Vaccines against SARS-CoV-2 variants and future pandemics.

INTRODUCTION: Vaccination continues to be the most effective method for controlling COVID-19 infectious diseases. Nonetheless, SARS-CoV-2 variants continue to evolve and emerge, resulting in significant public concerns worldwide, even after more than 2 years since the COVID-19 pandemic. It is important to better understand how different COVID-19 vaccine platforms work, why SARS-CoV-2 variants continue to emerge, and what options for improving COVID-19 vaccines can be considered to fight against SARS-CoV-2 variants and future pandemics. AREA COVERED: Here, we reviewed the innate immune sensors in the recognition of SARS-CoV-2 virus, innate and adaptive immunity including neutralizing antibodies by different COVID-19 vaccines. Efficacy comparison of the several COVID-19 vaccine platforms approved for use in humans, concerns about SARS-CoV-2 variants and breakthrough infections, and the options for developing future COIVD-19 vaccines were also covered. EXPERT OPINION: Owing to the continuous emergence of novel pathogens and the reemergence of variants, safer and more effective new vaccines are needed. This review also aims to provide the knowledge basis for the development of next-generation COVID-19 and pan-coronavirus vaccines to provide cross-protection against new SARS-CoV-2 variants and future coronavirus pandemics.

Aryl Hydrocarbon Receptors: Evidence of Therapeutic Targets in Chronic Inflammatory Skin Diseases.

The aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, is important for xenobiotic metabolism and binds to various endogenous and exogenous ligands present in the skin. AhR is known to be associated with diseases in various organs; however, its functions in chronic inflammatory skin diseases, such as atopic dermatitis (AD) and psoriasis (PS), have recently been elucidated. Here, we discuss the molecular mechanisms of AhR related to chronic inflammatory skin diseases, such as AD and PS, and the mechanisms of action of AhR on the skin immune system. The importance of AhR molecular biological pathways, clinical features in animal models, and AhR ligands in skin diseases need to be investigated. In conclusion, the therapeutic effects of AhR ligands are demonstrated based on the relationship between AhR and skin diseases. Nevertheless, further studies are required to elucidate the detailed roles of AhR in chronic inflammatory skin diseases.

A self-pressure-driven blood plasma-separation device for point-of-care diagnostics.

We aimed to develop a portable, simple-to-use, and self-pressure-driven blood plasma-separation device that can be combined with rapid diagnostic test kits. This simple, disposable, and electrical equipment-free apparatus has been designed to separate plasma from a few microliters of blood with only hand-powered operation. The refined plasma sample is then delivered to multiple lateral flow assay kits directly connected to the device for the detection of various serological markers. The required time for all steps was just 1 min. We validated the device through multifaceted experiments. The developed multifunctional device enables to perform all blood test steps of diagnostic medical examination at the point-of-care.

Aryl Hydrocarbon Receptor Repressor Is Hypomethylated in Psoriasis and Promotes Psoriasis-like Inflammation in HaCaT Cells.

It is known that DNA hypomethylation of aryl hydrocarbon receptor repressor (AhRR), one of the epigenetic markers of environmental pollutants, causes skin diseases. However, the function and mechanisms are still unknown. We aimed to determine whether AhRR is hypomethylated in PBMC of psoriasis patients, as well as to examine the expression of psoriasis-related inflammatory cytokines and antimicrobial peptides after 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment in HaCaT cells overexpressing or silencing AhRR. AhRR was determined by qPCR, Western blot, immunohistochemistry, and immunocytochemistry in skin tissue and HaCaT cells. DNA methylation of AhRR was performed by Infinium Human Methylation450 BeadChip in PBMC of psoriasis patients and methylation-specific PCR (MSP) in HaCaT cells. NF-κB pp50 translocation and activity were performed by immunocytochemistry and luciferase reporter assay, respectively. We verified AhRR gene expression in the epidermis from psoriasis patients and healthy controls. AhRR hypomethylation in PBMC of psoriasis patients and pAhRR-HaCaT cells was confirmed. The expression level of AhRR was increased in both TCDD-treated HaCaT cells and pAhRR-HaCaT cells. NF-κB pp50 translocation and activity increased with TCDD. Our results showed that AhRR was hypomethylated and overexpressed in the lesional skin of patients with psoriasis, thereby increasing AhRR gene expression and regulating pro-inflammatory cytokines through the NF-κB signaling pathway in TCDD-treated HaCaT cells.

Multiplex Molecular Point-of-Care Test for Syndromic Infectious Diseases.

Point-of-care (POC) molecular diagnostics for clinical microbiology and virology has primarily focused on the detection of a single pathogen. More recently, it has transitioned into a comprehensive syndromic approach that employs multiplex capabilities, including the simultaneous detection of two or more pathogens. Multiplex POC tests provide higher accuracy to for actionable decisionmaking in critical care, which leads to pathogen-specific treatment and standardized usages of antibiotics that help prevent unnecessary processes. In addition, these tests can be simple enough to operate at the primary care level and in remote settings where there is no laboratory infrastructure. This review focuses on state-of-the-art multiplexed molecular point-of-care tests (POCT) for infectious diseases and efforts to overcome their limitations, especially related to inadequate throughput for the identification of syndromic diseases. We also discuss promising and imperative clinical POC approaches, as well as the possible hurdles of their practical applications as front-line diagnostic tests.

Paper-Based Multiplex Surface-Enhanced Raman Scattering Detection Using Polymerase Chain Reaction Probe Codification.

We construct a multiplex surface-enhanced Raman scattering (SERS) platform based on a plasmonic paper substrate and a double-labeled probe for the detection of multiple fluorescent dyes at high sensitivity in a single-wavelength light source system. Plasmonic paper, made of silver nanodots on three-dimensional cellulose fibers, enables highly sensitive SERS biosensing based on localized surface plasmon resonance (LSPR). The proposed method enables the identification and quantification of a range of fluorescent dyes ranging from picomolar to millimolar concentrations. The use of 5' fluorescent dyes and 3' biotin-modified probes as SERS-coded probes renders possible the separation of fluorescent dyes with streptavidin-coated magnetic beads (SMBs) and the sensitive detection of multiple dyes after the reverse transcription polymerase chain reaction (RT-PCR). This experimental study reveals the multiplex detection capability of PCR-based SERS under existing PCR conditions without modifying primer and probe sequences. The combination of magnetic bead-based separation and paper SERS platform is efficient, economical, and can be used for the simultaneous detection of two or more pathogens.

Lithium bromide: an inexpensive and efficient catalyst for imine hydroboration with pinacolborane at room temperature.

An efficient protocol for the hydroboration of imines is reported. Lithium halide salts are effective catalysts to convert aldimines and ketimines to their corresponding amines. Here, we report excellent isolated yield of secondary amines (>95%) using 3 mol% lithium bromide in THF at room temperature. In addition, DFT calculations for a plausible reaction pathway are reported.

Correction: A new point-of-care test for the diagnosis of infectious diseases based on multiplex lateral flow immunoassays.

Correction for 'A new point-of-care test for the diagnosis of infectious diseases based on multiplex lateral flow immunoassays' by Hanbi Kim et al., Analyst, 2019, 144, 2460-2466.

Development of Label-Free Colorimetric Assay for MERS-CoV Using Gold Nanoparticles.

Worldwide outbreaks of infectious diseases necessitate the development of rapid and accurate diagnostic methods. Colorimetric assays are a representative tool to simply identify the target molecules in specimens through color changes of an indicator (e.g., nanosized metallic particle, and dye molecules). The detection method is used to confirm the presence of biomarkers visually and measure absorbance of the colored compounds at a specific wavelength. In this study, we propose a colorimetric assay based on an extended form of double-stranded DNA (dsDNA) self-assembly shielded gold nanoparticles (AuNPs) under positive electrolyte (e.g., 0.1 M MgCl2) for detection of Middle East respiratory syndrome coronavirus (MERS-CoV). This platform is able to verify the existence of viral molecules through a localized surface plasmon resonance (LSPR) shift and color changes of AuNPs in the UV-vis wavelength range. We designed a pair of thiol-modified probes at either the 5' end or 3' end to organize complementary base pairs with upstream of the E protein gene (upE) and open reading frames (ORF) 1a on MERS-CoV. The dsDNA of the target and probes forms a disulfide-induced long self-assembled complex, which protects AuNPs from salt-induced aggregation and transition of optical properties. This colorimetric assay could discriminate down to 1 pmol/µL of 30 bp MERS-CoV and further be adapted for convenient on-site detection of other infectious diseases, especially in resource-limited settings.

A new point-of-care test for the diagnosis of infectious diseases based on multiplex lateral flow immunoassays.

Infectious diseases are transmissible or communicable illnesses and can spread quickly in some areas and become epidemics. It is critical to quickly diagnose initial infections and prevent further spread through in vitro diagnosis. However, current detection strategies have exhibited a lack of balance with regard to accuracy, time consumption, and portability until recently (e.g. serology, culturing, molecular tests, etc.). Alternatively, many studies have focused on point-of-care testing (POCT), which combines simple, rapid, and exact on-site diagnostic platforms. Moreover, multiplex detectability is necessary for emergency treatment depending on the stage of the disease or interactional infections. The lateral flow assay (LFA) is the most popular diagnostic tool that meets the required standards for colorimetric assays. Here, we review lateral flow assays based on the immune reactions for the simultaneous diagnosis of infectious diseases as the POC test. The assays employed various forms and approaches in terms of the multiplexing level system for improving the sensitivity and specificity. We briefly describe the state-of-the-art infection diagnostic methods and published performances that have been classified into three categories based on the application forms of the lateral flow immunoassay. Also, we discuss further uses of LFA and other technologies for more effective infectious disease POCT.

A Nanoplasmonic Biosensor for Ultrasensitive Detection of Alzheimer's Disease Biomarker Using a Chaotropic Agent.

Blood-based diagnosis (hemodiagnosis) of Alzheimer's disease (AD) is emerging as a promising alternative to cerebrospinal-fluid-based methods because blood contains various kinds of AD biomarkers, including amyloid beta 1-40, 1-42, and τ (tau) protein. However, with current technology, the accuracy of the blood-plasma-based methods is relatively low compared to the traditional methods because the concentration of AD biomarkers in blood plasma is incredibly low, and diverse interference is present in blood plasma, which hinders precise detection. Here, we suggest a nanoplasmonic biosensor using gold nanorods with a chaotropic agent for precise ultrasensitive detecting of Alzheimer's disease biomarkers in human plasma. This nanoplasmonic biosensor is based on the localized surface plasmon resonance (LSPR), which is extremely sensitive to the point where it can respond to an insignificant change of the refractive index around the gold nanoparticles. Also, using guanidine hydrochloride as a chaotropic agent, we can overcome the obstacles of blood-based AD diagnostics. In more detail, this agent interrupts the network between water molecules and weakens the hydrophobic interactions between proteins, remarkably improving detection capabilities to target τ protein. By reducing the overlapping ranges between protein levels in an age-matched control and AD patients' plasma, this system can accurately diagnose AD patients. This platform also can analyze disease from mild cognitive impairment using standardized blood biomarker tau protein, which is related to Alzheimer's disease. As a result, our platform can be applied to clinical trials, and thus it has excellent potential in the medical field.

Eucalyptus globulus Inhibits Inflammasome-Activated Pro-Inflammatory Responses and Ameliorate Monosodium Urate-Induced Peritonitis in Murine Experimental Model.

Eucalyptus globulus Labill. (E. globulus, Myrtaceae) is used in Europe as a traditional folk remedy for inflammation-related disorders such as arthritis, diabetes, asthma, and gout. We investigated this study to evaluate the protective effects of E. globulus extract (EG) on inflammatory responses, and provide scientific and mechanistic evidence in in vitro and in vivo experimental models. LPS-stimulated murine bone marrow-derived macrophages (BMDMs) were used to study the regulatory effect of EG on inflammasome activation in vitro. Monosodium urate (MSU)-induced peritonitis was used to study the effect of EG in an in vivo murine model. EG suppressed IL-[Formula: see text] secretion via the regulation of apoptosis-associated speck-like proteins containing a CARD (ASC) oligomerization and caspase-1 maturation, leading to the inhibition of inflammasome activation. In the in vivo study, EG suppressed the MSU-induced peritonitis by attenuating interleukin (IL)-1[Formula: see text], providing scientific support for its traditional use in the treatment of inflammation-related disorders.

A shape-code nanoplasmonic biosensor for multiplex detection of Alzheimer's disease biomarkers.

Alzheimer's disease (AD) is a neurodegenerative disease associated with the loss of nerve cells in the brain. The disease is affected by multifactorial pathways and leads to changes in related biomolecular levels as AD progresses. Therefore, AD should be diagnosed with combined detection of several lesions to improve accuracy. Amyloid beta 1-40, 1-42 and τ (tau) protein are milestones in AD pathology and can be used as main screening and diagnostic target markers. Here, we suggest a highly selective biosensor for detection of AD core biomarkers on one platform through distinct localized surface plasmon resonance (LSPR) depending on gold nanoparticles shapes, called a shape-code biosensor. This plasmonic sensor consists of only gold nanoparticles and antibody, but does not need additory methods for precise separation from multifarious samples and identification of markers. Under physiological condition, we determined a detection limit of 34.9fM for amyloid beta (Aß) 1-40, 26fM for Aß 1-42 and 23.6fM for τ protein corresponding to the ~ 1, ~ 2.23 and ~ 3.12nm of Rayleigh scattering peak shift on shape-code plasmon system for each biomarker in mimicked blood. This is the first highly sensitive shape-code biosensor to detect AD biomarkers which can be used to diagnose AD easily in the future.

Actinidia arguta extract attenuates inflammasome activation: Potential involvement in NLRP3 ubiquitination.

ETHNOPHARMACOLOGICAL RELEVANCE: Actinidia arguta (A. arguta) has been widely used in Asian countries as a traditional medicinal herb to treat inflammation-related diseases, such as gastritis, bronchitis, and arthritis. AIM OF THE STUDY: The inhibitory effect of A. arguta leaves' extract (AA) on inflammasome activation was investigated to verify its traditional use in treating inflammation-related diseases. MATERIALS AND METHODS: Bone marrow-derived macrophages (BMDMs) primed by lipopolysaccharide (LPS) were activated by selective inflammasome stimulators, and the effect of AA on inflammasome activation was investigated. A monosodium urate crystal (MSU)-induced peritonitis mouse model was used to study the in vivo efficacy of AA on inflammasome activation. RESULTS: In the in vitro study, AA regulated NLRP3 ubiquitination and apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization, leading to the inhibition of NLRP3 inflammasome-mediated interleukin (IL)-1ß secretion. The inhibitory effect of AA on inflammasome activation in vitro was further confirmed in vivo using an MSU-induced peritonitis mouse model. CONCLUSION: AA provided scientific evidence, substantiating the traditional claims for its use in the treatment of inflammation and inflammation-mediated metabolic disorders, including gout.

Protective effects of Cinnamomum cassia (Lamaceae) against gout and septic responses via attenuation of inflammasome activation in experimental models.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum cassia (C. cassia, Lauraceae family), commonly used for treating dyspepsia, gastritis, blood circulation, and inflammatory diseases is considered as one of the 50 fundamental herbs in traditional Chinese medicine. AIM OF THE STUDY: The anti-inflammatory action of an ethanol extract of C. cassia (CA), and its underlying mechanisms were explored in both in vitro cellular and in vivo murine models. MATERIALS AND METHODS: Bone marrow-derived macrophages (BMDMs) were used to study the regulatory effect of CA on inflammasome activation. A lipopolysaccharide (LPS)-induced sepsis mouse model and a monosodium urate (MSU)-induced gout model were employed to study the effect of CA on in vivo efficacy. RESULTS: CA improved the survival rate in the LPS-induced septic shock mouse model and inhibited inflammasome activation including NLRP3, NLRC4, and AIM2, leading to suppression of interleukin-1ß secretion. Further, ASC oligomerization and its speck formation in cytosol were attenuated by CA treatment. Furthermore, CA improved both survival rate of LPS-induced septic shock and gout murine model. CONCLUSIONS: CA treatment significantly attenuated danger signals-induced inflammatory responses via regulation of inflammasome activation, substantiating the traditional claims of its use in the treatment of inflammation-related disorders.