[The effects of nucleotide-binding oligomerization domain-like receptor 3 inflammasome on obstructive sleep apnea and its complications].

Obstructive sleep apnea (OSA) is a sleep disorder with a high incidence and severe impact on the human body, which can induce systemic chronic inflammatory responses. Chronic inflammation is an important cause of exacerbation of OSA and its associated complications. Nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) is an inflammasome that is widely found in epithelial cells and immune cells and plays an important role in inflammatory diseases as an important component of innate immunity. Research evidence suggests that the activation of NLRP3 inflammasomes can exacerbate the damage to neurons, endothelial cells, lung and kidney caused by OSA, and these effects can be eliminated by genetic or pharmacological deletion of NLRP3. Targeting inhibition of NLRP3 inflammasome may serve as a co-therapeutic strategy for OSA-induced related complications. This article reviews NLRP3 inflammasome and its mechanism in OSA-related concurrent diseases, which can provide scientific basis for prevention and intervention of OSA and its related complications.

[Prevalence of allergic rhinitis in Chinese children from 2001 to 2021: Meta analysis].

Objective: To analyze the prevalence of allergic rhinitis in Chinese children from 2001 to 2021, in order to provide data support for the prevention and treatment of allergic rhinitis in children. Methods: "Allergic rhinitis" "children" "adolescent" "infant" "prevalence" "epidemiology" were used in the main search terms. The combination of Mesh words and free words was adopted. CNKI, CBM, VIP, WanFang Data, PubMed, Web of Science, Embase and The Cochrane Library for publications between January 1, 2001 and December 31, 2021 were searched systemically and data were extracted from eligible studies by two independent reviewers. Supplementary collection was made by identifying retrospective references from the included literature. After study quality assessment, Meta analysis was completed using Stata 16.0 software. Results: A total of 20 cross-sectional studies were included, involving 54 886 cases. Meta analysis results showed that the overall prevalence of allergic rhinitis among the participants was 18.46% (95%CI:14.34%-22.59%). Subgroup analysis showed that the prevalence of allergic rhinitis from 2012 to 2021 (19.75%) was higher than that from 2001 to 2011 (14.81%), and the difference was statistically significant (P<0.001). The prevalence of different regions from high to low was East China (22.77%), North China (20.82%), Northwest China (17.77%), Central China (16.62%), Southwest China (16.33%), Northeast China (16.16%) and South China (7.29%) respectively, the difference was statistically significant (P<0.001). The prevalence of male (20.73%) was higher than that of female (16.34%), and the difference was statistically significant (P<0.001). The prevalence of Han nationality(17.31%) was higher than that of ethnic minorities (15.93%), and the difference was statistically significant (P<0.001). Conclusion: The prevalence of allergic rhinitis in Chinese children is high and the prevalence in children varies by publication year, region, sex and nationality.

Repeatability of vessel density measurement in human skin by OCT-based microangiography.

PURPOSE: To investigate the repeatability of vessel density measurement at human arm skin in healthy subjects with OCT-based microangiography (OMAG). METHODS: Four locations including volar wrist, volar forearm, shoulder, and volar upper arm were scanned using an optimized swept source OCT system, working at center wavelength of 1300 nm and A-line rate of 100 kHz. Three scans were acquired at each location at the same visit. Vascular images of papillary dermis, reticular dermis, and the whole dermis layer were generated with OMAG processing and automatic segmentation algorithms. The vessel density (VD) of each layer was calculated based on vascular images, and the repeatability of the VD at the same physiological location was thereafter assessed. RESULTS: Fifteen healthy volunteers were included. High repeatability of VD was found for wrist, forearm, shoulder, and upper arm (coefficient of variation (CV)=2.4, 2.7, 2.7, 2.0, and intraclass correlation coefficient (ICC)=0.906, 0.854, 0.943, 0.916 respectively). The VD measurements showed no significant difference between the four locations in any of the three layers, ie papillary layer (P=.1063), reticular layer (P=.3371), and whole dermis layer (P=.3233). CONCLUSION: Quantification of VD by using OCT/OMAG is repeatable when imaging skin tissue beds in healthy individuals.

Positive selection sites in tertiary structure of Leguminosae chalcone isomerase 1.

Isoflavonoids and the related synthesis enzyme, chalcone isomerase 1 (CHI1), are unique in the Leguminosae, with diverse biological functions. Among the Leguminosae, the soybean is an important oil, protein crop, and model plant. In this study, we aimed to detect the generation pattern of Leguminosae CHI1. Genome-wide sequence analysis of CHI in 3 Leguminosae and 3 other closely related model plants was performed; the expression levels of soybean chalcone isomerases were also analyzed. By comparing positively selected sites and their protein structures, we retrieved the evolution patterns for Leguminosae CHI1. A total of 28 CHI and 7 FAP3 (CHI4) genes were identified and separated into 4 clades: CHI1, CHI2, CHI3, and FAP3. Soybean genes belonging to the same chalcone isomerase subfamily had similar expression patterns. CHI1, the unique chalcone isomerase subfamily in Leguminosae, showed signs of significant positive selection as well as special expression characteristics, indicating an accelerated evolution throughout its divergence. Eight sites were identified as undergoing positive selection with high confidence. When mapped onto the tertiary structure of CHI1, these 8 sites were observed surrounding the enzyme substrate only; some of them connected to the catalytic core of CHI. Thus, we inferred that the generation of Leguminosae CHI1 is dependent on the positively selected amino acids surrounding its catalytic substrate. In other words, the evolution of CHI1 was driven by specific selection or processing conditions within the substrate.

Noncontact all-optical measurement of corneal elasticity.

We report on a noninvasive and noncontact all-optical method to measure the elasticity of the cornea. We use a pulsed laser to excite surface acoustic waves (SAW) that propagate on the corneal surface, then use a phase-sensitive optical coherence tomography system to remotely record the SAWs from which the corneal elasticity is estimated. In addition, the system is able to provide real-time tomographic images of the cornea being examined, an important consideration for clinical studies. While precisely maintaining a range of intraocular pressures (IOP), a series of measurements is performed on ex vivo intact primate eyes. The measurement results not only demonstrate the feasibility of the proposed system to remotely measure the corneal elasticity, but also suggest a strong correlation between the corneal stiffness and the true IOP.

Molecular evolution of two consecutive carotenoid cleavage dioxygenase genes in strigolactone biosynthesis in plants.

Strigolactones are newly discovered plant hormones that perform various functions, from signaling in symbiotic interactions with arbuscular mycorrhizal fungi to controlling outgrowth of axillary buds. We examined the phylogenetic relationships of two carotenoid cleavage dioxygenase genes (CCD7 and CCD8) that are involved in consecutive upstream steps of the proposed strigolactone biosynthesis pathway. The CCD7 and CCD8 sequences from 11 model species, divided into two clades, correspond to sequences from monocotyledons and dicotyledons. However, the sequences from the primitive moss, Physcomitrella patens, appeared to be evolutionarily distinct from those of the angiosperms. CCD7 and CCD8 are much conserved, since no significant positive selection was detected among these plants. Ks values indicated that CCD7 and CCD8 diverged about 290 to 430 million years ago. As essential genes in the strigolactone pathway, the divergence timing of the conserved CCD7 and CCD8 genes reflects the approximate time of generation of strigolactone as a regulatory substance. This timing calculation also coincides with initiation of symbiosis between plants and microorganisms, inferred from the fossil record. Molecular evolution analyses of genes in metabolic pathways can provide insight concerning gene evolution.

MicroRNA-145 inhibits proliferation and promotes apoptosis of HepG2 cells by targeting ROCK1 through the ROCK1/NF-κB signaling pathway.

OBJECTIVE: Hepatocellular carcinoma (HCC) is a malignant cancer with a high fatality rate, and the expression of microRNA-145 (miR-145) is significantly low in HCC tissue. Therefore, the effect of miR-145 on HCC was explored. PATIENTS AND METHODS: Primary hepatocellular carcinoma samples and corresponding normal samples, and HepG2 cells were analyzed using flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Real-time quantitative reverse transcription-polymerase chain reaction, Western blotting, and dual-luciferase reporter assay. RESULTS: miR-145 expression was significantly downregulated in HCC tissue and HepG2 cells as compared to normal liver tissue. After HepG2 cells were transfected with miR-145 mimics, miR-145 expression was recovered, accompanied by a significantly lower cell number, inhibition of the G1/S phase transition, and promotion of the apoptosis of HepG2 cells, as well as changes in levels of G1/S-specific cyclin-E1 (CCNE1) and activated caspase-3. Furthermore, the rho-associated protein kinase 1 (ROCK1) levels were opposite the levels of miR-145 expression in vivo and in vitro, and additional experiments with co-transfection of miR-145 mimics and pEGFP-N3-3'UTR provided the direct evidence that the ROCK1 gene is a target of miR-145. Moreover, a significant decrease or increase in the expression of ROCK1 was associated with nuclear factor-kB (NF-κB)(p65) activity, and lipopolysaccharide (LPS) significantly increased NF-κB(p65) activity, accompanied by recovery of the reduction in the number of HepG2 cells for miR-145 mimics. The NF-κB activity and cell number were significantly (p < 0.05, p < 0.01) increased in response to the overexpression of the ROCK1 gene in HepG2 cells. CONCLUSIONS: We showed that miR-145 can target and downregulate ROCK1 expression, and it controls HCC by inhibiting the cell cycle and activating apoptosis via the ROCK1/NF-κB signaling pathway. Our findings will provide a new perspective for the therapy of HCC.

Long non-coding RNA FENDRR inhibits NSCLC cell growth and aggressiveness by sponging miR-761.

OBJECTIVE: The aim of this paper is to investigate the functions of long noncoding RNA (lncRNA) FOXF1 Adjacent Non-Coding Developmental Regulatory RNA (FENDRR) in the growth and aggressiveness of non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: The expression of FENDRR in NSCLC tissues and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and colony formation assays were conducted to explore the roles of FENDRR on the growth of NSCLC cell. The wound healing and transwell invasion assays were conducted to explore the impact of FENDRR on NSCLC cell migration and invasion. The apoptosis of NSCLC cell was detected using flow cytometer-based Annexin V/Propidium Iodide (PI) dual staining. The xenograft model was conducted to investigate the effect of FENDRR on the growth of NSCLC cell in vivo. The expression of Ki67 was measured by immunohistochemical (IHC) staining using Ki67 antibody. Bioinformatics analysis and Luciferase reporter assay were applied to identify that miR-761 was the target of FENDRR. Additional, colony formation and transwell experiments were utilized to confirm that FENDRR inhibited the growth and aggressiveness of NSCLC cell by regulating miR-761. RESULTS: We found a marked down-regulation of FENDRR in NSCLC tissues compared to tumor-adjacent tissues. FENDRR down-expression was detected in four NSCLC cell lines (H1650, HCC827, H1975 and A549) compared to the human non-tumorigenic bronchial epithelial cell, BEAS-2B. Low expression of FENDRR was identified as a predictive factor for poor prognosis of patients with NSCLC. The over-regulation of FENDRR inhibited the proliferation, migration and invasion capacities of NSCLC cell and promoted the apoptosis of NSCLC cell in vitro whereas the down-regulation of FENDRR caused the opposite results. Moreover, the over-expression of FENDRR restrained the growth of NSCLC cell in vivo. We found that there were potential binding sites between FENDRR and miR-761 and the level of miR-761 was inversely associated with the expression of ENDRR in NSCLC tissues. Finally, the rescue experiments suggested that the anti-oncogenic role of FENDRR was at least partially mediated by miR-761 in NSCLC. CONCLUSIONS: We found that FENDRR was down-expressed in NSCLC and the over-expression of FENDRR inhibited the malignant phenotypes of NSCLC cell by binding to miR-761 competitively.

Chitosan microchannel scaffolds for tendon tissue engineering characterized using optical coherence tomography.

Tendon tissue engineering requires the generation of a uniaxially orientated collagen type I matrix with several organization scales that confer mechanical functionality upon the tendon. A combination of factors in a dose- and time-dependent manner, such as growth factors and mechanical environment, may be the key to an in vitro-engineered tendon. To define the progress of tissue development within a scaffold, on-line systems need to be applied to monitor the newly generated matrix. To address this challenge, we designed a new porous chitosan scaffold with microchannels (diameter: 250 microm), which allows primary porcine tenocytes to proliferate in a bundle-like structure. The cell proliferation and extracellular matrix (ECM) production within the microchannels were successfully assessed under sterile conditions using optical coherence tomography (OCT). A semi-quantitative method that calculated the microchannel occupation ratio (the degree of cell proliferation and tissue turnover based on the total backscattered intensity in the microchannels) was developed. We further investigated the effect of different culture conditions on tendon cell matrix formation. Using a perfusion bioreactor, we demonstrated how fluid flow can increase (p < 1e(3)) ECM production within the microchannels significantly more than static culture. Our study illustrates how using a guiding scaffold in combination with the fast and non-destructive assessment of the microstructure using OCT allows discrimination between the parameters affecting the production and the organization of the ECM.

Effects of age and gender on in vitro properties of human liver microsomal monooxygenases.

Aging in humans is associated with marked declines in the disposition of numerous drugs and other xenobiotics that require hepatic biotransformation before elimination. Considerable pharmacokinetic evidence in humans, coupled with data on in vitro liver microsomal monooxygenase functions generated in inbred male rodent models, has implicated impaired liver phase I drug metabolism (i.e., diminished efficacy of microsomal monooxygenases) in reduced drug clearance in the elderly. This study (1) assessed the in vitro activities and amounts of liver microsomal monooxygenases as a function of donor age and gender in healthy humans and (2) provides the most extensive and comprehensive data to date demonstrating the absence of significant age- and gender-dependent differences in the activities and contents of human liver monooxygenases.

Effects of aging and phenobarbital on the rat liver microsomal drug-metabolizing system.

Significant declines in the non-induced activities of liver microsomal drug-metabolizing enzymes and in the amount of cytochrome P-450 occur between maturity (16 months) and senescence (27 months) in male Fischer 344 rats, whereas there are essentially no differences between very young (1 month) and mature animals. Several hepatic responses to chronic phenobarbital administration also demonstrate marked age-dependent changes. The livers of young and mature animals exhibit: (1) greater hepatomegaly; (2) faster rates of induction and post-induction recovery of microsomal mixed function oxidase enzyme activities and hemoprotein concentration; and (3) higher maximally induced levels of these components in comparison to senescent rats. When considered with information from previous studies, the present data suggest that the age-related decline in liver drug metabolism may be due to qualitative and/or quantitative changes in the structural and/or functional components of the hepatic microsomal mixed function oxidase system.

Age-dependent alterations in rat liver microsomal NADPH-cytochrome c (P-450) reductase: a qualitative and quantitative analysis.

The hepatic drug-metabolizing capacities of rodents and man exhibit age-dependent declines. The extensive use of medication in geriatric patients demonstrates the need to characterize the mechanism(s) responsible for this reduced liver function. An analysis of microsomal NADPH-cytochrome c (P-450) reductase in young adult (3 months), mature (9 months) and senescent (27 months) male Fischer 344 rats revealed specific age-related qualitative and quantitative changes in this enzyme. The specific activity of the purified enzyme from young animals was two-fold higher than that recovered from the other age groups. In addition, there was: (1) no change in molecular weight, (2) alterations in heat inactivation profiles, (3) an apparent reduction in substrate affinity, and (4) a two-fold loss of enzyme activity per unit of immunoprecipitable material as a function of animal age. Our data suggest that this important liver drug-metabolizing enzyme undergoes post-translational modifications in its conformation which are reflected in the above parameters and which, ultimately, affect its efficacy.

Age-dependent alterations in the physicochemical properties of rat liver microsomes.

Aging results in a significant decline in liver drug metabolism which is largely attributable to changes in the microsomal mixed function oxidase system. For example, the mixed function oxidase system in the livers of senescent rats is characterized by: (1) a reduced cytochrome P-450 content; (2) a decline in the specific activity of NADPH-cytochrome c (P-450) reductase; and (3) a slower rate of ethylmorphine N-demethylation in comparison to young adult animals. Since several factors intrinsic to the microsomes may influence the efficacy of the mixed function oxidase system, e.g. the phospholipid and cholesterol contents, the saturation index of the fatty acids and the fluidity of the membranes, we conducted a physicochemical analysis of liver microsomes isolated from young adult (3-4 months), mature (12-16 months) and senescent (25-27 months) male Fischer rats. Although the microsomal cholesterol content did not change appreciably between maturity and senescence, there was a marked decline in the total phospholipid content. This resulted in a significant increase in the cholesterol/phospholipid ratio, 0.49 to 0.65 between 16 and 27 months of age. The age-related changes in the total phospholipid content were largely reflected in each of the major fractions, i.e. phosphatidylcholine, phosphatidylinositol and phosphatidylethanolamine + phosphatidylserine. Small increases in the relative percentages of highly unsaturated fatty acid species were offset by similar decreases in the more frequent and more saturated species as a function of increased age. As a result, the net change in the fatty acid saturation index was probably minimal. However, the increase in the cholesterol/phospholipid ratio most likely contributes to the significant decline in the order parameter of microsomes isolated from old rats which, in turn, may impair the functional capacity of the hepatic mixed function oxidase system.

Age-dependent changes in rat liver microsomal NADPH cytochrome C (P-450) reductase: a kinetic analysis.

Rat liver microsomal NADPH cytochrome c (P-450) reductase (EC 1.6.2.4) exhibits several marked age-dependent changes, including a decline in specific activity, reduced inducibility and enhanced thermostability, which are indicative of an alteration in the quality of this enzyme. The present study examined the kinetic profile of the microsomal-bound enzyme in an effort to further define the effects of aging on the hepatic mixed function oxidase system. Intact microsomes isolated from young adult (3 months), mature (16 months) and senescent (27 months) rats were subjected to an extensive double reciprocal kinetic analysis employing NADPH and cytochrome c as substrates. The Km values obtained with the initial substrate (NADPH) remained unchanged with animal age, whereas there was a decline in this parameter for the artificial acceptor substrate, cytochrome c. The Vmax values for both substrates were reduced as a function of increasing age, perhaps reflecting a concomitant decline in the relative amount(s) of efficient reductase in the microsomes.

Aging effects on hepatic NADPH cytochrome P450 reductase, CYP2B1&2, and polymeric immunoglobulin receptor mRNAs in male Fischer 344 rats.

Aging perturbs the expression of many liver proteins, but the mechanisms remain unresolved. Expression of hepatic NADPH cytochrome P450 reductase, phenobarbital-induced CYP2B1&2, and the polymeric immunoglobulin receptor (pIgR) decline as a function of aging. We examined the effect of aging on the expression of the mRNA transcripts of these proteins, as well as those of alpha 2u-globulin and beta-actin in male F344 rats. Despite age-related losses in the expression of P450 reductase and plasma membrane-bound pIgR in the rat liver (approximately 30-50%), aging is is accompanied by 1) no change and 2) a modest decline (< 20%) in their respective mRNA steady state levels. On the other hand, the expression of phenobarbital-induced microsomal CYP2B1&2 and the steady state level of its mRNA exhibit parallel age-dependent shifts. The mRNA transcript for alpha 2u-globulin declines between maturity and old age, whereas the beta-actin mRNA level remains unchanged. These preliminary data are consistent with previous studies which suggest that aging may perturb hepatic CYP2B1&2 and alpha 2u-globulin at the transcriptional level, whereas changes in the expression of P450 reductase and pIgR may reflect posttranscriptional modifications.

Doppler optical coherence tomography for measuring flow in engineered tissue.

The engineering of human tissue represents a major paradigm shift in clinical medicine. Early embodiments of tissue engineering are currently being taken forward to the clinic by production methods that are essentially extensions of laboratory manual procedures. However, to achieve the status of routine large-scale clinical practice, automation and scale-out processes are required. This in turn will require the development of reliable on-line monitoring and control systems. This paper examines one demand of crucial importance, namely the real time in vitro monitoring of the flow characteristics through growing tissue since this has a complex interrelationship. Doppler optical coherence tomography (DOCT) is a recently developed imaging technique for studying the rheological properties of tissues in vivo. Capable of non-invasive imaging in real time with high resolution, it is potentially ideal for the continuous monitoring of engineered tissues in vitro. As a base line, the current status of DOCT in vivo is therefore reviewed. This paper also reports the first preliminary use of DOCT in tissue engineering. The application described involves the imaging of a fully developed laminar flow through a combined tissue fabrication/bioreactor with a tissue-engineered construct (substitute blood vessel) in situ.

The potential of optical coherence tomography in the engineering of living tissue.

The better repair of human tissue is an urgent medical goal and in order to achieve a safe outcome there is a parallel need for sensitive, non-invasive methods of assessing the quality of the engineered tissues and organs prior to surgical implantation. Optical coherence tomography (OCT) can potentially fulfil this role. The current status of OCT as an advanced imaging tool in clinical medicine, developmental biology and material science is reviewed and the parallels to the engineering of living tissue and organs are discussed. Preliminary data are also presented for a tissue engineering bioreactor with in situ OCT imaging. The data suggest that OCT can be utilized as a real time, non-destructive, non-invasive tool to critically monitor the morphology of tissue-engineered constructs during their fabrication and growth.

[Antagonizing effect of sodium ferulate on the changes of hepatic antioxidative function induced by ethanol in mice].

Effects of ethanol at different dosages on hepatic antioxidative and detoxicating functions and the antagonizing effect of sodium ferulate have been investigated in mice. The data showed that ethanol (11.4 g.kg-1, ig) could induce the increase of hepatic glutathione peroxidase (GSH-Px) activity and decreases of hepatic glutathione reductase (GSH-Re), superoxide dismutase (SOD) and glutathione S-transferase (GST) activities and reduce glutathione (GSH) content. At the same time, serum GST activity was increased. Pretreatment with sodium ferulate (100 mg.kg-1 ig, qd x 10 d) completely reversed these changes induced by ig ethanol in mice, indicating that sodium ferulate could protect mice from ethanol-induced acute hepatotoxicity. The hepato-protective mechanism of sodium ferulate may be related to intensification of the function of glutathione oxidative-reductive enzymes, enhancement of SOD activity and promotion of glutathione conjugation. The results also indicate that the serum GST level is a sensitive indicator in ethanol-induced hepatotoxicity.