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Hexon modification to improve the activity of oncolytic adenovirus vectors against neoplastic and stromal cells in pancreatic cancer.

Primary pancreatic carcinoma has an unfavourable prognosis and standard treatment strategies mostly fail in advanced cases. Virotherapy might overcome this resistance to current treatment modalities. However, data from clinical studies with oncolytic viruses, including replicating adenoviral (Ad) vectors, have shown only limited activity against pancreatic cancer and other carcinomas. Since pancreatic carcinomas have a complex tumor architecture and frequently a strong stromal compartment consisting of non-neoplastic cell types (mainly pancreatic stellate cells = hPSCs) and extracellular matri

Thrombosis-related circulating miR-16-5p is associated with disease severity in patients hospitalised for COVID-19.

SARS-CoV-2 tropism for the ACE2 receptor, along with the multifaceted inflammatory reaction, is likely to drive the generalized hypercoagulable and thrombotic state seen in patients with COVID-19. Using the original bioinformatic workflow and network medicine approaches we reanalysed four coronavirus-related expression datasets and performed co-expression analysis focused on thrombosis and ACE2 related genes. We identified microRNAs (miRNAs) which play role in ACE2-related thrombosis in coronavirus infection and further, we validated the expressions of precisely selected miRNAs-related to thro…

Immunity and vaccine development in the bovine theilerioses.

There are three economically important bovine Theileria species: Theileria annulata, which causes tropical theileriosis and occurs across no … ntification of a range of other antigens, especially from the schizont stage. Theileria parva has a tropism for T cells. Vaccination is currently by the 'infection and treatment' method, which involves challenging with a controlled dose of sporozoite stabilate and the simultaneous administration of long-acting tetracyclines. The immunity thus induced is m …

[Hepatitis C in a psychiatric setting: A forgotten reservoir?].

Hepatitis C is a transmissible hepatic and extra-hepatic disease caused by the hepatitis C virus (HCV). HCV develops into a chronic infectio … fits into the individualized psychiatric care. Many recent data suggest that HCV also has a neural tropism, in particular within glial cells, such as astrocytes or oligodendrocytes. As such, HCV foments inflammatory processes in the brain and contributes to cognitive impairments and psychiatric symptoms such as anxiety or depression. At the individual le …

THE STRENGTHS, WEAKNESSES, OPPORTUNITIES, AND THREATS (SWOTs) ANALYSES OF THE EBOLA VIRUS - PAPER RETRACTED.

BACKGROUND: Owing to the extreme virulence and case fatality rate of ebola virus disease (EVD), there had been so much furore, panic and pub … and recombine to generate mutant or reassortant virulent strains; Ebola virus has a broad cellular tropism; Natural Reservoir of ebola virus is unconfirmed but fruit bats, arthropods, and plants are hypothesized; Ebola virus primarily targets and selectively destroys the immune system; Ebola viruses possess accessory proteins that inhibits the host' immu …

[Deep lung--cellular reaction to HIV].

UNLABELLED: The course of HIV infection is accompanied by a wide individual variability. The complex and large interplay between host and vi … ptors for HIV, allowed a better understanding of the mechanisms underlying viral cellular entry and tropism. On this issue several authors have reported that in addition to the CD4 molecule, most strains of HIV use the chemokine receptor CCR5 for viral attachment and entry into the host cells. This receptor seems to be very important in disease transmissi …

Imaging and Hemodynamic Mechanisms of Cardiac Remodeling with SGLT2 Inhibitors Across Heart Failure Phenotypes: A Systematic Review.

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors, originally developed as glucose-lowering agents for type 2 diabetes mellitus, … red trial at low risk of bias (EFFORT) was neutral; the largest volumetric estimates came from EMPA-TROPISM, which published no adjusted between-group estimate. The only prespecified, adjusted and confidence-interval-bearing volumetric estimates were those of SUGAR-DM-HF (left ventricular end-systolic volume index -6.0 mL/m2, 95% CI -10.8 to -1.2; end-dia …

Comparison of the Utility of Amplitude-Spectral and Coherence Features of Psychotropic Drugs' Action on ECoG Signal for Pharmaco-EEG Based Drug Screening in Rats.

A naive Bayesian classifier (NBC) combined with principal component analysis (PCA) effectively differentiates the dose-dependent effects of … am) and 5-ethyl-5-phenyl-2,4,6(1H,3H,5H)-pyrimidinetrione. The test set included various drugs with tropism for the targets of the training set drugs: dopamine receptor antagonists chlorpromazine, droperidol, tiapride and raclopride, H1-histamine blockers diphenhydramine and promethazine, 5-HT2-receptor blockers ritanserin and glemenserin, acetylcholinest …

Eugenia caryophyllata Thunb.: A comprehensive review of the traditional uses, phytochemistry, pharmacology, and quality control.

ETHNOPHARMACOLOGY RELEVANCE: In traditional Chinese medicine, Eugenia caryophllyata Thunb. (Clove) is considered warm in nature and pungent in flavor, entering the spleen, stomach, lung, and kidney meridians (In traditional Chinese medicine theory, "meridian tropism" refers to the selective therapeutic effect of a medicinal substance on certain zang-fu organs and meridians of the human body. This herb primarily acts on the spleen, stomach, lung, and kidney, as well as their corresponding meridians). Its core functions are warming the middle to descend counterflow, dispelling cold to alleviate …

A virus-packageable CRISPR screen identifies host factors mediating interferon inhibition of HIV.

UNLABELLED: Interferon (IFN) inhibits HIV replication by inducing antiviral effectors. To comprehensively identify IFN-induced HIV restriction factors, we assembled a CRISPR sgRNA library of Interferon Stimulated Genes (ISGs) into a modified lentiviral vector that allows for packaging of sgRNA-encoding genomes in trans into budding HIV-1 particles. We observed that knockout of Zinc Antiviral Protein (ZAP) improved the performance of the screen due to ZAP-mediated inhibition of the vector. A small panel of IFN-induced HIV restriction factors, including MxB, IFITM1, Tetherin/BST2 and TRIM5alpha

Virological characteristics of a SARS-CoV-2-related bat coronavirus, BANAL-20-236.

BACKGROUND: Although several SARS-CoV-2-related coronaviruses (SC2r-CoVs) were discovered in bats and pangolins, the differences in virologi … that of SARS-CoV-2. INTERPRETATION: Compared to SARS-CoV-2, we demonstrated that B236 exhibited a tropism toward intestinal cells rather than respiratory cells. Our results are consistent with a previous report showing that B236 is enterotropic in macaques. Altogether, our report strengthens the assumption that SC2r-CoVs in horseshoe bats replicate prim …

Унификация модели множественного склероза.

Множественный склероз (MS) представляет собой сложное нейродегенеративное расстройство с неразрешенной причиной, ставшей предметом интенсивных исследований. Для разъяснения курса болезни были предложены различные предлагаемые модели. Первостепенные механизмы, как предполагается, основываются на автоматическом иммунитете, в том числе с помощью вирусного имитации эпитопов, хотя и были описаны трудности с классической моделью автономного иммунитета для MS. Одна предыдущая идея, которая включает в себя рассмотрение вирусной самореактивности, заключается в том, что реактивированный вирус HHV-6A мож

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… HHV-6A has tropism for a relatively broad variety of cell and tissue types, owing to use of the complement receptor CD46, expressed on all nucleated human cells, as a cellular receptor [ 36 , 37 ]. … For example, it could be argued that HHV-6B reactivation might have been similarly mis-assigned in the previous studies—perhaps in more exaggerated fashion owing to different cellular and tissue tropisms. …

Leveraging the bacteria for enhanced cancer immunotherapy: from a perspective of synthetic biology.

In recent years, synthetic biology has been widely applied to engineer and program cellular behaviors. Using this approach, bacteria can be designed to express immunotherapeutic agents, improve tumor targeting, and deliver therapeutic payloads directly to tumor sites. To further improve efficacy, strategies such as hypoxia-responsive promoters, bacterial swarming, and extracellular vesicles (EVs) have been investigated, along with the synergistic effects of combining bacterial therapy with other treatments (e.g., photodynamic therapy, chemotherapy, immune checkpoint inhibitors). This review su

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… Engineered tumor tropism via synthetic biology As a direct application strategy, bacterial tumor tropism can be classified into two categories: non-engineered (native) tropism and engineered tropism. … Genetic engineering can further enhance tumor tropism by endowing bacteria with synthetic adhesion properties. …

Adeno-associated virus as a delivery vector for gene therapy of human diseases.

Adeno-associated virus (AAV) has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different tissues. Recombinant AAV (rAAV) has been engineered for enhanced specificity and developed as a tool for treating various diseases. However, as rAAV is being more widely used as a therapy, the increased demand has created challenges for the existing manufacturing methods. Seven rAAV-based gene therapy products have received regulatory approval, but there continue to be concerns about safely using high-dos

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… A minor modification to the surface amino acids can alter the receptor binding affinity to affect transduction and tropism. … Codon optimization methods might introduce unexpected immunogenicity and toxicity as well as impair other traits such as tropism. …

Application of Perinatal Derivatives on Oncological Preclinical Models: A Review of Animal Studies.

The increasing cancer incidence has certified oncological management as one of the most critical challenges for the coming decades. New anticancer strategies are still needed, despite the significant advances brought to the forefront in the last decades. The most recent, promising therapeutic approaches have benefitted from the application of human perinatal derivatives (PnD), biological mediators with proven benefits in several fields beyond oncology. To elucidate preclinical results and clinic outcomes achieved in the oncological field, we present a narrative review of the studies resorting

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… A specific tropism and homing displayed by injected hDMSC was observed by Vegh and colleagues in the NMU-induced mammary tumors. … The tropism of hUC-MSC-ILZ-sTRAIL towards lung cancer cells was assessed in an orthotopic mouse model. These cells showed ability to migrate to the tumor location only 24 h after administration. …

[Repurposing of chlorpromazine in COVID-19 treatment: the reCoVery study].

OBJECTIVES: The ongoing COVID-19 pandemic comprises a total of more than 2,350,000 cases and 160,000 deaths. The interest in anti-coronaviru … ion in the lungs (20-200 times higher than in plasma), which is critical because of the respiratory tropism of SARS-CoV-2; (ii) CPZ is highly concentrated in saliva (30-100 times higher than in plasma) and could therefore reduce the contagiousness of COVID-19; (iii) CPZ can cross the blood-brain barrier and could therefore prevent the neurological forms o …

Oncogenes: The Passport for Viral Oncolysis Through PKR Inhibition.

The transforming properties of oncogenes are derived from gain-of-function mutations, shifting cell signaling from highly regulated homeostatic to an uncontrolled oncogenic state, with the contribution of the inactivating mutations in tumor suppressor genes P53 and RB, leading to tumor resistance to conventional and target-directed therapy. On the other hand, this scenario fulfills two requirements for oncolytic virus infection in tumor cells: inactivation of tumor suppressors and presence of oncoproteins, also the requirements to engage malignancy. Several of these oncogenes have a negative i

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… The tumor-specific natural or genetically engineered tropism is largely based upon a defect in the type I interferon (IFN) response of many tumor cells. 18 , 27 While in the normal tissues, IFN activation leads to inhibition of the viral replication. 28 Viral oncolysis dependent on PKR inactivation … and/or Genetic Transformed) The convergence of both oncogenes and some molecules encoded by viruses toward PKR is related to the basic condition for tumoral proliferation and viral infection: the maintenance or enhancement of protein synthesis rate. 42 Oncolytic viruses with natural tropism find PKR …

Oncolytic myxoma virus and engineering strategies for advanced cancer immunotherapy.

In cancer immunotherapy, oncolytic viruses (OVs) offer an alternative approach to kill malignant cells by inducing cancer-specific host immune system activation. Given the ongoing need for safe and effective viral vectors for immunotherapy, non-zoonotic animal viruses have attracted significant interest. Here, we review the oncolytic myxoma virus (MYXV) and emphasize its emerging role in cancer immunotherapy. We critically discuss recent advances in cancer therapy using MYXV, primarily focused on engineered viral modifications. Furthermore, we briefly review alternative delivery strategies for

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… MYXV tropism The cellular tropism of MYXV is very broad, since it can infect rabbit cells, certain primate cells, and human cancer cells. 20 Currently, no specific receptors for MYXV binding are known. … These receptors are crucial for determining the tropism of the virus. …

ICAR 2011. Italian Conference on AIDS and Retroviruses, Florence, Italy, 27-29 March 2011. Abstracts.

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… Tropism determination was performed by using Geno2Pheno algorithm. All V3 mutations, including the mutations used for tropism prediction (Sing T et al., Antiviral Therapy 2007), with prevalence >1% were considered. … Plasma, PBMC and CSF tropism determinations were concordant in 26/33 patients (21 R5 and 5 X4). The tropism was discordant in 5/33 patients, with the X4 virus in plasma and R5 in CSF; the HIV tropism in PBMCs was X4 in 3 patients. …

Adding recombinant AAVs to the cancer therapeutics mix.

Gene therapy is a powerful biological tool that is reshaping therapeutic landscapes for several diseases. Researchers are using both non-viral and viral-based gene therapy methods with success in the lab and the clinic. In the cancer biology field, gene therapies are expanding treatment options and the possibility of favorable outcomes for patients. While cellular immunotherapies and oncolytic virotherapies have paved the way in cancer treatments based on genetic engineering, recombinant adeno-associated virus (rAAV), a viral-based module, is also emerging as a potential cancer therapeutic thr

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… Given the tropism of several AAVs to liver, HCC is a viable, strong cancer target for AAV gene therapy. … of non-transformed tissues does not always match the tropism profile of AAV infection of tumor tissues. …