Dynamic variation of Paris polyphylla root-associated microbiome assembly with planting years.

MAIN CONCLUSION: P. polyphylla selectively enriches beneficial microorganisms to help their growth. Paris polyphylla (P. polyphylla) is an important perennial plant for Chinese traditional medicine. Uncovering the interaction between P. polyphylla and the related microorganisms would help to utilize and cultivate P. polyphylla. However, studies focusing on P. polyphylla and related microbes are scarce, especially on the assembly mechanisms and dynamics of the P. polyphylla microbiome. High-throughput sequencing of the 16S rRNA genes was implemented to investigate the diversity, community assembly process and molecular ecological network of the bacterial communities in three root compartments (bulk soil, rhizosphere, and root endosphere) across three years. Our results demonstrated that the composition and assembly process of the microbial community in different compartments varied greatly and were strongly affected by planting years. Bacterial diversity was reduced from bulk soils to rhizosphere soils to root endosphere and varied over time. Microorganisms benefit to plants was selectively enriched in P. polyphylla roots as was its core microbiome, including Pseudomonas, Rhizobium, Steroidobacter, Sphingobium and Agrobacterium. The network's complexity and the proportion of stochasticity in the community assembly process increased. Besides, nitrogen metabolism, carbon metabolism, phosphonate and phosphinate metabolism genes in bulk soils increased over time. These findings suggest that P. polyphylla exerts a selective effect to enrich the beneficial microorganisms and proves the sequential increasing selection pressure with P. polyphylla growth. Our work adds to the understanding of the dynamic processes of plant-associated microbial community assembly, guides the selection and application timing of P. polyphylla-associated microbial inoculants and is vital for sustainable agriculture.

Estimation of appropriate dietary intake of iodine among lactating women in China based on iodine loss in breast milk.

OBJECTIVE: Data on iodine loss in breast milk, which are critical for establishing the appropriate dietary iodine intake for lactating women, is currently limited. A study was conducted to assess iodine loss in breast milk among Chinese lactating women to estimate the appropriate dietary intake of iodine. METHODS: A total of 54 pairs of healthy, lactating women and their infants aged 0-6 months were recruited from Tianjin and Luoyang cities in China. A 4 days infant weighing study was conducted to assess iodine loss in the breast milk of lactating women. Mothers were required to weigh and record their infants' body weights before and after each feeding for a 24 h period from 8:00 am to 8:00 am. During the weighing study, 2812 breast milk samples and 216 24-h urine samples were collected from each lactating mother for four consecutive days. In addition, a 3 days 24 h dietary record, including salt weighing and drinking water samples collecting, was performed by each lactating mother to determine dietary iodine intake during the weighing study. RESULTS: The average dietary iodine intake of lactating women was 323 ± 80 µg/d. The median breast milk iodine concentration and 24 h urinary iodine concentration of lactating women were 154 (122-181) and 135 (104-172) µg/L, respectively. The mean volume of breast milk and the mean iodine loss in the breast milk of lactating women were 711 ± 157 mL/d and 112 ± 47 µg/d, respectively. The appropriate dietary intake of iodine among lactating Chinese women is approximately 260 µg/d. CONCLUSIONS: Based on the iodine loss in breast milk (110 µg/d) found in this study, and the estimated average requirement of iodine for adults, the appropriate dietary intake of iodine among lactating Chinese women is 260 µg/d, which is higher than the 240 µg/d recommended by the China Nutrition Science Congress in 2013.

Feiyanning downregulating CXCLs/CXCR2 axis to suppress TANs infiltration in the prevention of lung cancer metastasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Tumor-associated neutrophils (TANs) play an important role in tumor metastasis. The Traditional Chinese medicine (TCM) Feiyanning (FYN) has been clinically proven to effectively prevent the recurrence and metastasis of lung cancer, improve immunity, and prolong the survival period of lung cancer patients. However, its anti-metastatic immune mechanism has not been fully elucidated. To this end, we studied the mechanism of FYN's regulation of neutrophils infiltration in the tumor microenvironment (TME). AIM OF THE STUDY: To explore the anti-metastatic mechanism of FYN from the perspective of anti-immunosuppressive phenotype neutrophils infiltration in the TME. MATERIALS AND METHODS: TCM network pharmacological analysis was used to predict Feiyanning effective target. Flow cytometry was used to detect the proportion of immune cell subsets in the TME. Lung metastases were investigated in C57 mice by tail vein injection. Protein expression was evaluated by immunohistochemistry and Western blot. Gene expression was evaluated by qRT-PCR. RESULTS: FYN could reshape the tumor immune microenvironment. It prevents Tregs, M2 macrophages, and neutrophils infiltration, as well as recruits T cells, NK cells, and DCs, and improves DCs activation. In addition, FYN could regulate the polarization of TANs, inhibit the infiltration of neutrophils with an immunosuppressive phenotype, downregulate CXCLs/CXCR2 axis and inhibitory factors like Arg-1 and TGF-ß, and up-regulate the immune effector molecule ICAM-1. Furthermore, FYN increases anti-tumor immune effects in the TME to prevent tumor cells from spreading to the lungs. CONCLUSION: This study clarifies the potential mechanism of FYN in regulating neutrophils infiltration and anti-metastasis. FYN may regulate neutrophils infiltration in the TME by regulating CXCLs/CXCR2 axis.

CACA Guidelines for Holistic Integrative Management of Breast Cancer.

Purpose: Breast cancer is now the most common malignant tumor worldwide. About one-fourth of female cancer patients all over the world suffer from breast cancer. And about one in six female cancer deaths worldwide is caused by breast cancer. In terms of absolute numbers of cases and deaths, China ranks first in the world. The CACA Guidelines for Holistic Integrative Management of Breast Cancer were edited to help improve the diagnosis and comprehensive treatment in China. Methods: The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to classify evidence and consensus. Results: The CACA Guidelines for Holistic Integrative Management of Breast Cancer include the epidemiology of breast cancer, breast cancer screening, breast cancer diagnosis, early breast cancer treatment, advanced breast cancer treatment, follow-up, rehabilitation, and traditional Chinese medicine treatment of breast cancer patients. Conclusion: We to standardize the diagnosis and treatment of breast cancer in China through the formulation of the CACA Guidelines.

Prednisone inhibits the focal adhesion kinase/receptor activator of NF-κB ligand/mitogen-activated protein kinase signaling pathway in rats with adriamycin-induced nephropathy.

The aim of the present study was to investigate the mechanisms underlying the effects of prednisone on adriamycin-induced nephritic rat kidney damage via the focal adhesion kinase (FAK)/receptor activator of nuclear factor-κB ligand (RANKL)/mitogen­activated protein kinase (MAPK) signaling pathway. An adriamycin­induced nephritic rat model was established to investigate these mechanisms. A total of 30 healthy male Sprague­Dawley rats were randomly assigned to the normal, model or prednisone group. Samples of urine were collected over the course of 24 h at days 7, 14, and 28, and renal cortex tissue samples were harvested at days 14, and 28 following nephritic rat model establishment. The total urinary protein content was measured by biuret colorimetry. Pathological changes in the kidney tissue samples were observed using an electron microscope. The mRNA expressions levels of FAK, RANKL, p38, extracellular signal­regulated kinase (ERK), c­Jun N­terminal kinase (JNK), and nephrin were then quantified by reverse transcription­quantitative polymerase chain reaction. In addition, the protein expressions levels of FAK, RANKL, p38, ERK, JNK, phosphorylated (p)­FAK, p­ERK, and p­JNK were quantified by western blotting. As compared with the normal group, the protein expression levels of FAK, RANKL, p-FAK, p38 and p-ERK in the model group were increased. In the prednisone group, the protein expression levels of p-ERK decreased, as compared with the normal group. In the prednisone group, the urinary protein levels, the protein expression levels of FAK, RANKL, p38, p-FAK, p-p38 and the mRNA expression levels of FAK, p38, RANKL, ERK, JNK decreased, as compared with the model group. In the prednisone group, the mRNA and protein expression levels of nephrin and the serum expression levels of RANKL increased, the serum expression levels of osteoprotegerin (OPG) were decreased, as compared with the model group. No significant changes in the protein expression levels of JNK were observed among the groups. These results suggested that prednisone is able to protect podocytes from apoptosis, and reduce urinary protein levels by inhibiting the FAK/RANKL/MAPK signaling pathway in kidney tissue samples. Serum prednisone may induce osteoporosis via the OPG/RANK/RANKL signaling pathway.

[Effect of modified sijunzi decoction on the bone metabolism of adriamycin induced nephropathy rats].

OBJECTIVE: To explore the effect of Modified Sijunzi Decoction (MSD) on the bone metabolism of prednisone intervened adriamycin-induced nephropathy rats. METHODS: The adriamycin-induced nephropathy rat model was prepared. Totally 50 SD rats were randomly divide into five groups, i.e., the model group, the hormone group, the Chinese medicine (CM) group, the CM + hormone group, and the normal control group. The 24-h urine samples were collected on the 7th, 21st, and 35th day after modeling. The 24-h urine protein was measured by biuret colorimetry. Serum levels of osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB ligand (RANKL), osteocalcin (BGP), and tartrate-resistant acid phosphatase (TRACP) were determined by ELISA. Expressions of OPG and RANKL in the tibia tissue were detected using real-time quantitative PCR and Western blot. RESULTS: (1) Compared with the normal control group, the 24-h urine protein increased in each group on the 7th, 21st, and 35th day (P < 0.05, P < 0.01). Compared with the model group, the 24-h urinary protein decreased in the hormone group and the CM + hormone group (P < 0.05, P < 0.01). The decrement was more obvious along with the treatment time went by (P < 0.05, P < 0.01). There was statistical difference in the reduction of urine protein on the 35th day between the CM group and the model group (P < 0.05). (2) Compared with the 21st-day of the same group, the serum levels of TRACP and RANKL increased (P < 0.05, P < 0.01). Compared with the model group, the serum levels of the TRACP and RANKL increased (P < 0.05, P < 0.01), OPG and BGP decreased (P < 0.05, P < 0.01) in the hormone group. Compared with the CM group at the same period, serum OPG level decreased and the RANKL level increased in the hormone group and the CM + hormone group (P < 0.05, P < 0.01). Besides, the serum level of TRACP increased and BGP decreased (P < 0.05, P < 0.01). Compared with the hormone group at the same period, OPG and BGP increased (P < 0.05, P < 0.01), RANKL decreased (P < 0.01) in the CM + hormone group. On the 35th day TRACP decreased (P < 0.01). (3) Compared with the normal group, mRNA expressions of OPG and RANKL on the 21st day increased (P < 0.05, P < 0.01), mRNA expressions of OPG and RANKL on the 35th day decreased in the model group (P < 0.01). Compared with the CM group at the same period, OPG mRNA expression decreased (P < 0.01) and RANKL mRNA expression increased in the hormone group (P < 0.05). OPG mRNA expression decreased in the CM +hormone group (P < 0.05). (4) Compared with the hormone group on the 21st day, the OPG level decreased and the RANKL protein increased (both P < 0.05). RANKL decreased in the CM + hormone group (P < 0.05). Compared with the model group at the same period, OPG decreased and RANKL increased in the hormone group (P < 0.01). Compared with the CM group at the same period, OPG decreased (P < 0.01), RANKL increased (P < 0.01) in the hormone group and the CM + hormone group. Compared with the hormone group at the same period, OPG increased and RANKL decreased in the CM + hormone group (both P < 0.01). CONCLUSIONS: Prednisone could induce osteoporosis through the OPG/RANKL/RANK pathway. MSZ could slow down the formation of prednisone-induced osteoporosis through promoting osteoblast differentiation, and inhibiting osteoclastogenesis.

Effects of Yishenjiangzhuo granules on immunity and bone metabolism in patients with stage 3-4 chronic kidney disease.

OBJECTIVE: To determine the effects of Yishenjiangzhuo granules (YJG) on bone metabolism and to explore the changes in levels of bone Gla protein (BGP), tartrate-resistant acid phosphatase (TRAP), as well as their relationships with levels of B cells, regulatory T cells (Treg) and interleukin (IL)-17 in patients with stage 3-4 chronic kidney disease (CKD) before and after treatment. METHODS: Fifty-three stage 3-4 CKD patients were divided randomly into two groups: YJG treatment and control. Peripheral blood was taken from two groups of CKD patients and 21 healthy subjects in the normal group. The parameters determined were the levels of CD4+, CD19+, CD19+ CD69+, CD19+ av, Treg (CD4 + CD25 + CD127lo), BGP, TRAP, IL-17, calcium, phosphate, blood urea nitrogen, serum creatinine (SCr), hemoglobin (Hb) in peripheral blood, and urinary creatinine. Calcium-phosphate products and endogenous creatinine clearance rate (CCr) were calculated according to standard protocols. RESULTS: In YJG and control groups, SCr levels were lowered (P < 0.01) after treatment, whereas CCr (P < 0.05) as well as Hb and albumin levels (P < 0.01) were increased. The changes in levels of CCr and SCr in the YJG group were more significant. After treatment, CD19+CD69+ and Treg levels in the two groups varied (P < 0.01) compared with those of the normal group; the level of CD19+ increased but the levels of CD4+ and CD19 + AV decreased (P < 0.01) in both groups. Compared with the control group, the changes of CD19+ and CD19 + AV in the YJG group were more apparent (P < 0.05). Compared with the normal group, levels of IL-17 in both groups increased significantly (P < 0.01), and the difference in the control group was more significant (P < 0.05). After treatment, the TRAP level increased (P < 0.05), but the difference in BGP level (P > 0.05) was not significant. CONCLUSION: In stage 3-4 CKD patients, B cells and IL-17 participated in the induction of osteoclast activation. YJG could also elevate the level of B cells and decrease their apoptosis, but showed no significant effects on active B cells, IL-17 or osteoclast activity.