Xing Tong’s research while affiliated with Soochow University and other places

Purpose: There has been a persistent claim that dairy products contain calcium-leaching proteins, although the soundness of such a claim has been challenged. A meta-analysis of randomized controlled trials (RCTs) on the effects of milk-derived protein supplementation on bone health indices in adults was performed to reconcile the controversy surrounding the potential skeletal safety concerns of proteins of dairy origin. Methods: The PubMed and Web of Science databases were searched for relevant RCTs. A random-effects model was used to generate pooled effect sizes and 95% confidence intervals. Results: Milk-derived protein supplementation did not significantly affect whole-body BMD (n = 7 RCTs) and BMD at the lumbar spine (n = 10), hip (n = 8), femoral neck (n = 9), trochanter (n = 5), intertrochanter (n = 2), and ultradistal radius (n = 2). The concentrations of bone formation markers (bone-specific alkaline phosphatase [n = 11], osteocalcin [n = 6], procollagen type 1 amino-terminal propeptide [n = 5]), bone resorption markers (N-terminal telopeptide of type 1 collagen [n = 7], C-terminal telopeptide of type 1 collagen [n = 7], deoxypyridinoline [n = 4]), and parathyroid hormone (n = 7) were not significantly affected. However, increased insulin-like growth factor-1 (IGF-1) concentrations (n = 13) were observed. Reduced IGF-1 concentrations were observed when soy protein was used as a comparator, and increased IGF-1 concentrations were observed when carbohydrate was used. Conclusion: Our findings do not support the claim that proteins of dairy origin are detrimental to bone health.

An energy-restricted weight-loss approach has limitations when it used in the elderly, especially because of muscle loss. We aimed to assess the effects of whey protein (WP) or WP hydrolysate (WPH) combined with an energy-restricted diet (ERD) on weight reduction and muscle preservation in older women with overweight and obesity. A total of 60 women were randomized to the control (ERD), WP (ERD + 20 g/d WP) or WPH (ERD + 20 g/d WPH) group, using a 1:1:1 allocation ratio. After an 8-week intervention, body composition, gut microbiota, and serum metabolomics changes were compared among the three groups. The reductions in body weight (−1.11 ± 1.11 vs. −2.34 ± 1.35, p < 0.05), BMI (−0.46 ± 0.45 vs. −0.97 ± 0.54, p < 0.05), and body fat (−0.70 ± 0.92 vs. −2.45 ± 1.65, p < 0.01) were higher in the WPH group than in the control group. Body fat (%) was significantly decreased in the two protein groups. Fat-free mass did not significantly change among the three groups. Serum metabolomics showed that the tricarboxylic acid cycle pathway was upregulated in the WPH group. No significant changes in microbiota were observed among the groups. In conclusion, WP or WPH supplementation combined with an energy-restricted diet benefits older women during weight loss. WPH was more effective, possibly due to increased energy metabolism.

Whey protein (WP) and whey protein hydrolysates (WPH) may have the potency to promote weight loss, preserve muscle and improve gut microbiota composition. The present study explored the effect of WPH vs WP on weight management in obese middle-aged mice in the content of changes in fat mass, muscle mass and gut microbiota composition. The present results showed that WPH significantly reduced energy intake, attenuated weight gain and improved blood lipids and glucose. Moreover, WPH reduced ectopic fat deposition and enhanced antioxidant capacity in muscle, but did not significantly affect muscle mass. WPH failed to reverse the microbial diversity reduction caused by a high-fat diet, but increased Akkermansia and Clostridium XVIII abundances and decreased Alistipes abundance. In conclusion, WPH is expected to have good prospects in weight management in middle age.

This study aimed to investigate the preventive effects of lactoferrin (Lf) on chronic alcoholic liver injury (ALI) in female mice. Female C57BL/6J mice were randomly divided into four groups: control group (CON), ethanol administration group (EtOH), low-dose Lf treatment group (LLf), and high-dose Lf group (HLf). In the last three groups, chronic ALI was induced by administering 20% ethanol ad libitum for 12 weeks. Mice in the CON and EtOH groups were fed with AIN-93G diet. Meanwhile, 0.4% and 4% casein in the AIN-93G diet were replaced by Lf as the diets of LLf and HLf groups, respectively. HLf significantly reduced hepatic triglyceride content and improved pathological morphology. HLf could inhibit cytochrome P450 2E1 overexpression and promote alcohol dehydrogenase-1 expression. HLf activated protein kinase B and AMP-activated protein kinase (AMPK), as well as upregulating nuclear-factor-erythroid-2-related factor-2 expression to elevate hepatic antioxidative enzyme activities. AMPK activation also benefited hepatic lipid metabolism. Meanwhile, HLf had no obvious beneficial effects on gut microbiota. In summary, Lf could alleviate chronic ALI in female mice, which was associated with redox balance and lipid metabolism regulation.

To investigate the effect of piperine on pancreatic β cell apoptosis, mice were fed with high-fat diet and injected with 40 mg/kg streptozotoci to establish diabetic model. The mice in the piperine group received 30 mg/kg body weight of piperine by gavage for 12 weeks. Compared with the model group, piperine intervention significantly decreased fasting blooding glucose, and increased homeostasis model assessment (HOMA)-β. Piperine also increased pancreatic superoxide dismutase and decreased malondialdehyde. Piperine significantly decreased the apoptotic rate of pancreatic β-cells, and the protein expression of Bax/Bcl-2 ratio, also up-regulated the protein expression of phosphorylated PI3K and AKT in pancreas. In addition, apoptosis was induced in mouse insulinoma 6 cells by palmitate. Piperine treatment decreased apoptosis, protein expression of Bax/Bcl-2 ratio, and cytochrome C in cells. Thus, piperine plays a beneficial role on diabetic mice by improving pancreatic β-cell dysfunction, this might be associated with regulation on PI3K/Akt-mediated anti-apoptosis signaling.

Scope Lactoferrin (Lf) has a protective potential to liver, but whether it can prevent alcoholic liver injury (ALI) remains unclear. Methods and results Four groups of male C57BL/6J mice were fed with different diets, namely, AIN-93G diet for control (CON) and ethanol (EtOH) groups, and AIN-93G diet with 0.4% and 4% casein replaced by Lf for low-dose Lf (LLf) and high-dose Lf (HLf) groups, respectively. ALI was induced by giving 20% ethanol ad libitum combined with four “binges”. Lf could remarkably decrease EtOH-induced mortality. Lf promoted aldehyde dehydrogenase-2 (ALDH2) expression and suppressing cytochrome P450 2E1 (CYP2E1) overexpression, resulting in the reduced hepatic superoxide and inflammation levels, which ultimately led to the hepatic injury alleviation. However, HLf increased acetyl-CoA carboxylase and fatty acid synthase protein levels, which suggested that excessive intake might weaken the beneficial effects of Lf. Moreover, LLf increased the relative abundances of Akkermansia and Lactobacillus. Additionally, we found that Lf likely exerted action in its digestive product forms rather than intact Lf molecular in normal condition. Conclusion LLf could ameliorate ALI, which was associated with the regulation of hepatic alcohol metabolism and the modulation of gut microbiota. However, excessive Lf intake might result in a diminished benefit. This article is protected by copyright. All rights reserved

Rationale: Iron-saturated Lf (Holo-Lactoferrin, Holo-Lf) exhibits a superior anticancer property than low iron-saturated Lf (Apo-Lf). Ferroptosis is an iron-dependent cell death characterized by the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS). Radiotherapy also exerts its therapeutic effect through ROS. Methods: The effect of different iron-saturated Lf on ferroptosis and radiotherapy were tested on triple-negative breast cancer (TNBC) cell line MDA-MB-231 and non-TNBC cell line MCF-7. Results: Holo-Lf significantly increased the total iron content, promoted ROS generation, increased lipid peroxidation end product, malondialdehyde (MDA), and enhanced ferroptosis of MDA-MB-231 cells. By contrast, Apo-Lf upregulated SLC7a11 expression, increased GSH generation and inhibited ferroptosis of MDA-MB-231 cells. However, non-TNBC MCF-7 cells were resistant to Holo-Lf-induced ferroptosis because MCF-7 cells have a higher redox balance capacity than MDA-MB-231 cells. More importantly, Holo-Lf downregulated HIF-1α expression, ameliorated the hypoxia microenvironment in subcutaneous MDA-MB-231 tumors, and promoted radiation-induced DNA damage to hypoxic MDA-MB-231 cells. Finally, the efficacy of radiotherapy to MDA-MB-231 tumors was enhanced by Holo-Lf. Conclusion: Holo-Lf could induce ferroptosis in MDA-MB-231 cells and sensitize MDA-MB-231 tumors to radiotherapy.

Background: Lactoferrin (LF) is a multifunctional glycoprotein that can regulate lipid metabolism, lower cholesterol, reduce body weight, and prevent atherosclerosis. Bile acid (BA) metabolism plays an important role in removing excess cholesterol from the body. However, studies on the effects of LF on BA metabolism are limited and inconsistent. Methods: Male C57BL/6J mice aged 6-8 weeks were fed with a normal diet (control group), high-fat/high-cholesterol diet containing cholate (HFCCD group), or HFCCD and 1.0% LF in drinking water (LF group) for 8 weeks. Serum and hepatic lipid profiles, and glucose tolerance were measured. Fecal BA composition was determined through ultra-high performance liquid chromatography-tandem mass spectrometry. The gene expression of BA synthase in the liver and farnesoid X receptor (FXR)-mediated BA negative feedback regulation pathway in the liver and ileum were analyzed via RNA analysis. Results: HFCCD resulted in abnormal cholesterol levels in the serum and liver. LF intervention significantly increased the serum high-density lipoprotein cholesterol level by 24.9% and decreased the hepatic total cholesterol content by 26%. LF treatment significantly increased the BA content per gram by 109.8%, the total amount of BA excretion by 153.5% and conjugated BAs by 87.6% in the feces. Furthermore, LF upregulated the expression of the hepatic sterol 12α-hydroxylase (CYP8B1) gene, which expresses important enzymes in the classical pathway of BA synthesis, and the bile acid-CoA amino acid N-acetyltransferase (BAAT) gene, which is responsible for the formation of conjugated BAs. The FXR-mediated pathways in the enterohepatic axis, including FXR, fibroblast growth factor 15, and fibroblast growth factor receptor 4, were inhibited by LF. Conclusions: LF ameliorated hepatic cholesterol deposition in mice fed with a high-fat and high cholesterol diet containing cholate. LF elevated the conjugated BA level, inhibited the ileum FXR and FXR-mediated enterohepatic axis, and increased BA synthesis and excretion.

In China, the frequency of mild hypertension cases remains prevalently high. Meanwhile, diets containing functional ingredients that control blood pressure have received considerable attention. In this randomized, controlled intervention study, 65 participants were randomly assigned to consume 30 g of whey protein or maltodextrin daily for 12 weeks. Blood pressure, body composition, biochemical analysis in plasma, and flow‐mediated dilation (FMD), an index for evaluating endothelial function, were measured. Finally, 54 participants (27 participants in each group) completed the study. At the end of the intervention, the average systolic blood pressure (SBP) was 129.5 ± 7.7 mmHg in the control group and 128.2 ± 6.9 mmHg in the whey protein group (p = 0.052). In the overweight and obese participants, the SBP was significantly lower in the whey protein group than in the control group (126.5 ± 6.9 mmHg vs. 128.8 ± 7.4 mmHg, p = 0.033), and body fat, fat percentage, and waist circumference significantly decreased in the whey protein group (p = 0.010, 0.016, 0.019, respectively). No difference was observed between the control and whey protein groups with regard to the changes in plasma lipids, inflammatory cytokines, antioxidative indexes, endothelium‐1, nitric oxide, angiotensin II, and angiotensin‐converting enzyme. The increase in FMD was significantly higher in the whey protein group than in the control group (5.2% vs. 0.3%, p = 0.040). In conclusion, whey protein significantly decreased SBP in pre‐ and mildly hypertensive adults, who are also overweight and obese. Whey protein also improved endothelial function. The lowering effect of blood pressure was probably related to body fat loss in these participants.

In the original publication, the funding and conflict of interest statements were not correct.