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Background: A cytokine storm (CS) is a rapidly occurring, complex, and highly lethal systemic acute inflammatory response induced by pathogens and other factors. Currently, no clinical therapeutic drugs are available with a significant effect and minimal side effects. Given the pathogenesis of CS, natural products have become important resources for bioactive agents in the discovery of anti-CS drugs. Purpose: This study aimed to provide guidance for preventing and treating CS-related diseases by reviewing the natural products identified to inhibit CS in recent years. Methods: A comprehensive literature review was conducted on CS and natural products, utilizing databases such as PubMed and Web of Science. The quality of the studies was evaluated and summarized for further analysis. Results: This study summarized more than 30 types of natural products, including 9 classes of flavonoids, phenols, and terpenoids, among others. In vivo and in vitro experiments demonstrated that these natural products could effectively inhibit CS via nuclear factor kappa-B, mitogen-activated protein kinase, and Mammalian target of rapamycin (mTOR) signaling pathways. Moreover, the enzyme inhibition assays revealed that more than 20 chemical components had the potential to inhibit ACE2, 3CL-protease, and papain-like protease activity. The experimental results were obtained using advanced technologies such as biochips and omics. Conclusions: Various natural compounds in traditional Chinese medicine (TCM) extracts could directly or indirectly inhibit CS occurrence, potentially serving as effective drugs for treating CS-related diseases. This study may guide further exploration of the therapeutic effects and biochemical mechanisms of natural products on CS.

Acute lung injury (ALI) is a serious pulmonary complication that often arises from pneumonia, respiratory tract infections caused by bacteria or viruses, and other factors. It is characterized by acute onset and high mortality. Angong Niuhuang Wan (AGNHW) is a renowned emergency medicine in traditional Chinese medicine, known as the ''cool open (febrile disease) three treasures'' and regarded as the first of the ''three treasures''. Previously studies have confirmed that AGNHW has anti-inflammatory effects, improves cerebral circulation, reduces brain edema, and protects vascular endothelium. However, the active components and pharmacological mechanisms of AGNHW in treating ALI remain unclear. In this study, we confirmed that AGNHW can inhibit cytokine storm activity and reduce inflammation induced by LPS in ALI mice. We then analyzed differential proteins using proteomic technology and identified 741 differential proteins. By combining network pharmacological analysis, we deeply discussed the key active components and mechanism of AGNHW in treating ALI. By constructing the interaction network between disease and drug, we identified 21 key active components (such as Quercetin, Kaempferol, and Crocetin) and 25 potential core targets (such as PIK3CG, p65, and MMP9). These candidate targets play an important role in anti-inflammation and immune regulation. Through enrichment analysis of core targets, we found several pathways related to ALI, such as the NF-κB signaling pathway, TNF signaling pathway, and Toll-like receptor signaling pathway. This indicates that AGNHW plays a therapeutic role in ALI through multi-components, multi-targets, and multi-pathways.

Traditional Chinese medicine offer unique advantages in mitigating and preventing early or intermediate stage for treating heart failure (HF). The purpose of this study was to assess the in vivo therapeutic efficacy of Xin-shu-bao (XSB) at different stages of HF following induction of a myocardial infarction (MI) in mice and use mass spectrometry-based proteomics to identify potential therapeutic targets for different stages of HF based on the molecular changes following XSB treatment. XSB had high cardioprotective efficacy in the pre-HF with reduced ejection fraction (HFrEF) stages, but had a weak or no effect in the post-HFrEF stages. This was supported by echocardiographic measurements showing that XSB decreased ejection fraction and fractional shortening in HF. XSB administration improved cardiac function in the pre- and post-HFrEF mouse model, ameliorated deleterious changes to the morphology and subcellular structure of cardiomyocytes, and reduced cardiac fibrosis. Proteomics analysis showed that XSB intervention exclusively targeted thrombomodulin (THBD) and stromal interaction molecule 1 (STIM1) proteins when administered to the mice for both 8 and 6 weeks. Furthermore, XSB intervention for 8, 6, and 4 weeks after MI induction increased the expression of fibroblast growth factor 1 (FGF1) and decreased arrestin β1 (ARRB1), which are classic biomarkers of cardiac fibroblast transformation and collagen synthesis, respectively. Overall, the study suggests that early intervention with XSB could be an effective strategy for preventing HFrEF and highlights potential therapeutic targets for further investigation into HFrEF remediation strategies.

Abstract Background Compound K (CK) is the minor ginsenoside present in fermented Panax ginseng extract. Despite the pharmacological efficacy of CK, its industrial use has been restricted due to its low water solubility and poor permeability. To overcome this defect, our study was to synthesize gold nanoparticles from CK (CK-AuNPs) to investigate their potential as anticancer candidates. Methods To biologically synthesize CK-AuNPs, a novel strain, Curtobacterium proimmune K3, was isolated from fermented ginseng beverage, then combined with CK and gold salts to biosynthesize gold nanoparticles (CurtoCK-AuNPs). Their physicochemical characteristics were evaluated using UV–Vis spectrometry, FE-TEM, EDX, elemental mapping, XRD, SAED, DLS and TGA. Results CurtoCK-AuNPs exerted significant selective cytotoxic effects on AGS human gastric cancer cells. Fluorescence staining with Hoechst, propidium iodide, and MitoTracker demonstrated that CurtoCK-AuNPs induce apoptosis and mitochondrial damage, respectively. Quantitative real-time PCR and western blotting analyses showed that cytotoxic effect of CurtoCK-AuNPs were involved in apoptosis, based on their activation of Bax/Bcl-2, cytochrome c, caspase 9, and caspase 3, as well as their suppression of PI3K–Akt signaling. Conclusion Our findings provide data for understanding the molecular mechanisms of nanoparticles; thus, providing insight into the development of alternative medications based on gold nanoparticles of ginseng-derived CK.

AimsThis study aimed to construct a lymph node metastasis-related gene signature to predict prognosis and immune infiltration in patients with cervical cancer.MethodsClinical and RNA sequencing data of 193 patients with cervical cancer, which were divided into lymph node metastasis (N1) and non-lymph node metastasis (N0) groups, were acquired from TCGA. Differentially expressed genes (DEGs) between the N1 and N0 groups were detected, and protein-protein interaction combined with LASSO analysis was conducted to further screen lymph node metastasis-related genes. Univariate and multivariate Cox regression analyses were performed to establish a predictive signature. The genetic features, potential biological behavior, and immune infiltration characteristics of the predictive signature were explored. Furthermore, the sensitivity of patients to chemotherapy drugs was estimated based on the predictive signature and the expression of TEKT2 and RPGR was investigated in the cervical cancer tissue samples.ResultsA total of 271 lymph node metastasis-related DEGs, including 100 upregulated and 171 downregulated genes, were identified. Two genes, TEKT2 and RPGR, were associated with lymph node metastasis and prognosis in cervical cancer, and were used to construct a lymph node metastasis-related predictive signature. Based on the predictive signature, patients with cervical cancer were divided into high- and low-risk groups. The high-risk group, characterized by a higher tumor mutation burden and somatic mutation rate, indicated a poor overall survival. The activation of immune infiltration and increased expression of checkpoint genes were observed in the high-risk group, indicating that they might benefit from immunotherapy. Cytarabine, FH535, and procaspase-activating compound-1 were estimated as reasonable chemotherapy options for patients in the high-risk group, whereas two taxanes and five tyrosine kinase inhibitors, including etoposide and vinorelbine, had therapeutic significance for patients in the low-risk group. The expression of TEKT2 and RPGR was significantly downregulated in cervical cancer tissues, especially in metastatic lymph node tissues.DiscussionThe lymph node metastasis-related predictive signature based on TEKT2 and RPGR showed good performance in predicting the survival outcomes of patients with cervical cancer. The risk score of the predictive signature was related to genetic variation and immune infiltration, which could guide immunotherapy and chemotherapy strategies.

(1) Background: Nanotechnology is being widely applied for anticancer strategies with few side effects. Nanoparticles (NPs) prepared from natural extracts are promising candidates for cancer treatment because of their unique physicochemical characteristics. This study aimed to prepare gold nanoparticles (AuNPs) from Phyllanthus emblica fruit extract (PEFE) using Bifidobacterium animalis subsp. lactis (B. lactis) and to evaluate their anticancer activity against the human gastric adenocarcinoma cell-line (AGS). (2) Methods: The safety of microbial biosynthesis AuNPs (PEFE-AuNPs) was assessed by evaluating the cytotoxicity. The anticancer activity of PEFE-AuNPs was investigated in AGS cells in terms of apoptosis and autophagy. (3) Results: PEFE-AuNPs exhibited significant cytotoxicity against AGS cells but not against normal cells. The apoptosis induced by PEFE-AuNPs in AGS cells was associated with PTEN-induced kinase 1 (PINK1)-Parkin mediated reduction of mitochondrial membrane potential and activation of intracellular signaling apoptosis pathways. The anticancer activity of PEFE-AuNPs was associated with induction of apoptosis through inhibition of autophagy, downregulation of LC3-II/LC3-I and Beclin-1 expression, and upregulation of p62 expression in AGS cells. (4) Conclusions: This study is the first to demonstrate the anticancer activity of PEFE-AuNPs against AGS cells. Our results provide a good starting point for the development of new anticancer products based on gold nanoparticles of P. emblica fruit extract.

Crabapple is a valuable tree species in gardens due to its captivating array of flower and leaf colors, rendering it a favored choice in landscaping. The economic and ornamental values of Malus crabapple are closely associated with the biosynthesis of anthocyanin, a pigment responsible for its vibrant hues. The intricate regulation of anthocyanin biosynthesis involves the concerted activity of various genes. However, the specific mechanism governing this process in crabapple warrants in-depth exploration. In this study, we explored the inhibitory role of MsMYB62-like in anthocyanin biosynthesis. We identified MsDFR and MsANS as two downstream target genes of MsMYB62-like. These genes encode enzymes integral to the anthocyanin biosynthetic pathway. The findings demonstrate that MsMYB62-like directly binds to the promoters of MsDFR and MsANS, resulting in the downregulation of their expression levels. Additionally, our observations indicate that the plant hormone cytokinins exert a suppressive effect on the expression levels of MsMYB62-like, while concurrently upregulating MsDFR and MsANS. This study reveals that the MsMYB62-like-MsDFR/MsANS module plays an important role in governing anthocyanin levels in Malus crabapple. Notably, the regulatory interplay is modulated by the plant hormone cytokinins.