BioFactors最新文献

β-Secretase (BACE1) is the key enzyme responsible for generating amyloid-β (Aβ) peptides, whose aggregation and plaque formation are major hallmarks of Alzheimer's disease (AD). Owing to its central role in Aβ production, BACE1 has become a widely studied therapeutic target in the search for disease-modifying treatments for AD. However, evidence of numerous physiological substrates indicates that BACE1 participates in diverse biological processes, from the development and maintenance of the nervous system through control of neuronal differentiation and axonal myelination to immune response mediation by promotion of cell–cell interactions. These functions prompted research into the enzyme's role in other neurodegenerative disorders such as Parkinson's disease, Niemann–Pick type C disease, and Creutzfeldt–Jakob disease, whose pathophysiology includes aberrant protein aggregation and/or cognitive decline leading to dementia as seen in AD, as well as in neurological conditions such as schizophrenia and epilepsy, which are characterized by impaired neurotransmission and seizures, respectively. This review summarizes current knowledge on BACE1 substrates involved in nervous system regulation and immune response, highlights its roles at the molecular and genetic levels across aforementioned disorders, and outlines outcomes from clinical trials of BACE1 inhibitors.

After Alzheimer's disease, Parkinson's disease (PD) is the second most common neuropathological condition. It is a progressive degenerative disease at superannuation that affects the central nervous system (CNS) and slowly disable patients doing regular activities like walking, speaking, and writing. Early diagnosis of this disease helps to manage the patients and provide them therapy effectively. From the past few years, gait, electroencephalogram (EEG) signals and speech signals have been inspected to detect this disease at an early stage, out of which the most frequently considered one is speech signal, as it is reported by the researchers that 90% of the PD patients suffer from speech disorders. Also, speech signal analysis is a non-invasive and cost-effective method to detect PD at an early stage, and it helps to build telediagnosis models for prediction. Classical speech signal processing methodologies adopted in PD detection sometimes suffer from inadequate understanding of the effect of PD speech generation models and how that is reflected on speech signals captured from the PD patients. Artificial intelligence (AI) based methods attempts to learn those models from the given data in the best possible way to distinguish PD patients from the healthy controls. This paper's primary goal is to survey AI methodologies to detect PD using speech signals as reported in the publications between 2020 and 2024. As deep learning (DL) is a subset of machine learning (ML) and ML is a subset of AI, we consider 55 research publications related to ML and DL methods adopted for speech signal-based PD diagnosis. All the articles were published by IEEE and we have considered key words like “Machine learning approaches in Parkinson's disease detection from speech signals,” “Application of Deep learning in Parkinson Disease detection from speech signals,” “Artificial Intelligence in Parkinson's disease detection”; to find the articles reviewed in this study. This comprehensive review article reveals that both ML and DL algorithms have demonstrated encouraging outcomes, and the need of focused effort on more explainable AI based methods that can be clinically interpreted and hence potentially can be trusted for early diagnosis of Parkinson's disease.

Natural products are one of the pillars of the drug discovery process, as they provide various scaffolds and diverse biological activity. Cepharanthine (CEP), an alkaloid with a bisbenzyl-isoquinoline skeleton, was isolated from the Stephania genus. The research articles on this alkaloid invariably cite its usefulness due to its biological activity. The relevant keywords were searched in various databases, and two independent reviewers carefully removed the duplicates. The alkaloid exhibits multiple biological activities, such as anti-inflammatory, antioxidant, and anti-viral, apart from anti-cancer activities. It has been used to treat diverse medical conditions, including venomous snakebites. One of the key reactions of this alkaloid involves its ability to reverse multidrug resistance.

Soy isoflavones have been extensively studied for their beneficial effects in various diseases. Oxidative stress induces inflammation and myonecrosis in early disease stages in both mdx mice and human patients with Duchenne muscular dystrophy (DMD). This study aimed to investigate the effects of hydroethanolic soy extract (HSE) on dystrophic muscle in mdx mice (a mouse model of DMD), based on the estrogenic action of total soy isoflavones in reducing oxidative stress and inflammation. Phytochemical profiling of HSE was performed by UPLC-PDA-MS, and in silico molecular docking identified putative targets of the main isoflavones. Fourteen-day-old male mdx mice were treated orally with HSE (57 mg/kg/day, ~2 mg/kg genistein) for 45 days. Muscle function, biochemical markers, histopathology, and molecular indicators of inflammation and oxidative stress were evaluated. HSE contained multiple isoflavone classes, showing strong binding affinities for monoamine oxidase and estrogen receptors. The isoflavone-rich HSE showed no toxic effects in mdx mice and demonstrated a clear protective influence on skeletal muscle pathology. Treatment with HSE led to improved muscle integrity, as evidenced by increased muscle strength and a marked reduction in markers of muscle damage such as IgG-positive fibers and serum CK levels. Additionally, HSE effectively mitigated the inflammatory response, with significant downregulation of NF-κB, reduction of inflammatory and macrophage infiltration areas, and attenuation of oxidative stress markers. The antioxidant response was enhanced, reflected by lower ROS production, decreased lipid peroxidation (4-HNE and lipofuscin), and elevated levels of endogenous antioxidants (catalase and GSH). Moreover, HSE appeared to support muscle regeneration by increasing the proportion of centrally nucleated fibers while modulating myogenic regulatory pathways, as indicated by decreased MyoD expression. Isoflavone-rich HSE safely improved muscle integrity and function in mdx mice by attenuating oxidative stress and inflammation through modulation of the ROS/NF-κB pathway. These findings highlight the therapeutic potential of soy-derived isoflavones as a complementary approach for managing DMD.

Pancreatic adenocarcinoma accounts for 90% of pancreatic cancer cases, the deadliest kind. PC patients' poor immunotherapy, chemotherapy, and other responses lead to a generally failed treatment strategy. Thus, understanding molecular processes is essential for creating novel PC therapies. The natural chemical andrographolide (ADG) from Andrographis paniculata shows anticancer properties against various cancer types. The method by which ADG fights pancreatic cancer is unknown. In PC cell lines, ADG inhibited cell proliferation and migration, caused G0/G1 phase arrest, and caused cell death due to reactive oxygen species, iron accumulation, malondialdehyde production, and glutathione (GSH) exhaustion. Ferrostatin-1 inhibited ADG-induced cell death. A molecular docking investigation demonstrated that ADG directly binds to heat shock protein 90 (HSP90). ADG suppresses HSP90 expression, and tanespimycin prevents ADG-induced cytotoxicity, showing that HSP90 is ADG's main target in activating intracellular activities. Tests using immunoprecipitation, degradation, and in vitro ubiquitination showed that the ADG-HSP90 pair targeted and broke down glutathione peroxidase 4 (GPX4), allowing it to be tagged for destruction. ADG also reduced cell development, caused apoptosis, increased reactive oxygen species and iron, synthesized malondialdehyde, depleted glutathione, and ubiquitinated and degraded GPX4. In subcutaneous in vivo tumors, ferroptosis caused by ADG inhibits tumor development. HSP90 is a new ADG target. After connecting to and complexing with HSP90, ADG targeted and deleted GPX4, triggering ferroptosis in PC. The findings strongly suggest that ADG may treat PC. ADG's pharmacokinetics and other effects must be studied in patients' clinical trials to make it a pancreatic cancer therapy option.