Background and Objectives: Pruritus is a common and disabling symptom affecting as much as 50-90% of chronic kidney disease (CKD) patients undergoing dialysis. The pruritus experienced by these patients is often resistant to common anti-pruritic agents and has an overall negative impact on quality of life. With its antioxidant property and anti-inflammatory effects, omega-3 fatty acids have been used to alleviate pruritus. The objective of this study is to assess the effect of omega-3 fatty acid supplementation in reducing the severity of pruritus among dialytic CKD patients. Methods: Various electronic databases were searched from inception to August 2022. Randomized controlled trials comparing the effect of omega-3 fatty acids versus placebo on the pruritus scores were included. The studies were independently assessed by three reviewers. Revman version 5.4 was used to analyze the data extracted from the studies while heterogeneity was evaluated using Chi2 and I2. Results: A total of four studies with a population of 166 patients were included in the meta-analysis. The results show an overall beneficial effect of omega-3 fatty acids with a standardized mean difference of -1.40 (CI -1.74 to -1.05, Z=7.95, p value <0.00001). With a Chi2 of 2.91 (p=0.41) and I2 of 0%, there was no significant heterogeneity observed in the pooled analysis. Conclusion Overall, the results of the meta-analysis support the finding that omega-3 fatty acid supplementation may have a beneficial effect on reducing the severity of pruritus among CKD patients on dialysis.
Fatty Acids, Omega-3 ; Renal Insufficiency, Chronic ; Pruritus

OBJECTIVES

Carica papaya has been widely used commercially for skin care due to its therapeutic benefits. The potential of its flower to promote hair growth has been traditionally recognized in other countries but not in the Philippines. In this study, we explored the effect of various extracts of C. papaya flower in the biological activities associated with hair loss, including 5α-reductase inhibition and antioxidation, as well as identified the putative compounds present in the most potent extract.

The flowers of C. papaya were macerated separately with ethanol, ethyl acetate, and hexane to obtain their corresponding crude extracts. These extracts were subjected to antioxidant tests via 2,2′-diphenyl-1-picrylhydrazyl (DPPH), and ferric-reducing antioxidant power (FRAP) assays. The total phenolic and flavonoid contents (TPC and TFC) of the crude extracts were determined, as well as the ability of the extracts to inhibit 5α-reductase. The compounds present in the most potent extract were determined using ultraperformance liquid chromatography quadrupole time of flight mass spectrometer (UPLC/MS-QToF).

Ethyl acetate extract displayed significantly higher DPPH activity (0.001755 ± 0.00092 ascorbic acid equivalent antioxidant capacity) and 5α-reductase inhibitory activity (115.18 ± 11.61 mg dutasteride/g) compared to ethanol (DPPH: p=0.0121; 5α-reductase: p=0.0016) and hexane (DPPH: p=0.0038; 5α-reductase: p < 0.0001) extracts. Similarly, ethyl acetate extract gave the highest FRAP (0.4842 ± 0.0936 mg ascorbic acid/g) activity, TFC (0.0403 mg quercetin/g), and TPC (0.0463 mg gallic acid/g) among the extracts. Forty-nine compounds were annotated in the ethyl acetate extract, with seven (7) putatively identified as fatty acids (9-hydroxy-10,12-pentadecadienoic acid, 9,12,15-octadecatrienoic acid), hydroxyflavone (5-methylkaempferol), alkaloid (allomatrine), dipeptide derivative (aurantiamide acetate), bufotalinin, and 6β-acetoxy-5-epilimonin based on the Traditional Chinese Medicine Library.

These results suggest that local C. papaya flowers can be a source of hair growth-promoting agents via their antioxidant and 5α-reductase inhibitory potential.

Objective: Bariatric surgery effectively treats non-alcoholic fatty liver disease (NAFLD). The glutamate-serine-glycine (GSG) index has emerged as a non-invasive diagnostic marker for NAFLD, but its ability to monitor treatment response remains unclear. This study investigates the GSG index's ability to monitor NAFLD's response to bariatric surgery. Methodology: Ten NAFLD participants were studied at baseline and 6 months post-bariatric surgery. Blood samples were collected for serum biomarkers and metabolomic profiling. Hepatic steatosis [proton density fat fraction (PDFF)] and fibroinflammation (cT1) were quantified with multiparametric magnetic resonance imaging (mpMRI), and hepatic stiffness with magnetic resonance elastography (MRE). Amino acids and acylcarnitines were measured with mass spectrometry. Statistical analyses included paired Student’s t-test, Wilcoxon-signed rank test, and Pearson’s correlation. Results: Eight participants provided complete data. At baseline, all had hepatic steatosis (BMI 39.3 ± 5.6 kg/m2, PDFF ≥ 5%). Post-surgery reductions in PDFF (from 12.4 ± 6.7% to 6.2 ± 2.8%, p = 0.013) and cT1 (from 823.3 ± 85.4ms to 757.5 ± 41.6ms, p = 0.039) were significant, along with the GSG index (from 0.272 ± 0.03 to 0.157 ± 0.05, p = 0.001). Conclusion The GSG index can potentially be developed as a marker for monitoring the response of patients with NAFLD to bariatric surgery.
Non-alcoholic Fatty Liver Disease ; Amino Acids ; Metabolomics

Pregnancy ; Female ; Humans ; Milk, Human ; Overweight/genetics* ; Fatty Acids, Unsaturated ; Fatty Acids ; Adiponectin/genetics*

Genkwa Fols, Kansui Radix, and Euphorbiae Pekinensis Radix in Shizao Decoction(SZD) are toxic to intestinal tract. Jujubae Fructus in this prescription can alleviate the toxicity, but the mechanism is still unclear. Therefore, this study aims to explore the mechanism. To be specific, 40 normal Sprague-Dawley(SD) rats were classified into the normal group, high-dose and low-dose SZD groups, and high-dose and low-dose SZD without Jujubae Fructus(SZD-JF) groups. The SZD groups were given(ig) SZD, while SZD-JF groups received the decoction without Jujubae Fructus. The variation of body weight and spleen index were recorded. The patho-logical changes of intestinal tissue were observed based on hematoxylin and eosin(HE) staining. The content of malondialdehyde(MDA) and glutathione(GSH) and activity of superoxide dismutase(SOD) in intestinal tissue were measured to evaluate the intestinal injury. Fresh feces of rats were collected to detect intestinal flora structure by 16S ribosomal RNA gene(16S rDNA) sequencing technology. The content of fecal short chain fatty acids and fecal metabolites was determined by gas chromatography-mass spectrometer(GC-MS) and liquid chromatography-mass spectrometer ultra-fast liquid chromatography-quadrupole-time-of-flight mass spectrometer(UFLC-Q-TOF-MS), separately. Spearman's correlation analysis was employed to analyze the differential bacteria genera and differential metabolites. RESULTS:: showed that high-dose and low-dose SZD-JF groups had high content of MDA in intestinal tissue, low GSH content and SOD activity, short intestinal villi(P<0.05), low diversity and abundance of intestinal flora, variation in the intestinal flora structure, and low content of short chain fatty acids(P<0.05) compared with the normal group. Compared with high-dose and low-dose SZD-JF groups, high-dose and low-dose SZD groups displayed low content of MDA in intestinal tissue, high GSH content and SOD activity, recovery of the length of intestinal villi, increased abundance and diversity of intestinal flora, alleviation of dysbacteria, and recovery of the content of short chain fatty acids(P<0.05). According to the variation of intestinal flora and fecal metabolites after the addition of Jujubae Fructus, 6 differential bacterial genera(Lactobacillus, Butyricimonas, Clostridia＿UCG-014, Prevotella, Escherichia-Shigella, Alistipes),4 differential short chain fatty acids(such as acetic acid, propionic acid, butyric acid, valeric acid) and 18 differential metabolites(such as urolithin A, lithocholic acid, and creatinine) were screened out. Beneficial bacteria such as Lactobacillus were in positive correlation with butyric acid and urolithin A(P<0.05). The pathogenic bacteria such as Escherichia-Shigella were in negative correlation with propionic acid and urolithin A(P<0.05). In summary, SZD-JF caused obvious intestinal injury to normal rats, which could lead to intestinal flora disorder. The addition of Jujubae Fructus can alleviate the disorder and relieve the injury by regulating intestinal flora and the metabolites. This study discusses the effect of Jujubae Fructus in relieving the intestinal injury caused by SZD and the mechanism from the perspective of intestinal flora-host metabolism, which is expected to serve as a reference for clinical application of this prescription.
Rats ; Animals ; Rats, Sprague-Dawley ; Propionates/pharmacology* ; Gastrointestinal Microbiome ; Fatty Acids, Volatile/pharmacology* ; Butyrates/pharmacology*

To investigate the effect of Huazhi Rougan Granules(HZRG) on autophagy in a steatotic hepatocyte model of free fatty acid(FFA)-induced nonalcoholic fatty liver disease(NAFLD) and explore the possible mechanism. FFA solution prepared by mixing palmitic acid(PA) and oleic acid(OA) at the ratio of 1∶2 was used to induce hepatic steatosis in L02 cells after 24 h treatment, and an in vitro NAFLD cell model was established. After termination of incubation, cell counting kit-8(CCK-8) assay was performed to detect the cell viability; Oil red O staining was employed to detect the intracellular lipid accumulation; enzyme-linked immunosorbnent assay(ELISA) was performed to measure the level of triglyceride(TG); to monitor autophagy in L02 cells, transmission electron microscopy(TEM) was used to observe the autophagosomes; LysoBrite Red was used to detect the pH change in lysosome; transfection with mRFP-GFP-LC3 adenovirus was conducted to observe the autophagic flux; Western blot was performed to determine the expression of autophagy marker LC3B-Ⅰ/LC3B-Ⅱ, autophagy substrate p62 and silent information regulator 1(SIRT1)/adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway. NAFLD cell model was successfully induced by FFA at 0.2 mmol·L~(-1) PA and 0.4 mmol·L~(-1) OA. HZRG reduced the TG level(P<0.05, P<0.01) and the lipid accumulation of FFA-induced L02 cells, while elevated the number of autophagosomes and autophagolysosomes to generate autophagic flux. It also affected the functions of lysosomes by regulating their pH. Additionally, HZRG up-regulated the expression of LC3B-Ⅱ/LC3B-Ⅰ, SIRT1, p-AMPK and phospho-protein kinase A(p-PKA)(P<0.05, P<0.01), while down-regulated the expression of p62(P<0.01). Furthermore, 3-methyladenine(3-MA) or chloroquine(CQ) treatment obviously inhibited the above effects of HZRG. HZRG prevented FFA-induced steatosis in L02 cells, and its mechanism might be related to promoting autophagy and regulating SIRT1/AMPK signaling pathway.
Humans ; Non-alcoholic Fatty Liver Disease/metabolism* ; Sirtuin 1/metabolism* ; AMP-Activated Protein Kinases/metabolism* ; Fatty Acids, Nonesterified/metabolism* ; Autophagy ; Liver

Heart failure (HF) has become a major challenge in the treatment of global cardiovascular diseases. Great progress has been made in the drug treatment of HF, however, rehospitalization rate and mortality of patients with HF are still high. Hence, there is an urgent need to explore new treatment strategy and new underlying pathogenic mechanisms. In recent years, some researchers have suggested that regulation of ketone body metabolism may become a potentially promising therapeutic approach for HF. Some studies showed that the oxidative utilization of fatty acids and glucose was decreased in the failing heart, accompanied by the increase of ketone body oxidative metabolism. The enhancement of ketone body metabolism in HF is a compensatory change during HF. The failing heart preferentially uses ketone body oxidation to provide energy, which helps to improve the body's cardiac function. This review will discuss the potential significance of ketone body metabolism in the treatment of HF from three aspects: normal myocardial ketone body metabolism, the change of ketone body metabolism in HF, the effect of ketogenic therapy on HF and its treatment.
Humans ; Heart Failure/metabolism* ; Myocardium/metabolism* ; Ketone Bodies/metabolism* ; Cardiovascular Diseases ; Fatty Acids/metabolism* ; Energy Metabolism

OBJECTIVE: To investigate the effect of titanium dioxide nanoparticles (TiO₂ NPs) on the expression profile of circular ribonucleic acid (circRNA) in human hepatocytes through in vitro cell experiments, and to attempt to understand the potential mechanism of hepatotoxicity through bioinformatics analysis. METHODS: TiO₂ NPs were characterized from the aspects of particle size, shape and agglomeration state. The cell counting kit-8 (CCK8) was used to detect the cytotoxicity of TiO₂ NPs against human hepatocellular carcinoma cells (HepG2) after exposure to 0, 1.56, 3.13, 6.25, 12.5, 25, 50, 100, and 200 mg/L TiO₂ NPs for 24 h or 48 h. The cells were treated at doses of 0 mg/L TiO₂ NPs (control group) and 100 mg/L TiO₂ NPs (treatment group), and collected after exposure for 48 h, and then RNA from the extracted cell samples was collected and sequenced. The differential circRNAs between the control and the TiO₂ NPs treatment groups were screened, and then the enrichment pathway of the differential circRNA target gene was analyzed by multivariate statistics. According to the sequencing results, significantly altered genes and important genes in the significant enrichment pathways were screened, and real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) was performed to verify the results. RESULTS: TiO₂ NPs were spherical anatase with a hydrated particle size of (323.50±85.44) nm and a Zeta potential of (-21.00±0.72) mV in a serum-free medium. The results of the CCK8 cytotoxicity assay showed that with the increase of TiO₂ NPs concentration, cell viability gradually decreased. A total of 11 478 circRNAs were found by RNA sequencing. Compared with the control groups, TiO₂ NPs treatment groups (100 mg/L) had a total of 89 differential circRNAs, of which 59 were up-regulated and 30 were down-regulated. Analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed that the targeted genes of differential circRNAs were mainly enriched in fatty acid degradation, Fanconi anemia pathway, and fatty acid metabolism. The expression levels of circRNA.6730, circRNA.3650 and circRNA.4321 were significantly different between the TiO₂ NPs treatment group and the control group, which were consistent with the sequencing results. CONCLUSION TiO₂ NPs can induce changes in circRNA expression profile, and epigenetics may play an important role in the mechanism of hepatotoxicity.
Humans ; RNA/genetics* ; RNA, Circular/genetics* ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Titanium ; Nanoparticles ; Chemical and Drug Induced Liver Injury ; Fatty Acids

OBJECTIVE: To explore the driving gene of hepatocellular carcinoma (HCC) occurrence and progression and its potential as new therapeutic target of HCC. METHODS: The transcriptome and genomic data of 858 HCC tissues and 493 adjacent tissues were obtained from TCGA, GEO, and ICGC databases. Gene Set Enrichment Analysis (GSEA) identified EHHADH (encoding enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase) as the hub gene in the significantly enriched differential pathways in HCC. The downregulation of EHHADH expression at the transcriptome level was found to correlate with TP53 mutation based on analysis of the TCGA- HCC dataset, and the mechanism by which TP53 mutation caused EHHADH downregulation was explored through correlation analysis. Analysis of the data from the Metascape database suggested that EHHADH was strongly correlated with the ferroptosis signaling pathway in HCC progression, and to verify this result, immunohistochemical staining was used to examine EHHADH expression in 30 HCC tissues and paired adjacent tissues. RESULTS: All the 3 HCC datasets showed signficnatly lowered EHHADH expression in HCC tissues as compared with the adjacent tissues (P < 0.05) with a close correlation with the degree of hepatocyte de-differentiation (P < 0.01). The somatic landscape of HCC cohort in TCGA dataset showed that HCC patients had the highest genomic TP53 mutation rate. The transcriptomic level of PPARGC1A, the upstream gene of EHHADH, was significantly downregulated in HCC patients with TP53 mutation as compared with those without the mutation (P < 0.05), and was significantly correlated with EHHADH expression level. GO and KEGG enrichment analyses showed that EHHADH expression was significantly correlated with abnormal fatty acid metabolism in HCC. The immunohistochemical results showd that the expression level of EHHADH in HCC tissues was down-regulated, and its expression level was related to the degree of hepatocytes de-differentiation and the process of ferroptosis. CONCLUSION TP53 mutations may induce abnormal expression of PPARGC1A to cause downregulation of EHHADH expression in HCC. The low expression of EHHADH is closely associated with aggravation of de-differentiation and ferroptosis escape in HCC tissues, suggesting the potential of EHHADH as a therapeutic target for HCC.
Humans ; Carcinoma, Hepatocellular/genetics* ; Transcriptome ; Liver Neoplasms/genetics* ; Gene Expression Profiling ; Fatty Acids ; Peroxisomal Bifunctional Enzyme

Intestinal flora and its metabolites are closely related to the progression of type 2 diabetes mellitus(T2DM). Eubacterium is one of the dominant intestinal flora, and its metabolites short-chain fatty acids (SCFAs) play a leading role in regulating intestinal metabolic balance. It has been reported that SCFAs can regulate the secretion of glucagon-like peptide-1, improve the function of pancreatic β cells, participate in bile acids metabolism and regulate the production of inflammatory factors in T2DM. Based on the above research background, this article mainly reviews the relationship between Eubacterium and its metabolite SCFAs and T2DM and its regulatory mechanism.
Humans ; Diabetes Mellitus, Type 2 ; Eubacterium/metabolism* ; Fatty Acids, Volatile/metabolism* ; Gastrointestinal Microbiome