Dipeptidyl peptidase 4 inhibitors vs. metformin for new-onset dementia: a propensity score-matched cohort study.

BACKGROUND: Hypoglycemic pharmacotherapy interventions for alleviating the risk of dementia remains controversial, particularly about dipeptidyl peptidase 4 (DPP4) inhibitors versus metformin. Our objective was to investigate whether the initiation of DPP4 inhibitors, as opposed to metformin, was linked to a reduced risk of dementia. METHODS: We included individuals with type 2 diabetes over 40 years old who were new users of DPP4 inhibitors or metformin in the Chinese Renal Disease Data System (CRDS) database between 2009 and 2020. The study employed Kaplan-Meier and Cox regression for survival analysis and the Fine and Gray model for the competing risk of death. RESULTS: Following a 1:1 propensity score matching, the analysis included 3626 DPP4 inhibitor new users and an equal number of metformin new users. After adjusting for potential confounders, the utilization of DPP4 inhibitors was associated with a decreased risk of all-cause dementia compared to metformin (hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.45-0.89). Subgroup analysis revealed that the utilization of DPP4 inhibitors was associated with a reduced incidence of dementia in individuals who initiated drug therapy at the age of 60 years or older (HR 0.69, 95% CI 0.48-0.98), those without baseline macrovascular complications (HR 0.62, 95% CI 0.41-0.96), and those without baseline microvascular complications (HR 0.67, 95% CI 0.47-0.98). CONCLUSION: In this real-world study, we found that DPP4 inhibitors presented an association with a lower risk of dementia in individuals with type 2 diabetes than metformin, particularly in older people and those without diabetes-related comorbidities.

The association of low serum uric acid with mortality in older people is modified by kidney function: National Health and Nutrition Examination Survey (NHANES) 1999-2018.

BACKGROUND: In older individuals, the role of low serum uric acid (SUA) as risk factor for mortality is debated. We therefore studied whether SUA levels, particularly low SUA concentrations, are associated with all-cause and cardiovascular (CV) mortality in older population, and to clarify potential effect modification of kidney function. METHODS: We identified 14,005 older people in National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2018. SUA was measured only at baseline. The relationship between SUA and mortality was assessed using Cox proportional hazards models and restricted cubic spline Cox regression stratified by the estimated glomerular filtration rate (eGFR). RESULTS: During mean 8.3 years of follow-up, 4852 all-cause death and 1602 CV death were recorded. A significant U-shaped association was observed between SUA with all-cause mortality, with the lowest risk concentration of 5.5 mg/dL. Comparing to the reference group (5 to 7 mg/dL), the HR of 2 to < 5 mg/dL group was 1.11 (1.03-1.21) and 1.14 (1.00-1.30). This relationship was more pronounced in participants with an eGFR ≥ 60 ml/min/1.73m2 (HR, 1.16; 95%CI, 1.06-1.28). This situation similarly occurred in Urine protein negative group (HR, 1.14; 95%CI, 1.04-1.25). CONCLUSIONS: Low SUA concentrations are associated with an increased risk in all-cause and CV mortality among older participants. Extremely low SUA concentrations are especially undesirable, especially in the older adults with normal kidney function.

Immunosuppression versus Supportive Care on Kidney Outcomes in IgA Nephropathy in the Real-World Setting.

BACKGROUND: The efficacy of immunosuppression in the management of immunoglobulin A (IgA) nephropathy remains highly controversial. The study was conducted to assess the effect of immunosuppression, compared with supportive care, in the real-world setting of IgA nephropathy. METHODS: A cohort of 3946 patients with IgA nephropathy, including 1973 new users of immunosuppressive agents and 1973 propensity score-matched recipients of supportive care, in a nationwide register data from January 2019 to May 2022 in China was analyzed. The primary outcome was a composite of 40% eGFR decrease of the baseline, kidney failure, and all-cause mortality. A Cox proportional hazard model was used to estimate the effects of immunosuppression on the composite outcomes and its components in the propensity score-matched cohort. RESULTS: Among 3946 individuals (mean [SD] age 36 [10] years, mean [SD] eGFR 85 [28] ml/min per 1.73 m 2 , and mean [SD] proteinuria 1.4 [1.7] g/24 hours), 396 primary composite outcome events were observed, of which 156 (8%) were in the immunosuppression group and 240 (12%) in the supportive care group. Compared with supportive care, immunosuppression treatment was associated with 40% lower risk of the primary outcome events (adjusted hazard ratio, 0.60; 95% confidence interval, 0.48 to 0.75). Comparable effect size was observed for glucocorticoid monotherapy and mycophenolate mofetil alone. In the prespecified subgroup analysis, the treatment effects of immunosuppression were consistent across ages, sexes, levels of proteinuria, and values of eGFR at baseline. Serious adverse events were more frequent in the immunosuppression group compared with the supportive care group. CONCLUSIONS: Immunosuppressive therapy, compared with supportive care, was associated with a 40% lower risk of clinically important kidney outcomes in patients with IgA nephropathy.

Potential therapeutic drug targets and pathways prediction for premature ovarian insufficiency -Based on network pharmacologic method.

ETHNOPHARMACOLOGICAL RELEVANCE: The incidence of premature ovarian insufficiency (POI) is gradually increasing, the proportion is rising especially in female infertility patients. The risk of death of POI patients with cardiovascular disease also increases significantly. The cause of POI is complex and unclear, and clinical treatment is still in the exploratory stage, are two major constraints of treating POI. Traditional Chinese medicine (TCM) is widely used in the treatment of POI, and it is a good way to combine the development of modern new drugs with the help of TCM to predict the therapeutic targets. AIM OF THE STUDY: In this study, four herbs commonly used in clinical treatment of POI, namely Radix Paeoniae, Polygonatum sibiricum, Rehmannia glutinosa and Eucommia ulmoides were selected to predict their mechanism in the treatment of POI, using network pharmacology methods. Then verify the predicted targets by animal test. Aim to find more effective POI potential core treatment targets and main pathways. MATERIALS AND METHODS: We screened the active ingredients of drugs from the TCM System Pharmacology Analysis Platform (TCMSP), Performed target prediction of active ingredients from databases such as SwissTargetPrediction and compare and analyze the POI-related targets retrieved from them to obtain potential targets for drug treatment of POI. Used STRING database to construct a protein interaction network, Cytoscape 3.7.2 software to construct an active ingredient-target-pathway network, and DAVID database to conduct the Kyoto Encyclopedia of Genes and Genomes (KEGG) on the intersection targets and gene ontology (GO) enrichment analysis. RESULTS: The result is: there were 25 key targets for the treatment of POI with Radix Paeoniae Alba, 31 for the treatment of POI by Eucommia ulmoides, 28 for the treatment of POI by Polygonatum sibiricum, and 8 key targets for the treatment of Rehmannia glutinosa. The intersection targets of four herbs were defined as the core targets, which are CYP19A1, EGF, ESR1, ESR2, MDM2, AR, PCYP17A1, PPARG. Four Chinese herbs treat POI mainly through HIF-1 signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway, Estrogen signaling pathway etc. A mouse model of POI was constructed based on the results of network pharmacology to verify the predicted targets. The results showed that the protein expression of the core target changed, and the estrogen level was increased by reducing the expression of peroxisome proliferator-activated receptor gamma (PPARG). CONCLUSIONS: This study predicts the mechanism of multiple herbs in the treatment of POI, screens out more potential therapeutic drug targets and main pathways of POI treatment and provides new ideas for the subsequent development of POI therapeutic drugs.

Enhancing Spin-Based Sensor Sensitivity by Avoiding Microwave Field Inhomogeneity of NV Defect Ensemble.

The behavior of the magnetic field sensitivity of nitrogen-vacancy (NV) centers as a function of microwave power and the inhomogeneous distribution of MW fields was systematically studied. An optimal structure for exciting spin structures by MW signals was designed using two parallel loop antennas. The volume of the homogeneous regions was approximately 42 mm3, and the associated diameter of the diamond reached up to 5.2 mm with 1016 NV sensors. Based on this structure, the detection contrast and voltage fluctuation of an optically detected magnetic resonance (ODMR) signal were optimized, and the sensitivity was improved to 5 nT/√Hz. In addition, a pulse sequence was presented to fully eliminate the MW broadening. The magnetic field sensitivity was improved by approximately one order of magnitude as the π-pulse duration was increased to its coherence time. This offers a useful way to improve the sensitivity of spin-based sensors.

Zein Colloidal Particles and Cellulose Nanocrystals Synergistic Stabilization of Pickering Emulsions for Delivery of ß-Carotene.

In this study, we utilized different types of particles to stabilize ß-carotene-loaded Pickering emulsions: spherical hydrophobic zein colloidal particles (ZCPs) (517.3 nm) and rod-shaped hydrophilic cellulose nanocrystals (CNCs) (115.2 nm). Either of the particles was incapable of stabilizing Pickering emulsions owing to their inappropriate wettability. When the mass ratio of ZCPs and CNCs was 1:4, the Pickering emulsion showed the best physical and photothermal stability. Compared to the ZCP-stabilized Pickering emulsion (9.29%), the retention rate of ß-carotene in the Pickering emulsion costabilized by ZCPs and CNCs was increased to 60.23% after 28 days of storage at 55 °C. Confocal microscopy and cryoscanning electron microscopy confirmed that different types of particles could form a multilayered structure or induce the formation of an interparticle network. Furthermore, the complexation of ZCPs and CNCs delayed the lipolysis of the emulsion during in vitro digestion. The free fatty acid (FFA) release rate of Pickering emulsions in the small intestinal phase was reduced from 19.46 to 8.73%. Accordingly, the bioaccessibility of ß-carotene in Pickering emulsions ranged from 9.14 to 27.25% through adjusting the mass ratio and addition sequence of distinct particles at the interface. The Pickering emulsion with the novel particle-particle complex interface was designed in foods and pharmaceuticals for purpose of enhanced stability, delayed lipolysis, or sustained nutrient release.

Development of curcumin loaded core-shell zein microparticles stabilized by cellulose nanocrystals and whey protein microgels through interparticle interactions.

Novel multilayered core-shell microparticles were developed to deliver curcumin using positively charged zein microparticles coated with negatively charged cellulose nanocrystals (CNCs) and positively charged whey protein microgels (WPMs) at pH 4. Different levels of WPMs (0.10%-1.50%, w/v) were utilized to regulate the structure, stability, and in vitro digestion of curcumin loaded zein-CNC core-shell microparticles. The size of zein-CNC-WPM core-shell microparticles ranged from 2087.7 to 2928.2 nm. The electrostatic attraction and hydrogen bonding were mainly involved in the assembly of the core-shell microparticles through particle-particle interactions. The microstructure of the core-shell microparticles was dependent on the level of the WPM. When its appropriate level was adopted (0.50%-1.00%, w/v), the WPM formed a protective shell for zein-CNC-WPM core-shell microparticles. The retention rate of curcumin in the core-shell microparticles increased by 47.56% and 32.79% during light and thermal treatment, respectively. Excess microgels facilitated the bridging aggregation and formation of a network structure on the particle surface, which further reduced their stability and greatly restricted the curcumin release. The potential of nanosized protein microgels was explored to stabilize and modulate the physicochemical properties of multilayered core-shell microparticles through interparticle interactions.

Structural design of zein-cellulose nanocrystals core-shell microparticles for delivery of curcumin.

The novel core-shell microparticles were fabricated to deliver curcumin by using hydrophobic zein microparticles as the core and hydrophilic cellulose nanocrystals (CNCs) as the shell. Different concentrations (0.10-1.50%, w/v) of CNCs were utilized to regulate the microstructure, physicochemical stability, and in vitro digestion of the core-shell microparticles. The size of the microparticles ranged from 1017.3 to 3663.7 nm. Electrostatic attraction and hydrophobic interactions were responsible for the assembly of zein-CNCs core-shell microparticles. The microstructure of the microparticles was dependent on the CNCs level. The retention rate of curcumin in the core-shell microparticles was increased by 76.41% after UV radiation. Furthermore, the rise of CNCs level delayed the release of curcumin from the microparticles in gastrointestinal tract and reduced its bioaccessibility. The potential of utilizing hydrophilic nanoparticles was explored to stabilize hydrophobic microparticles through interparticle interactions, which was useful to develop the novel core-shell microparticles for the application in functional foods.