Catabolism of phenolics from grape peel and its effects on gut microbiota during in vitro colonic fermentation.

BACKGROUND: Grape peels, the main by-products of wine processing, are rich in bioactive ingredients of phenolics, including proanthocyanidins, flavonoids and anthocyanins. Phenolics have the function of regulating intestinal microbiota and promoting intestinal health. From the perspective of the dietary nutrition of grape peel phenolics (GPP), the present study aimed to investigate the influence of GPP on the composition and metabolism of human gut microbiota during in vitro fermentation. RESULTS: The results indicated that GPP could decrease pH and promote the production of short-chain fatty acids. ACE and Chao1 indices in GPP group were lower than that of the Blank group. GPP enhanced the levels of Lachnospiraceae UCG-004, Bacteroidetes and Roseburia, but reduced the Firmicutes/Bacteroidetes ratio. Kyoto Encyclopedia of Proteins and Genome enrichment pathways related to phenolic acid metabolism mainly included flavonoid, anthocyanin, flavone and flavonol biosynthesis. Gut microbiota could accelerate the release and breakdown of phenolic compounds, resulting in a decrease in the content of hesperetin-7-O-glucoside, delphinidin-3-O-glucoside and cyanidin-3-rutinoside etc. In vitro antibacterial test found that GPP increased the diameters of the inhibition zones of Escherichia coli and Staphylococcus aureus in a dose-dependent manner. CONCLUSION: The results of the present study revealed that GPP might be a potential prebiotic-like to prevent diseases by improving gut health. The findings could provide a theoretical basis for the potential to exploit GPP as dietary nutrition to maintain intestinal function. © 2024 Society of Chemical Industry.

Epidemiology and Association Rules Analysis for Pulmonary Tuberculosis Cases with Extrapulmonary Tuberculosis from Age and Gender Perspective: A Large-Scale Retrospective Multicenter Observational Study in China.

Background: Tuberculosis (TB), a multisystemic disease with protean presentation, remains a major global health problem. Although concurrent pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) cases are commonly observed clinically, knowledge regarding concurrent PTB-EPTB is limited. Here, a large-scale multicenter observational study conducted in China aimed to study the epidemiology of concurrent PTB-EPTB cases by diagnostically defining TB types and then implementing association rules analysis. Methods: The retrospective study was conducted at 21 hospitals in 15 provinces in China and included all inpatients with confirmed TB diagnoses admitted from Jan 2011 to Dec 2017. Association rules analysis was conducted for cases with concurrent PTB and various types of EPTB using the Apriori algorithm. Results: Evaluation of 438,979TB inpatients indicated PTB was the most commonly diagnosed (82.05%) followed by tuberculous pleurisy (23.62%). Concurrent PTB-EPTB was found in 129,422 cases (29.48%) of which tuberculous pleurisy was the most common concurrent EPTB type observed. The multivariable logistic regression models demonstrated that odds ratios of concurrent PTB-EPTB cases varied by gender and age group. For PTB cases with concurrent EPTB, the strongest association was found between PTB and concurrent bronchial tuberculosis (lift = 1.09). For EPTB cases with concurrent PTB, the strongest association was found between pharyngeal/laryngeal tuberculosis and concurrent PTB (lift = 1.11). Confidence and lift values of concurrent PTB-EPTB cases varied with gender and age. Conclusions: Numerous concurrent PTB-EPTB case types were observed, with confidence and lift values varying with gender and age. Clinicians should screen for concurrent PTB-EPTB in order to improve treatment outcomes.

Repair of Retinal Degeneration by Human Amniotic Epithelial Stem Cell-Derived Photoreceptor-like Cells.

The loss of photoreceptors is a major event of retinal degeneration that accounts for most cases of untreatable blindness globally. To date, there are no efficient therapeutic approaches to treat this condition. In the present study, we aimed to investigate whether human amniotic epithelial stem cells (hAESCs) could serve as a novel seed cell source of photoreceptors for therapy. Here, a two-step treatment with combined Wnt, Nodal, and BMP inhibitors, followed by another cocktail of retinoic acid, taurine, and noggin induced photoreceptor-like cell differentiation of hAESCs. The differentiated cells demonstrated the morphology and signature marker expression of native photoreceptor cells and, intriguingly, bore very low levels of major histocompatibility complex (MHC) class II molecules and a high level of non-classical MHC class I molecule HLA-G. Importantly, subretinal transplantation of the hAESCs-derived PR-like cells leads to partial restoration of visual function and retinal structure in Royal College of Surgeon (RCS) rats, the classic preclinical model of retinal degeneration. Together, our results reveal hAESCs as a potential source of functional photoreceptor cells; the hAESCs-derived photoreceptor-like cells could be a promising cell-replacement candidate for therapy of retinal degeneration diseases.

The prevalence and risks of major comorbidities among inpatients with pulmonary tuberculosis in China from a gender and age perspective: a large-scale multicenter observational study.

In clinical practice, PTB patients have concurrent many types of comorbidities such as pneumonia, liver disorder, diabetes mellitus, hematological disorder, and malnutrition. Detecting and treating specific comorbidities and preventing their development are important for PTB patients. However, the prevalence of most comorbid conditions in patients with PTB is not well described. We conducted a large-scale, multicenter, observational study to elucidate and illustrate the prevalence rates of major comorbidities in inpatients at 21 hospitals in China. The 19 specific comorbidities were selected for analysis in this patient cohort, and stratified the inpatient cohort according to age and gender. A total of 355,929 PTB inpatients were included, with a male:female ratio of 1.98 and the proportion of ≥ 65 years PTB inpatients was the most. Approximately 70% of PTB inpatients had at least one defined type of comorbidity. The prevalence of 19 specific comorbidities in inpatients with PTB was analyzed, with pneumonia being the most common comorbidity. The prevalence of most comorbidities was higher in males with PTB except thyroid disorders, mental health disorders, etc. The prevalence of defined most comorbidities in patients with PTB tended to increase with increasing age, although some specific comorbidities tended to increase initially then decrease with increasing age. Our study describes multiple clinically important comorbidities among PTB inpatients, and their prevalence between different gender and age groups. The results will enhance the clinical aptitude of physicians who treat patients with PTB to recognize, diagnose, and treat PTB comorbidities early.

Human Amniotic Epithelial Stem Cells: A Promising Seed Cell for Clinical Applications.

Perinatal stem cells have been regarded as an attractive and available cell source for medical research and clinical trials in recent years. Multiple stem cell types have been identified in the human placenta. Recent advances in knowledge on placental stem cells have revealed that human amniotic epithelial stem cells (hAESCs) have obvious advantages and can be used as a novel potential cell source for cellular therapy and clinical application. hAESCs are known to possess stem-cell-like plasticity, immune-privilege, and paracrine properties. In addition, non-tumorigenicity and a lack of ethical concerns are two major advantages compared with embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). All of the characteristics mentioned above and other additional advantages, including easy accessibility and a non-invasive application procedure, make hAESCs a potential ideal cell type for use in both research and regenerative medicine in the near future. This review article summarizes current knowledge on the characteristics, therapeutic potential, clinical advances and future challenges of hAESCs in detail.

Analysis of heavy metal content in edible honeysuckle (Lonicera japonica Thunb.) from China and health risk assessment.

Honeysuckle is a commonly used medicine for health care and treatment. To detect heavy metal pollution in honeysuckle from China and quantify the health risk of heavy metal via dietary intake, the Pb, Cd, Cr, As, Hg, Ni, Mn, Cu, and Zn contents in honeysuckle samples were determined by ICP-MS. The dissolution rate of heavy metals in honeysuckle was measured by decoction and soaking. The hazard quotient (HQ) and total hazard index (HI) were used to evaluate the noncarcinogenic risk of nine heavy metals in honeysuckle, and the carcinogenic risks of Cd and As were evaluated using the carcinogen risk. Cd exhibited the maximum permissive limit standard-exceeding rate (40.2%) in honeysuckle, followed by Cu (37.6%) and Pb (8.5%). As and Hg did not exceed the standard values, and Cr, Ni, Mn, and Zn had no limits. In a decoction fluid after 30 min of boiling, the transfer rates of Pb, Cd, As, Ni, Mn, Cu, and Zn ranged from 11.9% to 19.9%, whereas that of Cr was low (1.0%). In a soaking fluid, the transfer rates ranged from 17.0% to 56.9%; no transfer rate was detected for Hg in neither the decoction fluid nor the soaking fluid. In addition, the 95th percentile Rs of As and Cd in honeysuckle were 5.93 × 10-6 and 8.12 × 10-5, respectively. The carcinogenic risk of Cd at 56.99th percentile reached the threshold set by the World Health Organization (1.0 × 10-5). The results showed that intake of Pb, Cd, Cr, As, Hg, Ni, Mn, Cu, and Zn by the human body through honeysuckle could not cause noncarcinogenic damage. The element As had no carcinogenic risk, but Cd had a carcinogenic risk to a certain extent.

Pharmacological evidence: a new therapeutic approach to the treatment of chronic heart failure through SUR2B/Kir6.1 channel in endothelial cells.

Both iptakalim (Ipt) and natakalim (Nat) activate the SUR2B/Kir6.1 channel, an ATP-sensitive potassium channel (KATP) subtype, with high selectivity. In this study we investigated the therapeutic effects of Ipt and Nat against isoproterenol-induced chronic heart failure (ISO-CHF) in rats, and demonstrated a new therapeutic approach to the treatment of CHF through activation of the SUR2B/Kir6.1 channel in endothelial cells. In ISO-CHF rats, oral administration of Nat (1, 3, 9 mg·kg-1·d-1) or Ipt (3 mg·kg-1·d-1) for 60 days significantly improved cardiac dysfunction, reversed cardiac remodeling, significantly attenuated the pathological increases in BNP levels, and improved endothelial dysfunction by adjusting the balance between endothelin and NO systems. The therapeutic effects of Nat were prevented by the selective KATP blocker glibenclamine (Gli, 50 mg·kg-1·d-1), confirming that these effects were mediated through activation of the SUR2B/Kir6.1 channel in endothelial cells. The molecular mechanisms underlying the therapeutic effects of Nat were further addressed using proteomic methods. We identified 724 proteins in the plasma of ISO-CHF rats; 55 proteins were related to Nat. These differentially expressed proteins were mainly involved in single-organism processes and the regulation of biological quality relative to CHF, including proteasome (Psm) and ATP protein clusters. We screened out PRKAR2ß, GAS6/eNOS/NO and NO/PKG/VASP pathways involved in the amelioration of CHF among the 24 enriched pathways. We further confirmed 6 protein candidates, including PRKAR2ß, GAS6 and VASP, which were involved in the endothelial mechanisms, and ATP, TIMP3 and AGT, which contributed to its cardiovascular actions. This study demonstrates a new pharmacological approach to the treatment of CHF through activation of the SUR2B/Kir6.1 channel in endothelial cells, and that the eNOS/VASP pathways are involved in its signaling mechanisms.

Sensitivity of KATP channels to cellular metabolic disorders and the underlying structural basis.

AIM: ATP-sensitive potassium (KATP) channels formed by a combination of SUR/Kir6.x subunits play a crucial role in protection against hypoxic or ischemic injuries resulting from cell metabolic disorders. In this study we investigated the effects of Na-azide, a metabolic inhibitor, on KATP channels expressed in Xenopus oocytes, and explored the structure basis for their sensitivity to cell metabolic disorders. METHODS: Six subtypes of KATP channels (wild SUR1/Kir6.2, SUR2B/Kir6.2, SUR1/Kir6.1, SUR2B/Kir6.1, SUR2A/Kir6.2 and SUR2A/Kir6.1), as well as eleven subtypes of KATP channels with mutant subunits were expressed in Xenopus oocytes. KATP currents were recorded using a two-electrode voltage clamp recording technique. The drugs were applied through bath. RESULTS: Except SUR2A/Kir6.1, five subtypes of KATP channels were activated by Na-azide (3 mmol/L) with an order of the responses: SUR1/Kir6.2>SUR2B/Kir6.2>SUR1/Kir6.1>SUR2B/Kir6.1>SUR2A/Kir6.2, and the opening rate (t1/2) was SUR1/Kir6.x>SUR2B/Kir6.x>SUR2A/Kir6.2. Furthermore, Kir6.2, rather than Kir6.1, had intrinsic sensitivity to Na-azide, and the residues involved in ATP-binding (R50 and K185) or pH-sensing (H175) were associated with the sensitivity of the Kir6.2 subunit to Na-azide. Moreover, the residues (K707 and K1348) within the Walker A (WA) motifs of two nucleotide-binding domains (NBDs) were essential for SUR2B/Kir6.x (especially SUR2B/Kir6.1) channel activation by Na-azide, suggesting a key role for Mg-adenine nucleotide binding and/or hydrolysis in the SUR2B subunit. CONCLUSION: Among the six subtypes of KATP channels, SUR1/Kir6.2 is the most sensitive, whereas SUR2A/Kir6.1 is insensitive, to cell metabolic disorders. The Kir6.2 subunit, rather than the Kir6.1 subunit, has intrinsic sensitivity to cell metabolic disorders. The residues (K707 and K1348) within the WA motifs of SUR2B are important for the sensitivity of SUR2B/Kir6.x channels to cell metabolic disorders.

Differential modulation of GABAA and NMDA receptors by α7-nicotinic receptor desensitization in cultured rat hippocampal neurons.

AIM: To explore the modulatory effect of desensitized α7-containing nicotinic receptors (α7-nAChRs) on excitatory and inhibitory amino acid receptors in cultured hippocampal neurons and to identify the mechanism underlying this effect. METHODS: Whole-cell patch-clamp recordings were performed on cultured rat hippocampal neurons to measure α7-nAChR currents and to determine the role of desensitized α7-nAChRs on brain amino acid receptor activity. RESULTS: Pulse and perfusion applications of the α7-nAChR agonist choline were applied to induce different types of α7-nAChR desensitization in cultured hippocampal neurons. After a brief choline pulse, α7-nAChR was desensitized as a result of receptor activation, which reduced the response of the A type γ-aminobutyric acid (GABAA) receptor to its agonist, muscimol, and enhanced the response of the NMDA receptor to its agonist NMDA. By contrast, the responses of glycine or AMPA receptors to their agonists, glycine or AMPA, respectively, were not affected. Pretreatment with the α7-nAChR antagonist methyllycaconitine (MLA, 10 nmol/L) blocked the choline-induced negative modulation of the GABAA receptor and the positive modulation of the NMDA receptor. The regulation of the GABAA and NMDA receptors was confirmed using another type of α7-nAChR desensitization, which was produced by a low concentration of choline perfusion. The negative modulation of the GABAA receptor was characterized by choline-duration dependency and intracellular calcium dependency, but the positive modulation of the NMDA receptor was not associated with cytoplasmic calcium. CONCLUSION: Brain GABAA and NMDA receptors are modulated negatively and positively, respectively, by desensitized α7-nAChR as a result of choline pretreatment in cultured hippocampal neurons.

Natakalim Ameliorates Isoproterenol-Induced Chronic Heart Failure by Protecting against Endothelial Dysfunction.

The pharmacological effects and underlying mechanisms of natakalim, a novel SUR2B/Kir6.1-KATP channel opener, against chronic heart failure induced by isoproterenol in rats were investigated. Male Wistar rats were administered isoproterenol subcutaneously (85 mg/kg, 7 days) to induce chronic heart failure and were then treated with natakalim or saline for 6 weeks. Their blood pressure, heart rates and cardiac functions were measured using an 8-channel physiological recorder. Sophisticated technologies such as histological analysis, ELISA, radioimmunoassay, immunohistochemistry, real-time PCR and western blotting were employed for analysis. Natakalim (1, 3, 9 mg/kg/day, orally) or saline was administered for 6 weeks orally via a gastric tube to rats that had been injected with isoproterenol. Natakalim remarkably inhibited changes in left ventricular hemodynamic parameters and decreased the heart mass index, the left ventricular weight index, right ventricular weight index and lung weight index. Histological examination demonstrated no significant hypertrophy or fibrosis in the hearts of the natakalim-treated rats. Mechanistically, natakalim attenuates the elevation of plasma nitric oxide (NO) level and inducible NO synthase in cardiac tissue induced by isoproterenol. Additionally, natakalim inhibits the endothelin signaling system by decreasing both the content of endothelin-1 in the plasma and the protein levels of cardiac endothelin receptors A and B. Moreover, natakalim could augment the plasma prostacyclin concentration. In conclusion, our study provides evidence that natakalim effectively ameliorates isoproterenol-induced chronic heart failure in rats by protecting against endothelial dysfunction.

The new antihypertensive drug iptakalim activates ATP-sensitive potassium channels in the endothelium of resistance blood vessels.

AIM: To investigate the mechanisms underlying the activation of ATP-sensitive potassium channels (K(ATP)) by iptakalim in cultured rat mesenteric microvascular endothelial cells (MVECs). METHODS: Whole-cell KATP currents were recorded in MVECs using automated patch clamp devices. Nucleotides (ATP, ADP and UDP) were added to the internal perfusion system, whereas other drugs were added to the cell suspension on NPC-1 borosilicate glass chips. RESULTS: Application of iptakalim (10 and 100 µmol/L) significantly increased the whole-cell K(ATP) currents, which were prevented by the specific K(ATP) blocker glibenclamide (1.0 µmol/L). The opening of K(ATP) channels by iptakalim depended upon the intracellular concentrations of ATP or NDPs: iptakalim activated K(ATP) channels when the intracellular ATP or NDPs were at 100 or 1000 µmol/L, and was ineffective when the non-hydrolysable ATP analogue ATPγS (1000 µmol/L) was infused into the cells. In contrast, the K(ATP) opener pinacidil activated K(ATP) channels when the intracellular concentrations of ATP or NDPs ranged from 10 to 5000 µmol/L, and even ATPγS (1000 µmol/L) was infused into the cells. CONCLUSION: Iptakalim activates K(ATP) channels in the endothelial cells of resistance blood vessels with a low metabolic status, and this activation is dependent on both ATP hydrolysis and ATP ligands.

Bioavailability, tissue distribution, and excretion characteristics of the novel carbonic anhydrase inhibitor tolsultazolamide in rats.

AIM: Tolsultazolamide, a novel carbonic anhydrase inhibitor, is designed for the prophylaxis and treatment of acute mountain sickness. The aim of this study was to investigate the pharmacokinetics, tissue distribution, and excretion characteristics of tolsultazolamide and the sex difference in pharmacokinetics in rats. METHODS: For pharmacokinetic study, rats were intravenously injected tolsultazolamide at 1 and 2 mg/kg or orally administered tolsultazolamide at 20, 40, or 80 mg/kg) in a pharmacokinetic study. The concentrations of tolsultazolamide in plasma were determined with high-performance liquid chromatography, with a liquid-liquid extraction. For tissue distribution study, tolsultazolamide (80 mg/kg) was orally administered to overnight fasted rats (six per group and three per sex). Samples were collected from the brain, heart, lung, liver, spleen, muscle, kidney, stomach, fat, intestines, pancreas and sexual gland. For excretion study, tolsultazolamide (40 mg/kg) was orally administered to 6 rats (three per sex). The urine, feces, and bile samples were collected at 24, 48, and 72 h. RESULTS: After its intravenous administration, tolsultazolamide was rapidly eliminated from the plasma, with T1/2 of about 60-90 min. The AUC0-t and the initial concentration (C0) values were proportional to the intravenous doses. After its oral administration, tolsultazolamide showed dose-independent pharmacokinetic characteristics, with Tmax and T1/2 of approximately 2 h and 5-7 h, respectively, and good oral absolute bioavailability of about 60%. Tolsultazolamide was distributed widely in various tissues. The highest tolsultazolamide levels were detected in the stomach, intestine, spleen, lung, and kidney. Total excretion of unchanged tolsultazolamide in the urine, feces, and bile was less than 2%. The Cmax and AUC of tolsultazolamide were significantly higher in female rats than those in male rats. Clearance and volume of distribution were greater in male rats than those in female rats. The oral absolute bioavailability was also significantly different between female rats (about 83%) and male rats (about 37%). CONCLUSION: Tolsultazolamide was well absorbed and widely distributed in the rat, and very little of the unchanged form was excreted. Sex had a significant effect on the pharmacokinetics of tolsultazolamide.

Proteomics reveals potential non-neuronal cholinergic receptor-effectors in endothelial cells.

AIM: The non-neuronal acetylcholine system (NNAS) in endothelial cells participates in modulating endothelial function, vascular tone, angiogenesis and inflammation, thus plays a critical role in cardiovascular diseases. In this study, we used a proteomic approach to study potential downstream receptor-effectors of NNAS that were involved in regulating cellular function in endothelial cells. METHODS: Human umbilical vein endothelial cells were incubated in the presence of acetylcholine, oxotremorine, pilocarpine or nicotine at the concentration of 10 µmol/L for 12 h, and the expressed proteins in the cells were separated and identified with two-dimensional electrophoresis (2-DE) and LC-MS. The protein spots with the largest changes were identified by LC-MS. Biowork software was used for database search of the peptide mass fingerprints. RESULTS: Over 1200 polypeptides were reproducibly detected in 2-DE with a pH range of 3-10. Acetylcholine, oxotremorine, pilocarpine and nicotine treatment caused 16, 9, 8 and 9 protein spots, respectively, expressed differentially. Four protein spots were identified as destrin, FK506 binding protein 1A (FKBP1A), macrophage migration inhibitory factor (MIF) and profilin-1. Western blotting analyses showed that treatment of the cells with cholinergic agonists significantly decreased the expression of destrin, FKBP1A and MIF, and increased the expression of profilin-1. CONCLUSION: A set of proteins differentially expressed in endothelial cells in response to cholinergic agonists may have important implications for the downstream biological effects of NNAS.

Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-beta-cyclodextrin nanoparticles enhance drug delivery and attenuate autophagy in folate receptor-positive cancer cells.

BACKGROUND: Active targeting endocytosis mediated by the specific interaction between folic acid and its receptor has been a hotspot in biological therapy of many human cancers. Various studies have demonstrated that folate and its conjugates could facilitate the chemotherapeutic drug delivery into folate receptor (FR)-positive tumor cells in vitro and in vivo. In order to utilize FA-FR binding specificity to achieve targeted delivery of drugs into tumor cells, we prepared Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-ß-cyclodextrin nanoparticles for enhancing drug delivery in cancer cells. On this context, the aim of our study was to develop a novel nano-delivery system for promoting tumor-targeting drug delivery in folate receptor-positive Hela cells. RESULTS: We prepared folic acid (FA)-decorated bovine serum albumin (BSA) conjugated carboxymethyl-ß-cyclodextrin (CM-ß-CD) nanoparticles (FA-BSA-CM-ß-CD NPs) capable of entrapping a hydrophobic Gefitinib. It was observed that nanoparticles are monodisperse and spherical nanospheres with an average diameter of 90.2 nm and negative surface charge of -18.6 mV. FA-BSA-CM-ß-CD NPs could greatly facilitate Gefitinib uptake and enhance the toxicity to folate receptor-positive Hela cells. Under the reaction between FA and FR, Gefitinib loaded FA-BSA-CM-ß-CD NPs induced apoptosis of Hela cells through elevating the expression of caspase-3 and inhibited autophagy through decreasing the expressing of LC3. It also confirmed that clathrin-mediated endocytosis and macropinocytosis exerted great influence on the internalization of both NPs. CONCLUSIONS: These results demonstrated that FA may be an effective targeting molecule and FA-BSA-CM-ß-CD NPs provided a new strategy for the treatment of human cancer cells which over-expressed folate receptors.

A taxonomic study of Cheiloneurus Westwood (Hymenoptera, Encyrtidae) from China.

Fourteen species of Cheiloneurus from China are studied. Cheiloneurusguangxiensis Zu, sp. nov., is described as new to science, and C.boldyrevi Trjapitzin & Agekyan, 1978, C.bouceki Anis & Hayat, 2002, C.gonatopodis Perkins, 1906, and C.hadrodorys Anis & Hayat, 2002 are newly recorded from China. A key to Chinese species based on females is also presented.

Effects of sucrase enzymatic hydrolysis combined with Maillard reaction on soy protein hydrolysates: Bitterness and functional properties.

In this study, sucrase was added to convert non-reducing sugars into reducing sugars in skim obtained by enzyme-assisted aqueous extraction processing (EAEP), then the variation of soy protein hydrolysates (SPH) from the skim under different Maillard reaction times were studied. We conducted one-factor experiment and selected 2 mg/mL sucrase for enzymatic hydrolysis for 2 h. The structure of SPH was investigated by Fourier transform infrared spectroscopy, intrinsic fluorescence spectroscopy, and amino acid composition. Results showed that the Maillard reaction loosened the SPH structure and produced new functional groups. Sensory evaluation, electronic tongue, electronic nose and GC-MS were used to study the sensory characteristics of SPH, we found that the bitterness value was significantly reduced to 1.71 from 4.63 after 2 h of the Maillard reaction. The change of bitterness was related to amino acid composition and the production of pyrazine. Additionally, the iron reduction ability, DPPH free radical scavenging ability, and emulsifying activity reached the highest at 2 h of reaction with 0.80, 73.94 %, and 56.09 %. The solubility, emulsifying stability, and foaming capacity increased and gradually stabilized with the increasing reaction time. Therefore, this paper presents an effective method for generating SPH with low bitterness and high functional properties.

Nanoceria-Mediated Cyclosporin A Delivery for Dry Eye Disease Management through Modulating Immune-Epithelial Crosstalk.

Dry eye disease (DED) affects a substantial worldwide population with increasing frequency. Current single-targeting DED management is severely hindered by the existence of an oxidative stress-inflammation vicious cycle and complicated intercellular crosstalk within the ocular microenvironment. Here, a nanozyme-based eye drop, namely nanoceria loading cyclosporin A (Cs@P/CeO2), is developed, which possesses long-term antioxidative and anti-inflammatory capacities due to its regenerative antioxidative activity and sustained release of cyclosporin A (CsA). In vitro studies showed that the dual-functional Cs@P/CeO2 not only inhibits cellular reactive oxygen species production, sequentially maintaining mitochondrial integrity, but also downregulates inflammatory processes and repolarizes macrophages. Moreover, using flow cytometric and single-cell sequencing data, the in vivo therapeutic effect of Cs@P/CeO2 was systemically demonstrated, which rebalances the immune-epithelial communication in the corneal microenvironment with less inflammatory macrophage polarization, restrained oxidative stress, and enhanced epithelium regeneration. Collectively, our data proved that the antioxidative and anti-inflammatory Cs@P/CeO2 may provide therapeutic insights into DED management.

Theaflavins mitigate diabetic symptoms in GK rats by modulating the INSR/PI3K-Akt/GSK-3 pathway and intestinal microbiota.

Dietary management and interventions are crucial in the clinical management of diabetes. Numerous active dietary components in black tea have demonstrated positive effects on blood glucose levels and metabolic functions. However, limited research has explored the potential of theaflavins (TF), polyphenols in black tea, for diabetes management. In this study, high-purity TF was administered to Goto-Kakizaki (GK) diabetic model rats for four weeks to investigate its impact on diabetic pathology and analyze the underlying mechanisms through liver transcriptomics, hepatocyte metabolomics, and gut microbiome analysis. The findings indicated that continuous administration of TF (100 mg/kg) significantly suppressed blood glucose levels, reduced insulin resistance, and decreased the expression of oxidative stress indicators and inflammatory factors in GK rats. Further analysis revealed that TF might alleviate insulin resistance by improving hepatic glycogen conversion and reducing hepatic lipid deposition through modulation of key pathways, such as peroxisome proliferator-activated receptors and PI3K/AKT/GSK-3 pathways within the liver, thereby ameliorating diabetic symptoms. Additionally, TF intake facilitated the restoration of the intestinal microbial community structure by reducing the abundance of harmful bacteria and increasing the abundance of beneficial bacteria. It also reduced endotoxin lipopolysaccharide production, thereby lowering the chances of insulin resistance development and enhancing its efficacy in regulating blood glucose levels. These findings offer a novel perspective on the potential of black tea and its active constituents to prevent and treat diabetes and other metabolic disorders, providing valuable references for identifying and applying active dietary components from tea.

The complete mitochondrial genome of Exoristobia philippinensis (Hymenoptera: Chalcidoidea: Encyrtidae) and phylogenetic analysis.

Exoristobia philippinensis (Hymenoptera: Encyrtidae) is a worldwide parasitic wasp. This work presents the mitochondrial genome (mitogenome) of E. philippinensis for the first time. The complete mitochondrial genome of E. philippinensis was sequenced and annotated, which was 15,751 bp in length, and encoded 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), and two ribosomal RNA genes (rRNAs). All 13 PCGs were initiated by the ATN (ATG, ATT, and ATA) codon, terminated with the stop codon TAA except for ND1 which ends with TAG. Phylogenetic analysis showed that E. philippinensis has a sister relationship with the genus Lamennaisia.

Effect of mulberry leaf or mulberry leaf extract on glycemic traits: a systematic review and meta-analysis.

Mulberry leaf (ML) and mulberry leaf extract (MLE) have numerous biological properties, such as regulating sugar and lipid metabolism, reducing blood glucose, and increasing insulin secretion. The aim of this study was to perform a systematic review and meta-analysis of randomized clinical trials to examine the effect of ML/MLE supplementation on glycemic traits in adults, including fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), and fasting plasma insulin (FPI). Twelve clinical trials (615 participants) fulfilled the eligibility criteria for the present meta-analysis, which included sensitivity analysis and GRADE (grading of recommendations assessment, development, and evaluation) certainty. Based on the heterogeneity between included studies, a random effects model was applied in the meta-analysis, and the results are expressed as WMD (weighted mean differences) with 95% CI (confidence intervals). Meta-analysis showed that ML/MLE supplementation resulted in a significant reduction in FBG by -0.47 mmol L-1, HbA1c by -2.92 mmol mol-1, and FPI by -0.58 µIU mL-1. In addition, subgroup analysis indicated that long-term supplementation of ML/MLE (≥8 weeks) was more effective for regulation of the glycemic traits in the non-healthy and baseline FPG >6.1 mmol L-1 subgroups. Glycemic regulation by ML/MLE may be attributed to the phytochemicals they contain, which are mainly 1-deoxynojirimycin, flavonoids, phenolics, and polysaccharides.