A reappraisal on amyloid cascade hypothesis: the role of chronic infection in Alzheimer's disease.

Alzheimer disease (AD) is a progressive neurological disorder that accounted for the most common cause of dementia in the elderly population. Lately, 'infection hypothesis' has been proposed where the infection of microbes can lead to the pathogenesis of AD. Among different types of microbes, human immunodeficiency virus-1 (HIV-1), herpes simplex virus-1 (HSV-1), Chlamydia pneumonia, Spirochetes and Candida albicans are frequently detected in the brain of AD patients. Amyloid-beta protein has demonstrated to exhibit antimicrobial properties upon encountering these pathogens. It can bind to microglial cells and astrocytes to activate immune response and neuroinflammation. Nevertheless, HIV-1 and HSV-1 can develop into latency whereas Chlamydia pneumonia, Spirochetes and Candida albicans can cause chronic infections. At this stage, the DNA of microbes remains undetectable yet active. This can act as the prolonged pathogenic stimulus that over-triggers the expression of Aß-related genes, which subsequently lead to overproduction and deposition of Aß plaque. This review will highlight the pathogenesis of each of the stated microbial infection, their association in AD pathogenesis as well as the effect of chronic infection in AD progression. Potential therapies for AD by modulating the microbiome have also been suggested. This review will aid in understanding the infectious manifestations of AD.

Nanoprotection from SARS-COV-2: would nanotechnology help in Personal Protection Equipment (PPE) to control the transmission of COVID-19?

The coronavirus disease 2019 (COVID-19) has caused a worldwide outbreak. The severe acute respiratory syndrome coronavirus 2 virus can be transmitted human-to-human through droplets and close contact where personal protective equipment (PPE) is imperative to protect the individuals. The advancement of nanotechnology with significant nanosized properties can confer a higher form of protection. Incorporation of nanotechnology into facemasks can exhibit antiviral properties. Nanocoating on surfaces can achieve self-disinfecting purposes and be applied in highly populated places. Moreover, nano-based hand sanitizers can confer better sterilizing efficacies with low skin irritation as compared to alcohol-based hand sanitizers. The present review discusses the incorporation of nanotechnology into nano-based materials and coatings in facemasks, self-surface disinfectants and hand sanitizers, in the hope to contribute to the current understanding of PPE to combat COVID-19.

A closer look at the mycobiome in Alzheimer's disease: Fungal species, pathogenesis and transmission.

Candida spp., Malassezia spp., Cladosporium spp. and Alternaria spp. are among the most common fungi detected in the brain of patients with Alzheimer's disease (AD). These fungi are opportunistic organisms, where they often cause infection among immunocompromised patients. Coincidentally, these fungi can reach the brain and cause fungal meningitis. In general, they enter the brain via systemic infection due to disrupted epithelial barrier from skin and gut colonization. Once it reaches the brain, Candida species has been postulated to induce fungal glial granulomas with amyloid precursor protein (APP) accumulated inside. Cleavage of APP can lead to the production of amyloid beta (Aß). Malassezia species can lead to neuroinflammation via activating helper T-cell (Th) 1 and Th17 immune response. Besides that, the pathogenesis of Cladosporium species and Alternaria species in AD remains unknown, but it could be related to the neuroinflammation. These two fungal species may have involved in acetylcholinesterase (AChE) inhibitor production in the brain. All these four fungi can be detected at the same time in the brain, which contribute to chronic neuroinflammation and neurodegeneration in the brain. This review hopes to shed some light in understanding the presence of fungi in the brain and their possible role in AD pathogenesis.

Antibody-drug conjugates: Principles and opportunities.

Antibody-drug conjugates (ADCs) are immunoconjugates that combine the specificity of monoclonal antibodies with a cytotoxic agent. The most appealing aspects of ADCs include their potential additive or synergistic effects of the innate backbone antibody and cytotoxic effects of the payload on tumors without the severe toxic side effects often associated with traditional chemotherapy. Recent advances in identifying new targets with tumor-specific expression, along with improved bioactive payloads and novel linkers, have significantly expanded the scope and optimism for ADCs in cancer therapeutics. In this paper, we will first provide a brief overview of antibody specificity and the structure of ADCs. Next, we will discuss the mechanisms of action and the development of resistance to ADCs. Finally, we will explore opportunities for enhancing ADC efficacy, overcoming drug resistance, and offer future perspectives on leveraging ADCs to improve the outcome of ADC therapy for cancer treatment.