Differential DNA methylation landscape of miRNAs genes in mice liver fibrosis.

BACKGROUND: Patients with chronic liver disease were found nearly all to have liver fibrosis, which is characterized by excess accumulation of extracellular matrix (ECM) proteins. While ECM accumulation can prevent liver infection and injury, it can destroy normal liver function and architecture. miRNA's own regulation was involved in DNA methylation change. The purpose of this study is to detect DNA methylation landscape of miRNAs genes in mice liver fibrosis tissues. METHODS: Male mice (10-12 weeks) were injected CCl4 from abdominal cavity to induced liver fibrosis. 850 K BeadChips were used to examine DNA methylation change in whole genome. The methylation change of 16 CpG dinucleotides located in promoter regions of 4 miRNA genes were detected by bisulfite sequencing polymerase chain reaction (BSP) to verify chip data accuracy, and these 4 miRNA genes' expressions were detected by RT-qPCR methods. RESULTS: There are 769 differential methylation sites (DMS) in total between fibrotic liver tissue and normal mice liver tissue, which were related with 148 different miRNA genes. Chips array data were confirmed by bisulfite sequencing polymerase chain reaction (R = 0.953; P < 0.01). GO analysis of the target genes of 2 miRNA revealed that protein binding, cytoplasm and chromatin binding activity were commonly enriched; KEGG pathway enrichment analysis displayed that TGF-beta signaling pathway was commonly enriched. CONCLUSION: The DNA of 148 miRNA genes was found to have methylation change in liver fibrosis tissue. These discoveries in miRNA genes are beneficial to future miRNA function research in liver fibrosis.

CD36: The Bridge between Lipids and Tumors.

It has been found that the development of some cancers can be attributed to obesity, which is associated with the excessive intake of lipids. Cancer cells undergo metabolic reprogramming, shifting from utilizing glucose to fatty acids (FAs) for energy. CD36, a lipid transporter, is highly expressed in certain kinds of cancer cells. High expressions of CD36 in tumor cells triggers FA uptake and lipid accumulation, promoting rapid tumor growth and initiating metastasis. Meanwhile, immune cells in the tumor microenvironment overexpress CD36 and undergo metabolic reprogramming. CD36-mediated FA uptake leads to lipid accumulation and has immunosuppressive effects. This paper reviews the types of FAs associated with cancer, high expressions of CD36 that promote cancer development and progression, effects of CD36 on different immune cells in the tumor microenvironment, and the current status of CD36 as a therapeutic target for the treatment of tumors with high CD36 expression.

Research Progress of Bioactive Components in Sanghuangporus spp.

The species in Sanghuangporus are a group of edible mushrooms with a long history of oral use in East Asia as a health-improvement method. They should be classified under the genus Sanghuangporus rather than mistakenly in Phellinus or Inonotus. The major components in this genus consist of polysaccharides, polyphenols, triterpenoids, and flavonoids, all of which exist in the fruiting bodies and mycelia. For extraction, studies have shown methods using hot water, ethanol, DES solvent, and alkaline, followed by purification methods including traditional anion column, Sevag solution, macroporous resin, and magnetic polymers. Proven by modern medical technology, these components possess promising anti-inflammatory, antioxidative, antitumor, and immunoregulation effects; additionally, they have health-improving effects including pulmonary protection, hypoglycemic properties, sleep improvement, gout mitigation, antiaging, neuroprotection, and muscle-strengthening abilities. Several toxicity studies have revealed their safety and recommend a dose of 1 g/kg for mice. As a newly emerged concept, functional food can provide not only life-sustaining nutrients but also some health-improving effects. In conclusion, we substantiate Sanghuang as a functional food by comprehensively presenting information on extraction and purification methods, component medical and structural properties, and nontoxicity, hoping to benefit the development of Sanghuang species as a group of functional food.

[Genetic analysis of two families with abnormal findings upon prenatal diagnosis].

OBJECTIVE: To carry out genetic analysis on two families with carriers of small terminal translocations using karyotyping analysis and genomic copy number variation sequencing (CNV-seq). METHODS: Two couples undergoing prenatal diagnosis at the Tianjin Central Hospital of Obstetrics and Gynecology respectively on April 12, 2020 and December 17, 2021 were selected as the study subjects. With informed consent, amniotic fluid and peripheral blood samples were collected and subjected to conventional karyotyping and CNV-seq analysis for the detection of chromosomal microdeletion/duplications. RESULTS: Both couples had given births to children with chromosomal aberrations previously, and both fetuses were found to have abnormal karyotypes. CNV-seq showed that they had harbored microdeletion/duplications, and their mothers had both carried balanced translocations involving terminal fragments of chromosomes. CONCLUSION: For fetuses with small chromosomal segmental abnormalities, their parental origin should be traced, and the diagnosis should be confirmed with combined genetic techniques.

Experimentally determined critical power for self-focusing of femtosecond vortex beams in air by a fluorescence measurement.

The filamentation of the femtosecond vortex beam has attracted much attention because of the unique filamentation characteristics, such as annular distribution and helical propagation, and related applications. The critical power for self-focusing of the femtosecond vortex beams is a key parameter in the filamentation process and applications. But until now, there is no quantitative determination of the critical power. In this work, we experimentally determine the self-focusing critical power of femtosecond vortex beams in air by measuring fluorescence using a photomultiplier tube. The relation between the self-focusing critical power and the topological charge is further obtained. Our work provides a simple method to determine the self-focusing critical power not only for vortex beams but also for Airy, Bessel, vector, and other structured laser beams.

Distinguishing the nonlinear propagation regimes of vortex femtosecond pulses in fused silica by evaluating the broadened spectrum.

The nonlinear propagation dynamics of vortex femtosecond laser pulses in optical media is a topic with significant importance in various fields, such as nonlinear optics, micromachining, light bullet generation, vortex air lasing, air waveguide and supercontinuum generation. However, how to distinguish the various regimes of nonlinear propagation of vortex femtosecond pulses remains challenging. This study presents a simple method for distinguishing the regimes of nonlinear propagation of femtosecond pulses in fused silica by evaluating the broadening of the laser spectrum as the input pulse power gradually increases. The linear, self-focusing and mature filamentation regimes for Gaussian and vortex femtosecond pulses in fused silica are distinguished. The critical powers for self-focusing and mature filamentation of both types of laser pulses are obtained. Our work provides a rapid and convenient method for distinguishing different regimes of nonlinear propagation and determining the critical powers for self-focusing and mature filamentation of Gaussian and structured laser pulses in optical media.

Lactoferrin Alleviates Ethanol-Induced Injury via Promoting Nrf2 Nuclear Translocation in BRL-3A Rat Liver Cells.

Our previous animal studies found that the preventive effects of lactoferrin (Lf) on alcoholic liver injury (ALI) are associated with nuclear factor E2-related factor 2 (Nrf2). To further explore the causality, experiments were performed using rat normal liver BRL-3A cells. Lf treatment reduced ethanol-induced death and apoptosis; meanwhile, Lf treatment alleviated excessive LDH release. These findings confirmed the protection of Lf against ethanol-induced injury in BRL-3A cells. Mechanistically, Lf treatment reversed the reduction in nuclear Nrf2 induced by ethanol without affecting the cytoplasmic Nrf2 level, which led to antioxidant enzyme activity restoration. However, the blocking of Nrf2 nuclear translocation by ML385 eliminated the protective effects of Lf. In a conclusion, Lf protects BRL-3A cells from ethanol-induced injury via promoting Nrf2 nuclear translocation.

Influence of a pinhole diameter on the experimental determination of critical power for femtosecond filamentation in air.

Filamentation of intense femtosecond laser pulses in optical media has attracted great attention due to its various unique characteristics and potential applications. It is an important task to determine the critical power for the filamentation especially in many applications, which can be obtained by evaluating the transmitted pulse energy through a pinhole located in the filamentation region as a function of input laser energy. The pinhole diameter is very crucial to the measurement. However, there is no report on the experimental determination of critical power for filamentation in air by using the pinhole method and the influence of the pinhole diameter on the determination. In this paper, we numerically and experimentally investigate the influence of pinhole diameter on the determination of the filamentation critical power. The obtained critical power tends to a reasonable value as the decrease of the pinhole diameter, because the transmitted energy through the pinhole with a smaller diameter is more sensitive to the change of energy distribution in the beam cross section during the beginning process of filamentation. Under our experimental condition, the pinhole diameter as small as ∼50 µm is applicable to be used to determine the critical power for filamentation of femtosecond laser pulses in air.

Intense vector supercontinuum radiation from femtosecond filamentation.

Intense vector supercontinuum (SC) radiation with spatial polarization is obtained by using 800nm femtosecond vector laser beams in the air. The SC generated by azimuthally, radially, cylindrically polarized beams, and higher-order vector beams are investigated, respectively. The results show that the SC generated by vector beams is greatly enhanced compared to that by a Gaussian beam. The energy density of SC radiation reaches the order of 1µJ/nm in a bandwidth of 258 nm from 559 nm to 817 nm and 0.1 µJ/nm from 500 nm to 559 nm. Furthermore, by checking the polarization distribution of SC in different wavelengths from visible to near-infrared bands, we find that the SC maintains nearly the same polarization distribution as pump pulses. This work provides an effective and convenient way to generate powerful SC vector beams which may facilitate potential applications including optical communication, micro/nano-fabrication, and super-resolution microscopy.

The monocyte to high-density lipoprotein cholesterol ratio is a risk factor for frequent premature ventricular complexes: a retrospective cohort study.

BACKGROUND: Little is known about the link between the monocyte to high-density lipoprotein cholesterol ratio (MHR) and frequent premature ventricular complexes (PVCs). This investigation aimed to evaluate the link between the MHR and frequent PVCs in patients, as well as their outcomes, using the axis, burden, coupling interval-ventricular tachycardia (ABC-VT) risk score (ARS). METHODS: Two hundred patients with frequent PVCs and 70 controls were retrospectively enrolled, and their general data were gathered. The MHR and ARS were calculated. Then, patients developing frequent PVCs were classified into a medium-/high-risk subgroup and a low-risk subgroup according to ARS. The results were evaluated employing comparative statistical analyses, Spearman's correlation, logistic regression analyses, and receiver operating characteristic (ROC) curves. RESULTS: The MHR in the controls was obviously lower than that in the frequent PVC group. In addition, the MHR was the lowest in the control group and highest in the medium-/high-risk subgroup, with that of the low-risk subgroup falling in the middle. Spearman's correlation analyses showed that the MHR was positively correlated with the ARS (ρ = 0.307, P < 0.001). Ultimately, the MHR was found to be a risk factor for frequent PVCs in the multivariate analysis. In addition, an MHR cutoff point of 254.6 featured 67.50% sensitivity and 67.14% specificity for predicting frequent PVCs, and the area under the curve (AUC) reached 0.694 (95% confidence interval: 0.623-0.766) (P < 0.001). CONCLUSIONS: The MHR is positively and independently correlated with frequent PVCs and can be used as a practical, cost-saving and simple biomarker of inflammation owing to its value in predicting frequent PVCs. In addition, the MHR is crucial to risk stratification and prognosis, which may give it clinical value in the prevention and management of frequent PVCs.

Apple polyphenols extract alleviated dextran sulfate sodium-induced ulcerative colitis in C57BL/6 male mice by restoring bile acid metabolism disorder and gut microbiota dysbiosis.

To investigate and compare the preventive effects of apple polyphenols extract (APE) with phloretin on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC), 60 male mice were treated with 125 or 500 mg/(kg bw d) APE or 100 mg/(kg bw d) phloretin, the single-ingredient of APE, for continuous 3 weeks by intragastric administration, meanwhile, mice were provided with 3% DSS dissolved in drinking water to induce UC during the third week. Both APE and phloretin significantly ameliorated DSS-induced UC by inhibiting body weight loss, preventing colon shortening and mucosa damage. Except the same mechanisms of the inhibited activation of NF-κB signaling, decreased hyodeoxycholic acid level and increased abundance of Verrucomicrobia at phylum and Bacteroides and Akkermansia at genus, APE increased ß-muricholic acid level and decreased Bacterodetes abundance, while phloretin decreased Firmicutes abundance. Furthermore, APE treatment showed much lower disease activity index score, less body weight loss and lighter spleen than phloretin. Thus, our study supported the potentiality of APE as a promising dietary intervention for the prevention of experimental UC.

Apple polyphenol extract alleviates lipid accumulation in free-fatty-acid-exposed HepG2 cells via activating autophagy mediated by SIRT1/AMPK signaling.

Defective degradation of intracellular lipids induced by autophagy is causally linked to the development of non-alcoholic fatty liver disease (NAFLD). Natural agents that can restore autophagy could therefore have the potentials for clinical applications for this public health issue. Herein, we investigated the effects of apple polyphenol extract (APE) on fatty acid-induced lipids depositions in HepG2 cells. APE treatment alleviated palmitic acid and oleic acid-induced intracellular lipid accumulation, concomitant with the increased autophagy, restored lysosomal acidification, inhibited lipid synthesis and slight promotion of fatty acid oxidation. Mechanistically, APE up-regulated the expression of SIRT1, activated LKB1/AMPK pathway and inhibited mTOR signaling. Over-expressed or knock-down SIRT1 positively regulated AMPK and ATG7 expressions. SIRT1 and ATG7 knock-down impaired APE induction of improved lipid accumulation, increased intracellular TG content. Thus, APE induction of autophagy to ameliorate fatty acid-induced lipid deposition is SIRT1 dependent, APE conserved preventive potentials for clinical hepatosteatosis.

Polyphenols intervention is an effective strategy to ameliorate inflammatory bowel disease: a systematic review and meta-analysis.

Whether polyphenols could ameliorate inflammatory bowel disease (IBD) is still conflicting. To explore the efficacy of polyphenols as an adjuvant therapy for IBD, we conducted this systematic review and meta-analysis. Literature search was performed using PubMed, Web of Science, Scopus and Cochrane databases. Finally, 12 randomized controlled trials (RCTs) were included. In contrast to control group, curcumin treatment significantly improved clinical remission in intention-to-treat (ITT) (OR = 3.36, 95% CI: 1.09-10.37) and per-protocol (PP) analysis (OR = 5.13, 95% CI: 1.84-14.27). Meanwhile, curcumin could significantly ameliorate endoscopic remission (OR = 5.69, 95% CI: 1.28-25.27) and clinical response (OR = 4.69, 95% CI: 1.03-21.47) in PP analysis. Heterogeneity was present across the studies. In conclusions, polyphenols might be an effective adjuvant treatment for ameliorating IBD. Considering the relatively few studies included in our present study, further clinical trials are required to verify the effects of polyphenols on IBD.

Dietary citrus and/or its extracts intake contributed to weight control: Evidence from a systematic review and meta-analysis of 13 randomized clinical trials.

Randomized controlled trials, being published in English and investigating the associations of at least 4 weeks intervention of citrus and/or its extracts on weight loss among adults, were searched from PubMed, Web of Science, Scopus, and Cochrane by June 2019 to conduct a meta-analysis. Thirteen articles, including 921 participants, were selected and evaluated by modified Jadad scale. Pooled results by the random-effects model showed that citrus and/or its extracts administration significantly reduced 1.280 kg body weight (95% CI: -1.818 to -0.741, p = 0.000, I2 = 81.4%), 0.322 kg/m2 BMI (95% CI: -0.599 to -0.046, p = 0.022, I2 = 87.0%), 2.185 cm WC (95% CI: -3.804 to -0.566, p = 0.008, I2 = 98.3%), and 2.137 cm HC (95% CI: -3.775 to -0.500, p = 0.011, I2 = 96.2%), respectively, but no significantly decreased effects on WHR and body fat were observed. Subgroup analysis deduced the different effects of study location, intervention duration on body weight associated indices. No publication bias was observed. Our meta-analysis supported the beneficial effects of citrus and/or its extracts supplement on body weight control, and future well-designed studies are required to firmly establish the clinical efficacy of citrus and/or its extracts intervention on body weight.

Alcohol Drinking and the Risk of Chronic Kidney Damage: A Meta-Analysis of 15 Prospective Cohort Studies.

The relationship between alcohol drinking and chronic kidney damage, mainly including declined glomerular filtration rate (GFR), proteinuria, and end-stage renal disease, was conflicting. Thus, a meta-analysis was conducted to investigate their potential associations. PubMed and Web of Science were searched to identify prospective studies assessing the associations between alcohol drinking and chronic kidney damage published up to March 2019. Random-effects model was employed to pool the relative risks (RR) with 95% confidence intervals (CIs). Subgroup meta-analyses stratified by the basic characteristics of subjects were performed. A total of 15 cohort studies were included in the present study, with 268,723 participants and 31,766 incident cases. Participants with low (<13 g/d), moderate (13 to 26 g/d), and high (26 to 60 g/d) dose of alcohol drinking had 12% (RR: 0.88, 95% CI: 0.83 to 0.93), 24% (RR: 0.76, 95% CI: 0.70 to 0.83), and 21% (RR: 0.79, 95% CI: 0.71 to 0.88) lower risk of chronic kidney damage compared with the reference group (non- or occasional drinkers), respectively. The lower risk for chronic kidney damage remained significant for the declined GFR, or in men, or for participants aged less than 55 yrs, or studies with longer than 8 yrs of follow-up, while severe alcohol drinking (≥60 g/d) insignificantly increased 7% risk of chronic kidney damage (RR: 1.07, 95% CI: 0.53 to 2.15). No obvious heterogeneity and no publication bias were observed. Based on our meta-analysis, participants with alcohol drinking less than 60 g/d were at lower risk of declined GFR, especially in men or participants aged less than 55 yrs. Much more prospective cohort studies are required to confirm our present findings.

Joint associations of serum uric acid and ALT with NAFLD in elderly men and women: a Chinese cross-sectional study.

BACKGROUND: Epidemiological evidence suggests sex difference in serum uric acid (SUA) and alanine aminotransferase (ALT) might be a potential explanation for the gender difference in prevalence of non-alcoholic fatty liver disease (NAFLD). However, few epidemiology data in China have tested this hypothesis. METHODS: We conducted a cross-sectional study to assess the joint associations between SUA and serum ALT with NAFLD among elderly Chinese men and women. RESULTS: Among 7569 participants with a mean age of 59.8 years (± 13.4 years), 56.6% of women and 43.4% of men were diagnosed as NAFLD, respectively. A positive association between SUA and NAFLD prevalence was observed in both men and women. NAFLD prevalence was 2.74 times (95% CI 2.00-3.76) higher for men and 4.60 times (95% CI 3.39-6.24) higher for women with the highest quintiles of SUA levels compared to those with the lowest levels. SUA levels were significantly associated with prevalence of mild- and severe-steatosis (P < 0.01). In addition, the ORs of NAFLD among participants with high SUA levels and high serum ALT was 10.75 (95% CI 3.56-32.46) for men and 7.96 (95% CI 2.83-22.39) for women, compared with those with low SUA levels and low serum ALT. CONCLUSIONS: SUA levels were positively associated with NAFLD prevalence, and the association was slightly stronger in women than in men. A significant joint association of SUA and serum ALT with NAFLD prevalence was observed in all participants, which was slightly stronger in men than in women.

The novel protein C3orf43 accelerates hepatocyte proliferation.

BACKGROUND: Our previous study found that single-pass membrane protein with coiled-coil domains 1 (C3orf43; XM_006248472.3) was significantly upregulated in the proliferative phase during liver regeneration. This indicates that C3orf43 plays a vital role in liver cell proliferation. However, its physiological functions remains unclear. METHODS: The expressions of C3orf43 in BRL-3A cells transfected with C3orf43-siRNA (C3-siRNA) or overexpressing the vector plasmid pCDH-C3orf43 (pCDH-C3) were measured via RT-qPCR and western blot. Cell growth and proliferation were determined using MTT and flow cytometry. Cell proliferation-related gene expression was measured using RT-qPCR and western blot. RESULTS: It was found that upregulation of C3orf43 by pCDH-C3 promoted hepatocyte proliferation, and inhibition of C3orf43 by C3-siRNA led to the reduction of cell proliferation. The results of qRT-PCR and western blot assay showed that the C3-siRNA group downregulated the expression of cell proliferation-related genes like JUN, MYC, CCND1 and CCNA2, and the pCDH-C3 group upregulated the expression of those genes. CONCLUSION: These findings reveal that C3orf43 may contribute to hepatocyte proliferation and may have the potential to promote liver repair and regeneration.

[Apple polyphenol inhibited the proliferation and migration of breast cancer cell MDA-MB-231 mediated by UHRF1].

OBJECTIVE: To investigate the effects of apple polyphenol on cell proliferation and migration of breast cancer cell line MDA-MB-231, and explore the potential mechanism. METHODS: The breast cancer cells in the logarithmic phase were treated with 0, 50, 100, 200, 400 and 800 µg/m L of apple polyphenol for 24, 48 and 72 h, then Trypan blue staining was employed to detect cell vitality; CCK8 kit was used to determine cell growth and proliferation; cell migration ability was observed by scratch experiment, and the change of proteins expression level was assessed by Western blot. RESULTS: Apple polyphenol could content-dependently inhibit breast cancer cell's vitality and proliferation between 0 and 800 µg/m L, decrease the proteins level of ubiquitinlike with PHD and ring finger domain 1( UHRF1) and matrix metalloproteinases-2( MMP2), and the protein levels of DNA methyltransferases 3 a( DNMT3 a) and DNMT3 b, themolecular targets of UHRF1, also decreased. Apple polyphenol inhibition of cell 's migration was more significant between 400 and 800 µg/mL. CONCLUSION: Apple polyphenol inhibited the vitality, cell growth and proliferation, and migration of breast cancer cells MDA-MB-231 by decreasing the proteins expression of UHRF1 and MMP2, and the downstream targets of UHRF1, DNMT3 a and DNMT3 b, also decreased.

Analysis of the ways and methods of signaling pathways in regulating cell cycle of NIH3T3 at transcriptional level.

BACKGROUND: To analyze the ways and methods of signaling pathways in regulating cell cycle progression of NIH3T3 at transcriptional level, we modeled cell cycle of NIH3T3 and found that G1 phase of NIH3T3 cell cycle was at 5-15 h after synchronization, S phase at 15-21 h, G2 phase at 21-22 h, M phase at 22-25 h. RESULTS: Mouse Genome 430 2.0 microarray was used to detect the gene expression profiles of the model, and results showed remarkable changes in the expressions of 64 cell cycle genes and 960 genes associated with other physiological activity during the cell cycle of NIH3T3. For the next step, IPA software was used to analyze the physiological activities, cell cycle genes-associated signal transduction activities and their regulatory roles of these genes in cell cycle progression, and our results indicated that the reported genes were involved in 17 signaling pathways in the regulation of cell cycle progression. Newfound genes such as PKC, RAS, PP2A, NGR and PI3K etc. belong to the functional category of molecular mechanism of cancer, cyclins and cell cycle regulation HER-2 signaling in breast cancer signaling pathways. These newfound genes could promote DNA damage repairment and DNA replication progress, regulate the metabolism of protein, and maintain the cell cycle progression of NIH3T3 modulating the reported genes CCND1 and C-FOS. CONCLUSION: All of the aforementioned signaling pathways interacted with the cell cycle network, indicating that NIH3T3 cell cycle was regulated by a number of signaling pathways.

DNA methylation dynamics in the rat EGF gene promoter after partial hepatectomy.

Epidermal growth factor (EGF), a multifunctional growth factor, is a regulator in a wide variety of physiological processes. EGF plays an important role in the regulation of liver regeneration. This study was aimed at investigating the methylation level of EGF gene throughout liver regeneration. DNA of liver tissue from control rats and partial hepatectomy (PH) rats at 10 time points was extracted and a 354 bp fragment including 10 CpG sites from the transcription start was amplified after DNA was modified by sodium bisulfate. The result of sequencing suggested that methylation ratio of four CpG sites was found to be significantly changed when PH group was compared to control group, in particular two of them were extremely striking. mRNA expression of EGF was down-regulated in total during liver regeneration. We think that the rat EGF promoter region is regulated by variation in DNA methylation during liver regeneration.