The association between tea consumption and non-malignant digestive system diseases: A Mendelian randomized study.

BACKGROUND: Tea consumption might be closely related to non-malignant digestive diseases. Nevertheless, this correlation remains inadequately comprehended. Therefore, our objective was to elucidate the essence of these connections. METHODS: This study employed a Mendelian randomization approach to investigate the impact of tea consumption on specific digestive disorders. Genetic data associated with tea consumption were obtained from the UK Biobank (UKB), encompassing 447,485 participants. We chose a gene-wide association study with no sample overlap and UKB as our data source for all outcomes. The primary analytical method utilized was inverse variance weighting, and multiple analytical models were employed to enhance the analysis's reliability and ensure robust results. RESULT: Our investigation revealed that tea consumption was linked to an elevated susceptibility to gastroesophageal reflux disease (GERD). However, there was a lack of substantial evidence suggesting an association between tea intake and Crohn's disease (CD), ulcerative colitis (UC), or non-alcoholic fatty liver disease (NAFLD). CONCLUSIONS: Our study suggests that the excessive consumption of tea may heighten the likelihood of GERD. These results hold potential significance in guiding dietary pattern modifications for individuals with GERD. Furthermore, there may be value in implementing GERD monitoring and preventive measures in populations with elevated tea consumption.

Comparative Pharmacokinetics Research of 13 Bioactive Components of Jieyu Pills in Control and Attention Deficit Hyperactivity Disorder Model Rats Based on UPLC-Orbitrap Fusion MS.

Jieyu Pills (JYPs), a Chinese medicine consisting of 10 herbal elements, have displayed promising clinical effectiveness and low by-effects in the treatment of depression. Prior investigations mostly focused on elucidating the mechanism and therapeutic efficacy of JYPs. In our earlier study, we provided an analysis of the chemical composition, serum pharmacochemistry, and concentrations of the main bioactive chemicals found in JYPs. However, our precise understanding of the pharmacokinetics and metabolism remained vague. This study involved a comprehensive and meticulous examination of the pharmacokinetics of 13 bioactive compounds in JYPs. Using UPLC-Orbitrap Fusion MS, we analyzed the metabolic characteristics and established the pharmacokinetic parameters in both control rats and model rats with attention deficit hyperactivity disorder (ADHD) following oral administration of the drug. Before analysis, plasma samples that were collected at different time intervals after the administration underwent methanol pre-treatment with Puerarin used as the internal standard (IS) solution. Subsequently, the sample was chromatographed on a C18 column employing gradient elution. The mobile phase consisted of methanol solution containing 0.1% formic acid in water. The electrospray ionization source (ESI) was utilized for ionization, whereas the scanning mode employed was selected ion monitoring (SIM). The UPLC-Orbitrap Fusion MS method was subjected to a comprehensive validation process to assess its performance. The method demonstrated excellent linearity (r ≥ 0.9944), precise measurements (RSD < 8.78%), accurate results (RE: -7.88% to 8.98%), and appropriate extraction recoveries (87.83-102.23%). Additionally, the method exhibited minimal matrix effects (87.58-101.08%) and satisfactory stability (RSD: 1.52-12.42%). These results demonstrated adherence to the criteria for evaluating and determining biological material. The 13 bioactive compounds exhibited unique pharmacokinetic patterns in vivo. In control rats, all bioactive compounds except Ferulic acid exhibited linear pharmacokinetics within the dose ranges. In the ADHD model, the absorption rate and amount of most of the components were both observed to have increased. Essentially, this work is an important reference for examining the metabolism of JYPs and providing guidelines for clinical therapy.

Screening and characterization of an anti-inflammatory pectic polysaccharide from Cucurbita moschata Duch.

Pectin polysaccharides have demonstrated diverse biological activities, however, the inflammatory potential of pectin polysaccharides extracted from Cucurbita moschata Duch remains unexplored. This study aims to extract, characterize and evaluate the effects of pumpkin pectin polysaccharide on lipopolysaccharide (LPS)-induced inflammatory response in RAW264.7 cells and dextran sulfate sodium (DSS)-induced colitis in mice, along with its underlying mechanism of action. Initially, we extracted three fractions of pectin polysaccharides from pumpkin and screened them for anti-inflammatory activity in LPS-induced macrophages, identifying CMDP-3a as the most potent anti-inflammatory fraction. Subsequently, CMDP-3a underwent comprehensive characterization through chromatography and spectroscopic analysis, revealing CMDP-3a as an RG-I-HG type pectin polysaccharide with →4)-α-D-GalpA-(1 â†’ and →4)-α-D-GalpA-(1 â†’ 2,4)-α-L-Rhap-(1 â†’ as the main chain. Further, in the LPS-induced RAW264.7 cells model, treatment with CMDP-3a significantly down-regulated the mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and pro-inflammatory cytokines (IL-1ß, TNF-α, and IL-6) by inhibiting the MAPK and NF-κB signaling pathways. Finally, in a mouse colitis model, CMDP-3a administration obviously inhibited DSS-induced pathological alterations and reduced inflammatory cytokine expressions in the colonic tissues by down-regulating the TLR4/NF-κB and MAPK pathways. These findings provide a molecular basis for the potential application of CMDP-3a in reducing inflammatory responses.

Dietary purple potato supplement attenuates DSS-induced colitis in mice: impact on mitochondrial function.

Inflammatory bowel disease (IBD) is a condition characterized by disrupted intestinal barrier function, abnormal immune response, and mucosal structure loss. This study evaluated the beneficial role of purple potato (PP) supplementation against IBD symptoms using a murine model of dextran sulfate sodium (DSS)-induced colitis, and further explored the underlying mechanisms. Six-week-old C57BL/6J male mice were randomized into two groups and fed a standard rodent diet with or without 10% PP powder for 7 weeks. At the 5th week of dietary supplements, mice in each group were further divided into two subgroups and were either induced with or without 2.5% DSS induction for 7 days, followed by 7 days of recovery. Data showed that PP supplementation ameliorated the disease activity index in DSS-treated mice and reversed the colonic structure loss, mucosal damage, macrophage infiltration, and pro-inflammatory cytokine secretion induced by DSS in the colonic tissue. PP supplementation also restored the levels of tight junction proteins and caudal type homeobox 2 in DSS-treated mice. Furthermore, dietary PP enhanced peroxisome proliferator-activated receptor-γ coactivator-1α signaling pathway, mitochondrial biogenesis, mitochondrial proteostasis, and protein-folding capacity. In summary, dietary PP ameliorated DSS-induced colitis and improved gut structures and barrier function, which was associated with improved mitochondrial function. These results support further investigation of PP as a potential dietary intervention for IBD.

Hydrogel Encapsulating Wormwood Essential Oil with Broad-spectrum Antibacterial and Immunomodulatory Properties for Infected Diabetic Wound Healing.

The integration of hydrogels with bio-friendly functional components through simple and efficient strategies to construct wound dressings with broad-spectrum antibacterial and immunomodulatory properties to promote the healing of infected diabetic wounds is highly desirable but remains a major challenge. Here, wormwood essential oil (WEO) is effectively encapsulated in the hydrogel via an O/W-Pickering emulsion during the polymerization of methacrylic anhydride gelatin (GelMA), acrylamide (AM), and acrylic acid N-hydroxysuccinimide ester (AAc-NHS) to form a multifunctional hydrogel dressing (HD-WEO). Compared with conventional emulsions, Pickering emulsions not only improve the encapsulation stability of the WEO, but also enhance the tensile and swelling properties of hydrogel. The synergistic interaction of WEO's diverse bioactive components provides a broad-spectrum antibacterial activity against S. aureus, E. coli, and MRSA. In addition, the HD-WEO can induce the polarization of macrophages from M1 to M2 phenotype. With these advantages, the broad-spectrum antibacterial and immunomodulatory HD-WEO effectively promotes the collagen deposition and neovascularization, thereby accelerating the healing of MRSA-infected diabetic wounds.

Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies.

BACKGROUND: The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. RESULTS: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. CONCLUSIONS: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

YuPingFeng (YPF) upregulates caveolin-1 (CAV1) to alleviate pulmonary fibrosis through the TGF-ß1/Smad2 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) is considered a valuable asset in China's medical tradition. YPF is a classic prescription that has been derived from the "Jiu Yuan Fang" formula and consists of three herbs: Huangqi (Astragalus membranaceus Bunge), Baizhu (Atractylodes rubra Dekker), and Fangfeng (Saposhnikovia divaricata (Turcz.) Schischk). This prescription is widely acclaimed for its exceptional pharmacological properties, including potent antioxidant effects, hormone regulation, and immune modulation effects. AIM OF THE STUDY: Previous research provides evidence suggesting that YPF may have therapeutic effects on pulmonary fibrosis. Further exploration is essential to confirm its effectiveness and elucidate the fundamental processes. MATERIALS AND METHODS: First, the active components and target genes of YPF were extracted from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Next, the GSE53845 dataset, which contains information on pulmonary fibrosis, was downloaded from the GEO database. Network informatics methods was then be utilized to identify target genes associated with pulmonary fibrosis. A YPF-based network of protein-protein interactions was constructed to pinpoint possible target genes for pulmonary fibrosis treatment. Additionally, an in vitro model of pulmonary fibrosis induced by bleomycin (BLM) was established to further investigate and validate the possible mechanisms underlying the effectiveness of YPF. RESULTS: In this study, a total of 24 active ingredients of YPF, along with 178 target genes associated with the treatment, were identified. Additionally, 615 target genes related to pulmonary fibrosis were identified. Functional enrichment analysis revealed that 18 candidate genes (CGs) exhibited significant responses to tumor necrosis factor, NF-kB survival signaling, and positive regulation of apoptosis processes. Among these CGs, CAV1, VCAM1, and TP63 were identified as key target genes. Furthermore, cell experiments confirmed that the expression of CAV1 protein and RNA expression was increased in pulmonary fibrosis, but significantly decreased after treatment with YPF. Additionally, the expression of pSmad2, α-SMA, TGF-ß1, and TNF-α was also decreased following YPF treatment. CONCLUSIONS: Network pharmacology analysis revealed that YPF exhibits significant potential as a therapeutic intervention for pulmonary fibrosis by targeting various compounds and pathways. This study emphasizes that the efficacy of YPF in treating pulmonary fibrosis may be attributed to its ability to up-regulate CAV1 expression and inhibiting pulmonary fibrosis via modulation of the TGF-ß1/Smad2 signaling pathway. These findings underscore the promising role of YPF and its ability to potentially alleviate pulmonary fibrosis.

Study of the curative effect of Zhang's Xibi formula and its underlying mechanism involving inhibition of inflammatory responses and delay of knee osteoarthritis.

OBJECTIVE: To verify the clinical efficacy of Zhang's Xibi formula (ZSXBF) and explain the mechanism underlying its therapeutic effect. METHODS: Preliminary elucidation of the clinical efficacy of ZSXBF in treating KOA in self-control studies, exploration of its mechanism of action with network pharmacology methods, and validation in animal experiments. RESULTS: In clinical studies, ZSXBF administration effectively improved patient quality of life and reduce pain. Network pharmacology was used to explore the possible mechanisms underlying its treatment effect, and after verification in clinical experience and animal experiments, it was found that ZSXBF regulated the expression of immune-related proteins such as IL-17, ERK1, and TP53 in mouse knee joints. CONCLUSION: ZSXBF, which is a traditional Chinese medicine compound that is used to clear heat and detoxify, can effectively improve the clinical symptoms of KOA patients, and its underlying mechanism includes the regulation of human immune-related proteins.

Changes in Coffee Intake, Added Sugar and Long-Term Weight Gain - Results from Three Large Prospective US Cohort Studies.

BACKGROUND: Consumption of both caffeinated and decaffeinated coffee has been reported to attenuate long-term weight gain. Whether the association between coffee consumption and weight gain depends on the addition of sugar, cream, or coffee whitener remains unclear. OBJECTIVE: We aimed to study the associations between changes in coffee consumption, caffeine intake, and weight changes by considering the addition of sugar, cream, or a nondairy coffee whitener. METHODS: We used 3 large prospective cohorts - the Nurses' Health Study (1986 - 2010), Nurses' Health Study II (1991 - 2015) and Health Professional Follow-up Study (1991 - 2014). We applied multivariable linear regression models with robust variance estimators to assess the association of changes in coffee habits within each 4-y interval with concurrent weight changes. Results across the 3 cohorts were pooled using inverse-variance weights. RESULTS: After multivariable adjustment, each 1 cup per day increment in unsweetened caffeinated coffee was associated with a reduction in 4-y weight gain of -0.12 kg (95 % CI: -0.18, -0.05 kg) and of -0.12 kg (95 % CI: -0.16, -0.08 kg) for unsweetened decaffeinated coffee. The habits of adding cream or nondairy coffee whitener were not significantly linked to weight changes. Adding a teaspoon of sugar was associated with a 4-y weight gain of +0.09 kg (0.07, 0.12 kg). Stratified analyses suggested stronger magnitude of the observed associations with younger age and higher baseline BMI. Neither caffeine nor coffee modified the association of adding sugar to any food or beverage with weight changes. CONCLUSIONS: An increase in intake of unsweetened caffeinated and decaffeinated coffee was inversely associated with weight gain. The addition of sugar to coffee counteracted coffee's benefit for possible weight management. To the contrary, adding cream or coffee whitener was not associated with greater weight gain.

Trends and hotspots of acupuncture for allergic rhinitis: A bibliometric analysis from 2002 to 2022.

OBJECTIVE: The study aims to investigate and visualize the hotspots of acupuncture for Allergic rhinitis (AR) over the past two decades and pinpoint future trends in this field. METHOD: We conducted a systematic search of English-language articles or reviews on acupuncture for AR in the Web of Science Core Collection from 2002 to 2022. Using Citespace, VOSviewer, and Bibliometrix, we analyzed and visualized the publications, countries, institutions, authors, journals, and keywords from various angles. RESULT: The study identified 197 documents, 80 journals, 458 keywords, and 928 authors associated with acupuncture for AR. Although article publication fluctuated over the past 20 years, an overall upward trend emerged, with rapid growth during the second decade. China contributed the most to acupuncture research on AR and had the closest collaborations with the United States and Germany. China Medical University was the most prolific institution, and Benno Brinkhaus was the most productive and influential author. The most published journal was Medicine, while the Journal of Allergy and Clinical Immunology was the most frequently cited journal. The highest frequency keywords included acupuncture, allergic rhinitis, and asthma. Randomized controlled trials and alternative & complementary medicine remained significant research hotspots, while rhinoconjunctivitis is expected to be the emerging focus of future investigations. CONCLUSION: acupuncture has experienced robust development for the treatment of allergic rhinitis over the last two decades, with rhinoconjunctivitis and clinical research being the anticipated trends and frontiers of future research.

Methyl Donor Nutrient Intake and Incidence of Type 2 Diabetes: Results From Three Large U.S. Cohorts.

OBJECTIVE: We examined whether intake of methyl donor nutrients, including vitamins B2, B6, and B12 and folate, from foods and/or supplements is associated with type 2 diabetes risk. RESEARCH DESIGN AND METHODS: We included 203,644 women and men from the Nurses' Health Study (1984-2016), Nurses' Health Study 2 (1991-2017), and Health Professionals Follow-Up Study (1986-2016). Dietary data were collected every 2-4 years with use of semiquantitative food-frequency questionnaires. Cox proportional hazards models with time-varying covariates were used to evaluate associations between each nutrient and type 2 diabetes risk. We combined cohort-specific hazard ratios (HRs) using inverse variance-weighted fixed-effects meta-analyses. RESULTS: During 4,900,181 person-years of follow-up, we documented 19,475 incident type 2 diabetes cases. In multivariable-adjusted meta-analyses, participants in the highest quintiles of total vitamin B2 and B6 intakes had lower risk of diabetes compared with those in the lowest quintiles (HR 0.93 [95% CI 0.89, 0.98] for B2 and 0.93 [0.89, 0.97] for B6). With stratification by source, significant associations remained for B2 from food but not from supplements. Neither association for B6 from food nor association for B6 from supplements attained significance. No association was observed between total B12 intake and diabetes. However, B12 from food was marginally associated with higher diabetes risk (1.05 [1.00-1.11]) but not after additional adjustment for red meat intake (1.04 [0.99-1.10]). No evidence of association was observed between intakes of folate and diabetes. CONCLUSIONS: The results of our study suggest that higher intake of vitamin B2 and B6, especially B2 from food sources, may be associated with a modestly lower type 2 diabetes risk.

Omega-3 Fatty Acid Biomarkers and Incident Atrial Fibrillation.

BACKGROUND: The relationship between omega-3 fatty acids and atrial fibrillation (AF) remains controversial. OBJECTIVES: This study aimed to determine the prospective associations of blood or adipose tissue levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with incident AF. METHODS: We used participant-level data from a global consortium of 17 prospective cohort studies, each with baseline data on blood or adipose tissue omega-3 fatty acid levels and AF outcomes. Each participating study conducted a de novo analyses using a prespecified analytical plan with harmonized definitions for exposures, outcome, covariates, and subgroups. Associations were pooled using inverse-variance weighted meta-analysis. RESULTS: Among 54,799 participants from 17 cohorts, 7,720 incident cases of AF were ascertained after a median 13.3 years of follow-up. In multivariable analysis, EPA levels were not associated with incident AF, HR per interquintile range (ie, the difference between the 90th and 10th percentiles) was 1.00 (95% CI: 0.95-1.05). HRs for higher levels of DPA, DHA, and EPA+DHA, were 0.89 (95% CI: 0.83-0.95), 0.90 (95% CI: 0.85-0.96), and 0.93 (95% CI: 0.87-0.99), respectively. CONCLUSIONS: In vivo levels of omega-3 fatty acids including EPA, DPA, DHA, and EPA+DHA were not associated with increased risk of incident AF. Our data suggest the safety of habitual dietary intakes of omega-3 fatty acids with respect to AF risk. Coupled with the known benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption can be maintained.

Extracorporeal Shock Wave Combined with Warm Acupuncture for External Humeral Epicondylitis: A Randomized Clinical Trial.

Objective: The purpose of this study was to evaluate the clinical efficacy of extracorporeal shock wave combined with warm acupuncture for external humeral epicondylitis. Methods: Eighty-two patients with external humeral epicondylitis were randomly divided into an observation group and a control group. Patients in the control group were treated with extracorporeal shock waves while those in observation group with warm acupuncture on the basis of the control group. Patients in both groups were evaluated by Visual Analogue Scale (VAS), Mayo Elbow Performance Score (MEPS), Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) before and after treatment. The inflammatory factors such as IL-6, IL-10, TNF-ɑ and clinical outcomes were contrasted before and after treatment. Results: There were statistically significant differences in VAS score, MEPS score and DASH score between the two groups before and after treatment (P<0.05), and the improvement of each score in the observation group was more obvious than that in the control group. After treatment, the inflammatory factors of the two groups were lower than those before treatment, and the difference was statistically significant (P<0.05). The decrease of inflammatory factors in the observation group was more obvious than that in the control group. The total effective rate of the observation group was higher than that of the control group, and the difference was statistically significant (P<0.05). Conclusion: Extracorporeal shock wave combined with warm acupuncture could effectively improve the pain symptoms and dysfunction of external humeral epicondylitis and reduce the expression of inflammatory factors, and its effect may be better than that of extracorporeal shock wave treatment alone. Clinical Trial Registration: ChiCTR2200066075.

Exopolysaccharide riclin and anthocyanin-based composite colorimetric indicator film for food freshness monitoring.

Food freshness monitoring is vital to ensure food safety. Recently, packaging materials incorporating pH-sensitive films have been employed to monitor the freshness of food products in real time. The film-forming matrix of the pH-sensitive film is essential to maintain the desired physicochemical functions of the packaging. Conventional film-forming matrices, such as polyvinyl alcohol (PVA), have drawbacks of low water resistance, poor mechanical properties, and weak antioxidant ability. In this study, we successfully synthesise PVA/riclin (P/R) biodegradable polymer films to overcome these limitations. The films feature riclin, an agrobacterium-derived exopolysaccharide. The uniformly dispersed riclin conferred outstanding antioxidant activity to the PVA film and significantly improved its tensile strength and barrier properties by forming hydrogen bonds. Purple sweet potato anthocyanin (PSPA) was used as a pH indicator. The intelligent film with added PSPA provided robust surveillance of volatile ammonia and changed its color within 30 s in the pH range of 2-12. This multifunctional colorimetric film also engendered discernible color changes when the quality of shrimp deteriorated, demonstrating its great potential as an intelligent packaging material to monitor food freshness.

Design and Application of Hybrid Polymer-Protein Systems in Cancer Therapy.

Polymer-protein systems have excellent characteristics, such as non-toxic, non-irritating, good water solubility and biocompatibility, which makes them very appealing as cancer therapeutics agents. Inspiringly, they can achieve sustained release and targeted delivery of drugs, greatly improving the effect of cancer therapy and reducing side effects. However, many challenges, such as reducing the toxicity of materials, protecting the activities of proteins and controlling the release of proteins, still need to be overcome. In this review, the design of hybrid polymer-protein systems, including the selection of polymers and the bonding forms of polymer-protein systems, is presented. Meanwhile, vital considerations, including reaction conditions and the release of proteins in the design process, are addressed. Then, hybrid polymer-protein systems developed in the past decades for cancer therapy, including targeted therapy, gene therapy, phototherapy, immunotherapy and vaccine therapy, are summarized. Furthermore, challenges for the hybrid polymer-protein systems in cancer therapy are exemplified, and the perspectives of the field are covered.

Beverage consumption and mortality among adults with type 2 diabetes: prospective cohort study.

OBJECTIVE: To investigate the intake of specific types of beverages in relation to mortality and cardiovascular disease (CVD) outcomes among adults with type 2 diabetes. DESIGN: Prospective cohort study. SETTING: Health professionals in the United States. PARTICIPANTS: 15 486 men and women with a diagnosis of type 2 diabetes at baseline and during follow-up (Nurses' Health Study: 1980-2018; and Health Professionals Follow-Up Study: 1986-2018). Beverage consumption was assessed using a validated food frequency questionnaire and updated every two to four years. MAIN OUTCOME MEASURES: The main outcome was all cause mortality. Secondary outcomes were CVD incidence and mortality. RESULTS: During an average of 18.5 years of follow-up, 3447 (22.3%) participants with incident CVD and 7638 (49.3%) deaths were documented. After multivariable adjustment, when comparing the categories of lowest intake of beverages with the highest intake, the pooled hazard ratios for all cause mortality were 1.20 (95% confidence interval 1.04 to 1.37) for sugar sweetened beverages (SSBs), 0.96 (0.86 to 1.07) for artificially sweetened beverages (ASBs), 0.98 (0.90 to 1.06) for fruit juice, 0.74 (0.63 to 0.86) for coffee, 0.79 (0.71 to 0.89) for tea, 0.77 (0.70 to 0.85) for plain water, 0.88 (0.80 to 0.96) for low fat milk, and 1.20 (0.99 to 1.44) for full fat milk. Similar associations were observed between the individual beverages and CVD incidence and mortality. In particular, SSB intake was associated with a higher risk of incident CVD (hazard ratio 1.25, 95% confidence interval 1.03 to 1.51) and CVD mortality (1.29, 1.02 to 1.63), whereas significant inverse associations were observed between intake of coffee and low fat milk and CVD incidence. Additionally, compared with those who did not change their consumption of coffee in the period after a diabetes diagnosis, a lower all cause mortality was observed in those who increased their consumption of coffee. A similar pattern of association with all cause mortality was also observed for tea, and low fat milk. Replacing SSBs with ABSs was significantly associated with lower all cause mortality and CVD mortality, and replacing SSBs, ASBs, fruit juice, or full fat milk with coffee, tea, or plain water was consistently associated with lower all cause mortality. CONCLUSIONS: Individual beverages showed divergent associations with all cause mortality and CVD outcomes among adults with type 2 diabetes. Higher intake of SSBs was associated with higher all cause mortality and CVD incidence and mortality, whereas intakes of coffee, tea, plain water, and low fat milk were inversely associated with all cause mortality. These findings emphasize the potential role of healthy choices of beverages in managing the risk of CVD and premature death overall in adults with type 2 diabetes.

Chondroprotective Mechanism of Eucommia ulmoides Oliv.-Glycyrrhiza uralensis Fisch. Couplet Medicines in Knee Osteoarthritis via Experimental Study and Network Pharmacology Analysis.

Background: Knee osteoarthritis (KOA) is the primary prevalent disabling joint disorder among osteoarthritis (OA), and there is no particularly effective treatment at the clinic. Traditional Chinese medicine (TCM) herbs, such as Eucommia ulmoides Oliv. and Glycyrrhiza uralensis Fisch. (E.G.) couplet medicines, have been reported to exhibit beneficial health effects on KOA, exact mechanism of E.G. nevertheless is not fully elucidated. Purpose: We assess the therapeutic effects of E.G. on KOA and explore its underlying molecular mechanism. Methods: UPLC-Q-TOF/MS technique was used to analyze the active chemical constituents of E.G. The destabilization of the medial meniscus model (DMM) was employed to evaluate the chondroprotective action of E.G. in KOA mice using histomorphometry, µCT, behavioral testing and immunohistochemical staining. Additionally, network pharmacology and molecular docking were used to predict potential targets for anti-KOA activities of E.G., which was further verified through in vitro experiments. Results: In vivo studies have shown that E.G. could significantly ameliorate DMM-induced KOA phenotypes including subchondral bone sclerosis, cartilage degradation, gait abnormality and thermal pain reaction sensibility. E.G. treatment could also promote extracellular matrix synthesis to protect articular chondrocytes, which was indicated by Col2 and Aggrecan expressions, as well as reducing matrix degradation by inhibiting MMP13 expression. Interestingly, network pharmacologic analysis showed that PPARG might be a therapeutic center. Further study proved that E.G.-containing serum (EGS) could up-regulate PPARG mRNA level in IL-1ß-induced chondrocytes. Notably, significant effects of EGS on the increment of anabolic gene expressions (Col2, Aggrecan) and the decrement of catabolic gene expressions (MMP13, Adamts5) in KOA chondrocytes were abolished due to the silence of PPARG. Conclusion: E.G. played a chondroprotective role in anti-KOA by inhibiting extracellular matrix degradation, which might be related to PPARG.

Dietary phytoestrogens and total and cause-specific mortality: results from 2 prospective cohort studies.

BACKGROUND: Evidence regarding dietary phytoestrogens in relation to mortality remains limited. OBJECTIVES: The objective of the study is to examine the associations of intake of isoflavones, lignans, and coumarins with total and cause-specific mortality in US males and females. METHODS: We followed 75,981 females in the Nurses' Health Study (1984-2018) and 44,001 males in the Health Professionals Follow-up Study (1986-2018), who were free of cardiovascular disease (CVD), diabetes, or cancer at baseline. Their diet was repeatedly assessed using validated food frequency questionnaires every 2-4 y. Associations with mortality were assessed using time-dependent Cox models with adjustments for demographics, dietary and lifestyle factors, and medical history. RESULTS: During 3,427,156 person-years of follow-up, we documented 50,734 deaths, including 12,492 CVD deaths, 13,726 cancer deaths, and 24,516 other non-CVD and noncancer deaths. After multivariable adjustment, the higher total phytoestrogen intake was associated with lower risk of total CVD and other non-CVD and noncancer mortality: comparing extreme quintiles, the pooled HRs (95% CIs) were 0.89 (0.87, 0.92), 0.90 (0.85, 0.96), and 0.86 (0.82, 0.90), respectively. We did not find a significant association with cancer mortality [0.97 (0.92, 1.03)]. For individual phytoestrogens in relation to total mortality, the pooled HRs (95% CIs) comparing extreme quintiles were 0.90 (0.87, 0.92) for isoflavones, 0.93 (0.90, 0.96) for lignans, and 0.93 (0.90, 0.95) for coumarins. Individual phytoestrogens were also significantly associated with lower risk of CVD mortality and other types of mortality. Primary food sources of phytoestrogens, including tofu, soy milk, whole grains, tea, and flaxseed, were also inversely associated with total mortality. CONCLUSIONS: A higher intake of total phytoestrogens, including isoflavones, lignans, and coumarins, and foods rich in these compounds was associated with lower risk of total and certain cause-specific mortality in generally healthy US adults. These data suggest that these phytochemicals and their dietary sources may be integrated into an overall healthy diet to achieve a longer life span.

How to Regulate the Migration Ability of Emulsions in Micro-Scale Pores: Droplet Size or Membrane Strength?

Micro visualization has become an important means of solving colloid and interface scientific problems in enhanced oil recovery. It can establish a relationship between a series of performance evaluations of an oil-water interface under macroscopic dimensions and the actual application effect in confined space, and more truly and reliably reflect the starting and migration behavior of crude oil or emulsion in rock pores. In this article, zwitterionic surfactant alkyl sulfobetaine (ASB) and anionic extended surfactant alkyl polyoxypropylene sulfate (A145) were employed as flooding surfactants. The macroscopic properties of the surfactant solutions, such as the oil-water interfacial tension (IFT), the interfacial dilational rheology and the viscosity of crude oil emulsions, have been measured. At the same time, we link these parameters with the oil displacement effect in several visual glass models and confirm the main factors affecting the migration ability of emulsions in micro-scale pores. The experimental results show that ASB reduces the IFT through mixed adsorption with crude oil fractions. The flat arrangement of the large hydrophilic group of ASB molecules enhances the interactions between the surfactant molecules on the oil-water interface. Compared with sulfate, betaine has higher interfacial membrane strength and emulsion viscosity. A145 has a strong ability to reduce the IFT against crude oil because of the larger size effect of the PO chains at the oil side of the interface. However, the membrane strength of A145 is moderate and the emulsion does not show a viscosity-increasing effect. During the displacement process, the deformation ability of the front emulsions or oil banks is the main controlling factor of the displacement efficiency, which is determined by the membrane strength and emulsion viscosity. The strong interfacial membrane strength and the high emulsion viscosity are not conducive to the migration of droplets in pore throats and may result in low displacement efficiency.

Isolation of female germline stem cells from neonatal piglet ovarian tissue and differentiation into oocyte-like cells.

It has been generally accepted that the number of oocyte pool in mammalian ovaries is limited and irreversibly consumed throughout the adulthood until menopause, which has been challenged by the existence of female germline stem cells (FGSCs) and their differentiation potentials into oocytes through mitosis. However, there have been a few reports about the existence of porcine FGSCs (pFGSCs) in the neonatal piglet ovarian tissues. In this study, the pFGSCs were isolated from the one day post partum (1 dpp) piglet ovaries by a differential anchoring velocity method combined with the magnetic cell sorting (MACS) using VASA antibody. The gene expression levels and in vitro differentiation potentials of pFGSCs were subsequently analyzed. The results showed that Oct4, C-kit, Vasa, Stella, Ifitm3 and Dazl were expressed in the pFGSCs. A small portion of pFGSCs (2.81 ± 0.76%) spontaneously differentiated into oocyte-like cells (OLCs) with a mean diameter of 50 µm and gene expressions of Vasa, Ifitm3, Blimp1, Gdf9, Zp3, Dazl and Stella. Compared with that of the spontaneous differentiation system, the differentiation rates of pFGSCs into OLCs were significantly increased after the co-supplementations of porcine follicular fluid (PFF) and retinoic acid (RA). Taken together, these above results revealed the direct evidences for the existence of pFGSCs in 1 dpp piglet ovaries and the in vitro differentiation potential of pFGSCs into OLCs, benefiting future research related to the in vitro establishment of livestock FGSCs and the in vitro differentiation of pFGSCs.