Long-chain acyl-CoA synthetase-4 regulates endometrial decidualization through a fatty acid ß-oxidation pathway rather than lipid droplet accumulation.

OBJECTIVE: Lipid metabolism plays an important role in early pregnancy, but its effects on decidualization are poorly understood. Fatty acids (FAs) must be esterified by fatty acyl-CoA synthetases to form biologically active acyl-CoA in order to enter the anabolic and/or catabolic pathway. Long-chain acyl-CoA synthetase 4 (ACSL4) is associated with female reproduction. However, whether it is involved in decidualization is unknown. METHODS: The expression of ACSL4 in human and mouse endometrium was detected by immunohistochemistry. ACSL4 levels were regulated by the overexpression of ACSL4 plasmid or ACSL4 siRNA, and the effects of ACSL4 on decidualization markers and morphology of endometrial stromal cells (ESCs) were clarified. A pregnant mouse model was established to determine the effect of ACSL4 on the implantation efficiency of mouse embryos. Modulation of ACSL4 detects lipid anabolism and catabolism. RESULTS: Through examining the expression level of ACSL4 in human endometrial tissues during proliferative and secretory phases, we found that ACSL4 was highly expressed during the secretory phase. Knockdown of ACSL4 suppressed decidualization and inhibited the mesenchymal-to-epithelial transition induced by MPA and db-cAMP in ESCs. Further, the knockdown of ACSL4 reduced the efficiency of embryo implantation in pregnant mice. Downregulation of ACSL4 inhibited FA ß-oxidation and lipid droplet accumulation during decidualization. Interestingly, pharmacological and genetic inhibition of lipid droplet synthesis did not affect FA ß-oxidation and decidualization, while the pharmacological and genetic inhibition of FA ß-oxidation increased lipid droplet accumulation and inhibited decidualization. In addition, inhibition of ß-oxidation was found to attenuate the promotion of decidualization by the upregulation of ACSL4. The decidualization damage caused by ACSL4 knockdown could be reversed by activating ß-oxidation. CONCLUSIONS: Our findings suggest that ACSL4 promotes endometrial decidualization by activating the ß-oxidation pathway. This study provides interesting insights into our understanding of the mechanisms regulating lipid metabolism during decidualization.

Progesterone inhibits endometrial cancer growth by inhibiting glutamine metabolism through ASCT2.

Endometrial carcinoma (EC) is a common malignancy that originates from the endometrium and grows in the female reproductive system. Surgeries, as current treatments for cancer, however, cannot meet the fertility needs of young women patients. Thus, progesterone (P4) therapy is indispensable due to its effective temporary preservation of female fertility. Many cancer cells are often accompanied by changes in metabolic phenotypes, and abnormally dependent on the amino acid glutamine. However, whether P4 exerts an effect on EC via glutamine metabolism is unknown. In the present study, we found that P4 could inhibit glutamine metabolism in EC cells and down-regulate the expression of the glutamine transporter ASCT2. This regulation of ASCT2 affects the uptake of glutamine. Furthermore, the in vivo xenograft studies showed that P4 inhibited tumor growth and the expression of key enzymes involved in glutamine metabolism. Our study demonstrated that the direct regulation of glutamine metabolism by P4 and its anticancer effect was mediated through the inhibition of ASCT2. These results provide a mechanism underlying the effects of P4 therapy on EC from the perspective of glutamine metabolism.

Melatonin suppresses tumor proliferation and metastasis by targeting GATA2 in endometrial cancer.

Endometrial cancer (EC) is a reproductive system disease that occurs in perimenopausal and postmenopausal women. However, its etiology is unclear. Melatonin (MT) has been identified as a therapeutic agent for EC; however, its exact mechanism remains unclear. In the present study, we determined that GATA-binding protein 2 (GATA2) is expressed at low levels in EC and regulated by MT. MT upregulates the expression of GATA2 through MT receptor 1A (MTNR1A), whereas GATA2 can promote the expression of MTNR1A by binding to its promoter region. In addition, in vivo and in vitro experiments showed that MT inhibited the proliferation and metastasis of EC cells by upregulating GATA2 expression. The protein kinase B (AKT) pathway was also affected. In conclusion, these findings suggest that MT and GATA2 play significant roles in EC development.

Network crafting, goal attainment, and work-to-family facilitation among hotel employees: the mediating roles of positive affect and information exchange.

Background: The hospitality industry is experiencing new developmental opportunities after the coronavirus pandemic, such as the expansion of digital presence, the introduction of wellness offerings to cater to health-conscious guests, and a growing focus on local and sustainable tourism. However, despite these positive changes, we still lack knowledge on how hospitality workers can proactively adjust their work conditions to excel in their professional domain while also flourishing in their family domain. Thus, the current study proposed and examined how network crafting behaviors can have positive effects on hotel employees' work goal attainment and work-to-family facilitation. Based on the affectivity theories and the social cognitive theory, we examined the mediating roles of positive affect and information exchange on the relationship between network crafting behaviors and work goal attainment and work-to-family facilitation. Methods: We collected data from three 5-star hotels in Jinan, China. We sent out the surveys in three waves to avoid the common method bias. We obtained 199 valid responses in total in three waves and entered them into the data analysis. Structural equation modeling was conducted to examine our hypotheses. Results: We found that network crafting was positively related to hotel employees' work goal attainment and work-to-family facilitation. We also confirmed the mediating roles of positive affect and information exchange in this relationship. Conclusion: We revealed a dual process of network crafting - that is, a positive affective process and an information exchange process. We contribute to the social network and networking literature by highlighting an optimization-oriented networking strategy, rather than one simply maximizing networks. We enrich the work-family enrichment literature by suggesting an effective behavioral strategy that can transmit the resources and gains from one domain to the other domain.

Icaritin inhibits endometrial carcinoma cells by suppressing O-GlcNAcylation of FOXC1.

BACKGROUND: Icaritin has a wide range of pharmacological activities, including significant an-titumor activity. However, the mechanism of action of icaritin in endometrial cancer (UCEC) remains unknown. FOX proteins are a highly conserved transcription factor superfamily that play important roles in epithelial cell differentiation, tumor metastasis, angiogenesis, and cell cycle regulation. FOXC1 is an important member of the FOX protein family. FOXC1 is aberrantly expressed in endometrial cancer and may play a role in the migration and invasion of endometrial cancer; however, its mechanism of action has not yet been reported. O-GlcNAc glycosylation is a common post-translational modification. In endometrial cancer, high levels of O-GlcNAcylation promote cell proliferation, migration, and invasion. Cancer development is often accompanied by O-GlcNAc modification of proteins; however, O-GlcNAc modification of the transcription factor FOXC1 has not been reported to date. PURPOSE: To investigate the inhibitory effects of icaritin on RL95-2 and Ishikawa endometrial cancer cells in vitro and in vivo and to elucidate the possible molecular mechanisms. METHODS/STUDY DESIGN: CCK8, colony formation, migration, and invasion assays were used to determine the inhibitory effects of icaritin on endometrial cancer cells in vitro. Cell cycle regulation was assayed by flow cytometry. Protein levels were measured based on western blotting. The level of FOXC1 expression in endometrial cancer tissues was determined by immunohistochemistry. To assess whether icaritin also has activity in vivo, its effect on tumor xenografts was evaluated. RESULTS: Immunohistochemical analysis of clinical samples revealed that FOXC1 expression was significantly higher in endometrial cancer tissues than in normal tissues. Downregulation of FOXC1 inhibited the proliferative, colony formation, migration, and invasive abilities of RL95-2 and Ishikawa endometrial cancer cells. Icaritin inhibited the proliferation, colony formation, migration, and invasion of endometrial cancer cells and blocked the cell cycle in S phase. Icaritin affected O-GlcNAc modification of FOXC1 and thus the stability of FOXC1, which subsequently triggered the inhibition of endometrial cancer cell proliferation. CONCLUSION: The anti-endometrial cancer effect of icaritin is related to the inhibition of abnormal O-GlcNAc modification of FOXC1, which may provide an important theoretical foundation for the use of icaritin against endometrial cancer.

Emerging field: O-GlcNAcylation in ferroptosis.

In 2012, researchers proposed a non-apoptotic, iron-dependent form of cell death caused by lipid peroxidation called ferroptosis. During the past decade, a comprehensive understanding of ferroptosis has emerged. Ferroptosis is closely associated with the tumor microenvironment, cancer, immunity, aging, and tissue damage. Its mechanism is precisely regulated at the epigenetic, transcriptional, and post-translational levels. O-GlcNAc modification (O-GlcNAcylation) is one of the post-translational modifications of proteins. Cells can modulate cell survival in response to stress stimuli, including apoptosis, necrosis, and autophagy, through adaptive regulation by O-GlcNAcylation. However, the function and mechanism of these modifications in regulating ferroptosis are only beginning to be understood. Here, we review the relevant literature within the last 5 years and present the current understanding of the regulatory function of O-GlcNAcylation in ferroptosis and the potential mechanisms that may be involved, including antioxidant defense system-controlled reactive oxygen species biology, iron metabolism, and membrane lipid peroxidation metabolism. In addition to these three areas of ferroptosis research, we examine how changes in the morphology and function of subcellular organelles (e.g., mitochondria and endoplasmic reticulum) involved in O-GlcNAcylation may trigger and amplify ferroptosis. We have dissected the role of O-GlcNAcylation in regulating ferroptosis and hope that our introduction will provide a general framework for those interested in this field.

A review of hydrogen chloride removal from calcium- and sodium-based sorbents.

With the steady progress of ultra-low emissions in various industries, the management of unconventional pollutants is gradually attracting attention. A such unconventional pollutant that negatively affects many different processes and pieces of equipment is hydrogen chloride (HCl). Although it has strong advantages and potential in the treatment of industrial waste gas and synthesis gas, the process technology of removing HCl by calcium- and sodium-based alkaline powder has not yet been thoroughly studied. The impact of reaction factors on the dechlorination of calcium- and sodium-based sorbents is reviewed, including temperature, particle size, and water form. The most recent developments in sodium- and calcium-based sorbents for capturing hydrogen chloride were presented, and the dechlorination capabilities of various sorbents were contrasted. In the low-temperature range, sodium-based sorbents had a stronger dechlorination impact than calcium-based sorbents. Surface chemical reactions and product layer diffusion between solid sorbents and gases are crucial mechanisms. Meanwhile, the effect of the competitive behavior of SO2 and CO2 with HCl on the dechlorination performance has been taken into account. The mechanism and necessity of selective hydrogen chloride removal are also provided and discussed, and future research directions are pointed out to provide the theoretical basis and technical reference for future industrial practical applications.

Analysis of genetic profiling, pathomics signature, and prognostic features of primary lymphoepithelioma-like carcinoma of the renal pelvis.

The genetic features of primary lymphoepithelioma-like carcinoma (LELC) of the upper urinary tract have not been systematically explored. In this study, tumor mutation profiling was performed using whole-genome sequencing in two patients with LELC of the renal pelvis. Novel candidate variants relevant to known disease genes were selected using rare-variant burden analysis. Subsequently, a population-based study was performed using the Surveillance, Epidemiology, and End Results (SEER), PubMed, MEDLINE, Embase, and Scopus databases to explore clinical features and prognostic risk factors. Immunohistochemical analysis revealed seven positive cytokeratin-associated markers in tumor cells and five positive lymphocyte-associated markers in and around the tumor area. Sub-sequently, we identified KDM6A as the susceptibility gene and LEPR as the driver gene by Sanger sequencing in case 2 of LELC of the renal pelvis. Three mutation sites of the existing targeted drugs were screened: CA9, a therapeutic target for zonisamide; ARVCF, a therapeutic target for bupropion; and PLOD3, a therapeutic target for vitamin C. In a population-based study, patients with primary LELC of the upper urinary tract had clinical outcomes similar to those of patients with primary upper urinary tract urothelial carcinoma (UUT-UC) before and after propensity score matching at 1 : 5. Focal subtype was an independent prognostic factor for the overall survival of patients with LELC of the upper urinary tract. The carcinogenesis of primary LELC may be due to different genetic variations, including single-nucleotide variants, insertion and deletions, structural variations, and repeat regions, which may provide the basis for clinical diagnosis and treatment. The prognosis of LELC in the upper urinary tract is similar to that of UUT-UC. We suggest that the focal subtype can serve as a prognostic factor for LELC of the upper urinary tract; however, further studies are required to confirm this.

Supercritical water gasification of hyperaccumulators for hydrogen production and heavy metal immobilization with alkali metal catalysts.

The high moisture content and heavy metal concentration of hyperaccumulator are the main bottlenecks of resource utilization. Supercritical water gasification technology was used to convert Sedum plumbizincicola (a hyperaccumulator of Zn and Cd) into hydrogen gas and to immobilize HMs into biochar. Homogeneous alkali metal catalysts such as NaOH, Na2CO3 and Ca(OH)2 were added to optimize the experimental conditions. The results showed that NaOH was effective in capturing CO2in-situ, thereby shifting the water-gas shift reaction equilibrium in the forward direction. And the increase of NaOH concentration had a significant promotion effect on hydrogen production. In the non-catalytic gasification of Sedum plumbizincicola, the highest hydrogen (1.5 mol/kg) and H2 selectivity (22.9%) with greater carbon gasification efficiency (19.3%) and lower H2 gasification efficiency (8.7%) of the gas products were obtained at 400 °C with 6 wt% material concentration for 20 min. However, NaOH at 5% mass fraction maximized hydrogen and H2 selectivity up to 7.5 and 98.2%, respectively. Alkali catalyst not only promoted the generation of hydrogen-rich bio-gas but also enhanced the immobilization efficiency of heavy metals. Compared to non-catalytic, when the addition amount of NaOH was 1 wt%, the Zn、Mn、Cd、Pb、Cr accumulated in biochar increased significantly for 76.8, 42.5, 80.8, 75.6 and 80.0%, respectively. This study highlights the remarkable ability of SCWG with alkali catalyst for hydrogen production and heavy metal stabilization.

Identification of distinct genomic features reveals frequent somatic AHNAK and PTEN mutations predominantly in primary malignant melanoma presenting in the ureter.

BACKGROUND: Primary malignant melanoma of the ureter is extremely rare. Genetic variants to the increased risk of developing the disease have not yet been investigated. METHODS: Tumour mutation profiling for primary malignant melanoma of the ureter was performed by whole-exome sequencing. Immunohistochemistry was performed to verify histopathological features and the variants of predisposing genes and driver mutation genes. Furthermore, we conducted a literature review and Surveillance, Epidemiology and End Result-based study by searching public databases. RESULTS: We identified 38 somatic single nucleotide variants and 9 somatic insertions and deletions (INDELs) in tumour specimens. After filtering with the Cancer Gene Census database, seven predisposing genes and two driver mutation genes were identified. Moreover, the immunohistochemical profile showed that tumour cells were positive for Melan-A, melanoma gp100 human melanoma black 45 (HMB45), S100 beta and P53. The expression levels of two driver mutation genes (phosphatase and tensin homolog (PTEN) and desmoyokin (AHNAK) and five predisposing genes (AT-rich interaction domain 1B (ARID1B), catalase, eukaryotic translation initiation factor 4 gamma 3 (EIF4G3), ANK3 and collagen type I) were significantly downregulated in tumour tissues compared to paracancerous tissues. In the literature review and Surveillance, Epidemiology and End Results-based study, patients with primary malignant melanoma of the urinary tract had worse clinical outcomes than patients with primary urothelial carcinoma after 1:2 propensity score matching (P = 0.010). Additionally, Cox multivariate analysis for patients with primary malignant melanoma of the urinary tract indicated that distant metastasis (hazard ratio = 1.185; P = 0.044) was an independent predictor for overall survival, and tumour focality (hazard ratio = 0.602; P = 0.017) and non-surgery (hazard ratio = 0.434; P = 0.003) were independent factors for tumour progression. CONCLUSIONS: Our study is the first to provide evidence that the distinct phenotypes of primary malignant melanoma of the ureter may be due to different genetic variations. The prognosis of primary malignant melanoma of the urinary tract was poorer than that of primary urothelial carcinoma of the urinary tract.

O-GlcNAc modification mediates aquaporin 3 to coordinate endometrial cell glycolysis and affects embryo implantation.

Introduction: O-linked ß-D-N-acetylglucosamine (O-GlcNAc) modification is a post-translational modification in which a single O-GlcNAc is added to serine or threonine residues in nuclear, cytoplasmic, and mitochondrial proteins, and is involved in a variety of physiological processes. Objectives: In the present study, the role of O-GlcNAcylation in embryo implantation was evaluated. Furthermore, whether O-GlcNAcylation is involved in orchestrating glucose metabolism to influence endometrial cell physiological functions was investigated. Methods: Different endometrial tissues were detected using immunohistochemistry. Pregnant mouse models were established to verify molecular expression. O-GlcNAc transferase and aquaporin 3 (AQP3) knockdown were used to detect embryo implantation efficiency in vitro and in vivo. Western blotting and immunofluorescence were used to detect protein expression and stability. Dual luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to verify the binding transcription factor. Glycolysis was detected using bioenergy analyzer, and metabolites were analyzed using isotope 13C-labeled LC-MS. Metabolic-related genes were determined using RNA sequencing. Results: Activation of endometrial hexosamine biosynthetic pathway (HBP) caused elevated O-GlcNAcylation during the window of implantation, affecting endometrial cell function and embryo implantation. Specifically, elevated O-GlcNAcylation increased glucose uptake via glucose transporter 1 (GLUT1) leading to glucose metabolic flow into the pentose phosphate pathways and HBP, which regulate the metabolic reprogramming of endometrial cells. Furthermore, O-GlcNAcylation mediated the intracellular transport of glycerol to support and compensate for glycolysis through regulation of AQP3. Unexpectedly, elevated AQP3 also increased glucose uptake via GLUT1. These processes maintained higher metabolic requirements for endometrial physiology. Furthermore, the transcription factor SP1 specifically bound to the AQP3 promoter region, and O-GlcNAcylation of SP1 increased its stability and transcriptional regulation of AQP3 which is associated with O-GlcNAcylation of SP1. Conclusion: Overall, O-GlcNAcylation regulated glucose metabolism in endometrial cells, and AQP3-mediated compensation provides new insights into the communication between glycolysis and O-GlcNAcylation.

Caveolin-1 knockout mice have altered serum N-glycan profile and sialyltransferase tissue expression.

Caveolin-1 (Cav-1) is a constitutive protein within caveolar membranes. Previous studies from our group and others indicated that Cav-1 could mediate N-glycosylation, α2,6-sialylation, and fucosylation in mouse hepatocarcinoma cells in vitro. However, little is known about the effect of Cav-1 expression on glycosylation modifications in vivo. In this study, the N-glycan profiles in serum from Cav-1-/- mice were investigated by lectin microarray and mass spectrometric analysis approaches. The results showed that levels of multi-antennary branched, α2,6-sialylated, and galactosylated N-glycans increased, while high-mannose typed and fucosylated N-glycans decreased in the serum of Cav-1-/- mice, compared with that of wild-type mice. Furthermore, the real-time quantitative PCR analysis indicated that α2,6-sialyltransferase gene expression decreased significantly in Cav-1-/- mouse organ tissues, but α2,3- and α2,8-sialyltransferase did not. Of them, both mRNA and protein expression levels of the ß-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) had dramatically reduced in Cav-1-/- mice organ tissues, which was consistent with the α2,6-sialyl Gal/GalNAc level reduced significantly in tissues instead of serum from Cav-1-/- mice. These results provide for the first time the N-glycans profile of Cav-1-/- mice serum, which will facilitate understanding the function of Cav-1 from the perspective of glycosylation.

Migration and transformation of heavy metals in hyperaccumulators during the thermal treatment: a review.

The pollution of heavy metals (HMs) in the soil has become one of the important factors affecting the national environment and human health. Phytoremediation, as a technology to deal with HM pollution in soil, has been extensively studied and applied due to its sustainability and environmental friendliness. However, hyperaccumulators polluted by HMs need to be properly treated to avoid secondary pollution to the environment. This paper reviews the migration and transformation of HMs during the incineration, pyrolysis, gasification, and hydrothermal treatment of hyperaccumulators; comprehensively evaluates the advantages and disadvantages of each technology in the treatment of HM-enriched hyperaccumulators; and analyzes the current development status and unsolved problems in detail for each technology. Generally speaking, thermal treatment technology can fix most of the HMs of exchangeable fraction in biochar, reducing its bioavailability and biotoxicity. In addition, the application direction and research focus of the target product are discussed, and it is clarified that in the future, it is necessary to further optimize the reaction conditions and explore the mechanism of HM immobilization to maximize the immobilization of HMs and improve the quality and output of the target product.

Paired-like homeodomain transcription factor 2 affects endometrial cell function and embryo implantation through the Wnt/ß-catenin pathway.

The successful implantation of embryos is crucial for pregnancy in mammals. This complex process is inevitably dependent on the development of the endometrium. The paired-like homeodomain transcription factor 2 (PITX2) is involved in a variety of biological processes, but whether it is involved in embryo implantation has not been reported. In this study, we aimed to investigate uterine expression and regulation of PITX2 during implantation. We found that PITX2 was elevated in the human endometrium in the secretory phase. The results of the pregnant mouse models showed that PITX2 expression was spatiotemporal in mouse endometrial tissue throughout peri-implantation period, and it was significantly upregulated at the time of implantation. Interestingly, PITX2 was mainly localized to the glandular epithelium cells on D2.5-3.5 of pregnancy, while D5.5-6.5 was largely expressed in stromal cells. In vitro, PITX2 regulated endometrial cells proliferation, migration, invasion, and other functions through the Wnt/ß-catenin signaling pathway. In addition, a significant decrease in the rate of embryo implantation was observed after injecting PITX2 small interfering RNA into the uterine horn. These results demonstrate the effects of PITX2 on the physiological function of endometrial cells and embryo implantation, suggesting a role in the endometrial regulatory mechanism during implantation.

A Bibliometric Analysis and Review of Supercritical Fluids for the Synthesis of Nanomaterials.

Since the 1990s, supercritical fluids for the synthesis of nanomaterials have been paid more and more attention by researchers and have gradually become one of the most important ways to prepare nanomaterials. In this study, literature data on "supercritical fluids for the synthesis of nanomaterials" from 1998 to 2020 were obtained from the Web of Science database, and the data were processed and analyzed by the bibliometric method combined with Microsoft office 2019, Origin 2018, VOSviewer, and other software, so as to obtain the research status and development trend of "supercritical fluids for the synthesis of nanomaterials". The results show that since literature on "supercritical fluids for the synthesis of nanomaterials" appeared for the first time in 1998, the number of articles published every year has risen. In terms of this field, China has become the second-largest publishing country after the United States, and China and the United States display a lot of cooperation and exchanges in this field. "Supercritical CO2", "supercritical water", "supercritical antisolvent", "surface modification", and so on have become the research hotspots of "supercritical fluids for the synthesis of nanomaterials".

Progesterone Regulates Glucose Metabolism Through Glucose Transporter 1 to Promote Endometrial Receptivity.

Successful embryo implantation requires receptive endometrium, which is conducive to the process of embryo recognition, adhesion, and invasion within a certain period of time and is inseparable from the dynamic interaction between 17ß-estradiol (E2) and progesterone (P4). Proper glucose metabolism is critical for the profound physiological changes in the endometrium entering the receptive state. And glucose transporters (GLUTs) are responsible for intracellular uptake of glucose and are the first step in glucose metabolism. Prior literature has reported the presence of GLUTs in the endometrium. However, we still do not understand the specific mechanisms of this process. In this study, we identified the effect of P4 on glucose transporter 1 (GLUT1) using in vivo animal models and determined the regulation of glucose metabolism by P4 in cells. We highly suspect that this pregnancy failure may be due to reduced GLUT1-mediated glucose metabolism, resulting in a decrease in endometrial receptivity caused by an inadequate energy supply and synthesis of substrate. Here, we propose a possible mechanism to explain how embryo implantation is affected by P4 and glucose utilization under abnormal endometrial conditions.

Whole-Exome Sequencing Reveals New Potential Mutations Genes for Primary Mucosa-Associated Lymphoid Tissue Lymphoma Arising From the Kidney.

Low-grade B cell lymphomas of mucosa-associated lymphoid tissue (MALT) lymphomas involving the kidney were extremely rare, genetic alteration or molecular features was not yet explored, which may lead to limited choices for postoperative adjuvant or targeted. Whole-exome sequencing based tumor mutation profiling was performed on the tumor sample from a 77-year-old female presenting with discomfort at the waist was pathologically diagnosed as MALT lymphomas in the right kidney. We identified 101 somatic SNVs, and the majority of the identified SNVs were located in CDS and intronic regions. A total of 190 gain counts of CNVs with a total size of 488,744,073 was also investigated. After filtering with the CGC database, seven predisposing genes (ARID4A, COL2A1, FANCL, ABL2, HSP90AB1, FANCA, and DIS3) were found in renal MALT specimen. Furthermore, we compared somatic variation with known driver genes and validated three mutational driver genes including ACSL3, PHOX2B, and ADCY1. Sanger sequencing of germline DNA revealed the presence of a mutant base T of PHOX2B and a mutant base C of ADCY1 in the sequence, which were discovered for the first time in MALT lymphomas involving the kidney. Moreover, immunohistochemical analysis revealed that tumor cells were positive for CD20, CD79a, PAX5, CD21, and CD23, and expression of CD3, CD5, and CD8 were observed in reactive T lymphocytes surrounding tumor cells. These findings illustrated that concurrent aberrant PHOX2B and ADCY1 signaling may be a catastrophic event resulting in disease progression and inhibition of the putative driver mutations may be alternative adjuvant therapy for MALT lymphoma in the kidney which warrants further clinical investigation.

MicroRNA­21 contributes to renal cell carcinoma cell invasiveness and angiogenesis via the PDCD4/c­Jun (AP­1) signalling pathway.

Accumulating evidence has demonstrated that microRNAs are associated with malignant biological behaviour, including tumorigenesis, cancer progression and metastasis via the regulation of target gene expression. Our previous study demonstrated that programmed cell death protein 4 (PDCD4), which is a tumour suppressor gene, is a target of microRNA­21 (miR­21), which affects the proliferation and transformation capabilities of renal cell carcinoma (RCC) cells. However, the role of miR­21 in the molecular mechanism underlying the migration, invasion and angiogenesis of RCC remains poorly understood. The effects of miR­21 on the invasion, migration and angiogenesis of RCC cells was determined through meta­analysis and regulation of miR­21 expression in vitro. After searching several databases, 6 articles including a total of 473 patients met the eligibility criteria for this analysis. The combined results of the meta­analysis revealed that increased miR­21 expression was significantly associated with adverse prognosis in patients with RCC, with a pooled hazard ratio estimate of 1.740. In in vitro experiments, we demonstrated that a miR­21 inhibitor decreased the number of migrating and invading A498 and 786­O RCC cells, along with a decrease in PDCD4, c­Jun, matrix metalloproteinase (MMP)2 and MMP9 expression. Additionally, inhibition of miR­21 was revealed to reduce tube formation and tube junctions in the endothelial cell line HMEC­1 by affecting the expression of angiotensin­1 and vascular endothelial growth factor A, whereas PDCD4 small interfering RNA exerted opposite effects on the same cells. Overall, these findings, along with evidence­based molecular biology, demonstrated that miR­21 expression promoted the migration, invasion and angiogenic abilities of RCC cells by directly targeting the PDCD4/c­Jun signalling pathway. The results may help elucidate the molecular mechanism underlying the development and progression of RCC and provide a promising target for microRNA­based therapy.

O­GlcNAc modification influences endometrial receptivity by promoting endometrial cell proliferation, migration and invasion.

O­linked ß­N­acetylglucosamine (O­GlcNAc) modification is a dynamic post­translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling. This dynamic modification is dependent on the ambient glucose concentration and is catalyzed and removed by O­GlcNAc transferase (OGT) and O­GlcNAcase (OGA), respectively. The present study aimed to determine the role of O­GlcNAcylation during embryo implantation by inhibiting or enhancing its function and expression. The results revealed that the expression of O­GlcNAc­modified proteins in the human secretory endometrium was higher than that of the endometrium during the proliferative phase, as determined via western blotting and immunohistochemistry. Additionally, the level of endometrial O­GlcNAc modification increased gradually from the pre­receptive to the receptive phase, which was then decreased during the non­receptive phase. In endometrial cells, RNA interference was utilized to reduce the expression of two key O­GlcNAc synthesis and decomposition enzymes, OGT and OGA, to indirectly increase or decrease levels of O­GlcNAc modification. The results revealed that increasing the level of O­GlcNAc modification enhanced cellular proliferation, migration, invasion and adhesion, thereby promoting embryo implantation. It is hypothesized that O­GlcNAc modification serves an important role in the regulation of endometrial receptivity and embryo implantation. The results of the present study may have important implications for the understanding of female fertility and may help improve infertility treatments.

The impact of advanced proteomics in the search for markers and therapeutic targets of bladder cancer.

Bladder cancer is the most common cancer of the urinary tract and can be avoided through proper surveillance and monitoring. Several genetic factors are known to contribute to the progression of bladder cancer, many of which produce molecules that serve as cancer biomarkers. Blood, urine, and tissue are commonly analyzed for the presence of biomarkers, which can be derived from either the nucleus or the mitochondria. Recent advances in proteomics have facilitated the high-throughput profiling of data generated from bladder cancer-related proteins or peptides in parallel with high sensitivity and specificity, providing a wealth of information for biomarker discovery and validation. However, the transmission of screening results from one laboratory to another remains the main disadvantage of these methods, a fact that emphasizes the need for consistent and standardized procedures as suggested by the Human Proteome Organization. This review summarizes the latest discoveries and progress of biomarker identification for the early diagnosis, projected prognosis, and therapeutic response of bladder cancer, informs the readers of the current status of proteomic-based biomarker findings, and suggests avenues for future work.