Correlative factors of poor prognosis and abnormal cellular immune function in patients with Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a serious disease causing human dementia and social problems. The quality of life and prognosis of AD patients have attracted much attention. The role of chronic immune inflammation in the pathogenesis of AD is becoming more and more important. AIM: To study the relationship among cognitive dysfunction, abnormal cellular immune function, neuroimaging results and poor prognostic factors in patients. METHODS: A retrospective analysis of 62 hospitalized patients clinical diagnosed with AD who were admitted to our hospital from November 2015 to November 2020. Collect cognitive dysfunction performance characteristics, laboratory test data and neuroimaging data from medical records within 24 h of admission, including Mini Mental State Examination Scale score, drawing clock test, blood T lymphocyte subsets, and neutrophils and lymphocyte ratio (NLR), disturbance of consciousness, extrapyramidal symptoms, electroencephalogram (EEG) and head nucleus magnetic spectroscopy (MRS) and other data. Multivariate logistic regression analysis was used to determine independent prognostic factors. the modified Rankin scale (mRS) was used to determine whether the prognosis was good. The correlation between drug treatment and prognostic mRS score was tested by the rank sum test. RESULTS: Univariate analysis showed that abnormal cellular immune function, extrapyramidal symptoms, obvious disturbance of consciousness, abnormal EEG, increased NLR, abnormal MRS, and complicated pneumonia were related to the poor prognosis of AD patients. Multivariate logistic regression analysis showed that the decrease in the proportion of T lymphocytes in the blood after abnormal cellular immune function (odd ratio: 2.078, 95% confidence interval: 1.156-3.986, P < 0.05) was an independent risk factor for predicting the poor prognosis of AD. The number of days of donepezil treatment to improve cognitive function was negatively correlated with mRS score (r = 0.578, P < 0.05). CONCLUSION: The decrease in the proportion of T lymphocytes may have predictive value for the poor prognosis of AD. It is recommended that the proportion of T lymphocytes < 55% is used as the cut-off threshold for predicting the poor prognosis of AD. The early and continuous drug treatment is associated with a good prognosis.

Physicochemical, Antioxidant, Sensory, and Starch Digestibility Properties of Steamed Bread Fortified with Tamarillo Powder.

The effects of lyophilized tamarillo powder (TP) on the physicochemical, antioxidant, sensory, and starch digestibility characteristics of steamed breads were studied. The TP was used to substitute 5-20% of wheat flour to make steamed breads, assigned as T5, T10, T15, and T20, respectively. The results showed that TP is rich in dietary fiber (36.45%). Its extract is rich in bioactive components, including phenolic compounds (28.90 mg GAE/g extract), ascorbic acid (3.25 mg/g extract), total anthocyanins (316.35 µg C3GE/g extract), and total carotenoids (12.68 µg ßCE/g extract) and has good antioxidant capacity. As the level of TP increased, the color of steamed breads became darker, redder, and yellower; the texture became harder, and the overall consumption preference decreased. However, their bioactive components content and antioxidant activity increased. The starch hydrolysis percentage of T5 (43.82%), T10 (41.57%), T15 (37.41%), and T20 (35.63%) at 180 min was significantly lower than that of the control (49.80%) (p < 0.05). The in vitro predicted glycemic index (80.02) of T20 was categorized as a medium-GI food when bread was used as the reference. On a nine-point hedonic test, control and T5 had the highest overall preference scores (7.1-7.4). The T20 supplemented with extra 15-20% water improved its volume and specific volume, and the overall preference scores (7.4-7.5) were not significantly different from the control (p > 0.05). Overall, a partial replacement of wheat flour with TP in steamed bread making could be developed as a new type of medium-GI value food containing more bioactive components and effective antioxidant capacity.

Methylated Septin9 has moderate diagnostic value in colorectal cancer detection in Chinese population: a multicenter study.

BACKGROUND: The detection rate of methylated Septin9 (mSEPT9) in colorectal cancer (CRC) is varied greatly across the studies. This study aimed to evaluate the diagnostic ability of mSEPT9 in CRC, and compare the diagnostic efficacy with fecal immunochemical test (FIT). METHODS: 326 subjects from four centers were prospectively recruited, including 179 CRC and 147 non-CRC subjects. The plasma was collected for mSEPT9 and CEA, AFP, CA125, CA153 and CA199 test, and fecal samples for FIT tests. Sensitivity, specificity and area under the curve (AUC) of receiver operating characteristic curve were calculated to evaluate the diagnostic value of each biomarker. RESULTS: The positive rate in mSEPT9 and FIT, and the level of CEA, CA125 and CA199 were significantly higher in CRC compared with non-CRC subjects. The mSEPT9 positive rate was not associated with TNM stage and tumor stage. The sensitivity, specificity and AUC of mSEPT9 in diagnostic CRC were 0.77, 0.88 and 0.82, respectively, while the value in FIT was 0.88, 0.80 and 0.83, respectively. mSEPT9 and FIT have higher AUC value than that of CEA, CA125 and CA199. Combination of both mSEPT9 and FIT positive increased sensitivity and AUC to 0.98 and 0.83, respectively, but the specificity was declined. mSEPT9 has a slightly low sensitivity in diagnosis of colon cancer (0.87) compared with rectal cancer (0.93). CONCLUSION: mSEPT9 demonstrated moderate diagnostic value in CRC detection, which was similar to the FIT but superior to the CEA, CA125 and CA199. Combination of mSEPT9 and FIT further improved diagnostic sensitivity in CRC. TRIAL REGISTRATION: ChiCTR2000038319.

Application of modern neuroimaging technology in the diagnosis and study of Alzheimer's disease.

Neurological abnormalities identified via neuroimaging are common in patients with Alzheimer's disease. However, it is not yet possible to easily detect these abnormalities using head computed tomography in the early stages of the disease. In this review, we evaluated the ways in which modern imaging techniques such as positron emission computed tomography, single photon emission tomography, magnetic resonance spectrum imaging, structural magnetic resonance imaging, magnetic resonance diffusion tensor imaging, magnetic resonance perfusion weighted imaging, magnetic resonance sensitive weighted imaging, and functional magnetic resonance imaging have revealed specific changes not only in brain structure, but also in brain function in Alzheimer's disease patients. The reviewed literature indicated that decreased fluorodeoxyglucose metabolism in the temporal and parietal lobes of Alzheimer's disease patients is frequently observed via positron emission computed tomography. Furthermore, patients with Alzheimer's disease often show a decreased N-acetylaspartic acid/creatine ratio and an increased myoinositol/creatine ratio revealed via magnetic resonance imaging. Atrophy of the entorhinal cortex, hippocampus, and posterior cingulate gyrus can be detected early using structural magnetic resonance imaging. Magnetic resonance sensitive weighted imaging can show small bleeds and abnormal iron metabolism. Task-related functional magnetic resonance imaging can display brain function activity through cerebral blood oxygenation. Resting functional magnetic resonance imaging can display the functional connection between brain neural networks. These are helpful for the differential diagnosis and experimental study of Alzheimer's disease, and are valuable for exploring the pathogenesis of Alzheimer's disease.

[Cathepsin B Affects the Activation of Nucleotide-binding Domain and Leucine-rich-repeat-containing Family and Pyrin Domain-containing 3 Inflammasome via Transient Receptor Potential Mucolipin-1].

Objective To explore the effects of cathepsin B(CTSB)on the activation of nucleotide-binding domain and leucine-rich-repeat-containing family and pyrin domain-containing 3(NLRP3)inflammasome via transient receptor potential mucolipin-1(TRPML1)in cell oxidative stress model and specific gene silencing cell model. Methods BV2 cells cultured in vivo were treated separately or simultaneously with hydrogen peroxide(H2O2),calcium-sensitive receptor agonist gadolinium trichloride(GdCl3),and CTSB inhibitor CA-074Me,and interleukin-1(IL-1)beta and caspase-1 protein were detected by enzyme-linked immunosorbent assay.The growth activity of BV2 cells in each group was measured by MTT.BV2 cells were treated with different concentrations of H2O2.Cystatin C mRNA and TRPML1 mRNA in BV2 cells were detected by real-time quantitative polymerase chain reaction and the proteins of TRPML1,CTSB,cathepsin D(CTSD),cathepsin L(CTSL)and cathepsin V(CTSV)were detected by Western blot.Specific small interfering RNA was designed for TRPML1 gene target sequence.TRPML1 gene silencing cell lines(named Tr-si-Bv2 cells)were established in BV2 cells and treated with or without H2O2.TRPML1,CTSB and transcription factor EB(TFEB)proteins in Tr-si-Bv2 cells or control cells were detected by Western blot. Results After treatment with H2O2,the expression of caspase-1 protein and NLRP3 mRNA in BV2 cells was increased,and IL-1beta protein in BV2 cells was significantly increased after treatment with GdCl3(P=0.0036).After treatment with CA-074Me,the doses of NLRP3 mRNA(P=0.037),caspase-1(P=0.021),and IL-1ß(P= 0.036)were significantly reduced.Cells in the H2O2 group and H2O2+GdCl3 group grew more slowly.The expressions of CTSB mRNA and TRPML1 mRNA,or CTSB and TRPML1 proteins in BV2 cells in the treatment group with 200 µmol/L of H2O2 concentration were similar.H2O2-induced CTSB protein expression was inhibited after silencing TRPML1 gene.The changes of other cathepsins were not affected for the different concentration of H2O2.In the BV2 cells treated with TRPML1 gene silencing,the expression of CTSB protein was significantly reduced and the difference was statistically significant(P=0.021)between the H2O2 +siRNA treatment group and the H2O2 treatment group.Conclusion CTSB regulates the activation of NLRP3 inflammasome in the oxidative stress model of microglia cells,probably mediated by calcium channel protein TRPML1.

Downregulation of signal transduction and STAT3 expression exacerbates oxidative stress mediated by NLRP3 inflammasome.

Activated nucleotide binding to the oligonucleotide receptor protein 3 (NLRP3) inflammasome is possibly involved in the pathogenesis of Alzheimer's disease through oxidative stress and neurogenic inflammation. Low expression of the signal transducer and activator of transcription 3 (STAT3) gene may promote the occurrence of neurodegenerative diseases to some extent. To clarify the roles of the NLRP3 inflammasome and STAT3 expression in oxidative stress, (1) SHSY5Y cells were incubated with 1 mM H2O2 to induce oxidative stress injury, and the expression of human-cell-specific signal transduction, STAT3-shRNA silencing signal transduction and STAT3 were detected. Cells were pretreated with Ca2+ chelator BAPATA-AM (0.1 mM) for 30 minutes as a control. (2) Western blot assay was used to analyze the expression of caspase-1, NLRP3, signal transduction and STAT3. Enzyme-linked immunosorbent assay was used to analyze interleukin-1ß levels. Flow cytometry was carried out to calculate the number of apoptotic cells. We found that H2O2 treatment activated NLRP3 inflammasomes and decreased phosphorylation of signal transduction and STAT3 serine 727. BAPTA-AM pretreatment abolished the H2O2-induced activation of NLRP3 inflammasomes, caspase-1 expression, interleukin-1ß expression and apoptosis in SHSY5Y cells, and had no effect in cells with downregulated STAT3 expression by RNAi. The findings suggest that downregulation of signal transduction and STAT3 expression may enhance the oxidative stress mediated by NLRP3, which may not depend on the Ca2+ signaling pathway.

Deficit in learning and memory of rats with chronic fluorosis correlates with the decreased expressions of M1 and M3 muscarinic acetylcholine receptors.

To reveal the molecular mechanism of deficit in learning and memory induced by chronic fluorosis, the expression of muscarinic acetylcholine receptors (mAChRs) and oxidative stress were investigated. Sixty Sprague-Dawley (SD) rats were divided randomly into two groups (30 cases in each), i.e., the control group (<0.5 ppm fluoride in drinking water) and the fluoride group (50 ppm fluoride) for 10 months of treatment. The pups born from SD mothers with or without chronic fluorosis were selected at postnatal days 1, 7, 14, 21 and 28 for experiments (10 for each age). Spatial learning and memory were evaluated by Morris water maze test. The expressions of M1 and M3 mAChRs at the protein and mRNA levels were determined by Western blotting and real-time PCR, respectively. In addition, the contents of (·)OH, H2O2, O2(·-) and malondialdehyde (MDA), and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in brains were quantitated by biochemical methods. Our results showed that as compared to controls, the abilities of learning and memory were declined in the adult rats and the offspring rats of postnatal day 28 in the fluoride groups; the expressions of both M1 and M3 mAChRs were significantly reduced at protein and mRNA levels; and the levels of (·)OH, H2O2, O2(·-) and MDA were significantly increased, while the activities of SOD and GSH-Px decreased. Interestingly, the decreased protein levels of M1 and M3 mAChRs were significantly correlated with the deficits of learning and memory and high level of oxidative stress induced by chronic fluorosis. Our results suggest that the mechanism for the deficits in learning and memory of rats with chronic fluorosis may be associated with the decreased expressions of M1 and M3 in mAChRs, in which the changes in the receptors might be the result of the high level of oxidative stress occurring in the disease.