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There is clinical evidence showing that the Pelargonium sidoides root extract EPs 7630 is a safe and effective treatment for a range of acute infectious respiratory illnesses. Moreover, EPs 7630 has been shown to reduce the use of antibiotics, which is important in the context of rising antibiotic resistance levels. A wide range of mechanisms appears to contribute to the beneficial effects of EPs 7630, e.g. antibacterial, antiviral, immunomodulatory, and epithelial barrier effects. This broad spectrum of pharmacological activities seems to enable the clinical activity of EPs 7630 against multiple respiratory infections. In particular, the combination of antiviral and immunomodulatory effects may enable EPs 7630 to tackle acute viral respiratory infections both in early stages of the disease process, which are driven by virus replication, as well as in later stages, which are caused by an overshooting immune response. Hence, EPs 7630 is a prime example of a plant extract with evidence-based clinical efficacy, including a solid understanding of the underlying mechanisms of action. The example of EPs 7630 demonstrates that plant extracts have a potential role as evidence-based clinical treatments and that they deserve pre-clinical and clinical testing and investigation in the same way as any other drug class., Competing Interests: Authors JC, MW, and MM received a consultancy fee for the preparation of this review article from Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany. Moreover, the article processing fee was paid by Dr. Willmar Schwabe GmbH & Co. KG. The funder had the following involvement in the study: Support with the identification of relevant literature, critical proofreading; support with the design of figures. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Cinatl, Wass and Michaelis.)

Knowledge of the molecular pathogenesis of acute myeloid leukemia has advanced in recent years. Despite novel treatment options, acute myeloid leukemia remains a survival challenge for elderly patients. We have recently shown that the triphosphohydrolase SAMHD1 is one of the factors determining resistance to Ara-C treatment. Here, we designed and tested novel and simpler virus-like particles incorporating the lentiviral protein Vpx to efficiently and transiently degrade SAMHD1 and increase the efficacy of Ara-C treatment. The addition of minute amounts of lentiviral Rev protein during production enhanced the generation of virus-like particles. In addition, we found that our 2nd generation of virus-like particles efficiently targeted and degraded SAMHD1 in AML cell lines with high levels of SAMHD1, thereby increasing Ara-CTP levels and response to Ara-C treatment. Primary AML blasts were generally less responsive to VLP treatment. In summary, we have been able to generate novel and simpler virus-like particles that can efficiently deliver Vpx to target cells., (© 2024. The Author(s).)

Only 20% of patients with muscle-invasive bladder carcinoma respond to cisplatin-based chemotherapy. Since the natural phytochemical sulforaphane (SFN) exhibits antitumor properties, its influence on the adhesive and migratory properties of cisplatin- and gemcitabine-sensitive and cisplatin- and gemcitabine-resistant RT4, RT112, T24, and TCCSUP bladder cancer cells was evaluated. Mechanisms behind the SFN influence were explored by assessing levels of the integrin adhesion receptors β1 (total and activated) and β4 and their functional relevance. To evaluate cell differentiation processes, E- and N-cadherin, vimentin and cytokeratin (CK) 8/18 expression were examined. SFN down-regulated bladder cancer cell adhesion with cell line and resistance-specific differences. Different responses to SFN were reflected in integrin expression that depended on the cell line and presence of resistance. Chemotactic movement of RT112, T24, and TCCSUP (RT4 did not migrate) was markedly blocked by SFN in both chemo-sensitive and chemo-resistant cells. Integrin-blocking studies indicated β1 and β4 as chemotaxis regulators. N-cadherin was diminished by SFN, particularly in sensitive and resistant T24 and RT112 cells, whereas E-cadherin was increased in RT112 cells (not detectable in RT4 and TCCSup cells). Alterations in vimentin and CK8/18 were also apparent, though not the same in all cell lines. SFN exposure resulted in translocation of E-cadherin (RT112), N-cadherin (RT112, T24), and vimentin (T24). SFN down-regulated adhesion and migration in chemo-sensitive and chemo-resistant bladder cancer cells by acting on integrin β1 and β4 expression and inducing the mesenchymal-epithelial translocation of cadherins and vimentin. SFN does, therefore, possess potential to improve bladder cancer therapy.

The oral consumption of alcohol (ethanol) has a long tradition in humans and is an integral part of many cultures. The causal relationship between ethanol consumption and numerous diseases is well known. In addition to the well-described harmful effects on the liver and pancreas, there is also evidence that ethanol abuse triggers pathological skin conditions, including acne. In the present study, we addressed this issue by investigating the effect of ethanol on the energy metabolism in human SZ95 sebocytes, with particular focus on qualitative and quantitative lipogenesis. It was found that ethanol is a strong trigger for lipogenesis, with moderate effects on cell proliferation and toxicity. We identified the non-oxidative metabolism of ethanol, which produced fatty acid ethyl esters (FAEEs), as relevant for the lipogenic effect-the oxidative metabolism of ethanol does not contribute to lipogenesis. Correspondingly, using the Seahorse extracellular flux analyzer, we found an inhibition of the mitochondrial oxygen consumption rate as a measure of mitochondrial ATP production by ethanol. The ATP production rate from glycolysis was not affected. These data corroborate that ethanol-induced lipogenesis is independent from oxygen. In sum, our results give a causal explanation for the prevalence of acne in heavy drinkers, confirming that alcoholism should be considered as a systemic disease. Moreover, the identification of key factors driving ethanol-dependent lipogenesis may also be relevant in the treatment of acne vulgaris.

Ethnopharmacological Relevance: Plants and fungi have a long tradition in ethnopharmacology for the treatment of infectious diseases including viruses. Many of these natural products have also been used to combat SARS-CoV-2 infections or symptoms of the post- and long-COVID form, owing to the scarcity of clinically approved therapeutics., Aim of the Study: The ongoing threat posed by SARS-CoV-2, along with the rapidly evolving new variants, requires the development of new antiviral compounds. The aim of this study was to identify anti-SARS-CoV-2 herbal and fungal extracts used in traditional medicine against acute respiratory infection, inflammation, and related symptoms. Additionally, we sought to characterize their bioactive constituents., Materials and Methods: The antiviral activity and cell cytotoxicity of 179 herbal and fungal extracts were evaluated using two SARS-CoV-2 infection assays in Caco-2 cells. 19 plant extracts with and without anti-SARS-CoV-2 activity underwent detailed dereplication using molecular networking., Results: Extracts from Angelica sinensis (Oliv.) Diels roots, Annona squamosa L. seeds, Azadirachta indica A. Juss. fruits, Buddleja officinalis Maxim. flowers, Burkea africana Hook. bark and Clinopodium menthifolium (Host) Stace aerial parts showed a potent anti SARS-CoV-2 activity (IC 50  < 5 μg/ml) with only moderate cytotoxicity (CC 50  > 60 μg/ml, Caco-2). By performing the dereplication with a bioactivity-featured molecular network (MN) on the extract library level, rather than on the level of individual extracts, we could pinpoint compounds characteristic for active extracts. Thus, a straight-forward identification of potential anti-SARS-CoV-2 natural compounds was achieved prior to any fractionation or isolation efforts., Conclusions: A sophisticated hyphenation of empirical knowledge with MS-based bioinformatics and automated compound annotation was applied to decipher the chemical space of the investigated extracts. The correlation with experimentally assessed anti-SARS-CoV-2 activities helped in predicting compound classes and structural elements relevant for the antiviral activities. Consequently, this accelerated the identification of constituents from the investigated mixtures with inhibitory effects against SARS-CoV-2., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The Mpox virus can cause severe disease in the susceptible population with dermatologic and systemic manifestations. Furthermore, ophthalmic manifestations of mpox infection are well documented. Topical trifluridine (TFT) eye drops have been used for therapy of ophthalmic mpox infection in patients, however, its efficacy against mpox virus infection in this scenario has not been previously shown. In the present study, we have established ophthalmic cell models suitable for the infection with mpox virus. We show, that TFT is effective against a broad range of mpox isolates in conjunctival epithelial cells and keratocytes. Further, TFT remained effective against a tecovirimat-resistant virus strain. In the context of drug combinations, a nearly additive effect was observed for TFT combinations with brincidofovir and tecovirimat in conjunctival epithelial cells, while a slight antagonism was observed for both combinations in keratocytes. Altogether, our findings demonstrate TFT as a promising drug for treatment of ophthalmic mpox infection able to overcome tecovirimat resistance. However, conflicting results regarding the effect of drug combinations with approved compounds warrant close monitoring of such use in patients., (© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)