AA Group Research Articles

Rs7853346 Polymorphism in lncRNA-PTENP1 and rs1799864 Polymorphism in CCR2 are Associated with Radiotherapy-Induced Cognitive Impairment in Subjects with Glioma Via Regulating PTENP1/miR-19b/CCR2 Signaling Pathway.

LncRNA-PTENP1 was reported to promote multiple myeloma cancer stem cell proliferation, and the G allele of rs7853346 polymorphism in lncRNA-PTENP1 was demonstrated to enhance the effect of lncRNA-PTENP1. In this study, we aimed to study the potential effect of lncRNA-PTENP1 and CCR2 mRNA polymorphisms on cognitive impairment in glioma patients. In this study, 279 glioma patients were recruited and grouped according to their genotypes of rs7853346 in PTENP1 and rs1799864 in CCR1. Pathogenic parameters were collected from patients before radiotherapy (month 0) or at month 1 and month 3 after radiotherapy to study the effect of rs7853346 and rs1799864 on cognitive impairment. Sequence analysis, luciferase assay, real-time PCR, and Western blot were performed to study the regulatory relationships between lncRNA-PTENP1, miR-18b, and CCR2. The glioma patient groups exhibited no significant differences concerning basic characteristics. However, the CG&GG/GG genotype alleviated radiotherapy-induced cognitive impairment by exhibiting the highest MMSE among the four groups. On the contrary, parameters including the severity of depression, bladder control, global health status, itchy skin, and weakness of legs all showed no difference among different patient groups at month 0, month 1, and month 3. Also, a long-term positive effect of CG&GG/GG genotype on role functioning and social functioning was also observed after radiotherapy. Compared with patients carrying the CC genotype of rs7853346, the expression of lncRNA-PTENP1 was reduced while the miR-19b level was elevated in patients carrying the CG&GG genotypes of rs7853346. Moreover, the expression of CCR2 mRNA was the highest in the CC/GA&AA group and the lowest in the CG&GG/GG group. Subsequent sequence analysis and luciferase assay indicated that miR-19b could bind to lncRNA-PTENP1 and 3'UTR of CCR2 mRNA, and the knockdown of lncRNA-PTENP1 led to evident up-regulation of miR-19b and down-regulation of CCR2 mRNA/protein in a cellular model, thus verifying the presence of the lncRNA-PTENP1/miR-19b/CCR2 mRNA signaling pathway. In conclusion, by studying the changes in the key parameters of glioma patients who were subjected to radiotherapy, we concluded that the rs7853346 polymorphism in lncRNA-PTENP1 and the rs1799864 polymorphism in CCR2 could independently affect cognitive impairment, while a more significant combined effect on cognitive impairment was exerted in glioma patients via the signaling pathway of PTENP1/miR-19b/CCR2.

Effect of Haemoglobin Variants on Glycemic Indices

Haemoglobin genotypes have been known to be linked with groups of diseases such as diabetes. The aim of this study is to assess the impact of haemoglobin variants on glycemic indices (fasting blood glucose and glycated haemoglobin) in subjects in Bayelsa State, Nigeria. A total of 150subjects were enrolled for the study with AA group = 99 subjects and AS group = 51 subjects. 4mls of blood was collected into EDTA bottle for each subject and was assayed for Hb electrophoresis and glycated haemoglobin (HbA1C) using electrophoretic method and automated CLOVER A1c Analyser respectively. 2mls was collected into fluoride oxalate bottle for spectrophotometric analysis of fasting blood glucose (FBG). Results revealed that there were no significant differences in the FBG and HbA1C mean levels of the two studied groups (AA and AS). This study has shown that AA and AS blood genotypes may not have any impact on FBG and HbA1C glycemic parameters.

LTA4H rs2660845 association with montelukast response in early and late-onset asthma.

Leukotrienes play a central pathophysiological role in both paediatric and adult asthma. However, 35% to 78% of asthmatics do not respond to leukotriene inhibitors. In this study we tested the role of the LTA4H regulatory variant rs2660845 and age of asthma onset in response to montelukast in ethnically diverse populations. We identified and genotyped 3,594 asthma patients treated with montelukast (2,514 late-onset and 1,080 early-onset) from seven cohorts (UKBiobank, GoSHARE, BREATHE, Tayside RCT, PAGES, GALA II and SAGE). Individuals under montelukast treatment experiencing at least one exacerbation in a 12-month period were compared against individuals with no exacerbation, using logistic regression for each cohort and meta-analysis. While no significant association was found with European late-onset subjects, a meta-analysis of 523 early-onset individuals from European ancestry demonstrated the odds of experiencing asthma exacerbations by carriers of at least one G allele, despite montelukast treatment, were increased (odds-ratio = 2.92, 95%confidence interval (CI): 1.04–8.18, I2 = 62%, p = 0.0412) compared to those in the AA group. When meta-analysing with other ethnic groups, no significant increased risk of asthma exacerbations was found (OR = 1.60, 95% CI: 0.61–4.19, I2 = 85%, p = 0.342). Our study demonstrates that genetic variation in LTA4H, together with timing of asthma onset, may contribute to variability in montelukast response. European individuals with early-onset (≤18y) carrying at least one copy of rs2660845 have increased odd of exacerbation under montelukast treatment, presumably due to the up-regulation of LTA4H activity. These findings support a precision medicine approach for the treatment of asthma with montelukast.

Comparison of clinical outcomes of 2 platforms for topography-guided LASIK in primary eyes.

To compare differences in visual, refractive, and ablating outcomes between corneal topography-guided laser in situ keratomileusis (LASIK) by SCHWIND AMARIS and WaveLight Contoura for myopia and myopic astigmatism correction. Department of Refractive Surgery, Guangzhou Aier Eye Hospital, Guangzhou, China. Prospective nonrandomized study. Patients treated with LASIK to correct ametropia and corneal higher-order aberrations (HOAs) with 6.5 mm of plan optical zone were recruited. In the AMARIS platform, there were 2 centration strategies: the symmetric (AA) and asymmetric (AS) offset modes. In the WaveLight platform, there was only symmetric offset (ES) mode. HOAs, contrast sensitivity, effective optical zone (EOZ), ablation depth, and ablating center were evaluated 3 months after the operation. The study included 138 eyes. At 3 months after operation, the postoperative manifest refractive spherical equivalent was 0.04 ± 0.34 diopters (D), 0.06 ± 0.25 D, and -0.09 ± 0.21 D in AS, AA, and ES groups, respectively (P = .018). The EOZs of the AS and AA groups were 5.01 mm and 4.96 mm, and both were larger than 4.88 mm in the ES group (P = .04 and .03, respectively). The ablation depth of the AS group was 103.6 μm, which were larger than 86.6 μm in the AA group and 91.2 μm in the ES group. The SCHWIND AMARIS and WaveLight EX500 corneal topography-guided LASIK achieved comparable and excellent visual and refractive outcomes. The EX500 Contoura LASIK ablated less corneal tissue because of the smaller EOZ compared with the AMARIS, with a similar plan optical zone.

The Protective Effects of Indole-3-carbinol on Stomach Injury in Rats

The objective of this research was to analyze the protective effect of indole-3-carbinol against the stomach injury induced by acetylsalicylic acid. Male rats were randomly divided into eight groups of six animals in each group. Control group, OMP group, I3C group, OMP+I3C group, AA group, AA+OMP group, AA+I3C group, and AA+OMP+I3C group. The control rats were received distilled water and the experimental rats were received AA at a dose of 500 mg/kg body weight, OMP at a dose of 20 mg/kg body weight, and I3C at a dose of 50 mg/kg body weight either alone or in combination with each other, orally for seven consecutive days. Results of the present study showed ulcer protection in indole-3-cabinol treated rats was confirmed by histoarchitecture, which was comprised of the reduced size of ulcer crater and restoration of mucosal epithelium. Thus, reduced neutrophil infiltration, antiapoptotic and antioxidant action have a pivotal role in the gastroprotective effect of indole-3-carbinol. Keywords: Histopathological; Stomach; Acetylsalicylic acid; Indole-3-carbinol; Rats

The Ethanol Extract of Musa sapientum Linn. Peel Inhibits Melanogenesis through AKT Signaling Pathway

Hyperpigmentation caused by melanin overproduction can be induced by UV radiation. The quest for effective depigmenting agents continues because many anti-melanin agents have restricted use and/or produce side-effects. The present study was aimed to investigate the inhibitory activity of Musa sapientum Linn. (AA group) peel ethanol extracts (MPE) on α-melanocyte stimulating hormone (α-MSH)-induced melanin production. In addition, the molecular mechanism related to this process was examined in B16F10 mouse melanoma cells. The results indicated that MPE remarkably inhibited melanogenesis in α-MSH-stimulated B16F10 cells. Microphthalmia-associated transcription factor (MITF) and tyrosinase expressions were suppressed by MPE in a concentration-dependent manner. In addition, MPE significantly decreased the expression of melanosome transfer protein markers (Rab27a and Pmel17) in a dose-dependent manner. This study found that the elevated phosphorylation of AKT in the B16F10 cells was diminished by MPE treatment. Furthermore, microtubule-associated protein 1 light chain 3 (LC3)-II and p62 (autophagy markers) were affected after the B16F10 cells were treated with MPE. This study demonstrated that MPE might be an effective agent for anti-melanogenesis through the AKT pathway, subsequently diminishing MITF expression and tyrosinase enzyme family production. The findings indicated that MPE could potentially serve as a depigmenting agent in cosmeceuticals.

Long-term amlodipine-based combination therapy attenuates seasonal variation of blood pressure in hypertensive patients

ABSTRACT Objectives: This study was to investigate whether long-term amlodipine-based combination therapy attenuates seasonal variation of office blood pressure (BP) in hypertensive patients. Methods: The data of 206 patients recruited in the Nanchang site of CHIEF trial were retrospectively analyzed. All patients received an amlodipine-based therapy for thres years after reaching target BP with a 12-week titration treatment. Among them, 106 patients received amlodipine plus amiloride/hydrochlorothiazide (AA group) and 100 received amlodipine plus telmisartan (AT group) therapies. These patients were followed up every three months . The difference between the highest and lowest values of outdoor temperature in each three months was calculated as the seasonal temperature difference (T-d) and seasonal BP difference was calculated in the similar way. BP control rates in each season were calculated. Results: In the three years, the highest SBP and DBP values occurred in winter and the lowest values in summer. As a result, the BP control rate in summer was the highest and that in winter was the lowest, especially for SBP. Although T-d levels were similar during three following-up years, the seasonal SBP/DBP differences in 2011 were significantly lower than 2009 (10.03 ± 5.74/6.96 ± 3.72 vs 14.36 ± 8.19/9.78 ± 5.21 mmHg, P < .05), suggesting seasonal variation in BP was obviously reduced. Meanwhile, similar change was observed in AA and AT groups. Conclusions: Besides lower BP effectively, long-term amlodipine-based combination therapy could alleviate the seasonal BP variation in high-risk hypertensive patients.

Schizophrenia-associated variation at ZNF804A correlates with altered experience-dependent dynamics of sleep slow waves and spindles in healthy young adults.

The rs1344706 polymorphism in ZNF804A is robustly associated with schizophrenia and schizophrenia is, in turn, associated with abnormal non-rapid eye movement (NREM) sleep neurophysiology. To examine whether rs1344706 is associated with intermediate neurophysiological traits in the absence of disease, we assessed the relationship between genotype, sleep neurophysiology, and sleep-dependent memory consolidation in healthy participants. We recruited healthy adult males with no history of psychiatric disorder from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Participants were homozygous for either the schizophrenia-associated ‘A’ allele (N = 22) or the alternative ‘C’ allele (N = 18) at rs1344706. Actigraphy, polysomnography (PSG) and a motor sequence task (MST) were used to characterize daily activity patterns, sleep neurophysiology and sleep-dependent memory consolidation. Average MST learning and sleep-dependent performance improvements were similar across genotype groups, albeit more variable in the AA group. During sleep after learning, CC participants showed increased slow-wave (SW) and spindle amplitudes, plus augmented coupling of SW activity across recording electrodes. SW and spindles in those with the AA genotype were insensitive to learning, whilst SW coherence decreased following MST training. Accordingly, NREM neurophysiology robustly predicted the degree of overnight motor memory consolidation in CC carriers, but not in AA carriers. We describe evidence that rs1344706 polymorphism in ZNF804A is associated with changes in the coordinated neural network activity that supports offline information processing during sleep in a healthy population. These findings highlight the utility of sleep neurophysiology in mapping the impacts of schizophrenia-associated common genetic variants on neural circuit oscillations and function.

Disease-Modifying Effect of Japanese Cedar Pollen Sublingual Immunotherapy Tablets

Japanese cedar (JC) pollinosis is a common allergic rhinitis in Japan. JC pollen sublingual immunotherapy (SLIT) tablets are licensed for the treatment of JC pollinosis. To assess the disease-modifying effects of JC pollen SLIT tablets over 5 years (2014-2019), comprising a 3-year treatment period and 2-year follow-up. A total of 1042 patients with JC pollinosis (aged 5-64 years) were included in the study. An optimal dose-finding study was performed in the first 15 months, after which 240 patients in the placebo (P) group and 236 patients in the optimalactive dose (A) group (5000 Japanese allergy units) were re-randomized to receive P or A for an additional 18 months (designated AA, AP, PA, and PP groups). Clinical efficacy was evaluated by the total nasal symptom and medication score (TNSMS) during the peak symptom period of each JC pollen season over 3 years of treatment and 2 years of observation after treatment cessation. The AA, AP, and PA groups exhibited significantly reduced TNSMS; however, the largest relative reduction was seen in the AA group both during the treatment period (third season, 46.3% vs PP, P < .001) and during the 2-year follow-up period (fourth and fifth seasons, 45.3% and 34.0% vs PP, respectively; P < .001). The most common adverse drug reactions were mild reactions at the administration site. JC pollen SLIT tablets show sustained clinical efficacy during 3 years of treatment and sustained disease-modifying effects for at least 2 years after treatment cessation.

RETRACTED: Molsidomine alleviates acetic acid-induced colitis in rats by reducing oxidative stress, inflammation and apoptosis

Ulcerative colitis (UC) is a subcategory of intestinal inflammatory bowel disease characterized by up-regulation of proinflammatory cytokines and oxidative stress. The current study was designed to assess the probable protective effect of the nitric oxide (NO) donor, molsidomine, in experimental colitis model in rats. Rats were haphazardly classified into four groups: control, acetic acid, acetic acid + molsidomine (1 mg/kg) and acetic acid + molsidomine (2 mg/kg). Molsidomine (1 and 2 mg/kg/day) was administered by intra-peritoneal injection for 7 days prior to induction of UC. On the 8th day, colitis was induced by intra-rectal instillation of 2 ml of (4% v/v) acetic acid in normal saline using a pediatric plastic catheter. The rats were sacrificed 1 day following colitis induction, blood samples were obtained; colons and livers were isolated then underwent macroscopic, biochemical, histopathological and immunohistochemical examination. Pretreatment with molsidomine significantly reduced disease activity index, colon mass index, colonic macroscopic and histological damage. Besides, molsidomine significantly reduced the serum levels of alanine transaminase (ALT) (58.7 ± 8.9 & 59.7 ± 8 vs 288.75 ± 31.4 in AA group) and aspartate transaminase (AST) (196.2 ± 37.4 & 204 ± 30 vs 392.7 ± 35.6 in AA group). Moreover, molsidomine effectively decreased malondialdehyde (MDA) and total nitrate/nitrite (NOx) contents, and up regulated the enzymatic activity of superoxide dismutase (SOD) and glutathione level (GSH) in colonic and hepatic tissues. With regard to anti-inflammatory mechanisms, molsidomine suppressed tumor necrosis factor-alpha (TNF-α) (792.5 ± 16.7 & 448 ± 12.1 vs 1352.5 ± 45.8 in AA group) in colonic tissues and (701 ± 19 & 442.5 ± 22.5 vs 1501 ± 26 in AA group) in hepatic tissues as well as nuclear transcription factor kappa B (NF-kB/p65) levels (416.2 ± 4.1 & 185.5 ± 14.2 vs 659.2 ± 11.5 in AA group) in colonic tissues and (358 ± 6.2 & 163.5 ± 9.6 vs 732.5 ± 5.5 in AA group) in hepatic tissues. In addition, molsidomine significantly decreased inducible nitric oxide synthase (iNOS) levels (8.1 ± 0.1 & 4.9 ± 0.1 vs 16 ± 0.1 in AA group) in colonic tissues and (8.6 ± 0.3 & 6.1 ± 0.1 vs 17.8 ± 0.1 in AA group) in hepatic tissues, and myeloperoxidase (MPO) contents (10.5 ± 0.4 & 6.6 ± 0.3 vs 20.9 ± 0.6 in AA group) in colonic tissues and (13.1 ± 0.2 & 6.3 ± 0.06 vs 23.9 ± 1.4 in AA group) in hepatic tissues at p > 0.05. Furthermore, it suppressed apoptosis by reducing expression of Caspase 3 and Bax in colonic and hepatic tissues. Therefore, molsidomine might be a promising candidate for the treatment of UC.

Immune checkpoint inhibitors plus anlotinib versus anlotinib alone as third-line treatment in advanced non-small-cell lung cancer: a retrospective study.

Aim: This study was conducted to evaluate the efficacy of immune checkpoint inhibitors (ICIs) plus anlotinib versus anlotinib alone to provide guidance for clinical treatment of non-small-cell lung cancer. Patients & methods: The records of 139 patients with advanced non-small-cell lung cancer who received at least one dose of ICIs plus anlotinib (IA group) or single-agent anlotinib(AA group)were retrospectively reviewed. The efficacy of the treatments, survival outcomes and adverse events were analyzed. The primary end point was investigator-assessed progression-free survival (PFS). Result: The IA group had a significantly prolonged median PFS (mPFS: 5.8 vs 4.2months; p=0.022) compared with the AA group (hazard ratio: 0.68; 95% CI: 0.68-0.97). In patients with brain metastases, the IA group exhibited improved efficacy (mPFS: 6.0 vs 3.8months; p=0.034) compared with the AA group (hazard ratio: 0.49; 95% CI: 0.23-1.05). Conclusion: ICIs plus anlotinib significantly improved efficacy compared with anlotinib alone and showed substantial potential for the control of intracranial lesions.

The Internet as a Space for Anonymous Alcoholics during the SARS-COV-2 (Covid-19) Pandemic

INTRODUCTION: For over a year, Poland, alongside the entire world, has been facing the SARS-COV-2 (COVID-19 pandemic). This emergency has caused an immense social crisis, affecting especially the individual. The lack of social activity, including direct communication, along severe limitations on public and professional lives, have become a threat to mental health of people in almost all countries of the world. This state can be particularly difficult and dangerous to people with addiction. In the recovery process for alcoholics, a special role is often played by the Alcoholics Anonymous groups.&#x0D; &#x0D; OBJECTIVES: Due to the pandemic, meetings of AA groups (as well as other therapeutic groups) have been suspended until further notice. Due to this - due to necessity, not choice - such groups have moved to the online space. This raises a question if internet group meetings can make up for the lack of AA group meetings in physical space.&#x0D; &#x0D; METHODS: The research had an exploratory character. It was conducted between the start of June and the start of July 2020. 225 people participated. The research was conducted using quantitative methods, using a questionnaire designed specifically for this purpose.&#x0D; &#x0D; RESULTS: The research results indicate that the COVID-19 pandemic affected almost all of our respondents. The way the AA meetings work changed. Compared to live meetings, the frequency of meetings increased, the satisfaction from participation simultaneously decreased. Major flaws of online meetings are seen in the discomfort of respondents: some people stopped attending meetings after they moved to the internet. The positive sides of online meetings mainly had to do with the possibility of meeting and contacting new people living far and with organisational matters. The frequency of attending therapy with specialists/therapists decreased during the pandemic, while the frequency of contact with one&amp;rsquo;s sponsor increased. The overwhelming majority of respondents declared that they did not break abstinence during the pandemic. Those who did were usually people who had spent little time (usually a year, five years at most) in abstinence. The pandemic did not influence subjective appraisal of life quality. &#x0D; &#x0D; CONCLUSION: Our research showed that after the pandemic, our respondents would prefer to return to traditional, live AA meetings, organized as they used to be before COVID-19. Online meetings would only serve a useful, but ultimately complementary role.

Left ventricular function and cardiac valvar annular dimensions among children with sickle cell anemia compared to those with hemoglobin AA type in Enugu, Nigeria.

Enumerating the relationship between cardiac structures, function and chamber sizes in children with sickle cell anemia would help in delineating some cardiovascular abnormalities which will aid the Pediatric cardiologist and the cardiac surgeons in a number of decision-making situations. The objectives of this study are to assess the dimension of cardiac structures and left ventricular function in children with sickle cell anemia in steady state and controls using echocardiography. A cross-sectional prospective study that assessed cardiac structures and left ventricular function among fifty-one children with sickle cell anemia (HBSS) and compared with fifty children with HB AA type serving as controls. A significant high proportion of children with sickle cell anemia had abnormal Valvar dimension and left ventricular function above two standard deviations (2-SD) from the mean of the standard population compared to the control group, showing a statistically significant difference (χ2 = 10.42, p= 0.001).All the mean annular valves diameter, left ventricular internal dimension in systole and diastole, inter-sinus distance diameter and sinu-tubular junction diameter are higher in children with sickle cell anemia than controls and this is statistically significant. (p<0.005). This result shows that children with sickle cell anemia have increased valvar size diameter compared with those with normal hemoglobin type. A significantly higher proportion of respondents in type SS group had abnormal left ventricular systolic and diastolic dysfunction when compared with those in type AA group.

Minor allele of rs55763075 located in MTHFR is associated with the risk of cognitive impairment after anesthesia via modulating miR-34b

This study aimed to investigate the association between cognitive impairment after general anesthesia and rs55763075 polymorphisms. We enrolled and grouped patients undergoing general anesthesia according to their genotypes of rs55763075 polymorphism. Mini–Mental State Examination (MMSE) scoring was performed to evaluate the cognitive status of patients. Quantitative real-time PCR was carried out to analyze the expression of methylenetetrahydrofolate reductase (MTHFR) mRNA and miR-34b while Western blot was performed to evaluate the expression of MTHFR protein. Furthermore, we studied the effect of rs55763075 polymorphism on the expression of MEHFR via luciferase assay. Accordingly, we found that the MMSE score in GG/GA groups was significantly higher than that in AA group. And a significant reduction of MTHFR mRNA expression was observed in the serum and peripheral blood mononuclear cells (PBMCs) of patients carrying AA genotype compared with the patients carrying GG/GA genotypes. Moreover, the MTHFR expression was much lower in the cultured AA-genotyped cells transfected with miR-34b. Luciferase assay results also showed that miR-34b transfection reduced luciferase activity in the cells carrying A allele but not in cells carrying G allele. In summary, the data of this study showed that minor allele (A) of rs55763075 polymorphisms in the 3'-untranslated region of MTHFR mRNA generated a potential binding site for miR-34b, which led to reduced level of folic acid in the patients carrying the AA genotype. Furthermore, we found that the MMSE score of AA-genotyped patients was lower than that of patients carrying GG/GA genotypes.

The changing definition of Alzheimer's disease

Widely used criteria for the diagnosis of Alzheimer's disease were established in 1984. These criteria outlined a typical clinical picture, recommended laboratory testing to exclude other causes of dementia, required neuropathological examination for a definitive diagnosis, and categorised individuals without pathological verification as having probable or possible Alzheimer's disease. 1 McKhann G Drachman D Folstein M Katzman R Price D Stadlan EM Clinical diagnosis of Alzheimer's disease: report of the NINCDS–ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984; 34: 939-944 Crossref PubMed Google Scholar For more than 20 years, Alzheimer's disease remained a probabilistic clinical-pathological syndrome; syndromes are notoriously non-specific and the Alzheimer's disease syndrome was no exception. 2 Knopman DS DeKosky ST Cummings JL et al. Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001; 56: 1143-1153 Crossref PubMed Scopus (1318) Google Scholar The gradual appearance of biomarkers (initially non-specific MRI measures of brain atrophy and PET measures of glucose hypometabolism; later CSF and PET measures of amyloid β and pathological tau) resulted in new criteria, proposed by an International Working Group (IWG), for incorporation of biomarkers into the diagnostic assessment. 3 Dubois B Feldman HH Jacova C et al. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS–ADRDA criteria. Lancet Neurol. 2007; 6: 734-746 Summary Full Text Full Text PDF PubMed Scopus (3090) Google Scholar , 4 Dubois B Feldman HH Jacova C et al. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria. Lancet Neurol. 2014; 13: 614-629 Summary Full Text Full Text PDF PubMed Scopus (1745) Google Scholar Continued evolution of these criteria resulted in the term preclinical dementia, introduced by a US National Institute on Aging–Alzheimer's Association (NIA–AA) workgroup and the IWG. 5 Dubois B Hampel H Feldman HH et al. Preclinical Alzheimer's disease: definition, natural history, and diagnostic criteria. Alzheimers Dement. 2016; 12: 292-323 Summary Full Text Full Text PDF PubMed Scopus (696) Google Scholar , 6 Sperling RA Aisen PS Beckett LA et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging–Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011; 7: 280-292 Summary Full Text Full Text PDF PubMed Scopus (3999) Google Scholar This term was meant to describe individuals with no symptoms but who expressed biomarkers indicating the presence of amyloid β and tau pathology, with the goal of identifying those in the very earliest stages of Alzheimer's disease who might benefit from therapeutic trials and, eventually, therapy. This description of asymptomatic individuals was controversial enough, but in 2018, the NIA–AA group introduced a research framework in which people with biomarkers indicating pathological accumulation of amyloid β and tau were categorised as having Alzheimer's disease (no longer modified by the term preclinical or probable), regardless of the presence of symptoms. 7 Jack Jr, CR Bennett DA Blennow K et al. NIA–AA Research Framework: toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018; 14: 535-562 Summary Full Text Full Text PDF PubMed Scopus (2228) Google Scholar Removing clinical criteria eliminated the syndromic aspect of Alzheimer's disease and its inherent non-specificity. However, this shift to an entirely biological or biomarker-based entity also raised questions and objections. In The Lancet Neurology, Bruno Dubois and colleagues from the IWG 8 Dubois B Villain N Frisoni G et al. Clinical diagnosis of Alzheimer's disease: recommendations of the International Working Group. Lancet Neurol. 2021; (publishing online April 29.)https://doi.org/10.1016/S1474-4422(21)00066-1 Summary Full Text Full Text PDF PubMed Scopus (10) Google Scholar critique the shortcomings of this approach, and propose updated criteria for the use of biomarkers in a clinical setting. Clinical diagnosis of Alzheimer's disease: recommendations of the International Working GroupIn 2018, the US National Institute on Aging and the Alzheimer's Association proposed a purely biological definition of Alzheimer's disease that relies on biomarkers. Although the intended use of this framework was for research purposes, it has engendered debate and challenges regarding its use in everyday clinical practice. For instance, cognitively unimpaired individuals can have biomarker evidence of both amyloid β and tau pathology but will often not develop clinical manifestations in their lifetime. Full-Text PDF

Postharvest senescent dark spot development mechanism of Musa acuminata ("Khai" banana) peel associated with chlorophyll degradation and stomata cell death.

The occurrence of the postharvest physiological disorder of dark spots on the peel of the ripened "Khai" banana has led to a reduction in its commercial value. The objective of the present study was to investigate the development mechanisms of senescence dark spots of the "Khai" (Musa AA group) banana peel in relation to chlorophyll degradation and stomata cell death. Freshly harvested bananas (commercial mature green stage) were let to ripened at 25±2°C (90%-95% RH). Peel color, senescent spots, DNA degradation, chlorophyll content, chlorophyll-degrading enzyme activities were assessed. The senescent dark spots developed on the ripened bananas right after 6days of storage, which coincided with remarkably increased DNA degradation, and a rapid decreased of hue angle value and total chlorophyll content which indicated the chlorophyll degradation. The activities of chlorophyllase, chlorophyll-degrading peroxidase and pheophytinase increased gradually to the highest point where the chlorophyll content drastically reduced and the appearance of the dark spots was first recorded after 6days of storage. These dark spots were observed to be surrounded with a bright luminescent ring of hypermodified fluorescent chlorophyll catabolites (FCCs), the product of chlorophyll breakdown. Additionally, the scanning electron microscope (SEM) revealed that the dark spots were found to have originated from the collapsed cells around the stomata of the ripened banana peel whereby the chlorophyll was entirely diminished. PRACTICAL APPLICATIONS: This research revealed the senescent dark spot development mechanisms of the "Khai" banana peel. The dark spot development symptom on the banana peel surface was caused by the senescence and cell death of the relevant stomata, further associated with chlorophyll degradation. Therefore, any further research into minimizing the dark spot symptom must focus on preventing or delaying stomata senescence and cell death.

CGRP protects bladder smooth muscle cells stimulated by high glucose through inhibiting p38 MAPK pathway in vitro

This study aimed to explore the effect of calcitonin gene-related peptide (CGRP) on bladder smooth muscle cells (BSMCs) under high glucose (HG) treatment in vitro. BSMCs from Sprague–Dawley rat bladders were cultured and passaged in vitro. The third-generation cells were cultured and divided into control group, HG group, HG + CGRP group, HG + CGRP + asiatic acid (AA, p-p38 activator) group, CGRP group, AA group, HG + CGRP + CGRP-8-37 (CGRP receptor antagonist) group and HG + LY2228820 (p38 MAPK inhibitor) group. The cell viability, apoptosis, malondialdehyde (MDA) and superoxide dismutase (SOD) levels of BSMCs were observed by the relevant detection kits. The expressions of α-SM-actin, p38 and p-p38 were detected by qRT-PCR or Western blot analysis. Compared with the control group, the cell viability, SOD and α-SM-actin levels of BSMCs were decreased and apoptotic cells, MDA and p-p38 levels were increased after HG treatment, while these changes could be partly reversed when BSMCs were treated with HG and CGRP or LY2228820 together. Moreover, AA or CGRP-8-37 could suppress the effect of CGRP on BSMCs under HG condition. Our data indicate that CGRP protects BSMCs from oxidative stress induced by HG in vitro, and inhibit the α-SM-actin expression decrease through inhibiting the intracellular p38 MAPK signaling pathway.

Optimization of Mouse Model of Aplastic Anemia Induced by Pan T Lymphocytes Combined with Irradiation

To establish the acquired aplastic anemia mouse model through the X-ray irradiation in combination with lymphocytes injection. AA Group: the purified Pan T lymphocytes from the spleen of C57BL/6J mice were enriched and injected to the mice through tail vein(5×106), the CB6F1 mice were exposed to 3,4 and 5 Gy X-ray irradiation; TBI Group: the CB6F1 mice were exposed to 3,4 and 5 Gy X-ray irradiation, and were injected with the same volume of PBS buffer; Control group: the CB6F1 mice were only injected with the same volume of PBS buffer. The peripheral blood routine was examined and the number of nucleated cells in bone marrow were calculated；the hematopoiesis changes in bone marrow was examined；flow cytometry was used to examine the distribution of T lymphocytes in bone marrow, and it also used to examine the apoptosis of bone marrow cells and the differentiation of spleen T lymphocytes. Compared with 4, 5 Gy irradiated mice in AA groups, the survival time of 3 Gy irradiated AA groups was significantly prolonged. 3, 4 and 5 Gy X-ray irradiation combined with Pan T lymphocyte injection could successfully induced severe reduction of red blood cells, blood neutrophils, and platelets, severe reduction of bone marrow nucleated cells, severe bone marrow hematopoietic failure, and the significant expansion of T lymphocytes ratio in the bone marrow. CD4+ and CD8+ T cells were both increased, but mainly on CD8+ T cells, and could promote the differentiation of T cells from naïve T cells to effector memory T cells. 3, 4 and 5 Gy X-ray irradiation combined with 5×106 pan-T cell injection could successfully induce acquired aplastic anemia through T lymphocyte hyperfunction. Compared with 4, 5 Gy irradiated AA group, the 3 Gy irradiated AA group shows significantly longer survival time, and the peripheral blood routine profile closely resembles the clinical manifestations of AA patients.

Deficient mitophagy pathways in sickle cell disease

Sickle cell disease (SCD) is characterised by chronic haemolysis and oxidative stress. Herein, we investigated 30 SCD patients and found 40% with elevated mitochondria levels (SS-mito+ ) in their mature red blood cells, while 60% exhibit similar mitochondria levels compared to the AA group (SS-mito- ). The SS-mito+ patients are characterised by higher reticulocytosis and total bilirubin levels, lower foetal haemoglobin, and non-functional mitochondria. Interestingly, we demonstrated decreased levels of mitophagy inducers, PINK1 and NIX, and higher levels of HSP90 chaperone in their red cells. Our results highlighted for the first time an abnormal retention of mitochondria in SCD linked with mitophagy-related proteins.

The UNCX Polymorphism is Associated with the Development of Renal Dysfunction after Lung Transplantation

<h3>Purpose</h3> Renal dysfunction is a well-known long-term complication which could increase mortality after non-renal solid organ transplantation. Recently, the UNCX variant (rs10277115), which encodes a paired-type homeobox transcription factor and has essential roles in skeleton formation and kidney development, has been shown to be associated with increased risk for chronic kidney disease in east Asian populations. However, the association between the UNCX variant and renal dysfunction after lung transplantation (LT) has not yet been elucidated. In the present study, we evaluated the association between the UNCX variant and the postoperative change of renal function after LT. <h3>Methods</h3> A total of 99 recipients of LT more than 18 years were genotyped for the functional polymorphism of the UNCX gene (rs10277115) and divided into two groups: the wild-type allele (AA) group and the heterozygous and homozygous mutant allele (AT/TT) group. The results of renal function tests were compared between the two groups. Delta creatinine (ΔCr) and delta eGFR (ΔeGFR) were defined as the difference between the postoperative level and the preoperative baseline level. <h3>Results</h3> The clinical characteristics of the patients were similar between the two groups. There were no significant differences in the previously described risk factors for renal function, including age, diabetes mellitus, hypertension and dyslipidemia. The postoperative change of ΔCr was significantly higher in the AA group than the AT/TT group after LT (Figure 1(a)). Moreover, the postoperative change of ΔeGFR was significantly lower in the AA group than the AT/TT group after LT (Figure 1(b)). The multivariate analysis revealed that the UNCX variant was independently associated with the levels of ΔCr and ΔeGFR. <h3>Conclusion</h3> The UNCX variant was associated with significant differences in Cr and eGFR in the long term and the development of renal dysfunction after LT.