UNASSIGNED: The main purpose of this paper is to explore the interaction between GAS5 and miR-135b-5p to understand their function in the metastasis, invasion, and proliferation of glioma. This may provide new ideas for the pathogenesis and treatment of glioma.
UNASSIGNED: Western blotting assays and RT‑qPCR were employed to investigate the expression of related genes in glioma tissues or cell lines. CCK-8 was used to examine the impact of GAS5 on cell viability. Motile activities were adopted by the transwell and wound healing experiments. A double luciferase experiment was performed to elucidate transcriptional regulation.
UNASSIGNED: GAS5 showed low expression in glioma cells and tissues, and up-regulation of GAS5 could depress the invasion, proliferation, and metastasis of glioma. GAS5 negatively regulates miR-135b-5p, which can counteract the cellular effects caused by GAS5. APC was the target of miR-135b-5p, and GAS5 can regulate the expression of APC by sponging miR-135b-5p. APC overexpression reversed the effects of miR-135b-5p promotion on glioma cells, while miR-135b-5p has the opposite function. As a downstream target gene of GAS5, miR-135b-5p was negatively regulated by GAS5. The restoration of miR-135b-5p can remarkably reverse the impact of GAS5 on glioma cells. In addition, GAS5 increased the expression of APC in glioma cells by inhibiting miR-135b-5p.
UNASSIGNED: GAS5 increased APC expression by restraining miR-135b-5p and partially blocked the progression of glioma, suggesting that it could be an advantageous therapeutic target for glioma intervention.

BACKGROUND: DNA methylation plays an important role in the carcinogenesis, progression, and prognosis of various human cancers. RASSF1A, BRCA1, APC, and p16 are the frequently methylated genes among patients with ovarian cancer. Therefore, our study aimed to better determine the prognostic and cancer characteristics effects of RASSF1A, BRCA1, APC, and p16 promoter methylation in ovarian cancer patients.
METHODS: Databases such as PubMed, Web of Science, EMBASE, CNKI, and WanFang were searched for published studies up to March 4, 2024. The outcomes are shown as OR and HR with their 95% CIs. Then, the random or fixed-effect model was performed to evaluate the effect sizes.
RESULTS: Finally, 27 articles were included in this meta-analysis. No significant relationships were observed between RASSF1A, BRCA1, and APC promoter methylation and the clinical prognostic (including overall survival and progression-free survival) and cancer characteristics (including ascites, lymph node metastasis, and pelvic peritoneal metastasis) in ovarian cancer. p16 promoter methylation was significantly related to poor progression-free survival (PFS) (HR = 1.52, 95% CI = 1.14-2.04) and overall survival (OS) (HR = 1.39, 95% CI = 1.06, to 1.83) in univariate and poor PFS in multivariate Cox regression models (HR = 1.42, 95% CI = 1.05-1.92). Besides, our results indicated that the clinical stage was associated with inferior OS while there was no significant association between tumor grade and OS.
CONCLUSIONS: RASSF1A, BRCA1, and APC promoter methylation were not significantly associated with clinical prognostic and cancer characteristics. p16 may be a useful biomarker for predicting PFS in ovarian cancer. Furthermore, the clinical stage was significantly associated with OS. In further research, more prospective and multicenter validation studies remain needed.

The existing aptamers for cadmium (Cd2+), the common toxic heavy metal contaminant in food, cannot meet the requirements for detecting Cd2+ in rapid detection methods. In previous work, we found that coupling aptamer-peptide conjugates (APCs) with peptides and aptamers can provide a less disruptive method with a significantly improved affinity. Moreover, we found that the spatial conformation of aptamers and peptides is crucial for obtaining proper affinity in APC. Therefore, we describe a simple design strategy to obtain a series of APCs with different affinities by designing peptide orientations (N-terminal, C-terminal). The best affinity was found for APC(C1-N) with a binding constant (Ka) of 2.23 × 106 M-1, indicating that the APC(C1-N) affinity was significantly increased by 829.17% over aptamer. Finally, a rolling-circle amplification (RCA)-coupled ratio fluorescence-based biosensor for Cd2+ detection was established with a detection limit of 0.0036 nM, which has great potential for practical aquatic product detection.

Sulfation is a crucial and prevalent conjugation reaction involved in cellular processes and mammalian physiology. 3\'-Phosphoadenosine 5\'-phosphosulfate (PAPS) synthase 2 (PAPSS2) is the primary enzyme to generate the universal sulfonate donor PAPS. The involvement of PAPSS2-mediated sulfation in adenomatous polyposis coli (APC) mutation-promoted colonic carcinogenesis has not been reported. Here, we showed that the expression of PAPSS2 was decreased in human colon tumors along with cancer stages, and the lower expression of PAPSS2 was correlated with poor prognosis in advanced colon cancer. Gut epithelial-specific heterozygous Apc deficient and Papss2-knockout (ApcΔgut-HetPapss2Δgut) mice were created, and the phenotypes were compared to the spontaneous intestinal tumorigenesis of ApcΔgut-Het mice. ApcΔgut-HetPapss2Δgut mice were more sensitive to gut tumorigenesis, which was mechanistically accounted for by the activation of Wnt/β-catenin signaling pathway due to the suppression of chondroitin sulfation and inhibition of the farnesoid X receptor (FXR)-transducin-like enhancer of split 3 (TLE3) gene regulatory axis. Chondroitin sulfate supplementation in ApcΔgut-HetPapss2Δgut mice alleviated intestinal tumorigenesis. In summary, we have uncovered the protective role of PAPSS2-mediated chondroitin sulfation and bile acids-FXR-TLE3 activation in the prevention of gut carcinogenesis via the antagonization of Wnt/β-catenin signaling. Chondroitin sulfate may be explored as a therapeutic agent for Papss2 deficiency-associated colonic carcinogenesis.

Components in blood play an important role in wound healing and subsequent tissue regeneration processes. The fibrin matrix and various bioactive molecules work together to participate in this complex yet vital biological process. As a means of personalized medicine, autologous platelet concentrates have become an integral part of various tissue regeneration strategies. Here, we focus on how autologous platelet concentrates play a role in each stage of tissue healing, as well as how they work in conjunction with different types of biomaterials to participate in this process. In particular, we highlight the use of various biomaterials to protect, deliver and enhance these libraries of biomolecules, thereby overcoming the inherent disadvantages of autologous platelet concentrates and enabling them to function better in tissue regeneration.

Gardner syndrome (GS) is a specific form of familial adenomatous polyposis (FAP), which manifests as colorectal polyps, multiple osteomas and soft tissue tumors, and in the oral cavity as osteomas of the jaws, odontomas, and abnormal tooth counts. The underlying cause of GS is attributed to mutations in the APC gene. Mutations in this gene disrupt the normal functioning of the protein and lead to the development of GS. To further investigate GS, a family affected by the syndrome was selected from Dongguan, Guangdong Province. The family members underwent a comprehensive survey, which involved collecting clinical data and peripheral venous blood samples. The samples were then used for genetic analysis. Whole exome sequencing (WES) and Sanger sequencing techniques were utilized to screen and identify specific mutation sites in the APC gene. The clinical findings for the GS family included the presence of gastrointestinal polyps and odontomas. After analyzing the genetic sequencing results, a novel mutation site c.4266dupA on the APC gene was found in the patients, which leading to the APC protein truncation. As a result of this study, it is suggested that odontoma may be an early indicator of GS. Additionally, the identification of this novel mutation site in the APC gene expands the known spectrum of genetic mutations associated with the disease. This discovery has significant implications for the early diagnosis of GS, thus enabling timely intervention to reduce the risk of developing colon cancer and other related diseases.

OBJECTIVE: The present study was aimed to investigate the APC expression, its promoter methylation status, the expression of β-Catenin, c-Myc and Cyclin D1 and further explore their prognostic value in Hepatocellular carcinoma (HCC).
METHODS: Serum samples from 90 HCC patients and 27 healthy donors were collected in this study. The methylation-specific PCR (MSP) was performed to evaluate promoter methylation status of APC gene. RT-qPCR was used to detect the mRNA expression of APC, β-Catenin, c-Myc and Cyclin D1, meanwhile the protein expression were analyzed by Western blot.
RESULTS: The positive rate of APC gene methylation in HCC patients (46.67%) was higher than healthy donors (11.11%). APC gene exhibited marked hypermethylation in the patients of TNM III-IV stage when compared to the patients of TNM I-II stage , the methylation status of APC gene was correlated with tumor size and lymph node metastasis whereas the APC gene methylation showed no relationship with the patient\'s sex and age. APC methylation may be associated with APC expression level, APC expression in HCC cells is silenced by aberrant promoter hypermethylation. In HCC patients with methylated APC, the mRNA and protein expression of β-Catenin, c-Myc and Cyclin D1 were higher than the unmethylated patient subgroup and healthy donors.
CONCLUSIONS: The downregulation of APC in HCC samples was associated with promoter hypermethylation. APC methylation could be used as a novel diagnostic biomarker in HCC, which was associated with regulation of Wnt/β-Catenin signal pathway.

Desmoid tumors (DT) represent the second high risk of tumor in familial adenomatous polyposis (FAP) patients. Although FAP-associated DTs (FAP-DT) are caused by germline mutations in the adenomatous polyposis coli (APC) gene, extracolonic manifestations, sex, family history, genotype, and the ileal pouch anal anastomosis procedure are all linked to the development of DTs in FAP patients. Multidisciplinary management has replaced aggressive surgery as the preferred treatment of DTs. There is growing evidence to support the use of active surveillance strategy as first-line treatment for FAP-DT patients. Radiotherapy for intra-abdominal desmoids is now rarely used because of severe late toxicity. Pharmacotherapy, however, represents a promising future with the improvement of traditional cytotoxic drugs and the investigation of targeted drugs. Although nonsurgery treatment has been used widely nowadays, surgery remains the mainstay when symptomatic or life-threatening DTs are present. Further research will be needed for more optimal clinical practice.

The Wnt/β-catenin signaling pathway is a growth control pathway involved in various biological processes as well as the development and progression of cancer. Colorectal cancer (CRC) is one of the most common malignancies in the world. The hyperactivation of Wnt signaling is observed in almost all CRC and plays a crucial role in cancer-related processes such as cancer stem cell (CSC) propagation, angiogenesis, epithelial-mesenchymal transition (EMT), chemoresistance, and metastasis. This review will discuss how the Wnt/β-catenin signaling pathway is involved in the carcinogenesis and progression of CRC and related therapeutic approaches.

UNASSIGNED: Breast cancer (BC) is a major health concern in the BRICS-plus, a group of developing nations consisting of Brazil, Russia, India, China, South Africa, and 30 other Asian countries, with nearly half of the world\'s population. This study aims to identify potential risk factors contributing to the burden of BC by assessing its epidemiological and socio-demographic changes.
UNASSIGNED: Data on BC outcomes were obtained from the 2019 Global Burden of Disease Survey. The age-period-cohort (APC) modeling technique was used to evaluate the nonlinear impacts of age, cohort, and period on BC outcomes and reported risk attributable mortality and disability adjusted life years (DALYs) rate changes between 1990 and 2019.
UNASSIGNED: In 2019, there were 0.90 million female BC cases and 0.35 million deaths in the BRICS-plus region, with China and India having the largest proportion of incident cases and deaths, followed by Pakistan. Lesotho experienced the highest annualized rates of change (AROC: 2.61%; 95%UI: 1.99-2.99) in the past three decades. Birth cohorts\' impact on BC varies greatly between the BRICS-plus nations, with Pakistan suffering the largest risk increase in the most recent cohort. High body mass index (BMI), high fasting plasma glucose (FPG), and a diet high in red meat contributed to the highest death and DALYs rates in most BRICS-plus nations in 2019, and there was a strong negative link between SDI and death and DALYs rate.
UNASSIGNED: The study found that the burden of BC varies significantly between BRICS-plus regions. Thus, BRICS-plus nations should prioritise BC prevention, raise public awareness, and implement screening efficiency measures to reduce the burden of BC in the future, as well as strengthen public health policies and initiatives for important populations based on their characteristics and adaptability.