The aim of this study is to evaluate an AAV vector that can selectively target breast cancer cells and to investigate its specificity and anti-tumor effects on breast cancer cells both in vitro and ...in vivo, offering a new therapeutic approach for the treatment of EpCAM-positive breast cancer.
In this study, a modified AAV2 viral vector was used, in which EpCAM-specific DARPin EC1 was fused to the VP2 protein of AAV2, creating a viral vector that can target breast cancer cells. The targeting ability and anti-tumor effects of this viral vector were evaluated through in vitro and in vivo experiments.
The experimental results showed that the AAV2M
virus could specifically infect EpCAM-positive breast cancer cells and accurately deliver the suicide gene HSV-TK to tumor tissue in mice, significantly inhibiting tumor growth. Compared to the traditional AAV2 viral vector, the AAV2M
virus exhibited reduced accumulation in liver tissue and had no impact on tumor growth.
This study demonstrates that AAV2M
is a gene delivery vector capable of targeting breast cancer cells and achieving selective targeting in mice. The findings offer a potential gene delivery system and strategies for gene therapy targeting EpCAM-positive breast cancer and other tumor types.
Class II lanthipeptide synthetases (LanMs) are relatively promiscuous to core peptide variations. Previous studies have shown that different LanMs catalyze identical reactions on the same core ...sequence fused to their respective cognate leaders. We characterized a new LanM enzyme from
NIES-88, MalM, and demonstrated that MalM and ProcM exhibited disparate dehydration and cyclization patterns on identical core peptides. Our study provided new insights into the regioselectivity of LanMs and showcased an appropriate strategy for lanthipeptide structural diversity engineering.
Thioamitides are apoptosis-inducing ribosomally synthesized and post-translationally modified peptides (RiPPs) with substantial post-translational modifications (PTMs), whose biosynthetic details ...remain elusive. We reconstituted their key PTMs through
enzymatic reactions and gene coexpressions in
and rigorously demonstrated the order of those modifications. Notably, thioamitide biosynthesis involves N- to C-terminal thioamidations and employs both leader-dependent and leader-independent reactions followed by leader removal by successive degradation. Our study provides a comprehensive overview of thioamitide biosynthesis and lays the foundation for thioamitide engineering in
.
We have generated an iPSCs line (CTGUi001-A) from dermal fibroblasts of a 16-year-old male Fabry disease patient with a novel GLA gene mutation (c.156C > A) using Sendai virus encoding the four ...Yamanaka factors OCT4, SOX2, KLF4, and c-MYC. The CTGUi001-A iPSC line displayed typical embryonic stem cell-like morphology, carried the GLA gene mutation, expressed several pluripotent stem cell makers, retained normal karyotype (46, XY) and was capable of forming teratomas containing three germ layers.
α-receptor agonists have been reported to be safe and effective for treating or preventing spinal-induced hypotension during cesarean delivery. As a pure α
adrenergic agonist, methoxamine has ...potential advantages of reducing myocardial oxygen consumption and protecting the heart in obstetric patients compared to phenylephrine. The aim of this study was to determine the optimal prophylactic methoxamine infusion dose that would be effective for preventing spinal-induced hypotension in 50% (ED
) and 95% (ED
) of parturients.
Eighty parturients with a singleton pregnancy scheduled for elective cesarean delivery were randomly allocated to receive prophylactic methoxamine infusion at one of four different fixed-rates: 1 μg/kg/min (group M1), 2 μg/kg/min (group M2), 3 μg/kg/min (group M3), or 4 μg/kg/min (group M4). An adequate response was defined as absence of hypotension (maternal SBP < 80% of baseline or SBP < 90 mmHg). The values for ED
and ED
of prophylactic methoxamine infusion were determined by probit regression model. The outcomes of maternal hemodynamics and fetal status were compared among the groups.
The calculated ED
and ED
(95% confidence interval) of prophylactic methoxamine infusion dose were 2.178 (95% CI 1.564 to 2.680) μg/kg/min and 4.821 (95% CI 3.951 to 7.017) μg/kg/min, respectively. The incidence of hypotension decreased with increasing methoxamine infusion dose (15/20, 11/20, 7/20 and 2/20 in group M1, M2, M3 and M4 respectively, P < 0.001). 1-min Apgar scores and umbilical arterial PaO2 were lower but umbilical arterial PaCO2 was higher in Group M1. No difference was found in the other incidence of adverse effects and neonatal outcomes among groups.
Under the conditions of this study, when prophylactic methoxamine infusion was given at a fixed-rate based on body weight for preventing spinal-induced hypotension in obstetric patients, the values for ED
and ED
were 2.178 μg/kg/min and 4.821 μg/kg/min respectively.
Chinese Clinical Trial Registry (ChiCTR), registry number of clinical trial: ChiCTR-1,800,018,988 , date of registration: October 20, 2018.
Cav3 channels play an important role in modulating chronic pain. However, less is known about the functional changes of Cav3 channels in superficial spinal dorsal horn in neuropathic pain states. ...Here, we examined the effect of partial sciatic nerve ligation (PSNL) on either expression or electrophysiological properties of Cav3 channels in superficial spinal dorsal horn. Our in vivo studies showed that the blockers of Cav3 channels robustly alleviated PSNL-induced mechanical allodynia and thermal hyperalgesia, which lasted at least 14 days following PSNL. Meanwhile, PSNL triggered an increase in both mRNA and protein levels of Cav3.2 but not Cav3.1 or Cav3.3 in rats. However, in Cav3.2 knockout mice, PSNL predominantly attenuated mechanical allodynia but not thermal hyperalgesia. In addition, the results of whole-cell patch-clamp recordings showed that both the overall proportion of Cav3 current-expressing neurons and the Cav3 current density in individual neurons were elevated in spinal lamina II neurons from PSNL rats, which could not be recapitulated in Cav3.2 knockout mice. Altogether, our findings reveal that the elevated functional Cav3.2 channels in superficial spinal dorsal horn may contribute to the mechanical allodynia in PSNL-induced neuropathic pain model.
Background
The genetic improvement in growth and food habit domestication of largemouth bass (
Micropterus salmoides
) have made breakthroughs in past decades, while the relevant work on disease ...resistance were rarely carried out. Major histocompatibility complex (
MHC
) genes, which are well known as their numbers and high polymorphisms, have been used as candidate genes to mine disease-resistant-related molecular markers in many species.
Methods and results
In present study, we developed and characterized 40 polymorphic and biallelic InDel markers from the major histocompatibility complex genes of largemouth bass. The minor allele frequency, observed heterozygosity, expected heterozygosity and polymorphic information content of these markers ranged from 0.0556 to 0.5000, 0.1111 to 0.6389, 0.1064 to 0.5070, and 0.0994 to 0.3750, respectively. Three loci deviated significantly from Hardy-Weinberg equilibrium, while linkage disequilibrium existed at none of these loci.
Conclusion
These InDel markers might provide references for the further correlation analysis and molecular assisted selection of disease resistance in largemouth bass.
Background： Hemoglobin A 1 c （HbA1 c） measurement is of great value for the diagnosis and monitoring of diabetes. Many manufacturers have developed various experiments to determine the HbAlc ...concentration. However, the longitudinal use of these tests requires strict quality management. This study aimed to analyze the quality of HbAlc measurement systems in China using six sigma techniques to help improve their performances. Methods： A total of 135 laboratories were involved in this investigation in 2015. Bias values and coefficients of variation were collected from an HbA 1 c trueness verification external quality assessment program and an internal quality control program organized by the National Center of Clinical Laboratories in China. The sigma （σ） values and the quality goal index （QGI） were used to evaluate the performances of different groups, which were divided according to principles and instruments. Results： The majority of participants （88, 65.2%） were scored as ＂improvement needed （σ 〈 3）＂, suggesting that the laboratories needed to improve their measurement performance. Only 8.2% （11/135） of the laboratories were scored as ＂world class （σ≥ 6）＂. Among all the 88 laboratories whose σ values were below 3, 52 （59.1%） and 23 （26.1%） laboratories needed to improve measurement precision （QGI 〈8.0） and trueness （QGI 〉 1.2）, respectively; the remaining laboratories （13, 14.8%） needed to improve both measurement precision and trueness. In addition, 16.1% （5/31） and 15.0% （3/20） of the laboratories in ＂TO SOH＂ and ＂ARKRAY＂ groups, respectively, were scored as ＂world class＂, whereas none of the laboratories in ＂BIO-RAD＂ group were scored as ＂world class＂. Conclusions： This study indicated that, although participating laboratories were laboratories with better performance in China, the performances were still unsatisfactory. Actions should be taken to improve HbAlc measurement performance before we can include HbAlc assays in diabetes diagnosis in China.
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