A Biomimetic Multifunctional Nanoframework for Symptom Relief and Restorative Treatment of Acute Liver Failure.

Acute liver failure (ALF) is a rare and serious condition characterized by major hepatocyte death and liver dysfunction. Owing to the limited therapeutic options, this disease generally has a poor prognosis and a high mortality rate. When ALF cannot be reversed by medications, liver transplantation is often needed. However, transplant rejection and the shortage of donor organs still remain major challenges. Most recently, stem cell therapy has emerged as a promising alternative for the treatment of liver diseases. However, the limited cell delivery routes and poor stability of live cell products have greatly hindered the feasibility and therapeutic efficacy of stem cell therapy. Inspired by the functions of mesenchymal stem cells (MSCs) primarily through the secretion of several factors, we developed an MSC-inspired biomimetic multifunctional nanoframework (MBN) that encapsulates the growth-promoting factors secreted by MSCs via combination with hydrophilic or hydrophobic drugs. The red blood cell (RBC) membrane was coated with the MBN to enhance its immunological tolerance and prolong its circulation time in blood. Importantly, the MBN can respond to the oxidative microenvironment, where it accumulates and degrades to release the payload. In this work, two biomimetic nanoparticles, namely, rhein-encapsulated MBN (RMBN) and N-acetylcysteine (NAC)-encapsulated MBN (NMBN), were designed and synthesized. In lipopolysaccharide (LPS)/d-galactosamine (D-GalN)-induced and acetaminophen (APAP)-induced ALF mouse models, RMBN and NMBN could effectively target liver lesions, relieve the acute symptoms of ALF, and promote liver cell regeneration by virtue of their strong antioxidative, anti-inflammatory, and regenerative activities. This study demonstrated the feasibility of the use of an MSC-inspired biomimetic nanoframework for treating ALF.

Recent advances in bioaffinity strategies for preclinical and clinical drug discovery: Screening natural products, small molecules and antibodies.

Bioaffinity drug screening strategies have gained popularity in preclinical and clinical drug discovery for natural products, small molecules and antibodies owing to their superior selectivity, the large number of compounds to be screened and their ability to minimize the time and expenses of the drug discovery process. This paper provides a systematic summary of the principles of commonly used bioaffinity-based screening methods, elaborates on the success of bioaffinity in clinical drug development and summarizes the active compounds, preclinical drugs and marketed drugs obtained through affinity screening methods. Owing to the high demand for new drugs, bioaffinity-guided screening techniques will play a greater part in clinical drug development.

MYC Oncogene: A Druggable Target for Treating Cancers with Natural Products.

Various diseases, including cancers, age-associated disorders, and acute liver failure, have been linked to the oncogene, MYC. Animal testing and clinical trials have shown that sustained tumor volume reduction can be achieved when MYC is inactivated, and different combinations of therapeutic agents including MYC inhibitors are currently being developed. In this review, we first provide a summary of the multiple biological functions of the MYC oncoprotein in cancer treatment, highlighting that the equilibrium points of the MYC/MAX, MIZ1/MYC/MAX, and MAD (MNT)/MAX complexes have further potential in cancer treatment that could be used to restrain MYC oncogene expression and its functions in tumorigenesis. We also discuss the multifunctional capacity of MYC in various cellular cancer processes, including its influences on immune response, metabolism, cell cycle, apoptosis, autophagy, pyroptosis, metastasis, angiogenesis, multidrug resistance, and intestinal flora. Moreover, we summarize the MYC therapy patent landscape and emphasize the potential of MYC as a druggable target, using herbal medicine modulators. Finally, we describe pending challenges and future perspectives in biomedical research, involving the development of therapeutic approaches to modulate MYC or its targeted genes. Patients with cancers driven by MYC signaling may benefit from therapies targeting these pathways, which could delay cancerous growth and recover antitumor immune responses.

A comprehensive quality evaluation for Huangqi Guizhi Wuwu decoction by integrating UPLC-DAD/MS chemical profile and pharmacodynamics combined with chemometric analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqi Guizhi Wuwu Decoction (HGWD), a classical Chinese formula originally recorded in Jin Kui Yao Lue, was used for the treatment of human "blood impediment" (a type of "Bi" syndrome). In clinical practice, HGWD has been applied to treat rheumatoid arthritis (RA). AIM OF THE STUDY: The characterization of chemical markers reflecting both efficacy and chemical characteristics is of great significance for TCM quality control. With the anti-RA effects of HGWD as an example, the aim of this study was to develop a comprehensive strategy combining the overall chemical profile and biological activity data to identify chemical markers. MATERIALS AND METHODS: First, an ultra-performance liquid chromatography-diode array detector (UPLC-DAD) fingerprint was established and validated to evaluate the holistic quality of HGWD of different origins. Characteristic markers associated with HGWD from different geographical origins were screened by a combination of UPLC-DAD fingerprint and chemometrics methods. Second, the chemical profiles of the 15 batches of HGWD samples were characterized by UPLC coupled tohybrid linear ion trap-Orbitrap mass spectrometry (UPLC-HRMS). The in vitro anti-RA activities of the 15 HGWD samples were then evaluated. Third, spectrum-effect relationship analysis was performed to identify bioactive compounds that could potentially be used as quality markers. Finally, a UPLC-triple quadrupole tandem mass spectrometry approach was optimized and established for quantitative analysis of the characteristic and quality markers in 15 batches of HGWD. RESULTS: In total, 30 common peaks were assigned in the UPLC-DAD fingerprint. Nine peaks were recognized and considered characteristic markers: protocatechuic acid, coumarin, cinnamic acid, oxypaeoniflorin, paeoniflorin, calycosin, formononetin, catechin, and albiflorin. Furthermore, ninety-five common compounds were identified in the UPLC-HRMS chemical profile. The pharmacological analysis indicated that the anti-RA activities of the 15 HGWD samples were vastly different. The spectrum-effect relationship analysis revealed 30 potential bioactive constituents positively correlated with anti-RA activity. Among them, five compounds with relative amounts >1%, paeoniflorin, astragaloside IV, hexahydrocurcumin, formononetin and calycosin-7-glucoside, were selected as quality markers, and their activity was verified in LPS-induced RAW264.7 macrophages. Finally, the above 12 representative components were simultaneously quantified in the 15 batches of HGWD samples. CONCLUSION: Combining a holistic chemical profile with representative component evaluation, this systematic strategy could be a reliable and effective method to improve quality evaluations of HGWD.

From mundane to classic: Sinomenine as a multi-therapeutic agent.

Sinomenine is an active substance extracted from the traditional Chinese medicine Sinomenium acutum. Sinomenine has been shown to mediate a wide range of pharmacological actions and is known to possess good anti-inflammatory, immunosuppressive, antitumor, neuroprotective, antiarrhythmic and other pharmacological effects. Understanding the underlying mechanisms and the association between the targets and the pharmaceutical effects on different diseases is crucial to the discovery and design of new treatment strategies. In this review, we aim to give a systematic and comprehensive overview of the research progress of sinomenine over the past 20 years. We first describe the metabolism of sinomenine in vivo and then summarize the pharmacological actions of sinomenine on different diseases. Furthermore, the potential binding properties of sinomenine and the potential of developing new sinomenine-based drugs are also reviewed.

Pan-cancer analysis of NFE2L2 mutations identifies a subset of lung cancers with distinct genomic and improved immunotherapy outcomes.

BACKGROUND: Mutations in the KEAP1-NFE2L2 signaling pathway were linked to increased tumorigenesis and aggressiveness. Interestingly, not all hotspot mutations on NFE2L2 were damaging; some even were activating. However, there was conflicting evidence about the association between NFE2L2 mutation and Nrf2-activating mutation and responsiveness to immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) and other multiple cancers. METHODS: The study with the largest sample size (n = 49,533) explored the landscape of NFE2L2 mutations and their impact response/resistance to ICIs using public cohorts. In addition, the in-house WXPH cohort was used to validate the efficacy of immunotherapy in the NFE2L2 mutated patients with NSCLC. RESULTS: In two pan-cancer cohorts, Nrf2-activating mutation was associated with higher TMB value compared to wild-type. We identified a significant association between Nrf2-activating mutation and shorter overall survival in pan-cancer patients and NSCLC patients but not in those undergoing ICIs treatment. Similar findings were obtained in cancer patients carrying the NFE2L2 mutation. Furthermore, in NSCLC and other cancer cohorts, patients with NFE2L2 mutation demonstrated more objective responses to ICIs than patients with wild type. Our in-house WXPH cohort further confirmed the efficacy of immunotherapy in the NFE2L2 mutated patients with NSCLC. Lastly, decreased inflammatory signaling pathways and immune-depleted immunological microenvironments were enriched in Nrf2-activating mutation patients with NSCLC. CONCLUSIONS: Our study found that patients with Nrf2-activating mutation had improved immunotherapy outcomes than patients with wild type in NSCLC and other tumor cohorts, implying that Nrf2-activating mutation defined a distinct subset of pan-cancers and might have implications as a biomarker for guiding ICI treatment, especially NSCLC.

Anomalous Nernst Effect Induced Terahertz Emission in a Single Ferromagnetic Film.

Despite its important role in understanding ultrafast spin dynamics and revealing novel spin/orbit effects, the mechanism of the terahertz (THz) emission from a single ferromagnetic nanofilm upon a femtosecond laser pump still remains elusive. Recent experiments have shown exotic symmetry, which is not expected from the routinely adopted mechanism of ultrafast demagnetization. Here, by developing a bidirectional pump-THz emission spectroscopy and associated symmetry analysis method, we set a benchmark for the experimental distinction of the THz emission induced by various mechanisms. Our results unambiguously unveil a new mechanism─anomalous Nernst effect (ANE) induced THz emission due to the ultrafast temperature gradient created by a femtosecond laser. Quantitative analysis shows that the THz emission exhibits interesting thickness dependence where different mechanisms dominate at different thickness ranges. Our work not only clarifies the origin of the ferromagnetic-based THz emission but also offers a fertile platform for investigating the ultrafast optomagnetism and THz spintronics.

A Novel Bromophenol Compound from Leathesia nana Inhibits Breast Cancer in a Direct Tumor Killing and Immunotherapy Manner.

Considering the resistance and toxicity of traditional chemotherapeutic drugs, seeking potential candidate for treating breast cancer effectively is a clinical problem that should be solved urgently. Natural products have attracted extensive attention, owing to their multi-target advantages and low toxicity. In the current study, the effects of XK-81, a novel bromophenol compound extracted from Leathesia nana, on breast cancer, and its underlying mechanisms, were explored. Firstly, data from in vitro experiments indicated that 4T-1, one of common mouse breast cancer cell lines, was a XK-81-susceptible cell line, and ferroptosis was the major death manner in response to XK-81 treatment, which was evidenced by increasing intracellular Fe2+ and ROS level with condensed mitochondrial membrane densities, as well as decreasing the protein expressions of SLC7A11 and GPX4. In vivo, XK-81 suppressed the growth of 4T-1 breast-tumor in both BALB/C mice and zebrafish. Obviously, XK-81 decreased the protein expression of SLC7A11 and GPX4 in tumor tissues, hinting at the occurrence of ferroptosis. Moreover, XK-81 increased CD8+ T cells and NK cells numbers and regulated M1/M2 macrophage ratio in tumor tissues, indicating XK-81's immunotherapeutic effect. Additionally, the secretions of immune-related cytokines, including TNF-α, IL-1ß, and IL-12, were elevated with XK-81 stimulation in RAW 264.7 cells. Intriguingly, compared with doxorubicin-induced heart damage, XK-81 demonstrated the therapeutic advantage of little cardiotoxicity on the heart. XK-81 demonstrated potential antitumor advantage by both directly inducing ferroptosis-mediated death of tumor cells and immunization.

Glycyrrhizae Radix et Rhizoma: The popular occurrence of herbal medicine applied in classical prescriptions.

Glycyrrhizae Radix et Rhizoma is a well-known herbal medicine with a wide range of pharmacological functions that has been used throughout Chinese history. This review presents a comprehensive introduction to this herb and its classical prescriptions. The article discusses the resources and distribution of species, methods of authentication and determination chemical composition, quality control of the original plants and herbal medicines, dosages use, common classical prescriptions, indications, and relevant mechanisms of the active content. Pharmacokinetic parameters, toxicity tests, clinical trials, and patent applications are discussed. The review will provide a good starting point for the research and development of classical prescriptions to develop herbal medicines for clinical use.

Exploring the active components and potential mechanisms of Rosa roxburghii Tratt in treating type 2 diabetes mellitus based on UPLC-Q-exactive Orbitrap/MS and network pharmacology.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a global disease with growing prevalence that is difficult to cure. Rosa roxburghii Tratt is an edible and medicinal plant, and modern pharmacological studies have shown that it has potential anti-diabetic activity. This is the first study to explore the active components and potential mechanisms of Rosa roxburghii Tratt fruit for treating T2DM based on UPLC-Q-Exactive Orbitrap/MS and network pharmacology. METHODS: The active components of Rosa roxburghii Tratt fruit were obtained from UPLC-Q-Exactive Orbitrap/MS analysis and retrieval in the SciFinder, PubMed, Web of Science, and CNKI databases. The potential targets of the active components were obtained from the SwissTargetPrediction and PharmMapper databases. The disease targets for T2DM were obtained from GeneCards, OMIM, TTD, DisGENent, and GEO databases. The intersection of the two datasets was used to obtain the potential targets of Rosa roxburghii Tratt fruit against T2DM. The target protein interaction network was constructed using the String database and Cytoscape software. The R software ClusterProfiler package was used for target enrichment analysis and the Cytoscape CytoNCA plug-in was used to screen core targets. Molecular docking and result visualization were performed using PyMOL and Autodock Vina software. RESULTS: We obtained 20 bioactive ingredients, including alphitolic acid, quercetin, and ellagic acid, as well as 13 core targets, such as AKT1, TNF, SRC, and VEGFA. All bioactive ingredients in Rosa roxburghii Tratt fruit were active against T2DM-related therapeutic targets. Rosa roxburghii Tratt fruit may play a therapeutic role in T2DM by regulating the PI3K/AKT, RAS, AGE-RAGE, and other signaling pathways. CONCLUSIONS: This study explored the active components and potential mechanisms of Rosa roxburghii Tratt fruit in the treatment of T2DM, laying the foundation for a further experimental study based on pharmacodynamic substances and their mechanisms of action.

Novel Anti-Cancer Products Targeting AMPK: Natural Herbal Medicine against Breast Cancer.

Breast cancer is a common cancer in women worldwide. The existing clinical treatment strategies have been able to limit the progression of breast cancer and cancer metastasis, but abnormal metabolism, immunosuppression, and multidrug resistance involving multiple regulators remain the major challenges for the treatment of breast cancer. Adenosine 5'-monophosphate (AMP)-Activated Protein Kinase (AMPK) can regulate metabolic reprogramming and reverse the "Warburg effect" via multiple metabolic signaling pathways in breast cancer. Previous studies suggest that the activation of AMPK suppresses the growth and metastasis of breast cancer cells, as well as stimulating the responses of immune cells. However, some other reports claim that the development and poor prognosis of breast cancer are related to the overexpression and aberrant activation of AMPK. Thus, the role of AMPK in the progression of breast cancer is still controversial. In this review, we summarize the current understanding of AMPK, particularly the comprehensive bidirectional functions of AMPK in cancer progression; discuss the pharmacological activators of AMPK and some specific molecules, including the natural products (including berberine, curcumin, (-)-epigallocatechin-3-gallate, ginsenosides, and paclitaxel) that influence the efficacy of these activators in cancer therapy; and elaborate the role of AMPK as a potential therapeutic target for the treatment of breast cancer.

Isolation and identification of angiogenesis-promoting components in Huanglian Jiedu decoction using live cell bio-specific extraction.

ETHNOPHARMACOLOGICAL RELEVANCE: Huanglian Jiedu Decoction (HLJDD) is a traditional heat-dissipating and detoxicating prescription used in Chinese medicine and has been extensively applied in the clinical treatment of ischemic stroke. Preliminary research confirmed that HLJDD exerts a neuroprotective effect on brain tissue injury caused by cerebral ischemia by promoting angiogenesis. However, the components of HLJDD responsible for its medicinal activity in ischemic injury remain unclear. AIM OF THE STUDY: The aim of this study was to identify the active components of HLJDD that could promote angiogenesis and investigate its underlying mechanism, as well as Hypoxia-inducible factor-1α (HIF-1α)/Vascular endothelial growth factor (VEGF) signalings in human umbilical vein endothelial cells (HUVECs). MATERIALS AND METHODS: The specific binding components of HLJDD with HUVECs were isolated and identified through a combination of live cell biospecific extraction, solid-phase extraction, and ultra performance liquid chromatography (UPLC)-Orbitrap Fusion Tribrid mass spectrometry (MS). Their pharmacological activity against oxygen-glucose deprivation-reperfusion (OGD/R) injury and in vitro pro-angiogenesis was validated using Cell Counting Kit-8 (CCK-8) and tube formation analysis, respectively. Finally, we explored the effect of active ingredients on the expression levels of HIF-1α and VEGF using enzyme-linked immunosorbent assay. Molecular docking was used to predict the potential binding of six active components to phosphoinositide 3-kinase (PI3K), serine/threonine-specific protein kinase (AKT) and Von Hippel-Lindau (VHL) proteins, which are involved in the regulation of HIF-1α and are highly associated with angiogenesis. RESULTS: A total of 13 HUVECs-specific HLJDD components were identified, and 10 of them were shown to protect against OGD/R injury. We were the first to demonstrate that two of these components have a protective role in OGD/R-induced HUVECs injury. Additionally, seven of these 10 components exhibited angiogenesis-promoting activity, and two of these components were shown, for the first time, to promote angiogenesis in HUVECs. These effects might occur through the HIF-1α/VEGF pathway. Molecular docking results showed that all six active ingredients could stably bind to PI3K and AKT proteins, suggesting that these two proteins may be potential targets for six active ingredients. CONCLUSIONS: The approach employed in this study effectively identified proangiogenic components in HLJDD that might act via PI3K/AKT/HIF-1α/VEGF pathways and other mechanisms involved in angiogenesis. In conclusion, this study was the first to demonstrate four compounds with new bioactivities and could also provide insight into the isolation and discovery of new bioactive compounds existing in Chinese medicine with potential clinical value.

The safety of Chinese medicine: A systematic review of endogenous substances and exogenous residues.

BACKGROUND: Safety and toxicity have become major challenges in the internationalization of Chinese medicine. Inspite of its wide application, security problems of Chinese medicine still occur from time to time, raising widespread concerns about its safety. Most of the studies either only partially discussed the intrinsic toxicities or extrinsic harmful residues in Chinese medicine, or briefly described detoxification and attenuation methods. It is necessary to systematically discuss Chinese medicine's extrinsic and intrinsic toxic components and corresponding toxicity detoxification or detection methods as a whole. PURPOSE: This review comprehensively summarizes various toxic components in Chinese medicine from intrinsic and extrinsic. Then the corresponding methods for detoxification or detection of toxicity are highlighted. It is expected to provide a reference for safeguards for developing and using Chinese medicine. METHODS: A literature search was conducted in the databases, including PubMed, Web of Science,Wan-fang database, and the China National Knowledge Infrastructure (CNKI). Keywords used were safety, toxicity, intrinsic toxicities, extrinsic harmful residues, alkaloids, terpene and macrolides, saponins, toxic proteins, toxic crystals, minerals, heavy metals, pesticides, mycotoxins, sulfur dioxide, detoxification, detection, processing (Paozhi), compatibility (Peiwu), Chinese medicine, etc., and combinations of these keywords. All selected articles were from 2006 to 2022, and each was assessed critically for our exclusion criteria. Studies describe the classification of toxic components of Chinese medicine, the toxic effects and mechanisms of Chinese medicine, and the corresponding methods for detoxification or detection of toxicity. RESULTS: The toxic components of Chinese medicines can be classified as intrinsic toxicities and extrinsic harmful residues. Firstly, we summarized the intrinsic toxicities of Chinese medicine, the adverse effects and toxicity mechanisms caused by these components. Next, we focused on the detoxification or attenuation methods for intrinsic toxicities of Chinese medicine. The other main part discussed the latest progress in analytical strategies for exogenous hazardous substances, including heavy metals, pesticides, and mycotoxins. Beyond reviewing mainstream instrumental methods, we also introduced the emerging biochip, biosensor and immuno-based techniques. CONCLUSION: In this review, we provide an overall assessment of the recent progress in endogenous toxins and exogenous hazardous substances concerning Chinese medicine, which is expected to render deeper insights into the safety of Chinese medicine.

The effects of bioactive components from the rhizome of gastrodia elata blume (Tianma) on the characteristics of Parkinson's disease.

Parkinson's disease (PD) is an age-related chronic neurodegenerative disease caused by the death and degeneration of dopaminergic neurons in the substantia nigra of the midbrain. The decrease of the neurotransmitter dopamine in the patient's brain leads to various motor symptoms. PD drugs mainly enhance dopamine levels but cannot prevent or slow down the loss of dopaminergic neurons. In addition, they exhibit significant side effects and addiction issues during long-term use. Therefore, it is particularly urgent to develop novel drugs that have fewer side effects, can improve PD symptoms, and prevent the death of dopaminergic neurons. The rhizome of Gastrodia elata Blume (Tianma) is a well-known medicinal herb and has long been used as a treatment of nervous system-related diseases in China. Several clinical studies showed that formula comprising Tianma could be used as an add-on therapy for PD patients. Pharmacological studies indicated that Tianma and its bioactive components can reduce the death of dopaminergic neurons, α-synuclein accumulation, and neuroinflammation in various PD models. In this review, we briefly summarize studies regarding the effects of Tianma and its bioactive components' effects on major PD features and explore the potential use of Tianma components for the treatment of PD.

Potential Focal Adhesion Kinase Inhibitors in Management of Cancer: Therapeutic Opportunities from Herbal Medicine.

Focal adhesion kinase (FAK) is a multifunctional protein involved in cellular communication, integrating and transducing extracellular signals from cell-surface membrane receptors. It plays a central role intracellularly and extracellularly within the tumor microenvironment. Perturbations in FAK signaling promote tumor occurrence and development, and studies have revealed its biological behavior in tumor cell proliferation, migration, and adhesion. Herein we provide an overview of the complex biology of the FAK family members and their context-dependent nature. Next, with a focus on cancer, we highlight the activities of FAK signaling in different types of cancer and how knowledge of them is being used for screening natural compounds used in herbal medicine to fight tumor development.

Glycyrrhizic Acid and Its Derivatives: Promising Candidates for the Management of Type 2 Diabetes Mellitus and Its Complications.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease, which is characterized by hyperglycemia, chronic insulin resistance, progressive decline in ß-cell function, and defect in insulin secretion. It has become one of the leading causes of death worldwide. At present, there is no cure for T2DM, but it can be treated, and blood glucose levels can be controlled. It has been reported that diabetic patients may suffer from the adverse effects of conventional medicine. Therefore, alternative therapy, such as traditional Chinese medicine (TCM), can be used to manage and treat diabetes. In this review, glycyrrhizic acid (GL) and its derivatives are suggested to be promising candidates for the treatment of T2DM and its complications. It is the principal bioactive constituent in licorice, one type of TCM. This review comprehensively summarized the therapeutic effects and related mechanisms of GL and its derivatives in managing blood glucose levels and treating T2DM and its complications. In addition, it also discusses existing clinical trials and highlights the research gap in clinical research. In summary, this review can provide a further understanding of GL and its derivatives in T2DM as well as its complications and recent progress in the development of potential drugs targeting T2DM.

Mechanisms of carcinogenic activity triggered by lysine-specific demethylase 1A.

Epigenetics has emerged as a prime focus area in the field of cancer research. Lysine-specific demethylase 1A (LSD1), the first discovered histone demethylase, is mainly responsible for catalysing demethylation of histone 3 lysine 4 (H3K4) and H3K9 to activate or inhibit gene transcription. LSD1 is abnormally expressed in various cancers and participates in cancer proliferation, apoptosis, metastasis, invasion, drug resistance and other processes by interacting with regulatory factors. Therefore, it may serve as a potential therapeutic target for cancer. This review summarises the major oncogenic mechanisms mediated by LSD1 and provides a reference for developing novel and efficient anticancer strategies targeting LSD1.

A Novel Polysaccharide From Chuanminshen violaceum and Its Protective Effect Against Myocardial Injury.

We isolated and purified a novel polysaccharide from the root of Chuanminshen violaceum, namely, Chuanminshen violaceumis polysaccharide (CVP) and confirmed its structure and molecular weight. Furthermore, in vivo experiment, CVP's protective effect against myocardial ischemia-reperfusion (I/R) injury in mice was evidenced by significantly reducing I/R-induced myocardial infarction (MI) size, decreasing the secretion of heart damage biomarkers, and improving cardiac function. Then, the myocardial anoxia/reoxygenation (A/R) injury model was established to mimic reperfusion injury. Noticeably, ferroptosis was the major death manner for A/R-damaged H9c2 cells. Meanwhile, CVP significantly inhibited ferroptosis by decreasing intracellular Fe2+ level, enhancing GPX4 expression, and suppressing lipid peroxidation to confront A/R injury. In conclusion, CVP, with a clear structure, ameliorated I/R injury by inhibiting ferroptosis.

Nanocarriers for effective delivery: modulation of innate immunity for the management of infections and the associated complications.

Innate immunity is the first line of defense against invading pathogens. Innate immune cells can recognize invading pathogens through recognizing pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs). The recognition of PAMPs by PRRs triggers immune defense mechanisms and the secretion of pro-inflammatory cytokines such as TNF-α, IL-1ß, and IL-6. However, sustained and overwhelming activation of immune system may disrupt immune homeostasis and contribute to inflammatory disorders. Immunomodulators targeting PRRs may be beneficial to treat infectious diseases and their associated complications. However, therapeutic performances of immunomodulators can be negatively affected by (1) high immune-mediated toxicity, (2) poor solubility and (3) bioactivity loss after long circulation. Recently, nanocarriers have emerged as a very promising tool to overcome these obstacles owning to their unique properties such as sustained circulation, desired bio-distribution, and preferred pharmacokinetic and pharmacodynamic profiles. In this review, we aim to provide an up-to-date overview on the strategies and applications of nanocarrier-assisted innate immune modulation for the management of infections and their associated complications. We first summarize examples of important innate immune modulators. The types of nanomaterials available for drug delivery, as well as their applications for the delivery of immunomodulatory drugs and vaccine adjuvants are also discussed.