WTAP-mediated N6-methyladenosine modification promotes the inflammation, mitochondrial damage and ferroptosis of kidney tubular epithelial cells in acute kidney injury by regulating LMNB1 expression and activating NF-κB and JAK2/STAT3 pathways.

Acute kidney injury (AKI) is a serious complication of sepsis patients, but the pathogenic mechanisms underlying AKI are still largely unclear. In this view, the roles of the key component of N6-methyladenosine (m6A)-wilms tumor 1 associated protein (WTAP) in AKI progression were investigated. AKI mice model was established by using cecal ligation and puncture (CLP). AKI cell model was established by treating HK-2 cells with LPS. Cell apoptosis was analyzed by TdT-mediated dUTP Nick-End Labeling (TUNEL) staining and flow cytometry analysis. Cell viability was analyzed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The concentrations of inflammatory factors were examined with ELISA kits. Reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) and Fe2+ levels were detected with related kits. Gene expression was detected by western blot assay or quantitative real-time polymerase chain reaction (qRT-PCR) assay. The relation between WTAP and lamin B1 (LMNB1) was verified by Methylated RNA Immunoprecipitation (meRIP) assay, RIP assay, dual-luciferase reporter assay and Actinomycin D assay. CLP induced significant pathological changes in kidney tissues in mice and promoted inflammation, mitochondrial damage and ferroptosis. LMNB1 level was induced in HK-2 cells by LPS. LMNB1 knockdown promoted LPS-mediated HK-2 cell viability and inhibited LPS-mediated HK-2 cell apoptosis, inflammation, mitochondrial damage and ferroptosis. Then, WTAP was demonstrated to promote LMNB1 expression by m6A Methylation modification. Moreover, WTAP knockdown repressed LPS-treated HK-2 cell apoptosis, inflammation, mitochondrial damage and ferroptosis, while LMNB1 overexpression reversed the effects. Additionally, WTAP affected the pathways of NF-κB and JAK2/STAT3 by LMNB1. WTAP-mediated m6A promoted the inflammation, mitochondrial damage and ferroptosis in LPS-induced HK-2 cells by regulating LMNB1 expression and activating NF-κB and JAK2/STAT3 pathways.

Advances in the ocular complications after hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) has benefited an increasing number of patients with hematological disease in the clinic. It is a curative therapy for malignant and nonmalignant hematological diseases. With the advancement and further clinical application of HSCT in recent years, the life expectancy of patients has increased, but complications have become more common. The occurrence of ocular complications is receiving increasing attention because they can seriously affect the quality of life of patients. Ocular complications require increased attention from clinicians because of their negative impact on patients and increasing incidence. Most of recent reports on posttransplant ocular complications involve ocular manifestations of graft-versus-host disease (GVHD), and a few ocular complications that do not originate from GVHD have also been reported. This review summarizes the diagnosis, scoring criteria, pathophysiology, and clinical manifestations of and common therapies for ocular graft-versus-host disease(oGVHD) after HSCT, and includes a description of some rare cases and novel therapies.

Multiple iodide autocatalysis paths of chemo-hydrodynamical patterns in the Briggs-Rauscher reaction.

Autocatalytic feedback is often regarded as the core step for the chemo-hydrodynamical patterns in the nonlinear reaction system. The Briggs-Rauscher (BR) reaction shows sequential chemo-hydrodynamical patterns with three states, i.e. labyrinth, high iodine state, and rotating dendritic patterns. The short-lived labyrinth patterns, depending on [Mn2+]0, the ratio of [CH2(COOH)2]0 and [KIO3]0 and light intensities, result from iodide autocatalytic loop, which has three paths (involving Mn2+-induced radical reactions, the oxidation of iodomalonic compounds, and light-induced radical reactions, respectively). The high iodine state appears in a high ratio of [CH2(COOH)2]0 and [KIO3]0, relating to the autocatalytic path involving the oxidation of iodomalonic compounds. The light-induced radical autocatalytic path can act as a convenient control parameter to modulate the patterns in the first stage by increasing the iodine radicals. The dendritic patterns in the third stage result from the Marangoni effect caused by the evaporation of the solutions and reactions between H2O2 and iodine-containing species, which is independent of [CH2(COOH)2]0 and [Mn2+]0. This work contributes to a better understanding of the complex spatiotemporal patterns in the chemo-hydrodynamical system.

The absence of CsdA in Escherichia coli increases DNA replication and cell size but decreases growth rate at low temperature.

The CsdA protein is a highly conserved, DEAD-box RNA helicase and assists RNA structural remodeling at low temperature. We show that the fast-growing wild-type (WT) cells contain higher number of replication origins per cell with bigger cell size and the slowly growing cells possess less number of replication origins per cell with smaller cell size. The absence of CsdA leads to production of larger cells with higher number of origins per cell but slower growth at low temperature in an independent-manner of growth media. The phenotypes in ΔcsdA mutant are reversed by ectopic expression of CsdA or RNase R. A global transcription analysis shows that the absence of CsdA leads to significant decreases in transcription of about 200 genes at low temperature. These genes are associated with essential metabolic pathways, flagger assembly and cell division (minDE). It is likely that the slow growth of ΔcsdA cell results from the decreased transcription of essential metabolic genes, and the larger ΔcsdA cell could be a result of decreased transcription of minDE. The increased transcription of the nrdHIEF genes in ΔcsdA mutant is a likely reason that promotes DNA replication. We conclude that CsdA coordinates the cell cycle to growth by stabilizing mRNA of essential metabolic and cell division genes and degrading mRNA for nucleotide metabolic genes at low temperature.

Suicide attempt rate and the risk factors in young, first-episode and drug-naïve Chinese Han patients with major depressive disorder.

BACKGROUND: In recent years, the rates of suicide among young people have been increasing, and major depressive disorder (MDD) is regarded to be its main cause. Many factors such as thyroid dysfunction and metabolic abnormalities are thought to mediate this process, but the conclusions are inconsistent. This study investigated the rate of suicide attempts and associated risk factors among young, first-episode and drug-naïve Chinese Han patients with MDD. METHODS: A total of 917 patients with MDD (aged 18 ~ 35 years) were recruited. Demographic and clinical data were collected and thyroid function, fasting blood glucose and lipid profiles were measured. The Hamilton Depression Rating Scale-17 items (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), positive symptom subscale of Positive and Negative Syndrome Scale (PANSS) and clinical global impression of severity scale (CGI-S) were adopted to assess depression, anxiety, psychotic symptoms and disease severity respectively. RESULTS: The rate of suicide attempts was 19.5% in young MDD patients. There were significant differences in age (p = 0.003), education level (p = 0.001), age of onset (p = 0.004) and disease duration (p = 0.001) between patients with and without suicide attempts. Compared with patients without suicide attempts, patients with suicide attempts had significantly higher scores on the HAMD-17, HAMA, PANSS positive symptom subscale and CGI-S (all p < 0.001). Patients with suicide attempts had significantly higher levels of TSH (p < 0.001), TgAb (p = 0.004), TPOAb (p < 0.001), TG (p = 0.016), TC (p < 0.001), LDL (p < 0.001), and fasting glucose (p < 0.001), but significantly lower levels of HDL (p < 0.001). Logistic regression analysis showed that marital status (OR = 0.515, 95%CI: 0.280-0.950, p = 0.515), disease duration (OR = 1.100, 95%CI: 1.013-1.194, p = 0.024), HAMA score (OR = 1.313, 95%CI: 1.205-1.430, p < 0.001), CGI-S score (OR = 1.875, 95%CI: 1.339-2.624, p < 0.001), levels of FT3(OR = 0.717, 95%CI: 0.536-0.959, p = 0.025), TPOAb (OR = 1.004, 95%CI: 1.002-1.006, p < 0.001), TC (OR = 1.330, 95%CI: 1.011-1.750, p = 0.042) and LDL (OR = 0.736, 95%CI: 0.558-0.971, p = 0.030) were all independently associated with suicide attempts in young MDD patients. CONCLUSIONS: In China, the rate of suicide attempts in young patients with MDD is quite high and thyroid dysfunction and metabolic abnormalities may be implicated in its pathogenesis.

Molecular mechanism of benzo [a] pyrene regulating lipid metabolism via aryl hydrocarbon receptor.

BACKGROUND: Benzo [a] pyrene (BaP), a potent carcinogen, has been proved that it has toxicological effects via activation the aryl hydrocarbon receptor (AhR) pathway. AhR can participate in regulating lipogenesis and lipolysis. This topic will verify whether BaP regulates lipid metabolism via AhR. METHODS: (1) C57BL/6 mice were gavaged with BaP for 12 weeks to detect serum lipids, glucose tolerance, and insulin resistance. Morphological changes in white adipose tissue (WAT) were detected by Hematoxylin and Eosin staining. The mRNA expression levels of adipogenesis-related factors included recombinant human CCAAT/enhancer binding protein alpha (C/EBPα), peroxisome proliferator-activated receptor gamma (PPARγ), and fatty acid binding protein 4 (FABP4) and inflammatory factors included nuclear factor kappa-B (NF-κB), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-α) were detected using PCR. (2) Neutral lipid content changes in differentiated 3 T3-L1 adipocytes treated with BaP with and w/o AhR inhibitor were detected by Oil red staining. The protein expression levels of adipogenesis- and decomposition-related factors included PPARγ coactivator-1 alpha (PGC-1α), and peroxisome proliferation-activated receptor alpha (PPARα) were detected using western blotting. The mRNA expression levels of inflammatory factors were detected using PCR. RESULTS: (1) BaP inhibited body weight gain, decreased lipid content, increased lipid levels, and decreased glucose tolerance and insulin tolerance in mice; (2) BaP reduced the expressions of C/EBPα, PPARγ, FABP4, PGC-1α, and PPARα and increased the expressions of NF-κB, MCP-1, and TNF-α by activating AhR. CONCLUSION: BaP inhibit fat synthesis and oxidation while inducing inflammation by activating AhR, leading to WAT dysfunction and causing metabolic complications.

Modulation Effects of Permanganate and Manganese(II) Ions on the Oscillatory Dynamics in a Bromate-Sulfite Reaction System.

It is important to study nonlinear dynamical systems showing pH and temperature oscillations simultaneously. Here, we systematically investigated the bromate-sulfite reaction in its coupled system. Large-amplitude temperature oscillations could be measured accompanied by the pH oscillations with or without permanganate and manganese(II) ions. The modulation effects on the oscillatory dynamics of the bromate-sulfite reaction system produced by permanganate and manganese(II) ions were investigated in detail. On the one hand, with permanganate, an additional negative pH feedback process between permanganate and bisulfite occurs, leading to weakening the pH positive feedback. The above opposite effects make the period length change unmonotonically when adjusting the permanganate concentration and flow rate. On the other hand, with Mn2+ as the feedback agent, the nonmonotonic change of period was not obvious because it only contained one feedback loop, which can only reinforce negative feedback without affecting positive feedback.

Association of Thiamine Intake with Human Papillomavirus (HPV) Infection in American Women: A Secondary Data Analysis Based on the National Health and Nutrition Examination Survey from 2003 to 2016.

BACKGROUND Studies have shown that thiamine intake is associated with cervical cancer, but the relationship between thiamine and HPV infection remains unclear. In the present study, we used the National Health and Nutrition Examination Survey (NHANES) database to investigate whether HPV infection was associated with thiamine intake. MATERIAL AND METHODS A total of 13 471 women ages 18-59 years were selected from the NHANES database from 2003 to 2016. Using thiamine intake as the independent variable, HPV infection as the dependent variable, and sociodemographic data and other data as the covariates, we analyzed the relationship between thiamine and HPV infection by conducting a weighted logistic regression model in a cross-sectional research design. RESULTS The two-piecewise linear model indicated the inflection point of thiamine intake was 2.07 mg. On the left side of the inflection point, the difference in the thiamine intake of log2 conversion was related to the difference of 0.82 in HPV infection, which means that the increase of every 1 unit increase in thiamine intake is associated with the decrease of the HPV infection by 18%. On the right side of the inflection point, we did not observe a correlation between HPV infection and thiamine intake. CONCLUSIONS Thiamine intake is negatively correlated with HPV infection. Intake of an appropriate amount of thiamine can prevent HPV infection. The best preventive effect can be achieved when the intake is about 2 mg, and excessive intake will not increase the preventive effect.

Association of Menstrual Extension and Surgery Effectiveness with Ultrasound Parameters of Cesarean Section Scar Diverticulum in Patients Undergoing Transvaginal Uterine Diverticulum Repair.

The association of residual myometrium thickness (RMT) and scar defect depth (D) with menstrual abnormalities and the effectiveness of vaginal repair remain to be determined in patients with cesarean section scar diverticulum (CSD). To assess the value of ultrasound to predict vaginal repair effectiveness. This was a retrospective study of patients with CSD treated with vaginal repair between 01/2014 and 02/2016 at Shanghai First Maternity and Infant Hospital (Tongji University). Transvaginal ultrasound was performed before and 3 months after surgical repair. RMT, D, scar defect length (L), and scar defect width (W) were measured. Width (W), D, and L increased along the duration of menstrual period (P < 0.05). When the menstrual extension time was ≥15 days, RMT/D and RMT/(RMT + D) were smaller than in patients with period <15 days (P < 0.05). L was the most positively correlated ultrasonic parameter with menstrual prolongation (r = 0.492). RMT/D and RMT/(RMT + D) were negatively correlated with prolonged menstruation (r = -0.304 and -0.305, respectively). RMT/D and RMT/(RMT + D) were associated with the disappearance of CSD after vaginal repair (P < 0.05). The cutoff value of RMT/(RMT + D) was 0.496, with sensitivity of 53.0% and specificity of 61.4%. L of CSD is closely correlated with menstrual extension but has no relationship with the effectiveness of surgery. RMT/(RMT + D) is correlated with menstrual extension time ≥15 days and the effectiveness of vaginal repair.

Ketamine delays progression of oxidative and damaged cataract through regulating HMGB-1/NF-κB in lens epithelial cells.

OBJECTIVE: Lens epithelial cell (LEC) membrane damage is one of the pathogenesis of cataract. High mobility group box-1 (HMGB-1) and nuclear factor-κB (NF-κB) play vital roles in a variety of diseases, such as inflammation. Ketamine has numerous pharmacological effects that can inhibit inflammation. However, its role in cataract rats LECs has not yet been elucidated. MATERIALS AND METHODS: LECs were isolated from SD rats and cultured in vitro. The cells were randomly divided into three groups, including the control group, cataract model group induced by H2O2, and ketamine group treated by 10 mM ketamine under H2O2 environment. LECs proliferation was assessed by MTT assay. LECs apoptosis was evaluated by Caspase-3 activity detection. NF-κB mRNA and protein expressions were tested by real-time PCR and Western blot. HMGB-1 expressions in cells and supernatant were detected by real-time PCR and ELISA. TNF-α and IL-1ß secretions were detected by ELISA. RESULTS: In H2O2 model group, the LECs proliferation was significantly inhibited, the caspase-3 activity significantly increased, HMGB-1 mRNA and secretion significantly enhanced, NF-κB mRNA and protein levels significantly elevated, compared to the Control group (p < .05). While the TNF-α and IL-1ß secretions significantly up-regulated in H2O2 model group compared to the Control group (p < .05). Ketamine significantly promoted the LECs proliferation, significantly reduced the caspase-3 activity, and significantly declined the HMGB expression compared to H2O2 model group (p < .05). The NF-κB mRNA and protein levels were significantly decreased, TNF-α and IL-1ß secretions were significantly decreased in the Ketamine group compared with the model group (p < .05). CONCLUSIONS: Ketamine delays the progression of oxidative and damaged cataract by regulating HMGB-1/NF-κB expression, inhibiting TNF-α, IL-1ß, and apoptosis, and promoting cell proliferation.

Design of Acceptors with Suitable Frontier Molecular Orbitals to Match Donors via Substitutions on Perylene Diimide for Organic Solar Cells.

A series of perylene diimide (PDI) derivatives have been investigated at the CAM-B3LYP/6-31G(d) and the TD-B3LYP/6-31+G(d,p) levels to design solar cell acceptors with high performance in areas such as suitable frontier molecular orbital (FMO) energies to match oligo(thienylenevinylene) derivatives and improved charge transfer properties. The calculated results reveal that the substituents slightly affect the distribution patterns of FMOs for PDI-BI. The electron withdrawing group substituents decrease the FMO energies of PDI-BI, and the electron donating group substituents slightly affect the FMO energies of PDI-BI. The di-electron withdrawing group substituents can tune the FMOs of PDI-BI to be more suitable for the oligo(thienylenevinylene) derivatives. The electron withdrawing group substituents result in red shifts of absorption spectra and electron donating group substituents result in blue shifts for PDI-BI. The -CN substituent can improve the electron transport properties of PDI-BI. The -CH3 group in different positions slightly affects the electron transport properties of PDI-BI.

Molecular characterization and serological reactivity of a vacuolar ATP synthase subunit ε-like protein from Clonorchis sinensis.

The vacuolar ATPase enzyme complex (V-ATPase) pumps protons across membranes, energized by hydrolysis of ATP. Extensive investigations on structural and biochemical features of these molecules have implied their importance in the physiological process. In this study, a full-length sequence encoding a vacuolar ATP synthase subunit ε-like protein of Clonorchis sinensis (CsATP-ε) was isolated from our cDNA library. The hypothetical 226 amino acid sequence shared 76% identity with ATP-ε proteins of Schistosoma japonicum and above 55% identity with ATP-ε proteins from human and other eukaryotes. Characteristic Asp140 amino acid residues and seven B-cell epitopes were predicted in this sequence. The complete coding sequence of the gene was expressed in Escherichia coli. Recombinant CsATP-ε (rCsATP-ε) protein could be probed by anti-rCsATP-ε rat serum and C.sinensis-infected human serum in Western blotting experiment, indicating that it is an antigen of strong antigenicity. The high level of antibody titers (1:204,800) showed that CsATP-ε has a powerful immunogenicity. Both the increased level and the change trend of IgG1/IgG2a subtypes in serum showed that the rCsATP-ε can induce strong combined Th1/Th2 immune responses in rats and stimulate the immune response changes to the dominant Th2 from Th1 along with long time infection. The results of immunoblot and immunolocalization demonstrated that CsATP-ε was consecutively expressed at various developmental stages of the parasite, which was supported by real-time PCR analysis. In immunohistochemistry, CsATP-ε was localized on the intestine, vitellarium, and testicle of an adult worm and excretory bladder of metacercaria, implying that CsATP-ε may relate to energy intake and metabolism. This fundamental study would contribute to further researches that are related to growth and development and immunomodulation of C. sinensis.

Identification, sequence analysis, and characterization of serine/threonine protein kinase 17A from Clonorchis sinensis.

This is the first report of a novel protein from Clonorchis sinensis (C. sinensis), serine/threonine protein kinase 17A (CsSTK17A), which belongs to a member of the death-associated protein kinase (DAPK) family known to regulate diverse biological processes. The full-length sequence encoding CsSTK17A was isolated from C. sinensis adult cDNA plasmid library. Two transcribed isoforms of the gene were identified from the genome of C. sinensis. CsSTK17A contains a kinase domain at the N-terminus that shares a degree of conservation with the DAPK families. Besides, the catalytic domain contains 11 subdomains conserved among STKs and shares the highest identity with STK from Schistosoma mansoni (55.9%). Three-dimensional structure of CsSTK17A displays the canonical STK fold, including the helix C, P-loop, and the activation loop. We obtained recombinant CsSTK17A (rCsSTK17A) and anti-rCsSTK17A IgG. The rCsSTK17A could be probed by anti-rCsSTK17A rat serum, C. sinensis-infected rat serum and the sera from rats immunized with C. sinensis excretory-secretory products, indicating that it is a circulating antigen possessing a strong immunocompetence. Moreover, quantitative RT-PCR and western blotting analyses revealed that CsSTK17A exhibited the highest mRNA and protein expression level in eggs, followed by metacercariae and adult worms. Intriguingly, in the immunolocalization assay, CsSTK17A was intensively localized to the operculum region of eggs in uterus, as well as the vitelline gland of both adult worm and metacercaria, implying that the protein was associated with the reproduction and development of C. sinensis. Overall, these fundamental studies might contribute to further researches on signaling systems of the parasite.

Characterization of the secreted cathepsin B cysteine proteases family of the carcinogenic liver fluke Clonorchis sinensis.

Clonorchis sinensis excretory/secretory products (ESP) have gained high attentions because of their potential to be vaccine candidates and drug targets in C. sinensis prevention. In this study, we extensively profiled the characteristics of four C. sinensis cathepsin B cysteine proteases (CsCB1, CsCB2, CsCB3, and CsCB4). Bioinformatics analysis showed all CsCBs contained signal peptides at the N-terminal. Functional domains and residues were found in CsCB sequences. We expressed four CsCBs and profiled immune responses followed by vaccine trials. Recombinant CsCBs could induce high IgG titers, indicating high immunogenicity of CsCB family. Additionally, ELISA results showed that both IgG1 and IgG2a levels apparently increased post-immunization with all four CsCBs, showing that combined Th1/Th2 immune responses were triggered by CsCB family. Both Real-time polymerase chain reaction (RT-PCR) and Western blotting confirmed that four CsCBs have distinct expression patterns in C. sinensis life stages. More importantly, we validated our hypothesis that CsCBs were C. sinensis excretory/secretory products. CsCBs could be recognized by C. sinensis-infected sera throughout the infection period, indicating that secreted CsCBs are immune triggers during C. sinensis infection. The protective effect was assessed by comparing the worm burden and egg per gram (EPG) between CsCB group and control group, showing that worm burden (P < 0.01) and EPG (P < 0.01) in CsCB2 and CsCB3 groups were significantly lower than in control group. In conclusion, we profiled secreted cathepsin B cysteine proteases family for the first time and demonstrated that all CsCB family were C. sinensis excretory/secretory products that may regulate host immune responses.

Genome and transcriptomic analysis of the adaptation of Escherichia coli to environmental stresses.

In natural niches, bacteria are forced to spend most of their lives under various environmental stresses, such as nutrient limitation, heavy metal pollution, heat and antibiotic stress. To cope with adverse environments, bacterial genome can during the life cycle, produce potential adaptive mutants. The genomic changes, especially mutations, in the genes that encode RNA polymerase and transcription factors, might lead to variations in the transcriptome. These variations enable bacteria to cope with environmental stresses through physiological adaptation in response to stress. This paper reviews the recent contributions of genomic and transcriptomic analyses in understanding the adaption mechanism of Escherichia coli to environmental stresses. Various genomic changes have been observed in E. coli strains in laboratory or under natural stresses, including starvation, heavy metals, acidic conditions, heat shock and antibiotics. The mutations include slight changes (one to several nucleotides), deletions, insertions, chromosomal rearrangements and variations in copy numbers. The transcriptome of E. coli largely changes due to genomic mutations. However, the transcriptional profiles vary due to variations in stress selections. Cellular adaptation to the selections is associated with transcriptional changes resulting from genomic mutations. Changes in genome and transcriptome are cooperative and jointly affect the adaptation of E. coli to different environments. This comprehensive review reveals that coordination of genome mutations and transcriptional variations needs to be explored further to provide a better understanding of the mechanisms of bacterial adaptation to stresses.

Rapid and reliable ratiometric fluorescence detection of nitro explosive 2,4,6-trinitrophenol based on a near infrared (NIR) luminescent Zn(II)-Nd(III) nanoring.

Rapid and quantitative detection of 2,4,6-trinitrophenol (TNP) is very crucial for homeland security, military application, and environment protection. Herein, a nine-metal Zn(II)-Nd(III) nanoring 1 with a diameter of 2.3 nm was constructed by the use of a long-chain Schiff base ligand, which shows ratiometric fluorescence response to TNP with high selectivity and sensitivity. The fluorescence sensing behavior of 1 to TNP is expressed by a first-order equation I1060nm/I560nm = -0.0128*[TNP] + 0.9723, which can be used to quantitatively analyze TNP concentrations in solution. The limits of detection (LODs) to TNP based on the ligand-centered (LC) and Nd(III) emissions of 1 are 5.93 µM and 3.18 µM, respectively. The fluorescence response mechanism to TNP is attributed to the competitive absorption effect and photoinduced electron transfer (PET). The luminescence quenching of 1 is dominated by static process.

Expression levels of ADAMTS 5, 9, and 12 in endometrial polyps and their predictive value for the diagnosis and recurrence of endometrial polyps.

PURPOSE: Endometrial polyps (EPs) are common gynecological disorders for which no clear etiology has been found. ADAMTS have been associated with a variety of diseases. This study aimed to investigate the potential correlation between serologic levels of ADAMTS 5, 9, and 12 in patients with EPs. METHODS: A total of 88 patients were categorized into two groups: the EPs group, consisting of recurrent EPs and first occurrence EPs, and a control group. The study compared the general information and serum levels of ADAMTS 5, 9, and 12 between the groups. RESULTS: Regarding the general data, a statistically significant age difference (p < 0.05) was observed, while no significant differences were found in the other variables. After considering age as a confounding factor, the previously observed statistical significance in the differences of ADAMTS5 and 9 between the groups diminished. However, it was found that the concentrations of ADAMTS12 in both the EPs group and the recurrent EPs group were significantly higher compared to the control group and the first occurrence EPs group (p < 0.05). ROC curves were generated to determine the critical values of ADAMTS12 for predicting EPs and recurrent EPs, which were found to be 0.6962 ng/ml (sensitivity: 100 %, specificity: 39.5 %) and 0.8768 ng/ml (sensitivity: 75.0 %, specificity: 76.3 %), respectively. CONCLUSION: Our findings revealed elevated serologic levels of ADAMTS12 in the EPs group, particularly in the recurrent EPs group. Furthermore, ADAMTS-12 was identified as a valuable biomarker for assisting in the diagnosis and prediction of EPs recurrence.

Multifunctional electrospun polycaprolactone/chitosan/hEGF/lidocaine nanofibers for the treatment of 2 stage pressure ulcers.

In this study, a multifunctional nanofiber dressing that can promote antibacterial, analgesic and healing was prepared by electrospinning technology. Hydrophobic polycaprolactone (PCL)/chitosan (CS)/lidocaine hydrochloride (LID) and epidermal growth factor (EGF) were used as scaffold materials and dissolved in trifluoroacetic acid to prepare spinning solution. The morphology of PCEL dressing was observed by scanning electron microscopy. The fiber structure was dense and the average diameter was 297.0 nm. The water absorption capacity test and water contact angle measurement showed that the fiber had good water absorption and hydrophilicity (1302 %, 139.258°). Drug release was 84 % within 60 h. In the results of antibacterial experiment, the dressing showed certain antibacterial properties. The results of cell experiments show that the dressing can promote cell proliferation. In addition, coagulation experiments showed that the dressing could quickly coagulate the blood within 4 min. In addition, PCEL dressing promoted collagen deposition and vascularization through animal models of pressure sores. Therefore, multifunctional dressing can be used as an ideal auxiliary means for the treatment of pressure sores, and it is a promising alternative to chronic wound healing.

The mir-199b-5p encapsulated in adipocyte-derived exosomes mediates radioresistance of colorectal cancer cells by targeting JAG1.

Radiotherapy is a key treatment option for colorectal cancer, but its efficacy varies among patients. Our previous studies suggested that adipose tissue may confer the radioresistance of several abdominal tumors, such as pancreatic cancer, biliary cancer, and others. In the present work, the effects of adipocytes in regulating the radiosensitivity of colorectal cancer are explored for the first time. It was found that colony formation was increased and radiation-induced apoptosis decreased in colorectal cancer cells HCT8 and HCT116 co-cultured with adipocytes, which verified the mediation of adipocyte-driven radioresistance in colorectal cancer in vitro. Next, the colorectal cancer cells were incubated with adipocyte-derived exosomes, and a perceptible reduction in radiosensitivity was detected. Furthermore, to investigate the possible mechanisms involved, the exosomes were isolated, the encapsulated microRNAs were extracted and analyzed by small RNA sequencing. Based on bioinformatics analysis and qRT-PCR verification, miR-199b-5p was chosen for functional annotation. It was shown that miR-199b-5p expression was significantly upregulated after 6 Gy irradiation, and overexpressed miR-199b-5p significantly suppressed the radiosensitivity of HCT8 and HCT116 cells. In addition, jagged canonical Notch ligand 1(JAG1) was identified as the target gene of miR-199b-5p by using bioinformatics prediction and dual luciferase reporter gene assay. It was demonstrated that JAG1 conferred the radioresistance of colorectal cancer cells both in vivo and in vitro. Taken together, the present study demonstrates that adipocytes trigger the radioresistance of colorectal cancer cells, probably by targeting JAG1 through an adipocyte-derived exosomal miR-199b-5p.

Identification of disease-specific genes related to immune infiltration in nonalcoholic steatohepatitis using machine learning algorithms.

To identify disease signature genes associated with immune infiltration in nonalcoholic steatohepatitis (NASH), we downloaded 2 publicly available gene expression profiles, GSE164760 and GSE37031, from the gene expression omnibus database. These profiles represent human NASH and control samples and were used for differential genes (DEGs) expression screening. Two machine learning methods, the Least Absolute Shrinkage and Selection Operator regression model and Support Vector Machine Recursive Feature Elimination, were used to identify candidate disease signature genes. The CIBERSORT deconvolution algorithm was employed to analyze the infiltration of 22 immune cell types in NASH. Additionally, we constructed a NASH cell model using HepG2 cells treated with oleic acid and free fatty acids. The construction of the cell model was verified using oil red O staining, and Western blotting was used to detect the protein expression of the disease signature genes in both control and model groups. As a result, a total of 262 DEGs were identified. These DEGs were primarily associated with metal ion transmembrane transporter activity, sodium ion transmembrane transporter protein activity, calcium ion, and neuroactive ligand-receptor interactions. FOS, IGFBP2, dual-specificity phosphatase 1 (DUSP1), and IKZF3 were identified as disease signature genes of NASH by the least absolute shrinkage and selection operator and Support Vector Machine Recursive Feature Elimination algorithms for DEGs analysis. The receiver operating characteristic curves showed that FOS, IGFBP2, DUSP1, and IKZF3 had good diagnostic value (area under receiver operating characteristic curve > 0.8). These findings were validated in the GSE89632 dataset and through cellular assays. Immunocyte infiltration analysis revealed that NASH was associated with CD8 T cells, CD4 T cells, follicular helper T cells, resting NK cells, eosinophils, regulatory T cells, and γδ T cells. The FOS, IGFBP2, DUSP1, and IKZF3 genes were specifically associated with follicular helper T cells. Lipid droplet aggregation significantly increased in HepG2 cells treated with oleic acid and free fatty acids, indicating successful construction of the cell model. In this model, the expression of FOS, IGFBP2, and DUSP1 was significantly decreased, while that of IKZF3 was significantly elevated (P < .01, P < .001) compared with the control group. Therefore, FOS, IGFBP2, DUSP1, and IKZF3 can be considered as disease signature genes associated with immune infiltration in NASH.