In vitro antibacterial effects of Broussonetia papyrifera leaf extract and its anti-colitis in DSS-treated mice.

Recently, the hybrid Broussonetia papyrifera (BP) has been extensively cultivated and predominantly utilized in ruminants because of its high protein and bioactive compound content. In the present study, the effects of an ethanolic extract of BP leaves (BPE, 200 mg/kg) on mitigating 2% dextran sodium sulfate (DSS)-induced intestinal inflammation in mice were evaluated. BPE is rich in flavonoids, polyphenols, and polysaccharides, and displays potent antioxidant and antibacterial activities against pathogenic strains such as Clostridium perfringens, Salmonella Typhimurium, and Salmonella enterica subsp. enterica in vitro. In a mouse study, oral administration of DSS resulted in weight loss, incidence of diarrhea, enlargement of the liver and spleen, impaired colonic morphology, downregulation of both gene and protein expression related to intestinal antioxidant (Nrf2) and barrier function (ZO-1), decreased diversity of colonic microbiota, and 218 differentially altered colonic metabolites; however, co-treatment with BPE did not restore these modified aspects except for the liver index and colonic bacterial diversity. The singular treatment with BPE did not manifest evident side effects in normal mice but induced a mild occurrence of diarrhea and a notable alteration in the colonic metabolite profile. Moreover, a single BPE administration augmented the abundance of the commensal beneficial bacteria Faecalibaculum and Akkermansia genera. Overall, the extract of BP leaves did not demonstrate the anticipated effectiveness in alleviating DSS-induced intestinal inflammation.

Nicotinamide mononucleotide supplementation protects the intestinal function in aging mice and D-galactose induced senescent cells.

The nicotinamide adenine dinucleotide (NAD+) level shows a temporal decrease during the aging process, which has been deemed as an aging hallmark. Nicotinamide mononucleotide (NMN), a key NAD+ precursor, shows the potential to retard the age-associated functional decline in organs. In the current study, to explore whether NMN has an impact on the intestine during the aging process, the effects of NMN supplementation on the intestinal morphology, microbiota, and NAD+ content, as well as its anti-inflammatory, anti-oxidative and barrier functions were investigated in aging mice and D-galactose (D-gal) induced senescent IPEC-J2 cells. The results showed that 4 months of NMN administration had little impact on the colonic microbiota and NAD+ content in aging mice, while it significantly increased the jejunal NAD+ content and improved the jejunal structure including increasing the villus length and shortening the crypt. Moreover, NMN supplementation significantly up-regulated the mRNA expression of SIRT3, SIRT6, nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), the catalytic subunit of glutamate-cysteine ligase (GCLC), superoxide dismutase 2 (SOD2), occludin, and claudin-1, but down-regulated the mRNA expression of tumor necrosis factor alpha (TNF-α). Specifically, in the D-gal induced senescent IPEC-J2 cells, 500 µM NMN restored the increased mRNA expression of interleukin 6 (IL6ST), IL-1A, nuclear factor (NF-κB1), and claudin-1 to normal levels to some extent. Furthermore, NMN treatment significantly affected the mRNA expression of antioxidant enzymes including NQO1, GCLC, SOD 2 and 3, and GSH-PX1, 3 and 4. In addition, 200 µM NMN enhanced the cell viability and total antioxidant capacity and lowered the reactive oxygen species level of senescent IPEC-J2 cells. Notably, NMN restored the down-regulated protein expression of occludin and claudin-1 induced by D-gal. The above data demonstrated the potential of NMN in ameliorating the structural and functional decline in the intestine during aging.

The Impacts of Short-Term NMN Supplementation on Serum Metabolism, Fecal Microbiota, and Telomere Length in Pre-Aging Phase.

Aging is a natural process with concomitant changes in the gut microbiota and associate metabolomes. Beta-nicotinamide mononucleotide, an important NAD+ intermediate, has drawn increasing attention to retard the aging process. We probed the changes in the fecal microbiota and metabolomes of pre-aging male mice (C57BL/6, age: 16 months) following the oral short-term administration of nicotinamide mononucleotide (NMN). Considering the telomere length as a molecular gauge for aging, we measured this in the peripheral blood mononuclear cells (PBMC) of pre-aging mice and human volunteers (age: 45-60 years old). Notably, the NMN administration did not influence the body weight and feed intake significantly during the 40 days in pre-aging mice. Metabolomics suggested 266 upregulated and 58 downregulated serum metabolites. We identified 34 potential biomarkers linked with the nicotinamide, purine, and proline metabolism pathways. Nicotinamide mononucleotide significantly reduced the fecal bacterial diversity (p < 0.05) with the increased abundance of Helicobacter, Mucispirillum, and Faecalibacterium, and lowered Akkermansia abundance associated with nicotinamide metabolism. We propose that this reshaped microbiota considerably lowered the predicated functions of aging with improved immune and cofactors/vitamin metabolism. Most notably, the telomere length of PBMC was significantly elongated in the NMN-administered mice and humans. Taken together, these findings suggest that oral NMN supplementation in the pre-aging stage might be an effective strategy to retard aging. We recommend further studies to unravel the underlying molecular mechanisms and comprehensive clinical trials to validate the effects of NMN on aging.

Dietary phytoestrogen intake and lung cancer risk: an analysis of the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial.

Phytoestrogens (PEs) have estrogen-like activity and were found to lower incidences of several hormone-dependent cancers. Emerging evidence suggests that estrogen may play a role in lung cancer carcinogenesis. We aim to evaluate dietary PE intake and lung cancer risk using data from the Prostate, Lung, Colorectal and Ovarian cancer screening trial. A total of 1706 lung cancer cases were identified. The association between lung cancer risk and PE intake (in quartiles) was calculated using the Cox proportional hazard models adjusting for potential confounders. Stratified analyses by smoking status, sex and histology were also performed. The highest quartile of total PE intake was associated with a reduced risk of lung cancer compared with the lowest quartile [hazard ratio (HR) = 0.85, 95% confidence interval (CI): 0.73-0.99 for >1030 µg/day versus <290 µg/day] (P trend = 0.56). Similar patterns were observed among ever smokers (HR = 0.84, 95% CI: 0.71-0.98), non-small cell histology (HR = 0.84, 95% CI: 0.72-0.99), male (HR = 0.84, 95% CI: 0.69-1.03) and female (HR = 0.80, 95% CI: 0.64-0.99 for 510-1030 µg/day, HR = 0.84, 95% CI: 0.67-1.06 for >1030 µg/day versus <290 µg/day) subjects with no significant linear trend observed. Despite a lower consumption compared with the Asian population, increased PE intake still appears to decrease lung cancer risk in a Caucasian-dominant population. Future studies are needed to replicate these results in independent cohorts and shed a light on the potential mechanism of the protective effect of PEs on lung carcinogenesis and the interaction between PEs, smoking and endogenous estrogens.

Network pharmacology-based identification for therapeutic mechanism of Ling-Gui-Zhu-Gan decoction in the metabolic syndrome induced by antipsychotic drugs.

BACKGROUND: The metabolic syndrome (MetS) is a common side effect of second-generation antipsychotic drugs (SGAs), leading to poor prognosis in patients with mental illness. The traditional Chinese herbal formula Ling-Gui-Zhu-Gan decoction (LGZGD) is a clinically validated remedy for SGAs-induced MetS, but its underlying mechanism remains unclear. METHODS: A network pharmacology-based analysis was performed to explore predicted plasma-absorbed components, putative therapeutic targets, and main pathways involved in LGZGD bioactivity. We constructed a target interaction network between the predicted targets of LGZGD and the known targets of MetS, after which we extracted major hubs using topological analysis. Thereafter, the maximum value of "edge betweenness" of all interactions was defined as a bottleneck, which suggested its importance in connecting all targets in the network. Finally, a pathway enrichment analysis of major hubs was used to reveal the biological functions of LGZGD. RESULTS: This approach identified 120 compounds and 361 candidate targets of LGZGD. According to the data generated in this study, the interaction between JUN and APOA1 plays a vital role in the treatment of SGAs-induced MetS using LGZGD. Interestingly, JUN was a putative target of LGZGD and APOA1 is one of the known targets of both MetS and SGAs (olanzapine and clozapine). LGZGD was significantly associated with several pathways including PI3K-Akt signaling, insulin resistance, and MAPK signaling pathway. CONCLUSIONS: LGZGD might inhibit JUN and thereby increases the expression of APOA1 to maintain metabolic homeostasis via some vital pathways.

Utilization Patterns of Single Fraction Radiation Therapy for Multiple Myeloma.

BACKGROUND: Patients with multiple myeloma (MM) are living longer than ever before thanks to new therapies. As a consequence, radiation therapy (RT) is increasingly important in the management of bone lesions from MM. Current American Society for Radiation Oncology guidelines recommend greater usage of 8 Gy in 1 fraction for treatment of these lesions. The objective of this study is to analyze utilization of 8 Gy in 1 fraction for treatment of MM bone lesions in the United States utilizing the National Cancer Data Base (NCDB). MATERIALS AND METHODS: The NCDB was used to identify patients with MM treated with palliative RT for painful bony lesions in the period between 2004 and 2014. Utilization rate of RT in this patient population as well as single-fraction (SFRT) versus multiple-fraction RT (MFRT) was compared according to demographic, socioeconomic, and logistic details. RESULTS: A total of 95,190 patients met our inclusion criteria. Of these, 10,261 (10.8%) patients received RT, and a total of 243 (2.4%) of these patients received SFRT over the 10-year period. There was an 11.73% annual increase (P = .0001) in SFRT utilization from 2004 to 2014. Older age, black race, longer distance from the treatment facility, lower degree of education, treatment at an academic or integrated healthcare network, worse comorbidities, and more recent diagnoses were all associated with increased usage of SFRT. CONCLUSION: SFRT for the management of MM painful bony metastases remains underutilized. Trends show that radiation oncologists do not appear to be changing their approach to treating this disease.

Strong inhibition of celastrol towards UDP-glucuronosyl transferase (UGT) 1A6 and 2B7 indicating potential risk of UGT-based herb-drug interaction.

Celastrol, a quinone methide triterpene isolated from Tripterygium wilfordii Hook F., has various biochemical and pharmacological activities, and is now being developed as a promising anti-tumor agent. Inhibitory activity of compounds towards UDP-glucuronosyltransferase (UGT) is an important cause of clinical drug-drug interactions and herb-drug interactions. The aim of the present study is to investigate the inhibition of celastrol towards two important UDP-glucuronosyltransferase (UGT) isoforms UGT1A6 and UGT2B7. Recombinant UGT isoforms and non-specific substrate 4-methylumbelliferone (4-MU) were used. The results showed that celastrol strongly inhibited the UGT1A6 and 2B7-mediated 4-MU glucuronidation reaction, with 0.9 ± 0.1% and 1.8 ± 0.2% residual 4-MU glucuronidation activity at 100 µM of celastrol, respectively. Furthermore, inhibition kinetic study (Dixon plot and Lineweaver-Burk plot) demonstrated that celastrol noncompetitively inhibited the UGT1A1-mediated 4-MU glucuronidation, and competitively inhibited UGT2B7-catalyzed 4-MU glucuronidation. The inhibition kinetic parameters (Ki) were calculated to be 0.49 µM and 0.045 µM for UGT1A6 and UGT2B7, respectively. At the therapeutic concentration of celastrol for anti-tumor utilization, the possibility of celastrol-drug interaction and celastrol-containing herbs-drug interaction were strongly indicated. However, given the complicated nature of herbs, these results should be viewed with more caution.

Initial exploration on the new thought for diagnosis and treatment of systemic lupus erythematosus by integrative Chinese and Western medicine / 中国中西医结合杂志

The pathological changes of systemic lupus erythematosus (SLE) could involve multiple organs and systems, showing a complicated and multivariate clinical features. Since the authors held that the previous clinical disease-syndrome integrative thought can not embody the regularity in the diagnosis and treatment of SLE, in order to establish a novel operable thought of syndrome differentiation which could reflect the clinical practice of SLE, they suggested, in accordance with their clinical experience, that the basis for integration of the disease and its syndromes should not be SLE itself but the clinical manifestations of the organs and systems, such as fever, nervous system injury, lupus kidney, thrombocytopenic purpura of SLE, etc. They claimed that the new clinical thought of diagnosis and treatment will contribute to conduct systematic and standard research on SLE, and the regulation of TCM therapy based on syndrome differentiation would be more closer to the clinical practice of SLE.

Effects of tanguticum maxim polysaccharide on ulcerative colitis induced by TNBS in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate the effects of Tanguticum Maxim polysaccharide (TMP-1) on TNBS-induced colitis in rats.</p><p><b>METHOD</b>Rats with TNBS/ethanol-induced colitis were used and treated with TMP-1 and dexamethasone (DX). Seventy-two rats, including animals with TNBS-induced colitis, were treated with saline, TMP-1 (100, 200, 400 mg.kg-1) and DX. White blood cells were counted on the fifth day and the rats were killed by ether on the sixth day. SOD activity in serum, MPO and SOD activity of colonic tissue were measured.</p><p><b>RESULT</b>The remarkable effects of TMP-1 at dosage of 200, 400 mg.kg-1 on TNBS-induced colitis were observed. The ulcerative area was diminished and weight of colon was reduced. White blood cell population was reduced, SOD activity in serum and SOD activity of colon tissue were remarkably increased, and, MPO activity of colonic tissue was reduced.</p><p><b>CONCLUSION</b>TMP-1 has significant effects on TNBS-induced colitis in rats with lower side effects, which suggests the effective component of rhubarb on colitis perhaps is TMP. The mechanism of the actions of TMP may relate to its antiflammation, antioxidation and immunoloregulation.</p>