Longitudinal transcriptional analysis of peripheral blood leukocytes in COVID-19 convalescent donors.

BACKGROUND: SARS-CoV2 can induce a strong host immune response. Many studies have evaluated antibody response following SARS-CoV2 infections. This study investigated the immune response and T cell receptor diversity in people who had recovered from SARS-CoV2 infection (COVID-19). METHODS: Using the nCounter platform, we compared transcriptomic profiles of 162 COVID-19 convalescent donors (CCD) and 40 healthy donors (HD). 69 of the 162 CCDs had two or more time points sampled. RESULTS: After eliminating the effects of demographic factors, we found extensive differential gene expression up to 241 days into the convalescent period. The differentially expressed genes were involved in several pathways, including virus-host interaction, interleukin and JAK-STAT signaling, T-cell co-stimulation, and immune exhaustion. A subset of 21 CCD samples was found to be highly "perturbed," characterized by overexpression of PLAU, IL1B, NFKB1, PLEK, LCP2, IRF3, MTOR, IL18BP, RACK1, TGFB1, and others. In addition, one of the clusters, P1 (n = 8) CCD samples, showed enhanced TCR diversity in 7 VJ pairs (TRAV9.1_TCRVA_014.1, TRBV6.8_TCRVB_016.1, TRAV7_TCRVA_008.1, TRGV9_ENST00000444775.1, TRAV18_TCRVA_026.1, TRGV4_ENST00000390345.1, TRAV11_TCRVA_017.1). Multiplexed cytokine analysis revealed anomalies in SCF, SCGF-b, and MCP-1 expression in this subset. CONCLUSIONS: Persistent alterations in inflammatory pathways and T-cell activation/exhaustion markers for months after active infection may help shed light on the pathophysiology of a prolonged post-viral syndrome observed following recovery from COVID-19 infection. Future studies may inform the ability to identify druggable targets involving these pathways to mitigate the long-term effects of COVID-19 infection. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04360278 Registered April 24, 2020.

Corrigendum: Effect of chlorogenic acid supplementation in MPTP-intoxicated mouse.

[This corrects the article DOI: 10.3389/fphar.2018.00757.].

Human Papillomavirus Genome based Detection and Typing: A Holistic Molecular Approach.

Human Papillomavirus (HPV) is a species specific double-stranded DNA virus infecting human cutaneous or mucosal tissues. The genome structure of HPV is extremely polymorphic hence making it difficult to discriminate between them. HPV exhibits numerous dissimilar types that can be subdivided into high-risk (HR), probably high-risk and low-risk (LR), causing numerous types of cancers and warts around the genital organs in humans. Several screening methods are performed in order to detect cytological abnormalities and presence or absence of HPV genome. Currently available commercial kits and methods are designed to detect only a few HR/LR-HPV types, which are expensive adding to the economic burden of the affected individual and are not freely available. These gaps could be minimized through Polymerase Chain reaction (PCR) method, which is a gold standard and a cost-effective technique for the detection of most HPV (both known and unknown) types by using specific consensus primers in minimal lab setup. In this context, numerous studies have validated the effectiveness of different sets of consensus primers in the screening of HPVs. Numerous consensus primers, such as E6, E6/E7, GP-E6/E7, MY09/11, GP5+/GP6+, SPF10, and PGMY09/11 have been developed to detect the presence of HPV DNA. In addition, HPV detection sensitivity could be achieved through consensus primer sets targeting specific ORF regions like L1 and E6, which may finally assist in better diagnosis of several unknown HR-HPVs. The present review, provides a summary of the available methods, kits and consensus primer sets for HPV genome based detection, their advantages and limitations along with future goals to be set for HPV detection.

Effect of Chlorogenic Acid Supplementation in MPTP-Intoxicated Mouse.

Oxidative stress and neuroinflammation play a key role in dopaminergic (DA) neuronal degeneration, which results in the hindrance of normal ongoing biological processes in the case of Parkinson's disease. As shown in several studies, on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, different behavioral parameters have suggested motor impairment and damage of antioxidant defence. Thus, some specific biological molecules found in medicinal plants can be used to inhibit the DA neuronal degeneration through their antioxidant and anti-inflammatory activities. With this objective, we studied chlorogenic acid (CGA), a naturally occurring polyphenolic compound, for its antioxidant and anti-inflammatory properties in MPTP-intoxicated mice. We observed significant reoccurrence of motor coordination and antioxidant defence on CGA supplementation, which has been in contrast with MPTP-injected mice. Moreover, in the case of CGA-treated mice, the enhanced expression of tyrosine hydroxylase (TH) within the nigrostriatal region has supported its beneficial effect. The activation of glial cells and oxidative stress levels were also estimated using inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP) immunoreactivity within substantia nigra (SN) and striatum of MPTP-injected mice. Administration of CGA has prevented the neuroinflammation in SN by regulating the nuclear factor-κB expression in the MPTP-induced group. The significant release of certain pro-inflammatory mediators such as tumor necrosis factor-α and interleukin (IL)-1ß has also been inhibited by CGA with the enhanced expression of anti-inflammatory cytokine IL-10. Moreover, reduced GFAP staining within the nigrostriatal region has supported the fact that CGA has significantly helped in the attenuation of astrocyte activation. Hence, our study has shown that CGA supplementation shows its therapeutic ability by reducing the oxidative stress and neuroinflammation in MPTP-intoxicated mice.

Mucuna pruriens Protects against MPTP Intoxicated Neuroinflammation in Parkinson's Disease through NF-κB/pAKT Signaling Pathways.

Till date, drugs that have been used to manage Parkinson's disease (PD) have only shown symptomatic relief with several adverse effects besides their inability to prevent neurodegeneration. Neuroinflammation plays an important role in the advancement of PD and can be targeted for its effective treatment. Researchers have suggested that herbal plants exhibiting the anti-inflammatory and anti-oxidant properties are therefore beneficial to human health. Conventionally, Mucuna pruriens (Mp) seeds are used for maintaining male virility in India. Reportedly, Mp is used as a rejuvenator drug having neuroprotective property. Our study aimed to investigate effects of aqueous extract of Mp (100 mg/kgbwt) on neuroinflammation, orally administered to mice intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as well as the molecular mechanism involved in the progression of PD. In this study, we have observed significant behavioral abnormalities beside decreased antioxidant defense in MPTP intoxicated mice. We have also observed significant increase in inflammatory parameters like Glial Fibrillary Acidic Protein, Inducible Nitric Oxide Synthase, Intercellular Cell Adhesion Molecule, and Tumor Necrosis Factor alpha in substantia nigra pars compacta (SNpc) of parkinsonian mice, while Mp treatment has notably reduced these inflammatory parameters. Mp also inhibited the MPTP induced activation of NF-κB and promoted pAkt1 activity which further prevented the apoptosis of the dopaminergic neurons. Moreover, Mp exhibited significant antioxidant defense by inhibiting the lipid peroxidation and nitrite level, and by improving catalase activity and enhancing GSH level in nigrostriatal region of mouse brain. Mp also recovered the behavioral abnormalities in MPTP treated mice. Additionally, Mp treatment considerably increased the immunoreactivity of Tyrosine Hydroxylase and Dopamine Transporter in SNpc of parkinsonian mice. Our high performance liquid chromatography analysis of the Mp seed extract have shown L-DOPA, gallic acid, phytic acid, quercetin, and catechin equivalents as the major components which might cause neuroprotection in PD mice. Our result suggested that Mp extract treatment containing L-DOPA and a mixture of rich novel phytochemicals significantly alleviates the MPTP induced neurotoxicity by NF-κB and pAkt pathway. The findings observed thereby indicate that Mp extract have suggestively ameliorated MPTP induced neuroinflammation, restored the biochemical and behavioral abnormalities in PD mouse and thus provided a scientific basis for its traditional claim.