Interferon-Stimulated Gene 15 Knockout in Mice Impairs IFNα-Mediated Antiviral Activity.

Type I interferon (IFN) plays an important role in the host defense against viral infection by inducing expression of interferon-stimulated genes (ISGs). In a previous study, we found that porcine interferon-stimulated gene 15 (ISG15) exhibited antiviral activity against PRV in vitro. To further investigate the antiviral function of ISG15 in vivo, we utilized ISG15 knockout (ISG15-/-) mice in this study. Here, we demonstrate that ISG15-/- mice were highly susceptible to PRV infection in vivo, as evidenced by a considerably reduced survival rate, enhanced viral replication and severe pathological lesions. However, we observed no significant difference between female and male infected WT and ISG15-/- mice. Moreover, ISG15-/- mice displayed attenuated antiviral protection as a result of considerably reduced expression of IFNß and relevant ISGs during PRV replication. Furthermore, excessive production of proinflammatory cytokines may be closely related to encephalitis and pneumonia. In further studies, we found that the enhanced sensitivity to PRV infection in ISG15-/- mice might be caused by reduced phosphorylation of STAT1 and STAT2, thereby inhibiting type I IFN-mediated antiviral activity. Based on these findings, we conclude that ISG15 is essential for host type I IFN-mediated antiviral response.

Pathological impact and medical applications of electromagnetic field on melanoma: A focused review.

Electromagnetic Field (EMF) influences melanoma in various ways. EMF can be classified into extremely low-frequency electromagnetic field, low-frequency magnetic field, static moderate magnetic field, strong electromagnetic field, alternating magnetic field, and magnetic nanoparticles. Each type of EMF influences melanoma development differently, and the detailed influence of each specific type of EMF on melanoma is reviewed. Furthermore, EMF influences melanoma cell polarity and hence affects drug uptake. In this review, the impacts of EMF on the effectiveness of drugs used to treat melanoma are listed according to drug types, with detailed effects according to the types of EMF and specific melanoma cell lines. EMF also impacts clinical therapies of melanoma, including localized magnetic hyperthermia, focalized thermotherapy, proton radiation treatment, nanostructure heating magnetic hyperthermia, radiation therapy, Polycaprolactone-Fe3O4 fiber mat-based bandage, and optune therapy. Above all, EMF has huge potential in melanoma treatment.

Gut Microbiome Signatures Are Predictive of Cognitive Impairment in Hypertension Patients-A Cohort Study.

Growing evidence has demonstrated that hypertension was associated with dysbiosis of intestinal flora. Since intestinal microbes could critically regulate neurofunction via the intestinal-brain axis, the study aimed to reveal the role and prediction value of intestinal flora alteration in hypertension-associated cognitive impairment. A cohort of 97 participants included 63 hypertension patients and 34 healthy controls. The structure of intestinal flora was analyzed by V3-V4 16S rRNA amplicon sequencing. The cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and 31 patients were considered to have cognitive impairment (MoCA < 26). Patients with cognitive impairment had considerable alterations in intestinal flora structure, composition, and function compared with normal-cognitive patients. In particular, the abundance of LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) and SCFA-producing taxon (Prevotella) significantly changed in cognition-impaired patients. Tax4Fun predication results showed downregulation of glycan biosynthesis and metabolism in hypertension patients with cognitive impairment. Additionally, the pathway was demonstrated to be significantly correlated with LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia-Shigella) and SCFA-producing taxon Prevotella. Furthermore, the taxa-based multiple joint prediction model (9×) was demonstrated to have excellent diagnostic potential for cognitive impairment of hypertension patients (AUC = 0.944). The current study revealed the involvement of intestinal microbiota dysbiosis in cognition-impaired hypertension patients and provided an objective predictive index for this cognition disorder.

Association of visceral adiposity index with new-onset type 2 diabetes and impaired fasting glucose in hypertensive Chinese adults.

PURPOSE: Visceral adiposity index (VAI) is a reliable indicator for the distribution and function of adipose tissue in the body. The relation of VAI with new-onset type 2 diabetes and new-onset impaired fasting glucose (IFG) remains uncertain. We aimed to investigate the prospective relation of VAI with new-onset type 2 diabetes and new-onset IFG in Chinese hypertensive adults. METHODS: A total of 14,838 hypertensive adults free of type 2 diabetes at baseline were included from the China Stroke Primary Prevention Trial. The primary outcome was new-onset type 2 diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥ 7.0 mmol/L at the exit visit. The secondary outcome was new-onset IFG, defined as fasting glucose < 6.1 mmol/L at baseline, while fasting glucose ≥ 6.1 mmol/L and < 7.0 mmol/L at the exit visit. RESULTS: Over a median of 4.5 years' follow-up, 1612 (10.9%) participants developed type 2 diabetes. When VAI was categorized into quartiles, compared with participants in quartile 1-3 (< 2.80), significantly higher risk of new-onset type 2 diabetes (OR 1.30; 95% CI 1.08-1.56) and new-onset IFG (OR 1.28; 95% CI 1.08-1.52) was found in those in quartile 4 (≥ 2.80). Moreover, the positive associations were consistent in participants with or without single abnormal VAI components, including general obesity, abdominal obesity, elevated triglycerides and low high-density lipoprotein cholesterol (HDL-C) levels; or with different numbers of abnormal VAI components (all P interactions > 0.05). CONCLUSION: Our study suggested a positive relation of VAI with the risk of new-onset type 2 diabetes and new-onset IFG in Chinese hypertensive patients, independent of its components. LEVEL OF EVIDENCE: Level III, a well-designed cohort.

Impact of exercise on hippocampal neurogenesis in hyperglycemic diabetes.

Hyperglycemic diabetes is a chronic metabolic disorder characterized by high level of plasma glucose. Numerous studies have shown that hy-perglycemic diabetes leads to brain dysfunction including cognitive im-pairment and emotional disorders. This study evaluated the impact of exercise on brain dysfunction, hippocampal neurogenesis, and cogni-tive impairment in hyperglycemic diabetes. The present study suggests that exercise improves hyperglycemic control and prevents decline of cognition through increasing hippocampal neurogenesis. Understanding the mechanism of exercise for hippocampal neurogenesis can lead to the development of therapeutic strategies for metabolic disorders.

Hearing-impaired population performance and the effect of hearing interventions on Montreal Cognitive Assessment (MoCA): Systematic review and meta-analysis.

BACKGROUND: Older adults are at high risk of developing age-related hearing loss (HL) and/or cognitive impairment. However, cognitive screening tools rely on oral administration of instructions and stimuli that may be impacted by HL. This systematic review aims to investigate (a) whether people with HL perform worse than those without HL on the Montreal Cognitive Assessment (MoCA), a widely used screening tool for cognitive impairment, and what the effect size of that difference is (b) whether HL treatment mitigates the impact of HL. METHOD: We conducted a systematic review and meta-analysis including studies that reported mean MoCA scores and SDs for individuals with HL. RESULTS: People with HL performed significantly worse on the MoCA (4 studies, N = 533) with a pooled mean difference of -1.66 points (95% confidence interval CI -2.74 to -0.58). There was no significant difference in MoCA score between the pre- vs post-hearing intervention (3 studies, N = 75). However, sensitivity analysis in the cochlear implant studies (2 studies, N = 33) showed improvement of the MoCA score by 1.73 (95% CI 0.18 to 3.28). CONCLUSION: People with HL score significantly lower than individuals with normal hearing on the standard orally administered MoCA. Clinicians should consider listening conditions when administering the MoCA and report the hearing status of the tested individuals, if known, taking this into account in interpretation or make note of any hearing difficulty during consultations which may warrant onward referral. Cochlear implants may improve the MoCA score of individuals with HL, and more evidence is required on other treatments. J Am Geriatr Soc 68:-, 2020.

Timed Up-and-Go Dual-Task Testing in the Assessment of Cognitive Function: A Mixed Methods Observational Study for Development of the UDDGait Protocol.

New methods to screen for and identify early-stage dementia disorders are highly sought after. The purpose of this pilot study is to develop a study protocol for a dual-task test aimed at aiding the early detection of dementia disorders. We used the Timed Up-and-Go (TUG) test, which is a mobility task involving starting in a sitting position, standing up, walking three meters to cross a line on the floor, turning around, walking back and sitting down again. We combined TUG with the verbal task of naming different animals. Pilot study participants were 43 individuals with and without established dementia diagnoses who attended a clinic for memory assessment. Video-recorded test performances were systematically analysed. Deviant test performances concerning the interplay between test administration and participants' responses to the assessment instructions were revealed and led to refinements being made to the final study protocol. Exploration of the dual-task test outcome measures in a sub-sample of 22 persons, ten with and twelve without dementia, indicated that step-length and number of named animals after the turning point of the dual-task test might constitute appropriate measures for examining this kind of sample. We concluded that the refined study protocol is feasible for testing individuals undergoing initial memory assessments and healthy controls. Follow-up studies with larger samples are being carried out and will bring new knowledge to this area of research. It may also provide an opportunity for further studies exploring possibilities for broad clinical implementation.

Murine Skin-resident γδT Cells Impair the Immune Response to HSV in Skin.

BACKGROUND: HSV is an important cause of brain infection. Virus entry is often through breeches in the skin. γδT cells play an immunoprotective role in mice after corneal, genital or footpad (subcutaneous) HSV infection. METHODS: Here we report that the presence of γδT cells in murine skin is associated with increased severity of herpetic disease, reduced protective cytokine responses and increased viral spread from the skin to the sensory ganglia in the zosteriform model. γδT cell-deficient (TCR δ -/-) mice displayed significantly decreased herpetic lesion severity after flank HSV infection compared to WT C57BL/6 controls at both primary and secondary skin infection sites. RESULTS: Viral titer at the primary skin site was similar to WT mice in γδT cell-deficient mice, but was significantly decreased in the ganglia and secondary skin site. γδT cell-deficient mice showed increased Th1 responses by both T cells and non-T cells at the primary site, and decreased T-cell Th17 responses and immune infiltration at the secondary site. CONCLUSION: Cytokine responses of epidermal and dermal γδT cells to HSV also differed in WT mice (Th1 in epidermis, and Th17 in the dermis), suggesting a functional dichotomy between these two subsets. Our data suggest that in contrast to other mouse models of HSV infection, skinresident γδT cells promote the pathogenesis of HSV in skin.

Micronuclei in Exfoliated Buccal Cells of Children Living in a Cluster Area of Salento (Southern Italy) with a High Incidence of Lung Cancer: The IMP.AIR Study.

During the years 2014⁻2016 the University of Salento performed the "Impact of Air Quality on Health of Residents in the Municipalities of Cutrofiano, Galatina, Sogliano Cavour, Soleto and Sternatia" (IMP.AIR) study, an epidemiological-molecular research project aiming to evaluate early DNA damage in children living in an area of Salento with high incidence of lung cancer among the male population. One hundred and twenty-two children aged 6⁻8 years attending primary school were enrolled and the frequency of micronucleated cells (MNC) in oral mucosa was evaluated. In addition, a questionnaire was administered to parents to obtain information about personal data, anthropometric characteristics and lifestyles (physical activity, food habits, family context) of the children and perform a multivariate analysis to detect any factors associated with MNC occurrence. Data on airborne pollutants detected in the study area were acquired by the Regional Agency for the Environmental Protection. The presence of MNC was highlighted in about 42% of children with a mean MNC frequency of 0.49‰. The frequency of MNC was associated to obesity, consumption of red or processed meat and having a mother who smokes. Moreover, the prevalence of biomarkers was higher than in another area of Salento not included in the cluster area.

Effects of Zinc Supplementation on DNA Damage in Rats with Experimental Kidney Deficiency.

This study was carried out to determine the effect of zinc on oxidative DNA damage in rats with experimental acute and chronic kidney deficiency. Six groups of five Wistar-Albino rats each were assigned as controls (C), acute kidney deficiency (AKD), zinc-supplemented (+Zn), acute kidney deficiency, zinc-supplemented (AKD + Zn), chronic kidney deficiency (CKD) and zinc-supplemented chronic kidney deficiency (CKD + Zn). The levels of 8-Oxo-2'-deoxyguanosine (8-OHdG) were determined, being the lowest in the CKD group (p < 0.05), higher in the C group than those of rats with CKD but lower than that of all the other groups (p < 0.05). There were no significant differences between the controls and the CKD + Zn group, or between the AKD and the +Zn groups. Among all groups, the highest 8-OHdG level was found in the AKD + Zn group (p < 0.05). DNA damage was greater in acute renal failure than in rats with chronic renal failure. The DNA damage in the zinc group was significantly higher than in the controls.