Association between oxidative balance score and diabetic kidney disease, low estimated glomerular filtration rate and albuminuria in type 2 diabetes mellitus patients: a cross-sectional study.

Objective: The oxidative balance score (OBS) is a comprehensive concept that includes 20 oxidative stressors and can be used to assess individual pro-oxidant versus antioxidant exposure, and the aim of the present study was to investigate the association between OBS and the risk of diabetic kidney disease (DKD), low estimated glomerular filtration rate (low-eGFR) and albuminuria in patients with diabetes mellitus (DM). Methods: This cross-sectional study included nationally representative consecutive National Health and Nutrition Examination Survey DM patients aged 18 years and older from 2003-2018. The continuous variable OBS was converted into categorical variables by quartiles, and weighted multiple logistic regression analyses and restricted triple spline models were used to explore the relationships. We also performed subgroup analyses and interaction tests to verify the stability of the results. Results: A total of 5389 participants were included, representing 23.6 million non-institutionalized US residents. The results from both multivariate logistic regression analysis and restricted cubic spline models indicated that OBS and dietary OBS levels were negatively associated with the risk of DKD, low-eGFR, and albuminuria, without finding a significant correlation between lifestyle OBS and these clinical outcomes. Compared to the lowest OBS quartile group, the prevalence risk of DKD (OR = 0.61, 95% CI: 0.46-0.80), low-eGFR (OR = 0.46, 95% CI: 0.33-0.64) and albuminuria (OR = 0.68, 95% CI: 0.51-0.92) decreased by 39%, 54% and 32%, respectively, in the highest OBS quartile group. The results remained stable in subgroup analyses and no interaction between subgroups was found. Conclusion: Higher levels of OBS and dietary OBS were associated with a lower risk of DKD, low-eGFR, and albuminuria. These findings provided preliminary evidence for the importance of adhering to an antioxidant-rich diet and lifestyle among individuals with diabetes.

Comparative efficacy of exercise modalities for general risk factors, renal function, and physical function in non-dialysis chronic kidney disease patients: a systematic review and network meta-analysis.

BACKGROUND: Exercise therapy can effectively manage chronic kidney disease (CKD) risk factors and improve renal function and physical fitness, but the challenge lies in choosing the right exercise type tailored to patients' condition. METHODS: An electronic search of databases including PubMed, The Cochrane Library, EMBASE, Web of Science, VIP, WanFang, and CNKI was performed. The random effects model was used. Mean difference was employed as the effect size for continuous variables, with 95% confidence interval (CI) provided. RESULTS: A total of 36 RCTs were included in this study. Compared to conventional therapy (CT), the combination of three exercise therapies with CT resulted in notable benefits in enhancing six minutes walk test (6MWT) capacity, 24-h urinary protein quantity (24hUTP), systolic blood pressure (SBP), diastolic blood pressure (DBP). Resistance exercise therapy (RT) + CT were more effective than CT to reduce serum creatinine (Scr), body mass index (BMI), and hemoglobin A1c (HbA1c) and improve estimated glomerular filtration rate (eGFR). In terms of improving peak oxygen uptake (VO2 peak), only two exercise modalities were involved, aerobic exercise therapy (AT) and combined (Resistance-Aerobic) exercise therapy (CBT), both of which were more efficacious than CT. The efficacy ranking overall demonstrated clear benefits for RT in enhancing eGFR and 6MWT, decreasing Scr, BMI, SBP, DBP, and HbA1c, while AT was more suitable for boosting VO2 peak, and CBT had greater potential for reducing 24hUTP. CONSLUSIONS: Exercise therapy combined with CT offers significant advantages over CT in many cases, but no single exercise modality is universally effective for all indicators.

Therapeutic of a white adipose tissue-specific bivalent aptamer in obesity.

The white adipose tissue-specific aptamer Adipo8 can specificity bindwith mature adipocytes or tissues and inhibit adipogenesis.In this research, we exploredthe effect of Adipo8 intervention on the transcriptome in the process of adipogenesis using mRNA-level sequencing,analyzed the mechanism ofAdipo8 ininhibiting adipogenesis. The results showed that Adipo8 can inhibit lipid formation and downregulate PPARγ and C/EBPα in differentiated 3 T3-L1 cells. Transcriptome mRNA sequencing of 3 T3-L1 cells after Adipo8 interventionrevealed that Adipo8 might inhibit the biological function of adipogenesis by downregulating Acsl1 and Plin1 to inhibit fatty acid metabolism and PPAR signaling pathways.After that, using Spacer18 to connect the optimized and truncated Adipo8, we constructed a bivalent aptamer Adipo8cBand compared the affinity, biological effects, and biological stability between the aptamers in differentiated and mature 3 T3-L1 cells. At the cellular level,the affinity, biological effects, and serum stability of Adipo8cB were verified to be superior to those of Adipo8in 3 T3-L1 cells.We then investigated the biological properties of Adipo8cB as a lipid-inhibiting drug invivo, using C57BL/6J mice with diet-induced obesity. The body weight, blood sugar, lipid levels, liver function, glucose tolerance, and other related indicators in each group of mice were observed and compared after intervention with the bivalent aptamers Adipo8cB and Adipo8. Both Adipo8cB and Adipo8 effectively prevented weight gain caused by fat accumulation in micewith diet induced obesity, while also reducing blood lipid levels, improving glucose tolerance, and protecting against liver steatosis, moreover, Adipo8cB has a better effect than Adipo8.

Visible Light-Induced Radical Cascade Difluoromethylation/Cyclization of Unactivated Alkenes: Access to CF2H-Substituted Polycyclic Imidazoles.

An efficient and mild protocol for the visible light-induced radical cascade difluoromethylation/cyclization of imidazoles with unactivated alkenes using easily accessible and bench-stable difluoromethyltriphenylphosphonium bromide as the precursor of the -CF2H group has been developed to afford CF2H-substituted polycyclic imidazoles in moderate to good yields. This strategy, along with the construction of Csp3-CF2H/C-C bonds, is distinguished by mild conditions, no requirement of additives, simple operation, and wide substrate scope. In addition, the mechanistic experiments have indicated that the difluoromethyl radical pathway is essential for the methodology.

Texture characterization of 3D printed fibrous whey protein-starch composite emulsion gels as dysphagia food: A comparative study on starch type.

Texture-modified, multi-nutrient composite foods are essential in clinical treatment for dysphagia individuals. Herein, fibrous whey protein-stabilized emulsion and different crystalline starches (wheat, corn, rice, potato, sweet potato, cassava, mung bean and pea) were used to structure composite emulsion gels (CEGs). These CEGs then underwent 3D printing to explore the feasibility of developing a dysphagia diet. The network of molded CEGs was mainly maintained by hydrophobic interactions and hydrogen bonds. Rice and cassava starches were better suited for structuring soft-textured CEGs. Compared with molded CEGs, 3D printing decreased hydrogen bonds and the compactness of the nano-aggregate structure within the gel system, forming a looser gel network and softening the CEGs. Interestingly, these effects were more pronounced for the CEGs with high initial hardness. This study provided new strategy to fabricate CEGs as dysphagia diet using fibrous whey protein and starch, and to design texture-modified foods for patients using 3D printing.

Effects of wall materials on the physicochemical properties of spray-dried bitter gourd (Momordica charantia L.) powders.

Bitter gourd has numerous health-promoting effects on the human body. However, its use has been greatly limited due to its poor acceptance by consumers, resulting from its strong bitterness. This study investigated the effects of five wall materials, namely, soybean protein isolate, gum arabic, maltodextrin, resistant starch, and a soybean lecithin calcium caseinate mixture, on the physicochemical properties of spray-dried bitter gourd powders. The results showed that all five wall materials reduced the moisture content, water activity, browning degree, agglomeration, and bitterness of the spray-dried bitter gourd powder. Maltodextrin was found to be the most effective at reducing water activity, while soybean protein isolate was best at protecting the colour, and the soybean lecithin calcium caseinate mixture was best at reducing hygroscopicity and masking bitterness. Additionally, all five wall materials improved the preservation of flavonoids, saponins, and vitamin C, with soybean protein isolate being the most effective in improving the total flavonoid retention ratio and the soybean lecithin calcium caseinate mixture being the best in improving the retention ratios of total saponins and vitamin C. The spray-dried bitter gourd powder prepared with soybean protein isolate had the highest antioxidant activity and α-glucosidase inhibitory activity. These results are significant for understanding the relationship between wall materials and the physicochemical properties of spray-dried powder. Additionally, these materials provide bitter gourd product manufacturers with useful guidance for producing high-quality products. Furthermore, the results could provide useful insights for processing fruits with similar product characteristics, thus contributing to the enrichment of food processing knowledge.

Association of different domains of physical activity with diabetic kidney disease: a population-based study.

Background: The aim of this cross-sectional study was to elucidate the associations between various domains of physical activity, such as occupation-related (OPA), transportation-related (TPA), leisure-time (LTPA) and overall physical activity (PA), and diabetic kidney disease. Methods: Our study encompassed 2,633 participants, drawn from the cross-sectional surveys of the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018, and employed survey-weighted logistic regression, generalized linear regression, and restricted cubic spline (RCS) analyses to ascertain the relationship between different domains of physical activity and diabetic kidney disease. Results: After controlling for all confounders, multivariate logistic regression analyses revealed a lack of correlation between the various domains of physical activity and the prevalence of diabetic kidney disease. Multiple generalized linear regression analyses showed that durations of PA (ß = 0.05, 95% CI, 0.01-0.09, P = 0.012) and TPA (ß = 0.32, 95% CI, 0.10-0.55, P = 0.006) were positively associated with eGFR levels; and LTPA durations were inversely associated with UACR levels (ß = -5.97, 95% CI, -10.50 - -1.44, P = 0.011). The RCS curves demonstrated a nonlinear relationship between PA, OPA, and eGFR, as well as a nonlinear correlation between PA and ACR. Subgroup and sensitivity analyses largely aligned with the outcomes of the multivariate generalized linear regression, underscoring the robustness of our findings. Conclusion: Our population-based study explored the association between different domains of physical activity and diabetic kidney disease. Contrary to our expectations, we found no significant association between the duration of physical activity across all domains and the prevalence of diabetic nephropathy. Nonetheless, renal function markers, including eGFR and UACR, exhibited significant correlations with the duration of total physical activity (TPA) and leisure-time physical activity (LTPA), respectively, among diabetic patients. Interestingly, our findings suggest that diabetic patients engage in physical activity to preserve renal function, ensuring moderate exercise durations not exceeding 35 hours per week.

Association between previous consumption of sugar-sweetened beverages and diabetes remission in patients with newly diagnosed type 2 diabetic ketoacidosis.

This study examined the potential correlation between the immoderate intake of sugar-sweetened beverages (SSBs) and the subsequent rate of diabetes remission (DR). 206 individuals who met the eligibility criteria between January 2019 and June 2022 were recruited. Inquiries were conducted to gather information on the participants' beverage consumption before the onset. Subsequently, the participants were separated into the diabetes remission group (DR group) and nondiabetes remission group (NDR group) depending on whether they met the diagnostic criteria for diabetes remission. Baseline clinical elements within the two groups were juxtaposed, and factors influencing diabetes remission were identified through logistic regression analyses. The cutoff values of each critical factor were determined based on the receiver operating characteristic curve. One hundred and nine patients reported a history of SSB consumption, while the remaining 58 reported no such history. After 1 year, 40 patients achieved remission from diabetes. Compared with the NDR group, a higher SSBs ratio, body mass index (BMI), and blood creatinine (BCr) was observed in the DR group after adjusting for confounders, SSBs (odds ratio [OR] = 3.503; 95% confidence interval [CI] = 1.334-9.202; p = 0.011) and BCr (OR = 1.038; 95% CI = 1.003-1.079; p = 0.042) emerged as independent predictors of DR. The composite index of SSBs and BCr efficaciously predicted DR (area under the ROC curve [AUC] = 0.810, p < 0.001). SSBs and BCr were independent risk factors for DR. The amalgamation of these markers could more accurately predict DR.

Impact of Oil Bodies on Structure, Rheology and Function of Acid-Mediated Soy Protein Isolate Gels.

Oil bodies (OBs) are naturally occurring pre-emulsified oil droplets that have broad application prospects in emulsions and gels. The main purpose of this research was to examine the impact of the OB content on the structure and functional aspects of acid-mediated soy protein isolate (SPI) gel filled with OBs. The results indicated that the peanut oil body (POBs) content significantly affected the water holding capacity of the gel. The rheological and textural analyses showed that POBs reduced the gel strength and hardness. The scanning electron and confocal laser scanning microscopy analyses revealed that POBs aggregated during gel formation and reduced the gel network density. The Fourier transform infrared spectrum (FTIR) analysis demonstrated that POBs participated in protein gels through hydrogen bonds, steric hindrance and hydrophobic interactions. Therefore, OBs served as inactive filler in the acid-mediated protein gel, replaced traditional oils and provided alternative ingredients for the development of new emulsion-filled gels.

Tea Polysaccharide Ameliorates High-Fat Diet-Induced Renal Tubular Ectopic Lipid Deposition via Regulating the Dynamic Balance of Lipogenesis and Lipolysis.

Renal tubular ectopic lipid deposition (ELD) plays a significant role in the development of chronic kidney disease, posing a great threat to human health. The present work aimed to explore the intervention effect and potential molecular mechanism of a purified tea polysaccharide (TPS3A) on renal tubular ELD. The results demonstrated that TPS3A effectively improved kidney function and slowed the progression of tubulointerstitial fibrosis in high-fat-diet (HFD)-exposed ApoE-/- mice. Additionally, TPS3A notably suppressed lipogenesis and enhanced lipolysis, as shown by the downregulation of lipogenesis markers (SREBP-1 and FAS) and the upregulation of lipolysis markers (HSL and ATGL), thereby reducing renal tubular ELD in HFD-fed ApoE-/- mice and palmitic-acid-stimulated HK-2 cells. The AMPK-SIRT1-FoxO1 axis is a core signal pathway in regulating lipid deposition. Consistently, TPS3A significantly increased the levels of phosphorylated-AMPK, SIRT1, and deacetylation of Ac-FoxO1. However, these effects of TPS3A on lipogenesis and lipolysis were abolished by AMPK siRNA, SIRT1 siRNA, and FoxO1 inhibitor, resulting in exacerbated lipid deposition. Taken together, TPS3A shows promise in ameliorating renal tubular ELD by inhibiting lipogenesis and promoting lipolysis through the AMPK-SIRT1-FoxO1 signaling pathway.

Investigating the thermal stability and calcium resistance of O/W emulsions prepared with glycosylated whey protein hydrolysates modified by different saccharides.

The poor thermal stability and ion tolerance of whey protein hydrolysates (WPH) restrict its application in emulsions, while glycosylation shows potential benefits in improving WPH stability. However, the relationship between saccharides with different Mw and the glycosylation behavior of WPH rich in short peptides is unclear. In response, the effect of different saccharides on glycosylated WPH rich in short peptides and its emulsion stability were investigated. Grafted small Mw saccharides were more beneficial to the emulsion stability of WPH. Specifically, grafting xylose effectively inhibited 121 °C sterilization and 5 mM CaCl2-induced coalescence of WPH emulsion (687.50 nm) by comprehensively enhancing steric hindrance, conformational flexibility and electrostatic repulsion, and dissociating large aggregates into small aggregates. Conversely, grafting maltodextrin (30,590 Da) reduced thermal stability of WPH emulsion (4791.80 nm) by steric shielding and bridging flocculation. These findings provide new sights into glycosylation mechanism for WPH and achieving its application in nutritional emulsions.

Rheological properties of indica rice determined by starch structure related enzymatic activities during after-ripening.

The processing quality of indica rice must undergo ripening after harvest to achieve stability and improvement. However, the mechanism underlying this process remains incompletely elucidated. Starch, the predominant component in indica rice, plays a crucial role in determining its properties. This study focused on analyzing the rheological properties and starch fine structure, as well as the related biosynthetic enzymes of indica rice during the after-ripening process. The results showed that after-ripened rice exhibited increased elastic modulus (G') and viscous modulus (G″), accompanied by a decrease in the loss tangent (Tan δ), indicating an enhancement in viscoelasticity and the gel network structure. Moreover, the proportions of amylopectin super long chains (DP 37-60) decreased, while those of medium chains (DP 13-24 and DP 25-36) or short chains (DP 6-12) of amylopectin increased. Additionally, the activities of starch branching enzyme (SBE) and starch debranching enzyme (DBE) declined over the after-ripening period. Pearson correlation analysis revealed that the rheological properties of after-ripened rice were correlated with the chain length distribution (CLD) of starch, which, in turn, was associated with its related endogenous enzymes. These findings provied new insights into understanding the quality changes of after-ripened indica rice.

Association Between Liver Fibrosis Score and Diabetic Kidney Disease: A Retrospective Cross-Sectional Study of Hospitalized Patients.

OBJECTIVES: To investigate the association between liver fibrosis score and diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM). METHODS: A total of 897 hospitalized patients with T2DM were included in this study. Each patient completed DKD screening. Logistic regression analysis was used to assess the predictive value of non-alcoholic fatty liver disease fibrosis score (NAFLD-FS) and fibrosis-4 (FIB-4) for the occurrence of DKD and risk for DKD progression, respectively. RESULTS: The prevalence of DKD and risk for its progression significantly increased with increasing NAFLD-FS risk category. DKD prevalence also increased with increasing FIB-4 risk category. Multivariate logistic regression analysis showed that the "high-risk" NAFLD-FS had a significantly higher risk of DKD (odds ratio [OR]: 1.89, 95% confidence interval [CI]: 1.16-3.08) and risk for DKD progression (OR: 2.88, 95% CI: 1.23-6.78), and the "intermediate-risk" FIB-4 had a significantly higher risk of DKD (OR: 1.41, 95% CI: 1.00-1.98). Subgroup analysis showed that the association between NAFLD-FS and FIB-4 and DKD was significant in the female subgroup, whereas the association between the "high-risk" NAFLD-FS and risk for DKD progression was significant in the male subgroup. CONCLUSIONS: NAFLD-FS and FIB-4 are strongly associated with DKD and risk for DKD progression in patients with T2DM. Additionally, sexual dimorphism exists in this association.

Targeting 14-3-3θ-mediated TDP-43 pathology in amyotrophic lateral sclerosis and frontotemporal dementia mice.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are characterized by cytoplasmic deposition of the nuclear TAR-binding protein 43 (TDP-43). Although cytoplasmic re-localization of TDP-43 is a key event in the pathogenesis of ALS/FTD, the underlying mechanisms remain unknown. Here, we identified a non-canonical interaction between 14-3-3θ and TDP-43, which regulates nuclear-cytoplasmic shuttling. Neuronal 14-3-3θ levels were increased in sporadic ALS and FTD with TDP-43 pathology. Pathogenic TDP-43 showed increased interaction with 14-3-3θ, resulting in cytoplasmic accumulation, insolubility, phosphorylation, and fragmentation of TDP-43, resembling pathological changes in disease. Harnessing this increased affinity of 14-3-3θ for pathogenic TDP-43, we devised a gene therapy vector targeting TDP-43 pathology, which mitigated functional deficits and neurodegeneration in different ALS/FTD mouse models expressing mutant or non-mutant TDP-43, including when already symptomatic at the time of treatment. Our study identified 14-3-3θ as a mediator of cytoplasmic TDP-43 localization with implications for ALS/FTD pathogenesis and therapy.

Nitric oxide-releasing multifunctional catechol-modified chitosan/oxidized dextran hydrogel with antibacterial, antioxidant, and pro-angiogenic properties for MRSA-infected diabetic wound healing.

The study presents a multifunctional catechol-modified chitosan (Chi-Ca)/oxidized dextran (Dex-CHO) hydrogel (CDP-PB) that possesses antibacterial, antioxidant, and pro-angiogenic properties, aimed at improving the healing of diabetic wounds. The achievement of the as-prepared CDP-PB hydrogel with superb antibacterial property (99.9 %) can be realized through the synergistic effect of phenylboronic acid-modified polyethyleneimine (PEI-PBA) and photothermal therapy (PTT) of polydopamine nanoparticles loaded with the nitric oxide (NO) donor BNN6 (PDA@BNN6). Notably, CDP-PB hydrogel achieves ∼3.6 log10 CFU/mL MRSA of inactivation efficiency under 808 nm NIR laser irradiation. In order to mitigate oxidative stress, the Chi-Ca was synthesized and afterward subjected to a reaction with Dex-CHO via a Schiff-base reaction. The catechol-containing hydrogel demonstrated its effectiveness in scavenging DPPH, •OH, and ABTS radicals (> 85 %). In addition, the cellular experiment illustrates the increased migration and proliferation of cells by the treatment of CDP-PB hydrogel in the presence of oxidative stress conditions. Moreover, the findings from the animal model experiments provide evidence that the CDP-PB hydrogel exhibited efficacy in the eradication of wound infection, facilitation of angiogenesis, stimulation of granulation, and augmentation of collagen deposition. These results indicate the potential of the CDP-PB hydrogel for use in clinical applications.

Comparisons in phytochemical components and in vitro digestion properties of corresponding peels, flesh and seeds separated from two blueberry cultivars.

Highbush blueberries (HB) and rabbiteye blueberries (RB) were separated into peels, flesh, and seeds to assess the compositions of nutriment, anthocyanins, soluble sugars and fatty acids, and the in vitro digesting abilities. Total phenolics contents (TPC) of 51-56 mg GAE/g DW were found in blueberry peels. Compared with HB peels, RB peels showed much higher TPC, but only contained 35 phenolics and lacked peonidin-3-O-rutinoside. Glucose, fructose, and sucrose were all present in HB and RB, but RB flesh had a higher acid-sugar ratio. Unsaturated fatty acid concentrations in HB and RB seeds were comparable (26.65 and 26.43 mg/g, respectively). However, HB seeds have 35 fatty acids, but RB seeds lacked cis-4,7,10,13,16,19-docosahexaenoic acid and cis-10-pentadecenoic acid. The in vitro digestion test showed that the whole fruit/peels/flesh of RB had a higher recovery and bioavailability index of phenolics and anthocyanins. Therefore, the reuse of blueberry pomace needs to be emphasized. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01326-w.

Edible traditional Chinese medicines improve type 2 diabetes by modulating gut microbiotal metabolites.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder with intricate pathogenic mechanisms. Despite the availability of various oral medications for controlling the condition, reports of poor glycemic control in type 2 diabetes persist, possibly involving unknown pathogenic mechanisms. In recent years, the gut microbiota have emerged as a highly promising target for T2DM treatment, with the metabolites produced by gut microbiota serving as crucial intermediaries connecting gut microbiota and strongly related to T2DM. Increasingly, traditional Chinese medicine is being considered to target the gut microbiota for T2DM treatment, and many of them are edible. In studies conducted on animal models, edible traditional Chinese medicine have been shown to primarily alter three significant gut microbiotal metabolites: short-chain fatty acids, bile acids, and branched-chain amino acids. These metabolites play crucial roles in alleviating T2DM by improving glucose metabolism and reducing inflammation. This review primarily summarizes twelve edible traditional Chinese medicines that improve T2DM by modulating the aforementioned three gut microbiotal metabolites, along with potential underlying molecular mechanisms, and also incorporation of edible traditional Chinese medicines into the diets of T2DM patients and combined use with probiotics for treating T2DM are discussed.

Purification, structural characteristics and anti-atherosclerosis activity of a novel green tea polysaccharide.

A new homogeneous polysaccharide (TPS3A) was isolated and purified from Tianzhu Xianyue fried green tea by DEAE-52 cellulose and Sephacryl S-500 column chromatography. Structural characterization indicated that TPS3A mainly consisted of arabinose, galactose, galacturonic acid and rhamnose in a molar ratio of 5.84: 4.15: 2.06: 1, with an average molecular weight of 1.596 × 104 kDa. The structure of TPS3A was characterized as a repeating unit consisting of 1,3-Galp, 1,4-Galp, 1,3,6-Galp, 1,3-Araf, 1,5-Araf, 1,2,4-Rhap and 1-GalpA, with two branches on the C6 of 1,3,6-Galp and C2 of 1,2,4-Rhap, respectively. To investigate the preventive effects of TPS3A on atherosclerosis, TPS3A was administered orally to ApoE-deficient (ApoE-/-) mice. Results revealed that TPS3A intervention could effectively delay the atherosclerotic plaque progression, modulate dyslipidemia, and reduce the transformation of vascular smooth muscle cells (VSMCs) from contractile phenotype to synthetic phenotype by activating the expression of contractile marker alpha-smooth muscle actin (α-SMA) and inhibiting the expression of synthetic marker osteopontin (OPN) in high-fat diet-induced ApoE-/- mice. Our findings suggested that TPS3A markedly alleviated atherosclerosis by regulating dyslipidemia and phenotypic transition of VSMCs, and might be used as a novel functional ingredient to promote cardiovascular health.

Human placenta-derived mesenchymal stem cells ameliorate diabetic kidney disease by modulating the T helper 17 cell/ regulatory T-cell balance through the programmed death 1 / programmed death-ligand 1 pathway.

AIM: To investigate the therapeutic effects and immunomodulatory mechanisms of human placenta-derived mesenchymal stem cells (PMSCs) in diabetic kidney disease (DKD). METHODS: Streptozotocin-induced DKD rats were administered an equivalent volume of saline or PMSCs (1 × 106 in 2 mL phosphate-buffered saline per rat) for 3 weeks. Eight weeks after treatment, we examined the biochemical parameters in the blood and urine, the ratio of T helper 17 cells (Th17) and regulatory T cells (Treg) in the blood, cytokine levels in the kidney and blood, and renal histopathological changes. In addition, we performed PMSC tracing and renal transcriptomic analyses using RNA-sequencing. Finally, we determined whether PMSCs modulated the Th17/Treg balance by upregulating programmed death 1 (PD-1) in vitro. RESULTS: The PMSCs significantly improved renal function, which was assessed by serum creatinine levels, urea nitrogen, cystatin C levels, urinary albumin-creatinine ratio, and the kidney index. Further, PMSCs alleviated pathological changes, including tubular vacuolar degeneration, mesangial matrix expansion, and glomerular filtration barrier injury. In the DKD rats in our study, PMSCs were mainly recruited to immune organs, rather than to the kidney or pancreas. PMSCs markedly promoted the Th17/Treg balance and reduced the levels of pro-inflammatory cytokines (interleukin [IL]-17A and IL-1ß) in the kidney and blood of DKD rats. In vitro experiments showed that PMSCs significantly reduced the proportion of Th17 cells and increased the proportion of Treg cells by upregulating PD-1 in a cell-cell contact manner and downregulating programmed death-ligand 1 (PD-L1) expression in PMSCs, which reversed the Th17/Treg balance. CONCLUSION: We found that PMSCs improved renal function and pathological damage in DKD rats and modulated Th17/Treg balance through the PD-1/PD-L1 pathway. These findings provide a novel mechanism and basis for the clinical use of PMSCs in the treatment of DKD.

Saponins from Momordica charantia exert hypoglycemic effect in diabetic mice by multiple pathways.

The antidiabetic activity of saponins extracted from Momordica charantia (MCS) on streptozotocin-induced diabetic mice was investigated in order to elucidate the mechanism of MCS for exerting hypoglycemic effects. Saponins were first extracted from M. charantia L. and their composition was analyzed. The diabetic Kunming mice were fed low-dose saponins from M. charantia L. and high-dose MCS, using normal mice and diabetic mice as controls. Body weight, blood glucose level, oral glucose tolerance, serum C-peptide level, hepatic antioxidant capacity, hepatic glycogen and hexokinase in liver tissues, serum blood lipid level, and alpha-glucosidase activity in small intestines were measured, and microstructure of pancreatic islet was analyzed. The results showed that the total content of seven triterpenoid compounds in MCS was 18.24 µg/mg, with Momordicoside K having the highest content at 11.66 µg/mg. Diabetic mice treated with MCS at 100 and 200 mg/kg body weight daily for 30 days showed a maximum glucose reduction (p < .05) of 12.63% and 26.47%, respectively. MCS significantly decreased levels of postprandial hyperglycemia, serum lipid, α-glucosidase activity, and liver malondialdehyde. Additionally, levels of serum C-peptide and liver glycogen, as well as hexokinase and antioxidant enzyme activity, were significantly increased compared to the diabetic control groups. Histopathological results showed that MCS markedly reduced degenerative changes in islet ß-cells. It is concluded that MCS exerts antidiabetic effects by improved hypoglycemic, hypolipidemic, and antioxidant effects, increased hexokinase activity and glycogen synthesis, and enhanced reparative effects on the histological architecture and insulin secretion function of the pancreas.