Associations and Potential Multiple Mechanisms between Subjective Hearing Loss and Cognitive Impairment.

BACKGROUND: Subjective hearing loss (SHL) refers to an individual's self-assessment of their hearing loss. The association and underlying mechanisms between SHL and cognitive impairment still necessitate elucidation. OBJECTIVES: To validate potential mechanisms between SHL and cognitive impairment. DESIGN: Cross-section. SETTING: Shanghai, China. PARTICIPANTS: A total of 2369 individuals from communities and the cognitive disorder clinic. MEASUREMENTS: All participants were subjected to a comprehensive neuropsychological assessment, encompassing the Hearing Handicap Inventory for the Elderly-Screening Version (HHIE-S). The participants' brain ß-amyloid (Aß) deposition status, plasma biomarkers associated with Alzheimer's disease (AD), and cardiovascular risk factors were also collected. RESULTS: In individuals with a heightened SHL, elevated HHIE-S score was linked to diminished cognitive and daily functioning as well as heightened levels of depressed mood. This correlation was observed in auditory memory performance but not in visual memory. The influence of SHL on cognitive function was mediated by depressed mood. SHL was associated with diabetes and smoking, whereas cognitive function was associated with hyperlipidemia and alcohol consumption. In individuals with positive brain Aß deposition, SHL demonstrated associations with cognitive function independent of plasma Aß42/40 ratio, P-tau181, neurofilament light chain, and APOE allele status. CONCLUSION: SHL has an independent effect on cognitive impairment. The findings do no provide evidence for the common cause mechanism. Instead, the findings support the presence of a cognitive resource mechanism and an impoverished environment mechanism, along with the potential for a pathological interaction mechanism.

[Predictor of clinical response to subcutaneous immunotherapy with dust mites in polysensitized allergic rhinitis patients].

Objective: To evaluate the efficacy of 1-year subcutaneous immunotherapy (SCIT) with dust mites in polysensitized allergic rhinitis (AR) patients and to analyze the serological markers associated with clinical response. Methods: A retrospective analysis of data from 69 polysensitized AR patients who completed 1-year SCIT with dust mites from Oct 2020 to Mar 2022 in Shandong Provincial ENT Hospital was conducted. The median patient age was 21 years, including 41 males and 28 females. The changes in symptoms and serum IgE, IgG4 assessed before and after treatment were evaluated. The differences in serological markers between effective and ineffective groups were analyzed. Multivariate regression analysis was used to investigate the predictors of clinical response. SPSS 22.0 software was used for data processing. Results: After immunotherapy, there was a significant reduction in symptom scores and a substantial improvement in the quality of life of polysensitized AR patients (all P<0.001). Dust mite specific IgG4 (sIgG4) significantly increased and dust mite specific IgE (sIgE)/sIgG4 significantly decreased (all P<0.05). sIgE, total IgE (tIgE), sIgE/tIgE and sIgE/sIgG4 were significantly lower in ineffective group than those in effective group (all P<0.05). The clinical response of SCIT related only to dust mite sIgE (r=0.29, P=0.036), and sIgE≥53.86 kU/L had the best sensitivity (77.78%) and specificity (57.89%) to predict effective SCIT in polysensitized AR patients. Conclusions: One-year dust mite SCIT is effective for polysensitized AR patients. Pre-treatment serum dust mite sIgE≥53.86 kU/L may play a role in predicting clinical response of dust mite SCIT in polysensitized AR patients.

Adenosine diphosphate-ribosylation factor-like 15 can regulate glycolysis and lipogenesis related genes in colon cancer.

This study was designed to investigate the potential key genes of ADP-ribosylation factor-like 15 (ARL15) regulating glycolysis and lipogenesis in colon cancer. Hematoxylin-eosin (HE) staining and immunohistochemistry were used to observe the expression of ARL15 in 10 normal colon tissues and 10 colon cancer tissues. Immunofluorescence staining was used to observe the expression position of ARL15 in normal human colorectal mucosa cells (FHC) and colon cancer cells (HCT116 and SW620) with a confocal microscope. The ARL15 plasmid and small interfering RNA (siRNA) were constructed. After transfection, the expression levels of glycolysis and lipogenesis regulatory enzymes and messenger RNA (mRNA) transcription of ARL15 in over-expressed and silenced colon cancer cells were detected by Western blotting and real-time quantitative PCR (qRT-PCR). High expression of ARL15 in colon cancer tissue and low expression in normal colon tissue, and all expression are in the cytosol. The expression position of ARL15 in the FHC, HCT116, and SW620 cells was consistent and mainly distributed in the cytosol. After the pCMV-3Tag-2-ARL15 plasmid was transfected in HCT116, the protein expressions of FASN, AKT, P-AKT, P-GSK, SREBP-1 (p125) (p<0.01), and AMPK (p<0.001) were higher than those in the control group. The mRNA transcription level of FASN, GSK, AMPKa1, and SREBP-1 gene was higher than control group after the over-expression of ARL15. After the ARL15-siRNA was transfected in HCT116, the protein expression levels of PKM2, PFK, FASN, AKT, P-AKT, P-GSK, and AMPK decreased compared with the control group, (p<0.05). The mRNA transcription level of FASN, GSK, AMPKα1 gene was lower than control group after the low-expression of ARL15 (p<0.05). After adding 2 µM JIB-04, ARL15 in HCT116 showed statistical differences compared with the control group at 12 h, 24 h and 36 h (p<0.05). After adding 2 µM JIB-04, the protein expression levels of AKT, p-GSK, FASN, AMPK and SREBP-1 in HCT116 cells decreased significantly after 24 h. It was also found that the expression levels of AKT, P-GSK, FASN, AMPK and SREBP-1 genes in the dose-adding group were significantly lower than those in the control group. In summary, ARL15 may promote the occurrence of colon cancer by increasing the expression of protein kinase B/AMP-activated protein kinase (AKT/AMPK) downstream regulatory enzymes for glycogenesis and lipogenesis. JIB-04 can target ARL15 and affect its expression as well as the expressions of glucose and lipid metabolity-related proteins in AKT and AMPK signaling pathways.

[Expression of mucin-4 in meningiomas and its diagnostic significance].

Objective: To investigate the expression of mucin-4 (MUC4) in meningiomas. Methods: Totally 258 cases of meningiomas and 165 cases of other brain tumors were collected from the First Affiliated Hospital of China University of Science and Technology (Anhui Provincial Hospital) from 2011 to 2017. MUC4, EMA, PR, SSTR-2 protein expression was detected by immunohistochemistry, and their expression in meningiomas and other tumor tissue was compared. Results: The 258 patients with meningioma included 85 males and 173 females, with a mean age of 69 years. Among the meningiomas, 192, 54 and 12 were WHO grades Ⅰ, Ⅱ and Ⅲ respectively. The overall expression rate of MUC4 in meningiomas was 67.8% (175/258), including 46/46 (100.0%) in meningothelial meningiomas, 3/3 in secretory meningiomas, 44/45 (97.8%) in angiomatous meningiomas, 37/41 (90.2%) in atypical meningiomas, 3/4 in metaplastic meningiomas, 2/3 in microcystic meningiomas, 7/11 in psammomatous meningiomas, 7/11 in chordoid meningiomas, 14/28 (50.0%) in transitional meningiomas, 1/2 in clear cell meningiomas, 1/2 in papillary meningiomas, 4/9 in anaplastic meningiomas, 7/52 (13.5%) in fibrous meningiomas, and 0/1 in rhabdoid meningiomas. In addition, MUC4 was expressed in 44 EMA negative meningiomas and in four SSTR-2 negative meningiomas. PR, EMA, SSTR-2 were expressed in 149 cases (57.7%), 173 cases (67.1%), 235 cases (91.1%) of meningiomas, respectively. MUC4 was not expressed in other tumors in the central nervous system, including schwannomas, neurofibromas, solitary fibrous tumors/hemangiopericytoma (SFT/HPC), hemangioblastoma, gliomas and ependymomas. Conclusion: MUC4 is widely expressed in meningiomas and has great value in distinguishing meningiomas from other non-meningeal epithelial tumorsof the central nervous system.

SP1-induced upregulation of long noncoding RNA LINC00313 contributes to papillary thyroid cancer progression via the miR-422a.

OBJECTIVE: Long noncoding RNA LINC00313 (LINC00313) has been reported to be dysregulated in several tumors, including papillary thyroid carcinoma (PTC). Our present study aimed to further explore the potential mechanism of LINC00313 in the progression of papillary thyroid carcinoma (PTC). PATIENTS AND METHODS: RT-PCR was performed to detect the expression of LINC00313 in both PTC tissues and cell lines. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were performed to explore whether SP1 could bind to the promoter region of LINC00313 and activate its transcription. The biological functional correlation of LINC00313 was determined by down-regulating the expression of LINC00313 on PTC cell proliferation, apoptosis, migration and invasion. The regulating relationship between LINC00313 and miR-422a was investigated in PTC cells using luciferase reporter assays. RESULTS: We observed that LINC00313 expression was significantly up-regulated in both PTC tissues and cell lines. Next, the results of bioinformatics analysis and luciferase reporter assays indicated that the transcription factor SP1 can bind to the promoter region of LINC00313 resulting in the overexpression of LINC00313 in PTC. Moreover, functional study revealed that knockdown of LINC00313 significantly suppressed cells proliferation, migration, invasion and EMT. Finally, our results indicated that LINC00313 functioned as an oncogene in PTC in part through serving as a competing endogenous RNA to modulate mi-422a expression. CONCLUSIONS: Overall, our data demonstrated that SP1-induced LINC00313 contributed to PTC progression by via competitively binding to miR-422a, which may provide a novel therapeutic strategy for PTC.

Micro124-mediated AHR expression regulates the inflammatory response of chronic rhinosinusitis (CRS) with nasal polyps.

MicroRNAs represent a component of the innate immune responses that can restrain inflammatory signaling, miR124 is an important member of inflammation-associated miRNAs, and abnormal miR124 expression is observed in many inflammatory diseases and immune disorders. However, the role and signaling pathways of miR124 in chronic rhinosinusitis with nasal polyps (CRSwNPs) have not been studied in detail. The aryl hydrocarbon receptor (AHR) is a ligand-inducible transcription factor that is highly conserved in evolution and plays important roles in the inflammatory response process. In our study, we describe the role of miR124 in the inflammatory response of CRS with nasal polyps. We found that the expression of miR124 was decreased in nasal polyps, and negatively correlated with the expression of AHR. MiR124 can inhibit AHR expression by directly target 3' untranslated region (3'-UTR) of AHR. To further investigate the relationship between miR124, AHR and CRS inflammatory response, we transfect HNEpC cells with miR124 mimic, miR124 inhibitors or siRNA of AHR, then all the results showed that miR124 could regulates cellular inflammatory response through negatively regulating AHR expression. This study demonstrated that the regulation of AHR expression by miR124 is critical to the development of inflammatory response in CRSwNPs.

The relationship between lung function and the clinical and histopathological features in Chinese patients with nasal polyps.

OBJECTIVE: To investigate lung function in Chinese patients suffering from chronic rhinosinusitis with nasal polyps and examine its association with histopathological features. METHODS: The lung function of 99 patients with nasal polyps was measured. Haematoxylin and eosin and immunohistochemistry staining were performed to evaluate any inflammatory cells and epithelial tissue remodelling. RESULTS: Predicted maximal expiratory flow rate at 25 per cent vital capacity was reduced (p < 0.05) in epithelial hyperplasia, and predicted maximal expiratory flow rate at 50 per cent vital capacity was reduced (p < 0.05) in goblet cell hyperplasia. Both peripheral blood eosinophilia and tissue eosinophilia nasal polyps manifested significantly reduced: forced expiratory volume in 1 second/forced vital capacity ratio, predicted maximal expiratory flow rate at 25, 50 and 75 per cent of vital capacity, and predicted maximal mid-expiratory flow. Peripheral blood eosinophils were negatively correlated with predicted maximal expiratory flow rate at 25 and 50 per cent of vital capacity, and predicted maximal mid-expiratory flow. Eosinophils in tissue were negatively correlated with all lung function parameters investigated except predicted forced vital capacity. CONCLUSION: Clinicians should be aware of lung function decline in nasal polyps patients, especially in those with tissue eosinophilia.

Effects of tea polyphenols and their polymers on MAPK signaling pathways in cancer research.

The biological activities and mechanisms of tea polyphenols and their polymerics have been attractive issues in cancer research. The inhibition of tea polyphenols on cancer cells decreased cell proliferation and increased apoptosis. Tremendous evidences have shown that tea polyphenols suppress tumor promotion by inhibiting enzyme activities and blocking signal transduction pathways. Specifically, the mitogen activated protein kinases (MAPK) pathways have been implicated as an important target molecular for cancer prevention and therapy. The purpose of this review is to discuss the relationship between tea polyphenols and MAPK signaling pathways in cancer.

The changes of catechins during the fermentation of green tea.

The dynamics of tea catechins and organic acids in fermented fluid and yeast cells were studied. The concentration of eight kinds of catechins solution decreased by from 29.6% to 47.6%, respectively, some catechins were absorbed and accumulated by yeast cells, but the amount in the cells was very low during the fermentation process. The investigation of catechins resolved in four citrate buffers with a pH range of 2.6-5.6 for 18 h showed that most catechins were stable in buffer solutions of pH 4.6 and 5.6, and significant losses took place in solutions of pH 2.6 and 3.6. However, most catechins were released and recovered by adjusting the pH value to 5.6, which suggested that catechins in extremely acidic buffer solutions might reversibly combine each other or with other compounds.

Isolation of immunoglobulin from egg yolk by anionic polysaccharides.

Isolation conditions of immunoglobulin in egg yolk (IgY) were optimized by the addition of various levels of Na-alginate (Alg), lambda-carrageenan (lambda-Cg), Na-carboxymethyl cellulose (CMC), and pectin (PC) to 6-fold diluted yolk. The mixtures were then reacted at pH 4.0-6.0 for 30 min. The optimal isolation conditions of IgY for Alg, lambda-Cg, and CMC were at the 0.1% level and at pH 5.0, while those for PC were at the 0.15% level and at the same pH. The remaining lipid and remaining protein in the supernatants thus obtained was 0.5-3.8% and 10-17%, respectively, and more than 90% of lipoproteins were precipitated. The IgY recovery was determined to be 33-74% by means of single radial immunodiffusion method when IgY was isolated under the optimal conditions. PC showed the best recovery of IgY, while lambda-Cg provided the least. The interactions between polysaccharides and lipoproteins were mainly ionic bonds, hydrophobic interactions, and hydrogen bonds as determined by the addition (0-2.0 M) of NaSCN or urea to the polysaccharide-lipoprotein precipitates.

[Inhibitory activity of Dianthus superbus L. and 11 kinds of diuretic Traditional Chinese medicines for urogenital Chlamydia trachomatis in vitro].

OBJECTIVE: To detect the susceptibility of urogenital chlamydia trachomatis(CT) to 12 kinds of diuretic traditional Chinese medicines. METHODS: The inhibitory activity of these medicines for CT was detected by microculture technique of McCoy cell in vitro. RESULTS: All the 12 kinds of diuretic traditional Chinese medicines had inhibitory activities for urogenital CT, with minimal inhibitory concentrations (MICs) from 0.122 mg.ml-1 to 62.5 mg.ml-1. The activities of Dianthus superbus L., Poria cocos(Shcw.) Woft, Polyporus umbellatus and Artemissia capillaris were stronger. The number and volume of CT inclusions reduced gradually and disappeared finally with the rise of concentration. CONCLUSION: All the 12 kinds of diuretic traditional Chinese medicines possess some inhibitory activity for urogenital CT.

Efficiency and protective effect of encapsulation of milk immunoglobulin G in multiple emulsion.

Milk immunoglobulin G (IgG), separated with protein G affinity chromatography, and IgG in colostral whey were encapsulated by 0.5% (w/v) of Tween 80, sucrose stearate, or soy protein, which were used as secondary emulsifiers in the water in oil in water type multiple emulsion. The residual contents of separated IgG and IgG in colostral whey, ranging from 58.7 to 49.7% and from 13.2 to 21.3%, respectively, in the inner water phase (water phase surrounded by oil phase) with emulsifiers were determined by ELISA. However, the emulsion stability decreased after 24 h, and the residual IgG content in the inner water phase was lowered. Encapsulation of IgG in the multiple emulsion increased the stability of separated IgG against acid (pH 2.0) and alkali (pH 12.0) by 21-56% and 33-62%, respectively, depending on the emulsifier used. Moreover, multiple emulsion also provided a remarkable protective effect on separated IgG stability against proteases. The residual contents of separated IgG in multiple emulsion, using Tween 80 as secondary emulsifier, incubated for 2 h with pepsin (pH 2.0) and trypsin and chymotrypsin (pH 7.6) (enzyme/substrate = 1/20) were 35.4, 72.5, and 82.3%, whereas those of separated IgG in enzyme solution were only 7.2, 33. 1, and 35.2%, respectively. However, the separated IgG loss during the preparation of multiple emulsion was almost 41-50%.

Rapid detection of glycoprotein G gene for the diagnosis and typing of herpes simplex virus infection in genital herpes.

OBJECTIVE: To develop a new, rapid, and convenient technique for the diagnosis and typing of herpes simplex virus (HSV) in genital herpes (GH). METHODS: Using samples from skin vesicle fluid and urogenital mucosal swabs of subjects with GH, conventional polymerase chain reaction (PCR) (directed to polymerase gene: PCRpG) were compared with a newly developed PCR (directed to HSV glycoprotein gene: PCRgG). Both PCR methods were compared with virus isolation culture (VI) with indirect immunofluorescent staining (IIF). RESULTS: 80 samples from 40 GH patients (25 males) were tested. Positive results were seen in 52.5% (42/80) using PCRgG compared with 40% (32/80) by VI. Most of PCRgG positive samples (95.1%) were caused by HSV-2 infection. In samples from healing lesions, HSV was detected more often by PCRgG, than by VI. The results of typing by PCRgG and IIF were highly consistent. CONCLUSION: PCRgG is more sensitive than VI and PCRgG in detecting HSV in urogenital samples from subjects with GH. PCRgG is a convenient technique for the rapid detection and typing of GH.

Temperature affects binding of murine monoclonal IgG antibodies to protein A.

Murine IgG subclasses show different affinities when they react with protein A. The temperature of application of the sample to protein A-Sepharose markedly influences the interaction of certain antibodies with this specific adsorbent. Elution of weakly bound mouse IgG could be carried out by mild temperature changes instead of lowering the pH, and this should be advantageous with certain immunoglobulins that are labile under acidic conditions.

Purification and characterization of carcinoembryonic antigen from GW-39, a xenografted human colonic tumor system.

Carcinoembryonic antigen (CEA) was purified from GW-39 human tumor xenografts in hamsters by immunoaffinity chromatography. Binding of the antigen to immobilized monoclonal antibody provided a high degree of purification of CEA in a single step. A recovery of 79% and a 750-fold purification were obtained. The purified CEA has a molecular size of 180 kilodaltons, an isoelectric point of 4.4, and a specific activity of 0.94. About 73% of the radiolabeled GW-39 CEA reacted with goat anti-CEA serum. The amino acid and carbohydrate compositions of the GW-39 CEA were comparable to those of CEA preparations from other sources.

Demethylation and denitrosation of nitrosamines by cytochrome P-450 isozymes.

Metabolism of nitrosamines was studied in a reconstituted monooxygenase system composed of cytochrome P-450 isozymes purified from liver microsomes of ethanol- and phenobarbital-treated rats. The ethanol-induced isozyme (P-450et) was efficient in catalyzing the demethylation of N-nitrosodimethylamine (NDMA), with a Km of 2.4 mM and Vmax of 7.2 nmol min-1 nmol P-450(-1), but less active with N-nitrosomethylbenzylamine and N-nitrosomethylaniline. The phenobarbital-induced form (P-450b) was ineffective in NDMA metabolism but was active in catalyzing the demethylation of N-nitrosomethylaniline, with an estimated Km of 0.08 mM and a Vmax of 7.2 nmol min-1 nmol-1. P-450et also catalyzed the denitrosation of NDMA with a Km of 13.6 mM and a Vmax of 1.36 nmol min-1 nmol-1. With control liver microsomes, multiple Km values were observed for the demethylation and denitrosation of NDMA. Involvement of superoxide radicals in the metabolism of NDMA was suggested by the action of superoxide dismutase, which inhibited the denitrosation by 43 to 73% and the demethylation by 13 to 22% in different monooxygenase systems. The P-450et-dependent NDMA demethylation was strongly inhibited by 2-phenylethylamine and 3-amino-1,2,4-triazole; these compounds were previously believed not to be inhibitors of P-450-dependent reactions but were found to inhibit microsomal NDMA demethylase. The present results establish the role of P-450 in nitrosamine metabolism and help to clarify some of the previous confusion in this area of research.

Effects of riboflavin deficiency on metabolism of nitrosamines by rat liver microsomes.

The effects of riboflavin deficiency on the metabolism of N-nitrosodimethylamine [(DMN) CAS: 62-75-9] and other nitrosamines were examined in rats. After weanling rats were put on a riboflavin-deficient diet, the development of the deficiency was monitored by the growth rate and the erythrocyte glutathione reductase activation coefficient. In the riboflavin-deficient rats, the liver microsomal NADPH-cytochrome c reductase activity was lower but the cytochrome P450 content was higher than that of the control. The metabolism of DMN was dependent on the severity of the deficiency. During mild deficiency, which was observed mainly with Sprague-Dawley rats, the microsomal DMN demethylase (DMNd) activity was elevated 30-80%, but the metabolism of N-nitrosomethylbenzylamine (CAS: 937-40-6) and three other nitrosamines was slightly decreased. Dietary restriction in the pair-fed group also caused an elevation of DMNd activity above that of the ad libitum control group due to a partial fasting effect. During severe deficiency, which was observed mainly with Wistar rats, however, the metabolism of DMN, as well as the oxidation of benzo[a]pyrene, was decreased. Preincubation with flavin adenine dinucleotide and flavin mononucleotide enhanced the DMNd activity of the microsomes from riboflavin-deficient rats but not that from control rats. The results suggest that, depending on the alterations of the monooxygenase enzyme system during the development of the deficiency, riboflavin deficiencies may have different effects on the metabolism of DMN and some other carcinogens.

Metabolism of nitrosamines by purified rabbit liver cytochrome P-450 isozymes.

The metabolism of nitrosamines by microsomal cytochrome P-450 (P-450) isozymes was studied in a reconstituted monooxygenase system. P-450 LM2, LM3a, LM3b and LM3c, LM4, and LM6 were purified, respectively, from the livers of phenobarbital-treated, ethanol-treated, untreated, isosafrole-treated, and imidazole-treated rabbits. Of these isozymes, LM3a had the highest N-nitrosodimethylamine demethylase (NDMAd) activity with a Km of 2.9 mM and Vmax of 9.3 nmol/min/nmol. LM2, LM4, and LM6 exhibited NDMAd activity only at high N-nitrosodimethylamine concentrations, and isozymes LM3b and LM3c had poor activity even at the highest substrate concentrations examined. LM2, however, was more active than LM3a in the metabolism of N-nitrosomethylaniline. With each isozyme (LM3a or LM4), only one Km for NDMAd was observed, whereas with rabbit liver microsomes, multiple Km of 0.07, 0.27, and 36.8 mM were obtained. P-450 isozymes also catalyzed the denitrosation of nitrosamines at rates comparable to or lower than the demethylation, and the ratio of these two reactions was different with different nitrosamines. 2-Phenylethylamine and 3-amino-1,2,4-triazole, which were believed previously to affect NDMAd by mechanisms independent of P-450, were shown to be potent inhibitors of P-450-dependent NDMAd. These results further establish the role of P-450 isozymes in the metabolism of nitrosamines and indicate that LM3a is apparently responsible for the increased N-nitrosodimethylamine metabolism associated with ethanol treatment.