[Buzhong Yiqi Decoction ameliorates spleen deficiency syndrome by regulating gut microbiota].

This study aims to decipher the mechanism of Buzhong Yiqi Decoction(BZYQD) in the treatment of spleen deficiency syndrome via gut microbiota. The mouse models of spleen deficiency syndrome were established by fecal microbiota transplantation(FMT, from patients with spleen deficiency syndrome) and administration of Sennae Folium(SF, 10 g·kg~(-1)), respectively, and treated with BZYQD for 5 d. The pseudosterile mice(administrated with large doses of antibiotics) and the mice transplanted with fecal bacteria from healthy human were taken as the controls. The levels of IgA, interleukin(IL)-2, IL-1ß, interferon(IFN)-γ, tumor necrosis factor-alpha(TNF-α), and 5-hydroxytryptamine(5-HT) in the intestinal tissue of two models were measured by enzyme-linked immunosorbent assay, and the CD8~+/CD3~+ ratio was determined by flow cytometry. The composition and changes of the gut microbiota were determined by 16S rRNA high-throughput sequencing and qPCR. Furthermore, the correlation analysis was performed to study the mediating role of gut microbiota in the treatment. The results showed that BZYQD elevated the IgA level, lowered the IL-1ß, TNF-α, and 5-HT levels, and decreased the CD8~+/CD3~+ ratio in the intestinal tissue of the two models. Moreover, BZYQD had two-way regulatory effects on the levels of IL-2 and IFN-γ. BZYQD inhibited the overgrowth and reduced the richness of gut microbiota in the SF model, and improved the gut microbiota structure in the two models. Algoriphagus, Mycobacterium, and CL500＿29＿marine＿group were the common differential genera in the two models compared with the control. Acinetobacter, Parabacteroides, and Ruminococcus were the differential genera unique to the FMT model, and Sphingorhabdus, Lactobacillus, and Anaeroplasma were the unique differential genera in the SF model. BZYQD was capable of regulating all these genera. The qPCR results showed that BZYQD increased the relative abundance of Akkermansia muciniphila and decreased that of Bacteroides uniformis in the two models. The correlation analysis revealed that the levels of above intestinal cytokines were significantly correlated with characteristic gut microorganisms in different mo-dels. The IL-1ß level had a significantly positive correlation with Acinetobacter and CL500＿29＿marine＿group in the two models, while the different levels of IL-2 and IFN-γ in the two models may be related to its different gut microbiota structures. In conclusion, BZYQD could regulate the disordered gut microbiota structure in different animal models of spleen deficiency syndrome to improve the intestinal immune status, which might be one of the mechanisms of BZYQD in treating spleen deficiency syndrome.

Association of serum vitamin D levels on Helicobacter pylori infection: a retrospective study with real-world data.

OBJECTIVE: The aim of this study was to determine whether serum vitamin D levels are associated with H. pylori infection and whether low serum vitamin D levels are an independent risk factor for H. pylori infection. METHODS: We conducted a retrospective analysis of a multicenter cohort study from 2017 to 2019. A total of 415 H. pylori+ patients and 257 H. pylori- patients aged between 18 and 75 years with both 13 C-urea breath test and serum vitamin D level results were included from four hospitals. A questionnaire was used to collect information on potential factors influencing H. pylori infection. RESULTS: Serum vitamin D levels were significantly lower in the H. pylori+ group than in the H. pylori- group (16.7 ± 6.6 ng/ml vs. 19.2 ± 8.0 ng/ml, p < 0.05). Using a cutoff value of 20 ng/ml, the H. pylori infection rate was significantly higher in the vitamin D-deficient group (< 20 ng/ml) than in the vitamin D-nondeficiency group (≥ 20 ng/ml) (66.5% vs. 51.0%, p < 0.001). Ordered logistic regression analysis showed that serum vitamin D levels < 20 ng/ml (OR: 1.652, 95% CI: 1.160-2.351, p = 0.005), higher education levels (OR: 1.774, 95% CI: 1.483-2.119, p < 0.001), family size ≥ 4 (OR: 1.516, 95% CI: 1.081-2.123, p = 0.016), and lower annual income (OR: 1.508, 95% CI: 1.289-1.766, p < 0.001) were independent risk factors for H. pylori infection. CONCLUSION: Lower serum vitamin D levels may be associated with an increased risk of H. pylori infection, and lower serum vitamin D levels are an independent risk factor for increasing H. pylori infection rates. Randomized controlled trials are needed to determine whether supplementation with vitamin D can reduce H. pylori infection rates.

Determinants of Willingness to Undergo Lung Cancer Screening among High-Risk Current and Ex-smokers in Sabah, Malaysia: A Cross-Sectional Pilot Study.

BACKGROUND: Attitudes towards smoking, lung cancer screening, and perceived risk of lung cancer have not been widely studied in Malaysia. The primary objective of this study was to describe the factors affecting the willingness of high-risk current smokers and ex-smokers to undergo low-dose computed tomography (LDCT) screening for lung cancer. METHODS: A prospective, cross-sectional questionnaire study was conducted in current smokers or ex-smokers aged between 55 and 80 years at three hospitals in Kota Kinabalu, Sabah, Malaysia. The questionnaire recorded the following parameters: perceived lung cancer risk; Prostate Lung Colon Ovarian Cancer 2012 risk prediction model excluding race and ethnicity predictor (PLCOm2012norace); demographic characteristics; psychosocial characteristics; and attitudes towards lung cancer and lung cancer screening. RESULTS: A vast majority of the 95 respondents (94.7%) indicated their willingness to undergo screening. Stigma of lung cancer, low levels of knowledge about lung cancer symptoms, concerns about financial constraints, and a preference for traditional medication were still prevalent among the respondents, and they may represent potential barriers to lung cancer screening uptake. A desire to have an early diagnosis (odds ratio [OR], 11.33; 95% confidence interval [CI], 1.53 to 84.05; p=0.02), perceived time constraints (OR, 3.94; 95% CI, 1.32 to 11.73; p=0.01), and proximity of LDCT screening facilities (OR, 14.33; 95% CI, 1.84 to 111.4; p=0.01) had significantly higher odds of willingness to undergo screening. CONCLUSION: Although high-risk current smokers and ex-smokers are likely to undergo screening for lung cancer, several psychosocial barriers persist. The results of this study may guide the policymakers and clinicians regarding the need to improve lung cancer awareness in our population.

Determinants of Willingness to Undergo Lung Cancer Screening among High- Risk Current and Ex-smokers in Sabah, Malaysia: A Cross-Sectional Pilot Study / 결핵및호흡기질환

Background@#Attitudes towards smoking, lung cancer screening, and perceived risk of lung cancer have not been widely studied in Malaysia. The primary objective of this study was to describe the factors affecting the willingness of high-risk current smokers and ex-smokers to undergo low-dose computed tomography (LDCT) screening for lung cancer. @*Methods@#A prospective, cross-sectional questionnaire study was conducted in current smokers or ex-smokers aged between 55 and 80 years at three hospitals in Kota Kinabalu, Sabah, Malaysia. The questionnaire recorded the following parameters: perceived lung cancer risk; Prostate Lung Colon Ovarian Cancer 2012 risk prediction model excluding race and ethnicity predictor (PLCOm2012norace); demographic characteristics; psychosocial characteristics; and attitudes towards lung cancer and lung cancer screening. @*Results@#A vast majority of the 95 respondents (94.7%) indicated their willingness to undergo screening. Stigma of lung cancer, low levels of knowledge about lung cancer symptoms, concerns about financial constraints, and a preference for traditional medication were still prevalent among the respondents, and they may represent potential barriers to lung cancer screening uptake. A desire to have an early diagnosis (odds ratio [OR], 11.33; 95% confidence interval [CI], 1.53 to 84.05; p=0.02), perceived time constraints (OR, 3.94; 95% CI, 1.32 to 11.73; p=0.01), and proximity of LDCT screening facilities (OR, 14.33; 95% CI, 1.84 to 111.4; p=0.01) had significantly higher odds of willingness to undergo screening. @*Conclusion@#Although high-risk current smokers and ex-smokers are likely to undergo screening for lung cancer, several psychosocial barriers persist. The results of this study may guide the policymakers and clinicians regarding the need to improve lung cancer awareness in our population.

Network pharmacological investigation into the mechanism of Kaixinsan powder for the treatment of depression.

Kaixinsan powder (KXS), a classic prescription of traditional Chinese Medicine (TCM), is widely used in the treatment of depression, but its mechanism remains unclear. The network pharmacology method was used to constructe the "herb-component-target" network, and elucidated KXS potential mechanisms of action in the treatment of depression. Moreover, molecular docking was applied to valid the important interactions between the ingredients and the target protein. The "herb-component-target" network indicated that the ingredients of Girinimbin, Gomisin B and Asarone, and the protein targets of ESR, AR and NR3C1 mostly contribute to the antidepressant effect of KXS. KEGG pathway analysis highlighted the most significant pathways associated with depression treatment, including neuroactive ligand-receptor interaction pathway, serotonergic synapse pathway, PI3K-Akt signaling pathway and MAPK signaling pathway. Go enrichment analysis indicated that the mechanism of KXS in treating depression was involved in the biological process of GPCR signal transduction, hormone metabolism and nerve cell apoptosis. Moreover, molecular docking results showed that Polygalaxanthone III, Girinimbine and Pachymic acid performed greater binding ability with key antidepressant target 5-HTR. In conclusion, this study preliminarily revealed key active components in KXS, including Gomisin B, Asarone, Ginsenoside Rg1, Polygalaxanthone III and Pachymic acid, could interact with multiple targets (5-HTR, DR, ADRA, AR, ESR, NR3C1) and modulate the activation of multiple pathways (Neuroactive ligand -receptor interaction pathway, serotonergic synapse pathway, PI3K-Akt signaling pathway and MAPK signaling pathway).

A randomized, multicenter and noninferiority study of amoxicillin plus berberine vs tetracycline plus furazolidone in quadruple therapy for Helicobacter pylori rescue treatment.

OBJECTIVE: Helicobacter pylori (H. pylori) infection is closely associated with gastric ulcers and gastric adenocarcinomas. We aimed to assess the efficacy and safety of a quadruple regimen with amoxicillin plus berberine vs tetracycline plus furazolidone in rescue therapy for H. pylori eradication. METHODS: We conducted a randomized, open-label, multicenter, noninferiority trial. Patients with previous treatment failures recruited from five centers were randomized (1:1) to receive a regimen with esomeprazole and bismuth plus either berberine and amoxicillin (the BA group) or tetracycline and furazolidone (the TF group) for 14 days. Their H. pylori infection status was confirmed 4-8 weeks after treatment. The primary outcome was the eradication rate. The secondary outcomes included the rates of symptom improvement, compliance, and adverse events. This study was registered at ClinicalTrials.gov (NCT03609892). RESULTS: Altogether 658 participants were consecutively enrolled. An intention-to-treat analysis demonstrated that the two regimens achieved a similar eradication rate (76.3% vs 77.5%; P = 0.781). The per-protocol analysis reached a similar result (81.5% vs 85.0%; P = 0.278). The eradication rate reached in the BA group was greater than the pre-established margin of noninferiority, at -10% (the lower bounds of the 95% CI were -7.66% and -9.43%, respectively). The rate of adverse events was lower for the BA group than the TF group (18.5% vs 26.1%, P = 0.024). Rates of compliance and symptom improvement were similar for the two therapies. CONCLUSION: The efficacy of both regimens in rescue treatment for H. pylori eradication was satisfactory, 14-day BA-based quadruple therapy is noninferior to the TF-based therapy.

Buxus alkaloid compound destabilizes mutant p53 through inhibition of the HSF1 chaperone axis.

BACKGROUND: P53 is the most frequently mutated gene in most tumour types, and the mutant p53 protein accumulates at high levels in tumours to promote tumour development and progression. Thus, targeting mutant p53 for degradation is one of the therapeutic strategies used to manage tumours that depend on mutant p53 for survival. Buxus alkaloids are traditionally used in the treatment of cardiovascular diseases. We found that triterpenoid alkaloids extracted from Buxus sinica found in the Yunnan Province exhibit anticancer activity by depleting mutant p53 levels in colon cancer cells. PURPOSE: To explore the anticancer mechanism of action of the triterpenoid alkaloid KBA01 compound by targeting mutant p53 degradation. STUDY DESIGN AND METHODS: Different mutant p53 cell lines were used to evaluate the anticancer activity of KBA01. MTT assay, colony formation assay and cell cycle analysis were performed to examine the effect of KBA01 on cancer cell proliferation. Western blotting and qPCR were used to investigate effects of depleting mutant p53, and a ubiquitination assay was used to determine mutant p53 ubiquitin levels after cells were treated with the compound. Co-IP and small interfering RNA assays were used to explore the effects of KBA01 on the interaction of Hsp90 with mutant p53. RESULTS: The triterpenoid alkaloid KBA01 can induce G2/M cell cycle arrest and the apoptosis of HT29 colon cancer cells. KBA01 decreases the stability of DNA contact mutant p53 proteins through the proteasomal pathway with minimal effects on p53 mutant protein conformation. Moreover, KBA01 enhances the interaction of mutant p53 with Hsp70, CHIP and MDM2, and knocking down CHIP and MDM2 stabilizes mutant p53 levels in KBA01-treated cells. In addition, KBA01 disrupts the HSF1-mutant p53-Hsp90 complex and releases mutant p53 to enable its MDM2- and CHIP-mediated degradation. CONCLUSION: Our study reveals that KBA01 depletes mutant p53 protein in a chaperone-assisted ubiquitin/proteasome degradation pathway in cancer cells, providing insights into potential strategies to target mutant p53 tumours.

Progressive study of the effect of superfine green tea, soluble tea, and tea polyphenols on the physico-chemical and structural properties of wheat gluten in noodle system.

In this study, the improving effects of green tea powder, soluble tea, and tea polyphenols on the mixing and tensile qualities of dough and texture of tea-enriched noodles, as well as the physico-chemical and structural properties of gluten proteins were progressively investigated. Dough strength and noodle texture were significantly increased by all the three tea products. Tea polyphenols in particular presented the most effective improvement with highest dough stability, resistance, and noodle chewiness. SEM indicated that tea products all induced a more developed gluten network, and polyphenol noodle showed the most continuous and ordered structure. FT-IR and fluorescence spectrum indicated that tea polyphenols promoted an enhancement in α-helix structure and the hydrophobic interactions. Tea polyphenols induced the SH/SS interchange during processing and cooking, and enhanced the water-solids interaction in noodles. AFM results showed that polyphenols induced the polymerization of gluten protein molecular chains, with increased chain height and width.

Influence of serum vitamin D level on Helicobacter pylori eradication: A multi-center, observational, prospective and cohort study.

OBJECTIVES: This study was designed to test whether serum vitamin D levels affected Helicobacter pylori (H. pylori) infection and eradication rates. METHODS: A multicenter observational prospective cohort study was conducted. A total of 496 H. pylori- positive (H. pylori+ ) and 257 H. pylori-negative (H. pylori- ) patients were enrolled from four hospitals in China. Baseline serum vitamin D levels were measured and a 13 C-urea breath test (UBT) was performed for all the participants. The H. pylori+ patients were divided into two subgroups based on their serum vitamin D levels (<10 or ≥10 ng/mL). A second 13 C-UBT was performed between 4 and 8 weeks after 14-day bismuth-containing quadruple eradication therapies. Factors potentially affecting H. pylori eradication were determined using a questionnaire survey. RESULTS: Serum vitamin D levels were significantly lower in the H. pylori+ group than in the H. pylori- group ([17.0 ± 6.9] ng/mL vs [19.2 ± 8.0] ng/mL, P = 0.000). H. pylori eradication rate significantly differed between patients with serum vitamin D levels of <10 ng/mL and ≥10 ng/mL (71.7% vs 87.3%, P = 0.005). A multivariate analysis showed that having serum vitamin D level ≥10 ng/mL was an independent risk factor for a successful H. pylori eradication (odds ratio 0.381, 95% confidence interval 0.183-0.791, P = 0.010). CONCLUSIONS: Serum vitamin D level may affect H. pylori infection and its eradication. Randomized controlled trials are needed to find out whether vitamin D supplements may increase the H. pylori eradication rate.

Vitis thunbergii var. taiwaniana Extracts and Purified Compounds Ameliorate Obesity in High-Fat Diet-Induced Obese Mice.

The increasing prevalence of obesity continues to gain more attention worldwide. In this study, diet-induced obese mice were used to evaluate the antiobesity effects of extracts, fractions, and purified compounds from Vitis thunbergii var. taiwaniana (VTT). The C57BL/6J mice were fed a 5-week high-fat diet (HF) concurrently with ethanol extracts (Et-ext, 80 mg/kg) from roots (R), stems (S), and leaves (L) by oral gavage daily. Only R-Et-ext interventions showed significant weight reduction in mice compared with those in the HF group; however, mouse plasma contents of total cholesterols (TC), total triglycerides (TG) and low-density lipoproteins (LDL) of all three Et-ext intervened groups showed significant reductions compared with those in the HF group. Furthermore, intervention with the ethyl acetate-partitioned fraction (EA-fra, 60 mg/kg) from R-Et-ext but not the n-butanol-partitioned fraction or water fraction from R-Et-ext showed significant weight reduction in mice compared with those in the HF group. The same molecular weights of three resveratrol tetramers, (+)-hopeaphenol, (+)-vitisin A, and (-)-vitisin B, were isolated from the EA-fra of VTT-R. The (+)-vitisin A and fenofibrate (25 mg/kg) but not the (+)-hopeaphenol and (-)-vitisin B interventions showed significant weight reduction in mice compared with those in the HF group. The total feed intake among the HF groups with or without interventions showed no significant differences. The mouse plasma contents of TC, TG, LDL, free fatty acid, and plasma lipase activity of the three resveratrol tetramer-intervened groups showed reductions in the mice compared with those in the HF group. It was proposed that the lipase inhibitory activities of VTT extracts and purified resveratrol tetramers might contribute in part to the antiobesity effect, and these results suggested that VTT may be developed as functional food for achieving antiobesity objectives and requires further investigation.

Effects of yam tuber protein, dioscorin, on attenuating oxidative status and learning dysfunction in d-galactose-induced BALB/c mice.

The yam tuber is a traditional Chinese medicine used in long-term treatment as a juvenescent substance. The purified yam tuber's major water-soluble protein, dioscorin, and its protease hydrolysates have been reported to have several biological activities. In this study, d-galactose (Gal) was subcutaneously injected into the dorsal necks of BALB/c mice daily for 10weeks (Gal group) to induce oxidative stress. By the fifth week, 20 or 80mg dioscorin/kg was orally administered daily combined with a daily Gal injection until the end of the study. The plasma malondialdehyde (MDA) level and advanced glycation end-products obtained after dioscorin oral administrations were lower compared to the Gal group. In addition, the latency and swimming distance in the mice that received dioscorin administration were significantly improved compared to the Gal group in the Morris water maze. Dioscorin administration resulted in higher GSH levels and oxygen radical antioxidant capacity (ORAC) activity and lower MDA and inducible nitric oxide synthase (iNOS) levels in the brain compared to mice in the Gal group. These elevated antioxidant activities following oral administration of yam dioscorin in vivo may reflect traditional juvenescent uses with the potential for anti-aging treatments.

Effects of different types of yam (Dioscorea alata) products on the blood pressure of spontaneously hypertensive rats.

The aim of the present study was to investigate different yam treatments, including powdered-yam-products (PYP) and liquid-yam-products (LYP), with respect to spontaneously hypertensive rats (SHRs) blood pressure. PYP included alcohol-insoluble-solids of yam tuber, hot-air-drying (HAD) of yam tuber slices, steam-cooked once or twice followed by HAD which were subsequently powdered. LYP included water extracts of yam tuber (WEY) heated at 90 degrees C (WEY90H) or 95 degrees C for 10 min (WEY95H), and then stored at 4 degrees C for different numbers of day. PYP, WEY, and WEYH were found effectively to reduce the blood pressure of SHR and should be beneficial in food processing in the development of functional foods for blood pressure regulation.

[Protective effects of Sini decoction on adriamycin-induced heart failure and its mechanism: role of superoxide dismutase].

OBJECTIVE: To investigate the role of superoxide dismutase (SOD) in Adriamycin (ADR)-induced heart failure and the protective effects of Sini decoction (SND). METHOD: SD rats were randomly divided into three groups, control group, heart failure group and SND group. ADR was injected in the rats of heart failure group and SND group by caudal vein. After injection, the rats in SND group were given SND (3.75 g x kg(-1) x d(-1), p.o.). Three weeks later, cardiac function, content of malondialdehyde (MDA) of both myocardium and mitochondria and activity of Cu-Zn SOD and Mn SOD were measured. The mRNA expression of Cu-Zn SOD and Mn SOD were also detected by RT-PCR. RESULT: Compared with control group, LVSP and +/- dp/dt max were obviously decreased, while LVEDP was markedly increased in the heart failure group. The mRNA expression and the activity of Cu-Zn SOD and Mn SOD in heart failure group were obviously lower than that in the controls'. In addition, the MDA content of both myocardium and mitochondria were clearly increased in heart failure rats. In SND-treated rats, the cardiac function, the activity and the mRNA expression of Cu-Zn SOD and Mn SOD were significantly elevated and the content of MDA was reduced, which had no statistic difference with the rats in control group. CONCLUSION: The data suggest that oxidative stress is present in the mitochondria of myocardium in ADR-induced heart failure rats and it can be eased by SND. The mechanism may be closely related to SOD.

Protective effects of Sini decoction on adriamycin-induced heart failure and its mechanism: role of superoxide dismutase / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the role of superoxide dismutase (SOD) in Adriamycin (ADR)-induced heart failure and the protective effects of Sini decoction (SND).</p><p><b>METHOD</b>SD rats were randomly divided into three groups, control group, heart failure group and SND group. ADR was injected in the rats of heart failure group and SND group by caudal vein. After injection, the rats in SND group were given SND (3.75 g x kg(-1) x d(-1), p.o.). Three weeks later, cardiac function, content of malondialdehyde (MDA) of both myocardium and mitochondria and activity of Cu-Zn SOD and Mn SOD were measured. The mRNA expression of Cu-Zn SOD and Mn SOD were also detected by RT-PCR.</p><p><b>RESULT</b>Compared with control group, LVSP and +/- dp/dt max were obviously decreased, while LVEDP was markedly increased in the heart failure group. The mRNA expression and the activity of Cu-Zn SOD and Mn SOD in heart failure group were obviously lower than that in the controls'. In addition, the MDA content of both myocardium and mitochondria were clearly increased in heart failure rats. In SND-treated rats, the cardiac function, the activity and the mRNA expression of Cu-Zn SOD and Mn SOD were significantly elevated and the content of MDA was reduced, which had no statistic difference with the rats in control group.</p><p><b>CONCLUSION</b>The data suggest that oxidative stress is present in the mitochondria of myocardium in ADR-induced heart failure rats and it can be eased by SND. The mechanism may be closely related to SOD.</p>

Patatin, the tuber storage protein of potato (Solanum tuberosum L.), exhibits antioxidant activity in vitro.

The potato (Solanum tuberosum L.) tuber storage protein, patatin, was purified to homogeneity with a molecular mass of 45 kDa. The purified patatin showed antioxidant or antiradical activity by a series of in vitro tests, including 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical (half-inhibition concentration, IC(50), was 0.582 mg/mL) scavenging activity assays, anti-human low-density lipoprotein peroxidation tests, and protections against hydroxyl radical-mediated DNA damages and peroxynitrite-mediated dihydrorhodamine 123 oxidations. Using electron paramagnetic resonance (EPR) spectrometry for hydroxyl radical detections, it was found that the intensities of the EPR signal were decreased by the increased amounts of patatin added (IC(50) was 0.775 mg/mL). Through modifications of patatin by iodoacetamide or N-bromosuccinimide, it was found that the antiradical activities of modified patatin against DPPH or hydroxyl radicals were decreased. It was suggested that cysteine and tryptophan residues in patatin might contribute to its antioxidant activities against radicals.