Clinical efficacy and safety evaluation of Dermatophagoides farinae drops in the treatment of allergic rhinitis with epistaxis.

Summary: Background. Epistaxis is frequently observed in allergic rhinitis (AR) patients. However, few studies focus on the outcome of epistaxis with treatment of AR patients. This study aimed to retrospectively analyze the efficacy and safety of AR patients with epistaxis treated with sublingual immunotherapy (SLIT). Methods. A total of 74 patients aged 4-60 years with house dust mite (HDM)-induced AR accompanied by epistaxis and who completed 1 year of SLIT treatment with standard Dermatophagoides farinae (D. farinae) drops were enrolled in this study. The symptom scores, total medication scores (TMS), combined symptom and medication score (CSMS), visual analog scales (VAS), and bleeding score (BS) were assessed, as well as the nasal endoscopic examinations were performed to observe nasal signs. Results. The levels of symptom scores, TMS, CSMS, VAS, and BS at 0.5 year and 1 year of SLIT treatment were significantly lower than those at the baseline (all p less than 0.01). Also, statistical differences were seen in CSMS (p less than 0.05) and VAS (p less than 0.01) between 0.5 year and 1 year. As expected, BS was positively correlated with CSMS (r = 0.617, 95% CI 0.517-0.699) and VAS (r = 0.777, 95% CI 0.719-0.822) at all three time points. Conclusions. SLIT with D. farinae drops was effective and safe for AR patients with epistaxis, resulting in improving the symptoms of rhinitis while relieving the symptoms of epistaxis.

Recovery of Third, Fourth, and Sixth Cranial Nerve Palsies in Pituitary Adenoma and Meningioma Patients.

BACKGROUND: This retrospective, observational cohort study aimed to determine recovery rate and recovery time of ocular motor nerve palsies (OMP) of third (CN III), fourth (CN IV), or sixth cranial nerves (CN VI)-and associated prognostic factors-in meningioma and pituitary adenoma (PA) patients. METHODS: A total of 25 meningioma (28 eyes) and 33 PA patients (36 eyes), treated at the Leiden University Medical Center in the Netherlands from January 1, 1978 to January 31, 2021, were included. OMPs were evaluated according to a newly created recovery scale using on-clinical and orthoptic examinations, which were performed every 3-4 months until palsy recovery, or at 18 months follow-up. RESULTS: Recovery rates of CN III (meningioma 23.5% vs PA 92.3%), CN IV (meningioma 20% vs PA 100%), and CN VI (meningioma 60% vs PA 100%) palsies were observed at 18 months follow-up, with differences between the 2 tumor types being observed in the treated patients only. Median recovery time of all OMPs combined was significantly longer in meningioma patients (37.9 ± 14.3 months vs 3.3 ± 0.1 months; P < 0.001). No significant protective or risk factors for recovery rate or time were identified. CONCLUSIONS: OMP recovery rates in treated patients were more favorable in patients with PA compared with patients with meningiomas, independent of OMP cause. With these new insights in OMP recovery, more accurate prognoses and appropriate follow-up strategies can be determined for meningioma and PA patients with OMPs.

[Construction of a diagnostic model for fatty liver using human body composition analysis].

Objective: To construct a diagnostic model for fatty liver using body composition analysis and further evaluate the diagnostic effect of the model on fatty liver. Methods: 726 cases with chronic liver disease who visited Tianjin Second People's Hospital from April 2019 to June 2022 and had body composition analysis tests were retrospectively enrolled and were divided into a fatty liver group (551 cases with fatty liver) and a control group (175 cases without fatty liver) according to the measured values of abdominal ultrasound and controlled attenuation parameter. An independent sample t-test and a non-parametric rank sum test were used for statistical processing. Logistic regression was used to construct a diagnostic model. Hosmer-Lemeshow was used to validate the fit of model. Receiver operating characteristic curve was used to confirm the diagnostic efficiency of the model. In addition, 341 cases of chronic liver disease who visited Tianjin Second People's Hospital were included to further verify the application effect of the model between July 2022 and February 2023. Results: Compared with the control group, the differences in various indicators of body composition analysis in the fatty liver group were statistically significant (P < 0.05). Basal metabolic rate (X1), visceral fat area (X2), and body fat (X3) were eventually included in the diagnostic model for BCA-FL (body composition analysis-fatty liver)= -7.771+0.002X1-0.035X2+0.456X3 with the Hosmer-Lemeshow test (P=0.059). The measured area under the receiver operating characteristic curve, the sensitivity, and the specificity were 0.888, 0.889, and 0.726, respectively, when the diagnostic threshold value was 0.615 with the Youden index and the receiver operating characteristic curve. In the validated model group, the area under the receiver operating characteristic curve, Youden index, sensitivity, and specificity were 0.875, 0.624, 0.799, and 0.825, respectively. Conclusion: The diagnostic model BCA-FL for fatty liver constructed using human body composition analysis has good diagnostic efficacy and is suitable for screening fatty liver in different basic liver disease populations.

[Risk prediction of metabolic syndrome and coronary artery disease in overweight and obese populations based on serum metabolomics].

Objective: By identifying different metabolites in the serum and clarifying the potential metabolic disorder pathways in metabolic syndrome (MS) and stable coronary artery disease patients, to evaluate the predictive value of specific metabolites based on serum metabolomics for the occurrence of MS and coronary heart disease in overweight or obese populations. Methods: This is a retrospective cross-sectional study. Patients with Metabolic Syndrome (MS group), patients with stable coronary heart disease (coronary heart disease group), and overweight or obese individuals (control group) recruited from the Central District of the First Affiliated Hospital of Zhengzhou University from 2017 to 2019 were assigned to the training set, meanwhile, the corresponding three groups of people recruited from the East District of the hospital during the same period were assigned to the validation test. The serum metabolomics profiles were determined by ultra-performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). Clinical characteristics (age, gender, body mass index (BMI), blood pressure, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), alanine aminotransferase (ALT), aspartate transaminase (AST), total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glomerular filtration rate (eGFR), creatinine (CR)) were also collected. Based on the orthogonal partial least-squares discrimination analysis (OPLS-DA) model, the significantly changed metabolites for MS and coronary artery disease patients were screened according to variable important in projection (VIP), and the receiver operating characteristic (ROC) analysis was evaluated for the risk prediction values of changed metabolites. Results: A total of 488 subjects were recruited in this study, the training set included 40 MS, 249 coronary artery disease patients and 148 controls, the validation set included 16 MS, 18 coronary artery disease patients and 17 controls. We made comparisons of the serum metabolites of coronary artery disease vs. controls, MS vs. controls, and coronary artery disease vs. MS, and a total of 22 different metabolites were identified. The disturbed metabolic pathways involved were phospholipid metabolism, amino acid metabolism, purine metabolism and other pathways. Through cross-comparisons, we identified 2 specific metabolites for MS (phosphatidylcholine (18∶1(9Z)e/20) and pipecolic acid), 4 specific metabolites for coronary artery disease (lysophosphatidylcholine (17∶0), PC(16∶0/16∶0), hypoxanthine and histidine), and 4 common metabolites both for MS and coronary artery disease (isoleucine, phenylalanine, glutathione and LysoPC(14∶0)). Based on the cut-off values from ROC curve, the predictive value of the above metabolites for the occurrence of MS in overweight or obese populations is 100%, the predictive value for the occurrence of coronary heart disease is 87.5%, and the risk predictive value for coronary heart disease in MS patients is 82.1%. Conclusions: The altered serum metabolites suggest that MS and coronary heart disease may involve multiple metabolic pathway disorders. Specific metabolites based on serum metabolomics have good predictive value for the occurrence of MS and coronary heart disease in overweight or obese populations.

[Effects of normobaric hyperoxia intervention on renal ischemia-reperfusion injury in rats].

Objective: To investigate the effects of normobaric hyperoxia intervention on renal ischemia-reperfusion injury in rats and its possible mechanism. Methods: Twenty-one adult male SD rats were enrolled and their right kidneys were excised. After two weeks, they were randomly assigned to 3 groups, with 7 rats in each group, namely sham-operated group (Group S), ischemia-reperfusion group (Group I/R), and normobaric hyperoxia+ischemia-reperfusion group (Group NBHO+I/R). In group S, only the left renal pedicle was isolated, but no ischemic treatment was performed. However, in group I/R and group NBHO+I/R, left renal pedicles were separated and left renal ischemia was induced by noninvasive arterial clamp for 45 min, and after 24 h of reperfusion, rats in group S and group I/R inhaled regular concentration of oxygen (21%), while rats in group NBHO+I/R inhaled high concentration of oxygen (60%), 2 h at each time, once a day for 7 days. On the 7th day after surgery, blood urea nitrogen (BUN) and creatinine (Cr) levels were measured by taking blood from the orbital veins of rats. The content of malondialdehyde (MDA) and superoxide dismutase (SOD) was detected from the left kidney tissues. The mRNA and protein contents of Keap1 and Nrf2 gene in kidney tissues were determined by qPCR and Western Blotting, respectively. Hematoxylin-eosin staining (HE) was employed to observe the pathological changes of kidney tissue. Immunohistochemical staining was used to measure the protein expression of Keap1 and Nrf2 in kidney tissues. Results: Compared with group S, the serum BUN [(10.7±1.7) mmol/L, (8.4±1.0) mmol/L vs (6.1±1.3) mmol/L, both P<0.05] and Cr [(81.0±3.7) µmol/L, (62.9±3.4) µmol/L vs (48.3±2.9) µmol/L, both P<0.05] levels of rats in the group I/R and group NBHO+I/R increased, and the I/R group had the most significant increase. Compared with group S, the MDA content of kidney tissue in the rats of group I/R and NBHO+I/R increased [(10.5±1.0) µmol/L, (8.6±0.8) µmol/L vs (6.5±0.5) µmol/L, both P<0.05], but the MDA content in group NBHO+I/R was lower than that of group I/R (P<0.05). Compared with group S, the SOD content in the kidney tissues of rats in both group I/R and group NBHO+I/R decreased. However, the SOD content of group NBHO+I/R was higher than that of group I/R (P<0.05). Compared with group S, the mRNA and protein contents of Keap1 gene in kidney tissues of group I/R and group NBHO+I/R decreased, and group NBHO+I/R had the most significant decrease (P<0.05). However, compared with group S, mRNA and protein expressions of Nrf2 gene increased in kidney tissues of group I/R and group NBHO+I/R, and NBHO+I/R group had the most significant increase (P<0.05). Postoperative pathological results suggested that compared with group S, the pathological damage of kidney tissues in group I/R and group NBHO+I/R increased, but the degree of damage in group NBHO+I/R was lower than that in group I/R. Conclusion: Normobaric hyperoxia intervention may have protective effects on renal ischemia-reperfusion injury in rats by activating Keap1-Nrf2 signaling pathway.

[Value of serum parathyroid hormone in the diagnosis of primary aldosteronism].

Objective: To explore the value of serum parathyroid hormone (PTH) in the diagnosis of primary aldosteronism (PA) and to investigate an optimal cut-off of serum PTH to distinguish PA from nonfunctional adrenal tumor (NFA). Methods: The clinical data of patients with adrenal incidentaloma in Chinese PLA General Hospital from January 1, 2017 to December 31, 2019 were collected. The data of PA and NFA by clinical characteristics and evaluation on endocrine function were retrospectively analyzed. The logistic regression model was used to find the potential risk factors of elevated PTH. The receiver operating characteristic(ROC) curve was used to evaluate the efficacy of PTH in diagnosis of PA and to explore the best cut-off value. Results: A total of 773 patients were included. There were 356 PA patients (203 males, 57.0%), aged (50±11) years and 417 NFA patients (219 males, 52.5%), aged (51±12) years. The serum PTH level in patients with PA was significantly higher than that in patients with NFA [63.1 (48.4, 80.3) ng/L vs 41.7 (34.1, 51.7) ng/L, P<0.05], as well as the proportion of patients with elevated PTH level (47.8% vs 7.2%, P<0.05). Logistic regression analysis showed that having PA and deficiency of Vitamin D were risk factors for PTH elevation (both P<0.05). The ROC curve showed that the best cut-off value of PTH for the diagnosis of PA in patients with vitamin D deficiency was 56.44 ng/L, with a sensitivity of 66.5% and a specificity of 83.0%, and that in patients with normal vitamin D was 48.81 ng/L, with a sensitivity of 70.5% and a specificity of 72.6%. Conclusions: Patients with PA tend to show increased levels of serum PTH compared with NFA patients. The level of serum PTH can be used as one of the valuable indexes in screening of PA.

[A comparative study of transperitoneal transmesenteric approach versus paracolic sulci approach laparoscopic adrenal tumorectomy for treatment of primary hyperaldosteronism on left side].

Objective: To compare the therapeutic effect of transperitoneal transmesenteric approach versus paracolic sulci approach laparoscopic adrenal tumorectomy for treatment of left-sided primary hyperaldosteronism. Methods: From January 2017 to July 2019, the clinical data of 70 patients with left-sided primary hyperaldosteronism (PHA) who underwent surgery in the First Hospital of Lanzhou University and five other hospitals in Gansu Province were retrospectively analyzed. There are 43 male and 27 female patients. Among them,28 patients were performed transperitoneal transmesenteric approach laparoscopic adrenal tumorectomy and 42 patients were performed transperitoneal paracolic sulci approach laparoscopic adrenal tumorectomy. The general information and perioperative data of the two groups were compared. Results: All 70 cases of surgery were successfully completed. As compared with the paracolic sulci approach group, the operation time was significantly shorter in the transmesenteric approach group[(26.7±8.8)vs (38.9±7.1)min,P<0.001)], and the estimated blood loss was less in the transmesenteric approach group[45(30,50) vs 50(40,60)ml,P=0.042]. There was no statistically significant difference in the postoperative hospitalization days between the two groups[(4.4±1.0)vs(4.5±1.0)d, P=0.669)]. The electrolytes and aldosterone to renin ratio returned to a healthy level in the postoperative one month, and the blood pressure also returned to a healthy level in 53 (75.7%) patients. Conclusion: Transperitoneal transmesenteric approach laparoscopic adrenal tumorectomy is safe and feasible, with a short operation time and relatively less estimated blood loss.

TIR-domain-containing adapter-inducing interferon-ß contributes to TLR3/TLR4 triggered apoptosis and inflammation in nucleus pulposus cells.

The senescence and degeneration of the intervertebral disc are closely related to the reduction of nucleus pulposus (NP) cells caused by apoptosis. TIR-domain-containing adapter-inducing interferon-ß (TRIF) is an adapter for Toll-like receptors 3/4 (TLR3/4), which involves in cell apoptosis. The aim of this study is to detect the role of TRIF in the apoptotic progress of NP cells. The expression of collagen II, aggrecan, TLR3/4, and TRIF were analyzed in different degrees of degenerated human NP samples from patients. NP cells were isolated from mild degenerated tissues and cultured with IL-1ß to accelerate the degradation, and treated with TLR3/4 protein. siRNA was used to silence TRIF gene expression, and TRLF-plasmid was used to upregulate TRLF gene expression. We used flow cytometry assay to analyze cell apoptosis. The expression of collagen II, aggrecan, TLF3/4, TRIF, caspase-8/3, MMP-13, TNF-α was determined by immunofluorescence, Western blot, or RT-PCR. That the expression of collagen II and aggrecan markedly decreased, but TLF3/4, TRIF, caspase-8/3, MMP-3, TNF-α, and IL-1ß were increased in severely degenerated disc tissues. IL-1ß treatment induced NP cell degeneration and TLF3/4, TRIF, caspase-8/3, MMP-3, TNF-α overexpression. TLF3/4 protein treatment promoted NP cell degeneration and apoptosis by upregulation of TRIF, caspase-8/3, MMP-3, and TNF-α. Furthermore, TRIF silencing reversed the negative effect of TLF3/4 overexpression, and TRIF overexpression played the same role in NP cell apoptosis. Based on these results, we believe that TRIF is activated in a degenerated intervertebral disc. TLF3/4 promotes NP cell apoptosis and inflammation through the TRLF adaptor. TRLF expression is positively related to the apoptosis and inflammation in NP cells. These results suggest a therapeutic potential of the TRIF in the treatment of disc degeneration.

LINC00662 promotes glycolysis and cell survival by regulating miR- 375/HIF-1α axis in ovarian cancer.

Ovarian cancer (OC) is one of the most common gynecological malignancies, with the highest mortality rate in women worldwide. LINC00662, a long non-coding RNA (lncRNA), was shown to play a vital role in many malignancies, while little is known about its role in OC. Firstly, our study determined the expression of LINC00662 in OC tissues and cells. Upregulation or downregulation of LINC00662 were performed in OC cells to explore its effects on cell proliferation and glycolysis of OC. The interaction between LINC00662 and miR-375 was verified using luciferase assays and RNA immunoprecipitation. Results showed that LINC00662 was highly expressed in OC tissues and cells, and patients with increased expression of LINC00662 were associated with shorter overall survival. Furthermore, functional assays proved that LINC00662 was essential for OC cell proliferation and glycolysis. Subsequently, our study further revealed that LINC00662 acted as a competitive RNA and it could modulate the expression of HIF-1α through directly binding with miR- 375. Collectively, upregulation of LINC00662 in ovarian cancer tissues is closely correlated to poor survival. LINC00662 might regulate HIF-1α expression via miR-375. These findings suggested that LINC00662 has the potential to be explored as a diagnostic biomarker for OC.

Strength of patient cohorts and biobanks for cardiomyopathy research.

In 2011 the Netherlands Heart Foundation allocated funding (CVON, Cardiovasculair Onderzoek Nederland) to stimulate collaboration between clinical and preclinical researchers on specific areas of research. One of those areas involves genetic heart diseases, which are frequently caused by pathogenic variants in genes that encode sarcomere proteins. In 2014, the DOSIS (Determinants of susceptibility in inherited cardiomyopathy: towards novel therapeutic approaches) consortium was initiated, focusing their research on secondary disease hits involved in the onset and progression of cardiomyopathies. Here we highlight several recent observations from our consortium and collaborators which may ultimately be relevant for clinical practice.

Increased intrinsic connectivity for structural atrophy and functional maintenance after acute ischaemic stroke.

BACKGROUND AND PURPOSE: Significant clinical recovery has commonly been observed in ischaemic stroke patients with irreversible brain structural damage. However, brain mechanisms that help to maintain clinical function remain unclear. METHODS: Sixty-two patients with acute ischaemic stroke underwent longitudinal clinical assessments and magnetic resonance scanning. The clinical recovery trajectory was evaluated using a hierarchical linear model and intrinsic connectivity was analysed with a seed-based approach to examine its changing pattern based on the regional volume changes calculated using voxel-wise analysis. RESULTS: It was observed that clinical outcome measures improved mainly in the short-term period (baseline versus 3 weeks) and then remained stable. Grey matter volume was reduced significantly in the bilateral caudate over the entire 3-year long-term period. Significant intrinsic connectivity increases were observed in the caudate-middle cingulum over the short-term period and in the caudate-precuneus and caudate-calcarine over the long-term period. Finally, it was found that increased caudate-calcarine connectivity was associated with reduced right caudate volume, and a positive correlation was found between increased caudate-middle cingulum connectivity and the amount of modified Rankin score changes. CONCLUSIONS: The increased intrinsic connectivity found in this study tends to be a compensatory mechanism for post-stroke structural damage, associated with clinical recovery. The study helps in understanding the significance of enhanced intrinsic connectivity in post-stroke long-term assessment and rehabilitation.

Prevalence and characteristics of adults with fetal alcohol spectrum disorder in corrections: a Canadian case ascertainment study.

BACKGROUND: Individuals with fetal alcohol spectrum disorder (FASD) experience a range of cognitive, affective, and physical deficits following prenatal alcohol exposure. They are thought to be overrepresented in criminal justice settings. However, limited evidence is available to inform prevalence. We sought to estimate the prevalence of FASD in a Northern Canadian correctional population. METHODS: Using an active case ascertainment approach we recruited a representative sample of 80 justice-involved adults (ages 18-40, 85% male) over an 18-month period from 2013 to 2015. Participants completed interdisciplinary clinical assessments comprising medical and psychological evaluations that adhered to the 2005 Canadian FASD Diagnostic Guidelines. RESULTS: We identified a high rate of FASD (17.5, 95% CI [9.2, 25.8%]) in this sample, and this rate could have been as high as 31.2% with confirmation of prenatal alcohol exposure. Most participants in this study presented with significant neurodevelopmental and cognitive deficits in at least two domains of functioning, irrespective of diagnosis, with only five of 80 participants (6.3%) demonstrating no cognitive impairment. CONCLUSIONS: Findings showed disproportionately high estimated FASD prevalence in this representative sample compared to general population estimates in both Canada and the U.S. (2-5%), underscoring the need for improved FASD screening and diagnosis in correctional settings, and education for clinicians working in the justice context. Strengthened health prevention and intervention efforts to support the needs of individuals with FASD outside the criminal justice context are needed.

Structure and mode of action of a novel antibacterial peptide from the blood of Andrias davidianus.

Andrias davidianus is widely recognized in traditional medicine as a cure-all to treat a plethora of ailments. In a previous study, a novel antibacterial peptide named andricin B was isolated from A. davidianus blood. In this study, we investigated andricin B structure and its mode of action. Circular dichroism spectra suggested that andricin B adopts a random coil state in aqueous solution and a more rigid conformation in the presence of bacteria. Moreover propidium iodide/fluorescein diacetate double staining indicated that bacteria treated with andricin B were not immediately eliminated. Rather, there is a gradual bacterial death, followed by a sublethal stage. Scanning electronic microscope imaging indicates that andricin B might form pores on cell membranes, leading to the release of cytoplasmic contents. These results were consistent with flow cytometry analysis. Furthermore, Fourier transform infrared spectroscopy suggests that andricin B induces changes in the chemical properties in the areas surrounding these "pores" on the cell membranes. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study suggested the new perspectives about the mode of action of antimicrobial peptide (AMP) active against sensitive bacteria. The AMP was able to be in a random coiled state in aqueous solution but to change to a more rigid one in the presence of sensitive bacteria. Exposure to AMP might not lead to immediate death of treated bacteria, rather bacteria concentration decreased gradually flattening at a sublethal stage. These findings will help people to understand better how the AMPs activate against sensitive bacteria.

Variable cardiac myosin binding protein-C expression in the myofilaments due to MYBPC3 mutations in hypertrophic cardiomyopathy.

BACKGROUND: Mutations in MYBPC3 are the most common cause of hypertrophic cardiomyopathy (HCM). These mutations produce dysfunctional protein that is quickly degraded and not incorporated in the myofilaments. Most patients are heterozygous and allelic expression differs between cells. We hypothesized that this would lead to cell-to-cell variation in cardiac myosin binding protein-C (cMyBP-C, encoded by MYBPC3 gene) protein levels. METHODS: Twelve HCM patients were included (six had no sarcomere mutations (HCMsmn) and served as the control group and six harbored mutations in the MYBPC3 gene (MYBPC3mut). Western blot and RNA sequencing analysis of cardiac tissue lysates were performed to detect overall cMyBP-C protein and mRNA levels. Cellular expression of cMyBP-C and α-actin was obtained by immunofluorescence staining. Quantification of cell-to-cell variation of cMyBP-C expression between cardiomyocytes was measured by determining the ratio of cMyBP-C:α-actin stained area of each cell. RESULTS: Protein and mRNA analysis revealed significantly reduced cMyBP-C levels in MYBPC3mut patients compared with HCMsmn patients (0.73 ±â€¯0.09 vs. 1.0 ±â€¯0.15, p < .05; 162.3 ±â€¯16.4 vs. 326.2 ±â€¯41.9 RPKM, p = .002), without any sign of truncated proteins. Immunofluorescence staining of individual cardiomyocytes in HCMsmn patients demonstrated homogenous and equal cMyBP-C:α-actin staining ratio. In contrast, MYBPC3mut patients demonstrated inhomogeneous staining patterns with a large intercellular variability per patient. Coefficient of variance for cMyBP-C/α-actin staining for each patient showed a significant difference between both groups (17.30 ±â€¯4.08 vs. 5.18 ±â€¯0.65% in MYBPC3mut vs. HCMsmn, p = .02). CONCLUSION: This is the first study to demonstrate intercellular variation of myofilament cMyBP-C protein expression within the myocardium from HCM patients with heterozygous MYBPC3 mutations.

Purification, characterization and application of a novel antimicrobial peptide from Andrias davidianus blood.

The Andrias davidianus has been known as a traditional Chinese medicine for a long time. Its blood is considered as a waste or by-product of the meat production industry. Although there are reports on isolation of the antimicrobial peptides from different resources, there are no reports of their isolation from A. davidianus blood. In this work, an antimicrobial peptide, andricin B, was isolated from the blood of A. davidianus by an innovative method in which the magnetic liposome adsorption was combined with reversed-phase high-performance liquid chromatography. The structure, antimicrobial activity and safety of andricin B were further investigated. Amino acid sequence was determined by N-terminal sequencing and found to be Gly-Leu-Thr-Arg-Leu-Phe-Ser-Val-Ile-Lys. Circular dichroism (CD) spectra and prediction of three-dimensional structure by bioinformatics software suggested the presence of a well-defined random coil conformation. Andricin B was found to be active against all bacteria tested in this study as well as some fungi. The minimum inhibitory concentrations (MICs) were in the range 8-64 µg ml-1 . Moreover, the haemolytic testing also suggested that andricin B could be considered safe at the MICs. Finally, andricin B was shown to inhibit the growth of Staphylococcus aureus in the cooked meat of A. davidianus. This study shows that andricin B is a promising novel antimicrobial peptide that may provide further insights towards the development of new drugs. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the pioneer study on screening and isolation of antimicrobial peptide from the blood of Andrias davidianus. Here, we have developed a novel method by combining magnetic liposomes adsorption with reversed-phase high-performance liquid chromatography to purify and screen the antimicrobial peptides. From this screen, we identified a novel antimicrobial peptide which we name as andricin B. Andricin B is unique as it checks the growth of both Gram-positive and Gram-negative bacteria as well as few fungal species.

Expression of glycosylated α-dystroglycan in newborn skeletal and cardiac muscles of fukutin related protein (FKRP) mutant mice.

INTRODUCTION: Mutations in the Fukutin related protein (FKRP) gene are characterized by a lack of functionally glycosylated α-dystroglycan (F-α-DG) in muscles. A small number of fibers retain the capacity to produce strong IIH6 reactive glycosylated-α-DG (g-α-DG) in muscles of both FKRP mutant animals and patients. METHODS: We examined the expression of g-α-DG in limb, diaphragm, and cardiac muscles of newborn FKRP mutants and LARGEmyd mice with IIH6 antibody. RESULTS: Near-normal levels of g-α-DG were detected in all 3 muscles in the FKRP448LNeo- mutant. Expression was limited within the first 8 postnatal days with decreasing levels. No expression was identified in LARGEmyd mice. CONCLUSIONS: Temporary expression of glycosylated-α-DG in newborn FKRP mutant muscles is LARGE- and mutant FKRP-dependent. The capability of mutant FKRP with a severe clinic phenotype to produce glycosylated-α-DG provides a new perspective for possible approaches to mitigate FKRP deficiency. Muscle Nerve 55: 582-590, 2017.

A comprehensive analysis of candidate gene signatures in oral squamous cell carcinoma.

This study aimed to unravel the molecular mechanism of oral squamous cell carcinoma (OSCC). With microarray dataset GSE30784, differentially expressed genes (DEGs) were identified between OSCC and control samples. The DEGs overlapped with genes obtained from online database MalaCards were determined as OSCCDEG, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A total of 5177 up-regulated and 6081 down-regulated DEGs were identified between OSCC and control. Out of the DEGs, 451 genes were overlapped with the 704 genes gained from MalaCards and regarded as "OSCCDEG". Up-regulated OSCCDEG were associated with cell cycle pathway, while down-regulated OSCCDEG were linked to ErbB pathway. ANGPT1, ANGPT2 and 3 hub proteins (EGFR, HSP90AA1, RB1) in the PPI network were associated with the survival rates of several tumors. The largest network module with the hub protein EGFR was associated with positive regulation of cell communication. The second largest module with the hub node FN1 was related to angiogenesis. For the third network module in connection with DNA metabolism, the hub protein was PCNA. ErbB and cell cycle pathways were crucial for OSCC. EGFR, FN1, PCNA, ANGPT1 and ANGPT2 might be potential biomarkers for OSCC. These findings help provide guidelines for treating OSCC.

Effects of Deltorphin II and Its Retroenantio Analog on Cardiac Tolerance to Ischemia and Reperfusion.

Selective agonist of δ2-opioid receptors deltorphin II and its retroenantio analog (0.12 mg/kg intravenously) were preventively injected to male Wistar rats 15 min prior to 45-min coronary occlusion or 5 min before 120-min reperfusion. Administration of deltorphin II before artery occlusion and before reperfusion decreased the infarct size/area at risk ratio. Deltorphin II prevented the appearance of ischemia-provoked ventricular arrhythmias and exerted no effect on HR and BP (systolic and diastolic). The retroenantio analog of deltorphin II produced no antiarrhythmic or infarct-limiting effects, but reduced HR without affecting BP. Deltorphin II can be viewed as a promising prototype for a medicinal remedy to treat acute myocardial infarction.

The relevance of Tim-3 polymorphisms and F protein to the outcomes of HCV infection.

Hepatitis C virus (HCV) is one of the major causes of liver inflammation. The aim of this study was to investigate the associations of T-cell immunoglobulin and mucin domain-3 (Tim-3) polymorphisms and the alternate reading frame protein (F protein) with the outcomes of HCV infection. Three single-nucleotide polymorphisms (SNPs; rs10053538, rs12186731, and rs13170556) of Tim-3 were genotyped in this study, which included 203 healthy controls, 558 hepatitis C anti-F-positive patients, and 163 hepatitis C anti-F-negative patients. The results revealed that the rs12186731 CT and rs13170556 TC and CC genotypes were significantly less frequent in the anti-F-positive patients [odds ratio (OR) = 0.54, 95 % confidence interval (CI) = 0.35-0.83, p = 0.005; OR = 0.26, 95 % CI = 0.18-0.39, p < 0.001; and OR = 0.19, 95 % CI = 0.10-0.35, p < 0.001, respectively), and the rs13170556 TC genotype was more frequent in the chronic HCV (CHC) patients (OR = 1.70, 95 % CI = 1.20-2.40, p = 0.002). The combined analysis of the rs12186731 CT and rs13170556 TC/CC genotypes revealed a locus-dosage protective effect in the anti-F-positive patients (OR = 0.22, 95 % CI = 0.14-0.33, p trend < 0.001). Stratified analyses revealed that the frequencies of the rs12186731 (CT + TT) genotypes were significantly lower in the older (OR = 0.31, 95 % CI = 0.15-0.65, p = 0.002) and female (OR = 0.30, 95 % CI = 0.17-0.52, p < 0.001) subgroups, and rs13170556 (TC + CC) genotypes exhibited the same effect in all subgroups (all p < 0.001) in the anti-F antibody generations. Moreover, the rs13170556 (TC + CC) genotypes were significantly more frequent in the younger (OR = 1.86, 95 % CI = 1.18-2.94, p = 0.007) and female (OR = 2.38, 95 % CI = 1.48-3.83, p < 0.001) subgroups of CHC patients. These findings suggest that the rs12186731 CT and rs13170556 TC/CC genotypes of Tim-3 provide potential protective effects with the F protein in the outcomes of HCV infection and that these effects are related to sex and age.

Characterization of a novel arabinose-tolerant α-L-arabinofuranosidase with high ginsenoside Rc to ginsenoside Rd bioconversion productivity.

AIMS: (i) To investigate the enzymatic characterization of α-L-arabinofuranosidase from Thermotoga thermarum DSM5069. (ii) To evaluate the performance of its excellent properties on converting ginsenoside Rc to ginsenoside Rd. METHODS AND RESULTS: The thermostable α-L-arabinofuranosidase (Tt-Afs) gene from T. thermarum DSM5069 was cloned and overexpressed. Recombinant Tt-Afs was purified, and its molecular weight was approx. 55 kDa. Its optimal activity was at pH 5·0 and 95°C. It has high selectivity for cleaving the outer arabinofuranosyl moieties at the C-20 carbon of ginsenoside Rc and its sugar-tolerance makes Tt-Afs a promising candidate for the production of ginsenoside Rd. In a reaction at 85°C and pH 5·0, 25 g l(-1) of ginsenoside Rc was transformed into 21·8 g l(-1) of Rd within 60 min, with a corresponding molar conversion of 99·4% and a high ginsenoside Rd productivity of 21800 mg l(-1) h(-1). CONCLUSIONS: We have successfully cloned and overexpressed the novel α-l-arabinofuranosidase from T. thermarum DSM5069. The high ginsenoside Rd productivity and detailed characterization of recombinant Tt-Afs was provided. SIGNIFICANCE AND IMPACT OF THE STUDY: The result shows a high productivity on the bioconversion from high concentration ginsenoside Rc to ginsenoside Rd, which also give rise to a potential commercial enzyme application.