Abstract The emergence and re-emergence of viruses has highlighted the need to develop new broad-spectrum antivirals to mitigate human infections. Pursuing our search for new bioactive plant-derived molecules, we study several diterpene derivatives synthesized from jatropholones A and B and carnosic acid isolated from Jatropha isabellei and Rosmarinus officinalis , respectively. Here, we investigate the antiviral effect of the diterpenes against human adenovirus (HAdV-5) that causes several infections for which there is no approved antiviral therapy yet. Ten compounds are evaluated and none of them present cytotoxicity in A549 cells. Only compounds 2, 5 and 9 inhibit HAdV-5 replication in a concentration-dependent manner, without virucidal activity, whereas the antiviral action takes place after virus internalization. The expression of viral proteins E1A and Hexon is strongly inhibited by compounds 2 and 5 and, in a lesser degree, by compound 9. Since compounds 2, 5 and 9 prevent ERK activation, they might exert their antiviral action by interfering in the host cell functions required for virus replication. Besides, the compounds have an anti-inflammatory profile since they significantly inhibit the levels of IL-6 and IL-8 produced by THP-1 cells infected with HAdV-5 or with an adenoviral vector. In conclusion, diterpenes 2, 5 and 9 not only exert antiviral activity against adenovirus but also are able to restrain pro-inflammatory cytokines induced by the virus.

Antiviral Effect of Natural and Semisynthetic Diterpenoids against Adenovirus Infection in vitro

Siglec 15 as a biomarker or a druggable molecule for non-small cell lung cancer.

In this study, we evaluated the use of hydrolates, co-products of essential oil distillation, as processing aids to improve the depuration process of Pacific oysters (Crassostrea gigas) as a post-harvest method aimed at reducing the norovirus (NoV) viral load. Live oysters were kept in water to which hydrolates of Thymus serpyllum and Citrus limon at 1% were added for 24 h. The concentration of NoV was quantified using the ISO 15216-1 quantitative real-time RT-PCR method in the oyster digestive tissue both before and after the treatment. The results showed a significant reduction of 0.2 log in the NoV GII concentration after 24 h of treatment with 1% C. limon hydrolate. Conversely, treatment with T. serpyllum did not appear to reduce the concentration of NoV compared to the control. Additionally, a sensory analysis was conducted through a blind survey comparing untreated and treated oysters. No changes in the sensory and physical characteristics of the oysters were observed, except for a decrease in the marine flavour intensity, which was positively perceived by consumers. These results indicate that the addition of hydrolates of C. limon at 1% during depuration might represent a promising processing aid for enhancing both the safety and acceptability of live oysters.

In Vivo Evaluation of the Potential of Thyme and Lemon Hydrolates as Processing Aids to Reduce Norovirus Concentration during Oyster Depuration

Chemical composition, antioxidant activity and extraction optimization of Distichochlamys orlowii rhizomes

High-risk human papillomavirus (HPV) infection is the main risk factor for cervical cancer (CC) development, where the continuous expression of E6 and E7 oncoproteins maintain the malignant phenotype. In Mexico, around 70% of CC cases are diagnosed in advanced stages, impacting the survival of patients. The aim of this work was to identify biomarkers affected by HPV-16 E6 and E7 oncoproteins that impact the prognosis of CC patients. Expression profiles dependent on E6 and E7 oncoproteins, as well as their relationship with biological processes and cellular signaling pathways, were analyzed in CC cells. A comparison among expression profiles of E6- and E7-expressing cells and that from a CC cohort obtained from The Cancer Genome Atlas (TCGA) demonstrated that the expression of 13 genes impacts the overall survival (OS). A multivariate analysis revealed that the downregulated expression of RIPOR2 was strongly associated with a worse OS. RIPOR2, including its transcriptional variants, were overwhelmingly depleted in E6- and E7-expressing cells. Finally, in a Mexican cohort, it was found that in premalignant cervical lesions, RIPOR2 expression decreases as the lesions progress; meanwhile, decreased RIPOR2 expression was also associated with a worse OS in CC patients.

/pdf/ripor2-expression-decreased-by-hpv-16-e6-and-e7-oncoproteins-3v78kiav.pdf

RIPOR2 Expression Decreased by HPV-16 E6 and E7 Oncoproteins: An Opportunity in the Search for Prognostic Biomarkers in Cervical Cancer

Background NSCLC (non-small cell lung cancer) has become the malignancy with the highest incidence and mortality rate worldwide. Fructose-6-phosphate 2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) is a key regulator of glycolysis with both kinase and phosphatase activities. The Warburg effect, or increased glycolysis in tumors, provides the metabolic basis for cancer cell proliferation and metastasis, and the Warburg pathway enzyme PFKFB4 is a newly identified important kinase. This study aimed to elucidate the poor prognostic relevance of PFKFB4 in non-small cell lung cancer tissues and its relationship with immune cell infiltration, immune cell biomarkers, and immune checkpoints. Methods In this study, immunohistochemical methods were used to assess PFKFB4 expression levels in 140 surgical specimens from patients with histologically confirmed non-small cell lung cancer and to investigate the relationship between PFKFB4 expression levels and the patients’ clinicopathological characteristics. The impact of PFKFB4 expression on prognosis was evaluated using Kaplan–Meier survival analysis and Cox regression analysis. Results When compared to normal paracrine tissues, PFKFB4 expression was enhanced in lung cancer tissues, and Kaplan–Meier survival analysis revealed that patients with high PFKFB4 expression had a worse prognosis. In NSCLC, PFKFB4 was found to be associated with immune cell infiltration and immunological checkpoints. Conclusion PFKFB4 expression may be upregulated as a sign of poor prognosis in NSCLC, and PFKFB4 may be implicated not only in the genesis and progression of NSCLC but also in its immunological control.

https://www.dovepress.com/getfile.php?fileID=82582

Effect of PFKFB4 on the Prognosis and Immune Regulation of NSCLC and Its Mechanism

The Effects of β-Pinene, a Pine Needle Oil Monoterpene, on Adenovirus Type 3

Functional dysregulations in multiple regions are caused by excessive copper deposition in the brain for Wilson disease (WD). While the biological mechanism of these dysregulations was thought to be the absent or reduced expression of the ATP7B protein in the liver, mechanisms for such gene impacting brain function remain unexplored. Here, we used a large cohort of resting-state fMRI data (105 WD patients and 93 healthy controls) to derive the functional connectome gradient, and its WD-related alterations were further evaluated. Then, we used Neurosynth, clinical data, and whole-brain gene expression to examine the meta-analytic cognitive function, clinical phenotypes, and transcriptional specializations related to WD gradient alterations. In parallel, spatial correlation between gradient and gray matter volume was accessed for both WD patients and healthy controls. Compared to controls, WD patients exhibited principal gradient alterations in both global and system levels and regional alterations mainly distributed in the sensorimotor, visual, ventral attention, subcortical, and default mode networks. Meta-analytic terms and clinical characters showed the correlations of these gradient alterations in motor-related processing, higher-order cognition, neurological symptom, and age. Results of spatial correlation revealed structure-function decoupling in multiple networks, especially in subcortical and visual networks. Within the cortex, the gradient alterations derived transcriptional specializations of WD that mainly display properties indicative of ion homeostasis, neural development, and motor controls. Within the subcortical regions, we for the first time characterized the role of the ATP7B gene impacting subcortical function. Transcriptional specializations of WD within both cortex and subcortical regions were also associated with neurological and psychiatric disorders, explaining the mechanism underlying complex clinical symptoms from the biological level for WD. In addition, we further illustrated that structural lesion and gradient perturbation shared similar transcriptional specializations in both cortex and subcortical regions for WD. These findings bridged functional gradient perturbation to structural lesions and transcriptional profiles in WD, possibly promoting our understanding of the neurobiological underpinnings underlying the emergence of complex neurological and psychiatric phenotypes.

/pdf/functional-gradient-perturbation-in-wilson-disease-2qm1wg2m.pdf

Functional gradient perturbation in Wilson disease correlates with structural lesions and transcriptomic specializations

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Effect of PFKFB4 on the Prognosis and Immune Regulation of NSCLC and Its Mechanism

The Effects of β-Pinene, a Pine Needle Oil Monoterpene, on Adenovirus Type 3

Functional gradient perturbation in Wilson disease correlates with structural lesions and transcriptomic specializations