Dietary Zinc-Loaded Montmorillonite Supplementation Improves Growth Performance, Diarrhea, Intestinal Barrier Function and Regulating Gut Microbiota in Weaned Piglets.

This experiment was conducted to investigate whether low-dose zinc-loaded montmorillonite (Zn-MMT) could be used as a potential alternative for high-dose conventional ZnO in preventing diarrhea in weaned piglets. In total, 180 piglets were randomly divided to receive either of the three treatments, with six replicates per treatment and 10 piglets per replicate. The treatments were the control group (CT), the Zn-MMT group (ZM), and the ZnO group (ZO). Compared with the CT group, the ZM and ZO groups exhibited increased ADG at 14-28 days and during the whole period (p < 0.05), and a significantly decreased diarrhea rate during the whole period (p < 0.01). The activities of T-AOC and SOD were significantly increased (p < 0.05), whereas the MDA level decreased (p < 0.05) in the serum and colonic mucosa of Zn-MMT- and ZnO-fed piglets. Dietary supplementation with Zn-MMT and ZnO decreased the contents of IFN-γ, TNF-α, IL-1ß, IL-6, DAO, and LPS in the serum and colonic mucosa (p < 0.01), and increased the IL-10 level (p < 0.01). The relative mRNA expressions of TLR-4, claudin 2, Pbd1, and MUC2 were elevated in the colonic mucosa of the Zn-MMT and ZnO groups (p < 0.05). 16S rRNA gene sequencing analysis revealed that the abundances of Proteobacteria and Actinobacteria in the ileum and the populations of Ruminnococcus and Faecalibacterium in the cecum were higher in the CT group than in the other two groups. Collectively, dietary addition of Zn from Zn-MMT was comparable to Zn from ZnO for increasing growth performance, alleviating diarrhea, as well as improving mucosal barrier integrity, and regulating the gut microbiota of weaned piglets.

Natural flavonoids derived from herbal medicines are potential anti-atherogenic agents by inhibiting oxidative stress in endothelial cells.

As the common pathological basis of various cardiovascular diseases, the morbidity and mortality of atherosclerosis (AS) have increased in recent years. Unfortunately, there are still many problems in the treatment of AS, and the prevention and treatment of the disease is not ideal. Up to now, the occurrence and development of AS can roughly include endothelial cell dysfunction, vascular smooth muscle cell proliferation, inflammation, foam cell production, and neoangiogenesis. Among them, endothelial dysfunction, as an early event of AS, plays a particularly important role in promoting the development of AS. In addition, oxidative stress occurs throughout the causes of endothelial dysfunction. Some previous studies have shown that flavonoids derived from herbal medicines are typical secondary metabolites. Due to its structural presence of multiple active hydroxyl groups, it is able to exert antioxidant activity in diseases. Therefore, in this review, we will search PubMed, Web of Science, Elesvier, Wliey, Springer for relevant literature, focusing on flavonoids extracted from herbal medicines, and summarizing how they can prevent endothelial dysfunction by inhibiting oxidative stress. Meanwhile, in our study, we found that flavonoid represented by quercetin and naringenin showed superior protective effects both in vivo and in vitro, suggesting the potential of flavonoid compounds in the treatment of AS.

New insights into the persistent effect of transient cinnamaldehyde vapor treatment on the growth and aflatoxin synthesis of Aspergillus flavus.

The antimicrobial effects of continuous treatment with essential oils (EOs) in both liquid and gaseous phases have been intensively studied. Due to their rapid volatility, the effects of EOs on microorganisms after transient treatment are also worth exploring. In this work, the persistent effects of cinnamaldehyde (CA) vapor on Aspergillus flavus were detected by a series of biochemical analyses. Transcriptome analysis was also conducted to study the gene expression changes between recovered and normal A. flavus. When CA vapor was removed, biochemical analyses showed that the oxidative stress induced by the antimicrobial atmosphere was alleviated, and almost all the damaged functions were restored apart from mitochondrial function. Remarkably, the suppressed aflatoxin production intensified, which was confirmed by the up-regulation of most genes in the aflatoxin synthetic gene cluster, the velvet-related gene FluG and the aflatoxin precursor acetyl-CoA. Transcriptomic analysis also demonstrated significant changes in secondary metabolism, energy metabolism, oxidative stress, and amino acid metabolism in the recovery group. Taken together, these findings provide new insights into the mechanisms underlying the response of A. flavus to CA vapor treatment and will guide the rational application of EOs.

Targeting matrix metalloproteases: A promising strategy for herbal medicines to treat rheumatoid arthritis.

As a type of metalloproteinase, matrix metalloproteinases (MMPs) can be divided into collagenase, gelatinase, stromelysins, membrane-type (MT)-MMPs and heterogeneous subgroups according to their structure and function. MMP contents in the human body are strictly regulated, and their synthesis, activation and inhibition processes should be kept in a certain balance; otherwise, this would result in the occurrence of various diseases. Rheumatoid arthritis (RA) is a known immune-mediated systemic inflammatory disease that is affected by a variety of endogenous and exogenous factors. In RA development, MMPs act as important mediators of inflammation and participate in the degradation of extracellular matrix substrates and digestion of fibrillar collagens, leading to the destruction of joint structures. Interestingly, increasing evidence has suggested that herbal medicines have many advantages in RA due to their multitarget properties. In this paper, literature was obtained through electronic databases, including the Web of Science, PubMed, Google Scholar, Springer, and CNKI (Chinese). After classification and analysis, herbal medicines were found to inhibit the inflammatory process of RA by regulating MMPs and protecting joint structures. However, further preclinical and clinical studies are needed to support this view before these herbal medicines can be developed into drugs with actual application to the disease.

Regulation of mitochondrial dysfunction induced cell apoptosis is a potential therapeutic strategy for herbal medicine to treat neurodegenerative diseases.

Neurodegenerative disease is a progressive neurodegeneration caused by genetic and environmental factors. Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) are the three most common neurodegenerative diseases clinically. Unfortunately, the incidence of neurodegenerative diseases is increasing year by year. However, the current available drugs have poor efficacy and large side effects, which brings a great burden to the patients and the society. Increasing evidence suggests that occurrence and development of the neurodegenerative diseases is closely related to the mitochondrial dysfunction, which can affect mitochondrial biogenesis, mitochondrial dynamics, as well as mitochondrial mitophagy. Through the disruption of mitochondrial homeostasis, nerve cells undergo varying degrees of apoptosis. Interestingly, it has been shown in recent years that the natural agents derived from herbal medicines are beneficial for prevention/treatment of neurodegenerative diseases via regulation of mitochondrial dysfunction. Therefore, in this review, we will focus on the potential therapeutic agents from herbal medicines for treating neurodegenerative diseases via suppressing apoptosis through regulation of mitochondrial dysfunction, in order to provide a foundation for the development of more candidate drugs for neurodegenerative diseases from herbal medicine.

Lactose azocalixarene drug delivery system for the treatment of multidrug-resistant pseudomonas aeruginosa infected diabetic ulcer.

Diabetic wound is one of the most intractable chronic wounds that is prone to bacterial infection. Hypoxia is an important feature in its microenvironment. However, it is challenging for antimicrobial therapy to directly apply the existing hypoxia-responsive drug delivery systems due to the active targeting deficiency and the biofilm obstacle. Herein, we customizes a hypoxia-responsive carrier, lactose-modified azocalix[4]arene (LacAC4A) with the ability to actively target and inhibit biofilm. By loading ciprofloxacin (Cip), the resultant supramolecular nanoformulation Cip@LacAC4A demonstrates enhanced antibacterial efficacy resulting from both the increased drug accumulation and the controlled release at the site of infection. When applied on diabetic wounds together with multidrug-resistant Pseudomonas aeruginosa infection in vivo, Cip@LacAC4A induces definitely less inflammatory infiltration than free Cip, which translates into high wound healing performance. Importantly, such design principle provides a direction for developing antimicrobial drug delivery systems.

Mining on Alzheimer's diseases related knowledge graph to identity potential AD-related semantic triples for drug repurposing.

BACKGROUND: To date, there are no effective treatments for most neurodegenerative diseases. Knowledge graphs can provide comprehensive and semantic representation for heterogeneous data, and have been successfully leveraged in many biomedical applications including drug repurposing. Our objective is to construct a knowledge graph from literature to study the relations between Alzheimer's disease (AD) and chemicals, drugs and dietary supplements in order to identify opportunities to prevent or delay neurodegenerative progression. We collected biomedical annotations and extracted their relations using SemRep via SemMedDB. We used both a BERT-based classifier and rule-based methods during data preprocessing to exclude noise while preserving most AD-related semantic triples. The 1,672,110 filtered triples were used to train with knowledge graph completion algorithms (i.e., TransE, DistMult, and ComplEx) to predict candidates that might be helpful for AD treatment or prevention. RESULTS: Among three knowledge graph completion models, TransE outperformed the other two (MR = 10.53, Hits@1 = 0.28). We leveraged the time-slicing technique to further evaluate the prediction results. We found supporting evidence for most highly ranked candidates predicted by our model which indicates that our approach can inform reliable new knowledge. CONCLUSION: This paper shows that our graph mining model can predict reliable new relationships between AD and other entities (i.e., dietary supplements, chemicals, and drugs). The knowledge graph constructed can facilitate data-driven knowledge discoveries and the generation of novel hypotheses.

A Systematic Review of Randomized Controlled Trials on Interventions Adopting Body-Mind-Spirit (BMS) Model on Holistic Well-Being.

BACKGROUND: This systematic review aims to examine existing randomized controlled trials on interventions adopting Body-Mind-Spirit (BMS) model and evaluated the effectiveness of holistic well-being outcomes. Following three key concepts of the BMS model, our review questions included (1) How was BMS defined? (2) What activities were included, and how were they related to BMS dimensions? (3) What were interventionists' backgrounds, and whether they received BMS training? (4) What were holistic outcomes? and (5) What were the effectiveness and qualities of studies? METHODS: Searches were performed using nine databases for the studies published through August 2020. The process follows PRISMA protocol, and the "risk of bias" tool from the Cochrane Handbook was utilized to determine the quality of included studies. RESULTS: Across 20 included studies, 18 (90%) presented a BMS definition, but only seven (35%) included all three key concepts of the BMS model. Eight studies (40%) offered detailed descriptions of body, mind, and spirit sections, and 12 (60%) mentioned cultural factors. Only five (25%) specified the body, mind, and spirit activities, and only three (15%) reported the BMS training in detail. Seven studies (35%) showed effectiveness in holistic outcomes. Only three (15%) were considered as high quality. CONCLUSION: A unified definition of the BMS model and the guideline to apply the BMS model to design and implement interventions are highly recommended to provide a standard framework for researchers to conduct future studies. The reason for low quality is because the lack of adequate allocation concealment and blindings.

New Monoterpenoid Indoles with Osteoclast Activities from Gelsemium elegans.

The well-known toxic medicine Gelsemium elegans is widely and historically used to treat bone fracture and skin ulcers by the folk people of China. Two new monoterpenoid indole alkaloids, gelselegandines D and E, together with the known analogue gelegamine A were isolated from G. elegans. Their structures were elucidated by means of spectroscopic techniques and quantum chemical calculations. All isolated compounds were tested for the effects on RANKL-induced osteoclast formation. Interestingly, gelselegandine E and gelegamine A, respectively, showed significant promoting and inhibitory activities on osteoclastogenesis, while gelselegandine D had no activity under the same concentration. This work suggested the different configurations for the carbons near the C-19/20 oxygen rings of the isolated compounds may be the key active groups on osteoclast formation and provided the evidence for the rationality as the traditional treatment for bone-related diseases of G. elegans.

The Efficacy of Moxibustion on the Serum Levels of CXCL1 and ß-EP in Patients with Rheumatoid Arthritis.

OBJECTIVE: This study aims to evaluate the efficacy of moxibustion on joint swelling and pain and the levels of C-X-C motif chemokine ligand 1 (CXCL1), ß-endorphin (ß-EP) in serum of rheumatoid arthritis (RA) patients and to investigate the anti-inflammatory and analgesic mechanism of moxibustion on improving RA. METHODS: Sixty-eight patients with RA were randomly and equally classified into the control and treatment groups. The control group was treated with routine drug therapy, while the treatment group received routine drug therapy and moxibustion. Both groups were treated for eight weeks. The symptoms and laboratory indicators of RA patients were compared in the two groups before and after intervention. RESULTS: Sixty-one patients completed the study: four patients dropped out from the treatment group and three from the control group. Trial endpoints were change (∆) in symptoms, measured by Ritchie's articular index (RAI), swollen joint count (SJC), and laboratory indicators, measured by the level of CXCL1, ß-EP, tumor necrosis factor-a (TNF-α), and interleukin-1ß (IL-1ß). ∆RAI, ∆SJC, ∆CXCL1, ∆ß-EP, ∆TNF-α, and ∆IL-1ß in the treatment group were superior to the control group (13.50 [14.50] versus 6.00 [13.00] in ∆RAI, 4.00 [3.00] versus 2.00 [4.00] in ∆SJC, 0.04 ± 0.79 ng/mL versus -0.01 ± 0.86 ng/mL in ∆CXCL1, -2.43 [5.52] pg/mg versus -0.04 [4.09] pg/mg in ∆ß-EP, 3.45 [5.90] pg/mL versus 1.55 [8.29] pg/mL in ∆TNF-α, and 6.15 ± 8.65 pg/mL versus 1.28 ± 8.51 pg/mL in ∆IL-1ß; all P < 0.05). CONCLUSION: Moxibustion can improve the joint swelling and pain symptoms in patients with RA, which may be related to the fact that moxibustion can reduce the release of inflammatory factors in patients with RA and downregulate the level of CXCL1 and increase the level of ß-EP at the same time. This trial is registered with ChiCTR-IOR-17012282.

Research progress regarding potential effects of traditional Chinese medicine on postoperative intestinal obstruction.

OBJECTIVES: Postoperative intestinal obstruction is a common postoperative complication with typical symptoms of abdominal pain, vomiting, abdominal distension and constipation. The principal aim of this paper is to provide a full-scale review on the categories and characteristics of postoperative intestinal obstruction, pathophysiology, effects and detailed mechanisms of compounds and monomers from traditional Chinese medicine for treating postoperative intestinal obstruction. Moreover, the possible development and perspectives for future research are also analyzed. METHODS: Literature regarding postoperative intestinal obstruction as well as the anti-pio effect of aqueous extracts and monomers from traditional Chinese medicine in the last 20 years was summarized. KEY FINDINGS: To date, approximately 30 compounds and 25 monomers isolated from traditional Chinese medicine including terpenes, alkaloids, polysaccharides, flavonoids, phenylpropanoids and quinones, have exerted significant antipio effect. This paper reviews the effective doses, models, detailed mechanisms, and composition of these traditional Chinese medicine compounds, as well as the structure of these monomers. Moreover, challenges existed in the current investigation and further perspectives were discussed as well, hoping to provide a reference for future clinical treatment of postoperative intestinal obstruction and the development of new drugs. CONCLUSIONS: Above all, the convincing evidence from modern pharmacology studies powerfully supported the great potential of traditional Chinese medicine in the management of postoperative intestinal obstruction. Regrettably, less attention was currently paid on the mechanisms of traditional Chinese medicine compounds and monomers with antipio effect. Consequently, future study should focus on monomer-mechanism and structure-function relationship.

Effect of Moxibustion on ß-EP and Dyn Levels of Pain-Related Indicators in Patients with Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic immunodeficiency disease characterized by persistent synovial inflammation, pannus formation, and bone and cartilage destruction, resulting in joint malformations and function decline. OBJECTIVE: The purpose of this study is to evaluate the effect of moxibustion on clinical symptoms and levels of pain-related indicators beta-endorphin (ß-EP) and dynorphin (Dyn) in patients with RA and to explore the potential anti-inflammatory and analgesic mechanisms of moxibustion in RA treatment. METHODS: A total of 64 patients with RA who met the inclusion criteria were randomly and equally classified into the control and treatment groups. The control group received conventional treatment (oral methotrexate, folate, or leflunomide prescribed for a long time). The treatment group was treated with moxibustion at ST36 (Zusanli), BL23 (Shenshu), and Ashi points with respect to the control group. Patients' clinical symptoms and routine inspection indexes (rheumatoid factor [RF], erythrocyte sedimentation rate [ESR], and C-reactive protein [CRP]) were recorded before and after treatment. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), ß-EP, and Dyn were determined by enzyme-linked immunosorbent assay (ELISA). The software SPSS24.0 was used for statistical analysis. RESULTS: (1) Compared with the pretreatment result, both of the two groups' clinical symptoms and routine inspection indexes (RF, ESR, and CRP) improved (P < 0.05), and the improvement of clinical symptoms in the treatment group outperformed that in the control group (P < 0.05). (2) TNF-α and IL-1ß levels decreased significantly in the treatment group after treatment (P < 0.01), while no significant difference was observed in the control group (P > 0.05). (3) ß-EP and Dyn levels in the treatment group were significantly increased after treatment (P < 0.01, P < 0.01), but the control group showed no significant difference (P > 0.05, P > 0.05). It is worth mentioning that the serum TNF-α, IL-1ß, ß-EP, and Dyn levels between the two groups were significantly different after 8 weeks of treatment (P < 0.05). (4) Differences in the serum ß-EP and Dyn levels in the patients of the treatment group were correlated with TNF-α and IL-1ß levels after treatment, and the correlation was mainly negative (r < 0). CONCLUSION: Moxibustion can improve joint pain in patients with RA using conventional western medicine. One of the mechanisms may affect the serum ß-EP and Dyn levels by downregulating the inflammatory factors to play an anti-inflammatory and analgesic role.

Genus Alangium - A review on its traditional uses, phytochemistry and pharmacological activities.

The species from Alangium have been used as folk medicine to treat rheumatism, skin diseases, diabetes by the people of Southeast Asia. Previous phytochemical studies have shown this genus are rich sources of alkaloids, glycosides, and terpenoids, which have attracted considerable attention of many researchers due to their markedly diverse and complex architecture. The crude extracts as well as the monomeric compounds from the title genus possess anti-tumor, anti-inflammatory, antibacterial, anti-oxidant pharmacological activities. Besides, some isolates from Alangium exhibited the effects on skeletal, smooth muscle and the nervous system. As a large genus of medicinal plants, the medicinal value of Alangium has been widely reported, but there is no review that provide a systematic summary towards its chemical constituents and pharmacological activities, to our knowledge. This work aims to present a comprehensive overview on the traditional uses, phytochemistry, and pharmacological activities of medicinal plants in the genus Alangium, and to explore the evidence supporting its ethnopharmacological effectiveness.

Hydroxy-α-sanshool Possesses Protective Potentials on H2O2-Stimulated PC12 Cells by Suppression of Oxidative Stress-Induced Apoptosis through Regulation of PI3K/Akt Signal Pathway.

Zanthoxylum bungeanum pericarp is a commonly used herbal medicine in China with effects of anti-inflammatory and analgesic, improving learning and memory ability, while hydroxy-α-sanshool (HAS) is the most important active ingredient of Z. bungeanum pericarps. The purpose of this study was to investigate the neuroprotective effect of HAS and its related possible mechanisms using a H2O2-stimulated PC12 cell model. CCK-8 assay results showed that HAS had a significant protective effect on H2O2-stimulated PC12 cells without obvious cytotoxicity on normal PC12 cells. Flow cytometry and fluorescence microscope (DAPI staining and DCFH-DA staining) indicated that HAS could reduce the H2O2-induced apoptosis in PC12 cells via reduction of intracellular ROS and increase of mitochondrial membrane potential (MMP). Subsequently, results of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) determination suggested that HAS could increase the enzyme activities of SOD, CAT, and GSH-Px whereas it could decrease the MDA contents in H2O2-stimulated PC12 cells. Furthermore, the western blotting assays showed that HAS could upregulate the expressions of p-PI3k, Akt, p-Akt, and Bcl-2, while it could downregulate the expressions of cleaved caspase-3 and Bax in H2O2-stimulated PC12 cells. Collectively, it could be concluded according to our results that HAS possesses protective potentials on H2O2-stimulated PC12 cells through suppression of oxidative stress-induced apoptosis via regulation of PI3K/Akt signal pathway.