Glycyrrhiza polysaccharides may have an antitumor effect in γδT cells through gut microbiota and TLRs/NF-κB pathway in mice.

Tumor immunotherapy can be a suitable cancer treatment option in certain instances. Here we investigated the potential immunomodulatory effect of oral glycyrrhiza polysaccharides (GCP) on the antitumor function of γδT cells in intestinal epithelial cells in mice. We found that GCP can inhibit tumor growth and was involved in the regulation of systemic immunosuppression. GCP administration also promoted the differentiation of gut epithelia γδT cells into IFN-γ-producing subtype through regulation of local cytokines in gut mucosa. GCP administration increased local cytokine levels through gut microbiota and the gut mucosa Toll-like receptors / nuclear factor kappa-B pathway. Taken together, our results suggest that GCP might be a suitable candidate for tumor immunotherapy, although further clinical research, including clinical trials, are required to validate these results.

Role of epigenetics in the regulation of skin aging and geroprotective intervention: A new sight.

Multiple epigenetic factors play a regulatory role in maintaining the homeostasis of cutaneous components and are implicated in the aging process of the skin. They have been associated with the activation of the senescence program, which is the primary contributor to age-related decline in the skin. Senescent species drive a series of interconnected processes that impact the immediate surroundings, leading to structural changes, diminished functionality, and heightened vulnerability to infections. Geroprotective medicines that may restore the epigenetic balance represent valid therapeutic alliances against skin aging. Most of them are well-known Western medications such as metformin, nicotinamide adenine dinucleotide (NAD+), rapamycin, and histone deacetylase inhibitors, while others belong to Traditional Chinese Medicine (TCM) remedies for which the scientific literature provides limited information. With the help of the Geroprotectors.org database and a comprehensive analysis of the referenced literature, we have compiled data on compounds and formulae that have shown potential in preventing skin aging and have been identified as epigenetic modulators.

Associations of environmental factors with neurodegeneration: An exposome-wide Mendelian randomization investigation.

Neurodegenerative diseases (NDDs) remain a global health challenge. Previous studies have reported potential links between environmental factors and NDDs, however, findings remain controversial across studies and elusive to be interpreted as evidence of robust causal associations. In this study, we comprehensively explored the causal associations of the common environmental factors with major NDDs including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), based on updated large-scale genome-wide association study data through two-sample Mendelian randomization (MR) approach. Our results indicated that, overall, 28 significant sets of exposure-outcome causal association evidence were detected, 12 of which were previously underestimated and newly identified, including average weekly beer plus cider intake, strenuous sports or other exercises, diastolic blood pressure, and body fat percentage with AD, alcohol intake frequency with PD, apolipoprotein B, systolic blood pressure, and forced expiratory volume in 1 s (FEV1) with ALS, and alcohol intake frequency, hip circumference, forced vital capacity, and FEV1 with MS. Moreover, the causal effects of several environmental factors on NDDs were found to overlap. From a triangulation perspective, our investigation provided insights into understanding the associations of environmental factors with NDDs, providing causality-oriented evidence to establish the risk profile of NDDs.

Bergamot essential oil improves CUMS-induced depression-like behaviour in rats by protecting the plasticity of hippocampal neurons.

Bergamot essential oil (BEO) is an extract of the bergamot fruit with significant neuroprotective effect. This study was to investigate the effects and the underlying mechanism of BEO in mitigating depression. GC-MS were used to identify its constituents. Antidepressive properties of BEO were evaluated by sucrose preference test (SPT), force swimming test (FST) and open field test (OFT). Nissl staining was used to determine the number of Nissl bodies in hippocampus (HIPP) of rats. Changes in HIPP dendritic length and dendritic spine density were detected by Golgi-Cox staining. Immunohistochemistry and Western blot were used to detect the postsynaptic density protein-95 (PSD-95) and synaptophysin (SYP) in the HIPP of rats. The enzyme-linked immunosorbent assay was used to determine the 5-hydroxytryptamine (5-HT), insulin-like growth factor 1 (IGF-1) and interleukin-1ß (IL-1ß) in the HIPP, serum and cerebrospinal fluid (CSF) of rats. Inhaled BEO significantly improved depressive behaviour in chronic unpredictable mild stress (CUMS) rats. BEO increased Nissl bodies, dendritic length and spine density, PSD-95 and SYP protein in the HIPP. Additionally, BEO upregulated serum 5-HT, serum and CSF IGF-1, while downregulating serum IL-1ß. Collectively, inhaled BEO mitigates depression by protecting the plasticity of hippocampal neurons, hence, providing novel insights into treatment of depression.

Differential expression of circular RNAs in human umbilical cord mesenchymal stem cells treated with icariin.

Human umbilical cord mesenchymal stem cells (hUMSCs) belong to a multipotent stem cell population. Transplantation of icariin (ICA)-treated hUMSCs have better tissue repairing function in chronic liver injury. This study was to investigate whether the tissue-repairing effects and migration of hUMSCs after ICA treatment were regulated by circular RNAs (circRNAs). ICA was used to treat hUMSCs in vitro for 1 week and the expression profiles of circRNAs were generated using RNA sequencing. Differentially expressed circRNAs in hUMSCs after ICA intervention were screened. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were carried out to predict the potential function of dysregulated circRNAs. There were 52 differentially expressed circRNAs (32 circRNAs up-regulated and 20 circRNAs down-regulated) with fold change ≥2.0 before and after ICA treatment. ADP-ribosylation factors were associated with the dysregulated circRNAs among Gene Ontology analysis. Kyoto Encyclopedia of Genes and Genomes analysis showed that only endocytosis pathway was associated with up-regulated circRNAs, whereas 4 pathways including homologous recombination, RNA transport, axon guidance, and proteoglycans in cancer were related to down-regulated circRNAs. Fifty-two differentially expressed circRNAs and 238 predicted microRNAs were included in circRNAs-microRNAs network. The mechanism of ICA inducing hUMSCs migration may be through regulating circRNAs expression which affects ADP-ribosylation factors protein signal pathways.

Mechanic evaluation of Wu-Mei-Pill on colitis-associated colorectal cancer: An integrated transcriptomics, metabolomics, and experimental validation study.

BACKGROUND: Chronic intestinal inflammatory diseases play a crucial role in the onset of colorectal cancer (CRC). Effectively impeding the progression of colitis-associated colorectal cancer (CAC) can be instrumental in hindering CRC development. Wu-Mei-Pill (WMP), a formulation comprising various herbal extracts, is clinically employed for CAC treatment, yet the underlying mechanism of WMP's efficacy in CAC remains unclear. Our study firstly demonstrated the effects and mechanisms of WMP on transcriptional and metabolic levels based on integrated transcriptomics and untargeted metabolomics and relative experimental validations. MATERIALS AND METHODS: A CAC mouse model was established through a single injection of azoxymethane (AOM) followed by intermittent dextran sodium sulfate (DSS) intervention, with subsequent WMP administration. Initially, the therapeutic impact of WMP on the CAC model was assessed by observing survival rate, body weight change, colon length, tumor number, tumor load, and pathological changes in the colon tissue of CAC mice post-WMP intervention. Subsequently, differential genes and metabolites in the colorectal tissue of CAC mice following WMP intervention were identified through transcriptomics and non-targeted metabolomics. Finally, the influence of WMP on the peroxisome proliferator activated receptor (PPAR) pathway, Wnt pathway, and CC motif chemokine ligand 3 (CCL3)/ CC motif chemokine receptor 1 (CCR1) axis in CAC mice was verified through western blot, immunofluorescence, and ELISA based on the results of transcriptomics and non-targeted metabolomics. RESULTS: WMP intervention enhanced survival, alleviated body weight loss, shortened colon length, tumor occurrence, and pathological changes in the colorectal tissue of CAC mice, such as glandular damage, tumourigenesis, and inflammatory cell infiltration. Transcriptomic and non-targeted metabolomic results revealed that WMP intervention up-regulated the expression of key regulatory mechanisms of fatty acid oxidation PPAR pathway-related genes (Pparg, Ppara, Cpt1a, and Acadm) and metabolites (L-carnitine and L-palmitoylcarnitine). Additionally, it down-regulated Wnt pathway-related genes (Wnt3, Axin2, Tcf7, Mmp7, Lgr5, Wnt5a, Fzd6, Wnt7b, Lef1, and Fzd10 etc.) and pro-inflammatory related genes (Il1b, Il6, Il17a, Ccl3, and Ccr1 etc.). Experimental validation demonstrated that WMP up-regulated PPAR pathway-related proteins [PPARγ, PPARα, carnitine palmitoyltransferase 1A (CPT1A), and acyl-CoA dehydrogenase medium chain (ACADM)] in the colorectal tissue of CAC mice. It also down-regulated Wnt pathway-related proteins [ß-catenin, T-cell factor (TCF), lymphoid enhancer-binding factor (LEF), and matrix metallopeptidase 7 (MMP7)], inhibited the nuclear translocation of the key transcription factor ß-catenin in the Wnt pathway, and suppressed epithelial-to-mesenchymal transition (EMT) activation induced by the Wnt pathway (up-regulated E-cadherin and down-regulated Vimentin). Furthermore, WMP intervention reduced pro-inflammatory factors [interleukin (IL)-6, IL-1ß, and IL-17A] and decreased CCL3/CCR1 axis factors, including CCL3 protein levels and diminished F4/80+CCR1+ positive expressed cells. CONCLUSION: WMP significantly inhibits CAC tumorigenesis by up-regulating PPARα-mediated fatty acid oxidation, inhibiting the Wnt signaling pathway-mediated EMT, and suppressing CCL3/CCR1-mediated inflammatory responses.

Tissue damage from chronic liver injury inhibits peripheral NK cell abundance and proinflammatory function.

One of the difficulties in the treatment of hepatocellular carcinoma is that it is impossible to eliminate the inhibitory effect of tumor microenvironment on immune response. Therefore, it is particularly important to understand the formation process of tumor microenvironment. Chronic inflammation is the core factor of cancer occurrence and the leading stage of inflammation-cancer transformation, and the NK cell subsets play an important role in it. Our study confirmed that in the stage of chronic liver injury, the local immunosuppressive microenvironment of the liver, that is, the damaged microenvironment, has been formed, but this inhibitory effect is only for peripheral NK cells and has no effect on tissue resident NK subsets. The markers of damage microenvironment are the same as those of tumor microenvironment.

The dynamic shifts of IL-10-producing Th17 and IL-17-producing Treg in health and disease: a crosstalk between ancient "Yin-Yang" theory and modern immunology.

The changes in T regulatory cell (Treg) and T helper cell (Th) 17 ratios holds paramount importance in ensuring internal homeostasis and disease progression. Recently, novel subsets of Treg and Th17, namely IL-17-producing Treg and IL-10-producing Th17 have been identified. IL-17-producing Treg and IL-10-producing Th17 are widely considered as the intermediates during Treg/Th17 transformation. These "bi-functional" cells exhibit plasticity and have been demonstrated with important roles in multiple physiological functions and disease processes. Yin and Yang represent opposing aspects of phenomena according to the ancient Chinese philosophy "Yin-Yang" theory. Furthermore, Yin can transform into Yang, and vice versa, under specific conditions. This theory has been widely used to describe the contrasting functions of immune cells and molecules. Therefore, immune-activating populations (Th17, M1 macrophage, etc.) and immune overreaction (inflammation, autoimmunity) can be considered Yang, while immunosuppressive populations (Treg, M2 macrophage, etc.) and immunosuppression (tumor, immunodeficiency) can be considered Yin. However, another important connotation of "Yin-Yang" theory, the conversion between Yin and Yang, has been rarely documented in immune studies. The discovery of IL-17-producing Treg and IL-10-producing Th17 enriches the meaning of "Yin-Yang" theory and further promotes the relationship between ancient "Yin-Yang" theory and modern immunology. Besides, illustrating the functions of IL-17-producing Treg and IL-10-producing Th17 and mechanisms governing their differentiation provides valuable insights into the mechanisms underlying the dynamically changing statement of immune statement in health and diseases.

Toxicity studies of condensed fuzheng extract in mice and rats.

Nutritional supplements have been used to improve immune function. Condensed fuzheng extract (CFE) is a well-known traditional Chinese medicine (TCM) formula that is predominantly made from sheep placenta, Astragalus mongholicus Bunge, and Polygonatum kingianum Collett & Hemsl. However, the toxicological profile of CFE has not been determined. In this study, we investigated the acute (14 days) and sub-chronic (90 days) oral toxicities of CFE in mice and rats and the phytochemical composition of CFE. Materials and methods: For the assessment of acute toxicity, 80 ICR mice of both sexes were randomly divided into four groups. Three groups were treated with 4500, 2250 and 1125 mg/kg/d bw CFE daily (n = 10/group per sex) for 14 days; a separate group was used as control. To test the sub-chronic toxicity, male and female Sprague Dawley rats were orally administered 8150, 4075 or 2037 mg/kg bw of CFE for 90 days; a control group was included. Hematological, biochemical, and histopathological markers were tested at the end of the experiment. The chemical composition of CFE was determined by UPLC-HRMS method. Results: In both acute and sub-chronic toxicity studies, no mortalities, indications of abnormality, or treatment-related adverse effects were observed. The LD50 of CFE was higher than 4500 mg/kg. There were no significant changes in the hematological and biochemical data in the treatment group compared with the control group (p > 0.05). Histopathological analyses of the heart, liver, spleen, lungs, kidneys, thymus, testes (male rats) and ovaries (female rats) revealed no anatomical changes of each organ. Phytochemical analysis of CFE revealed the presence of flavonoids (highest abundance), phenols and alkaloids. In conclusion, our results showed that CFE is a safe and non-toxic formula. We also reported phytochemicals in CFE that may possess important pharmacological effects.

Pro-inflammatory cytokines in stress-induced depression: Novel insights into mechanisms and promising therapeutic strategies.

Stress-mediated depression is one of the common psychiatric disorders with a high prevalence and suicide rate, there is a lack of effective treatment. Accordingly, effective treatments with few adverse effects are urgently needed. Pro-inflammatory cytokines (PICs) may play a key role in stress-mediated depression. Thereupon, both preclinical and clinical studies have found higher levels of IL-1ß, TNF-α and IL-6 in peripheral blood and brain tissue of patients with depression. Recent studies have found PICs cause depression by affecting neuroinflammation, monoamine neurotransmitters, hypothalamic pituitary adrenal axis and neuroplasticity. Moreover, they play an important role in the symptom, development and progression of depression, maybe a potential diagnostic and therapeutic marker of depression. In addition, well-established antidepressant therapies have some relief on high levels of PICs. Importantly, anti-inflammatory drugs relieve depressive symptoms by reducing levels of PICs. Collectively, reducing PICs may represent a promising therapeutic strategy for depression.

Global research trends of immunosenescence: A bibliometric study.

Background: Immunosenescence, an age-related deficit in immunity, associated with multiple disorders and making the successful aging a challenge. Although nearly 4000 articles have been published, only few review articles have summarized the research status. In order to better understand the most recent advances, hotspots and development trends in immunosenescence, it is very necessary to conduct a comprehensive bibliometric analysis. Hence, commonly used bibliometric analysis software CiteSpace and VOSviewer were employed to conduct a quantitative analysis and critical evaluation of publications in this study. Methods: Immunosenescence publications were screened from the Web of Science Core Collection (WoSCC). Microsoft Excel 2021, CiteSpace 5.8.R3, and VOSviewer 1.6.17 were used for bibliometric study. Results: A total of 3875 publications were retrieved from WoSCC. After screening by document type (article or review) (352 publications were excluded) and language of English (85 were excluded), 3438 studies were finally used for bibliometric analysis. The literature on immunosenescence had been continuously growing since 1991, and by 2020 it has skyrocketed 312 publications from 240 in 2019. USA (1111 publications, 35.01%) was the leading country of publications, followed by ITALY (379, 11.94%) and ENGLAND (366, 11.53%). Of the authors, Pawelec G from the Tubingen University of GERMANY contributed the greatest articles (93 publications). All the keywords could be divided into five clusters, and additional potent visualization bursts revealed that "gut microbiota," "health," "dysfunction," and "nivolumab" were the active hotspots presently. Conclusion: Based on the current data, we firstly concluded that there will be a dramatically rising publications on immunosenescence, and research teams from USA or GERMANY might be the best chooses for collaboration. Moreover, We particularly emphasized the development potential of mechanism and intervening strateges like "gut microbiota" and "nivolumab" in immunosenescence. We hope to provide new ideas for promoting the basic research and clinical application of immunosenescence.

Bazi Bushen alleviates skin senescence by orchestrating skin homeostasis in SAMP6 mice.

Bazi Bushen, a Chinese-patented drug with the function of relieving fatigue and delaying ageing, has been proven effective for extenuating skin senescence. To investigate the potential mechanism, senescence-accelerated mouse prone 6 (SAMP6) was intragastrically administered with Bazi Bushen for 9 weeks to induce skin homeostasis. Skin homeostasis is important in mitigating skin senescence, and it is related to many factors such as oxidative stress, SASP, apoptosis, autophagy and stem cell. In our study, skin damage in SAMP6 mice was observed using HE, Masson and SA-ß-gal staining. The content of hydroxyproline and the activities of SOD, MDA, GSH-PX and T-AOC in the skin were measured using commercial assay kits. The level of SASP factors (IL-6, IL-1ß, TNF-α, MMP2 and MMP9) in skin were measured using ELISA kits. The protein expressions of p16, p21, p53, Bax, Bcl-2, Cleaved caspase-3, LC3, p62, Beclin1, OCT4, SOX2 and NANOG were measured by western blotting. The expression of ITGA6 and COL17A1 was measured by immunofluorescence staining and western blotting. Our findings demonstrated that Bazi Bushen alleviated skin senescence by orchestrating skin homeostasis, reducing the level of oxidative stress and the expression of SASP, regulating the balance of apoptosis and autophagy and enhancing the protein expressions of ITGA6 and COL17A1 to improve skin structure in SAMP6 mice. This study indicated that Bazi Bushen could serve as a potential therapy for alleviating skin senescence.

Discovering Traditional Chinese Medicine (TCM) Formulas for Complex Diseases Based on a Combination of Reverse Systematic Pharmacology and TCM Meridian Tropism Theory: Taking COVID-19 as an Example.

OBJECTIVE: Infections and death have been a part of our daily lives since the COVID-2019 pandemic outbreak in 2019, and the societal and economic consequences have lingered for an unanticipated duration. Novel and effective treatments are still desperately needed around the world to combat the infection. Here, we discovered a novel traditional Chinese medicine formula (TCMF) to potentially combat COVID-19 through reverse systematic pharmacology (disease → targets → TCMF → disease). METHODS: Combining Integrative network pharmacology and the traditional Chinese medicine (TCM) theory, a TCMF for COVID-19 was identified. In silico physiological interactions between herbs and disease hub targets were validated by molecular docking and dynamics simulation. RESULTS: Based on disease-related gene/pathway targets and a combination of reverse pharmacology and TCM meridian tropism theory, a COVID-19-associated herb database was constructed. A new TCMF, including Gancao, Baitouweng, Congbai, and Diyu (GBCD), was discovered for anti-COVID-19 therapy. The KEGG and GO analyses of 49 intersecting genes suggested that GBCD could combat COVID-19 through antiviral, antiinflammation, immunoregulation, and cytoprotection activities. Moreover, these possible effects were validated through docking and MD simulation. CONCLUSIONS: To the best of our knowledge, this study is the first to combine reverse pharmacology and meridian tropism theories for TCMF development, and a novel herbal combination, GBCD, was discovered for anti-COVID-19 therapy.

Bazi Bushen maintains intestinal homeostasis through inhibiting TLR4/NFκB signaling pathway and regulating gut microbiota in SAMP6 mice.

BACKGROUND: Bazi Bushen is a Chinese patented medicine with multiple health benefits and geroprotective effects, yet, no research has explored its effects on intestinal homeostasis. In this study, we aimed to investigate the effect of Bazi Bushen on intestinal inflammation and the potential mechanism of gut microbiota dysbiosis and intestinal homeostasis in senescence-accelerated mouse prone 6 (SAMP6). The hematoxylin and eosin (H&E) staining and immunohistochemistry were performed to assess the function of the intestinal mucosal barrier. The enzyme-linked immunosorbent assay (ELISA) and Western blotting were used to determine the level of intestinal inflammation. The aging-related ß-galactosidase (SA-ß-gal) staining and Western blotting were used to measure the extent of intestinal aging. The 16S ribosomal RNA (16S rRNA) was performed to analyze the change in gut microbiota composition and distribution. RESULTS: Bazi Bushen exerted remarkable protective effects in SAMP6, showing a regulated mucosal barrier and increased barrier integrity. It also suppressed intestinal inflammation through down-regulating pro-inflammatory cytokines (IL-6, IL-1ß, and TNF-α) and inhibiting TLR4/NFκB signaling pathway (MYD88, p-p65, and TLR4). Bazi Bushen improved intestinal aging by reducing the area of SA-ß-gal-positive cells and the expression of senescence markers p16, p21, and p53. In addition, Bazi Bushen effectively rebuilt the gut microbiota ecosystem by decreasing the abundance of Bacteroides and Klebsiella, whiles increasing the ratio of Lactobacillus/Bacteroides and the abundance of Akkermansia. CONCLUSION: Our study shows that Bazi Bushen could serve as a potential therapy for maintaining intestinal homeostasis. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

AHR, a novel inhibitory immune checkpoint receptor, is a potential therapeutic target for chemoresistant glioblastoma.

PURPOSE: This study aims to elucidate the mechanism underlying temozolomide resistance in patients with MGMT promoter hypomethylated glioblastoma, which is correlated with poor prognosis. The objective is to identify therapeutic targets and drugs suitable for temozolomide-resistant glioblastoma patients using big data analysis. METHODS: In this retrospective study, transcriptome sequencing data from 457 glioblastoma patients, multi-omics data, and single-cell sequencing data were employed to assess the expression pattern, prognostic value, and biological functions of AHR in glioblastoma. The HERB database was utilized to screen for AHR-targeted drugs for glioblastoma treatment. Validation of our findings was conducted using multiplex immunofluorescence staining of clinical samples and T cells and tumor cells co-culture models. RESULTS: Our findings demonstrated that patients with MGMT promoter unmethylation did not benefit from postoperative temozolomide chemotherapy due to resistance arising from DNA repair function and tumor immune response. AHR was found to be expressed in immune cells and exhibited an immunomodulatory role in glioblastoma with MGMT promoter unmethylation. AHR was identified as a potential novel inhibitory immune checkpoint receptor, serving as a therapeutic target for temozolomide-resistant glioblastoma. Furthermore, targeting AHR with Semen aesculi markedly enhanced the cytotoxic effect of T cells on glioma cells. CONCLUSIONS: In addition to DNA repair function, the tumor immune response plays a pivotal role in temozolomide resistance of glioblastoma. Herbal compounds targeting AHR may offer an effective treatment for temozolomide-resistant glioblastoma.

Network pharmacology and experimental validation to elucidate the pharmacological mechanisms of Bushen Huashi decoction against kidney stones.

Introduction: Kidney stone disease (KS) is a complicated disease with an increasing global incidence. It was shown that Bushen Huashi decoction (BSHS) is a classic Chinese medicine formula that has therapeutic benefits for patients with KS. However, its pharmacological profile and mechanism of action are yet to be elucidated. Methods: The present study used a network pharmacology approach to characterize the mechanism by which BSHS affects KS. Compounds were retrieved from corresponding databases, and active compounds were selected based on their oral bioavailability (≥30) and drug-likeness index (≥0.18). BSHS potential proteins were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, whereas KS potential genes were obtained from GeneCards and OMIM, TTD, and DisGeNET. Gene ontology and pathway enrichment analysis were used to determine potential pathways associated with genes. The ingredients of BSHS extract were identified by the ultra-high-performance liquid chromatography coupled with quadrupole orbitrap mass spectrometry (UHPLC-Q/Orbitrap MS). The network pharmacology analyses predicted the potential underlying action mechanisms of BSHS on KS, which were further validated experimentally in the rat model of calcium oxalate kidney stones. Results: Our study found that BSHS reduced renal crystal deposition and improved renal function in ethylene glycol(EG)+ammonium chloride(AC)-induced rats, and also reversed oxidative stress levels and inhibited renal tubular epithelial cell apoptosis in rats. BSHS upregulated protein and mRNA expression of E2, ESR1, ESR2, BCL2, NRF2, and HO-1 in EG+AC-induced rat kidney while downregulating BAX protein and mRNA expression, consistent with the network pharmacology results. Discussion: This study provides evidence that BSHS plays a critical role in anti-KS via regulation of E2/ESR1/2, NRF2/HO-1, and BCL2/BAX signaling pathways, indicating that BSHS is a candidate herbal drug for further investigation in treating KS.

Condensed Fuzheng extract increases immune function in mice with cyclophosphamide-induced immunosuppression.

Our general purpose was to examine the effect of condensed Fuzheng extract (CFE) on the alleviation of immunosuppression. A mouse model of immunosuppression was established by intraperitoneal injection of CTX. A healthy control group received no CTX and no CFE; different intragastric doses of CFE were administered to three groups of mice for 28 days (4500, 2250, or 1125 mg/kg/day); a negative control received CTX alone, and a positive control received CTX and levamisole hydrochloride. We evaluated the effects of CFE on the immune system organs, cells, and molecules by comparing the different groups. CFE significantly improved immune system organs (spleen and thymus indices and histology), stimulated immune cell activities (number of white blood cells and lymphocytes, phagocytosis of mononuclear phagocytes, proliferation of splenic lymphocytes, antibody formation, and NK cell activity), and increased the levels of immunoglobulins (IgA, IgG, and IgM) and cytokines (IL-2 and IFN-γ). Thus CFE effectively alleviated CTX-mediated immunosuppression and oxidative stress and enhanced the immunological functions of mice.

Curcumin Targeting Non-Coding RNAs in Colorectal Cancer: Therapeutic and Biomarker Implications.

Colorectal cancer is one of the most common gastrointestinal malignancies, with high incidence rates, a low rate of early diagnosis, and complex pathogenesis. In recent years, there has been progress made in its diagnosis and treatment methods, but tumor malignant proliferation and metastasis after treatment still seriously affect the survival and prognosis of patients. Therefore, it is an extremely urgent task of current medicine to find new anti-tumor drugs with high efficiency and safety and low toxicity. Curcumin has shown potent anti-tumor and anti-inflammatory effects and is considered a hot spot in the research and development of anti-tumor drugs due to its advantages of precise efficacy, lower toxic side effects, and less drug resistance. Recent studies have revealed that curcumin has anti-tumor effects exerted on the epigenetic regulation of tumor-promoting/tumor-suppressing gene expression through the alteration of expression levels of non-coding RNAs (e.g., lncRNAs, miRNAs, and circRNAs). Herein, we summarize the interaction between curcumin and non-coding RNAs on the occurrence and development of colorectal cancer. The information complied in this review will serve as a scientific and reliable basis and viewpoint for the clinical application of non-coding RNAs in colorectal cancer.

Long non-coding RNAs play an important regulatory role in tumorigenesis and tumor progression through aerobic glycolysis.

Compared to normal cells, cancer cells generate ATP mainly through aerobic glycolysis, which promotes tumorigenesis and tumor progression. Long non-coding RNAs (LncRNAs) are a class of transcripts longer than 200 nucleotides with little or without evident protein-encoding function. LncRNAs are involved in the ten hallmarks of cancer, interestingly, they are also closely associated with aerobic glycolysis. However, the mechanism of this process is non-transparent to date. Demonstrating the mechanism of lncRNAs regulating tumorigenesis and tumor progression through aerobic glycolysis is particularly critical for cancer therapy, and may provide novel therapeutic targets or strategies in cancer treatment. In this review, we discuss the role of lncRNAs and aerobic glycolysis in tumorigenesis and tumor progression, and further explore their interaction, in hope to provide a novel therapeutic target for cancer treatment.

Glycyrrhetinic acid regulates impaired macrophage autophagic flux in the treatment of non-alcoholic fatty liver disease.

Macrophages are involved in hepatocyte steatosis and necroinflammation and play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Impaired autophagy function (decreased autophagy or blocked autophagic flow) leads to cell damage and death and promotes NAFLD progression. The experimental and clinical research of glycyrrhetinic acid (GA) in the treatment of NAFLD has gradually attracted attention with clear pharmacological activities such as immune regulation, antiviral, antitumor, antioxidant, liver protection, and anti-inflammatory. However, the effects of GA on the STAT3-HIF-1α pathway and autophagy in macrophages are still unclear, and its mechanism of action in the treatment of NAFLD remains to be further elucidated. We constructed a NAFLD mouse model through a high-fat and high-sugar diet to investigate the therapeutic effects of GA. The results showed that GA reduced weight, improved the pathological changes and hepatic lipid deposition of liver, and abnormally elevated the levels of serum biochemical (AST, ALT, TG, T-CHO, LDL-C, and HDL-C) and inflammatory indexes (IL-1ß, IL-4, IL-6, MCP-1, and TNF-α) in NAFLD mice. Further examination revealed that GA ameliorates excessive hepatic macrophage infiltration and hepatocyte apoptosis. The results of the cell experiments further elaborated that GA modulated the PA-induced macrophage STAT3-HIF-1α pathway and ameliorated impaired autophagic flux (blockade of autophagosome-lysosome fusion) and overactivation of inflammation. Excessive hepatocyte apoptosis caused by the uncontrolled release of inflammatory cytokines was also suppressed by GA. Conclusion: This study demonstrated that GA could regulate the STAT3-HIF-1α pathway of macrophages, ameliorate the impaired autophagy flux, and reduce the excessive production of inflammatory cytokines to improve the excessive apoptosis of liver cells, thus playing a therapeutic role on NAFLD.