Antenatal steroid as an independent risk factor for vitamin K2 deficiency in newborns: A Chinese single-center, retrospective study.

OBJECTIVES: To identified vitamin K2 deficiency rate and risk factors among newborns in China and assess the importance of high-risk maternal intakes of vitamin K2. METHODS: This retrospective study was performed at the Neonatology Department, the Affiliated Hospital of Guangdong Medical University, China. Routinely collected mother-neonate hospitalization data from July 2020 to January 2021 were analyzed. In total, data from 200 neonates who had completed vitamin K2 tests were utilized to assess the prevalence of vitamin K2 deficiency and identify the potential risk factors. According to the vitamin K2 level, the neonates were divided into 2 groups: cases (vitamin K2 deficiency) and controls (no vitamin K2 deficiency). The potential risk factors for vitamin K2 deficiency were evaluated by univariate and multivariate logistic regression. RESULTS: The vitamin K2 level in 24 of the 200 neonates was undetectable (<0.05 ng/mL). The prevalence of low serum vitamin K2 (<0.1 ng/ml) was 33%. Study subjects with antenatal corticosteroids use had an approximately 5-fold greater risk of developing vitamin K2 deficiency. In the univariate analyses, small-for-gestational-age (SGA), caesarean section, maternal gestational diabetes and premature rupture of the membranes were risk factors for vitamin K2 deficiency. In the multivariate logistic regression analysis, high antenatal corticosteroids use, cesarean section, and SGA were independently associated with vitamin K2 deficiency. CONCLUSION: The present study demonstrated that antenatal corticosteroids use is independently associated with vitamin K2 deficiency. This finding highlights the importance of routine vitamin K2 supplementation in late-stage pregnant women and neonates in China.

Effects and mechanism of Morus alba L. (Sangzhi) alkaloids combined with metformin on glucose metabolism in diabetic KKAy mice / 药学学报

To investigate the effects and mechanism of the combination of Morus alba L. (Sangzhi) alkaloids(SZ-A) and metformin (Met) on glucose metabolism in type 2 diabetic mice, KKAy mice were divided into four groups according to the glucose and lipid indexes: control group (control), Morus alba L. (Sangzhi) alkaloids group (SZ-A, 100 mg·kg-1), metformin group (Met, 100 mg·kg-1) and combined administration group (combination, Comb, 100 mg·kg-1 SZ-A + 100 mg·kg-1 Met). All groups were administered by gavage once daily for 7 weeks accompanied with monitoring food intake, water intake, body weight as well as glycemia. Additionally, oral glucose tolerance test (OGTT), insulin tolerance test (ITT) and oral sodium pyruvate tolerance test (OPTT) were performed at week 2, week 5, week 6, respectively. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (00004332). We determined the weight and lipid content of liver, and then performed the histopathological analysis after sacrificed. Furthermore, Western blot assay was used to detect the protein levels of key molecules of PI3K/PDK1/Akt/GLUT signaling pathway in liver, muscle and adipose tissue. Compared to the SZ-A or Met monotherapy group, SZ-A + Met significantly improved the glucose metabolism disorder, which was showed in reduced food intake, water intake, the level of fasting blood glucose, postprandial blood glucose and glycosylated hemoglobin A1c (HbA1c) of KKAy mice, as well as improved glucose tolerance, enhanced insulin sensitivity and inhibited gluconeogenesis. In addition, SZ-A + Met obviously up-regulated the protein expression levels in PI3K/PDK1/Akt/GLUT signaling pathway in liver, muscle and adipose tissue of KKAy mice. Moreover, the liver lipid accumulation and blood aminotransferase level of KKAy mice in the combined administration group were significantly reduced. Therefore, we concluded that the combination of SZ-A and Met improved glucose metabolism and inhibited the occurrence and development of T2DM via promoting glucose uptake and utilization, suggesting that the combination of SZ-A and Met is a more useful treatment for T2DM.

The effect and mechanism of metformin on peripheral neuropathy in type 1 diabetic rats / 药学学报

Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications occurring in both type 1 and type 2 diabetes mellitus patients, which often results in patients suffering from severe hyperalgesia and allodynia. Up to now, the clinical therapeutic effect of DPN is still unsatisfactory. Metformin is an anti-diabetic drug that has been safely and widely used for the treatment of type 2 diabetes for decades. Studies have shown that metformin can improve pain caused by DPN, but its effects on the nerve conduction velocity and morphology of the sciatic nerve of DPN, and the mechanism for improving DPN are not clear. Therefore, the STZ-induced model of type 1 DPN in SD rats was used to study the effects of metformin on DPN, and to preliminarily explore its mechanism in this study. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). After the model was established successfully, STZ diabetic rats were randomly divided into a model group and a metformin treatment group, and 10 normal SD rats were selected as the normal control group, and the rats were intragastrically administered for 12 weeks. The results showed that metformin significantly reduced blood glucose, glycosylated hemoglobin, food consumption and water consumption in STZ rats. Metformin markedly increased the motor nerve conduction velocity and mechanical stabbing pain threshold, prolonged the hot plate latency threshold, and improved the pathological morphological abnormalities of the sciatic nerve in STZ rats. In addition, metformin increased the content of glutathione (GSH), enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and reduced the content of malondialdehyde (MDA) in serum and sciatic nerve of STZ diabetic rats, as well as regulating the expression of genes related to oxidative stress in the sciatic nerve. Metformin obviously reduced the levels of pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in the serum in STZ rats, and inhibited the gene expression of these inflammatory factors in the sciatic nerve. In summary, metformin significantly increased nerve conduction velocity, improved sciatic nerve morphological abnormalities and pain in DPN rats, which may be related to its effect in improving oxidative stress and reducing inflammation.

Anti-diabetic effects of the fraction of alkaloids from Ramulus Mori, an innovative Sangzhi alkaloids as an α-glucosidase inhibitor / 药学学报

Sangzhi alkaloids (SZ-A) are derived from traditional Chinese medicine Ramulus Mori, serving well as an innovative antidiabetic drug, due to α-glucosidase inhibition. To evaluate the potency of glucosidase inhibitory effect of SZ-A, the enzyme-based screening platforms, including sucrase, maltase and amylase were established, and IC50 was calculated. The effects of SZ-A on postprandial blood glucose at a single dose, oral sucrose, starch and glucose loading were determined in normal ICR mice and alloxan-induced hyperglycemic mice. To confirm the anti-diabetic effects of SZ-A on glucose and lipid metabolism after long-term administration, the postprandial and fasting blood glucose, serum insulin, urinary glucose levels, glycosylated serum proteins and blood lipid levels were determined in high-fat fed C57 obese mice (pre-diabetic HFC57 mice) and diabetic rats induced by streptozotocin (STZ). The Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College approved all of the protocols for this research. We found that SZ-A exhibited a significant inhibitory effect on the sucrase and maltase. SZ-A showed no effect on amylase. In normal ICR mice and alloxan-induced hyperglycemic mice, SZ-A at a single dose significantly delayed and reduced the peak of blood glucose after sucrose or starch loading, but showed no effect on the increase of blood glucose after glucose loading. In STZ diabetic rats, SZ-A significantly reduced the postprandial or fasting blood glucose levels, glycosylated serum proteins and urinary glucose. SZ-A also reduced serum triglyceride (TG) and cholesterol (TC) levels after 3 weeks of treatment. SZ-A ameliorated the postprandial blood glucose or the fasting blood glucose elevation, and reduced the incidence of hyperglycemia in HFC57 mice. SZ-A decreased the basal insulin level, improved insulin sensitivity, and ameliorated glucose intolerance in pre-diabetic HFC57 mice. Our results indicated that SZ-A had a novel inhibitory activity on α-glucosidase, especially on disaccharidases. SZ-A at a single dose significantly reduced the peak of blood glucose elevation and delayed the increase of blood glucose in normal and diabetic mice after disaccharide and polysaccharide loading. Long-term SZ-A treatment improved glucose and lipid metabolic profiles by delaying carbohydrate absorption from the intestine and reduced the postprandial blood glucose levels in both pre-diabetic and diabetic animal models. Therefore, SZ-A application may display a beneficial role in preventing the development and complications of diabetes.

Advances of the mechanism study on berberine in the control of blood glucose and lipid as well as metabolism disorders / 药学学报

Berberine, an isoquinoline alkaloid isolated from some Chinese medicinal herbs such as Coptidis rhizoma, has been used for the treatment of diarrhea and other gastrointestinal infections as an antibacterial drug in Chinese medicine. In recent years, it was reported to have beneficial effects on the metabolism disorders states of diabetes. The mechanisms involve many aspects of the diabetes, including regulating the blood cholesterol and triglyceride, lowering blood glucose, ameliorating the insulin resistant state and influencing the function of the pancreatic beta cell.