SGLT2 inhibitor empagliflozin alleviates cardiac remodeling and contractile anomalies in a FUNDC1-dependent manner in experimental Parkinson's disease.

Recent evidence shows a close link between Parkinson's disease (PD) and cardiac dysfunction with limited treatment options. Mitophagy plays a crucial role in the control of mitochondrial quantity, metabolic reprogramming and cell differentiation. Mutation of the mitophagy protein Parkin is directly associated with the onset of PD. Parkin-independent receptor-mediated mitophagy is also documented such as BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) and FUN14 domain containing 1 (FUNDC1) for receptor-mediated mitophagy. In this study we investigated cardiac function and mitophagy including FUNDC1 in PD patients and mouse models, and evaluated the therapeutic potential of a SGLT2 inhibitor empagliflozin. MPTP-induced PD model was established. PD patients and MPTP mice not only displayed pronounced motor defects, but also low plasma FUNDC1 levels, as well as cardiac ultrastructural and geometric anomalies (cardiac atrophy, interstitial fibrosis), functional anomalies (reduced E/A ratio, fractional shortening, ejection fraction, cardiomyocyte contraction) and mitochondrial injury (ultrastructural damage, UCP2, PGC1α, elevated mitochondrial Ca2+ uptake proteins MCU and VDAC1, and mitochondrial apoptotic protein calpain), dampened autophagy, FUNDC1 mitophagy and apoptosis. By Gene set enrichment analysis (GSEA), we found overtly altered glucose transmembrane transport in the midbrains of MPTP-treated mice. Intriguingly, administration of SGLT2 inhibitor empagliflozin (10 mg/kg, i.p., twice per week for 2 weeks) in MPTP-treated mice significantly ameliorated myocardial anomalies (with exception of VDAC1), but did not reconcile the motor defects or plasma FUNDC1. FUNDC1 global knockout (FUNDC1-/- mice) did not elicit any phenotype on cardiac geometry or function in the absence or presence of MPTP insult, but it nullified empagliflozin-caused cardioprotection against MPTP-induced cardiac anomalies including remodeling (atrophy and fibrosis), contractile dysfunction, Ca2+ homeostasis, mitochondrial (including MCU, mitochondrial Ca2+ overload, calpain, PARP1) and apoptotic anomalies. In neonatal and adult cardiomyocytes, treatment with PD neurotoxin preformed fibrils of α-synuclein (PFF) caused cytochrome c release and cardiomyocyte mechanical defects. These effects were mitigated by empagliflozin (10 µM) or MCU inhibitor Ru360 (10 µM). MCU activator kaempferol (10 µM) or calpain activator dibucaine (500 µM) nullified the empagliflozin-induced beneficial effects. These results suggest that empagliflozin protects against PD-induced cardiac anomalies, likely through FUNDC1-mediated regulation of mitochondrial integrity.

Effectiveness and Safety of Trabeculectomy along with Amniotic Membrane Transplantation on Glaucoma: A Systematic Review.

PURPOSE: To determine the effectiveness and safety of trabeculectomy along with amniotic membrane transplantation (AMT) for glaucoma. METHODS: This systematic review was performed using RevMan 5.3. We searched PubMed, EMBASE, and the Cochrane Library and included studies published until September 2019. The treatment group included patients with AMT and trabeculectomy (group A), and the control group had only trabeculectomy (group B). We only included randomized controlled trials. The outcomes were intraocular pressure (IOP), complete success rate, number of antiglaucoma medications, and complications. RESULTS: Five studies, including 174 eyes (87 eyes in the AMT group and 87 eyes in the control group), were eligible in this review. The parameters had no significant difference in heterogeneity between the AMT and control groups preoperatively. In the AMT group, the mean IOP was significantly lower at 3 and 12 months after operation (P < 0.0001 and P = 0.02, respectively), while the number of complete successes in the AMT group was significantly higher at 6 and 12 months (P = 0.02 and P = 0.003, respectively) compared with the control group. Complications, including a flat anterior chamber and hyphema, appeared to be decreased in the AMT group compared to the control group (P = 0.02 and P = 0.02, respectively). No differences were observed in the number of antiglaucoma medications, hypotony, encapsulated bleb, or choroidal detachment. CONCLUSION: Compared with only trabeculectomy, it is more efficient and safer to add AMT to trabeculectomy during glaucoma filtering surgery.

The association between comorbidities and the quality of life among colorectal cancer survivors in the People's Republic of China.

BACKGROUND: Cancer survivors with certain comorbidities had lower quality of life (QOL). This study was performed to investigate the prevalence of comorbidities and the association between comorbidities and the QOL among Chinese colorectal cancer survivors (CCS). METHODS: A cross-sectional study was conducted among 1,398 CCS between April and July 2013 in Shanghai, People's Republic of China. All the participants were asked to complete a simplified Chinese version of the European Organization for Research and Treatment quality of life version 3 questionnaire and questions on sociodemographic characteristics and comorbidities. In order to mitigate the bias caused by confounding factors, multiple linear regression models were employed to calculate the adjusted means of QOL scores. RESULTS: The proportion of participants without any comorbidity was only 20.2%. The CCS with comorbidities except hypertension scored significantly lower on the European Organization for Research and Treatment quality of life version 3 questionnaire global health and functioning scales and Functional Assessment of Cancer Therapy-General scales but higher on the European Organization for Research and Treatment quality of life version 3 questionnaire symptom scores, indicating that they had poorer QOL, particularly for cardiovascular, respiratory, digestive, and musculoskeletal diseases. CONCLUSION: There exists a significant association between comorbidities and QOL among Chinese CCS, and participants with comorbidities generally reported lower QOL scores. These findings suggested comprehensive care for CCS.

Comorbid chronic diseases and their associations with quality of life among gynecological cancer survivors.

BACKGROUND: Many gynecological cancer survivors (GCS) have comorbid chronic diseases (CCD). This study was to estimate the impacts of CCD on quality of life (QOL) in GCS. METHODS: We collected cross-sectional self-reported survey data from 598 GCS between April and July 2013, in Shanghai, China. All the subjects were asked to complete a questionnaire containing the European Organization for Research and Treatment quality of life version 3 questionnaire (EORTC QLQ-C30) and questions on socio-demographic characteristics and CCD. In order to mitigate the bias caused by confounding factors, multiple linear models were employed to calculate adjusted means of QOL scores. RESULTS: Approximately three-quarters of subjects reported at least one CCD. The highest overall prevalence of all CCD was found in endometrial cancer survivors. Subjects with CCD generally reported lower scores for most EORTC QLQ-C30 scales when compared to subjects without CCD, indicating poorer QOL, particularly for cardiovascular diseases, respiratory diseases, digestive diseases, and musculoskeletal disease. CONCLUSIONS: The CCD are common health problems among GCS. CCD have significantly negative influence on QOL, and GCS with CCD generally reported lower QOL scores. These findings suggested comprehensive cares for GCS.

The influence of comorbid chronic diseases and physical activity on quality of life in lung cancer survivors.

PURPOSE: This study aimed to evaluate the influence of comorbid chronic diseases (CCD) and physical activity (PA) on quality of life (QOL) in lung cancer survivors (LCSs). METHODS: The study used a cross-sectional study design. A total of 701 LCSs were recruited from 17 comprehensive cancer rehabilitation clubs in Shanghai, China. Measurements used included the European Organization for Research and Treatment quality of life version 3 questionnaire (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy -General version 4 questionnaire (FACT-G). Independent variables were CCD and PA. Multiple linear regression models were used to control for the effect of sociodemographic characteristic. RESULTS: Subjects with CCD generally reported lower scores for most EORTC QLQ-C30 and FACT-G scales when compared to subjects without CCD, indicating poorer QOL. Subjects with PA generally reported higher scores for most EORTC QLQ-C30 and FACT-G scales when compared to subjects without PA, indicating better QOL. The influences of five times and more PA per week were larger than the influence of less than five times PA per week. Subjects without CCD and with PA generally reported similar scores for most EORTC QLQ-C30 and FACT-G scales when compared to others without CCD and PA. Subjects with CCD and PA generally reported higher scores for most EORTC QLQ-C30 and FACT-G scales when compared to other LCSs with CCD and without PA. CONCLUSIONS: CCD have significantly negative influence on QOL. PA has significantly positive influence on QOL among the LCSs with CCD, not among the other LCSs without CCD.

[The expressional alterations of CSF-1R after ischemic injury of cerebral cortex].

AIM: To observe the expressional alterations of colony stimulating factor-1 receptor (CSF-1R) after ischemic injury of cerebral cortex, and study the function of colony stimulating factor-1 (CSF-1)/CSF-1R signal during the process of ischemic injury and repair of central nervous system (CNS). METHODS: We examined the distribution and expression of CSF-1R in normal brain tissues and ischemic brain tissues by immunohistology and Western blot analysis. RESULTS: The expression of CSF-1R in neurons could be up-regulated by ischemic injury in CNS. CONCLUSION: CSF-1/CSF-1R might take part in the process of ischemic injury and repair.