Metabolic disorders in prediabetes: From mechanisms to therapeutic management.

Diabetes, one of the world's top ten diseases, is known for its high mortality and complication rates and low cure rate. Prediabetes precedes the onset of diabetes, during which effective treatment can reduce diabetes risk. Prediabetes risk factors include high-calorie and high-fat diets, sedentary lifestyles, and stress. Consequences may include considerable damage to vital organs, including the retina, liver, and kidneys. Interventions for treating prediabetes include a healthy lifestyle diet and pharmacological treatments. However, while these options are effective in the short term, they may fail due to the difficulty of long-term implementation. Medications may also be used to treat prediabetes. This review examines prediabetic treatments, particularly metformin, glucagon-like peptide-1 receptor agonists, sodium glucose cotransporter 2 inhibitors, vitamin D, and herbal medicines. Given the remarkable impact of prediabetes on the progression of diabetes mellitus, it is crucial to intervene promptly and effectively to regulate prediabetes. However, the current body of research on prediabetes is limited, and there is considerable confusion surrounding clinically relevant medications. This paper aims to provide a comprehensive summary of the pathogenesis of pre-diabetes mellitus and its associated therapeutic drugs. The ultimate goal is to facilitate the clinical utilization of medications and achieve efficient and timely control of diabetes mellitus.

Natural herb wormwood-based microneedle array for wound healing.

Artemisia argyi, commonly known as wormwood, is a traditional Chinese herbal food and medicine celebrated for its notable antibacterial and anti-inflammatory properties. This study explores a novel delivery method for wormwood, aiming for more convenient and versatile applications. Specifically, we present the first investigation into combining wormwood with microstructures to create a microneedle (MN) patch for wound healing. The wormwood microneedle (WMN) patch is formulated with milled wormwood sap, calcium carbonate, and sodium hyaluronate. The addition of 0.3% (w/v) sodium hyaluronate enhances the mechanical strength of the WMN patch. Pectin, derived from wormwood, is combined with calcium carbonate to create a gelatinous and solidified substance. The WMN patch exhibits a well-defined shape and sufficient mechanical strength to penetrate the epidermis, as confirmed by our results. In vitro experiments demonstrate the biocompatibility of the WMN patch with fibroblasts and highlight its antibacterial and anti-inflammatory properties. Furthermore, the patch facilitates collagen deposition at the wound site. In an excisional rat model, the WMN patch significantly accelerates the wound closure rate compared to the control group. Our findings suggest that the WMN patch has the potential to serve as a natural treatment for wound healing. Additionally, this approach can be extended to other biologically active substances with similar physiochemical characteristics in future applications.

Corrigendum: A novel Chinese herbal and corresponding chemical formula for cancer treatment by targeting tumor maintenance, progression, and metastasis.

[This corrects the article DOI: 10.3389/fphar.2022.907826.].

Anammox-Mediated Hydroxyapatite Granules: Physicochemical Properties, 3D Hierarchy, and Biofilm Thickness.

Biomineralization inspired the development of simultaneous biological transformations and chemical precipitation for simultaneous nitrogen removal and phosphorus recovery from wastewater, which could compensate for the incapacity of phosphorus management in the new biological route of anaerobic ammonium oxidation (anammox). In this study, we strengthened anammox-mediated biomineralization by long-term feeding of concentrated N, P, and Ca substrates, and a self-assembled matrix of anammox bacteria and hydroxyapatite (HAP) was fabricated in a granular shape, defined as HAP-anammox granules. HAP was identified as the dominant mineral using elemental analysis, X-ray diffraction, and Raman spectroscopy. The intensive precipitation of HAP resulted in a higher inorganic fraction and substantially improved settleability of anammox biomass, which facilitated HAP precipitation by acting as nucleation and metabolically elevated pH. By using X-ray microcomputed tomography, we visually represented the hybrid texture of interwoven HAP pellets and biomass, the core-shell layered architecture of different-sized HAP-anammox granules, and their homogeneously regulated thickness of the outer biofilm (from 118 to 635 µm). This unique architecture endows HAP-anammox granules with outstanding settleability, active biofilm, and tightly bonded biofilm with the carrier, which may explain the excellent performance of these HAP-anammox granules under various challenging operational conditions in previous studies.

Clinical efficacy of weight loss herbal intervention therapy and lifestyle modifications on obesity and its association with distinct gut microbiome: A randomized double-blind phase 2 study.

Goals: To assess the efficacy and safety of Chinese Medicine Prescription "W-LHIT" in subjects with simple obesity, and to explore its potential mechanism of action. Methods: Thirty-seven patients aged 18 to 60 from Wei-En hospital (Weifang City, Shandong, China), participated in a double blinded, placebo-controlled study. Subjects were randomly divided into 2 groups, 18 in treatment and 19 in placebo group. The treatment group took the "W-LHIT" capsules for two months, while the control group received placebo capsules. Both groups accepted healthy lifestyle education materials. After a 2-month treatment, the placebo group transferred to open-label treatment after unblinding. Results: 72.22% participants in the treatment group lost more than 5% of their body weight, compared with 36.84% in the placebo group (p < 0.001). Body weight loss and body mass index reduction of the treatment group were also significantly higher than those of the placebo group (p < 0.05). These changes were accompanied by increased abundance of Akkermansia muciniphila and Enterococcus faecium, and decreased abundance of Proteobacteria in gut microbiota. Furthermore, the treatment group also showed improvement in obesity-related comorbidities such as hypertension and elevation of liver enzymes. No serious adverse reactions were found during the study period. Weight did not rebound at a follow-up visit 2 months after treatment. Conclusion: W-LHIT significantly improved body weight and comorbid conditions without obvious adverse reaction or rebound weight gain. These effects were associated with increased abundance of probiotics in gut microbiota. W-LHIT may have a potential for treating obesity in conjunction with healthy lifestyle modifications.

Anammox upflow hybrid reactor: Nitrogen removal performance and potential for phosphorus recovery.

Echoing to the call of recovering high-value-added chemicals from wastewater and achieving carbon-neutral operation in wastewater treatment, an anammox upflow hybrid reactor was successfully applied for nitrogen removal, and the potential for phosphorus recovery was put forward. Moreover, the spatial pattern of removal capacities, and distribution of biomass and HAP precipitates were recognized and demonstrated as height-oriented. The intensity of HAP precipitates was highly consistent with the amount of anammox biomass and the relative abundance of the Candidatus Kuenenia, indicating that HAP formation was encouraged by the anammox reaction itself and heterogeneous nucleation induced by organic matters (proteins and polysaccharides). The fixed bed also played an important role in immobilizing the anammox biomass, secreted organic matrix, and HAP precipitates. This finding also provoked the thought that in the anammox process, HAP precipitation was more achievable, effective and practicable using the fixed-carrier system.

Decoupling of N and P aggravated upward along food chains in an urban river ecosystem.

Anthropogenic input of nutrient has profoundly influenced water quality and aquatic organisms, however, large and unbalanced nitrogen (N) and phosphorus (P) inputs (decoupling) can lead to a range of ecological health problems such as eutrophication. Whether and how the decoupling varies along the aquatic food chain remains poorly addressed. Here we chose an urban river ecosystem in the cosmopolis region of Beijing, with reclaimed water as the entire replenishment water source over 20 years, to demonstrate the decoupling pattern of N vs P across trophic levels. Results showed that organism C, N and P concentration increased, but N:P ratio decreased upward along the food chains, suggesting that this decoupling of N and P increased as trophic level ascends. Compared with natural freshwater ecosystem, the decoupling of N and P was aggravated in the reclaimed water river. Moreover, the homeostasis of N and P were higher at higher relative to lower trophic levels, and higher in macro-food chain relative to planktonic food chain. This study, for the first time, revealed the increasing decoupling of N vs P upward along the major food chains in an urban aquatic ecosystem, and could improve the understanding of nutrient cycling at the food chain level under human disturbance, and provide useful information for ecological restoration and eutrophication control of urban wetlands replenished with reclaimed water.

Environmental Variables Including Heavy Metals Significantly Shape the Soil Bacterial Community Structure in the Tatun Volcano Group, Northern Taiwan.

Recent studies suggested the presence of magma chambers from the Tatun volcano group under northern Taiwan's surface, the result of episodic volcanism for 0.2-2.8 million years. However, the microbial community in volcanic soil has not yet been characterized. Therefore, the present study investigated the spatial distribution of microbial communities and their relationships with environmental variables, including heavy metals. Next-generation sequencing was used to analyze the microbial community structures in three areas with different land uses: Lengshuikeng (recreational area), Zhuzihu (agricultural area), and Huangzuishan (conservation area). High contents of environmental factors, such as nitrogen (0.46-1.14%) and phosphorus (2.01-13.88 ppm), were detected. Large concentrations of heavy metals, such as copper (55.90-127.60 ppm) and zinc (36.13-147.73 ppm), were found among the three sites, whereas those of lead (83.13 ppm) and chromium (48.33 ppm) were higher in the Zhuzihu area. The most prevalent phylum across all sites was Proteobacteria, followed by Actinobacteria, Acidobacteria, and Chloroflexi, while the most abundant bacterial species was Koribacteraceae: NA_01, followed by Cyanobacteria: NA. A network ana-lysis showed that Koribacteracea: NA_01 positively correlated with bacterial groups, including Flavisolibacter sp., Oxalobacteraceae: NA, and Actinomycetales: NA_01. Based on Shannon and Simpson's diversity indices, the diversity of bacteria was significantly less in the Huangzuishan area than in the Lengshuikeng and Zhuzihu areas. Bacterial assemblages also significantly differed (P<0.05) among the three sites. The present results provide clear evidence to show that environmental variables, including heavy metals, are key factors affecting the bacterial community structure in volcanic soil.

Targeted Mitochondrial Epigenetics: A New Direction in Alzheimer's Disease Treatment.

Mitochondrial epigenetic alterations are closely related to Alzheimer's disease (AD), which is described in this review. Reports of the alteration of mitochondrial DNA (mtDNA) methylation in AD demonstrate that the disruption of the dynamic balance of mtDNA methylation and demethylation leads to damage to the mitochondrial electron transport chain and the obstruction of mitochondrial biogenesis, which is the most studied mitochondrial epigenetic change. Mitochondrial noncoding RNA modifications and the post-translational modification of mitochondrial nucleoproteins have been observed in neurodegenerative diseases and related diseases that increase the risk of AD. Although there are still relatively few mitochondrial noncoding RNA modifications and mitochondrial nuclear protein post-translational modifications reported in AD, we have reason to believe that these mitochondrial epigenetic modifications also play an important role in the AD process. This review provides a new research direction for the AD mechanism, starting from mitochondrial epigenetics. Further, this review summarizes therapeutic approaches to targeted mitochondrial epigenetics, which is the first systematic summary of therapeutic approaches in the field, including folic acid supplementation, mitochondrial-targeting antioxidants, and targeted ubiquitin-specific proteases, providing a reference for therapeutic targets for AD.

Combined Effects of Tanshinone IIA and an Autophagy Inhibitor on the Apoptosis of Leukemia Cells via p53, Apoptosis-Related Proteins and Oxidative Stress Pathways.

BACKGROUND: Acute myeloid leukemia (AML) is a kind of hematopoietic malignancy with limited response and acquired resistance to therapy. Inducing apoptosis and inhibiting autophagy in tumor cells is a combinational strategy for the development of anticancer therapeutics. Tanshinone IIA (TAIIA) is one of the major ingredients in Salvia miltiorrhiza, which is the most prescribed herb for the treatment of AML in Taiwan. Therefore, this study aimed to delineate the anticancer effects of TAIIA and its effect when combined with an autophagy inhibitor to treat AML. METHODS: The anticancer effects of a combination of TAIIA and the autophagy inhibitor 3-methladenine (3MA) on the human monocytic leukemia cell line THP-1 were explored. The apoptosis and cell cycle of the leukemia cells were examined by Annexin V and propidium iodide staining and analyzed by flow cytometry. The oxidative stress level was determined by a malondialdehyde (MDA) colorimetric assay, nitric oxide colorimetric assay and glutathione peroxidase (GPx) colorimetric assay. The expression of apoptosis-related proteins was determined by western blotting. RESULTS: TAIIA treatment significantly induced apoptosis via increased p53, Bax/Bcl, PARP, and caspase-3 signals and oxidative stress by enhancing MDA and nitrate/nitrite production and reducing GPx activity in THP-1 cells in a dose-dependent and time-dependent manner. The combination of the autophagy inhibitor 3MA enhanced TAIIA-induced apoptosis via the p53, Bax/Bcl, PARP, caspase-3, and oxidative stress pathways in THP-1 cells. CONCLUSION: The results suggest that TAIIA and autophagy inhibitors have combined effects on the apoptosis of leukemia cells, thus representing a novel and effective combination with the potential for application as a clinical therapy for AML.

Fitness Promotion in a Jump Rope-Based Homework Intervention for Middle School Students: A Randomized Controlled Trial.

Physical activity (PA) homework offers a promising approach for students to be physically active after school. The current study aims to provide holistic insights into PA homework design and the effects of implementation in practice. In total, ninety-three middle school students were randomly assigned to a homework group (HG) or control group (CG). Participants in HG (n = 47) were requested to complete jump rope homework three times per week for 12 weeks, while their counterparts in CG attended one health education class every week. A homework sheet was used to provide instructions and record information for exercise behaviors during homework completion. Physical fitness tests were conducted to investigate the effects of the jump rope homework on the physical fitness of middle school students. After the intervention, participants in HG reported moderate to vigorous PA during jump rope exercise. The average duration for each practice was approximately 48 min. The returned homework sheets accounted for 86.88% of all homework assignments, indicating a good completion rate. Compared with their counterparts in CG, participants performing jump rope exercise indicated greater improvement in speed, endurance, power, and core muscular endurance. Jump rope homework strengthened physical fitness for middle school students, which provided a valuable addition to comprehensive school PA practice.

A Novel Chinese Herbal and Corresponding Chemical Formula for Cancer Treatment by Targeting Tumor Maintenance, Progression, and Metastasis.

We characterized a so-called "heirloom recipe" Chinese herbal formula (temporarily named Formula X) that contains five Chinese medical botanical drugs, Huang-Lian (Coptis chinensis Franch. [Ranunculaceae]), Huang-Qin (Scutellaria baicalensis Georgi [Lamiaceae]), Bai-Wei (Vincetoxicum atratum (Bunge) C. Morren and Decne. [Apocynaceae]), E-Zhu (Curcuma aromatica Salisb. [Zingiberaceae]) and Bai-Zhu (Atractylodes macrocephala Koidz. [Asteraceae]). Formula X inhibited the growth of various cancer cells and decreased the expression levels of a panel of proteins, including CD133, Myc, PD-L1, and Slug, in cancer cells. We further found that the inhibition of growth and protein expression were exerted by Huang-Lian, Huang-Qin, and Bai-Wei (formula HHB), which exhibited the same biological effects as those of Formula X. Furthermore, we selected three active chemicals, berberine, baicalin, and saponin from Huang-Lian, Huang-Qin, and Bai-Wei, respectively, to produce a chemical formulation (formula BBS), which exhibited similar effects on cell growth and protein expression as those induced by formula HHB. Both the formulae HHB and BBS suppressed tumor growth in an animal study. Moreover, they decreased the protein levels of Myc and PD-L1 in tumor cells in vivo. In summary, we established a novel Chinese herbal formula and a chemical formula that targeted three important processes, tumor maintenance (tumor stem cells), progression, and metastasis, and that influenced the response of tumors to host immunosuppression, for the potentially effective treatment of cancer patients.

Inhibition of miRNA-1-Mediated Inflammation and Autophagy by Astragaloside IV Improves Lipopolysaccharide-Induced Cardiac Dysfunction in Rats.

Introduction: Astragaloside IV (AS-IV) is one of the main active components isolated from the traditional Chinese medicinal herb, Astragalus membranaceus. The present study was designed to investigate whether the regulation of microRNA-1 (miR-1)-mediated inflammation and autophagy contributes to the protective effect of AS-IV against cardiac dysfunction in rats treated with lipopolysaccharides (LPS). Methods: Animal model of cardiac dysfunction in rats or cellular model of injured H9c2 heart cell line was established by using LPS. Echocardiography, electron microscopy, enzyme-linked immunosorbent assay, immunofluorescence, quantitative RT-PCR, and Western blotting were used to determine the cardiac function and expression of inflammation- and autophagy-related proteins at both the mRNA and protein levels. Results: LPS caused cardiac dysfunction in rats or injury in H9c2 cells and induced inflammation and autophagy. Compared with LPS treatment, AS-IV treatment attenuated cardiac dysfunction or cell injury, accompanied by inhibition of inflammation and autophagy. However, the miR-1 mimics partly abolished the effects of AS-IV. In addition, the effect of the miR-1 inhibitor was similar to that of AS-IV in the LPS model. Further analyses showed that AS-IV treatment decreased the mRNA expression of miR-1 in the heart tissue of rats and H9c2 cells treated with LPS. Conclusion: These results suggest that AS-IV attenuated cardiac dysfunction caused by LPS by inhibiting miR-1-mediated inflammation and autophagy, thereby providing a novel mechanism for the protection against cardiac diseases.

Indigodole E from Strobilanthes cusia exhibits anti-IL-17A effect.

One new indazole alkaloid, indigodole E (1), was isolated from a traditional Chinese medicine Qing Dai prepared from the aerial parts of Strobilanthes cusia. The structure of 1 was elucidated by NMR, MS, UV, and IR spectra as well as optical rotation. Additionally, compound 1 could obviously inhibit not only IL-17A protein production at concentrations from 1.25 to 2.5 µg/mL, but also IL-17 gene expression at concentrations from 5.0 to 10.0 µg/mL without cytotoxicity toward Th17 and Jukat cells, respectively. Overall, indazole analogue 1 could be the anti-IL 17 A contributor of Qing Dai in this investigation.

Cordycepin prevents and ameliorates experimental autoimmune encephalomyelitis by inhibiting leukocyte infiltration and reducing neuroinflammation.

Multiple sclerosis (MS) is a neuroinflammatory autoimmune disease characterized by multifocal perivascular infiltration of immune cells in the central nervous system (CNS). Cordycepin (3'-deoxyadenosine), an adenosine analogue initially extracted from the fungus Cordyceps militarisa, is one of the candidates that has multiple actions. We investigated that cordycepin attenuated the activation of LPS-induced mouse bone marrow-derived dendritic cells (BMDCs) and human monocyte-derived dendritic cells (MoDCs) through the inhibition of the AKT, ERK, NFκB, and ROS pathways and impaired the migration of BMDCs through the downregulation of adhesion molecules and chemokine receptors in vitro. In experimental autoimmune encephalomyelitis (EAE) model, preventive treatment with cordycepin decreased the expression of trafficking factors in the CNS, inhibited the secretion of inflammatory cytokines (IFN-γ, IL-6, TNF-α, and IL-17), and attenuated disease symptoms. A chemokine array indicated that cordycepin treatment reversed the high levels of CCL6, PARRES2, IL-16, CXCL10, and CCL12 in the brain and spinal cord of EAE mice, consistent with the RNA-seq data. Moreover, cordycepin suppressed the release of neuroinflammatory cytokines by activated microglial cells, macrophages, Th17 cells, Tc1 cells, and Th1 cells in vitro. Furthermore, cordycepin treatment exerted therapeutic effects on attenuating the disease severity in the early disease onset stage and late disease progression stage. Our study suggests that cordycepin treatment may not only prevent the occurrence of MS by inhibiting DC activation and migration but also potentially ameliorates the progression of MS by reducing neuroinflammation, which may provide insights into the development of new approaches for the treatment of MS.

Evaluation of Activated Carbon Treatment on Overcoming the Interference of Rivaroxaban on the Detection of Functional Lupus Anticoagulant.

OBJECTIVE: The aim of this study was to review the role of activated carbon (AC) in eliminating the interference of rivaroxaban in the detection of lupus anticoagulants (LAs). METHODS: Normal pooled plasma was obtained as group N1, group N2 took 1 mL plasma from N1 and added AC, group N3 was prepared by mixing normal plasma with rivaroxaban, and group N3 was treated with AC according to our procedure, as group N4. Plasma from 22 patients was collected before and 6-12 h after rivaroxaban therapy, described as group P1 and group P2, respectively, and 1 mL plasma was taken from group P2 and treated with AC, as group P3. Anti-Xa and diluted Russell's viper venom time (dRVVT)/silica clotting time (SCT) index in each group were measured and compared. RESULTS: Rivaroxaban concentrations and anti-Xa had high intercorrelations in group N3, and the levels of anti-Xa and dRVVT/SCT index had high intercorrelations. After treatment with AC, influence of rivaroxaban was removed, with LA and coagulation factor assays not influenced. Rivaroxaban administration could affect LA assay results in patients, with all LA results increased. After treatment with AC, results of anti-Xa and LA tests recovered to the level before rivaroxaban therapy. CONCLUSIONS: We proposed a reference procedure for the LA detection of patients using rivaroxaban by AC, and activated carbon was proven to be a simple product to eliminate the interference of rivaroxaban.

Anti-IgE effect of small-molecule-compound arctigenin on food allergy in association with a distinct transcriptome profile.

BACKGROUND: Excessive production of IgE plays a major role in the pathology of food allergy. In an attempt to identify anti-IgE natural products, Arctium Lappa was one of the most effective herbs among approximately 300 screened medicinal herbs. However, little is known about its anti-IgE compounds. OBJECTIVE: To identify compounds from Arctium Lappa for targeted therapy on IgE production and explore their underlying mechanisms. METHODS: Liquid-liquid extraction and column chromatographic methods were used to purify the compounds. IgE inhibitory effects were determined on IgE-producing human myeloma U266 cells, peanut-allergic murine model and PBMCs from food-allergic patients. Genes involved in IgE inhibition in PBMCs were studied by RNA sequencing. RESULTS: The main compounds isolated were identified as arctiin and arctigenin. Both compounds significantly inhibited IgE production in U266 cells, with arctigenin the most potent (IC50=5.09µg/mL). Arctigenin (at a dose of 13 mg/kg) markedly reduced peanut-specific IgE levels, blocked hypothermia and histamine release in a peanut-allergic mouse model. Arctigenin also significantly reduced IgE production and Th2 cytokines (IL-5, IL-13) by PBMCs. We found 479 differentially expressed genes in PBMCs with arctigenin treatment (p < .001 and fold-change ≥1.5), involving 24 gene ontology terms (p < .001, FDR <0.05); cell division was the most significant. Eleven genes including UBE2C and BCL6 were validated by qPCR. CONCLUSION: Arctigenin markedly inhibited IgE production in U266 cells, peanut-allergic murine model and PBMCs from allergic patients by down-regulating cell division, cell cycle-related genes and up-regulating anti-inflammatory factors.

Analyzing the multi-target pharmacological mechanism of folium Artemisia argyi acting on breast cancer: a network pharmacology approach.

Background: Folium Artemisia argyi (FAA) is a traditional Chinese herbal medicine that is widely used in the clinic. However, the underlying mechanisms of its anticancer effects have not been fully elucidated. Methods: In this study, we applied a network pharmacology approach to identify the potential mechanisms of FAA against breast cancer. To be specific, we screened the active ingredients and potential targets of the FAA through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Meanwhile, we employed the oral bioavailability (OB) and drug-likeness (DL) to search for potential bioactive compounds of FAA. Breast cancer-related target genes data were gathered from the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases, and the protein-protein interaction (PPI) data were acquired from the Search Tool for the Retrieval of Interacting Genes (STRING) database. In addition, we constructed the network and performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Enrichment Analysis. Results: We obtained a total of nine active ingredients and 236 potential targets from FAA to construct a network, which showed that quercetin served as the major ingredient in FAA. AKT1 (RAC-alpha serine/threonine-protein kinase), MYC (Myc proto-oncogene protein), CASP3 (Caspase-3), EGFR (Epidermal growth factor receptor), JUN (Transcription factor AP-1), CCND1 (G1/S-specific cyclin-D1), VEGFA (Vascular endothelial growth factor A), ESR1 (Estrogen receptor), MAPK1 (Mitogen-activated protein kinase 1), and EGF (pro-epidermal growth factor) were identified as key targets of FAA in the treatment of breast cancer. The PPI cluster demonstrated that AKT1 was the seed in this cluster, indicating that AKT1 played a crucial role in connecting other nodes in the PPI network. This enrichment demonstrated that FAA was highly related to signal transduction, endocrine system, replication and repair, as well as cell growth and death. The enrichment results also verified that the underlying mechanisms of FAA against breast cancer might be attributed to the coordinated regulation of several cancer-related pathways, such as the MAPK and mammalian target of rapamycin (mTOR) signaling pathways, among others. Conclusions: This study identified the potential targets and pathways of FAA in the treatment of breast cancer using a network pharmacology approach, and systematically elucidated the mechanisms of FAA in the treatment of breast cancer.

Butanol Purified Food Allergy Herbal Formula-2 Has an Immunomodulating Effect ex-vivo in Pediatric Crohn's Disease Subjects.

Background: TNF-α has a major role in the pathogenesis of Crohn's disease (CD). In contrast, GM-CSF may be beneficial for its anti-inflammatory role in a subset of patients with CD with antibodies against GM-CSF as seen in prior trials of GM-CSF which resulted in clinical improvement in CD. We developed butanol purified Food Allergy Herbal Formula-2 (B-FAHF-2) by refining FAHF-2. FAHF-2 suppressed TNF-α production by human peripheral blood mononuclear cells (PBMCs) and colonic mucosa, and abrogated colitis in a murine model. We sought to examine the effect of B-FAHF-2 and the herbs that comprise it on TNF-α and GM-CSF production as a potential herbal therapy for the treatment of CD. Methods: B-FAHF-2 was examined using high pressure liquid chromatography (HPLC) and compared to the original formulation, FAHF-2. PBMCs from pediatric patients with CD were cultured with lipopolysaccharide and B-FAHF-2, individual herbs or medium alone. Colonic biopsy specimens were cultured with or without B-FAHF-2. TNF-α and GM-CSF were measured by enzyme-linked immunosorbent assay (ELISA). B-FAHF-2 efficacy was tested in vivo in the CD45Rbhi transfer model. Results: B-FAHF-2 had a similar HPLC fingerprint as FAHF-2 but decreased TNF-α production by PBMCs and colonic mucosa from pediatric CD subjects at 20% of the FAHF-2 dose. B-FAHF-2 increased GM-CSF production by PBMCs and colonic mucosa from pediatric CD subjects including those with antibodies to GM-CSF. Of B-FAHF-2's herbal constituents, only Huang Bai suppressed TNF-α and increased GM-CSF production. In the murine model, B-FAHF-2 treatment alleviated colitis. Conclusions: B-FAHF-2 decreased TNF-α production by PBMCs and colonic mucosa from pediatric subjects at a lower dose than FAHF-2. B-FAHF-2 also increased GM-CSF production by PBMCs independent of antibodies. B-FAHF-2 may have a benefit in CD patients.

Fat-1 Transgenic Mice With Augmented n3-Polyunsaturated Fatty Acids Are Protected From Liver Injury Caused by Acute-On-Chronic Ethanol Administration.

Alcohol-associated liver disease (ALD) is the leading cause of liver disease worldwide, and alcohol-associated hepatitis (AH), a severe form of ALD, is a major contributor to the mortality and morbidity due to ALD. Many factors modulate susceptibility to ALD development and progression, including nutritional factors such as dietary fatty acids. Recent work from our group and others showed that modulation of dietary or endogenous levels of n6-and n3-polyunsaturated fatty acids (PUFAs) can exacerbate or attenuate experimental ALD, respectively. In the current study, we interrogated the effects of endogenous n3-PUFA enrichment in a mouse model which recapitulates features of early human AH using transgenic fat-1 mice which endogenously convert n6-PUFAs to n3-PUFAs. Male wild type (WT) and fat-1 littermates were provided an ethanol (EtOH, 5% v/v)-containing liquid diet for 10 days, then administered a binge of EtOH (5 g/kg) by oral gavage on the 11th day, 9 h prior to sacrifice. In WT mice, EtOH treatment resulted in liver injury as determined by significantly elevated plasma ALT levels, whereas in fat-1 mice, EtOH caused no increase in this biomarker. Compared to their pair-fed controls, a significant EtOH-mediated increase in liver neutrophil infiltration was observed also in WT, but not fat-1 mice. The hepatic expression of several cytokines and chemokines, including Pai-1, was significantly lower in fat-1 vs WT EtOH-challenged mice. Cultured bone marrow-derived macrophages isolated from fat-1 mice expressed less Pai-1 and Cxcl2 (a canonical neutrophil chemoattractant) mRNA compared to WT when stimulated with lipopolysaccharide. Further, we observed decreased pro-inflammatory M1 liver tissue-resident macrophages (Kupffer cells, KCs), as well as increased liver T regulatory cells in fat-1 vs WT EtOH-fed mice. Taken together, our data demonstrated protective effects of endogenous n3-PUFA enrichment on liver injury caused by an acute-on-chronic EtOH exposure, a paradigm which recapitulates human AH, suggesting that n3-PUFAs may be a viable nutritional adjuvant therapy for this disease.