The Role of KLF4 in Alzheimer’s Disease

Krüppel-like factor 4 (KLF4), a member of the family of zinc-finger transcription factors, is widely expressed in range of tissues that play multiple functions. Emerging evidence suggest KLF4’s critical regulatory effect on the neurophysiological and neuropathological processes of Alzheimer’s disease (AD), indicating that KLF4 might be a potential therapeutic target of neurodegenerative diseases. In this review, we will summarize relevant studies and illuminate the regulatory role of KLF4 in the neuroinflammation, neuronal apoptosis, axon regeneration and iron accumulation to clarify KLF4’s status in the pathogenesis of AD

Effect of Inflammation on the Process of Stroke Rehabilitation and Poststroke Depression

A considerable body of evidence has shown that inflammation plays an important role in the process of stroke rehabilitation and development of poststroke depression (PSD). However, the specific molecular and cellular mechanisms involved remain unclear. In this review, we summarize how neuroinflammation affects stroke rehabilitation and PSD. We mainly focus on the immune/inflammatory response, involving astrocytes, microglia, monocyte-derived macrophages, cytokines (tumor necrosis factor alpha, interleukin 1), and microRNAs (microRNA-124, microRNA 133b). This review provides new insights into the effect of inflammation on the process of stroke rehabilitation and PSD and potentially offer new therapeutic targets of stroke and PSD

DataSheet_2_In-silico evaluation of an artificial pancreas achieving automatic glycemic control in patients with type 1 diabetes.pdf

Artificial pancreas (AP) is a useful tool for maintaining the blood glucose (BG) of patients with type 1 diabetes (T1D) within the euglycemic range. An intelligent controller has been developed based on general predictive control (GPC) for AP. This controller exhibits good performance with the UVA/Padova T1D mellitus simulator approved by the US Food and Drug Administration. In this work, the GPC controller was further evaluated under strict conditions, including a pump with noise and error, a CGM sensor with noise and error, a high carbohydrate intake, and a large population of 100 in-silico subjects. Test results showed that the subjects are in high risk for hypoglycemia. Thus, an insulin on board (IOB) calculator, as well as an adaptive control weighting parameter (AW) strategy, was introduced. The percentage of time spent in euglycemic range of the in-silico subjects was 86.0% ± 5.8%, and the patient group had a low risk of hypoglycemia with the GPC+IOB+AW controller. Moreover, the proposed AW strategy is more effective in hypoglycemia prevention and does not require any personalized data compared with the IOB calculator. Thus, the proposed controller realized an automatic control of the BG of patients with T1D without meal announcements and complex user interaction.</p

Role of BDNF-mTORC1 Signaling Pathway in Female Depression

Depression is a common psychological and mental disorder, characterized by low mood, slow thinking and low will, and even suicidal tendencies in severe cases. It imposes a huge mental and economic burden on patients and their families, and its prevention and treatment have become an urgent public health problem. It is worth noting that there is a significant gender difference in the incidence of depression. Studies have shown that females are far more likely to suffer from depression than males, confirming a close relationship between estrogen and the onset of depression. Moreover, recent studies suggest that the brain-derived neurotrophic factor- (BDNF-) mammalian target of rapamycin complex-1 (mTORC1) signaling pathway is a crucial target pathway for improving depression and mediates the rapid antidepressant-like effects of various antidepressants. However, it is not clear whether the BDNF-mTORC1 signaling pathway mediates the regulation of female depression and how to regulate female depression. Hence, we focused on the modulation of estrogen-BDNF-mTORC1 signaling in depression and its possible mechanisms in recent years

DataSheet_3_In-silico evaluation of an artificial pancreas achieving automatic glycemic control in patients with type 1 diabetes.pdf

Artificial pancreas (AP) is a useful tool for maintaining the blood glucose (BG) of patients with type 1 diabetes (T1D) within the euglycemic range. An intelligent controller has been developed based on general predictive control (GPC) for AP. This controller exhibits good performance with the UVA/Padova T1D mellitus simulator approved by the US Food and Drug Administration. In this work, the GPC controller was further evaluated under strict conditions, including a pump with noise and error, a CGM sensor with noise and error, a high carbohydrate intake, and a large population of 100 in-silico subjects. Test results showed that the subjects are in high risk for hypoglycemia. Thus, an insulin on board (IOB) calculator, as well as an adaptive control weighting parameter (AW) strategy, was introduced. The percentage of time spent in euglycemic range of the in-silico subjects was 86.0% ± 5.8%, and the patient group had a low risk of hypoglycemia with the GPC+IOB+AW controller. Moreover, the proposed AW strategy is more effective in hypoglycemia prevention and does not require any personalized data compared with the IOB calculator. Thus, the proposed controller realized an automatic control of the BG of patients with T1D without meal announcements and complex user interaction.</p

DataSheet_1_In-silico evaluation of an artificial pancreas achieving automatic glycemic control in patients with type 1 diabetes.pdf

Artificial pancreas (AP) is a useful tool for maintaining the blood glucose (BG) of patients with type 1 diabetes (T1D) within the euglycemic range. An intelligent controller has been developed based on general predictive control (GPC) for AP. This controller exhibits good performance with the UVA/Padova T1D mellitus simulator approved by the US Food and Drug Administration. In this work, the GPC controller was further evaluated under strict conditions, including a pump with noise and error, a CGM sensor with noise and error, a high carbohydrate intake, and a large population of 100 in-silico subjects. Test results showed that the subjects are in high risk for hypoglycemia. Thus, an insulin on board (IOB) calculator, as well as an adaptive control weighting parameter (AW) strategy, was introduced. The percentage of time spent in euglycemic range of the in-silico subjects was 86.0% ± 5.8%, and the patient group had a low risk of hypoglycemia with the GPC+IOB+AW controller. Moreover, the proposed AW strategy is more effective in hypoglycemia prevention and does not require any personalized data compared with the IOB calculator. Thus, the proposed controller realized an automatic control of the BG of patients with T1D without meal announcements and complex user interaction.</p

Isoalantolactone induces intrinsic apoptosis through p53 signaling pathway in human lung squamous carcinoma cells.

Isoalantolactone has recently been revealed to induce apoptosis in several types of cancer. However, little is reported on its anti-tumor potential on human lung cancer. Our present study was designed to investigate its effects on human lung squamous carcinoma SK-MES-1 cells. We found that Isoalantolactone induced cellular and DNA morphological changes and decreased the viability of SK-MES-1 cells. It significantly inhibited the growth of SK-MES-1 cells through apoptosis in a dose-dependent manner via activation of p53. It also induced cell cycle arrest at G1 phase. It can down-regulate Bcl-2 and up-regulate Bax, to induce dissipation of mitochondrial membrane potential and generation of reactive oxygen species. Caspase-3 was also activated by Isoalantolactone, with the cleavage of poly (ADP-ribose) polymerase. Our results reveal that Isoalantolactone induces intrinsic apoptosis in SK-MES-1 cells through p53 signaling pathway, which suggests that Isoalantolactone could be a potential leading compound for future development of anti-lung cancer drugs

Lychee Seed Saponins Improve Cognitive Function and Prevent Neuronal Injury via Inhibiting Neuronal Apoptosis in a Rat Model of Alzheimer’s Disease

Lychee seed is a traditional Chinese medicine and possesses many activities, including hypoglycemia, liver protection, antioxidation, antivirus, and antitumor. However, its effect on neuroprotection is still unclear. The present study investigated the effects of lychee seed saponins (LSS) on neuroprotection and associated mechanisms. We established a rat model of Alzheimer’s disease (AD) by injecting Aβ25–35 into the lateral ventricle of rats and evaluated the effect of LSS on spatial learning and memory ability via the Morris water maze. Neuronal apoptosis was analyzed by hematoxylin and eosin stain and terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP nick-end labeling analysis, and mRNA expression of caspase-3 and protein expressions of Bax and Bcl-2 by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. The results showed that LSS remarkably improved cognitive function and alleviated neuronal injury by inhibiting apoptosis in the hippocampus of AD rats. Furthermore, the mRNA expression of caspase-3 and the protein expression of Bax were downregulated, while the protein expression of Bcl-2 and the ratio of Bcl-2/Bax were increased by LSS. We demonstrate that LSS significantly improves cognitive function and prevent neuronal injury in the AD rats via regulation of the apoptosis pathway. Therefore, LSS may be developed as a nutritional supplement and sold as a drug for AD prevention and/or treatment

Flow cytometric analysis on ROS generation and MMP depolarization in SK-MES-1 cells treated with Isoalantolactone at 20 and 40 μM for 24 h.

<p>(A) Flow cytometric analysis of ROS stained with the fluorescent probe using DCFH-DA; (B) Flow cytometric analysis of MMP stained with the fluorescent probe Rhodamine 123; (C) Representative histograms expressed the percent of over expressed ROS cells; (D) Representative histograms expressed the percent of depolarized cells. All data are expressed as Mean ±SD of three independent experiments. Columns not sharing the same superscript letter differ significantly (P < 0.05).</p