Phosphofructokinase Platelet Overexpression Accelerated Colorectal Cancer Cell Growth and Motility.

Background: Glycolysis is a glucose metabolism pathway that generates the high-energy compound adenosine triphosphate, which supports cancer cell growth. Phosphofructokinase platelet (PFKP) plays a crucial role in glycolysis regulation and is involved in human cancer progression. However, the biological function of PFKP remains unclear in colorectal cancer (CRC). Methods: We analyzed the expression levels of PFKF in colon cancer cells and clinical samples using real-time PCR and western blot techniques. To determine the clinical significance of PFKP expression in colorectal cancer (CRC), we analyzed public databases. In addition, we conducted in vitro assays to investigate the effects of PFKP on cell growth, cell cycle, and motility. Results: An analysis by the Cancer Genome Atlas database revealed that PFKP was significantly overexpressed in CRC. We examined the levels of PFKP mRNA and protein, revealing that PFKP expression was significantly increased in CRC. The results of the univariate Cox regression analysis showed that high PFKP expression was linked to worse disease-specific survival (DSS) and overall survival (OS) [DSS: crude hazard ratio (CHR) = 1.84, 95% confidence interval (CI): 1.01-3.36, p = 0.047; OS: CHR=1.91, 95% CI: 1.06-3.43, p = 0.031]. Multivariate Cox regression analysis revealed that high PFKP expression was an independent prognostic biomarker for the DSS and OS of patients with CRC (DSS: adjusted HR = 2.07, 95% CI: 1.13-3.79, p = 0.018; AHR = 2.34, 95% CI: 1.29-4.25, p = 0.005). PFKP knockdown reduced the proliferation, colony formation, and invasion of CRC cells. In addition, the knockdown induced cell cycle arrest at the G0/G1 phase by impairing cell cycle-related protein expression. Conclusion: Overexpression of PFKP contributes to the growth and invasion of CRC by regulating cell cycle progression. PFKP expression can serve as a valuable molecular biomarker for cancer prognosis and a potential therapeutic target for treating CRC.

C/EBP-ß contributes to pig endometrial LE receptivity by targeting cell remodeling genes during implantation.

In brief: Transforming the endometrial luminal epithelium (LE) into a receptive state is a requisite event for successful embryo implantation. This study suggests the role of a transcription factor in regulating endometrial LE receptivity. Abstract: The endometrial luminal epithelium (LE) undergoes extensive remodeling during implantation to establish receptivity of the uterus in response to the conceptus signals, such as interleukin 1ß (IL1B). But the mechanisms remain to be fully understood. This study investigated the role of CCAAT/enhancer-binding protein ß (C/EBP-ß) in regulating pig endometrial LE receptivity. Our results showed that C/EBP-ß was expressed and activated only in the endometrial LE in an implantation-dependent manner. In addition, C/EBP-ß was highly activated at the pre-attachment stage compared to the attachment stage, and its activation was correlated with the expression of IL1B-dependent extracellular signal-regulated kinases1/2-p90 ribosomal S6 kinase signaling axis. Subsequent chromatin immunoprecipitation (ChIP)-sequencing analysis revealed that the binding of C/EBP-ß within the promoter was positively associated with the transcription of genes related to cell remodeling. One such gene is matrix metalloproteinase 8 (MMP8), which is responsible for extracellular matrix degradation. The expression of MMP8 was abundant at the pre-attachment stage but dramatically declined at the attachment stage in the endometrial LE. Consistent with C/EBP-ß, the expression and activation of MMP8 were limited to the endometrial LE in an implantation-dependent manner. Using ChIP-qPCR and electrophoresis mobility shift assay approaches, we demonstrated that C/EBP-ß regulated the expression of the MMP8 gene during implantation. Furthermore, we detected that MMP8 and one of its substrates, type II collagen, showed a mutually exclusive expression pattern in pig endometrial LE during implantation. Our findings indicate that C/EBP-ß plays a role in pig endometrial LE receptivity by regulating cell remodeling-related genes, such as MMP8, in response to conceptus signals during implantation.

Genetic Features of Reproductive Traits in Bovine and Buffalo: Lessons From Bovine to Buffalo.

Bovine and buffalo are important livestock species that have contributed to human lives for more than 1000 years. Improving fertility is very important to reduce the cost of production. In the current review, we classified reproductive traits into three categories: ovulation, breeding, and calving related traits. We systematically summarized the heritability estimates, molecular markers, and genomic selection (GS) for reproductive traits of bovine and buffalo. This review aimed to compile the heritability and genome-wide association studies (GWASs) related to reproductive traits in both bovine and buffalos and tried to highlight the possible disciplines which should benefit buffalo breeding. The estimates of heritability of reproductive traits ranged were from 0 to 0.57 and there were wide differences between the populations. For some specific traits, such as age of puberty (AOP) and calving difficulty (CD), the majority beef population presents relatively higher heritability than dairy cattle. Compared to bovine, genetic studies for buffalo reproductive traits are limited for age at first calving and calving interval traits. Several quantitative trait loci (QTLs), candidate genes, and SNPs associated with bovine reproductive traits were screened and identified by candidate gene methods and/or GWASs. The IGF1 and LEP pathways in addition to non-coding RNAs are highlighted due to their crucial relevance with reproductive traits. The distribution of QTLs related to various traits showed a great differences. Few GWAS have been performed so far on buffalo age at first calving, calving interval, and days open traits. In addition, we summarized the GS studies on bovine and buffalo reproductive traits and compared the accuracy between different reports. Taken together, GWAS and candidate gene approaches can help to understand the molecular genetic mechanisms of complex traits. Recently, GS has been used extensively and can be performed on multiple traits to improve the accuracy of prediction even for traits with low heritability, and can be combined with multi-omics for further analysis.

Spatial Transcriptomic and miRNA Analyses Revealed Genes Involved in the Mesometrial-Biased Implantation in Pigs.

Implantation failure is a major cause of early embryonic loss. Normally, the conceptus attachment is initiated at mesometrial side of the uterus and then spread to the anti-mesometrial side in pigs, however, the mechanisms that direct the mesometrial-biased attachment are largely unknown. In this study, the histological features of the entire uterine cross-section from gestational days 12 (pre-attachment stage) and 15 (post-attachment stage) were investigated and the differences in histological features between the mesometrial and anti-mesometrial side of the uterus were observed. Then, transcriptomic and miRNA analyses were performed on mesometrial and anti-mesometrial endometrium obtained from gestational days 12 and 15, respectively. Differentially expressed genes (DEGs) and miRNAs (DE-miRs) that were common to both or unique to either of the two anatomical locations of uterus were identified, respectively, indicating that differences in molecular response to the implanting conceptus exist between the two anatomical locations. In addition, we detected DEGs and DE-miRs between the two anatomical locations on the two gestational days, respectively. Of these DEGs, a number of genes, such as chemokine and T cell surface marker genes, were found to be significantly up-regulated mesometrially. Furthermore, we detected the interaction of CXCR4, CXCL11 and miR-9 using dual luciferase reporter assay. Taken together, this study revealed genes and pathways that might play the role of creating a receptive microenvironment at the mesometrial side, which is required to guide a proper positioning of conceptus in the uterus in pigs.

Clinical Analysis of Thyroglobulin Antibody and Thyroid Peroxidase Antibody and their Association with Vitiligo.

BACKGROUND: Recently, the abnormal presence of thyroglobulin antibody (TG-Ab) and thyroid peroxidase antibody (TPO-Ab) has been reported in vitiligo patients, but presence of TG-Ab and TPO-Ab in patients of different ages and gender, and its association with vitiligo and thyroid autoimmunity has rarely been reported. The aim of our research was to determine whether vitiligo was associated with thyroid autoimmunity and figure out its relationship with age and gender. MATERIALS AND METHODS: We analyzed TG-Ab, TPO-Ab in age and gender matched 87 vitiligo patients and 90 healthy controls, the patients of vitiligo who were positive for the presence of TG-Ab and TPO-Ab were followed up to confirm autoimmune thyroid disease subsequently. RESULTS: Results showed that the frequencies of TG-Ab (23.0%, 20/87) positivity and TPO-AB (24.1%, 21/87) in vitiligo patients were significantly higher than that in healthy controls (P < 0.05). Moreover, The positivity for of TG-Ab and TPO-Ab was higher in 11-20-year age group and 21-40-year age group than that in age matched healthy controls. We found female patients with vitiligo had higher positive frequencies of TG-Ab and TPO-Ab than healthy female controls. (34.1% vs. 8.8% and 34.1% vs. 11.1%, P = 0.000 and P = 0.011). When 20 patients with TG-Ab and TPO-Ab positivity were followed up for three monthes, 14 of them (70%) were diagnosed as having autoimmune thyroid disease compared with age-matched healthy controls (16.7%, χ(2) = 5.4, P = 0.02). CONCLUSION: TG-Ab and TPO-Ab are likely to be found in female teenagers with vitiligo, and are relevant with respect to subsequent development autoimmune thyroid disease.

[The subpopulation CD4(+); CD25(+); Foxp3(+);/CD127(low/-); regulatory T cells in peripheral blood of HIV-infected patients correlated with disease progression].

AIM: To explore the subpopulation of CD4(+); CD25(+); Foxp3(+); regulatory T cells (Treg), CD4(+); CD25(+); CD127(low/-); Treg in peripheral blood of HIV-infected patients and study its correlation with other immune indicators. METHODS: We enrolled 68 cases of HIV/AIDS patients without anti-HIV treatment [29 cases of long-term non-progressive (LTNP) group, 27 cases of typical progressive HIV infection group and 12 cases of AIDS group] and 20 healthy individuals as a control group. Blood samples of these cases were analyzed by flow cytometry after immunofluorescent staining to determine the levels of CD4(+); T cells, CD8(+); T cells, NK cells and CD4(+); CD25(+); Foxp3(+);/CD127(low/-); Treg. RESULTS: Except CD8(+); T cells, the levels of CD4(+); T, NK cells and CD4(+);/CD8(+); in peripheral blood of HIV/AIDS patients were significantly lower than those in the control group (P<0.05); With the progression of disease, the percentage and absolute count of CD4(+);T cells, the absolute counts of CD8(+);T cells and NK cells, and CD4(+);/CD8(+); T cell ratio in the LTNP group, HIV group and AIDS group decreased gradually, while the percentage of CD8(+);T cells increased gradually. Our multiple comparison analysis revealed that the percentages of CD4(+); CD25(+); Foxp3(+); Treg and CD4(+); CD25(+); CD127(low/-); Treg in CD4(+); T cells were significantly different among groups (P<0.05). With the progression of disease, the percentages of CD4(+); CD25(+); Foxp3(+); Treg and CD4(+); CD25(+); CD127(low/-); Treg increased gradually; in addition, the difference in the absolute count of CD4(+); CD25(+); Foxp3(+);/CD127(low/-); Treg was not statistically significant between LTNP group and healthy control group(P>0.05), so was between HIV and AIDS groups (P>0.05); no significant difference was found in every other two groups (P<0.05); the absolute count of CD4(+); CD25(+); Foxp3(+);/CD127(low/-); Treg decreased gradually. CONCLUSION: CD4(+); CD25(+); Foxp3(+);/CD127(low/-); Treg may play a role in the immunopathogenesis of persistent HIV infection.

[Investigation of enterotoxin gene in clinical isolates of Staphylococcus aureus].

OBJECTIVE: To detect the enterotoxin genes of Staphylococcus aureus (SA) isolated from clinical specimens and analyze the correlation between enterotoxin genes and drug resistance of SA. METHODS: The mecA gene and enterotoxin genes A-F of clinical SA isolates were identified by polymerase chain reaction (PCR), and the genes were sequenced to investigate the correlation of these genes to drug resistance. RESULTS: The detection rate of enterotoxin genes was 100% in 67 methicillin- resistant SA (MRSA), showing no significant difference from the rate in 57 methicillin-sensitive SA (MSSA) (83.5%, χ(2)=0.203, P>0.05). Of the 116 strains carrying enterotoxin genes (93.5%), the detection rates of SEA, SEB, SEC, SED and SEF were 90.5%, 6.9%, 61.3%, 5.2%, 25.9% and 93.5%, respectively, and none of the strains were positive for SEE gene. In these strains, 78 (67.2%) carried 2 or more enterotoxin genes, and the main genotypes were SEA and SEC (33.6%), SEA and SEF (7.8%), and SEA and SEC and SEF (13.8%). Compared with the strains carrying a single enterotoxin gene, those with multiple enterotoxin genes showed a higher drug resistance rate, among which 75% of the SA strains carrying SEA+SEC+SEF were resistant to SXT, significantly higher than the rates of SA carrying SEA (28.6%) and SEA+SEC (38.7%) (P<0.05). The SA strains carrying SEA+SEC+SEF and SEA+SEF showed significantly higher amikacin resistance rates than SA strain carrying SEA (75.0%, 77.0%, 21.5%, respectively, P<0.05). CONCLUSION: Clinical isolates of SA carrying multiple enterotoxin genes have a higher drug resistance rate than those with a single enterotoxin gene, suggesting the the important role of enterotoxin in multidrug resistance.

[Age related changes of serum sex hormone levels and tartrate-resistant acid phosphatase activity in healthy women].

OBJECTIVE: To study the changes of serum sex hormone levels and tartrate-resistant acid phosphatase (TRACP) activity in healthy women of different ages, and to provide parameters for basic and clinical research of osteoporosis. METHODS: Serum sex hormone (FSH, LH, E2, P) levels and TRACP activity were measured in 236 premenopausal healthy women aged 23-53 years and divided into 3 groups, and in 91 postmenopausal healthy women aged 48-71 years. RESULTS: Except serum FSH levels which were significantly higher in the third group than those of the other groups in premenopausal healthy women (P < 0.05), no significant difference in sex hormone levels and TRACP activity was found among the 3 groups; the postmenopausal group showed a significant increase in serum FSH, LH levels and TRACP activity and a significant decrease in serum E2, P levels, compared with the premenopausal groups (P < 0.01). There was a negative correlation between E2, P levels and TRACP activity in the postmenopausal women (r = -0.41 and -0.37, respectively, P < 0.01). CONCLUSION: Postmenopausal diminution of E2, P results in an increase of serum FSH and LH levels, and may bring about an increase of bone resorption, which results in the increase of TRACP activity.