Gene expression analyses of GH/IGF axis in triploid crucian carp with growth heterosis.

Hybridization and polyploid breeding are the main approaches used to obtain new aquaculture varieties. Allotriploid crucian carp (3n) with rapid growth performance was generated by mating red crucian carp (RCC) with allotetraploids (4n). Fish growth is controlled by the growth hormone (GH)/insulin-like growth factor (IGF) axis. In the present study, we examined the expression characteristics of GH/IGF axis genes in hybrids F1, 4n, 3n, RCC and common carp (CC). The results showed that GHRa, GHRb, IGF1, IGF2, and IGF-1Ra were highly expressed in 3n compared with RCC and CC, whereas IGF3 was undetectable in the liver in RCC, CC and 3n. GHRa and GHRb had low expression in the 4n group. In hybrid F1, GHRa expression was low, whereas GHRb was highly expressed compared to the levels in RCC and CC. Moreover, in hybrid F1, the expression of IGF3 was higher, and the expression of IGF1 and IGF2 was lower than that in the RCC and CC, whereas the expression of IGF-1Ra was similar to that in RCC and CC. For the IGFBP genes, IGFBP1 had higher expression in 3n compared than that in RCC and CC, while other IGFBP genes were not high expressed in 3n. Among the genes detected in this study, 11 genes were nonadditively expressed in 3n, with 5 genes in the transgressive upregulation model. We proposed that the 11 nonadditive expression of GH/IGF axis genes is related to growth heterosis in 3n. This evidence provides new insights into hybridization and polyploid breeding from the perspective of hormone regulation.

Transcriptome analysis of the Nile tilapia (Oreochromis niloticus) reveals altered expression of immune genes by cadmium.

Nile tilapia (Oreochromis niloticus) is a worldwide farmed fish and has been widely used for the study on comparative immunology in teleosts. It is well known that cadmium (Cd) can cause a variety of adverse effects in fish. However, data on the effects of Cd in fish liver and the defensive mechanisms of these effects using transcriptome approach are relatively scarce to date. In this study, by using an RNA sequencing approach, the gene expression profiling was performed in livers of tilapia exposed to 0 (control), 50, 100, and 200 µg/L of Cd for 2 months. The results showed that exposure to 50 µg/L Cd altered the expressions of 911 genes, while exposure to 100 and 200 µg/L Cd resulted in 4318 and 3737 differentially expressed genes compared to the control. Weighted correlation network analysis (WGCNA) and gene ontology (GO) analysis identified a 14-gene network linked to the immune system development. Further, in a fuzzy analysis, the GO term immune system development was enriched in cluster 3, and gene expression decreased with increasing Cd levels in a concentration-dependent manner. The qPCR and RNA-seq results identified 4 genes, i.e., dnmt3bb.1, sf3b1, SMARCAL1, and zap70, as convenient potential biological indicators for detecting waterborne Cd. The present results help systematically understand the effects of Cd on the hepatic transcriptome in tilapia.

Contamination and Carcinogenic Risks of Lead in Lip Cosmetics in China.

There are growing concerns about elevated lead (Pb) levels in lip cosmetics, yet in China, the largest lip cosmetic market, recent Pb contamination in lip cosmetics and associated Pb exposure remain unclear. Here, we measured Pb levels of 29 popular lip cosmetics in China and conducted the bioaccessibility-corrected carcinogenic risk assessments and sensitivity analysis regarding Pb exposure for consumers using Monte Carlo simulation. The Pb concentrations of collected samples ranged from undetectable (< 0.05 µg/kg) to 0.21 mg/kg, all of which were well below the Pb concentration limit set for cosmetics in China (10 mg/kg). The 50th percentile incremental lifetime cancer risk (ILCR) of Pb in Chinese cosmetics (1.20E-07) was below the acceptable level (1E-06), indicating that the application of lip cosmetics and subsequent Pb exposure does not pose carcinogenic risks to consumers in most cases. The results of this study provide new insights into understanding the Pb risk in lip cosmetics.

Effect of electroacupuncture at "Neiguan" (PC 6) and "Zusanli" (ST 36) on gastrointestinal hormone in the antral tissue of rats with functional dyspepsia. / 电针"å† å ³""足三里"å¯¹åŠŸèƒ½æ€§æ¶ˆåŒ–ä¸è‰¯å¤§é¼ èƒƒçª¦ç»„ç»‡èƒƒè‚ æ¿€ç´ çš„å½±å“.

OBJECTIVES: To observe the effects of electroacupuncture (EA) at "Neiguan" (PC 6) and "Zusanli"(ST 36) on the gastric emptying rate, the level of serotonin (5-HT) and the protein expression of motilin (MTL), ghrelin, substance P (SP) and vasoactive intestinal peptide (VIP) in the antral tissue of the rats with functional dyspepsia (FD) and explore the effect mechanism of EA in treatment of FD. METHODS: A total of 21 SPF male SD rat pups were randomly divided into a normal group, a model group and an EA group, with 7 rats in each group. In the model group and the EA group, FD model was prepared by the gavage with 0.1% sucrose iodoacetamide solution combined with the modified small platform method. After the successful modeling, EA was applied to "Neiguan" (PC 6) and "Zusanli"(ST 36) in the rats of the EA group, with disperse-dense wave, 20 Hz/100 Hz in frequency, stimulated for 30 min, once daily, for 7 days consecutively. Before and after intervention, the general condition of the rats was observed in each group. After the completion of intervention, the gastric emptying rate was measured, the morphological changes of gastric antral tissue were observed using HE staining, the level of 5-HT was detected with ELISA method, and the protein expression of MTL, ghrelin, SP, and VIP was determined with Western blot method in the antral tissue of rats. RESULTS: In the normal group, the rats were in a good mental state, with lustrous fur, flexible movement and the increase of food intake and body mass. In the model group, the rats were poor in mental state, lack of lustre in fur, preference for the body curled up, reduced activity and response; and a part of rats had loose stool, obviously enlarged gastric body and gastric food retention. In the EA group, the general condition of rats, e.g. the mental state, food intake and activity, were improved, the gastric body got smaller obviously and the gastric food retention was reduced when compared with the model group. The antral structure was intact, the glands were rich and no injury of the gastric mucosa was found, e.g. inflammatory reaction and edema in the rats of each group. Compared with the normal group, the gastric emptying rate was decreased (P<0.01), 5-HT level was increased (P<0.01), the protein expression of MTL and ghrelin was reduced (P<0.01) and that of VIP was elevated (P<0.01) in the rats of the model group. The gastric emptying rate was increased (P<0.01), 5-HT level was decreased (P<0.01), and the protein expression of MTL and ghrelin was elevated (P<0.05, P<0.01) in the rats of the EA group when compared with those in the model group. CONCLUSIONS: Electroacupuncture at "Neiguan" (PC 6) and "Zusanli"(ST 36) may effectively relieve gastric dysfunction, strengthen gastric motility and promote gastric emptying so as to alleviate the symptoms of dyspepsia in FD rats, and its mechanism may be related to the regulation of gastrointestinal hormones in the antral tissue.

[Effects of moxibustion at "Tianshu"（ST25） and "Shangjuxu" （ST37） on colonic metabolites and inflammatory factors in rats with Crohn's disease].

OBJECTIVE: To observe the effects of moxibustion at "Tianshu"（ST25） and "Shangjuxu"（ST37） on the colonic metabolites and inflammatory factors in rats with Crohn's disease（CD）, so as to explore the mechanisms of moxibustion in protecting colon of CD rats based on metabolomics. METHODS: Twelve rats were first randomly selected from 36 male SD rats as a normal group（NG）. The CD model was induced by 2, 4, 6 trinitrobenzene sulfonic acid（TNBS） enema on the rest 24 rats. After successful modeling, rats were randomly divided into model（TNBS） and moxibustion（TNBS+MOX） groups（n=10 rats/group）. Moxibustion was applied at bilateral ST25 and ST37 for 30 min, once daily for 7 consecutive days in the TNBS+MOX group, while rats in the NG and TNBS groups did not receive any interventions. Body weight of rats was recorded and disease activity index（DAI） was assessed during the experiment. After interventions, HE staining was performed to observe pathological damage of colon. Serum levels of inflammatory factors were measured by ELISA. NMR hydrogen spectroscopy was used to detect colonic metabolites of each group, and orthogonal partial least squares discriminant analysis（OPLS-DA） was used to screen differential colonic metabolites between groups, followed by pathway analysis using MetaboAnalyst 5.0 platform. RESULTS: After modeling, compared with the NG group, the body weight of the rats in the TNBS group was significantly decreased（P<0.05）, the DAI score was increased （P<0.05）, the colon had obvious inflammatory damage and the pathological injury index was increased（P<0.05）, and levels of serum tumor necrosis factor-α（TNF-α）, interleukin（IL）-1ß and interferon-γ（IFN-γ） were significantly increased（P<0.05）. After moxibustion intervention, compared with the TNBS group, the body weight was significantly increased（P<0.05）, while the levels of serum TNF-α, IL-1ß, IFN-γ, and DAI score of the rats in the TNBS+MOX group were significantly decreased（P<0.05）, with alleviated colonic inflammatory injury detected by HE staining. Compared with the NG group, the relative expressions of colonic hypoxanthine, betaine, creatine, inositol, taurine, uracil, and methanol of the TNBS group were decreased（P<0.05）, while the relative expressions of histidine, leucine, proline, lysine, isoleucine, phenylalanine, tyrosine, propionic acid, and valine were increased（P<0.05） in the TNBS group, among which, relative expressions of hypoxanthine, leucine, lysine, isoleucine, betaine, tyrosine, and taurine were reversed in the TNBS+MOX group relevant to the TNBS group, mainly involving phenylalanine, tyrosine and tryptophan biosynthesis, and taurine and subtaurine metabolism pathway. CONCLUSION: The mechanism of moxibustion at ST25 and ST37 for CD may be related to improving colon metabolic disorder state by regulating multiple metabolic metabolites and metabolic pathways, and reducing the level of inflammatory factors, so as to maintain intestinal immune homeostasis.

Metabolite Comparison between Spleen-Deficiency and Healthy Children.

Objective: From the perspective of metabolomics, this study compares the metabolomics characteristics of feces and urine between children with spleen-deficiency and healthy children to explain the scientific connotation of children with spleen-deficiency susceptibility to digestive system diseases from the metabolic level and provide a scientific basis for further research. Methods: This study included 20 children with spleen-deficiencies and 17 healthy children. Children's symptom scores, height, and weight were recorded in groups, and feces and urine samples were collected. The samples were detected using ultrahigh-performance liquid chromatography-mass spectrometry. The data were analyzed using multivariate statistical analysis such as principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). Related differential metabolites were identified through database comparisons between two groups based on the MS and KEGG. Results: Compared to healthy children, the metabolites glucuronic acid, xanthine, and indole-3-acetaldehyde tend to be reduced in children with spleen-deficiency. Moreover, these children showed an increase in metabolites such as quinic acid, adenine, 4-methyl-5-thiazole-ethanol, 3-formyl indole, and 5-hydroxy indole-3-acetic acid. The condition affected many of the critical metabolic pathways, including the metabolism of tryptophan, cysteine, methionine, and pentose phosphate. Conclusion: The children with spleen-deficiency had disorders at the metabolic level, which might be due to factors such as diet, personal preferences, and genes, leading to various symptoms, making spleen-deficiency children more prone to suffer from digestive diseases than healthy children. The results set a basis for the research on children's TCM constitution, which can be a reference to further studies to deal with the spleen-deficiency.

Acupuncture as a Complementary Therapy for Cancer-Induced Bone Pain: A Systematic Review and Meta-Analysis.

Background: Cancer-induced bone pain (CIBP) is a special type of cancer pain and lacks safe and effective treatments. Acupuncture is a potentially valuable treatment for CIBP, studies evaluating the effect of acupuncture on CIBP have increased significantly, but the safety and efficacy of acupuncture to control CIBP remains controversial. Objective: To provide the first meta-analysis to evaluate the safety and efficacy of acupuncture in CIBP management. Data Sources: CNKI, CBM, Wanfang, VIP Database, PubMed, Embase, and Cochrane Library were searched from their inception until 1 June 2022. Study Selection: RCTs with primary bone tumor patients or other types of primary cancer companied by bone metastases as the research subjects and to evaluate the efficacy of acupuncture treatment alone or combined with the control treatment were included. Meanwhile, RCTs should choose the pain score as the primary outcome and pain relief rate, frequency of breakthrough pain, analgesic onset time, analgesia duration, quality of life, and adverse events as reference outcomes. Data Collection and Analysis: We designed a data-extraction form that was used to extract key information from the articles. Data extraction study evaluation was conducted independently by two reviewers, and a third reviewer would resolve any disagreements. The risk of bias was assessed by the Cochrane Collaboration's tool for assessing the risk bias. The quality of the evidence for main outcomes was evaluated by the GRADE system. Mean differences (MD), relative risk (RR), and 95% confidence intervals (CIs) were calculated. The forest plots were performed using the Review Manager Software (5.3 version). Subgroup analysis was used to investigate the possible sources of potential heterogeneity. Descriptive analysis was performed in case of unacceptable clinical heterogeneity. Results: Thirteen RCTs (with 1,069 patients) were included, and all studies were at high risk of bias owing to lack of blinding or other bias. Eleven studies evaluated the effectiveness of acupuncture as a complementary therapy, and showed that acupuncture plus control treatment (compared with control treatment) was connected with reduced pain intensity (MD = -1.34, 95% CI -1.74 to -0.94; Q < 0.1; I 2 = 98%, P < 0.01). Subgroup analyses based on acupoints type partly explain the potential heterogeneity. The results also showed that acupuncture plus control treatment (compared with control treatment) was connected with relieving pain intensity, increasing the pain relief rate, reducing the frequency of breakthrough pain, shortening analgesic onset time, extending the analgesic duration, and improving the quality of life. We have no sufficient evidence to prove the effectiveness of acupuncture alone. Four RCTs reported only adverse events related to opioids' side effects. Evidence was qualified as "very low" because of low methodological quality, considerable heterogeneity, or a low number of included studies. Conclusion: Acupuncture has a certain effect as a complementary therapy on pain management of CIBP, which not only mitigates the pain intensity but also improves the quality of life and reduces the incidence of opioids' side effects, although the evidence level was very low. In future, a larger sample size and rigorously designed RCTs are needed to provide sufficient evidence to identify the efficacy and safety of acupuncture as a treatment for CIBP.

Taurine inhibits hydrogen peroxide-induced oxidative stress, inflammatory response and apoptosis in liver of Monopterus albus.

Fish are extremely vulnerable to environmental stimulation and produce oxidative stress. Among them, hydrogen peroxide is an oxidative stress source that cannot be ignored in fish, which can cause physical disorders, inflammation and even death. Taurine was revealed to reduce oxidative damage and inflammation caused by toxic substances, but whether it can reduce toxicity of rice field eel caused by H2O2 has not been determined. Thus, the intervention effects of taurine on H2O2-induced oxidative stress, inflammation, apoptosis, and autophagy in rice field eel. The results showed that oxidative injury in the liver was determined after H2O2 injection, as indicated by enhanced serum AST and ALT activities, inhibited the antioxidant function (increased MDA and ROS contents, decreased antioxidant enzymes, inhibited nrf2 transcription level), and induced inflammatory response (upregulated il-1ß, il-6, il-8, and il-12ß gene expression, downregulated tgf-ß1 gene expression, activated the transcription level of nf-κb, tlr-3, and tlr-7). In addition, bax, caspase3, beclin1, and Lc3B gene expression were significantly upregulated after H2O2 injection, while bcl2 and p62 gene expression were downregulated, leading to the occurrence of apoptosis and autophagy. In contrast, adding 0.2 and 0.5% taurine to feed significantly alleviated this damage, as indicated by the recovery of the aforementioned bioindicators, and the effect of 0.5% taurine addition is better than 0.2%. Overall, these results suggested that taurine can relieve the liver toxicity induced by H2O2, which enriched the toxic mechanism of H2O2 on fish and provided evidence for the protective effect of taurine on liver.

Using air cholangiography to reduce postendoscopic retrograde cholangiopancreatography cholangitis in patients with malignant hilar obstruction.

Background: Cholangitis after endoscopic retrograde cholangiopancreatography (ERCP) is a major problem for patients with hilar biliary obstruction. To date, it remains unclear whether air-contrast cholangiography (ACC) can reduce cholangitis in these patients. For this reason, our study assesses the efficacy of reducing cholangitis through ACC. Methods: This paper presents a retrospective study conducted at a tertiary university hospital. We enrolled patients who were diagnosed with hilar structures and underwent ERCP between January 2012 and December 2018. From 2015 onwards, ACC was performed following the successful selective cannulation into the dilated intrahepatic bile duct of these patients. The primary aim was to assess patients with cholangitis in both an ACC group and iodine contrast cholangiography (ICC) group. Results: This study included 80 patients, 35 of whom received ACC and 45 who received ICC. There were no differences between the 2 groups in terms of the number of patients who underwent endoscopic papillotomy, endoscopic nasobiliary drainage, endoscopic biliary stent placement, or other technical procedures or complications. A total of 19 patients (23.8%) presented with fever (cholangitis) after the ERCP procedure (4 ACC, 15 ICC; 11.4% vs. 33.3%, respectively; P=0.03). One patient in the ICC group who obtained a plastic stent for palliative drainage died 2 weeks post-ERCP. Among the other 18 cholangitis patients, 8 (1 ACC, 7 ICC) were treated with additional ERCP or percutaneous transhepatic biliary drainage (PTBD), while the remaining 10 only received antibiotics. One patient in the ICC group who obtained a plastic stent for palliative drainage died 2 weeks post-ERCP. Conclusions: We found that ACC significantly reduced the incidence of cholangitis in patients with hilar obstruction.

The Protective Effect of Taurine on Oxidized Fish-Oil-Induced Liver Oxidative Stress and Intestinal Barrier-Function Impairment in Juvenile Ictalurus punctatus.

Dietary lipids provide energy for growth and development and provide fatty acids necessary for normal structure and biological function. However, oxidized lipids cause oxidative stress and intestinal damage. An 8-week feeding trial with fresh fish oil (FFO, control group), oxidized fish oil (OFO), and taurine-supplemented diets (OFOT, OFO + 0.2% of taurine) was conducted to evaluate the protective effect of taurine on oxidized fish-oil-induced liver oxidative stress and intestine impairment in juvenile Ictaluruspunctatus. The results showed that (1) Growth performance was significantly lower in fish fed OFO than in those fed other diets, whereas the opposite occurred in the hepatosomatic index. (2) OFO-feeding significantly increased lipid deposition compared with the FFO group. The addition of taurine ameliorated the OFO-induced increase in lipid vacuolization in the liver, significantly upregulated lpl mRNA expression, and downregulated fas and srebp1 mRNA expression. (3) OFO-feeding significantly reduced oxidative damage of liver. Compared with the OFO group, the OFOT group remarkably upregulated antioxidant enzyme mRNA expression through the Nrf2-Keap1 signaling pathway based on the transcriptional expression. (4) OFO diets induced intestinal physical and immune barrier damage. Compared with the OFO group, OFOT diets remarkably downregulated il-1ß, il-6, tnf-α, and il-8 mRNA expression and upregulated tgf-ß mRNA expression through the NF-κB signaling pathway. Besides, the addition of taurine to OFO diets significantly upregulated zo-2 and zo-1 mRNA expression, and downregulated claudin-15 and claudin-12 mRNA expression. In conclusion, oxidized-fish-oil diets can cause negative physiological health effects in Ictaluruspunctatus, while adding taurine can increase growth and antioxidant ability, reduce lipid deposition, and improve intestinal health.

Speciation, transportation, and pathways of cadmium in soil-rice systems: A review on the environmental implications and remediation approaches for food safety.

Cadmium (Cd) contamination in paddy fields is a serious health concern because of its high toxicity and widespread pollution. Recently, much progress has been made in elucidating the mechanisms involved in Cd uptake, transport, and transformation from paddy soils to rice grains, aiming to mitigate the associated health risk; however, these topics have not been critically reviewed to date. Here, we summarized and reviewed the (1) geochemical distribution and speciation of Cd in soil-rice systems, (2) mobilization, uptake, and transport of Cd from soil to rice grains and the associated health risks, (3) pathways and transformation mechanisms of Cd from soil to rice grains, (4) transporters involved in reducing Cd uptake, transport, and accumulation in rice plants, (5) factors governing Cd bioavailability in paddy, and (6) comparison of remediation approaches for mitigating the environmental and health risks of Cd contamination in paddy fields. Briefly, this review presents the state of the art about the fate of Cd in paddy fields and its transport from soil to grains, contributing to a better understanding of the environmental hazards of Cd in rice ecosystems. Challenges and perspectives for controlling Cd risks in rice are thus raised. The summarized findings in this review may help to develop innovative and applicable methods for controlling Cd accumulation in rice grains and sustainably manage Cd-contaminated paddy fields.

Relative contribution of rice and fish consumption to bioaccessibility-corrected health risks for urban residents in eastern China.

There are global concerns about dietary exposure to metal(loid)s in foods. However, little is known about the relative contribution of rice versus fish to multiple metal(loid) exposure for the general population, especially in Asia where rice and fish are major food sources. We compared relative contributions of rice and fish consumption to multi-metal(loid) exposure on the city-scale (Nanjing) and province-scale in China. The effects of ingestion rate, metal(loid) level, and bioaccessibility were examined to calculate modeled risk from Cu, Zn, total As (TAs), inorganic As (iAs), Se, Cd, Pb, and methylmercury (MeHg). Metal(loid) levels in rice and fish samples collected from Nanjing City were generally low, except iAs. Metal(loid) bioaccessibilities in fish were higher than those in rice, except Se. Calculated carcinogenic risks induced by iAs intake (indicated by increased lifetime cancer risk, ILCR) were above the acceptable level (1 0 -4) in Nanjing City (median: 3 × 10-4 for female and 4 × 10-4 for male) and nine provinces (1.4 × 10-4 to 5.9 × 10-4) in China. Rice consumption accounted for 85.0% to 99.8% of carcinogenic risk. The non-carcinogenic hazard quotients (HQ) for single metals and hazard index (HI) for multi-metal exposure were < 1 in all cases, indicating of their slight non-carcinogen health effects associated. In Guangdong and Jiangsu provinces, results showed that rice and fish intake contributed similarly to the HI (i.e., 42.6% vs 57.4% in Guangdong and 54.6% vs 45.4% in Jiangsu). Sensitivity analysis indicated that carcinogenic risk was most sensitive to rice ingestion rate and rice iAs levels, while non-carcinogenic hazard (i.e., HQ and HI) was most sensitive to ingestion rate of fish and rice, and Cu concentration in rice. Our results suggest that rice is more important than fish for human dietary metal(loid) exposure risk in China, and carcinogenic risk from iAs exposure in rice requires particular attention.

Environmental Pollutant Benzo[a]pyrene Upregulated Long Non-coding RNA HZ07 Inhibits Trophoblast Cell Migration by Inactivating PI3K/AKT/MMP2 Signaling Pathway in Recurrent Pregnancy Loss.

Benzo(a)pyrene (BaP) is a ubiquitous environmental endocrine-disrupting chemical that is known to have toxic effects on reproduction. However, the underlying mechanisms describing how BaP and its metabolite benzo[a]pyrene-7, 8-diol-9, 10-epoxide (BPDE) induce recurrent pregnancy loss (RPL) are still largely unclear. In this study, we identified a novel long non-coding RNA (lnc-HZ07, NCBI MT936329) that was upregulated in trophoblast cells after exposure to BPDE, and lnc-HZ07 expression was significantly higher in RPL villous tissues than that in control villous tissues. Knockdown of lnc-HZ07 promoted trophoblast cell migration, whereas overexpression of lnc-HZ07 inhibited trophoblast cell migration. Further study showed that lnc-HZ07 inhibited trophoblast migration by downregulating matrix metalloproteinase 2 (MMP2) expression via dephosphorylation of AKT. These results demonstrated a novel regulatory pathway in which BaP downregulated AKT phosphorylation and inhibited MMP2 expression by upregulating lnc-HZ07, suggesting that lnc-HZ07 could be considered as a potential pathological marker of BaP-induced RPL and therapeutic target for this disease.

Transcriptomic evidence of luteinizing hormone-releasing hormone agonist (LHRH-A) regulation on lipid metabolism in grass carp (Ctenopharyngodon idella).

In this study, RNA sequencing was used to identify the hepatic gene expression profile in grass carp associated with luteinizing hormone-releasing hormone agonist (LHRH-A) treatment. A total of 93,912,172 reads were generated by HiSeq 4000 sequencing platform. After filtering, 83,450,860 clean reads were mapped to the reference genome. By calculating the FPKM of genes, 1475 differentially expressed genes were identified. PPAR signaling pathway was enriched with upregulated genes in LHRH-A injection group showing the regulation of the lipid metabolism by LHRH-A. The expression of eight key genes in PPAR signaling pathway was confirmed by qPCR and the results suggested that ACSL4A, ACSL4B, ANGPTL4, LPL, RXRBA and SLC27A1B were significantly stimulated by LHRH-A injection. This investigation provides the evidence that LHRH-A could play a role in lipid metabolism.

Retrospective analysis of LNM risk factors and the effect of chemotherapy in early colorectal cancer: A Chinese multicenter study.

BACKGROUND: Estimating the risk of lymph node metastasis (LNM) is crucial for determining subsequent treatments following curative resection of early colorectal cancer (ECC). This multicenter study analyzed the risk factors of LNM and the effectiveness of postoperative chemotherapy in patients with ECC. METHODS: We retrospectively analyzed the data of 473 patients with ECC who underwent general surgery in five hospitals between January 2007 and October 2018. The correlations between LNM and sex, age, tumor size, tumor location, endoscopic morphology, pathology, depth of invasion and tumor budding (TB) were directly estimated based on postoperative pathological analysis. We also observed the overall survival (OS) and recurrence in ECC patients with and without LNM after matching according to baseline measures. RESULTS: In total, 473 ECC patients were observed, 288 patients were enrolled, and 17 patients had LNM (5.90%). The univariate analysis revealed that tumor size, pathology, and lymphovascular invasion were associated with LNM in ECC (P = 0.026, 0.000, and 0.000, respectively), and the multivariate logistic regression confirmed that tumor size, pathology, and lymphovascular invasion were risk factors for LNM (P = 0.021, 0.023, and 0.001, respectively). There were no significant differences in OS and recurrence between the ECC patients with and without LNM after matching based on baseline measures (P = 0.158 and 0.346, respectively), and no significant difference was observed between chemotherapy and no chemotherapy in ECC patients without LNM after surgery (P = 0.729 and 0.052). CONCLUSION: Tumor size, pathology, and lymphovascular invasion are risk factors for predicting LNM in ECC patients. Adjuvant chemotherapy could improve OS and recurrence in patients with LNM but not always in ECC patients without LNM.

Effects of moxibustion and acupuncture at Zusanli (ST 36) and Zhongwan (CV 12) on chronic atrophic gastritis in rats.

OBJECTIVE: To evaluate the effects of moxibustion and acupuncture of Zusanli (ST 36) and Zhongwan (CV 12) acupoints on chronic atrophic gastritis (CAG) in rats, and to study the mechanisms behind their actions. METHODS: Forty-four male Sprague-Dawley rats were induced with CAG by intragastric administration of 40% ethanol combined with free drinking of N-methyl-N'nitro-N-nitrosoguanidine and irregular feeding for 12 weeks, followed by daily treatment with moxibustion or acupuncture for 2 weeks. Histopathologic examination, Western blotting of cytokines [epidermal growth factor (EGF), EGF receptor (EGFR), extracellular signal-regulated kinase (ERK), phosphorylated ERK (p-ERK)], and 1H NMR-based metabolic profiling of gastric tissues were used to measure changes related to CAG modeling and treatment. RESULTS: Moxibustion and acupuncture at Zusanli (ST 36) and Zhongwan (CV 12) each relieved CAG-induced abnormalities in histopathology and cytokine expression of ERK and p-ERK. Only moxibustion treatment regulated the expression of EGF and EGFR. Metabolites that were increased in gastric tissue by CAG induction (alanine, nicotinamide adenine dinucleotide phosphate, uracil DNA glycosylase, lactate, glycerol and adenosine) were restored to normal levels after moxibustion treatment; acupuncture treatment only normalized the levels of adenosine monophosphate and glycerol. CONCLUSION: Our findings suggest that moxibustion or acupuncture at Zusanli (ST 36) and Zhongwan (CV 12) can significantly improve the condition of CAG in rats. These treatments exert their effects on CAG through different mechanisms.

Environmental Pollutant Benzo[a]pyrene Induces Recurrent Pregnancy Loss through Promoting Apoptosis and Suppressing Migration of Extravillous Trophoblast.

METHODS: The implantation sites, fetus resorption, and abnormal fetuses were studied in pregnant mice treated with different doses of BaP by oral gavage from day 1 to day 10 of gestation. Additionally, apoptosis and related signaling pathway, and the migration and invasion of trophoblasts, were assessed before and after exposure of BPDE in Swan 71 trophoblast cell. Besides, the migration and invasion, and its related signaling pathway, were assessed in villi obtained from women. RESULTS: We observed a concentration-dependent incidence of abnormal murine fetuses, beginning with 0.1 mg/kg BaP; with a BaP concentration of 2 mg/kg, no fetuses developed. Correspondingly, a BPDE concentration-dependent apoptosis of human trophoblasts. Beginning with 0.5 µM BPDE exposure, Bax/Caspase-3 were increased and Bcl-2 decreased. Furthermore, BPDE also inhibited, in a dose-dependent manner, the migration of villous explants from elective abortion women, consistent with the reduced migration of villous explants from women with recurrent pregnancy loss (RPL), and reduced the cell immigration in Swan 71 trophoblasts, in a dose-dependent manner measured by transwell assays. CONCLUSIONS: Our study results provide mechanistic insight to the effect of BPDE on trophoblast dysfunction through enhanced cell apoptosis and inhibited migration, providing further experimental evidence to the causative links between BaP exposure and PRL.

Upregulation of FTX Promotes Osteosarcoma Tumorigenesis by Increasing SOX4 Expression via miR-214-5p.

BACKGROUND: Long-chain non-coding RNA (LncRNA) plays a key role in the biological processes of tumors. LncRNA-FTX has been the invasion of tumors. However, its function and mechanism in osteosarcoma have not been studied. METHODS: qRT-PCR was measured the expression levels of FTX and miR-214-5p in osteosarcoma. The protein levels of SRY-related HMG box transcription factor 4 (SOX4) were detected by Western Blot. Cholecystokinin (CCK-8) assay, cell colony formation and Transwell assay, Annexin V-FITC/PI assay were analyzed the effects of FTX and miR-214-5p on cell proliferation, cell invasion and apoptosis. The relationship between FTX, miR-214-5p and SOX4 was analyzed by bioinformatics analysis and Luciferase. The tumor changes in mice were detected by vivo experiments in nude mice. RESULTS: The expression levels of FTX were increased in osteosarcoma tissues and cell lines and negatively correlated with the expression levels of miR-214-5p. FTX could modulate the expression of miR-214-5p in osteosarcoma cell lines. sh-FTX inhibited the growth and metastasis of osteosarcoma. FTX could regulate the growth of osteosarcoma through miR-214-5p. The knockdown of miR-214-5p reversed the inhibitory effect of sh-FTX on osteosarcoma cell proliferation and growth in mice. Furthermore, FTX regulated the expression of SOX4 by acting as a sponge of miR-214-5p in osteosarcoma. CONCLUSION: FTX could promote proliferation, invasion and inhibited apoptosis by regulating miR-214-5p/SOX4 axis in osteosarcoma, suggesting that FTX might be a potential target for osteosarcoma treatment.

TRAF3 of blunt snout bream participates in host innate immune response to pathogenic bacteria via NF-κB signaling pathway.

Tumor necrosis factor receptor-associated factor 3 (TRAF3) is a multifunctional adaptor protein primarily involved in both bacterial defense and antiviral immunity in living organisms. However, the knowledge on TRAF3 in blunt snout bream (Megalobrama amblycephala), a freshwater fish with economic values, remained unclear. In the present study, we identified and characterized successfully Traf3 gene from M. amblycephala (maTraf3). The maTraf3 cDNA contained a 1722 bp open reading frame that encoded a protein of 573 amino acid residues. The deduced amino acid sequence comprised of a RING finger domain, two zinc finger motifs, a coiled-coil region and a MATH domain. Analysis of the transcriptional patterns of maTraf3 revealed that it was ubiquitously distributed in various tissues tested from M. amblycephala, with the abundance of expression in spleen and muscle. Following a challenge with Aeromonas hydrophila and lipopolysaccharide stimulation, the expression of maTraf3 was strongly enhanced at different time points in vitro and in vivo. MaTRAF3 was identified as a cytosolic protein and suggested to form aggregates or be associated with vesicles scattering in the cytoplasm. NF-κB transcription was activated by maTraf3 in reporter assay. The overexpression of maTraf3 produced high levels of pro-inflammatory cytokines such as IL-1ß, IL-6, IL-8 and TNF-α, implying its immune-regulatory role in M. amblycephala. Taken together, our results obtained in this study demonstrated the crucial role of maTraf3 in mediating host innate immune response to pathogen invasion via NF-κB signaling pathway, which might indicate a novel therapeutic approach to combat bacterial infection in fish.