Immune Responses to Middle East Respiratory Syndrome Coronavirus During the Acute and Convalescent Phases of Human Infection.

BACKGROUND: An understanding of immune responses against the Middle East respiratory syndrome (MERS) is important for the development of treatments and preventive measures. Here, we investigated the spectrum of immune responses occurring in patients with MERS during the early period of infection. METHODS: We obtained peripheral blood samples from 27 hospitalized patients recruited during the epidemic that occurred in 2015 in South Korea. Plasma cytokines/chemokines and antibodies were quantified. Virus-specific T cells were examined by intracellular cytokine staining after stimulation of peripheral blood mononuclear cells with overlapping peptides spanning whole virus structural proteins. RESULTS: At the acute phase of infection, elevated levels of plasma proinflammatory cytokines/chemokines were detected in proportion to the severity of the disease. Distinctively high frequencies of MERS coronavirus-reactive CD8+ T cells were also observed in patients with severe/moderate illness, whereas antibody and CD4+ T-cell responses were minimally detected at this stage. At the convalescent phase, disease severity-dependent antibody responses emerged and antigen-reactive cells were identified in both T-cell subsets. These T cells belonged to the T-helper 1 or type 1 cytotoxic T cell subtypes. While CD8+ T cells responded preferentially to the viral S protein compared with E/M/N proteins, especially at the acute stage, slightly more CD4+ T cells recognized E/M/N proteins compared with S protein at the convalescent phase. CONCLUSIONS: Our findings show an association between the early CD8+ T-cell response and the severity of the infection, and also provide basic information that may help to prepare effective control strategies for MERS in humans.

Clinical performance of the Roche Cobas Liat SARS-CoV-2 & influenza A/B assay: A systematic review and meta-analysis.

Respiratory tract infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses are persistent and critical. The Cobas Liat SARS-CoV-2 & influenza A/B assay (Multiplex Liat), the FDA-authorized point-of-care reverse transcriptase polymerase chain reaction (RT-PCR) assay, has a turnaround time of 20 min and high accuracy. This study evaluates the pooled performance of this assay to provide practical information. This meta-analysis was registered in PROSPERO (registration number: CRD42023467579). A systematic literature search was conducted within PubMed, Ovid-EMBASE, and the Cochrane Library for articles evaluating the accuracy of the Multiplex Liat assay through September 2023. A random-effects model was used to calculate the pooled diagnostic values with real-time RT-PCR (rRT-PCR) as a reference test. A total of 4,705 samples from eight studies were included in the primary meta-analysis. The overall pooled sensitivity and specificity of Multiplex Liat were 100.0 % (95 % confidence interval [CI] = 96.7 %-100.0 %) and 99.7 % (95 % CI = 98.7 %-99.9 %), respectively. The presence of variants of concern or in-house rRT-PCR assays as reference standards did not significantly affect the pooled diagnostic performance of the Multiplex Liat. When 5,333 samples from nine studies were assessed for sensitivity, the pooled sensitivity was 100.0 % (95 % CI = 85.8 %-100.0 %) without a significant difference. This meta-analysis demonstrates the usefulness of Multiplex Liat for the detection of SARS-CoV-2 based on pooled diagnostic values. These practical findings may facilitate appropriate settings for the diagnosis and management of patients with respiratory tract infections.

The effectiveness of nature-based therapy for community psychological distress and well-being during COVID-19: a multi-site trial.

During the COVID-19 pandemic, the world population faced various mental health challenges, highlighting a need for new community-based psychosocial interventions. This study aimed to investigate the effectiveness and feasibility of Nature-Based Therapy (NBT) for the community experiencing psychological distress during the pandemic. A multi-site trial comparing NBT and control groups was conducted in Korea with 291 participants exhibiting mild to severe depression or anxiety. A total of 192 participated in 30 sessions of therapeutic gardening, while 99 remained in the control group. Psychological distress and well-being were assessed using seven measures of depression, anxiety, daily activity, life satisfaction, mindfulness, stress, and loneliness. The effect sizes (Cohen's d) of NBT compared to the control group were medium to large: depression (0.583), anxiety (0.728), daily activity (1.002), life satisfaction (0.786), mindfulness (0.645), stress (0.903), and loneliness (0.695). Multilevel analysis revealed significant Time × Group interaction effects for all measures. Pearson correlation (r = - 0.28 to 0.71) showed that changes in all variables correlated significantly with each other, with small to large effect sizes. Therapeutic alliance at post-test positively moderated the intervention effects on the outcomes. We concluded that NBT is a promising psychosocial intervention for treating psychological distress for community dwellers.

Ultraviolet B radiation activates NF-κB and induces iNOS expression in HR-1 hairless mouse skin: role of IκB kinase-ß.

Exposure to ultraviolet B (UVB) radiation is known to cause inflammatory tissue damage and skin cancer. One of the molecular links between inflammation and cancer is the eukaryotic transcription factor nuclear factor-kappaB (NF-κB), which is known to regulate expression of various pro-inflammatory genes including inducible nitric oxide synthase (iNOS). The present study was aimed at elucidating the molecular mechanisms underlying UVB-induced NF-κB activation and iNOS expression in hairless mouse skin. Irradiation of male HR-1 hairless mouse skin with UVB (5 kJ/m(2) ) resulted in increased degradation of IκBα, nuclear translocation of p65 and p50, and the DNA binding of NF-κB. Exposure to UVB radiation induced the phosphorylation and the catalytic activity of an upstream kinase IκB kinase-ß (IKKß). Pharmacological inhibition of IKKß attenuated UVB-induced NF-κB activation in mouse skin. Irradiation of mouse skin with UVB also increased phosphorylation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinase. Pretreatment with SC-514, a specific inhibitor of IKKß, attenuated UVB-induced phosphorylation of ERK and p38 MAP kinase. A kinetic study showed that UVB significantly increased the expression of iNOS in mouse skin at 6 h postirradiation, which was abrogated by pretreatment with SC-514. In conclusion, the upstream kinase IKKß is involved in UVB-induced activation of MAP kinases and NF-κB, and expression of iNOS in mouse skin.

Oligonol inhibits UVB-induced COX-2 expression in HR-1 hairless mouse skin--AP-1 and C/EBP as potential upstream targets.

Oxidative stress and inflammatory tissue damage are two major events frequently implicated in carcinogenesis. Numerous polyphenolic compounds derived from plants possess antioxidant and anti-inflammatory activities and are hence effective in preventing cancer. Oligonol is a polyphenol formulation enriched with catechin-type oligomers. As an initial approach to assess the chemopreventive potential of oligonol, we have determined its effects on inflammatory as well as oxidative damage in mouse skin irradiated with UVB. Topical application of oligonol onto the dorsal skin of male HR-1 hairless mice 30 min prior to UVB exposure diminished epidermal hyperplasia and formation of 4-hydroxynonenal, a biochemical hallmark of lipid peroxidation. Topical application of oligonol also significantly inhibited UVB-induced cyclooxygenase (COX-2) expression in mouse skin. Oligonol diminished the DNA binding of activator protein-1 (AP-1) and CCAAT/enhancer binding protein (C/EBP), and the expression of C/EBPdelta in mouse skin exposed to UVB. Our study also revealed that oligonol attenuated UVB-induced catalytic activity as well as expression of p38 mitogen-activated protein (MAP) kinase. Moreover, UVB-induced phosphorylation of another upstream kinase Akt was attenuated by oligonol. Taken together, oligonol showed antioxidative and anti-inflammatory effects in UVB-irradiated mouse skin by inhibiting COX-2 expression via blockade of the activation of AP-1 and C/EBP, and upstream kinases including p38 MAP kinase and Akt.

Inhibitory effects of oligonol on phorbol ester-induced tumor promotion and COX-2 expression in mouse skin: NF-kappaB and C/EBP as potential targets.

Plant polyphenols possess anti-oxidant and anti-inflammatory activities and are hence potential candidates for preventing cancer. The present study was aimed at evaluating the anti-inflammatory and anti-tumor promoting activity of oligonol, a formulation of catechin-type oligomers, in mouse skin stimulated with a proto-type tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Pretreatment of mouse skin with oligonol significantly inhibited TPA-induced expression of cyclooxygenase-2 (COX-2). Oligonol diminished nuclear translocation and DNA binding of nuclear factor-kappaB (NF-kappaB) via blockade of phosphorylation and subsequent degradation of IkappaB alpha in TPA-treated mouse skin. Moreover, oligonol suppressed TPA-induced DNA binding of CCAAT/enhancer-binding protein (C/EBP) in mouse skin. Oligonol pretreatment also attenuated the phosphorylation and/or catalytic activities of extracellular signal-regulated protein kinase-1/2 (ERK1/2) and p38 mitogen-activated protein (MAP) kinase. Moreover, p38 MAP kinase inhibitor SB203580, but not the MEK inhibitor U0126, negated TPA-induced DNA binding of C/EBP. In addition, oligonol reduced the incidence and the multiplicity of papillomas and squamous cell carcinomas in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated and TPA-promoted mouse skin, and prolonged the survival of tumor-bearing mice. Pretreatment with oligonol diminished the levels of proliferating cell nuclear antigen and expression of COX-2 in papillomas and carcinomas, respectively, as compared to DMBA plus TPA treatment alone. Taken together, the above findings suggest that oligonol inhibits TPA-induced COX-2 expression by blocking the activation of NF-kappaB and C/EBP via modulation of MAP kinases and suppresses chemically induced mouse skin tumorigenesis.