N-glycosylation is one of the most important posttranslational modifications of proteins. It plays important roles in the biogenesis and functions of proteins by influencing their folding, intracellular localization, stability and solubility. N-glycans are synthesized by glycosyltransferases, a complex group of ubiquitous enzymes that occur in most kingdoms of life. A growing body of evidence shows that N-glycans may influence processing and functions of glycosyltransferases, including their secretion, stability and substrate/acceptor affinity. Changes in these properties may have a profound impact on glycosyltransferase activity. Indeed, some glycosyltransferases have to be glycosylated themselves for full activity. N-glycans and glycosyltransferases play roles in the pathogenesis of many diseases (including cancers), so studies on glycosyltransferases may contribute to the development of new therapy methods and novel glycoengineered enzymes with improved properties. In this review, we focus on the role of N-glycosylation in the activity of glycosyltransferases and attempt to summarize all available data about this phenomenon.

How glycosylation affects glycosylation: the role of N-glycans in glycosyltransferase activity.

Background The mechanism of rapidly increased non-small cell lung cancer (NSCLC) among never-smoking Chinese women has not been elucidated. Ovarian sex steroid hormones have been suggested to counteract lung cancer development, and sex hormone-binding globulin (SHBG) is essential in sex hormones regulation. This study aims to exploring single nucleotide polymorphisms (SNPs) in genomic regions associated with SHBG concentrations that contributed to never-smoking female NSCLC. Methods Candidate genes were selected by a genome-wide association (GWAS) meta-analysis and gene expression profiles of never-smoking NSCLC of Chinese women. The candidate SNPs limited to common minor allele frequency (MAF), missense variant, ethnic heterogeneous distribution, and SNPs were genotyped using the TaqMan method. A two-stage case-control design was adopted for exploration and validation of associations between candidate SNPs and risk of NSCLC. All participants were never-smoking Chinese women. Chi-square test and multivariate logistic regression were applied. Results Beginning with 12 genomic regions associated with circulating SHBG concentrations and gene expression profiles from never-smoking NSCLC in Chinese women, candidate SNP rs12233719 and rs7439366 both located in candidate gene UGT2 B7, which may be related to circulating SHBG concentrations and cancer risk, were identified. A two-stage case-control study was conducted in Shenyang and Tianjin represented as the training stage and validation stage, respectively. Under the dominant model, compared to individuals with the wild G/G genotype, the adjusted OR of those with the T allele was 1.58 (95% CI: 1.15-2.16) in Chinese Shenyang training set, and was 1.49 (95% CI: 1.02-2.18) in Chinese Tianjin validation set, both accompanied with a significant trend relationship consistently. UGT2B7 was upregulated in female NSCLC patients' tumor tissues and was associated with a poor prognosis in NSCLC. Conclusion Our findings indicated that a sex hormones regulation-related SNP rs12233719 was associated with never-smoking female lung cancer risk, which might partially explain NSCLC-susceptibility in Chinese women.

Association between sex hormones regulation‐related SNP rs12233719 and lung cancer risk among never‐smoking Chinese women

Awareness of drug interactions involving opioids is critical for patient treatment as they are common therapeutics used in numerous care settings including both chronic and disease related pain. Not only do opioids have narrow therapeutic indexes and are extensively used, but they have the potential to cause severe toxicity. Opioids are the classical pain treatment for patients who suffer from moderate to severe pain. More importantly, opioids are often prescribed in combination with multiple other drugs, especially in patient populations who typically are prescribed a large drug regimen. This review focuses on the current knowledge of common opioid drug-drug interactions (DDI), focusing specifically on hydrocodone, oxycodone, and morphine DDI. The DDI covered in this review include pharmacokinetic DDI arising from enzyme inhibition or induction, primarily due to inhibition of cytochrome p450 enzymes (CYPs). However, opioids such as morphine are metabolized by uridine-5'-diphosphoglucuronosyltransferases (UGTs), principally UGT2B7, and this is another important pathway for opioid-drug interactions. This review also covers several pharmacodynamic DDI studies as well as the basics of CYP and UGT metabolism including detailed opioid metabolism and the potential involvement of metabolizing enzyme gene variation in DDI. Based upon the current literature, further care is needed to fully investigate and describe the DDI potential with opioids in pain and related disease settings to improve clinical outcomes for patients. Significance Statement A review of the literature focusing on drug-drug interactions involving opioids is important because they can be toxic and potentially lethal, occurring through pharmacodynamic interactions as well as pharmacokinetic interactions occurring through inhibition or induction of drug metabolism.

Hydrocodone, oxycodone, and morphine metabolism and drug-drug interactions.

This year's program committee has put together a program of 7 refereed papers. These papers cover topics on programming language support for building kernels, kernel extensions, embedded systems, parallel data structures, big-data processing systems, and others.

Proceedings of the 8th Workshop on Programming Languages and Operating Systems

Polycystic Ovary Syndrome (PCOS) and osteoporosis, though seemingly unrelated, exhibit intricate connections influenced by genetic and epigenetic factors. PCOS, characterized by elevated androgen levels, insulin resistance, and increased body weight, has historically been considered protective against bone fragility disorders. However, emerging research suggests that chronic inflammation, prevalent in PCOS, can adversely affect bone health. Studies have demonstrated variable bone mineral density loss in PCOS, often associated with leptin resistance and hyperinsulinemia. Key genes such as INS, IGF1, CTNNB1, AKT1, and STAT3 play pivotal roles in the complex interplay between PCOS and osteoporosis, influencing insulin signaling, oxidative stress, and inflammatory pathways. Oxidative stress, a prominent element in PCOS, can lead to osteoporosis through hormonal imbalances, chronic inflammation, insulin resistance, and lifestyle factors. The insulin signaling pathway also significantly impacts both conditions by contributing to hormonal imbalances and bone health alterations. This intricate network of genetic and epigenetic factors underscores the need for a deeper understanding of their interrelationships. Thus, this review elucidates the multifaceted genetic, epigenetic, and inflammatory connections between PCOS and osteoporosis, highlighting their implications for bone health management in individuals with PCOS. 

Osteoporosis in polycystic ovary syndrome (PCOS) and involved mechanisms.

Introduction Microbiota in the human body are closely related to human diseases. Female urogenital tract and rectal microbes have been considered as important factors affecting female pregnancy, but the mechanism is unknown. Methods Cervical, vaginal, urethral, and rectal swabs were collected from 22 infertile patients and 10 controls, and follicular fluid was extracted from 22 infertile patients. The microbial composition of different sampling sites of infertile patients was examined. By comparing the microbial composition difference between infertile patients and controls and combining bioinformatics methods to analyze the potential impact of the female urogenital tract (cervical, vaginal and urethral) and rectal microbial diversity on female infertility and pregnancy outcomes. Results Lactobacillus predominated in the female urogenital tract, but its abundance decreased in infertile patients, whereas the abundance of Gardnerella and Atopobium increased. The microbial changes in the urethra had the same trend as that in the vagina. Compared with healthy controls, the cervical and rectal microbial diversity of infertile patients were significantly increased and decreased, respectively. There might be interactions between microbes in different parts of female. Geobacillus thermogeniticans was enriched in the urogenital tract and rectum of infertile patients, and has a good predictive effect on infertility. Compared with infertile patients, L. johnsonii was enriched in the vagina, urethra, and intestine of the control group. L. acidophilus in follicular fluid might be associated with Non-pregnancy. Conclusion This study found that the microbial composition of infertile patients was changed compared with that of healthy people. The translocation of Lactobacillus between the rectum and urogenital tract might play a protective barrier role. The changes of Lactobacillus and Geobacillus might be related to female infertility or pregnancy outcome. The study provided a theoretical basis for the future treatment of female infertility from the perspective of microorganisms by detecting the microbial changes associated with female infertility.

/pdf/urogenital-tract-and-rectal-microbiota-composition-and-its-20zm4iah.pdf

Urogenital tract and rectal microbiota composition and its influence on reproductive outcomes in infertile patients

Osteoporosis is now a worldwide public health problem that seriously endangers human health, but its causes have not yet been fully clarified. Recently, increasing evidence suggested that polymorph...

The associations of CYP19A1 rs700518 polymorphism with bone mineral density and risk of osteoporosis: a meta-analysis

Associations between UGT2B7 polymorphisms and cancer susceptibility: A meta-analysis.

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Papers

Urogenital tract and rectal microbiota composition and its influence on reproductive outcomes in infertile patients

The associations of CYP19A1 rs700518 polymorphism with bone mineral density and risk of osteoporosis: a meta-analysis

Associations between UGT2B7 polymorphisms and cancer susceptibility: A meta-analysis.