RNF113A targeted by miR-197 promotes proliferation and inhibits autophagy via CXCR4/CXCL12/AKT/ERK/Beclin1 axis in cervical cancer.

Ring Finger Protein 113 (RNF113A), an ubiquitin E3 ligase, is genetically associated with many biological processes, including proliferation, differentiation, cell death, and neurogenesis. Recently, RNF113A has been found to be an abnormal expression in many diseases, such as X-linked trichothiodystrophy syndrome and esophageal cancer. Here, we explore the potential mechanism of RNF113A in the progression of cervical cancer (CC). In this study, we evaluated the expression level and biological function of RNF113A in CC both in vitro and in vivo by bioinformatic prediction, DIA proteomic analysis, compensation experiment, Co-IP, dual-luciferase reporter assay and nude mouse xenograft to identify the RNF113A-associated autophagy pathways involved with tumorigenesis. Consistent with the prediction from biological information analysis, we found that RNF113A was highly expressed in human CC tissues and cells. In addition, this study illustrated that the high expression of RNF113A dramatically promoted proliferation and suppressed autophagy both in vitro and in vivo. In contrast, low expression of RNF113A enhanced autophagy activities and inhibited tumor growth in CC. We also found that miRNA-197, the level of which (negative correlation with RNF113A) declined in human CC, directly restrained the expression of RNF113A. Mechanistically, proteomic and mechanistic assays uncovered that RNF113A confirmed as the direct downstream target of miR-197, promoted proliferation and restrained autophagy in CC not through direct ubiquitination degradation of autophagy marker Beclin1 but via CXCR4/CXCL12/AKT/ERK/Beclin1 signal transduction axis. In summary, we found a new miR-197/RNF113 A/CXCR4/CXCL12/AKT/ERK/Beclin1 regulation pathway that plays an important part in the survival and progression of CC.

Development, validation and reliability testing of the hospice care environment scale.

BACKGROUND: WHO stated the environment is an important factor affecting the development of hospice care. The environment is the sum of factors affecting behavior besides the individual factors. Currently, a scale to comprehensively assess the hospice environment of nurse is still lacking. This study aimed to develop an instrument to investigate the environmental factors affecting hospice care of nurses. METHODS: Literature review and a semi-structured interview were conducted to form the items pool of the Hospice Care Environment Scale. Two rounds of Delphi expert consultation were conducted by 16 experts to revise the scale dimensions and entries to form the Hospice Care Environment Scale. A psychometric evaluation was then performed among 530 oncology nurses in a large tertiary oncology hospital in Hubei Province. The 500 valid questionnaires were randomly divided into two groups in a 1:1 ratio, sample 1 (n1 = 250) for item screening and sample 2 (n2 = 250) for quality evaluation of the resulting scale. Item analysis, reliability analysis, validity analysis and acceptability analysis were performed. RESULT: The Hospice Care Environment Scale consists of two dimensions and 13 entries. The Cronbach's α coefficient of the Hospice Care Environment Scale was 0.970, and the Cronbach's α coefficient of the two dimensions were 0.952 and 0.969, respectively, with the Item-content validity index and average Scale- content validity index of the scale was both 1.000. The validation factor analysis showed the standardized path coefficients of each item were basically above 0.5, and the factor structure model was stable and suitable. The average completion time of the scale was about 3 min, which had good feasibility. CONCLUSION: The Hospice Care Environment Scale to assess the environment of hospice care services, has good content and construct validity and reliability. This scale can provide guidance to evaluate the hospice care environment.

A Risk Evaluation Framework in System Control Subject to Sensor Degradation and Failure.

Sensor degradation and failure often undermine users' confidence in adopting a new data-driven decision-making model, especially in risk-sensitive scenarios. A risk assessment framework tailored to classification algorithms is introduced to evaluate the decision-making risks arising from sensor degradation and failures in such scenarios. The framework encompasses various steps, including on-site fault-free data collection, sensor failure data collection, fault data generation, simulated data-driven decision-making, risk identification, quantitative risk assessment, and risk prediction. Leveraging this risk assessment framework, users can evaluate the potential risks of decision errors under the current data collection status. Before model adoption, ranking risk sensitivity to sensor data provides a basis for optimizing data collection. During the use of decision algorithms, considering the expected lifespan of sensors enables the prediction of potential risks the system might face, offering comprehensive information for sensor maintenance. This method has been validated through a case study involving an access control.

DNA, protein and aptamer-based methods for seafood allergens detection: Principles, comparisons and updated applications.

The increasing number of people with seafood allergy has caused a series of problems for practitioners and consumers in the seafood industry year by year. Thereby, development of efficient, convenient and low-cost allergen detection methods is urgently needed. This review introduces three important existing seafood allergen detection methods associated with DNA-based, protein-based and aptamer-based. Their principles and biological characteristics are firstly presented. The core of these three methods are DNA amplification techniques, specific binding of antigens and antibodies, and specific binding of aptamers and ligands, respectively. Among them, DNA-based detection method is an indirect analysis, which takes the gene of allergen as the detection object and is characterized by good stability and high sensitivity. Protein-based and aptamer-based, methods employ indirect analysis for allergen detection. The difference is that the latter uses an easily synthesized and highly efficient aptamer as the detection probe, showing great promising potentials. The advantages and disadvantages of the three mentioned detection methods are also discussed. In the future, as more efficient and reliable detection methods for seafood allergens come into practice, the possibility of seafood allergy patients eating seafood products by mistake will be greatly reduced, which will ensure the food safety and the health of allergy patients.

Dermoscopy and reflection confocal microscope features of pigmented prurigo.

BACKGROUND: Pigmented prurigo (PP) is a chronic and recurrent inflammatory skin disease. PP is not common clinically, but it is easily misdiagnosed because of its diversified clinical manifestations in different stages. MATERIALS AND METHODS: We retrospectively analyzed the clinical, histopathological, dermoscopy, and reflectance confocal microscopy (RCM) features of 20 patients diagnosed as PP. RESULTS: The female predominance ratio was revealed with male to female of 1:4. Seven female patients were on a diet (without staple food) and one patient had a history of diabetes. Eight cases were suffered in spring, six cases in winter, three cases in summer, and three cases in autumn. Multiple sites were involved in 13 cases. Four patients had urticarial papules and plaques. Nineteen patients had erythematous papules with reticular distribution, of which 14 cases accompanied reticulate hyperpigmentation, four cases with papulovesicle, and two cases accompanied with pustules. One patient only showed reticulate hyperpigmentation. In the early lesions, dermatoscopy showed pink oval lesions, punctate or linear vessels, and pale yellow rings around the skin lesions. RCM is characterized by spongiosis, spongy vesicle, neutrophils scattered in the epidermis, which was consistent with epidermis spongiosis, neutrophils infiltrating into the upper epidermis and necrotic keratinocytes in histopathology. In the fully developed lesions, dermatoscopy showed pink lesions with brown pigment granules in the center and linear vessels in the edge. RCM showed that demarcation of epidermis and dermis is not clear, and inflammatory cells can be seen in the upper dermis and histopathologically lesions assumed a patchy lichenoid pattern, and the inflammatory cells infiltrating the dermis were dominated by lymphocytes. In the late lesions, dermatoscopy showed grainy grayish-brown or yellowish-brown pigmentation surrounding the hair follicle merging with each other. RCM showed that pigment granules were increased on the ring of basal cells, inflammatory cells were sparsely infiltrated in the dermal papilla and superficial layer, and epidermis slightly hyperplastic, with melanophages and a few lymphocytes infiltrating the superficial dermis in histopathology. CONCLUSION: PP is easily misdiagnosed and not always occurs in those on a restrictive diet. A combination of dermatoscopy and RCM is helpful for its diagnosis of PP.

Regenerated Silk Nanofibers for Robust and Cyclic Adsorption-Desorption on Anionic Dyes.

In recent years, adsorption-based membranes have been widely investigated to remove and separate textile pollutants. However, cyclic adsorption-desorption to reuse a single adsorbent and clear scientific evidence for the adsorption-desorption mechanism remains challenging. Herein, silk nanofibers were used to assess the adsorption potential for the typical anionic dyes from an aqueous medium, and they show great potential toward the removal of acid dyes from the aqueous solution with an adsorption rate of ∼98% in a 1 min interaction. Further, we measured the filtration proficiency of a silk nanofiber membrane in order to propose a continuous mechanism for the removal of acid blue dye, and a complete rejection was observed with a maximum permeability rate of ∼360 ± 5 L·m-2·h-1. The Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy studies demonstrate that this fast adsorption occurs due to multiple interactions between the dye molecule and the adsorbent substrate. The as-prepared material also shows remarkable results in desorption. A 50-time cycle exhibits complete adsorption and desorption ability, which not only facilitates high removal aptitude but also produces less solid waste than other conventional adsorbents. Additionally, fluorescent 2-bromo-2-methyl-propionic acid (abbreviated as EtOxPY)-silk nanofibers can facilitate to illustrate a clear adsorption and desorption mechanism. Therefore, the above-prescribed results make electrospun silk nanofibers a suitable choice for removing anionic dyes in real-time applications.

An overview of tropomyosin as an important seafood allergen: Structure, cross-reactivity, epitopes, allergenicity, and processing modifications.

Tropomyosin (TM) is a major allergen in crustaceans, which often causes allergy and is fatal to some consumers. Currently, the most effective treatment is to avoid ingesting TM, although most adverse events occur in accidental ingestion. In this review, the molecular characterization, epitopes, cross-reactivity, and pathogenesis of TM are introduced and elucidated. Modification of TM by traditional processing methods such as heat treatment and enzymatic hydrolysis, and innovative processing technologies including high-pressure treatment, cold plasma (CP), ultrasound, pulsed electric field (PEF), pulsed ultraviolet, microwave and irradiation are discussed in detail. Particularly, enzymolysis, PEF, and CP technologies show great potential for modifying TM and more studies are needed to verify their effectiveness for the seafood industry. Possible mechanisms and the advantages/disadvantages of these technologies for the mitigation of TM allergenicity are also highlighted. Further work should be conducted to investigate the allergenicity caused by protein segments such as epitopes, examine the interaction sites between the allergen and the processing techniques and reveal the reduction mechanism of allergenicity.

Effects of dietary plant essential oil supplementation on growth performance, nutrient digestibility and meat quality in finishing pigs.

This study was aimed to explore the effects of dietary plant essential oil (PEO) supplementation on growth performance and meat quality in finishing pigs. A total of eighteen Duroc × Landrace × Yorkshire finishing barrows with an average initial body weight of 79.86 ± 1.94 kg were randomly assigned to CON group (fed with a basal diet) and PEO group (fed with the basal diet containing 200 mg/kg PEO) with 9 replicates per treatment. The trial lasted for 42 days. The results showed that dietary PEO supplementation significantly increased ADG during phase I (1-21 days) and the overall experimental period (p < 0.05), tended to increase ADFI in phase II (22-42 days) and the overall experimental period (p = 0.09), decreased F/G in phase I (p < 0.05) and tended to decrease F/G during the overall experimental period (p = 0.08). Meanwhile, compared to the CON group, the digestibility of DM, GE and EE in the PEO group was improved remarkably (p < 0.05). PEO supplementation also significantly improved T-AOC and lowered MDA content in longissimus dorsi (p < 0.05), tended to increase the activity of T-SOD (p = 0.06). A higher IMF content (p = 0.09) and a lower shear force (p = 0.08) of longissimus dorsi were found in the PEO group than that in CON group (p = 0.09). Furthermore, pigs fed the PEO diet showed higher mRNA abundances of GLUT4, LPL, CPT-1, CD36, FABP and LDL-R in the liver, and GLUT4 and FAS in the longissimus dorsi (p < 0.05). In conclusion, PEO fed to finishing pigs improved the growth performance and nutrient digestibility. Furthermore, PEO supplementation had the potential role to improve pork quality by increasing the antioxidant capacity and IMF content, and decreasing the shear force of longissimus dorsi to a certain extent.

The Nutritional Significance of Intestinal Fungi: Alteration of Dietary Carbohydrate Composition Triggers Colonic Fungal Community Shifts in a Pig Model.

Carbohydrates represent the most important energy source in the diet of humans and animals. A large number of studies have shown that dietary carbohydrates (DCHO) are related to the bacterial community in the gut, but their relationship with the composition of intestinal fungi is still unknown. Here, we report the response of the colonic fungal community to different compositions of DCHO in a pig model. Three factors, ratio (2:1, 1:1, and 1:2) of amylose to amylopectin (AM/AP), level of nonstarch polysaccharides (NSP; 1%, 2%, and 3%), and mannan-oligosaccharide (MOS; 400, 800, and 1,200 mg/kg body weight), were considered according to an L9 (34) orthogonal design to form nine diets with different carbohydrate compositions. Sequencing based on an Illumina HiSeq 2500 platform targeting the internal transcribed spacer 1 region showed that the fungal community in the colon of the pigs responded to DCHO in the order of MOS, AM/AP, and NSP. A large part of some low-abundance fungal genera correlated with the composition of DCHO, represented by Saccharomycopsis, Mrakia, Wallemia, Cantharellus, Eurotium, Solicoccozyma, and Penicillium, were also associated with the concentration of glucose and fructose, as well as the activity of ß-d-glucosidase in the colonic digesta, suggesting a role of these fungi in the degradation of DCHO in the colon of pigs. Our study provides direct evidence for the relationship between the composition of DCHO and the fungal community in the colon of pigs, which is helpful to understand the function of gut microorganisms in pigs.IMPORTANCE Although fungi are a large group of microorganisms along with bacteria and archaea in the gut of monogastric animals, the nutritional significance of fungi has been ignored for a long time. Our previous studies revealed a distinct fungal community in the gut of grazing Tibetan pigs (J. Li, D. Chen, B. Yu, J. He, et al., Microb Biotechnol 13:509-521, 2020, https://doi.org/10.1111/1751-7915.13507) and a close correlation between fungal species and short-chain fatty acids, the main microbial metabolites of carbohydrates in the hindgut of pigs (J. Li, Y. Luo, D. Chen, B. Yu, et al., J Anim Physiol Anim Nutr 104:616-628, 2020, https://doi.org/10.1111/jpn.13300). These groundbreaking findings indicate a potential relationship between intestinal fungi and the utilization of DCHO. However, no evidence directly proves the response of intestinal fungi to changes in DCHO. Here, we show a clear alteration of the colonic fungal community in pigs triggered by different compositions of DCHO simulated by varied concentrations of starch, nonstarch polysaccharides (NSP), and oligosaccharides. Our results highlight the potential involvement of intestinal fungi in the utilization of nutrients in monogastric animals.

[3 + 2]-Annulation of pyridinium ylides with 1-chloro-2-nitrostyrenes unveils a tubulin polymerization inhibitor.

Indolizines and pyrazolo[1,5-a]pyridines were prepared via [3 + 2]-cycloaddition of pyridinium ylides to 1-chloro-2-nitrostyrenes. The synthesized molecules were evaluated for antiproliferative activities against a BE(2)-C neuroblastoma cell line with several compounds decreasing the viability of cancer cells. Indolizine 9db showed higher potency than that of all-trans-retinoic acid, an approved cancer drug. Mechanistically, it was found to inhibit tubulin polymerization and it is thus proposed that the discovered chemistry can be exploited for the development of novel microtubule-targeting anticancer agents.

MicroRNA-19b-3p suppresses gastric cancer development by negatively regulating neuropilin-1.

BACKGROUND: Gastric cancer (GC) remains one of the most common digestive malignancies worldwide and ranked third causes of cancer-related death. Mounting evidence has revealed that miRNAs exert critical regulatory roles in GC development. METHODS: Immunohistochemistry (IHC) and western blot assay were performed to determine the protein expression levels of neuropilin-1 (NRP1) and mRNA levels were confirmed by quantitative RT-PCR (qRT-PCR) in GC tissues. Kaplan-Meier analysis was performed to evaluate the prognostic value of NRP1 in GC. Knockdown of NRP1 was conducted to analyse its function in vitro and vivo. Luciferase reporter assay, western blot and qRT-qPCR were employed to identify the miRNAs which directly targeted NRP1. Furthermore, Bioinformatics analysis and experimental verification were used to explore the potential molecular mechanism and signalling pathway. RESULTS: In the current study, we revealed that NRP1 was highly expressed in GC tumor tissues and was associated with poor prognosis in GC patients. NRP1 knockdown inhibited GC cell growth, migration and invasion in vitro, while suppressed GC xenograft tumor development in vivo. Bioinformatics analysis predicted that miR-19b-3p down-regulated NRP1 expression by targeting its 3'-UTR. Functional assay demonstrated that miR-19b-3p inhibited GC cell growth, migration and invasion via negatively regulating NRP1. Overexpression NRP1 partially reversed the regulatory effect of miR-19b-3p. Moreover, we showed that miR-19b-3p/NRP1 axis regulated the epithelial-to-mesenchymal transition and focal adhesion in GC, which might contribute the GC development and progression. CONCLUSIONS: Taken together, our findings suggest a regulatory network of miR-19b-3p/NRP1 in GC development. The miR-19b-3p/NRP1 axis might be further explored as a potential diagnostic and therapeutic target in GC.

Capsulized faecal microbiota transplantation ameliorates post-weaning diarrhoea by modulating the gut microbiota in piglets.

Early weaning-induced stress causes diarrhoea, thereby reducing the growth performance of piglets. Gut bacterial dysbiosis has emerged as a leading cause of post-weaning diarrhoea. The present study aimed to investigate the effect of capsulized faecal microbiota transplantation (FMT) on the gut bacterial community, immune response and gut barrier function of piglets. Thirty-two weaned barrows were randomly divided into two groups. The recipient group was inoculated orally with capsulized faecal microbiota of healthy Tibetan pigs during the whole period of the trial, while the control group was given an empty capsule. The feed-to-gain ratio, diarrhoea ratio, and histological damage score of recipient piglets were significantly decreased. FMT treatment significantly increased the colon length of piglets. Furthermore, the relative abundances of Firmicutes, Euryarchaeota, Tenericutes, Lactobacillus, and Methanobrevibacter in the colon of recipient piglets were increased, and the relative abundances of Campylobacter and Proteobacteria were significantly decreased compared with those in the control group. CD4+ lymphocytes and CD4+/CD8+ ratio in the peripheral blood of recipient piglets were significantly increased. FMT treatment increased the IL-4 and IL-10 levels and decreased the TNF-α and INF-γ levels in the colonic tissue of piglets. The recipient piglets' mRNA expression of TLR2, TLR8, NF-κB, and iNOS was significantly regulated. In addition, FMT significantly enhanced the gene expression of ZO-1. Overall, treatment with capsulized FMT ameliorated diarrhoea in piglets, with significant effects on limiting colon inflammatory responses, downregulating the TLR signalling pathway and the gene expression of iNOS, and strengthening intestinal barrier function by modulating the constituents of the gut microbiota.

The fungal community and its interaction with the concentration of short-chain fatty acids in the caecum and colon of weaned piglets.

In sharp contrast to the numerous studies on bacteria, very little is known about the fungal community in mammalian gut. Recent studies on human and mice highlighted the importance of "mycobiota" in the metabolism and gut health of host, but our knowledge on the fungal composition and distribution in swine gut is very limited. In the current study, the fungal community in the caecal and colonic digesta from five weaned piglets was analysed based on an Illumina HiSeq 2500 platform targeting the internal transcribed spacer 1 region, and its relationship with the concentration of short-chain fatty acids was also investigated. Results revealed that the fungal profile in the caecal and colonic digesta of the piglets was distinct, and the caecal fungal diversity was significantly higher (p < .05). Basidiomycota and Ascomycota were the two predominant fungal phyla in the caecum and colon of the piglets. Comparing with that in colon, the abundance of Saccharomycopsis, Wallemia and Mrakia showed significantly higher (p < .05), and the abundance of Scheffersomyces, Aspergillus, Penicillium and Mucor was significantly lower in the caecum (p < .05). Canonical correspondence analysis showed a correlation between the fungal community and the concentration of isobutyrate, isovalerate, propionate and acetate in the digesta samples. Spearman's correlation indicated that the low-abundance genera, Fusarium, Plectosphaerella and Metarhizium, were positively correlated with of isobutyrate (p < .05), while Xeromyces were negatively correlated with acetate (p < .05), and Cornuvesica was negatively correlated with both acetate and propionate (p < .05). Results illuminated a probable interaction between the fungal composition and the bacterial degradation of protein and complex carbohydrates in the diet. These findings would be helpful to enhance our understanding of fungi in swine gut and provide a foundation for future work on the function of mycobiota in pigs.

Repression of TXNIP-NLRP3 axis restores intestinal barrier function via inhibition of myeloperoxidase activity and oxidative stress in nonalcoholic steatohepatitis.

Dysfunction of the intestinal barrier function occurs in hepatic injury, but the specific mechanisms responsible are largely unknown. Recently, NOD-like receptor 3 (NLRP3) inflammasome functions in impairing endothelial barrier function. In this study, we test the hypothesis that TXNIP-NLRP3 axis repression prevents against intestinal barrier function disruption in nonalcoholic steatohepatitis (NASH). First, lipopolysaccharide (LPS)-induced alterations in expression of ZO-1 and occludin, myeloperoxidase (MPO) activity, reactive oxygen species (ROS) level, and transepithelial electric resistance (TEER) in intestinal epithelial cells (IECs) isolated from C57BL/6 wild-type (WT) and TXNIP-/- mice were evaluated. The underlying regulatory mechanisms of TXNIP knockout in vivo were investigated with the detection of expressions of TXNIP, NLRP3 and ZO-1, and occludin, the interaction of TXNIP-NLRP3, MPO activity, ROS level, permeability of intestinal mucosa, levels of inflammatory factors in serum, and LPS concentration. We identified that TXNIP knockout promoted ZO-1 and occludin expression, yet reduced MPO activity, ROS level, and cell permeability in IECs, indicating restored the intestinal barrier function. However, LPS upregulated TXNIP and NLRP3 expression, as well as contributed to the interaction between TXNIP and NLRP3 in vitro. Furthermore, TXNIP was significantly upregulated in the intestinal mucosa of NASH mice and its knockout repaired the intestinal barrier disrupt, inhibited expression of inflammatory factors, and reduced LPS concentration as well as hepatic injury in vivo. Taken together, our findings demonstrated that inhibited the activation of the TXNIP-NLRP3 axis reduced MPO activity and oxidative stress and thus restoring the intestinal barrier function in NASH. TXNIP-NLRP3 axis may be a promising therapeutic strategy for the NASH treatment.

SUPREME-HN: a retrospective biomarker study assessing the prognostic value of PD-L1 expression in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: Programmed cell death ligand-1 (PD-L1) expression on tumor cells (TCs) is associated with improved survival in patients with head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy, although its role as a prognostic factor is controversial. This study investigates whether tumoral expression of PD-L1 is a prognostic marker in patients with recurrent and/or metastatic (R/M) HNSCC treated with standard chemotherapy. METHODS: This retrospective, multicenter, noninterventional study assessed PD-L1 expression on archival R/M HNSCC tissue samples using the VENTANA PD-L1 (SP263) Assay. PD-L1 high was defined as PD-L1 staining of ≥ 25% TC, with exploratory scoring at TC ≥ 10% and TC ≥ 50%. The primary objective of this study was to estimate the prognostic value of PD-L1 status in terms of overall survival (OS) in patients with R/M HNSCC. RESULTS: 412 patients (median age, 62.0 years; 79.9% male; 88.2% Caucasian) were included from 19 sites in seven countries. 132 patients (32.0%) had TC ≥ 25% PD-L1 expression; 199 patients (48.3%) and 85 patients (20.6%) had TC ≥ 10% and ≥ 50%, respectively. OS did not differ significantly across PD-L1 expression (at TC ≥ 25% cutoff median OS: 8.2 months vs TC < 25%, 10.1 months, P = 0.55) or the ≥ 10% and ≥ 50% cutoffs (at TC ≥ 10%, median OS: 9.6 months vs TC < 10%, 9.4 months, P = 0.32, and at TC ≥ 50%, median OS 7.9 vs TC < 50%, 10.0 months, P = 0.39, respectively). CONCLUSIONS: PD-L1 expression, assessed using the VENTANA PD-L1 (SP263) Assay, was not prognostic of OS in patients with R/M HNSCC treated with standard of care chemotherapies. Trial registration ClinicalTrials.gov, NCT02543476. Registered September 4, 2015.

Novel hypolipidemic conjugates of fatty acid and bile acid with lysine for linkage.

Novel fatty acid-bile acid conjugates (1a-1k) were designed and synthesized by coupling of the fatty acids to the 3-OH of bile acids using lysine for linkage. In the conjugates, the 24-COOH of the bile acids was kept intact to preserve liver-specific recognition. The ability of the newly synthesized conjugates (at 100 mg/kg dosage) to reduce total cholesterol (TC) and triglyceride (TG) levels in mice fed with high-fat diet (HFD) was evaluated. Conjugates of stearic acid with cholic acid and palmitic acid with ursodeoxycholic acid (at dosages of 50, 100, and 200 mg/kg) were further evaluated to determine their ability to reduce aspartate aminotransferase (AST), alanine aminotransferase (ALT), TC, and TG levels in mice fed with HFD. All conjugates showed potent hypolipidemic activity. Further investigation revealed that compounds 1c and 1 g not only dose-dependently reduced serum levels of TC and TG, but also inhibited the elevation of serum AST and ALT levels in mice fed with HFD. Thus, compounds 1c and 1 g are promising hypolipidemic agents with hepatocyte protective effects against HFD-induced liver damage.

Genome-wide association study identifies HLA-DR variants conferring risk of HBV-related acute-on-chronic liver failure.

OBJECTIVE: Acute-on-chronic liver failure (ACLF) is an extreme condition after severe acute exacerbation of chronic hepatitis B; however, the underlying genetic factors involved in its onset and progression are currently unclear. DESIGN: We carried out a genome-wide association study among 399 HBV-related ACLFs (cases) and 401 asymptomatic HBV carriers (AsCs, as controls) without antiviral treatment. The initial findings were replicated in four independent case-control sets (a total of 901 ACLFs and 1686 AsCs). The roles of risk variants on clinical traits of ACLF were also analysed. RESULTS: Among 1300 ACLFs and 2087 AsCs, we identified rs3129859 at human leucocyte antigen (HLA) class II region (chromosome 6p21.32) associated with HBV-related ACLF (combined P dominant =2.64×10-20, OR=1.83). Analysis identified HLA-DRB1*12:02 as the top susceptible HLA allele associated with ACLF (p=3.94×10-6, OR=2.05). The association of rs3129859 was robust in ACLF subgroups (ACLFs with liver cirrhosis, p=1.36×10-16; ACLFs without liver cirrhosis, p=1.52×10-7), and patients at low-replicative phase (p=6.36×10-11, OR=2.29) or HBV e antigen-negative chronic hepatitis B phase (p=1.51×10-14, OR=1.86). Clinical traits analysis in patients with ACLF showed that the risky rs3129859*C allele was also associated with prolonged prothrombin time, faster progression to ascites development and higher 28-day mortality. CONCLUSIONS: Our genome-wide association study identified HLA-DR as the major locus for susceptibility to HBV-related ACLF. Our findings highlight the importance of HLA class II restricted CD4+ T-cell pathway on the immunopathogenesis of HBV-related ACLF.

Baicalin Attenuates Alcoholic Liver Injury through Modulation of Hepatic Oxidative Stress, Inflammation and Sonic Hedgehog Pathway in Rats.

BACKGROUND/AIMS: Lipid accumulation, inflammatory responses and oxidative stress have been implicated in the pathology of alcoholic liver disease (ALD). Targeting inhibition of these features may provide a promising therapeutic strategy for ALD. Baicalin, a flavonoid isolated from Scutellaria baicalensis Georgi, has been shown to exert a hepatoprotective effect. However, its effects on ALD remain obscure. This study was aimed to investigate the effects of baicalin on alcohol-induced liver injury and its related mechanisms. METHODS: For in vivo experiments, rats were supplied intragastrical administration of alcohol continuously for 4 or 8 weeks, and then received baicalin treatment in the latter 4 weeks in the presence / absence of alcohol intake. Liver histology and function, inflammatory cytokines, oxidative mediators, and the components of the Sonic hedgehog pathway were evaluated. For in vitro experiments, alcohol-stimulated human normal liver cells LO2 were used. RESULTS: Baicalin treatment significantly alleviated alcoholic liver injury, improved liver function impaired by alcohol, and inhibited hepatocytes apoptosis. In addition, baicalin decreased the expression levels of proinflammatory cytokines TNF-α, IL-1ß, IL-6) and malonyldialdehyde (MDA), and increased the activities of antioxidant enzymes SOD and GSH-Px. Furthermore, baicalin modulated the activation of Sonic hedgehog (Shh) pathway. Administration of baicalin upregulated the expression of sonic hedgehog (Shh), patched (Ptc), Smoothened (Smo), and Glioblastoma-1(Gli-1). Blockade of the Shh pathway in cyclopamine abolished the effects of baicalin in vitro. CONCLUSION: Both in vivo and in vitro experimental results indicate that baicalin exerts hepatoprotective roles in alcohol-induced liver injury through inhibiting oxidative stress, inflammatory response, and the regulation of the Shh pathway.

Epidemiological Investigation and Risk Factors for Cervical Lesions: Cervical Cancer Screening Among Women in Rural Areas of Henan Province China.

BACKGROUND This cross-sectional study aimed to investigate the prevalence of cervical lesions and evaluate risk factors for cervical intraepithelial neoplasia (CIN) among women taking part in cervical cancer screening in rural areas of Henan province, China. MATERIAL AND METHODS Cervical cancer screening using the ThinPrep cytologic test (TCT) and gynecologic exam was conducted on 1315 women age 20-68 years in rural areas of Henan province, China. Colposcopy and biopsies were carried out for histopathologic diagnosis when indicated. Univariate and multivariate logistic regressions were performed to evaluate risk factors associated with cervical lesions. RESULTS Among 1315 women screened, CIN prevalence detected by histopathology was 1.22% (0.38% of CIN 1, 0.76% of CIN 2, and 0.08% of CIN 3). Cervical cancer prevalence was 2.66%. Multivariate analysis confirmed risk factors for cervical lesions included older age (the 21-40 age group vs. the 41-66 age group, OR=0.13, 95% CI: 0.03~0.57), postmenopause (OR=0.11, 95% CI: 0.03~0.45), cervical inflammation (OR=0.06, 95% CI: 0.01~0.31), and smoking (OR=6.78, 95% CI: 1.20~38.23). CONCLUSIONS Older age (41-66 years), presence of HPV infection, postmenopause, cervical inflammation, and smoking are strong risk factors for cervical lesions among women in rural areas of Henan province, China. Particular efforts should be made to provide cervical cancer screening for these women.

Plasma exchange-centered artificial liver support system in hepatitis B virus-related acute-on-chronic liver failure: a nationwide prospective multicenter study in China.

BACKGROUND: Plasma exchange (PE)-centered artificial liver support system reduced the high mortality rate of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). But the data were diverse in different medical centers. The present prospective nationwide study was to evaluate the effects of PE on patients with HBV-ACLF at different stages. METHODS: From December 2009 to December 2011, we evaluated 250 patients at different stages of HBV-ACLF from 10 major medical centers in China. All the laboratory parameters were collected at admission, before and after PE. RESULTS: Among the 250 patients who underwent 661 rounds of PE, one-month survival rate was 61.6%; 141 (56.4%) showed improvement after PE. Variables such as age (P=0.000), levels of total bilirubin (TB, P=0.000), direct bilirubin (P=0.000), total triglycerides (P=0.000), low-density lipoprotein (P=0.022), Na+ (P=0.014), Cl- (P=0.038), creatinine (Cr, P=0.007), fibrinogen (P=0.000), prothrombin time (PT, P=0.000), white blood cell (P=0.000), platelet (P=0.003) and MELD (P=0.000) were significantly related to prognosis. Multivariate logistic regression analysis showed that age, disease stage, TB, Cr and PT levels were independent risk factors of mortality among HBV-ACLF patients. CONCLUSIONS: PE can improve the clinical outcome of patients with HBV-ACLF. Levels of TB, Cr and PT, age and disease stage help to predict prognosis.