Artificial intelligence-based diagnosis of Alzheimer's disease with brain MRI images.

Alzheimer's disease, a primary neurodegenerative condition, predominantly impacts the elderly and pre-elderly population. This progressive neurological disorder is characterized by an array of symptoms including memory loss, cognitive decline, and various physiological and psychological disturbances, significantly compromising the quality of life of patients and their caregivers. Recent advancements in Magnetic Resonance Imaging (MRI) technology have catalyzed research in AI-enhanced diagnostics for Alzheimer's disease, fostering optimism for early detection and timely interventions. This progress has paved the way for the development of sophisticated algorithms and models adept at analyzing complex brain imaging data, thereby augmenting diagnostic accuracy and efficiency. This advancement fuels optimism regarding the transformative potential of AI-driven diagnostics in revolutionizing Alzheimer's disease management, with the prospect of facilitating more effective treatment strategies and improved patient outcomes. The objective of this review is to provide a comprehensive overview of recent developments in deep learning methodologies applied to brain MRI images for the classification of various stages of Alzheimer's disease, with a particular emphasis on early diagnosis. Furthermore, this review underscores the limitations of current research, discussing potential challenges and future research directions in this dynamic field.

Endoplasmic reticulum stress-activated glycogen synthase kinase 3ß aggravates liver inflammation and hepatotoxicity in mice with acute liver failure.

Endoplasmic reticulum stress (ER stress) has been increasingly recognized as an important mechanism in various liver diseases. However, its intrinsic physiological role in acute liver failure (ALF) remains largely undetermined. This study aimed to examine how ER stress orchestrates glycogen synthase kinase 3ß (GSK3ß) and inflammation to affect ALF. In a murine ALF model induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS), 4-phenylbutyric acid (4-PBA) is to be administered to relieve ER stress. The lethality rate, liver damage, cytokine expression, and the activity of GSK3ß were evaluated. How to regulate LPS-induced inflammation and TNF-α-induced hepatocyte apoptosis by ER stress was investigated in vitro. In vivo, ER stress was triggered in the liver with the progression of mice ALF model. ER stress was essential for the development of ALF because ER stress inhibition by 4-PBA ameliorated the liver damage through decreasing liver inflammation and hepatocyte apoptosis. 4-PBA also decreased GSK3ß activity in the livers of ALF mice. In vitro, ER stress induced by tunicamycin synergistically increased LPS-triggered pro-inflammatory cytokine induction and promoted the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway in bone marrow-derived macrophages; moreover, tunicamycin also cooperated with TNF-α to increase hepatocyte apoptosis. ER stress promoted LPS-triggered inflammation depending on GSK3ß activation because inhibition of GSK3ß by SB216763, the specific inhibitor of GSK3ß, resulted in downregulation of pro-inflammatory genes. ER stress contributes to liver inflammation and hepatotoxicity in ALF, particularly by regulating GSK3ß, and is therefore a potential therapeutic target for ALF.

Screening for serum biomarkers in patients with chronic hepatitis B with hepatitis B surface antigen seroclearance, following pegylated interferon alpha therapy.

Chronic hepatitis B (CHB) is one of the most common infectious disease worldwide and a leading cause of death. Hepatitis B surface antigen (HBsAg) has previously been proven to be a steady biomarker that may be used to predict clinical outcomes. The amount of circulating HBsAg has been reported to reflect the number of infected hepatocytes. An advantage of pegylated interferon alpha (peg-IFN-α) is that as a finite course of therapy, it can potentially lead to sustained disease remission in subsequent decades. HBsAg seroclearance can reportedly be achieved in some hepatitis B patients treated with peg-IFN-α; this is a major advantage of IFN-α, as compared with nucleoside analogue treatment. In the present study, a random phage display peptide library was used to screen for potential serum peptide biomarkers in predicting which patients with CHB would exhibit HBsAg seroclearance, following 48 weeks of peg-IFN-α therapy. A total of 30 patients with CHB who achieved HBsAg seroclearance following peg-IFN-α therapy and an additional 30 age-, gender-, hepatitis B e antigen (HBeAg) status- and hepatitis B virus genotype-matched patients with CHB without HBsAg seroclearance following peg-IFN-α therapy, were enrolled as a discovery cohort. In the discovery/screening phase, 17/20 of the randomly selected phage clones, exhibited a specific reaction with purified sera immunoglobulin G from the HBsAg clearance group, and 13/17 positive phage clones came from the same phage clone, with the inserted peptide sequence ETCRASCINESA (named IFNC1). In the validation phase, phage-ELISA results showed that the positive reaction rate of the IFNC1 peptide phage clone was 92.0% with the HBsAg seroclearance group (n=50), which was significantly higher, as compared with the randomly selected HBsAg non-clearance group (12.0%, n=50) and the healthy control group (8.0%, n=50). In conclusion, the newly identified mimic peptide IFNC1 showed a high predictive validity HBsAg seroclearance in patients with CHB, following peg-IFN-α therapy. Therefore IFNC1 may be a potential serum biomarker, which could be used to predict the treatment outcomes of peg-IFN-α therapy.

[Effect of grape procyanidins on expressions of Caspase-3 and Bax in ethanol-induced liver injury in mice].

OBJECTIVE: To study the effect of grape procyanidins (GPC) on the expressions of Caspase-3 and Bax in the liver of mice with ethanol-induced liver injury. METHOD: The mice were orally given at the different doses of GPC (50,100 and 200 mg/kg) and 4 g/kg ethanol, and killed after 4 weeks. The proliferation activity of the hepatic cells was determined by MTT assay,the levels of Caspase-3 and Bax protein expression in the cells were measured by immunohistochemistry method. RESULTS: The expression level of Caspase-3 and Bax protein in high dose group were 19.08% and 14.06%, respectively, and those of the ethanol-injured group were 51.78% and 58.08%. The differences between the two groups were significant (P < 0.05). The cell proliferation activity of high dose and medium dose group was higher than the cell proliferation activity of ethanol-injured group (P < 0.05). CONCLUSION: GPC could suppressing the expression of Caspase-3 and Bax in the liver of mice with ethanol-induced liver injury.

[Phenotypic variation in Actinobacillus actinomycetemcomitans].

OBJECTIVE: To investigate the colony variation in Actinobacillus actinomycetemcomitans (Aa) from rough to smooth and recognize its different morphology during laboratory translations. METHODS: Primary strains isolated from subgingival plaque of two juvenile periodontitis patients were repeatedly subcultured on agar plates and broth; for broth culture, every generation was translated in broth and on solid medium separately to observe the corresponding morphologies of Aa grow in broth. RESULTS: Three smooth strains of Aa from the broth culture were obtained. The process was about 7-8 generations: colonies changed from a small and adherence phenotype to a bigger and sediment ones and finally the culture supernatant became turbid; the corresponding morphologies grow on agar exhibiting an adherent, small rough colony phenotype which had a star-shaped internal structure converted gradually to a kind of bigger, opaque, nonadherent, smooth phenotype, then the colony extended out from the margin of the colony and finally converted to a flat, almost parent morphology and the same time the star-like inner structure converted to a simpler and smaller type and finally disappeared. We could not get completely smooth variants of Aa from agar. CONCLUSIONS: The variation in colony morphology of Aa from rough to smooth is a process, in which the colony was gradually wetter and bigger and at the same time gradually lost the inner structure. During this process three colony morphologies at least can be seen, including rough, opaque smooth and almost translucent smooth.