Polyphenol (-)-Epigallocatechin Gallate (EGCG) mitigated kidney injury by regulating metabolic homeostasis and mitochondrial dynamics involvement with Drp1-mediated mitochondrial fission in mice.

The study aimed to examine effects of (-)-epigallocatechin-3-gallate (EGCG) on energy metabolism and mitochondrial dynamics in mouse model of renal injury caused by doxorubicin (DOX). Here, mice were divided into Control group, EGCG-only treated group, DOX group, and three doses of EGCG plus DOX groups. Our results showed that EGCG behaved beneficial effects against kidney injury via attenuation of pathological changes in kidney tissue, which was confirmed by reducing serum creatinine (SCr), blood urea nitrogen (BUN), and apoptosis. Subsequently, changes in reactive oxygen species generation, malondialdehyde content, and activities of antioxidant enzymes were considerably ameliorated in EGCG + DOX groups when compared to DOX group. Furthermore, EGCG-evoked renal protection was associated with increases of mitochondrial membrane potential and decreases of mitochondrial fission protein Dynamin-related protein 1 (Drp1). Moreover, changing glycolysis into mitochondrial oxidative phosphorylation was observed, evidenced by controlling activities of malate dehydrogenase (MDH) and hexokinase (HK) in EGCG + DOX groups when compared to DOX group, indicating that reprogramming energy metabolism was linked to EGCG-induced renal protection in mice. Therefore, EGCG was demonstrated to have a protective effect against kidney injury by reducing oxidative damage, metabolic disorders, and mitochondrial dysfunction, suggesting that EGCG has potential as a feasible strategy to prevent kidney injury.

Polysaccharides as antioxidants and prooxidants in managing the double-edged sword of reactive oxygen species.

Polysaccharides, a class of naturally occurring carbohydrates, were widely presented in animals, plants, and microorganisms. Recently, health benefits of polysaccharides have attracted much attention due to their unique characteristics in reactive oxygen species (ROS) management. ROS, by-products of aerobic metabolism linked to food consumption, exhibited a dual role in protecting cells and fostering pathogenesis collectively termed double-edged sword. Some interesting studies reported that polysaccharides could behave as prooxidants under certain conditions, besides antioxidant capacities. Potentiation of the bright side of ROS could contribute to the host defense that was vitally important for the polysaccharides acting as biological response modifiers. Correspondingly, disease prevention of polysaccharides linked to the management of ROS production was systematically described and discussed in this review. Furthermore, major challenges and future prospects were presented, aiming to provide new insight into applying polysaccharides as functional food ingredients and medicine.

Deuteration of Arylthianthren-5-ium Salts in CD3OD.

Deuteration of arylthianthren-5-ium triflates with CD3OD or CD3OD/CD3COCD3 in the presence of Cs2CO3 by palladium catalysis or photoirradiation allowed the convenient synthesis of deuterated arenes in good yields. The Pd-catalyzed reaction generally gave better yields than the photoinduced deuteration, but exceptions also exist. They could complement each other in some cases. These reactions featured eco-friendly conditions, simplicity, inexpensive deuterium sources, good functional group tolerance, and a range of substrates. Since arylthianthren-5-ium salts could be readily synthesized from arenes and thianthrene 5-oxide, this protocol provided a formal aromatic C-H deuteration with high selectivity, enabling efficient deuterium labeling of multifunctionalized arenes and drug molecules.

Activity fingerprinting of polysaccharides on oral, gut, pancreas and lung microbiota in diabetic rats.

The modern rise in type 2 diabetes mellitus (T2DM) and its correlation to commensal microbiota have elicited global concern about the patterns of microbial action in the host. With the exception of that linked to gut, microbiota were also colonized in pancreas, oral, and lung, contributing to the physiopathology of T2DM. In this study, we aimed to explore the protective effects of Ganoderma atrum polysaccharide (PSG) and White Hyacinth Bean polysaccharide (WHBP) on the intestine, pancreas, oral, and lung microbiota in T2DM rats. Here we showed that, despite capacities of polysaccharides that exerted similar protective effects on hyperglycemia, dyslipidemia, insulin resistance and dysbacteriosis in T2DM rats, PSG and WHBP were able to be characterized by their own "target" bacteria, which could be proposed for activity-fingerprinting of polysaccharide species. Furthermore, we found a mutual bacteria spectrum in the pancreas and lung, and most bacteria could be tracked to oral or gut samples. Notably, the overlapping areas of the microbiota profile between organs (pancreas, lung) and saliva were more than in the gut, suggesting that a saliva sample was also of interest to serve as a "telltale sign" for judging pancreatic injury. Together, these microbiota interactions provided a new potential to harvest alternative samples for disease surveillance. Meanwhile, polysaccharides had anti-T2DM abilities, which could be distinguished by their own characteristic bacteria.

[Effect of WRAP53 ß Targeted Co-Inhibitory Pathways Based on Comprehensive Bioinformatics Analysis in Treating Squamous Cell Carcinoma of the Head and Neck].

Objective: To investigate the association between WD40-encoding RNA antisense to p53 ( WRAP53 ß), a telomerase new core subunit, and the clinical, genomic and immune infiltration characteristics of squamous cell carcinoma of the head and neck (HNSC), and to explore for potential joint targeted therapy of HNSC. Methods: Tumor IMmune Estimation Resource (TIMER) online modules were adopted to predict the association between WRAP53 ß expression and the clinical features, oncogene, and immune infiltration of HNSC in the Cancer Genome Atlas (TCGA) cohort. Tumor Immune Single-cell Hub (TISCH) was used to analyze WRAP53 ß expression at the single cell level. Analysis of the small molecule inhibitors potentially targeting WRAP53 ß was carried out by Computational Analysis of REsistance (CARE). In the in vitro verification experiment, recombinant lentiviral particles with the sh WRAP53 ß sequence were synthesized. Then, the oral squamous cell carcinoma cell line Cal27 (the sh WRAP53 ßgroup) stably expressing sh WRAP53 ß were constructed, and two control groups were set up (the shNC group consisting of Cal27 cells added with lentiviral particles containing non-specific control sequences and the Con group consisting of untreated Cal27 cells). MTT assay was done to examine the proliferation of cells in the three groups. Cellular immunofluorescence assay was done for further qualitative examination of the expression of P53 protein in the cells of the sh WRAP53 ß group and the shNC group. Western blot was done to measure the expression of WRAP53ß and γ-H2AX, a DNA damage protein, in the 18 th, 23 rd and 28 th passages of the sh WRAP53 ß group and the shNC group. Finally, specimens of 13 cases of oral squamous cell carcinoma and 7 cases of oral mucosal inflammation were collected, and the expression of WRAP53ß and γ-H2AX in the clinical specimens of oral squamous cell carcinoma was verified with immunohistochemistry. Resluts: TIMER analysis revealed that the expression level of WRAP53 ß in HNSC tissues was significantly higher than that in normal tissues. There was a significant positive correlation between WRAP53 ß expression and multiple genes in the p53 pathway, including CCNB1, CCNB2 and CDK1. Although no significant correlation between WRAP53 ß expression and infiltrating immune cells was found, WRAP53 ß was significantly positively correlated with the inflammatory factors IFN-γ and IL23A, and negatively correlated with IL-1A and IL-6 in HPV-positive carcinoma of the head and neck. TISCH single cell sequencing datasets also showed higher expression of WRAP53 ß in malignant cells, and very low or zero expression in immune cells. According to the CARE scores, the most potent WRAP53 ß co-inhibitory drugs were ATM, CDK1 and MDM4 targeted inhibitors. In vitro cell experiments showed that the proliferation ability of Cal27 cells decreased significantly in the sh WRAP53 ß group as compared with that of the control group between Day 5 and Day 7 ( P<0.05). Furthermore, the expression of P53 decreased significantly in the sh WRAP53 ß group. As compared with the control group, the expression of WRAP53ß in sh WRAP53 ß group significantly decreased in the 18 th, 23 rd and 28 th passages ( P<0.05), while γ-H2AX expression only decreased in the 18 th and 28 th passages ( P<0.05) according to the results of Western blot. Clinical specimens showed rather high positive expression rate of γ-H2AX in oral squamous cell carcinoma tissues (12/13), while the expression of WRAP53ß was not detected in oral mucositis samples (0/7). Conclusions: WRAP53 ß showed significantly higher expression level in HSNC, and was significantly associated with p53 pathway genes. ATM, CDK1 and MDM4 inhibitors may be potential WRAP53 ß co-inhibitory agents. RNA interference of WRAP53 ß expression may cause inhibition of DNA damage, thereby indicating therapeutic potential for HNSC.

Ganoderma atrum polysaccharide modulates the M1/M2 polarization of macrophages linked to the Notch signaling pathway.

Macrophages could be polarized into two major sub-populations including classically activated (M1) and alternatively activated (M2) macrophages. The present study aimed to investigate the effects of Ganoderma atrum polysaccharide (PSG-1) on the regulation of macrophage polarization and further explored the associated molecular mechanisms. In this work, a lipopolysaccharide (LPS) plus IFN-γ and IL-4 were used to establish an in vitro model of two extreme states, namely pro-inflammatory M1 and anti-inflammatory M2. The results showed that PSG-1 had effects on the behavior modification of macrophage polarization by reducing CD80 expression in LPS plus IFN-γ-induced M1 macrophages, and attenuating CD23 expression in IL-4-induced M2 macrophages. Further study revealed that PSG-1-modulated M1 and M2 macrophage polarization was associated with controlling phagocytosis, reactive oxygen species generation, NO and cytokines (IL-1ß, IL-6 and IL-10). Subsequently, the treatment of M1 macrophages with a combination of PSG-1 and a Notch-response inhibitor (DAPT) did not alter CD80 expression compared with DAPT alone, while several pro-inflammatory parameters were considerably decreased, suggesting that the Notch signaling pathway partly mediated the effects of PSG-1 on modulating macrophage polarization. Together, our findings suggested that PSG-1 could repair the chaos in the polarization of M1/M2 macrophages and the molecular mechanism linked to the Notch signaling pathway.

Chimonanthus nitens Oliv. essential oil mitigates lipopolysaccharide-induced acute lung injury in rats.

This study aimed to evaluate the effect of Chimonanthus nitens Oliv. essential oil (named CEO) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. In the present study, 21 compounds were characterized in CEO by gas chromatography-mass spectrometry analysis. Furthermore, animal data suggested that CEO could protect rats against ALI, as evidence by increasing white blood cell count, reducing immune organ index and improving lung histopathological changes in rats subjected to LPS. Reduction of the levels of IL-1ß was also shown during CEO-triggering lung protection in rats. Meanwhile, these protective effects of CEO were accompanied by the attenuation of lipid oxidation, and elevation of antioxidant enzymes, suggesting that enhancement of antioxidant defense was linked to its lung protection. Moreover, a combination with CEO and LPS significantly elevated short-chain fatty acids (SCFAs) compared with LPS alone via increasing propionic, i-butyric, butyric and i-valeric acid on LPS-induced ALI in rats. Therefore, our findings indicated that CEO could alleviate LPS-caused ALI in rats by controlling aberrant inflammation, correcting the redox system, and modulating SCFAs in rats.

The combination between NCSTN gene copy number variation and growth traits in Chinese cattle.

Copy number variation (CNV) has been used as an important source of phenotypic and genetic diversity in recent years. Nicastrin (NCSTN) gene is usually attached to human diseases such as Alzheimer's disease, and Acne inversa. However, there are no essays about the NCSTN gene combining with cattle breeds. In our study, we discovered different distributions of NCSTN gene copy number and associated it with phenotypic traits in four Chinese yellow cattle breeds (XN, PN, QC and YL). The result turned out that the CNV of the NCSTN gene was associated with several growth traits, such as cannon circumference, chest girth and rump length (p < 0.05). In general, we revealed the eminence over CNV of NCSTN gene and economic traits, suggesting that the CNV of the NCSTN gene can be considered to be a promising molecular breeding marker of Chinese beef cattle.

[Human mycobiome and diseases].

The proportion of mycobiome is less than 1% of human microbiome. However, fungal community plays a key role in human health and diseases. With high-throughput sequencing applications, the structure and composition of mycobiome in the mouth, lung, gut, vagina, and skin have been analyzed, and the role of microbiome in diseases has been investigated. Mycobiome also influences the composition of bacteriome and includes key species that maintain the structure and function of microbial communities. Fungi also influence host immune responses. In this review, we summarized the mycobiome com-position at various sites and different diseases and the interactions between fungi-bacteria and fungi-host.

Novel copy number variation of the KLF3 gene is associated with growth traits in beef cattle.

Copy number variation (CNV) related to complex traits, such as disease and quantitative phenotype, is considered an important and wealthy source of genetic and phenotypic diversity. It suggests that the copy number variation of function gene maybe leads to the phenotypic changes. Kupple like factor 3 (KLF3) gene is a vital transcription factor associated with the growth and development of muscle and adipose tissue. It has been mapped in a CNV region by animal genome re-sequencing. In this study, we detected the distribution diversity of KLF3 gene copy numbers in six Chinese cattle breeds (QC, NY, XN, PN, QDM and JX) and associated the phenotypic traits with it. Then, we analyzed the KLF3 gene transcription expression level in different tissues of Jiaxian (JX) cattle. Furthermore, we detected mRNA expression level of muscle and fat tissues of Jiaxian cattle (JX), Angus × Jiaxian (AJ). The results showed that the copy number in CNV loss was more frequent in QC than others. And we revealed a positive effect of KLF3 CNV on growth traits, such as body mass and heart girth (P < 0.05). In a word, we ascertained the significance between CNVs of KLF3 gene and growth traits in different cattle breeds, and our data indicates that the CNVs of KLF3 gene may as a marker for the future molecular breeding of Chinese beef cattle.

Mannose Receptor Mediates the Immune Response to Ganoderma atrum Polysaccharides in Macrophages.

The ability of mannose receptor (MR) to recognize the carbohydrate structures is well-established. Here, we reported that MR was crucial for the immune response to a Ganoderma atrum polysaccharide (PSG-1), as evidenced by elevation of MR in association with increase of phagocytosis and concentrations of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in normal macrophages. Elevation of MR triggered by PSG-1 also led to control lipopolysaccharide (LPS)-triggered inflammatory response via the increase of interleukin-10 (IL-10) and inhibition of phagocytosis and IL-1ß. Anti-MR antibody partly attenuated PSG-1-mediated anti-inflammatory responses, while it could not affect TNF-α secretion, suggesting that another receptor was involved in PSG-1-triggered immunomodulatory effects. MR and toll-like receptor (TLR)4 coordinated the influences on the TLR4-mediated signaling cascade by the nuclear factor-κB (NF-κB) pathway in LPS-stimulated macrophages subjected to PSG-1. Collectively, immune response to PSG-1 required recognition by MR in macrophages. The NF-κB pathway served as a central role for the coordination of MR and TLR4 to elicit immune response to PSG-1.

Ganoderma atrum polysaccharide ameliorates ROS generation and apoptosis in spleen and thymus of immunosuppressed mice.

Ganoderma atrum polysaccharide (PSG-1) is a bioactive compound with antioxidant and immunomodulatory activities. The aim of this study was to determine the effect of PSG-1 on reactive oxygen species (ROS) generation and apoptosis in spleen and thymus of cyclophosphamide (CTX)-induced immunosuppressed mice. The results showed that PSG-1 protected mice against CTX-mediated immunosuppression, as evidenced by enhancing the ratios of thymus and spleen weights to body weight, promoting T cell and B cell survival, and increasing levels of TNF-α and IL-2. Apoptosis, ROS generation and lipid peroxidation in the immune organs of the immunosuppressed animals were ameliorated by PSG-1. The immune benefits of PSG-1 were associated with the enhancement of the activities of glutathione peroxidase, superoxide dismutase and catalase in the immune organs, implying that antioxidant activities of PSG-1 may play an important role in PSG-1-evoked immune protection. Taken together, these findings have demonstrated that PSG-1 may ameliorate CTX-induced immunosuppression through reducing apoptosis and oxidative damage in immunological system.

(-)-Epigallocatechin-3-gallate alleviates doxorubicin-induced cardiotoxicity in sarcoma 180 tumor-bearing mice.

AIMS: (-)-Epigallocatechin-3-gallate (EGCG), a major green tea polyphenol compound, plays an important role in the prevention of cardiovascular disease and cancer. The present study aimed to investigate the effects of EGCG on doxorubicin (DOX)-induced cardiotoxicity in Sarcoma 180 (S180) tumor-bearing mice. MAIN METHODS: S180 tumor-bearing mice were established by subcutaneous inoculation of S180 cells attached to the axillary region. The extent of myocardial injury was accessed by the amount of lactate dehydrogenase (LDH) released in serum. Heart tissue was morphologically studied with transmission electron microscopy. Apoptosis, reactive oxygen species (ROS) generation, mitochondrial membrane potential (ΔÑ°m) as well as calcium concentration were measured by flow cytometric analysis. Expression levels of manganese superoxide dismutase (MnSOD) were analyzed by Western blot. KEY FINDINGS: Results showed that the combination with EGCG and DOX significantly inhibited tumor growth and enhanced induction of apoptosis compared with DOX alone. Moreover, administration of EGCG could suppress DOX-induced cardiotoxicity as evidenced by alleviating LDH release and apoptosis in cardiomyocyte. EGCG-evoked cardioprotection was in association with the increase of ΔÑ°m and MnSOD expression. EGCG was also found to attenuate ROS generation and myocardial calcium overload in Sarcoma 180 tumor-bearing mice subjected to DOX. SIGNIFICANCE: EGCG alleviated DOX-induced cardiotoxicity possibly in part mediated by increasing of MnSOD and Ñ°m, reducing myocardial calcium overload and subsequently attenuating the apoptosis and LDH release. Our findings suggest that co-administration of EGCG and DOX have potential as a feasible strategy to mitigate cardiotoxicity of DOX without compromising its chemotherapeutic value.

[Analysis of causes and whole microbial structure in a case of rampant caries].

OBJECTIVE: To analyze the whole microbial structure in a case of rampant caries to provide evidence for its prevention and treatment. METHODS: Clinical samples including blood, supragingival plaque, plaque in the caries cavity, saliva, and mucosal swabs were collected with the patient's consent. The blood sample was sent for routine immune test, and the others samples were stained using Gram method and cultured for identifying colonies and 16S rRNA sequencing. DNA was extracted from the samples and tested for the main cariogenic bacterium (Streptococcus mutans) with qPCR, and the whole microbial structure was analyzed using DGGE. RESULTS: The patient had a high levels of IgE and segmented neutrophils in his blood. Streptococci with extremely long chains were found in the saliva samples under microscope. Culture of the samples revealed the highest bacterial concentration in the saliva. The relative content of hemolytic bacterium was detected in the samples, the highest in the caries cavity; C. albicans was the highest in the dental plaque. In addition, 33 bacterial colonies were identified by VITEK system and 16S rDNA sequence phylogenetic analysis, and among them streptococci and Leptotrichia wade were enriched in the dental plaque sample, Streptococcus mutans, Fusobacterium nucleatum, and Streptococcus tigurinus in the caries cavity, and Lactobacillus in the saliva. S. mutans was significantly abundant in the mucosal swabs, saliva and plaque samples of the caries cavity as shown by qPCR. Compared to samples collected from a healthy individual and another two patients with rampant caries, the samples from this case showed a decreased bacterial diversity and increased bacterial abundance shown by PCR-DGGE profiling, and multiple Leptotrichia sp. were detected by gel sequencing. CONCLUSION: The outgrowth of such pathogenic microorganisms as S. mutans and Leptotrichia sp., and dysbiosis of oral microbial community might contribute to the pathogenesis of rampant caries in this case.

Ganoderma atrum Polysaccharide Ameliorates Hyperglycemia-Induced Endothelial Cell Death via a Mitochondria-ROS Pathway.

The aim of the present study was to examine the role of Ganoderma atrum polysaccharide (PSG-1) in reactive oxygen species (ROS) generation and mitochondrial function in hyperglycemia-induced angiopathy. In this work, ROS scavenger, oxidizing agent tert-butylhydroperoxide (tBH), mitochondrial permeability transition pore (mPTP) blockers, and caspase inhibition are used to investigate whether PSG-1 may promote survival of human umbilical vein cells (HUVECs) through preventing the overproduction of ROS and mitochondrial dysfunction. Experimental results show that exposure of HUVECs to 35.5 mmol/L glucose increases the proportion of cells undergoing apoptosis. PSG-1, mPTP blocker, or caspase inhibition can reduce apoptosis and ROS generation. PSG-1 also increases mitochondrial Bcl-2 protein formation and mitochondrial membrane potential (ΔΨm) but inhibits Bax translocation, cytochrome c release, and caspase activation. In summary, vascular protection of PSG-1 can be mediated by a mitochondria-ROS pathway. ROS generation and mPTP induction are critical for high glucose-mediated apoptosis. PSG-1 ameliorates endothelial dysfunction by inhibiting oxidative stress and subsequent mitochondrial dysfunction.