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Recent studies implicate the defects or altered expression of the orphan nuclear receptor Nurr1 gene in the substantia nigra in Parkinson's disease pathogenesis. In an attempt to corroborate the treatment-modifying disease that would replicate the effect of Nurr1, it has been found that amodiaquine and Nurr1 had the same chemical scaffolding, indicating a crucial structure-activity relationship. Interestingly, amodiaquine stimulate the transcriptional function of Nurr1 by physical interaction with its ligand-binding domain (LBD). However, the signaling route by which Nurr1 is activated by amodiaquine to cause the protective effect remains to be elucidated. We first demonstrated that amodiaquine treatment ameliorated behavioural deficits in 6-OHDA Parkinson's disease mouse model, and it promoted dopaminergic neurons protection signified by Tyrosine hydroxylase (TH) and dopamine transporter (DAT) mRNA; Tyrosine hydroxylase (TH) protein expression level and the immunoreactivity in the substantia nigra compacta. Subsequently, we used inhibitors to ascertain the effect of amodiaquine on Akt and P38 Mapk as crucial signaling pathways for neuroprotection. Wortmannin (Akt Inhibitor) induced a significant reduction of Akt mRNA; however, there was no statistical difference between the amodiaquine-treated group and the control group suggesting that amodiaquine may not be the active stimulant of Akt. Western blot analysis confirmed that the phosphorylated Akt decreased significantly in the amodiaquine group compared to the control group. In the same vein, we found that amodiaquine substantially increased the level of phosphorylated P38 Mapk. When P38 Mapk inhibited by SB203580 (P38-Mapk Inhibitor), the total P38 Mapk but not the phosphorylated P38 Mapk decreased significantly, while tyrosine hydroxylase significantly increased. These results collectively suggest that amodiaquine can augment tyrosine hydroxylase expression via phosphorylated P38 Mapk while negatively regulating the phosphorylated Akt in protein expression.Focal adhesion kinase (FAK), human myofibrillogenesis regulator-1 (MR-1), ephrin receptor type A4 (EphA4), proto-oncogene tyrosine kinase Src (Src), and protein kinase C (PKC) are important markers in proliferation, survival, and migration in some cancers. However, the significance of each is still unclear in different malignancies, including acute myeloid leukemia (AML). Therefore, this study was conducted to investigate their serum levels in Egyptian adult de novo AML patients (n = 70) against healthy volunteers (n = 20). We managed to study the correlation between each pair and to investigate their association with diagnosis, prognosis, and survival. Serum levels were analyzed using enzyme-linked immunosorbent assay (ELISA). We found that FAK, MR-1, Src, and PKC serum levels were significantly higher in AML patients compared to control (p less then 0.0001), and this was associated with significantly lower EphA4 level (p less then 0.0001). Interestingly, we also observed a significant negative correlation of FAK (p = 0.027), MR-1 (p = 0.003), Src (p = 0.038), and PKC (p = 0.03) with patients' overall survival (OS) while there was a positive significant correlation between EphA4 and OS (p = 0.007). In conclusion, this study suggests that FAK, MR-1, EphA4, Src, and PKC may be used as early diagnostic and prognostic markers with high sensitivity and specificity in AML patients and thus may be incorporated into the patients' early diagnostic and prognostic panels.Background The incidence of osteoporosis in Malaysia is increasing due to a fast-ageing population. Because of its silent nature, various osteoporosis risk assessment tools exist to detect high-risk patients and facilitate referrals for bone mineral density measurements. As an accessible point of contact, community pharmacists would benefit from the utilization of these tools and familiarity with guideline recommendations for osteoporosis screening. Aim This study aimed to investigate the awareness of osteoporosis risk assessment tools, practice behaviour towards osteoporosis, and knowledge of guideline recommendations among community pharmacists in the Klang Valley, Malaysia. Setting Community pharmacies. Methods This study was a cross-sectional study which sampled 284 community pharmacists practicing in the Klang Valley, using a stratified sampling approach. The study was conducted using a self-administered questionnaire which was divided into three sections demographic data, knowledge of osteoporosis risk ine recommendations among respondents was low. Conclusion There is some awareness of osteoporosis risk assessment tools but use in practice remains low among community pharmacists in Malaysia. There is potential to increase the use of these tools and knowledge of recommendations for osteoporosis screening and referral among community pharmacists.Little is known about the effects of exercise training (ET) on lexical characteristics during fluency task and its association with cerebellum functional connectivity. The purposes of this study were (1) to investigate whether ET alters response patterns during phonemic and semantic fluency tasks and (2) to assess the association between ET-related changes in cerebellum functional connectivity (FC) and lexical characteristics during fluency tasks. BGB-283 cost Thirty-five older adults (78.0 ± 7.1 years; 17 mild cognitive impairment (MCI) and 18 healthy cognition (HC)) underwent a 12-week treadmill ET. Before and after ET, cardiorespiratory fitness tests, phonemic and semantic fluency tests, and resting-state fMRI scans were administered. We utilized a seed-based correlation analysis to measure cerebellum FC and linear regression to assess the association of residualized ET-induced Δcerebellum FC with Δtask performance. Improved mean switches and frequency during the phonemic fluency task were observed following ET in all participants. There were significant associations between ET-induced increases in cerebellum FC and greater phonemic fluency task log frequency, increases in mean switches, and a reduction in the number of syllables in HC. Lastly, there was a significant interaction between group and cerebellar connectivity on phonemic fluency mean log frequency and number of syllables. A 12-week walking ET is related to enhanced phonemic fluency lexical characteristics in older adults with MCI and HC. The association between ET-induced increases in cerebellum FC and enhanced response patterns after ET suggests that the cerebellum may play an important role in ET-related improvement in phonemic fluency performance in cognitively healthy older adults.
We aimed to evaluate the efficacy of bandage contact lens (BCL) for the management of dry eye disease (DED) after cataract surgery.
A total of 120 patients (140 eyes) with age-related cataract and DED were enrolled in this study. Patients underwent standard micro-incision phacoemulsification surgeries and were divided into control or BCL groups. Slit-lamp biomicroscopic examination, Ocular Surface Disease Index, keratograph analysis and Schirmer I test were executed, and the levels of tear inflammatory molecules were detected.
In the control group, the NIAvg-BUT and Schirmer I test scores were significantly decreased at 1week post-operation compared with baseline levels (P = 0.035 and P = 0.009, respectively). In the BCL group, the NIF-BUT and Schemer I test scores were significantly improved at 1month after operation compared with the control group (P = 0.012 and P < 0.001, respectively). Levels of IL-6, IL-8 and ICAM-1 were significantly increased in the control group at 1month after the operation (P = 0.005, P = 0.038 and P = 0.022, respectively), while there was no difference in the BCL group. The increase in the IL-6 level in the control group was significantly higher compared with that in the BCL group (P = 0.047). In DED patients, there were significant correlations between ocular surface parameters and inflammatory molecules.
Cataract surgery could lead to the development or worsening of DED. The application of BCLs after cataract surgery could stabilize the ocular surface and tear film, improve the corneal healing and reduce the inflammation. Collectively, our findings suggested that proper use of BCLs after cataract surgery played an effective role in the management of DED.
ClinicalTrials, NCT04100031. Registered 18 September 2019-retrospectively registered.
ClinicalTrials, NCT04100031. Registered 18 September 2019-retrospectively registered.A novel cold-water-soluble polysaccharide (BEP), with a molecular weight of 6.0 × 106 Da, was isolated from Boletus edulis. BEP consists of galactose, glucose, xylose, mannose, glucuronic, and galacturonic acid in a ratio of 0.340.280.282.571.000.44. The IR results showed that BEP was an acid polysaccharide, containing α-type and β-type glucoside bonds. MTT assay showed BEP could inhibit cell proliferation significantly. Morphological observation demonstrated that BEP-treated MDA-MB-231 and Ca761 cells exhibited typical apoptotic morphological features. Flow cytometry analysis revealed that BEP caused mitochondrial membrane potential collapse. Annexin V-FITC/PI staining indicated that BEP induced apoptosis of MDA-MB-231 and Ca761 cells through cell block in S phase and G0/G1 phase, respectively. Western blot results showed that BEP could increase the Bax/Bcl-2 ratios, promote the release of cytochrome C, and activate the expression of caspase-3 and caspase-9 in MDA-MB-231 and Ca761 cells. In conclusion, our results demonstrated that BEP could inhibit the proliferation of breast cancer cells and induce apoptosis through mitochondrial pathways.The objective of this study was to identify subgroups of toddlers with DSM-5 ASD based on core ASD symptoms using a person-based analytical framework. This is a retrospective study of 500 toddlers (mean age 26 months, 79% male) with DSM-5 ASD. Data were analyzed using latent class analyses in which profiles were formed based on ASD symptomatology. Social communication (SC) symptoms favored a three-class solution, while restricted/repetitive behaviors (RRBs) favored a two-class solution. Classes with higher consistency of SC deficits were younger, with lower developmental functioning. The class with more RRBs was older, with higher functioning. If confirmed in other populations, these classes may more precisely characterize subgroups within the heterogeneous group of toddlers at time of ASD diagnosis.As the number of diagnosed adults living with autism spectrum disorder (ASD) continues to grow, a lack of resources and lack of available interventions exacerbate their low quality of life, including low levels of education and employment, and high levels of co-morbid anxiety and depression. Here we build upon existing research showing the effectiveness of contemplative interventions on individuals with ASD, to provide a low-cost biofeedback-enhanced training which can be implemented by non-professional staff, and may help autistic individuals grasp abstract contemplative techniques. We hypothesize that the intervention will decrease participants' anxiety and autism symptoms, and increase their self-awareness, self-determination, and empathy. Fourteen adults with ASD, residing in assisted living, were provided with 16 weekly half-hour contemplative-biofeedback sessions with non-professional trainers, in which they learned to reduce their arousal levels through combined biofeedback and contemplative techniques, and apply those to everyday life.
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