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 5&alpha;-reductase inhibitory activity (115.18 ± 11.61 mg dutasteride/g) compared to ethanol (DPPH: p=0.0121; 5&alpha;-reductase: p=0.0016) and hexane (DPPH: p=0.0038; 5&alpha;-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 5&alpha;-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

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

OBJECTIVE: To observe the effects of electroacupuncture at "Siguan" points on behavior, colonic 5-hydroxytryptamine (5-HT) and fecal short-chain fatty acids (SCFAs) in rats with post-stroke depression (PSD), and explore the effect mechanism of electroacupuncture at Siguan points on PSD. METHODS: Fifty SD rats were randomly divided into a sham-operation group, a stroke group, a PSD group, a drug group and an electroacupuncture group, with 10 rats in each one. The stroke model was established by middle cerebral artery occlusion (MCAO) method in the stroke group; except for the sham-operation group, the rats in the other groups were intervened with MCAO combined with solitary and chronic unpredictable mild stress (CUMS) to establish PSD model. In the electroacupuncture group, electroacupuncture was delivered at "Hegu" (LI 4) and "Taichong" (LR 3), with disperse-dense wave, 2 Hz/10 Hz in frequency, for 30 min in each intervention, once daily, for consecutive 21 days. Simultaneously, distilled water (0.01 L•kg^-1•d^-1) was administrated intragastrically. Fluoxetine solution (2.33 mg•kg^-1•d^-1) was given by gavage , once a day and for 21 days in the drug group. The same procedure of fixation and gavage with distilled water were adopted in the sham-operation group, the stroke group and the PSD group. Separately, before stroke modeling, after PSD modeling and after 21-day intervention, the consumption of sugar water and the scores of horizontal movement and vertical movement in open-field test were observed. After 21-day intervention, the content of colonic 5-HT was detected by immunohistochemical method, and that of fecal SCFAs was determined by gas chromatography mass spectrometry. RESULTS: After PSD modeling, compared with the stroke group, the sugar water consumption, the horizontal movement scores and vertical movement scores of the open-field test were all reduced in the PSD group, the drug group and the electroacupuncture group (P<0.05). After 21-day intervention, the sugar water consumption and the scores of horizontal movement and vertical movement of the open-field test were increased in the drug group and the electroacupuncture group (P<0.05) when compared with the PSD group; and the horizontal movement score in the electroacupuncture group was lower than that of the drug group (P<0.05). Compared with the sham-operation group, the contents of total fecal SCFAs and acetic acid were lower in the stroke group (P<0.05), and the contents of colonic 5-HT and total fecal SCFAs, acetic acid, propionic acid and butyric acid were reduced in the PSD group (P<0.05). In comparison with the PSD group, the contents of colonic 5-HT and total fecal SCFAs, acetic acid and propionic acid were increased in the drug group and the electroacupuncture group (P<0.05); and the content of colonic 5-HT in the electroacupuncture group was lower than that of the drug group (P<0.05). The level of colonic 5-HT was positively correlated with the contents of total fecal SCFAs and propionic acid (r=0.424, P=0.005; r=0.427, P=0.004). CONCLUSION Electroacupuncture at "Siguan" points can relieve the depression-like behavior of PSD rats, and its underlying mechanism may be related to the regulation of fecal SCFAs, which affects the release of colonic 5-HT.
Animals ; Rats ; Rats, Sprague-Dawley ; Propionates ; Serotonin ; Depression/therapy* ; Electroacupuncture ; Fatty Acids, Volatile ; Stroke/complications* ; Acetic Acid ; Butyric Acid ; Water

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

Rheumatoid arthritis(RA), a chronic autoimmune disease, is featured by persistent joint inflammation. The development of RA is associated with the disturbance of endogenous metabolites and intestinal microbiota. Gardeniae Fructus(GF), one of the commonly used medicinal food in China, is usually prescribed for the prevention and treatment of jaundice, inflammation, ache, fever, and skin ulcers. GF exerts an effect on ameliorating RA, the mechanism of which remains to be studied. In this study, ultra-perfor-mance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)-based serum non-target metabolomics and 16S rDNA high-throughput sequencing were employed to elucidate the mechanism of GF in ameliorating RA induced by complete Freund's adjuvant in rats. The results showed that GF alleviated the pathological conditions in adjuvant arthritis(AA) rats. The low-and high-dose GF lo-wered the serum levels of interleukin(IL)-6, tumor necrosis factor-α(TNF-α), IL-1β, and prostaglandin E2 in the rats(P<0.05, P<0.01). Pathways involved in metabolomics were mainly α-linolenic acid metabolism and glycerophospholipid metabolism. The results of 16S rDNA sequencing showed that the Streptococcus, Facklamia, Klebsiella, Enterococcus, and Kosakonia were the critical gut microorganisms for GF to treat AA in rats. Spearman correlation analysis showed that the three differential metabolites PE-NMe[18:1(9Z)/20:0], PC[20:1(11Z)/18:3(6Z,9Z,12Z)], and PC[20:0/18:4(6Z,9Z,12Z,15Z)] were correlated with the differential bacteria. In conclusion, GF may ameliorate RA by regulating the composition of intestinal microbiota, α-linolenic acid metabolism, and glycerophospholipid metabolism. The findings provide new ideas and data for elucidating the mechanism of GF in relieving RA.
Rats ; Animals ; Chromatography, Liquid ; Gardenia ; Tandem Mass Spectrometry ; Gastrointestinal Microbiome ; alpha-Linolenic Acid ; Metabolomics/methods* ; Arthritis, Rheumatoid/drug therapy* ; Inflammation ; Glycerophospholipids

Perfluorinated compounds, especially Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are widely detected in water environments in China. Considering the potential health risks of drinking water exposure routes, PFOA and PFOS have been added to the water quality reference index of the newly issued "Standards for Drinking Water Quality (GB5749-2022)", with limit values of 40 and 80 ng/L, respectively. This study analyzed and discussed the relevant technical contents for determining the limits of the hygiene standard, including the environmental existence level and exposure status of PFOA and PFOS, health effects, derivation of safety reference values, and determination of hygiene standard limits. It also proposed prospects for the future direction of formulating drinking water standards.
Humans ; Water Quality ; Drinking Water ; Fluorocarbons/analysis* ; Caprylates/analysis* ; China ; Water Pollutants, Chemical/analysis*

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