood samples from 25 CC patients, 30 cervical intraepithelial neoplasia (CIN) patients and 20 healthy women for understanding the immune alterations during the cervix carcinogenesis. In addition, we also explored the signatures of TCR repertoires in the cervical tumor tissues and paired sentinel lymph nodes from 16 CC patients and their potential value in predicting the prognosis of patients. Our results revealed that the diversity of circulating TCR repertoire gradually decreased during the cervix carcinogenesis and progression, but the circulating TCR repertoires in CC patients were more similar to CIN patients than healthy women. Interestingly, several clonotypes uniquely detected in CC patients tended to share similar CDR3 motifs, which differed from those observed in CIN patients. In addition, the TCR repertoire diversity in sentinel lymphatic nodes from CC patients was higher than in tumor tissues. More importantly, less clonotypes in TCR repertoire of sentinel lymphatic node was associated with the poor prognosis of the patients. Overall, our findings suggested that TCR repertoire might be a potential indicator of immune monitoring and a biomarker for predicting the prognosis of CC patients. Although functional studies of T cell populations are clearly required, this study have expanded our understanding of T cell immunity during the development of CC and provided an experimental basis for further studies on its pathogenesis and immunotherapy