Effects of dynamic high-pressure microfluidization treatment on the structural, physicochemical, and digestive properties of wheat starch-Lonicera caerulea berry polyphenol complex.

Polyphenol complexes can improve the physicochemical and functional properties of starch. In this study, a wheat starch-Lonicera caerulea berry polyphenol complex (WS-LCBP) was prepared using dynamic high-pressure microfluidization (DHPM). The effects of different DHPM pressures (150 and 250 MPa), number of cycles (1 and 3), and LCBP content (0 %, 6 %, 8 %, and 10 %) on the multiscale structure, physicochemical properties, and in vitro digestibility of WS-LCBP were examined. After a single 250 MPa DHPM cycle, Average particle size and water separation rate of WS were reduced by 42.40 % and 16.67 %, the freeze-thaw stability was significantly improved (P < 0.05), and the resistant starch (RS) content 68.67 % was significantly increased (P < 0.05). WS-LCBP has a V-shaped starch structure, which hinders gelatinization and increases enthalpy. The RS content of the WS-LCBP ranged from 72.46 % to 89.09 %, which was significantly higher (P < 0.05) than that of wheat starch subjected to a single 150 MPa DHPM cycle (36.31 %). Three 250 MPa DHPM cycles were beneficial for the formation of WS-LCBP. However, excessive DHPM treatment pressure and frequency reduced the recombination rate of LCBP and wheat starch. This study provides reference data for the industrial production of nutritionally functional wheat-resistant starch using green technologies.

The involvement of keratinocytes in pruritus of chronic inflammatory dermatosis.

Frequent itching and incessant scratching are commonly observed in various chronic inflammatory skin conditions, including atopic dermatitis and psoriasis. The persistent and prolonged nature of pruritus can worsen one's quality of life. Keratinocytes (KCs), the predominant cells of the epidermis, have been confirmed to interact with sensory neurons and immune cells and be involved in chronic skin inflammatory diseases associated with pruritus. Initially, KCs and sensory neurons form a unique synapse-like connection within the epidermis, serving as the structural foundation for their interaction. Additionally, several receptors, including toll-like receptors and protease-activated receptor 2, expressed on KCs, become activated in an inflammatory milieu. On the one hand, activated KCs are sources of pro-inflammatory cytokines and neurotrophic factors, such as adenosine triphosphate, thymic stromal lymphopoietin, and nerve growth factor, which directly or indirectly participate in stimulating sensory neurons, thereby contributing to the itch sensations. On the other hand, KCs also function as primary transducers alongside intraepidermal nerve endings, directly initiating pruritic responses. This review summarizes the current literature and highlights the critical role of KCs in the development and persistence of chronic itch in inflammatory skin disorders.

Clinical features and genetic analysis of 15 Chinese children with dent disease.

OBJECTIVE:  The clinical characteristics, genetic mutation spectrum, treatment strategies and prognoses of 15 children with Dent disease were retrospectively analyzed to improve pediatricians' awareness of and attention to this disease. METHODS:  We analyzed the clinical and laboratory data of 15 Chinese children with Dent disease who were diagnosed and treated at our hospital between January 2017 and May 2023 and evaluated the expression of the CLCN5 and OCRL1 genes. RESULTS:  All 15 patients were male and complained of proteinuria, and the incidence of low-molecular-weight proteinuria (LMWP) was 100.0% in both Dent disease 1 (DD1) and Dent disease 2 (DD2) patients. The incidence of hypercalciuria was 58.3% (7/12) and 66.7% (2/3) in DD1 and DD2 patients, respectively. Nephrocalcinosis and nephrolithiasis were found in 16.7% (2/12) and 8.3% (1/12) of DD1 patients, respectively. Renal biopsy revealed focal segmental glomerulosclerosis (FSGS) in 1 patient, minimal change lesion in 5 patients, and small focal acute tubular injury in 1 patient. A total of 11 mutations in the CLCN5 gene were detected, including 3 missense mutations (25.0%, c.1756C > T, c.1166T > G, and c.1618G > A), 5 frameshift mutations (41.7%, c.407delT, c.1702_c.1703insC, c.137delC, c.665_666delGGinsC, and c.2200delG), and 3 nonsense mutations (25.0%, c.776G > A, c.1609C > T, and c.1152G > A). There was no significant difference in age or clinical phenotype among patients with different mutation types (p > 0.05). All three mutations in the OCRL1 gene were missense mutations (c.1477C > T, c.952C > T, and c.198A > G). CONCLUSION:  Pediatric Dent disease is often misdiagnosed. Protein electrophoresis and genetic testing can help to provide an early and correct diagnosis.

Systemic lupus erythematosus combined with Wilson's disease: a case report and literature review.

BACKGROUND: Systemic lupus erythematosus (SLE) and Wilson's disease (WD) are both systemic diseases that can affect multiple organs in the body. The coexistence of SLE and WD is rarely encountered in clinical practice, making it challenging to diagnose. CASE REPORT: We present the case of a 9-year-old girl who initially presented with proteinuria, haematuria, pancytopenia, hypocomplementemia, and positivity for multiple autoantibodies. She was diagnosed with SLE, and her blood biochemistry showed elevated liver enzymes at the time of diagnosis. Despite effective control of her symptoms, her liver enzymes remained elevated during regular follow-up. Laboratory tests revealed decreased serum copper and ceruloplasmin levels, along with elevated urinary copper. Liver biopsy revealed chronic active hepatitis, moderate inflammation, moderate-severe fibrosis, and a trend towards local cirrhosis. Genetic sequencing revealed compound heterozygous mutations in the ATP7B gene, confirming the diagnosis of SLE with WD. The girl received treatment with a high-zinc/low-copper diet, but her liver function did not improve. Upon recommendation following multidisciplinary consultation, she underwent liver transplantation. Unfortunately, she passed away on the fourth day after the surgery. CONCLUSIONS: SLE and WD are diseases that involve multiple systems and organs in the body, and SLE complicated with WD is rarely encountered in the clinic; therefore, it is easy to misdiagnose. Because penicillamine can induce lupus, it is not recommended. Liver transplantation is indicated for patients with liver disease who do not respond to medical treatment with WD. However, further research is needed to determine the optimal timing of liver transplantation for patients with SLE complicated with WD.

Inhibition of α-amylase digestion by a Lonicera caerulea berry polyphenol starch complex revealed via multi-spectroscopic and molecular dynamics analyses.

Polyphenol-starch complexes exhibit synergistic and beneficial effects on both polyphenols and resistant starches. This study evaluates the inhibitory effects and mechanisms of α-amylase on a Lonicera caerulea berry polyphenol-wheat starch (LPWS) complex following high hydrostatic pressure treatments of 400 MPa for 30 min and 600 MPa for 30 min. The IC50 values for α-amylase inhibition by the complex were 3.61 ± 0.10 mg/mL and 3.42 ± 0.08 mg/mL at a 10 % (w/w) polyphenol content. This interaction was further supported by Fourier-transform infrared spectroscopy and circular dichroism, which confirmed that the alpha helix component of the secondary structure of α-amylase was reduced due to the complex. Multifluorescence spectroscopy revealed that the complex induces changes in the microenvironment of fluorophores surrounding the α-amylase active site. Molecular dynamics simulations and molecular docking revealed that the active site of amylose within the complex becomes enveloped in polyphenol clusters. This wrapping effect reduced the hydrogen bonds between amylose and α-amylase, decreasing from 16 groups to just one group. In summary, the LPWS complex represents a low-digestible carbohydrate food source, thus laying the groundwork for the research and development of functional foods aimed at postprandial hypoglycemic effects.

A novel mutation of the RPGRIP1L gene in a Chinese boy with Joubert syndrome with oculorenal involvement.

BACKGROUND: Joubert syndrome (JS) is a rare genetically heterogeneous primary ciliopathy characterized by a pathognomonic cerebellar and brainstem malformation, the "molar tooth sign", and variable organ involvement (such as eye, kidney, liver, and skeleton). Here, we present a case of JS in a Chinese boy. CASE PRESENTATION: An 11-year-old Chinese boy presented with neonatal asphyxiation and hypoxia, strabismus, subsequent developmental delay, ataxia and end-stage kidney disease (ESKD). Routine blood tests showed severe anemia, increasing blood urea nitrogen and creatinine, elevated parathyroid hormone, hypocalcemia, hypokalemia and metabolic acidosis. Urine tests showed mild proteinuria. Ultrasound showed two small kidneys. Brain magnetic resonance imaging (MRI) showed dysplasia of the cerebellar vermis and extension of the upper cerebellar feet with the "molar tooth sign". Genetic analysis showed novel compound heterozygous mutations in the RPGRIP1L gene [p.L447fs*7(p.Leu447fsTer7) and p.G908V (p.Gly908Val)]. CONCLUSION: In the present study, we identified novel compound heterozygous mutations in the RPGRIP1L gene in a Chinese boy. The clinical and genetic findings of this study will expand the understanding of JS.

Chestnut Shell Polyphenols Inhibit the Growth of Three Food-Spoilage Bacteria by Regulating Key Enzymes of Metabolism.

The microbial contamination of food poses a threat to human health. Chestnut shells, which are byproducts of chestnut processing, contain polyphenols that exert various physiological effects, and thus have the potential to be used in food preservation. This study investigates the bacteriostatic effect and mechanism(s) of the action of chestnut shell polyphenols (CSPs) on three food-spoilage bacteria, namely Bacillus subtilis, Pseudomonas fragi, and Escherichia coli. To this end, the effect of CSPs on the ultrastructure of each bacterium was determined using scanning electron microscopy and transmission electron microscopy. Moreover, gene expression was analyzed using RT-qPCR. Subsequent molecular docking analysis was employed to elucidate the mechanism of action employed by CSPs via the inhibition of key enzymes. Ultrastructure analysis showed that CSPs damaged the bacterial cell wall and increased permeability. At 0.313 mg/mL, CSPs significantly increased the activity of alkaline phosphatase and lactate dehydrogenase, as well as protein leakage (p < 0.05), whereas the activity of the tricarboxylic acid (TCA) cycle enzymes, isocitrate dehydrogenase and α-ketoglutarate dehydrogenase, were inhibited (p < 0.05). The expression levels of the TCA-related genes gltA, icd, sucA, atpA, citA, odhA, IS178_RS16090, and IS178_RS16290 are also significantly downregulated by CSP treatment (p < 0.05). Moreover, CSPs inhibit respiration and energy metabolism, including ATPase activity and adenosine triphosphate (ATP) synthesis (p < 0.05). Molecular docking determined that proanthocyanidins B1 and C1, the main components of CSPs, are responsible for the antibacterial activity. Therefore, as natural antibacterial substances, CSPs have considerable potential for development and application as natural food preservatives.

Hyperoside Prevents Aß42-Induced Neurotoxicity in PC12 Cells and Caenorhabditis elegans.

Traditional Chinese medicines such as hyperoside-rich Acanthopanax senticosus and Crataegus pinnatifida have been confirmed to exhibit anti-oxidative stress properties. Hyperoside, the main ingredient of numerous antioxidant herbs, may have the ability to postpone the onset of neurodegenerative diseases. This study investigates the possible therapeutic mechanism of hyperoside as a natural antioxidant against Alzheimer's disease (AD) in Caenorhabditis elegans and PC12 cells. Specifically, hyperoside reduced reactive oxygen species (ROS) level and Aß42-induced neurotoxicity in C. elegans worms. Meanwhile, hyperoside reduced ROS production and increased mitochondrial membrane potentialin Aß42-induced PC12 cells, which possibly due to the increase of antioxidant enzymes activity and the diminution of malondialdehyde levels. Hoechst 33,342 staining and flow cytometry analysis results suggested that hyperoside reverses cell apoptosis. Network pharmacology predicts potentially relevant hyperoside targets and pathways in AD therapy. As anticipated, hyperoside reversed Aß42-stimulated downregulation of the PI3K/Akt/Nrf2/HO-1. The PI3K inhibitor LY294002 partially abolished the protective capability of hyperoside. The results of molecular docking further indicated that the PI3K/Akt pathways may be involved in the protection of Aß42-induced PC12 cells by hyperoside treatment. The study provides theoretical information for research and development of hyperoside as an antioxidant dietary supplement.

Chinese chestnut shell polyphenol extract regulates the JAK2/STAT3 pathway to alleviate high-fat diet-induced, leptin-resistant obesity in mice.

Chinese chestnut shell is a by-product of chestnut food processing and is rich in polyphenols. This study sought to investigate the effect of chestnut shell polyphenol extract (CSP) on weight loss and lipid reduction in a 12-week high-fat diet (HFD)-induced murine obesity model. CSP (300 mg per kg body weight) was administered intragastrically daily. AG490, a JAK2 protein tyrosine kinase inhibitor, was also intraperitoneally injected. The results showed that an HFD induced leptin resistance (LR). Compared to corresponding values in the HFD group, CSP treatment improved blood lipid levels, weight, and leptin levels in obese mice (p < 0.01). Additionally, CSP treatment enhanced enzyme activity by improving total antioxidant capacity, attenuating oxidative stress, and reducing fat droplet accumulation and inflammation in the liver, epididymal, and retroperitoneal adipose tissue. CSP also activated the LEPR-JAK2/STAT3-PTP1B-SOCS-3 signal transduction pathway in hypothalamus tissue and improved LR while regulating the expression of proteins related to lipid metabolism (PPARγ, FAS, and LPL) in white adipose tissue in the retroperitoneal cavity. However, the amelioration of lipid metabolism by CSP was dependent on JAK2. Molecular docking simulation further demonstrated the strong binding affinity of procyanidin C1 (-10.3983297 kcal mol-1) and procyanidin B1 (-9.12686729 kcal mol-1) to the crystal structure of JAK2. These results suggest that CSP may be used to reduce HFD-induced obesity with potential application as a functional food additive.

Clinical features and enzyme replacement therapy in 10 children with Fabry disease.

Objective: To summarize the clinical features, diagnosis and enzyme replacement therapy(ERT) of Fabry disease (FD) in children. Methods: The clinical data, laboratory tests, genetic variations and treatment of 10 FD children diagnosed in Shandong Provincial Hospital from September 2020 to June 2022 were retrospectively analyzed. Results: Among the 10 cases from 6 families, 7 patients were boys of 4 to 13 years of age, and 3 were girls of 12 to 15 years of age. There were 7 symptomatic patients, including 6 boys and 1 girl. All 7 patients presented with acral neuralgia. Five patients had little or no sweating. Five patients presented with cutaneous angiokeratoma. Two patients had abdominal pain. One patient developed joint symptoms. Four patients had corneal opacity. One patient had hearing loss; one patient had short stature. One patient had mild proteinuria and 1 patient had dysplasia of the right kidney with decreased eGFR (55.28 ml/min.1.73 m2). The left ventricular mass index was slightly elevated in 1 patient. Three patients had mild obstructive ventilatory dysfunction; a small amount of effusion in the intestinal space of the lower abdomen or mild fatty liver was found in 2 patients. Partial empty sella turcica in 1 patient. A total of 6 GLA gene variants were detected in 10 children, among which C.1059_1061delGAT (p.met353del) was a newly discovered mutation. Five children received ERT, of which 4 were treated with agalsidase beta and 1 was treated with agalsidase alpha. Only 1 patient had anaphylaxis. Lyso-GL-3 levels decreased significantly in the first 3 months of ERT initiation and remained relatively stable thereafter in 3 patients. The Lyso-GL-3 level was decreased, but renal impairment continued to progress in 1 patient treated with agalsidase alpha. Conclusion: The clinical manifestations of FD in childhood are diverse, and it is necessary to make a definite diagnosis by combining family history, enzyme activity, biomarkers, gene testing and other indicators. Pedigree screening and high-risk population screening are helpful for early identification, early diagnosis and early treatment. No serious adverse reactions were found during the short-term treatment with agalsidase alpha and beta.

Hawthorn fruit extract ameliorates H2O2-induced oxidative damage in neuronal PC12 cells and prolongs the lifespan of Caenorhabditis elegans via the IIS signaling pathway.

Hawthorn (Crataegus pinnatifida) fruit has a long history of use as traditional Chinese medicine and is shown to have many health benefits including antioxidant and anti-aging. In this study, the anti-aging mechanism of hawthorn fruit extract (HFE) is predicted by network pharmacology and further verified in H2O2-induced PC12 cells and Caenorhabditis elegans. Network pharmacology predicted that the antiaging mechanism of HFE is mainly involved in phosphoinositide 3-kinase (PI3K)/AKT and the insulin/insulin-like growth factor-1 (IIS) signaling pathway. HFE significantly improved cell viability, increased superoxide dismutase, catalase, and glutathione peroxidase activity, decreased lactate dehydrogenase release, the level of reactive oxygen species (ROS), and malondialdehyde content in H2O2-induced PC12 cells (p < 0.05). HFE significantly increased the mean lifespan of C. elegans by 28.43% (100 µg mL-1) and enhanced the stress resistance to H2O2, paraquat, juglone, ultraviolet radiation, and heat shock. HFE also suppressed the accumulation of aging pigments, improved the body bending ability, increased antioxidant enzyme activities, and reduced the contents of ROS and malondialdehyde. In addition, relevant gene expression, lifespan experiments with mutant strains, and molecular docking studies supported the results that HFE might extend lifespan through the IIS signal pathway.

Hawthorn extract inhibited the PI3k/Akt pathway to prolong the lifespan of Drosophila melanogaster.

HE is a natural extract with strong antioxidant capacity. Drosophila melanogaster was used to explore HE could delay aging in this study. We detected that 3 mg/ml HE could increase stress tolerance (heat, cold, starvation, oxidative stress), reduce intestinal dysfunction, and prolong the lifespan of D. melanogaster. Network pharmacology analysis showed HE could act through the PI3K-Akt pathway. Meanwhile, HE intervention inhibited the gene expression of InR, PI3K, and Akt-1, and further increased the gene expression of Atg1, Atg5, Atg8a, and Atg8b. Furthermore, HE inhibited the unnatural propagation of ISCs and increased the number of lysosomes. Supplement with HE may be an effective intervention for aging D. melanogaster. PRACTICAL APPLICATIONS: In recent years, diseases that come with aging have seriously affected people's healthy life. Hawthorn is a kind of nutrient-rich substance that is rich in flavonoids and thus has many potential biological and pharmacological functions. Our results showed that HE has good antioxidant properties and can maintain intestinal homeostasis, which provides a good theoretical basis for the development and research using HE as an effective natural antioxidant for the elderly.

Lonicera caerulea Berry Polyphenols Extract Alleviates Exercise Fatigue in Mice by Reducing Oxidative Stress, Inflammation, Skeletal Muscle Cell Apoptosis, and by Increasing Cell Proliferation.

Exercise fatigue can exert deleterious effects on the body. This study evaluated the effects and mechanisms by which Lonicera caerulea berry polyphenols extract (LCBP) improved the treadmill endurance of mice. Comparison was performed between the effects at 25°C and low temperatures (-5°C). Energy storage, product metabolism, and other biochemical indices were determined using vitamin C (VC) as a positive control. Co-immunoprecipitation was performed to detect the interaction between different proteins. Dietary supplementation with LCBP significantly prolonged the exhaustion time during treadmill exercise by 20.4% (25 °C) and 27.4% (-5 °C). LCBP significantly regulated the expression of antioxidant and inflammatory proteins, Bcl-2 /Bax apoptosis proteins, and the PKCα -NOx2 / Nox4 pathway proteins, and activated the expression of AMPK-PGC1α -NRF1-TFAM proteins in skeletal muscle mitochondria. The gene and protein expression of miRNA-133a/IGF-1/PI3K/Akt/mTOR in skeletal muscle cells was also activated. Molecular docking confirmed that the main components of LCBP such as cyanidin-3-glucoside, catechin, and chlorogenic acid, have strong binding affinity toward AMPKα. LCBP alleviates exercise fatigue in mice by reducing oxidative stress, inflammation, and apoptosis of skeletal muscle cells, enhances mitochondrial biosynthesis and cell proliferation, reduces fatigue, and enhances performance. These effects are also significant in a low-temperature environment (Graphical Abstract). Consequently, these results provide novel insights into the anti- fatigue roles of LCBP in exercise fatigue.

Regulatory effects of hawthorn polyphenols on hyperglycemic, inflammatory, insulin resistance responses, and alleviation of aortic injury in type 2 diabetic rats.

Hawthorn polyphenol extract (HPE) is beneficial for patients with type 2 diabetes (T2D). However, the mechanism underlying its beneficial effects remains unclear. We investigated the inhibitory effects and mechanisms of HPE on insulin resistance, inflammation, and aortic injury in T2D rats, using metformin (MF) as a positive control. High-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) was used to determine the primary polyphenols in HPE. Hematoxylin & Eosin (H&E) staining was used to evaluate pathological conditions of the skeletal muscle, liver, and aorta vessels in each group. The levels of serum and intestinal tissue oxidative stress, tumor necrosis factor α (TNF-α), and inflammatory interleukin-6 (IL-6) were also assessed. Western blotting was used to evaluate protein expression levels in the associated molecular pathway. Volatile organic compounds (VOCs) from colon contents were determined using headspace-gas chromatography-ion mobility chromatography. Our results showed that supplementation with 300 mg HPE/kg body weight over four weeks significantly improved total cholesterol (TC), total triglyceride (TG), insulin, and lipopolysaccharide (LPS) levels in diabetic rats (p < 0.01). The lesions of skeletal muscle, liver, and aorta in diabetic rats were significantly improved. HPE supplementation also significantly downregulated the inflammatory factors (IL-6, TNF-α, and MCP-1) in the liver of diabetic rats via the SIRT1/AMPK/NF-κB signaling pathway. Furthermore, HPE significantly reduced insulin resistance in T2D rats by upregulating the phosphorylation of glucose absorption protein (GLUT4) and insulin resistance-associated proteins, p-IRS1, p-AKT, and p-PI3K, in the rat liver (p < 0.01). The findings show that HPE could also alleviate aortic injury by activating SIRT1 and regulating the NF-κB and Wnt2/ß-catenin signaling pathways. Overall, the results of this study suggest that both HPE and MF have similar inhibitory effects on T2D in rats and that HPE could be used as a functional food component in the adjuvant treatment of T2D.

Hawthorn polyphenols reduce high glucose-induced inflammation and apoptosis in ARPE-19 cells by regulating miR-34a/SIRT1 to reduce acetylation.

Diabetic retinopathy is a major complication in patients with diabetes. Herein, we investigate how hawthorn polyphenol extract (HPE) affects high glucose-induced oxidation, inflammation, and apoptosis in ARPE-19 cells. HPLC-MS/MS was used to determine HPE content and composition. Reactive oxygen species (ROS) production was assessed using fluorescence microscopy, while glucose-induced gene and protein expressions were analyzed using real-time PCR and western blotting in cells transfected with miR-34a mimics. We found that treating cells with 10 µg/ml of HPE, 30 µM procyanidin B2, chlorogenic acid, epicatechin, or resveratrol (positive control) significantly reduced ROS production and decreased apoptosis and inflammation-related factors (p < .01). Moreover, the expression level of SIRT1 was increased, while that of acetylated NF-κB p65 and p53 proteins was decreased. These data suggest that HPE can inhibit oxidative damage, inflammation, and apoptosis through the AMPK/SIRT1/NF-κB pathway, and decrease miR-34a/SIRT1/p53 pathway activation in ARPE-19 cells, thereby demonstrating a potential use as a food additive to mitigate hyperglycemia-induced retinal damage. PRACTICAL APPLICATIONS: Hawthorn polyphenol extract (HPE) significantly reduced ROS levels, apoptosis, and the expression of inflammation-related factors in ARPE-19 cells. HPE also inhibited the AMPK/SIRT1/NF-κB and miR-34a/SIRT1/p53 pathways, which are involved in hyperglycemia-induced inflammation and apoptosis of ARPE-19 cells by regulating acetylation. Thus, HPE, as a potential food additive, may mitigate hyperglycemia-induced retinal damage.

Cerasus humilis Cherry Polyphenol Reduces High-Fat Diet-Induced Obesity in C57BL/6 Mice by Mitigating Fat Deposition, Inflammation, and Oxidation.

This study aimed to determine the anti-obesity effects and mechanisms of Cerasus humilis polyphenol (CHP) in C57BL/6 obese mice and 3T3-L1 cells. High-performance liquid chromatography-electrospray ionization-tandem mass spectrometry was used for the qualitative and quantitative identification of CHP components. The obese mice, induced by feeding high-fat diet (HFD), were treated with CHP (250 mg/kg/day) by gavage for 12 weeks. Orlistat was gavaged at 15.6 mg/kg bw/day, as a positive control group. The analysis revealed that the main components of CHP were procyanidin B2, cyanidin-3-glucoside, and pelargonidin-3-glucoside. CHP dietary supplementation significantly reduced body weight and improved blood lipid measurements in HFD-fed mice (p < 0.01). Moreover, it inhibited mRNA expression of miR-122, Srebp-1c, and Cpt1a (p < 0.01) and reduced hepatic lipid deposition, as seen by hematoxylin and eosin staining. CHP downregulated the protein expression of PPARγ and C/EBPα in HFD-induced obese mice and inhibited adipocyte differentiation (p < 0.01). Compared with the HFD group, CHP supplementation had an obvious anti-inflammatory effect (decreased protein expression, such as TNF-α, IL-6, and MCP1), reducing leptin levels and TNF-α secretion in serum and cells (p < 0.01). CHP significantly inhibited the expression of miR-27a/b (53.3 and 29.9%, p < 0.01) in mice retroperitoneal white adipocytes, enhancing the expression of the target gene Prdm16 and significantly upregulating Sirt1 (105.5%, p < 0.01) compared with the HFD group. Moreover, CHP supplementation effectively improved oxidative stress (ROS, T-AOC, SOD, CAT, and GSH-Px) induced by HFD in obese mice (p < 0.01). Thus, CHP mitigates adipocyte differentiation, browning of white adipocytes, and reduction of inflammation and antioxidant activity to reduce obesity. Consequently, these results provide novel insights into the anti-obesity roles of CHP in HFD-induced obesity.

Trehalose attenuates renal ischemia-reperfusion injury by enhancing autophagy and inhibiting oxidative stress and inflammation.

Renal ischemia-reperfusion (IR) injury is one of the most common acute kidney injuries, but there is still a lack of effective treatment in the clinical setting. Trehalose (Tre), a natural disaccharide, has been demonstrated to protect against oxidative stress, inflammation, and apoptosis. However, whether it could protect against IR-induced renal injury needs to be investigated. In an in vivo experiment, C57BL/6J mice were pretreated with or without Tre (2 g/kg) through a daily single intraperitoneal injection from 3 days before renal IR surgery. Renal function, apoptosis, oxidative stress, and inflammation were analyzed to evaluate kidney injury. In an in vitro experiment, mouse proximal tubular cells were treated with or without Tre under a hypoxia/reoxygenation condition. Western blot analysis, autophagy flux detection, and apoptosis assay were performed to evaluate the level of autophagy and antiapoptotic effect of Tre. The in vivo results showed that the renal damage induced by IR was ameliorated by Tre treatment, as renal histology and renal function were improved and the enhanced protein levels of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin were blocked. Moreover, autophagy was activated by Tre pretreatment along with inhibition of the IR injury-induced apoptosis, oxidative stress, and inflammation. The in vitro results showed that Tre treatment activated autophagy and protected against hypoxia/reoxygenation-induced tubular cell apoptosis and oxidative stress. Our results demonstrated that Tre protects against IR-induced renal injury, possibly by enhancing autophagy and blocking oxidative stress, inflammation, and apoptosis, suggesting its potential use for the clinical treatment of renal IR injury.

Ursodeoxycholic acid protects against cisplatin-induced acute kidney injury and mitochondrial dysfunction through acting on ALDH1L2.

Mitochondrial dysfunction plays an important role in acute kidney injury (AKI). Thus, the agents improving the mitochondrial function could be beneficial for treating AKI. Ursodeoxycholic acid (UDCA) has been demonstrated to prevent mitochondrial dysfunction under pathology, however, its role in AKI and the underlying mechanism remain unknown. This study aimed to evaluate the effect of UDCA on cisplatin-induced AKI. In vivo, C57BL/6 J mice were treated with cisplatin (25 mg/kg) for 72 h to induce AKI through a single intraperitoneal (i.p.) injection with or without UDCA (60 mg/kg/day) administration by gavage. Renal function, mitochondrial function and oxidative stress were analyzed to evaluate kidney injury. In vitro, mouse proximal tubular cells (mPTCs) and human proximal tubule epithelial cells (HK2) were treated with cisplatin with or without UDCA treatment for 24 h. Transcriptomic RNA-seq was preformed to analyze possible targets of UDCA. Our results showed that cisplatin-induced increments of serum creatinine (Scr), blood urea nitrogen (BUN), and cystatin C were significantly reduced by UDCA along with ameliorated renal tubular injury evidenced by improved renal histology and blocked upregulation of neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1). Meanwhile, the apoptosis induced by cisplatin was also markedly attenuated by UDCA administration. In vitro, UDCA treatment protected against tubular cell apoptosis possibly through antagonizing mitochondrial dysfunction and oxidative stress by targeting ALDH1L2 which was screened out by an RNA-seq analysis. Knockout of ALDH1L2 by CRISPR/Cas9 greatly blunted the protective effects of UDCA in renal tubular cells. Moreover, UDCA did not diminish cisplatin's antineoplastic effect in human cancer cells. In all, our results demonstrated that UDCA protects against cisplatin-induced AKI through improving mitochondrial function through acting on the expression of ALDH1L2, suggesting a clinical potential of UDCA for the treatment of AKI.

Protective effects of hawthorn (Crataegus pinnatifida) polyphenol extract against UVB-induced skin damage by modulating the p53 mitochondrial pathway in vitro and in vivo.

This study investigated the effect of a hawthorn polyphenol extract (HPE) on ultraviolet B (UVB)-induced damage in HaCaT cells and mice. High-performance liquid chromatography/electrospray ionization tandem mass spectrometry was used to analyze the phenolic composition of HPE. The protective effects of HPE and its main components were compared in HaCaT cells. An enzyme-linked immunosorbent assay was used to detect DNA damage (8-hydroxydeoxyguanosine levels). Flow cytometry and western blotting were used to measure the extent of apoptosis and the levels of apoptosis-related proteins, respectively. Treatment with HPE or its polyphenol components inhibited the UVB-induced damage by removing an excess of reactive oxygen species (ROS), reducing DNA damage and p53 activation, regulating the protein expression of B-cell lymphoma 2 family members toward antiapoptotic ratios, and reducing caspase activation. Similar effects were observed in a UVB-irradiated mouse skin, as detected using terminal deoxynucleotidyl transferase dUTP nick-end labeling, immunohistochemistry, and western blotting assays. These results suggest that HPE can be used as a natural dietary supplement for the prevention and treatment of UVB radiation-induced skin damage. PRACTICAL APPLICATIONS: Hawthorn (Crataegus pinnatifida) shows antioxidant, anti-inflammatory, and lipid-lowering effects. As natural, healthy, and effective additives, HPEs have been widely used in food and health products. The results of this study reveal the molecular mechanisms underlying HPE effects, showing that HPE reverses the effects of UVB irradiation via removal of an excess of ROS and reduction of DNA damage and p53 expression in vitro and in vivo. Consequently, HPE upregulates the expression of antiapoptotic BCL-2 and downregulates that of proapoptotic BAX, thereby reducing the activation of caspase-3/9 and inhibiting apoptosis. These findings suggest that HPE can be used as the base ingredient for antiphotoaging food products. This study provides both theoretical and experimental background for hawthorn deep processing and utilization.

Lonicera caerulea Berry Polyphenols Activate SIRT1, Enhancing Inhibition of Raw264.7 Macrophage Foam Cell Formation and Promoting Cholesterol Efflux.

Lonicera caerulea berry polyphenols (LCBP) are known to reduce cholesterol accumulation. Currently, it is unknown whether LCBP can activate Sirtuin 1 (SIRT1) to regulate the formation of RAW264.7 macrophage foam cells. In this study, the effect of LCBP on lipid accumulation in macrophages was evaluated. Fluorescently labeled ox-LDL and 25-NBD cholesterol were used to detect the ox-LDL uptake and cholesterol outflow rate from macrophages. Gene silencing was performed using siRNA to detect changes in the expression of the ATP-binding cassette transporter A1 (ABCA1), sterol regulatory element-binding protein 2 (SREBP2), and SIRT1 proteins using Western blotting, and changes in the expression of miR-33 were detected by real-time polymerase chain reaction. The results showed that treatment with 80 µg/mL LCBP significantly inhibited the accumulation of lipids in RAW264.7 macrophages induced by ox-LDL and reduced intracellular cholesterol levels by activating SIRT1 to enhance the expression of ABCA1, a cholesterol efflux gene, but not independent effect. Of the three key LCBP components investigated, chlorogenic acid was found to activate SIRT1 and regulate the expression of the cholesterol-related factors ABCA1, SREBP2, and miR-33; cyanidin-3-glucoside and catechins were effective to a lesser extent. Our results suggest a novel hypolipidemic mechanism of LCBP.