Clinical significance of lncRNA XIST expression in cholangiocarcinoma and its effect on cell migration and invasion.

BACKGROUND: Cholangiocarcinoma is a malignant tumor that occurs in the bile duct system, and the prognosis of patients is poor. Currently, research suggests that long non-coding RNAs (lncRNAs) in the treatment and prevention of cholangiocarcinoma. This study primarily focuses on the regulation and potential mechanism of the lncRNA XIST (XIST) in cholangiocarcinoma. METHODS: The levels of XIST and miR-126-3p in cholangiocarcinoma tissues and cells were detected using real-time quantitative polymerase chain reaction (RT-qPCR). Cell transfection status, including migration and invasion, was examined via the Transwell method. The relationship between XIST and miR-126-3p was observed by dual-luciferase gene reporter assay and verified by rescue assays. Additionally, the prognostic significance of XIST in cholangiocarcinoma was determined using Kaplan-Meier and multivariate Cox regression analyses. RESULTS: XIST expression was increased in cholangiocarcinoma, while miR-126-3p was decreased, in both tissues and cells. The successful construction of silencing XIST was found to inhibit the count of cell migration and invasion. XIST directly targeted miR-126-3p to regulate the progression of cholangiocarcinoma. CONCLUSION: XIST sponging miR-126-3p inhibited the progression of cholangiocarcinoma and improved the prognosis for patients. This finding provides new insights and opportunities for future studies on cholangiocarcinoma prognostic biomarkers.

Exposure to polycyclic aromatic hydrocarbons promotes the progression of low-grade cervical intraepithelial neoplasia: A population-based cohort study in China.

Low-grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high-risk human papillomavirus (HR-HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community-based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed-up at 6, 12, and 24 months, post-diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1-hydroxipayrene (1-OHP) level. Our results showed that the 1-OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P < .05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24-2.67), (1.98, 1.42-2.75), and (2.37, 1.61-3.49) at 6, 12, and 24 months, post-diagnosis, respectively. The effect was enhanced with HR-HPV positivity, as determined at 6 (1.82, 1.24-2.67), 12 (3.02, 1.74-5.23), and 24 (2.51, 1.48-4.26) months, post-diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR-HPV-positive patients than in HR-HPV-negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR-HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia.

Molecular Transmission Network and Drug Resistance in Treatment-Naive HIV-1-Infected Patients in the Liangshan District, China.

This study aimed to investigate the molecular transmission network and drug resistance in treatment-naive HIV-1-infected patients in the Liangshan District, China. The research subjects for this study were HIV-1-infected patients who did not receive any antiretroviral therapy (ART) in the Liangshan District between January 2022 and July 2023. Peripheral venous whole-blood samples were collected from the research subjects. Two milliliters of blood was used for CD4+ T lymphocyte counting detection. Ten milliliters of blood was centrifuged to separate the plasma and blood cells for quantitative detection of HIV-1 RNA and DNA and drug resistance testing of HIV-1. A total of 156 participants were included in this study (88 males and 68 females). The median age of the participants was 37 years. The findings revealed a positive correlation between the HIV-1 DNA and the HIV-1 RNA levels (r = 0.478, p < 0.001). However, a negative correlation was observed between the HIV-1 DNA levels and CD4+ T lymphocyte counts (r = -0.186, p = 0.020). Of the 156 participants, 145 were successfully tested for drug resistance of HIV-1 RNA and HIV-1 DNA simultaneously. Four cases failed the HIV-1 RNA drug resistance testing, and another two failed the HIV-1 DNA drug resistance testing. The most common HIV-1 subtype was the CRF07_BC recombinant. In this study, the overall incidence of transmitted drug resistance (TDR) was 8.33%. The resistance rates of non-nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI) were 7.69% and 0.64%, respectively. In addition, 32 participants were found to have drug-resistant mutations. The primary drug-resistant mutations were K103N, V179D, E157Q, and A128T, mainly against efavirenz (EFV) and nevirapine (NVP) resistance. The drug resistance of HIV-1-infected ART-naive patients in the Liangshan District cannot be ignored. HIV-1 drug resistance testing is recommended before initiating ART.

The impact of social participation on Subjective Wellbeing in the older adult: the mediating role of anxiety and the moderating role of education.

Introduction: The study aims to examine the mediating role of anxiety in the relationship between social participation and Subjective Wellbeing among Chinese older adults. Additionally, it investigates the moderating ed of education in this relationship. Methods: The data came from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) published by peking University, with a sample size of 10,626 individuals aged 60 years and above. SPSS 21.0 was used for the statistical analysis of the data, and Mplus 8.0 was used for the statistical processing of the mediating and moderating effects analysis. Results: (1) The social participation significantly and positively predicated Subjective Wellbeing; (2) Anxiety partially mediated the eect between social participation and Subjective Wellbeing. The mediating eect value was 0.103; (3) Education plays a moderating role in the impact of social participation on subjective Wellbeing. Discussion: In summary, social participation can reduce the anxiety and enhance their Subjective Wellbeing. Meanwhile, the eet of social participation on Subjective Wellbeing was the greatest for the older adult with high education. The findings suggest that community-led activities can be initiated to improve social participation in the older adult. Furthermore, educational courses could be to support the healthy aging of older adults in China.

Erratum: [Corrigendum] Macleaya cordata extracts exert antiviral effects in newborn mice with rotavirus­induced diarrhea via inhibiting the JAK2/STAT3 signaling pathway.

[This corrects the article DOI: 10.3892/etm.2020.8766.].

LINC317.5 as a novel biomarker for hypertriglyceridemia in normal glucose metabolism.

The global rise in prediabetes and diabetes, with type 2 diabetes (T2DM) being predominant, highlights the association between T2DM and hypertriglyceridemia (HTG). Patients with both abnormal glucose levels and HTG require increased attention due to higher risks of complications and mortality. Therefore, this study aimed to find the key long non-coding RNA (lncRNA) of HTG in the abnormal glucose metabolism patients. We collected blood samples for RNA sequencing experiments and blood samples for validation in population. We have conducted RNA sequencing, weighted gene co-expression network analysis (WGCNA), quantitative real-time polymerase chain reaction (qRT-PCR) in a 82-vs-82-sample-size population and insulin induced HepG2, RNA- Fluorescence in situ hybridization (FISH) and Cell Counting Kit-8 (CCK-8). We also explored lipid metabolism related transcription factor and the related protein expression and processed key lncRNA by both interference expression and overexpression, and the related consequences were rescued by its target mRNA. ENST00000540317.5 (LINC317.5) was lower in HTG with abnormal glucose metabolism and was found in both cytoplasm and nucleus in HepG2, inversely regulating the accumulation of TG and its target mRNA TKFC. Relative expression of peroxisome proliferator-activated receptor alpha (PPARα) and peroxisome proliferator-activated receptor gamma (PPARγ) were decreasing, and SREBP-1c (sterol regulatory element-binding protein-1c) was increasing of the interference expression of LINC317.5. Interference expression of LINC317.5 significantly decreased the protein expression of ACADM and CPT1A, whereas increased the protein expression of FAS and ACC1. TKFC partly reduced the triglyceride (TG) accumulation of LINC317.5. In conclusion, we suggested LINC317.5-TKFC as a key for TG accumulation in the HepG2-insulin resistant (IR). These might provide information of non-invasive biomarkers for the HTG with abnormal glucose.

Functional assessment of a novel biallelic MYH3 variation causing CPSKF1B (contractures, pterygia, and spondylocarpotarsal fusion syndrome1B).

BACKGROUND: The MYH3-associated myosinopathies comprise a spectrum of rare neuromuscular disorders mainly characterized by distal arthrogryposis with or without other features like pterygia and vertebrae fusion. CPSKF1B (contractures, pterygia, and spondylocarpotarsal fusion syndrome1B) is the only known autosomal recessiveMYH3-associated myosinopathy so far, with no more than two dozen cases being reported. MATERIALS AND METHODS: A boy with CPSKF1B was recruited and subjected to a comprehensive clinical and imaging evaluation. Genetic detection with whole-exome sequencing (WES) was performed on the patient and extended family members to identify the causative variation. A series of in silico and in vitro investigations were carried out to verify the pathogenicity of the two variants of the identified compound heterozygous variation. RESULTS: The patient exhibited moderate CPSKF1B symptoms including multiarticular contractures, webbed neck, and spondylocarpotarsal fusion. WES detected a compound heterozygous MYH3 variation consisting of two variants, namely NM_002470.4: c.3377A>G; p. (E1126G) and NM_002470.4: c.5161-2A>C. It was indicated that the NM_002470.4: c.3377A>G; p. (E1126G) variant mainly impaired the local hydrogen bond formation and impacted the TGF-B pathway, while the NM_002470.4: c.5161-2A>C variant could affect the normal splicing of pre-mRNA, resulting in the appearance of multiple abnormal transcripts. CONCLUSIONS: The findings of this study expanded the mutation spectrum of CPSKF1B, provided an important basis for the counseling of the affected family, and also laid a foundation for the functional study of MYH3 mutations.

Unveiling dysregulated lncRNAs and networks in non-syndromic cleft lip with or without cleft palate pathogenesis.

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common congenital facial malformation with a complex, incompletely understood origin. Long noncoding RNAs (lncRNAs) have emerged as pivotal regulators of gene expression, potentially shedding light on NSCL/P's etiology. This study aimed to identify critical lncRNAs and construct regulatory networks to unveil NSCL/P's underlying molecular mechanisms. Integrating gene expression profiles from the Gene Expression Omnibus (GEO) database, we pinpointed 30 dysregulated NSCL/P-associated lncRNAs. Subsequent analyses enabled the creation of competing endogenous RNA (ceRNA) networks, lncRNA-RNA binding protein (RBP) interaction networks, and lncRNA cis and trans regulation networks. RT-qPCR was used to examine the regulatory networks of lncRNA in vivo and in vitro. Furthermore, protein levels of lncRNA target genes were validated in human NSCL/P tissue samples and murine palatal shelves. Consequently, two lncRNAs and three mRNAs: FENDRR (log2FC = - 0.671, P = 0.040), TPT1-AS1 (log2FC = 0.854, P = 0.003), EIF3H (log2FC = - 1.081, P = 0.041), RBBP6 (log2FC = 0.914, P = 0.037), and SRSF1 (log2FC = 0.763, P = 0.026) emerged as potential contributors to NSCL/P pathogenesis. Functional enrichment analyses illuminated the biological functions and pathways associated with these lncRNA-related networks in NSCL/P. In summary, this study comprehensively delineates the dysregulated transcriptional landscape, identifies associated lncRNAs, and reveals pivotal sub-networks relevant to NSCL/P development, aiding our understanding of its molecular progression and setting the stage for further exploration of lncRNA and mRNA regulation in NSCL/P.

BCL7A and BCL7B potentiate SWI/SNF-complex-mediated chromatin accessibility to regulate gene expression and vegetative phase transition in plants.

Switch defective/sucrose non-fermentable (SWI/SNF) chromatin remodeling complexes are multi-subunit machineries that establish and maintain chromatin accessibility and gene expression by regulating chromatin structure. However, how the remodeling activities of SWI/SNF complexes are regulated in eukaryotes remains elusive. B-cell lymphoma/leukemia protein 7 A/B/C (BCL7A/B/C) have been reported as subunits of SWI/SNF complexes for decades in animals and recently in plants; however, the role of BCL7 subunits in SWI/SNF function remains undefined. Here, we identify a unique role for plant BCL7A and BCL7B homologous subunits in potentiating the genome-wide chromatin remodeling activities of SWI/SNF complexes in plants. BCL7A/B require the catalytic ATPase BRAHMA (BRM) to assemble with the signature subunits of the BRM-Associated SWI/SNF complexes (BAS) and for genomic binding at a subset of target genes. Loss of BCL7A and BCL7B diminishes BAS-mediated genome-wide chromatin accessibility without changing the stability and genomic targeting of the BAS complex, highlighting the specialized role of BCL7A/B in regulating remodeling activity. We further show that BCL7A/B fine-tune the remodeling activity of BAS complexes to generate accessible chromatin at the juvenility resetting region (JRR) of the microRNAs MIR156A/C for plant juvenile identity maintenance. In summary, our work uncovers the function of previously elusive SWI/SNF subunits in multicellular eukaryotes and provides insights into the mechanisms whereby plants memorize the juvenile identity through SWI/SNF-mediated control of chromatin accessibility.

Study on serum miR-185-5p in assessing the injury severity and prognosis of patients with traumatic brain injury.

Background: This study aims to explore whether serum miR-185-5p levels are related to the injury severity and prognosis of traumatic brain injury patients. Methods: Serum miR-185-5p level was quantified in 120 TBI patients. The Glasgow Coma Scale (GCS) was used to grade the damage, and the Glasgow Outcome Scale (GOS) was used to evaluate the prognosis 3 months after TBI. Pearson correlation analysis was performed to determine the relationship between serum miR-185-5p level and injury severity and prognosis, and the value of serum miR-185-5p level to assess injury severity and prognosis was evaluated by receiver operating characteristic (ROC) curve. Results: Serum miR-185-5p level in moderate and severe TBI patients was higher than in mild TBI patients, and serum miR-185-5p was closely related to GCS score and GOS score. Serum miR-185-5p level higher than 0.36 could distinguish patients with mild to moderate TBI injury, with 72.97% sensitivity and 97.62% specificity, while that higher than 0.43 had 46.34% sensitivity and 91.89% specificity to distinguish moderate to severe TBI patients. Moreover, serum miR-185-5p levels higher than 0.36, with a sensitivity of 96.30% and a specificity of 60.24%, distinguished the poor prognosis of TBI patients. Serum miR185-5p level was an independent predictor of poor prognosis in TBI patients after 3 months and was effective in discriminating adverse outcomes at 3 months. Conclusions: Serum miR-185-5p level was significantly correlated with 3-month injury and adverse prognosis in TBI patients, suggesting that serum miR-185-5p level may be a biomarker that provides supplementary prognostic information and can be used to identify the risk of adverse prognosis in TBI patients.

Multi-omics analyses of serum metabolome, urine metabolome and gut microbiome reveal dysregulated glycerophospholipid metabolism in subacute cadmium-exposed wistar rats.

Data is limited on intestinal microbiota and metabolites in healthy residents exposed to cadmium (Cd), a population uniquely susceptible to Cd toxicity through contaminated foods. In this study, the 16 S rRNA gene sequencing, serum metabolomics and urine metabolomics were performed to examine the alterations of gut microbiota and metabolomics profile of wistar rats exposed to Cd. These findings indicated that Cd exposure markedly altered the structure of gut microbial community, reduced significantly microbiome diversity, and identified 5 phyla and 6 genera with significant changes. Specifically, the levels of Pseudoxanthomonas and Anaerovibrio upregulated and that of Akkermansia, Brachyspira, Aggregatibacter and SMB53 reduced in rats treated with Cd. Metabolomics profiles of the urine and serum of Cd-treated rats revealed that the abundance of glycerophospholipid metabolites and their derivatives were markedly altered. Glycerophospholipid metabolic pathways that were markedly enriched in metabolomics in both samples was also significantly predicted in gut microbiota analysis. Further, interaction analysis predicted that there might be a relationship between the differential glycerophospholipid metabolites and affected bacteria genera induced by Cd. These results suggested that subacute Cd could disrupt the intestinal microecologica equilibrium and glycerophospholipid metabolic homeostasis, and also provided potential differential microbiota and glycerophospholipid biomarkers between subacute Cd-exposed rats and healthy rats.

Does vitamin D have a potential role in precocious puberty? A meta-analysis.

Background: Precocious puberty, one of the common pediatric endocrine system diseases, has been related to reduced adult height, adverse psychological outcomes and long-term health consequences. Previous findings have found that low levels of vitamin D appear to be associated with the characteristics of precocious puberty such as early menarche. However, the effect of vitamin D on precocious puberty remains controversial. Methods: The published literature was searched from PubMed, Web of Science, Cochrane Library, MEDLINE, EMBASE, CNKI, Wan Fang and VIP databases up to October 2022. A randomized effect model was used to perform a meta-analysis to evaluate differences in vitamin D concentration between precocious puberty subjects and normal subjects, the risk of precocious puberty in subjects with low vitamin D levels, and the effect of supplementation of vitamin D on subjects with precocious puberty on medication. Results: Our study found that precocious puberty subjects had lower serum vitamin D levels than the normal population (standardized mean difference (SMD) = -1.16 ng ml-1 and 95% confidence interval (CI) = -1.41 and -0.91 ng ml-1). Meanwhile, the lower level of vitamin D was associated with the risk of precocious puberty (odd ratio (OR) = 2.25 and 95% CI = 1.66 and 3.04). Moreover, compared with gonadotropin-releasing hormone analogue (GnRHa) intervention alone, subjects receiving GnRHa + vitamin D intervention had significantly lower luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol levels and bone age, and higher predicted adult height (PAH). Conclusions: Vitamin D may have a potential role in precocious puberty and more data from large clinical trials are needed to confirm the findings.

Structure of a Pueraria root polysaccharide and its immunoregulatory activity on T and B lymphocytes, macrophages, and immunosuppressive mice.

In this experiment, the polysaccharide was extracted from Pueraria lobata (Willd.) Ohwi, and its structural characteristics and bioactivity were investigated. The results showed that Pueraria lobata polysaccharide (PLP) was composed of fucose, arabinose, galactose, glucose, xylose, mannose in a molar proportion of 0.09:1.25:2.19:95.74:0.43:0.30 with a number molar masses (Mn) weight of 14.463 kDa. Besides, FT-IR, Methylation, and NMR analysis revealed that PLP were mainly composed of the main chain →4)-α-Glcp (1→ and →4,6)-α-Glcp (1→, and the branched chain α-Glcp (1→. In vitro experiment, the results showed that PLP could stimulate the expression of surface molecules on RAW264.7 and (T and B) lymphocytes proliferation, simultaneously to stimulate their cytokines secretion. In vivo experiment, the immune organ index, cytokine content, and T lymphocyte subtype in cyclophosphamide-induced immunosuppressed mice could be improved by PLP. These data proved that PLP could be used as a useful immunomodulator to enhance the immune activity of RAW264.7, T, and B cells and improve the immune function of cyclophosphamide-treated mice.

Photolysis frequency of nitrophenols derived from ambient measurements.

Nitrophenols, a class of important intermediate products from the oxidation of aromatics, can participate in photochemistry and influence the atmospheric oxidative capacity. However, the reported photolysis frequencies of nitrophenols show considerable discrepancies. Here, measurements of nitrophenol, and methyl nitrophenol using a proton-transfer-reaction time-of-flight mass spectrometer (PTR-ToF-MS) at both urban and regional sites in southern China are used to constrain photolysis frequencies of nitrophenols. Considerable concentrations with a campaign average of 58 ± 32 ppt for nitrophenol and 97 ± 59 ppt for methyl nitrophenol were observed at the regional site. Based on the in-situ measurement dataset, a steady-state calculation was performed along with a zero-dimensional box model to analyze the budgets of nitrophenols. The result indicates that both primary emission and photolysis have significant impacts on nitrophenols. Primary emission contributes up to 88 % of the total nitrophenols production while photolysis accounts for up to 98 % of the total removal rate. The dominant sink of nitrophenols is photolysis with a rate of about 3.5 % ± 1.3 % of jNO2 for nitrophenol and 2.4 % ± 1.0 % of jNO2 for methyl nitrophenol. The results of this study suggest that using advanced mass spectrometry to accurately measure ambient nitrophenols, supplemented by an observation-based box model for budget analysis, provides an important indication for determining photolysis rate constants of nitrophenols.

hnRNP K induces HPV16 oncogene expression and promotes cervical cancerization.

PURPOSE: This study aims to explore the expression of hnRNP K in cervical carcinogenesis and to investigate the regulatory role of hnRNP K on HPV16 oncogene expression as well as biological changes in cervical cancer cells. METHODS: In total 1042 subjects, including 573 with the normal cervix and 469 with different grades of cervical lesions were enrolled in this study to explore the association between hnRNP K and HPV16 oncogene expression in cervical carcinogenesis. Additionally, the Gene Omnibus (GEO) database was used to analyze hnRNP K mRNA expression in cervical cancerization. Meanwhile, the effects of hnRNP K on cell biological functions and HPV16 oncogene expression were investigated in Siha cells. Moreover, Function analyses were conducted using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases after ChIP-seq. RESULTS: hnRNP K was highly expressed in cervical cancer and precancerous lesions, and positively correlated with HPV16 E6, but negatively correlated with HPV16 E2 and HPV16 E2/E6 ratio. hnRNP K induced cell proliferation, inhibited apoptosis and caused cell cycle arrest in the S phase, and particularly increased HPV16 E6 protein expression. CONCLUSION: This study revealed that hnRNP K overexpression has important warning significance for the malignant transformation of cervical lesions, and could be used as a potential therapeutic target for inhibiting the carcinogenicity of HPV16 and prevention of cervical carcinogenesis.

Amelioration effects of the soybean lecithin-gallic acid complex on iron-overload-induced oxidative stress and liver damage in C57BL/6J mice.

CONTEXT: Gallic acid (GA) and lecithin showed important roles in antioxidant and drug delivery, respectively. A complex synthesized from GA and soybean lecithin (SL-GAC), significantly improved bioavailability of GA and pharmacological activities. However, the antioxidant activity of SL-GAC and its effect on iron-overload-induced liver injury remains unexplored. OBJECTIVE: This study investigates the antioxidant properties of SL-GAC in vitro and in mice, and its remediating effects against liver injury by iron-overloaded. MATERIALS AND METHODS: In vitro, free radical scavenging activity, lipid peroxidation inhibition, and ferric reducing power of SL-GAC were measured by absorbance photometry. In vivo, C57BL/6J mice were randomized into 4 groups: control, iron-overloaded, iron-overloaded + deferoxamine, and iron-overloaded + SL-GAC. Treatments with deferoxamine (150 mg/kg/intraperitioneally) and SL-GAC (200 mg/kg/orally) were given to the desired groups for 12 weeks, daily. Iron levels, oxidative stress, and biochemical parameters were determined by histopathological examination and molecular biological techniques. RESULTS: In vitro, SL-GAC showed DPPH and ABTS free radicals scavenging activity with IC50 values equal to 24.92 and 128.36 µg/mL, respectively. In C57BL/6J mice, SL-GAC significantly reduced the levels of serum iron (22.82%), liver iron (50.29%), aspartate transaminase (25.97%), alanine transaminase (38.07%), gamma glutamyl transferase (42.11%), malondialdehyde (19.82%), total cholesterol (45.96%), triglyceride (34.90%), ferritin light chain (18.51%) and transferrin receptor (27.39%), while up-regulated the levels of superoxide dismutase (24.69%), and glutathione (11.91%). CONCLUSIONS: These findings encourage the use of SL-GAC to treat liver injury induced by iron-overloaded. Further in vivo and in vitro studies are needed to validate its potential in clinical medicine.

Dietary aluminium intake disrupts the overall structure of gut microbiota in Wistar rats.

Approximately, 40% of ingested dietary aluminium accumulates in the intestine, which has been considered a target organ for dietary aluminium exposure. The gut microbiota may be the first protective barrier against the toxic metal aluminium and a crucial mediator of the bioavailability of metal aluminium. We previously evaluated dietary aluminium intake and its health risks in a population from Jilin Province, China, and found that the average daily intake of aluminium in the diet of residents in Jilin Province was 0.163 mg/kg after the total diet survey. In the present study, the equivalent concentration of aluminium in rats was extrapolated by the average dietary aluminium intake in the population of Jilin Province based on body surface area. Furthermore, healthy adult Wistar rats were randomly divided into four groups (n = 15 for each group): a control group and three groups treated with aluminium solution (1, 10, and 100 mg/kg/day, intragastrically) for 28 days. Following treatment, necrosis of renal tubular epithelial cells, hyperplasia of bile ducts and hyperplasia of heart tissue, as well as fiber in the liver, kidney, and heart tissues of aluminium-treated rats were observed, although there were no significant changes in the spleen and brain. Subsequently, fecal samples were withdrawn for 16S rRNA gene sequence analysis. It was found that aluminium decreased the microbiota diversity and changed the overall community structure of the gut microbiota, including three phyla and four genera, together with the regulation of 12 signaling pathways. Collectively, treatment with aluminium markedly altered the structure of the gut microbiota, suggesting that the disorders of intestinal flora induced by aluminium may be an important mechanism for aluminium toxicity.

A Novel L-Phenylalanine Dipeptide Inhibits the Growth and Metastasis of Prostate Cancer Cells via Targeting DUSP1 and TNFSF9.

Prostate cancer (PCa) is a common malignant cancer of the urinary system. Drug therapy, chemotherapy, and radical prostatectomy are the primary treatment methods, but drug resistance and postoperative recurrence often occur. Therefore, seeking novel anti-tumor compounds with high efficiency and low toxicity from natural products can produce a new tumor treatment method. Matijin-Su [N-(N-benzoyl-L-phenylalanyl)-O-acetyl-L-phenylalanol, MTS] is a phenylalanine dipeptide monomer compound that is isolated from the Chinese ethnic medicine Matijin (Dichondra repens Forst.). Its derivatives exhibit various pharmacological activities, especially anti-tumor. Among them, the novel MTS derivative HXL131 has a significant inhibitory effect against prostate tumor growth and metastasis. This study is designed to investigate the effects of HXL131 on the growth and metastasis of human PCa cell lines PC3 and its molecular mechanism through in vitro experiments combined with proteomics, molecular docking, and gene silencing. The in vitro results showed that HXL131 concentration dependently inhibited PC3 cell proliferation, induced apoptosis, arrested cell cycle at the G2/M phase, and inhibited cell migration capacity. A proteomic analysis and a Western blot showed that HXL131 up-regulated the expression of proliferation, apoptosis, cell cycle, and migration-related proteins CYR61, TIMP1, SOD2, IL6, SERPINE2, DUSP1, TNFSF9, OSMR, TNFRSF10D, and TNFRSF12A. Molecular docking, a cellular thermal shift assay (CETSA), and gene silencing showed that HXL131 had a strong binding affinity with DUSP1 and TNFSF9, which are important target genes for inhibiting the growth and metastasis of PC3 cells. This study demonstrates that HXL131 exhibited excellent anti-prostate cancer activity and inhibited the growth and metastasis of prostate cancer cells by regulating the expression of DUSP1 and TNFSF9.