Liver Damage in Patients with HCV/HIV Coinfection Is Linked to HIV-Related Oxidative Stress

HIV infection aggravates the progression of liver damage in HCV-coinfected patients, with the underlying pathogenesis being multifactorial. Although high level of oxidative stress has been observed frequently in patients infected with HIV or HCV, the status of oxidative stress in HIV/HCV coinfection and its contribution to HCV liver damage have not been determined. This study involved 363 HBsAg-negative, anti-HCV-positive former blood donors recruited from a village in central China in July 2005; of these, 140 were positive for HIV. Of these 363 subjects, 282 were successfully followed up through July 2009. HIV/HCV-coinfected subjects had higher rates of end-stage liver disease-related death than those monoinfected with HCV. Liver ultrasound manifestations were poor in HIV-positive than in HIV-negative individuals, in both chronic HCV carriers and those with resolved HCV. Serum concentrations of total glutathione (tGSH), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), GSSG, and reduced GSH were higher in HIV-positive than HIV-negative subjects. GSSG concentrations were higher in HIV-infected subjects with abnormal ALT/AST levels than in those with normal ALT/AST levels and were associated with poorer liver ultrasound manifestations. These finding indicated that HIV infection accelerated HCV-associated liver damage in HIV/HCV-coinfected individuals. Increased oxidative stress, induced primarily by HIV coinfection, may contribute to aggravated liver damage

Bacillus megaterium BMJBN02 induces the resistance of grapevine against downy mildew

Grape downy mildew caused by Plasmopara viticola is one of the most destructive diseases of grapes. All grape cultivars are susceptible to P. viticola. However, the resistance of grape plants could be induced in plant defense with some help of microbes. In this study, Bacillus megaterium BMJBN02 obtained from farmland soil was shown to regulate the resistance of grapevine against downy mildew. The salicylic acid (SA) content and the expression of pathogenesis-related (PR) genes of grapes under different treatments were examined using high-performance liquid chromatography-mass spectrometry (HPLC-MS) and reverse transcription- quantitative polymerase chain reaction (RT-qPCR), and it was found that SA content and the expression of PR genes could play a role in regulating the resistance of grapevine against downy mildew. The five-year plot experiment showed that the resistance effectiveness of isolate BMJBN02 was approximately equal to that of 0.1 % nicotinyl morpholine (commercial fungicide). Therefore, this study provides a valuable candidate method that uses B. megaterium BMJBN02 by regulating the resistance of grape against downy mildew for quality and yield of grape in commercial productivity

MADS-Box Genes and Gibberellins Regulate Bolting in Lettuce (Lactuca sativa L.)

Bolting in lettuce is promoted by high temperature and bolting resistance is of great economic importance for lettuce production. But how bolting is regulated at the molecular level remains elusive. Here, a bolting resistant line S24 and a bolting sensitive line S39 were selected for morphological, physiological, transcriptomic and proteomic comparisons. A total of 12204 genes were differentially expressed in S39 vs S24. Line S39 was featured with larger leaves, higher levels of chlorophyll, soluble sugar, anthocyanin and auxin, consistent with its up-regulation of genes implicated in photosynthesis, oxidation-reduction and auxin actions. Proteomic analysis identified 30 differentially accumulated proteins in lines S39 and S24 upon heat treatment, and 19 out of the 30 genes showed differential expression in the RNA-Seq data. Exogenous gibberellins (GA) treatment promoted bolting in both S39 and S24, while 12 flowering promoting MADS-box genes were specifically induced in line S39, suggesting that although GA regulates bolting in lettuce, it may be the MADS-box genes, not GA, that plays a major role in differing the bolting resistance between these two lettuce lines

Degradable gene delivery systems based on Pluronics-modified low-molecular-weight polyethylenimine: preparation, characterization, intracellular trafficking, and cellular distribution

Wei Fan1,2,*, Xin Wu1,*, Baoyue Ding3,*, Jing Gao4, Zhen Cai1, Wei Zhang1, Dongfeng Yin1, Xiang Wang1, Quangang Zhu1, Jiyong Liu1, Xueying Ding4, Shen Gao1 1Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 2Department of Pharmaceutics, The 425th Hospital of PLA, Sanya, 3Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, 4Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China*These authors contributed equally to this workBackground: Cationic copolymers consisting of polycations linked to nonionic amphiphilic block polymers have been evaluated as nonviral gene delivery systems, and a large number of different polymers and copolymers of linear, branched, and dendrimeric architectures have been tested in terms of their suitability and efficacy for in vitro and in vivo transfection. However, the discovery of new potent materials still largely relies on empiric approaches rather than a rational design. The authors investigated the relationship between the polymers' structures and their biological performance, including DNA compaction, toxicity, transfection efficiency, and the effect of cellular uptake.Methods: This article reports the synthesis and characterization of a series of cationic copolymers obtained by grafting polyethyleneimine with nonionic amphiphilic surfactant polyether-Pluronic® consisting of hydrophilic ethylene oxide and hydrophobic propylene oxide blocks. Transgene expression, cytotoxicity, localization of plasmids, and cellular uptake of these copolymers were evaluated following in vitro transfection of HeLa cell lines with various individual components of the copolymers.Results: Pluronics can exhibit biological activity including effects on enhancing DNA cellular uptake, nuclear translocation, and gene expression. The Pluronics with a higher hydrophilic-lipophilic balance value lead to homogeneous distribution in the cytoplasm; those with a lower hydrophilic-lipophilic balance value prefer to localize in the nucleus.Conclusion: This Pluronic-polyethyleneimine system may be worth exploring as components in the cationic copolymers as the DNA or small interfering RNA/microRNA delivery system in the near future.Keywords: Pluronics, gene transfer, nonviral vectors, transfection efficiency, cellular uptak

Cell-cell interactions during the formation of primordial follicles in humans

Gametogenesis is a complex and sex-specific multistep process during which the gonadal somatic niche plays an essential regulatory role. One of the most crucial steps during human female gametogenesis is the formation of primordial follicles, the functional unit of the ovary that constitutes the pool of follicles available at birth during the entire reproductive life. However, the relation between human fetal germ cells (hFGCs) and gonadal somatic cells during the formation of the primordial follicles remains largely unexplored. We have discovered that hFGCs can form multinucleated syncytia, some connected via interconnecting intercellular bridges, and that not all nuclei in hFGC-syncytia were synchronous regarding meiotic stage. As hFGCs progressed in development, pre-granulosa cells formed protrusions that seemed to progressively constrict individual hFGCs, perhaps contributing to separate them from the multinucleated syncytia. Our findings highlighted the cell-cell interaction and molecular dynamics between hFGCs and (pre)granulosa cells during the formation of primordial follicles in humans. Knowledge on how the pool of primordial follicle is formed is important to understand human infertility.</p

A study of clinical and serological correlation of early myocardial injury in elderly patients infected with the Omicron variant

IntroductionMyocardial injury in elderly Omicron variant patients is a leading cause of severe disease and death. This study focuses on elucidating the clinical characteristics and potential risk factors associated with myocardial injury in elderly patients infected with the Omicron variant.MethodsMyocardial injury was defined based on elevated cardiac troponin concentrations exceeding the 99th percentile upper reference limit. Among 772 elderly Omicron-infected patients, categorized into myocardial injury (n = 263) and non-myocardial injury (n = 509) groups. The stratified log-rank statistic was used to compare the probability of patients developing intensive care. Receiver operating characteristic curves were used to determine the best cut-off values of clinical and laboratory data for predicting myocardial injury. Univariate and multivariate logistic regression was adopted to analyze the risk factors for myocardial injury.ResultsThe occurrence of myocardial injury in Omicron variant-infected geriatric patients was up to 34.07% and these patients may have a higher rate of requiring intensive care (P &lt; 0.05). By comparing myocardial injury patients with non-myocardial injury patients, notable differences were observed in age, pre-existing medical conditions (e.g., hypertension, coronary heart disease, cerebrovascular disease, arrhythmia, chronic kidney disease, and heart failure), and various laboratory biomarkers, including cycle threshold-ORF1ab gene (Ct-ORF1ab), cycle threshold-N gene (Ct-N), white blood cell count, neutrophil (NEUT) count, NEUT%, lymphocyte (LYM) count, LYM%, and D-dimer, interleukin-6, procalcitonin, C-reactive protein, serum amyloid A, total protein, lactate dehydrogenase, aspartate aminotransferase, glomerular filtration rate, blood urea nitrogen, and serum creatinine (sCr) levels (P &lt; 0.05). Furthermore, in the multivariable logistic regression, we identified potential risk factors for myocardial injury in Omicron variant–infected elderly patients, including advanced age, pre-existing coronary artery disease, interleukin-6 &gt; 22.69 pg/ml, procalcitonin &gt; 0.0435 ng/ml, D-dimer &gt; 0.615 mg/L, and sCr &gt; 81.30 μmol/L.ConclusionThis study revealed the clinical characteristics and potential risk factors associated with myocardial injury that enable early diagnosis of myocardial injury in Omicron variant-infected elderly patients, providing important reference indicators for early diagnosis and timely clinical intervention

Classification of Atretic Small Antral Follicles in the Human Ovary

The reproductive lifespan in humans is regulated by a delicate cyclical balance between follicular recruitment and atresia in the ovary. The majority of the small antral follicles present in the ovary are progressively lost through atresia without reaching dominance, but this process remains largely underexplored. In our study, we investigated the characteristics of atretic small antral follicles and proposed a classification system based on molecular changes observed in granulosa cells, theca cells, and extracellular matrix deposition. Our findings revealed that atresia spreads in the follicle with wave-like dynamics, initiating away from the cumulus granulosa cells. We also observed an enrichment of CD68+ macrophages in the antrum during the progression of follicular atresia. This work not only provides criteria for classifying three stages of follicular atresia in small antral follicles in the human ovary but also serves as a foundation for understanding follicular degeneration and ultimately preventing or treating premature ovarian failure. Understanding follicular remodeling in the ovary could provide a means to increase the number of usable follicles and delay the depletion of the follicular reserve, increasing the reproductive lifespan.</p