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Human cytomegalovirus (HCMV) is a ubiquitous pathogen that can cause permanent childhood disabilities following in utero infection and life threatening diseases in immune-compromised individuals such as those post transplantation. Without an effective vaccine, small molecule antiviral drugs are routinely used in high-risk transplant recipients, but the effectiveness of which is limited by side effects and drug resistance. The potentials of antibody-based passive immune therapies alone or in combination with the small molecule antivirals to treat or prevent HCMV infection have been actively studied. In this review, we focus on the recent publications on identification and characterization of monoclonal antibodies that have the potential to be developed as anti-HCMV therapies. We review the progress in clinical evaluation of antibody-based therapies to prevent HCMV-associated diseases.
Thiamine (Vitamin B1) deficiency (TD), although reduced in incidence, is still seen in infants. We describe a rarely reported form of infantile TD with life-threatening pulmonary hypertensive crisis and severe encephalopathy, with dramatic response to thiamine supplementation.
Study design Descriptive case series. Six young infants with mean age 76 days (range 1-3 months), manifesting rapidly progressive encephalopathy and cardio-pulmonary arrest were included. find more All infants underwent cardiac, neuroimaging and metabolic evaluations.
All six infants had similar presentation with severe pulmonary arterial hypertension (PAH), hypotensive shock, metabolic acidosis and severe encephalopathy. All infants were exclusively breast-fed. Thiamine treatmwnt resulted in dramatic improvement in haemodynamic and neurological function in all the infants. There were no major neurological deficits on follow up.
A high index of suspicion is warranted for this rarely described form of TD, as early identification helps in preventing mortality and morbidity.
A high index of suspicion is warranted for this rarely described form of TD, as early identification helps in preventing mortality and morbidity.CRISPR/Cas9-mediated gene-editing technology has gained attention as a new therapeutic method for intractable diseases. However, the use of CRISPR/Cas9 for cardiac conditions such as myocardial infarction remains challenging due to technical and biological barriers, particularly difficulties in delivering the system and targeting genes in the heart. In the present study, we demonstrated the in vivo efficacy of the CRISPR/Cas9 magnetoplexes system for therapeutic genome editing in myocardial infarction. First, we developed CRISPR/Cas9 magnetoplexes that magnetically guided CRISPR/Cas9 system to the heart for efficient in vivo therapeutic gene targeting during heart failures. We then demonstrated that the in vivo gene targeting of miR34a via these CRISPR/Cas9 magnetoplexes in a mouse model of myocardial infarction significantly improved cardiac repair and regeneration to facilitate improvements in cardiac function. These results indicated that CRISPR/Cas9 magnetoplexes represent an effective in vivo therapeutic gene-targeting platform in the myocardial infarction of heart, and that this strategy may be applicable for the treatment of a broad range of cardiac failures.This study aimed to investigate a protective effect of hydrolyzed wheat gluten (HWG) on Escherichia coli (E. coli)-induced intestinal barrier dysfunctions in broilers. Broilers fed a basal diet unsupplemented or supplemented with HWG (0.5% or 1%) were intraperitoneally injected with either E. coli O78 suspension (108 CFU/mL) or equal volume of vehicle on d 18 of age. Blood and tissue samples were collected 3rd d post infection. The results showed that E. coli-infection increased immune-organ indexes of spleen and thymus, enhanced serum diamine oxidase (DAO) level, impaired ileal villus structure and reduced tight junction mRNA levels (Occludin, Claudin-1, ZO-1, P less then 0.05), while increased mRNA levels of inflammatory cytokines (TNF-α, IFN-γ, IL-1β, IL-6, IL-8) and TLR4 in the ileum of broilers (P less then 0.05). The effects of E. coli O78 challenge on organ indexes of spleen and thymus, serum DAO level, mRNA levels of tight junctions were alleviated by 1% HWG supplementation, the upregulations of IL-1β and TLR4 were prevented by 0.5% HWG supplementation (P less then 0.05). In addition, increased IFN-γ of E. coli-infected broilers was abrogated by 0.5% or 1% HWG supplementation (P less then 0.05). In summary, dietary HWG supplementation ameliorated intestinal barrier dysfunctions triggered by E. coli-infection in the ileum of broilers. HWG supplementation might be a nutritional strategy to improve the intestinal mucosal barrier function of broilers.
Astaxanthin is a xanthophyll pigment found in algae and marine animals, having strong anti-oxidative, anti-tumoral, and anti-inflammatory effects. Additionally, melatonin has shown inhibitory effects on the growth of human breast cancer cells. The aim of the present study was to evaluate the effect of astaxanthin and the combined effects of astaxanthin and melatonin on breast cancer cells and the non-tumoral breast cell line.
The human breast cancer cell lines, T47D and MDA-MB-231, and non-tumorigenic cell line MCF 10A were treated and compared to astaxanthin, melatonin, and co-administration of these two compounds. Cell viability, apoptosis induction, Bcl-2 protein expression, and DNA damage were measured by MTT assay, acridine orange/ethidium bromide (AO/EB) staining, immunocytochemistry, and comet assay.
Astaxanthin at lower doses than melatonin reduced cell viability and Bcl2 expression, induced apoptosis and DNA damage in MDA-MB-231 and T47D. Meanwhile, the effects of astaxanthin on cell cytotoxicity, apoptosis, and DNA damage in MCF10A cells are insignificant compared to MDA-MB-231 and T47D. Moreover, the results indicated that astaxanthin in T47D cells caused more cell death compared to MDA-MB-231 cells. Astaxanthin induced cell death on breast cancer cells and without cell cytotoxicity for non-cancerous cells.
Furthermore, the presence of astaxanthin increased the function of melatonin-induced cell death in breast cancer cells.
Furthermore, the presence of astaxanthin increased the function of melatonin-induced cell death in breast cancer cells.Senecavirus A (SVA) is an emerging picornavirus associated with porcine idiopathic vesicular disease (PIVD), which is clinically indistinguishable from foot-and-mouth disease and other vesicular diseases in pigs. In recent years, the wide spread of SVA has caused huge economic losses to the world's pig industry. However, there are no vaccines currently available to prevent and control the infection of SVA due to the extensive diversity of SVA isolates and high cost of the pig model for vaccine evaluation. In the present study, a novel SVA CH-HNCY-2019 strain with unique amino-acid mutations in VP1, VP3 and 3C was isolated from the central part of China. A mouse model was proposed to for evaluation of the immunogenicity and protective efficacy of the inactivated CH-HNCY-2019 vaccine. The results indicated that one dose immunization of 107TCID50 inactivated CH-HNCY-2019 vaccine in mice induced a high titer of neutralizing antibody and complete protection. After challenging with the homologous virus, no viral RNA or histopathological damages were detected in the heart, liver, spleen, lung, kidney, intestine and brain tissues of the immunized mice. However, viral RNA and different degrees of histopathological damages were observed in all corresponding tissues of the unimmunized mice. In summary, the present study proved that mouse is a candidate animal model for the primary evaluation of the immunogenicity and protection efficacy of SVA vaccines for the first time. In addition, the inactivated SVA CH-HNCY-2019 vaccine was immunogenic and could protect mice against homologous viral challenges.T follicular helper (Tfh) cells help orchestrate optimal humoral immunity by helping B cells to produce affinity-matured, class-switched antibodies in germinal centers. Recent studies have unveiled the complexity and heterogeneity in Tfh cell populations, particularly with respect to their cytokine production. These distinct Tfh cell subsets help tune the class, magnitude and quality of the immunoglobulins produced by B cells, thus shaping the course of humoral responses. The Tfh cell-B cell axis-dependent antibody production is mostly beneficial, but at times can go awry and result in the generation of pathologic antibodies that can harm the host. While IgE class of antibodies are infamous for their detrimental role in allergic diseases, emerging evidence is indicative of their pathologic roles in other dysregulated immune states. Here, we discuss the role of Tfh cell subsets in the regulation of pathologic IgE production in allergies and other immunopathologic conditions.It is well recognized that underrepresented and systematically minoritized groups do not have balanced access to clinical trials as study participants or as research Investigators. However, comprehensive data on the perspective of expert clinicians is largely lacking in the current literature. In this pilot exploration, we collected the opinions of 33 subject matter experts (SME) to identify and explore potential barriers to diversification in clinical trials. The majority of respondents live in North America or Central or Western Europe and identified as not a member of an underrepresented or marginalized group (UMB), with about 15% of respondents being a member of a UMB. Overall, about a quarter of respondents reported making an intentional effort to recruit members of UMB as study participants and identified recruitment challenges linked to two areas psycho-social barriers and practical barriers. A variety of strategies were employed to improve recruitment including engagement with community leaders, targeted advertising, utilizing databases, and social media campaigns. About half of respondents reported difficulties recruiting Investigators from UMB backgrounds, stating culture and language barriers, perceived lack of interest in the field among individuals from UMB, and lack of information as possible reasons for the challenges.Cannabidiol (CBD) has become a fast-growing avenue for research in psychiatry, and clinicians are challenged with understanding the implications of CBD for treating mental health disorders. The goal of this review is to serve as a guide for mental health professionals by providing an overview of CBD and a synthesis the current evidence within major psychiatric disorders. PubMed and PsycINFO were searched for articles containing the terms "cannabidiol" in addition to major psychiatric disorders and symptoms, yielding 2952 articles. Only randomized controlled trials or within-subject studies investigating CBD as a treatment option for psychiatric disorders (N = 16) were included in the review. Studies were reviewed for psychotic disorders (n = 6), anxiety disorders (n = 3), substance use disorders (tobacco n = 3, cannabis n = 2, opioid n = 1), and insomnia (n = 1). There were no published studies that met inclusion criteria for alcohol or stimulant use disorder, PTSD, ADHD, autism spectrum disorder, or mood disorders.