Technical considerations and strategies for generating and optimizing humanized mouse tumor models in immuno-oncology research.

The field of cancer immunotherapy has experienced significant progress, resulting in the emergence of numerous biological drug candidates requiring in vivo efficacy testing and a better understanding of their mechanism of action (MOA). Humanized immune system (HIS) models are valuable tools in this regard. However, there is a lack of systematic guidance on HIS modeling.

THUMPD2 catalyzes the N2-methylation of U6 snRNA of the spliceosome catalytic center and regulates pre-mRNA splicing and retinal degeneration.

The mechanisms by which the relatively conserved spliceosome manages the enormously large number of splicing events that occur in humans (∼200 000 versus ∼300 in yeast) are poorly understood. Here, we show deposition of one RNA modification-N2-methylguanosine (m2G) on the G72 of U6 snRNA (the catalytic center of the spliceosome) promotes efficient pre-mRNA splicing activity in human cells. This modification was identified to be conserved among vertebrates.

The role of the ERK signaling pathway in promoting angiogenesis for treating ischemic diseases.

The main treatment strategy for ischemic diseases caused by conditions such as poor blood vessel formation or abnormal blood vessels involves repairing vascular damage and encouraging angiogenesis. One of the mitogen-activated protein kinase (MAPK) signaling pathways, the extracellular signal-regulated kinase (ERK) pathway, is followed by a tertiary enzymatic cascade of MAPKs that promotes angiogenesis, cell growth, and proliferation through a phosphorylation response. The mechanism by which ERK alleviates the ischemic state is not fully understood.

The PIWI-specific insertion module helps load longer piRNAs for translational activation essential for male fertility.

PIWI-clade proteins harness piRNAs of 24-33 nt in length. Of great puzzles are how PIWI-clade proteins incorporate piRNAs of different sizes and whether the size matters to PIWI/piRNA function. Here we report that a PIWI-Ins module unique in PIWI-clade proteins helps define the length of piRNAs.

Isorhynchophylline inhibits inflammatory responses in endothelial cells and macrophages through the NF-κB/NLRP3 signaling pathway.

Background: Atherosclerosis is a chronic inflammatory disease of arterial wall, which is closely related to inflammatory reaction. In this study, the anti-inflammatory effect of isorhynchophylline was studied by NF- κB / NLRP3 pathway.

Methods: (1) ApoE mice were fed with high-fat diet to establish atherosclerotic model, while C57 with the same genetic background was fed with common diet as control group.

A novel form of docetaxel polymeric micelles demonstrates anti-tumor and ascites-inhibitory activities in animal models as monotherapy or in combination with anti-angiogenic agents.

Malignant ascites (MA) is caused by intraperitoneal spread of solid tumor cells and results in a poor quality of life. Chemotherapy is a common first-line treatment for patients with MA. Taxotere (DTX) is widely used in solid tumor therapies.

The Effect of Psoralen on Glioma Based on Network Pharmacology and Potential Target Research.

Glioma is an aggressive tumor, currently there is no satisfactory management available. Psoralen, as a natural product, has been found to have an effect of treating cancer in recent years, but its effect on glioma has not been explored. In this study, we investigated the in vitro inhibition effect and potential targets of psoralen on glioma through network pharmacology and in glioma treatment experiments.

[Silk fibroin/collagen composite hydrogels with different matrix stiffness influence the growth and phenotype of human mammary epithelial cells].

Extracellular matrix (ECM) stiffness is closely related to the physiological and pathological states of breast tissue. The current study was aimed to investigate the effect of silk fibroin/collagen composite hydrogels with adjustable matrix stiffness on the growth and phenotype of normal breast epithelial cells. In this study, the enzymatic reaction of horseradish peroxidase (HRP) with hydrogen peroxide (HO) was used to change the degree of cross-linking of the silk fibroin solution.

Triage by PAX1 and ZNF582 Methylation in Women With Cervical Intraepithelial Neoplasia Grade 3: A Multicenter Case-Control Study.

Background: The colposcopy-conization inconsistency is common in women with cervical intraepithelial neoplasia grade 3 (CIN3). No adequate method has been reported to identify the final pathology of conization. In this study, we explored the ability of PAX1 and ZNF582 methylation to predict the pathological outcome of conization in advance.

A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription.

Since numerous RNAs and RBPs prevalently localize to active chromatin regions, many RNA-binding proteins (RBPs) may be potential transcriptional regulators. RBPs are generally thought to regulate transcription via noncoding RNAs. Here, we describe a distinct, dual mechanism of transcriptional regulation by the previously uncharacterized tRNA-modifying enzyme, hTrmt13.

Toward the Development of Personalized Syndrome Discriminant Systems: A Discriminant System for Hypertension with Liver Hyperactivity Syndrome.

Traditional Chinese medicine has shown promising results in treating the symptoms of hypertension, a major global health concern not yet fully managed by modern medicine. It is, therefore, of high priority to clarify the altered pathophysiology of hypertension in individuals with liver hyperactivity syndrome (HLYH) in response to effective treatments to better understand this disorder. The primary aim of this study was to construct a personalized syndrome discriminant system based on data capable of informing management strategies prior to the initiation of antihypertensive therapy or the implementation of screening strategies in at-risk HLYH.

THUMPD3-TRMT112 is a m2G methyltransferase working on a broad range of tRNA substrates.

Post-transcriptional modifications affect tRNA biology and are closely associated with human diseases. However, progress on the functional analysis of tRNA modifications in metazoans has been slow because of the difficulty in identifying modifying enzymes. For example, the biogenesis and function of the prevalent N2-methylguanosine (m2G) at the sixth position of tRNAs in eukaryotes has long remained enigmatic.

[Non-targeted metabolomics study and biomarker screening of prehypertensive liver-fire hyperactivity syndrome based on UPLC-Q-Exactive MS technology].

In this study, patients with prehypertensive liver-fire hyperactivity syndrome(LFHS) were selected as the research objects. The plasma samples of healthy volunteers and patients with prehypertensive LFHS were analyzed by non-targeted metabolomics based on UPLC-Q-Exactive MS. The differential biomarkers and metabolic pathways were screened out by multivariate statistics and metabolic pathway analysis, which revealed the characteristics of metabolic patterns of the syndrome.

The occurrence order and cross-talk of different tRNA modifications.

Chemical modifications expand the composition of RNA molecules from four standard nucleosides to over 160 modified nucleosides, which greatly increase the complexity and utility of RNAs. Transfer RNAs (tRNAs) are the most heavily modified cellular RNA molecules and contain the largest variety of modifications. Modification of tRNAs is pivotal for protein synthesis and also precisely regulates the noncanonical functions of tRNAs.

The treatment strategy of patients with positive margins after cervical cold knife conization-A 7-year retrospective study in China.

Objective: To explore treatment strategies for patients with positive margins after cervical cold knife conization (CKC) by estimating the risk of residual or recurrent CIN2 or worse (CIN2+).

Methods: A retrospective study included 569 patients receiving CKC for CIN3 in Xiangya Hospital from January 2013 to December 2017. Demographic characteristics and test results were obtained before CKC, after CKC, at 6, 12, and 24 months, then annually thereafter.

Effect of iron nanoparticles on passivation of cadmium in the pig manure aerobic composting process.

Cadmium (Cd) is a toxic metal ion in pig manure impacting on the ecosystem, and hence the immobilization of Cd by green synthesis of iron nanoparticles (G-nFe) is a potential approach. In this study, transformation of Cd (II) during the pig manure thermophilic aerobic composting process in the presence of G-nFe was investigated. The results show that the addition of G-nFe promoted the composting process and release of available phosphorus (AP).

Serum Metabolomics Study Based on LC-MS and Antihypertensive Effect of on Spontaneously Hypertensive Rats.

Our previous studies have shown that has an important role in lowering blood pressure, but its intervention mechanism has not been clarified completely in the metabolic level. Therefore, in this study, a combination method of HPLC-TOF/MS-based metabolomics and multivariate statistical analyses was employed to explore the mechanism and evaluate the antihypertensive effect of . Serum samples were analyzed and identified by HPLC-TOF/MS, while the acquired data was further processed by partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) to discover the perturbed metabolites.

Helicase POLQ-like (HELQ) as a novel indicator of platinum-based chemoresistance for epithelial ovarian cancer.

Objective: To investigate the role of HELQ in chemo-resistance of epithelial ovarian carcinoma (EOC), which is a critical factor of patients' prognosis.

Methods: Immunohistochemistry, survival analysis of our 87 EOC patients and bioinformatics analysis of The Cancer Genome Atlas (TCGA) datasets (Nature, 2011) disclosed the clinical importance of HELQ expression. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western Blot analyses of EOC tissue were used to confirm it.

Quantitative Serum Proteomic Analysis of Essential Hypertension Using iTRAQ Technique.

Essential hypertension (EH) is a risk factor for some severe diseases. This study aimed to screen out serum special proteins and seek interaction between them, which would provide new therapeutic targets and elucidate the comprehensive pathophysiological mechanism for EH. Patients with EH (Group A, = 47) and healthy controls (HC) (Group B, = 47) were recruited in this study.

Rhynchophylla total alkaloid rescues autophagy, decreases oxidative stress and improves endothelial vasodilation in spontaneous hypertensive rats.

Autophagy plays an important role in alleviating oxidative stress and stabilizing atherosclerotic plaques. However, the potential role of autophagy in endothelial vasodilation function has rarely been studied. This study aimed to investigate whether rhynchophylla total alkaloid (RTA) has a positive role in enhancing autophagy through decreasing oxidative stress, and improving endothelial vasodilation.

Kibdelosporangium metalli sp. nov., isolated from a rare earth mine.

A Gram-stain-positive, oxidase-negative, catalase-positive isolate forming sporangium-like globular bodies, isolated from the rare earth mine of Bayan Obo in China and designated strain KC 266T, was subjected to a comprehensive taxonomic study. Comparative 16S rRNA gene sequence analysis revealed that strain KC 266T represented a novel lineage within the genus Kibdelosporangium and showed highest 16S rRNA gene similarities to Kibdelosporangiumphilippinense (98.5 %), Kibdelosporangiumaridum subsp.

[The mechanism of action of valsartan studied by HPLC-TOF/MS].

High performance liquid chromatography-time-off-flight mass spectrometer (HPLC-TOFMS) technology coupled with partial least squares discriminant analysis (PLS-DA) processed by SIMCA-P software was applied to investigate serum endogenous metabolites alternations of valsartan in spontaneous hypertension rats (SHR). And MetPA platform was used to connect identified potential biomarkers in corresponding metabolic pathways to find possible therapeutic mechanism of valsartan. Valsartan significantly declined the blood pressure of SHRs (P < 0.

Enhanced Protective Effect of the Combination of Uncaria and Semen Raphani on Vascular Endothelium in Spontaneously Hypertensive Rats.

Endothelial dysfunction and low-grade inflammation are closely associated with hypertension and other cardiovascular diseases. The combination of Uncaria (U) and Semen Raphani (R) is common in traditional Chinese medicine for the treatment of hypertension and heart diseases. We aimed to investigate the therapeutic effect of the combination of Uncaria and Semen Raphani on spontaneously hypertensive rats (SHRs), and valsartan was used as a positive control.