Respiratory syncytial virus co-opts hypoxia-inducible factor-1α-mediated glycolysis to favor the production of infectious virus.

Respiratory syncytial virus (RSV) is the leading etiological agent of lower respiratory tract illness. However, efficacious vaccines or antiviral drugs for treating RSV infections are currently not available. Indeed, RSV depends on host cells to provide energy needed to produce progeny virions.

Pan-cancer analyses reveal multi-omics and clinical characteristics of RIO kinase 2 in cancer.

RIO kinase 2 has emerged as a critical kinase for ribosome maturation, and recently it has also been found to play a fundamental role in cancer, being involved in the occurrence and progression of glioblastoma, liver cancer, prostate cancer, non-small cell lung cancer, and acute myeloid leukemia. However, our knowledge in this regard is fragmented and limited and it is difficult to determine the exact role of RIO kinase 2 in tumors. Here, we conducted an integrated pan-cancer analysis comprising 33 cancer-types to determine the function of RIO kinase 2 in malignancies.

PIK-24 Inhibits RSV-Induced Syncytium Formation via Direct Interaction with the p85α Subunit of PI3K.

Phosphoinositide-3 kinase (PI3K) signaling regulates many cellular processes, including cell survival, differentiation, proliferation, cytoskeleton reorganization, and apoptosis. The actin cytoskeleton regulated by PI3K signaling plays an important role in plasma membrane rearrangement. Currently, it is known that respiratory syncytial virus (RSV) infection requires PI3K signaling.

EZH1/2 as targets for cancer therapy.

The enhancer of zeste homolog 2 (EZH2) and its highly related homolog EZH1 are considered to be epigenetic silencing factors, and they play key roles in the growth and differentiation of cells as the core components of polycomb repressive complex 2 (PRC2). EZH1 and EZH2 are known to have a role in human malignancies, and alterations in these two genes have been implicated in transformation of human malignancies. Inhibition of EZH1/2 has been shown to result in tumor regression in humans and has been studied and evaluated in the preclinical setting and in multiple clinical trials at various levels.

Total Saponins of Panax notoginseng Activate Akt/mTOR Pathway and Exhibit Neuroprotection in vitro and in vivo against Ischemic Damage.

Objective: To reveal the neuroprotective effect and the underlying mechanisms of a mixture of the main components of Panax notoginseng saponins (TSPN) on cerebral ischemia-reperfusion injury and oxygen-glucose deprivation/reoxygenation (OGD/R) of cultured cortical neurons.

Methods: The neuroprotective effect of TSPN was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, flow cytometry and live/dead cell assays. The morphology of dendrites was detected by immunofluorescence.

Inhibitory Effect of PIK-24 on Respiratory Syncytial Virus Entry by Blocking Phosphatidylinositol-3 Kinase Signaling.

Phosphoinositide-3 kinase signaling modulates many cellular processes, including cell survival, proliferation, differentiation, and apoptosis. Currently, it is known that the establishment of respiratory syncytial virus infection requires phosphoinositide-3 kinase signaling. However, the regulatory pattern of phosphoinositide-3 kinase signaling or its corresponding molecular mechanism during respiratory syncytial virus entry remains unclear.

AT-533, a novel Hsp90 inhibitor, inhibits breast cancer growth and HIF-1α/VEGF/VEGFR-2-mediated angiogenesis in vitro and in vivo.

The inhibition of angiogenesis is suggested to be an attractive strategy for cancer therapeutics. Heat shock protein 90 (Hsp90) is closely related to tumorigenesis as it regulates the stabilization and activated states of many client proteins that are essential for cell survival and tumor growth. Here, we investigated the mechanism whereby AT-533, a novel Hsp90 inhibitor, inhibits breast cancer growth and tumor angiogenesis.

Macrocyclic Diterpenoids from and Their Potential Anti-inflammatory Activity.

Guided by H NMR spectroscopic experiments using the aromatic protons as probes, 11 macrocyclic diterpenes (-) were isolated from the aerial parts of . Their full three-dimensional structures, including absolute configurations, were established unambiguously by spectroscopic analysis and single-crystal X-ray crystallographic experiments. Among the isolated compounds, compound is the third member thus far of a rare class of diterpenes featuring an unusual 5/10 fused ring system, and - are new jatrophane diterpenes.

Eleven New Triterpenoid Glycosides from the Roots of Ilex asprella.

Asprellosides A-K, nine new ursane-type triterpenoid glycosides (1-9), and two new oleanane-type triterpenoid glycosides (10 and 11), including six rare sulfated triterpenoid glycosides, were isolated from the roots of Ilex asprella. Their structures were determined on the basis of comprehensive spectroscopic analysis and chemical methods. Among these compounds, asprelloside B (2) and asprelloside C (3) are the first examples of triterpenoid glycosides bearing a rare 3,4-O-disulfo-xylopyranosyl residue.

Stilbene Glycoside Oligomers from the Roots of Polygonum multiflorum.

Five new trans-2,3,5,4'-tetrahydroxystilbene 2-O-β-d-glucopyranoside (TSG)-based stilbene glycoside oligomers (1-5) were isolated from the roots of Polygonum multiflorum. Their structures were elucidated by comprehensive spectroscopic analyses and chemical evidences. The absolute configurations of 1, 2, 4, and 5 were established by quantum-chemical electronic circular dichroism (ECD) calculations.

Antiviral activity of ethanol extract of Lophatherum gracile against respiratory syncytial virus infection.

Ethnopharmacological Relevance: Lophatherum gracile, an important medicinal plant, is used traditionally in the treatment of cough associated with lung heat and inflammation. In this study, an ethanol extract of L. gracile (DZY) was shown to inhibit respiratory syncytial virus (RSV) infection and RSV-induced inflammation in vitro and in vivo.

Matrine-Type Alkaloids from the Roots of Sophora flavescens and Their Antiviral Activities against the Hepatitis B Virus.

Eight new matrine-type alkaloids, flavesines G-J (1-4), alopecurine B (5), 7,11-dehydro-oxymatrine (6), 10-oxy-5,6-dehydromatrine (7), and 10-oxysophoridine (8), along with nine known analogues (9-17) were isolated from the roots of Sophora flavescens. Compounds 1-3 are the first natural matrine-type alkaloids with an open-loop ring D, while compound 4 represents an unprecedented dimerization pattern constructed from matrine and piperidine, and 5 is the first example of a matrine-type alkaloid with cleavage of the C-5-C-6 bond. The new structures were elucidated by means of spectroscopic data analysis (including NMR, MS, IR, and UV), and the absolute configurations were determined using single-crystal X-ray diffraction and ECD data.

Phloroglucinol Derivatives with Unusual Skeletons from Cleistocalyx operculatus and Their in Vitro Antiviral Activity.

Four novel phloroglucinol derivatives (1-4) featuring a 2,4-dimethyl-cinnamyl-phloroglucinol moiety, along with their putative biosynthetic precursors 5 and 6, were isolated from the leaves of Cleistocalyx operculatus. Compounds 1 and 2 are two pairs of new enantiomeric phloroglucinol dimers possessing an unprecedented polycyclic skeleton with a highly functionalized dihydropyrano[3,2- d]xanthene tetracyclic core. Compounds 3 and 4 are two new phloroglucinol-terpene adducts (PTAs) with a novel carbon skeleton.

Antiviral Triketone-Phloroglucinol-Monoterpene Adducts from Callistemon rigidus.

Callistrilones F - K (1 - 6), six new triketone-phloroglucinol-monoterpene hybrids were isolated from the twigs and leaves of Callistemon rigidus. Their structures with absolute configurations were established by a combination analysis of NMR spectra, X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compounds 3 and 4 exhibited moderate inhibitory activities against herpes simplex virus (HSV-1) with IC values of 10.

New Acetophenone Derivatives from Acronychia oligophlebia and Their Anti-inflammatory and Antioxidant Activities.

Seven new acetophenone derivatives (acroliones A - G, 1 - 7) and three known ones (8 - 10) were isolated from the leaves of Acronychia oligophlebia. Their structures were elucidated based on extensive spectroscopic analyses (IR, UV, HR-ESI-MS, 1D- and 2D-NMR), X-ray diffraction and comparison with literature data. The anti-inflammatory and antioxidant activities of all isolates were evaluated.

Multiflorumisides A-G, Dimeric Stilbene Glucosides with Rare Coupling Patterns from the Roots of Polygonum multiflorum.

Multiflorumisides A-G (1-7), seven new dimeric stilbene glucosides with two rare coupling patterns, were isolated from the roots of Polygonum multiflorum. The structures of these new dimeric stilbene glucosides were elucidated through comprehensive spectroscopic and chemical analyses. The absolute configurations of 3 and 5-7 were established by comparing their experimental and quantum-chemical ECD data.

Cajanusflavanols A-C, Three Pairs of Flavonostilbene Enantiomers from Cajanus cajan.

Three pairs of new flavonostilbene enantiomers, cajanusflavanols A-C (1-3), along with their putative biogenetic precursors 4-6, were isolated from Cajanus cajan. Compound 1 possesses an unprecedented carbon skeleton featuring a unique highly functionalized cyclopenta[1,2,3-de]isobenzopyran-1-one tricyclic core. Compounds 2 and 3 are the first examples of methylene-unit-linked flavonostilbenes.

Rearranged Phloroglucinol-Monoterpenoid Adducts from Callistemon rigidus.

Callisretones A (1) and B (2), two rearranged phloroglucinol-monoterpenoid adducts featuring an unprecedented isopropylcyclopenta[b]benzofuran backbone, together with their postulated biosynthetic precursors (3-9), were isolated from Callistemon rigidus. The previously assigned absolute configurations of viminalins H (7), L (8), and N (9) were revised and unequivocally established by X-ray diffraction data. A putative biosynthetic pathway toward callisretones A and B involving the rearrangement of the terpenoid motif is proposed.

Anhuienoside C Ameliorates Collagen-Induced Arthritis through Inhibition of MAPK and NF-κB Signaling Pathways.

Fr. Schmidt (Ranunculaceae) ( in Chinese) is used to treat punch injuries and rheumatoid arthritis (RA). Our previous report has shown that crude triterpenoid saponins from exhibited anti-arthritic effects on type II collagen-induced arthritis in rats.

Watsonianone A from Rhodomyrtus tomentosa Fruit Attenuates Respiratory-Syncytial-Virus-Induced Inflammation In Vitro.

Respiratory syncytial virus (RSV) is one of the most common respiratory pathogens. Immoderate inflammation plays a great role in causing RSV-induced diseases. In the present study, watsonianone A, isolated from the fruit of Rhodomyrtus tomentosa (Ait.

Sesquiterpene lactones from Elephantopus mollis and their anti-inflammatory activities.

Seven sesquiterpene lactones, 8-O-methacryloylelephanpane, 2,4-bis-O-methyl-8-O-methacryloylelephanpane, 4-O-ethyl-8-O-methacryloylelephanpane, 8-O-methacryloylisoelephanpane, 2-O-demethyltomenphantopin C, molephantin A, molephantin B, along with ten known ones, were isolated from Elephantopus mollis (Asteraceae). Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HRESIMS, 1D and 2D NMR). The isolates were evaluated for their anti-inflammatory activities on LPS-stimulated RAW 264.

Paris saponin-induced autophagy promotes breast cancer cell apoptosis via the Akt/mTOR signaling pathway.

Paris saponins possess anticancer, anti-inflammatory, and antiviral effects. However, the anticancer effect of Paris saponins has not been well elucidated and the mechanisms underlying the potential function of Paris saponins in cancer therapy are needed to be further identify. In this study, we report that saponin compounds isolated from Paris polyphylla exhibited antitumor activity against breast cancer cell lines, MCF-7 and MDA-MB-231.

[Study on Anti-RSV Activities and QSAR of Natural Caffeoylquinic Acid Derivates].

Objective: To study the inhibitory effects of natural caffeoylquinic acid derivates against respiratory syncytial virus（ RSV） in vitro and their quantitative structure-activity relationship.

Methods: The anti-RSV activities of caffeoylquinic acid derivates were detected by cytopathic effect（ CPE） method,MTT assay was adopted to evaluate the cytotoxicities of caffeoylquinic acid derivates and a three-dimensional quantitative structure-activity relationship（ 3D-QSAR） model was built.

Results: The caffeoylquinic acid derivates showed different levels of anti-RSV activity.

EM23, a natural sesquiterpene lactone, targets thioredoxin reductase to activate JNK and cell death pathways in human cervical cancer cells.

Sesquiterpene lactones (SLs) are the active constituents of a variety of medicinal plants and found to have potential anticancer activities. However, the intracellular molecular targets of SLs and the underlying molecular mechanisms have not been well elucidated. In this study, we observed that EM23, a natural SL, exhibited anti-cancer activity in human cervical cancer cell lines by inducing apoptosis as indicated by caspase 3 activation, XIAP downregulation and mitochondrial dysfunction.

Antiviral benzofurans from Eupatorium chinense.

Eleven benzofuran dimers, (+)-dieupachinins A-E, (-)-dieupachinins A-E and dieupachinin F, a benzofuran trimer trieupachinin A, as well as seven known compounds were isolated from the roots of Eupatorium chinense. The enantiomers of racemates dieupachinins A-E were separated by chiral HPLC. The structures with absolute configurations were elucidated on the basis of spectroscopic data, X-ray diffraction analysis, and circular dichroism experiments.