Deficiency of ASGR1 in pigs recapitulates reduced risk factor for cardiovascular disease in humans.

Genetic variants in the asialoglycoprotein receptor 1 (ASGR1) are associated with a reduced risk of cardiovascular disease (CVD) in humans. However, the underlying molecular mechanism remains elusive. Given the cardiovascular similarities between pigs and humans, we generated ASGR1-deficient pigs using the CRISPR/Cas9 system. These pigs show age-dependent low levels of non-HDL-C under standard diet. When received an atherogenic diet for 6 months, ASGR1-deficient pigs show lower levels of non-HDL-C and less atherosclerotic lesions than that of controls. Furthermore, by analysis of hepatic transcriptome and in vivo cholesterol metabolism, we show that ASGR1 deficiency reduces hepatic de novo cholesterol synthesis by downregulating 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), and increases cholesterol clearance by upregulating the hepatic low-density lipoprotein receptor (LDLR), which together contribute to the low levels of non-HDL-C. Despite the cardioprotective effect, we unexpectedly observed mild to moderate hepatic injury in ASGR1-deficient pigs, which has not been documented in humans with ASGR1 variants. Thus, targeting ASGR1 might be an effective strategy to reduce hypercholesterolemia and atherosclerosis, whereas further clinical evidence is required to assess its hepatic impact.

Sucralose regulates postprandial blood glucose in mice through intestinal sweet taste receptors Tas1r2/Tas1r3.

BACKGROUND: Non-nutritive sweeteners (such as sucralose) bind to sweet receptors Tas1r2/Tas1r3 on intestinal endocrine L cells after diets to upregulate blood glucose. However, the mechanism by which sucralose regulates postprandial blood glucose (PBG) has not been clarified to date. We hypothesized that the gut sweet taste receptor was one of the targets for sucralose to regulate PBG. The aim of this study was to examine the effect of sucralose on PBG based on the gut sweet taste receptor signaling pathway and to explore the mechanism. Therefore, we examined PBG, genes, and proteins associated with the gut sweet receptor pathway in sucralose-exposed mice. RESULTS: The results showed that after 12 weeks of sucralose exposure the PBG of mice increased significantly, and the expression of intestinal sweet taste receptors increased correspondingly. Within the concentration range of this experiment, a significant increase of PBG was observed in mice fed on sucralose with a concentration equal to or higher than 0.33 g L-1 . CONCLUSION: Long-term consumption of sucralose may increase body weight and the risk of elevated PBG, resulting in overexpression of sweetness receptors and glucose transporters. The mechanism of these effects might be the result of non-nutritive sweeteners binding to sweetness receptors Tas1r2/Tas1r3 in gut endocrine cells and upregulating Slc5a1 and Slc2a2. But we cannot rule out that the rise in PBG is the result of a combination of sweet receptors and gut microbes. Therefore, the effect of gut microbes on PBG needs to be studied further. © 2023 Society of Chemical Industry.

Meeting report: Xenotransplantation Development Conference in Neijiang, China.

A conference on progress in the development of xenotransplantation in China was held in Neijiang, Sichuan, in May 2023, and was attended by approximately 100 established researchers and trainees. Progress in xenotransplantation research was reviewed by both Chinese and foreign experts. The topics discussed ranged from genetic engineering of pigs and the results of pig-to-nonhuman primate organ transplantation to the requirements for designated pathogen-free (DPF) pig facilities and regulation of xenotransplantation. This conference served as an opportunity to collectively advance the development of xenotransplantation in China and pave the way for its clinical application.

Advantages of the retroperitoneal retrocolic space as the transplant site for encapsulated xenogeneic islets.

OBJECTIVE: Islet allotransplantation has demonstrated improved clinical outcomes using the hepatic portal vein as the standard infusion method. However, the current implantation site is not ideal due to the short-term thrombotic and long-term immune destruction. Meanwhile, the shortage of human organ donors further limits its application. To find a new strategy, we tested a new polymer combination for islet encapsulation and transplantation. Meanwhile, we explored a new site for xenogeneic islet transplantation in mice. METHOD: We synthesized a hydrogel combining alginate plus poly-ethylene-imine (Alg/PEI) for the encapsulation of rat, neonatal porcine, and human islets. Transplantation was performed into the retroperitoneal retro-colic space of diabetic mice. Control mice received free islets under the kidney capsule or encapsulated islets into the peritoneum. The biochemical indexes were measured, and the transplanted islets were harvested for immunohistochemical staining of insulin and glucagon. RESULTS: Mice receiving encapsulated rat, porcine and human islets transplanted into the retroperitoneal space maintained normoglycemia for a median of 275, 145.5, and 146 days, respectively. In contrast, encapsulated xenogeneic islets transplanted into the peritoneum, maintained function for a median of 61, 95.5, and 82 days, respectively. Meanwhile, xenogeneic islets transplanted free into the kidney capsule lost their function within 3 days after transplantation. Immunohistochemical staining of encapsulated rat, porcine and human islets, retrieved from the retroperitoneal space, allowed to distinguish morphological normal insulin expressing ß- and glucagon expressing α-cells at 70, 60, and 100 days post-transplant, respectively. CONCLUSION: Transplantation of Alg/PEI encapsulated xenogeneic islets into the retroperitoneal space provides a valuable new implantation strategy for the treatment of type 1 diabetes.

Anti-rheumatic drug-induced hepatitis B virus reactivation and preventive strategies for hepatocellular carcinoma.

To date, an estimated 300 million people worldwide have been infected with chronic hepatitis B virus (HBV). Although anti-HBV therapies have improved the long-term survival profile of chronic carriers, viral reactivation still poses a significant challenge for preventing HBV-related hepatitis, hepatocellular carcinoma (HCC), and death. Immuno-modulating drugs, which are widely applied in managing rheumatic conditions, are commonly associated with HBV reactivation (HBVr) as a result of drug-induced immune suppression. However, there are few reports on the risk of HBVr and the medication management plan for HBV carriers, especially rheumatic patients. In this review, we summarize immuno-modulating drug-induced HBVr during rheumatoid therapy and its preventive strategies for HBVr-induced liver diseases, especially cirrhosis and HCC. These findings will assist with developing treatments for rheumatic patients, and prevent HBV-related cirrhosis and HCC.

In vivo induction of regulatory T cells by anti-CD45RB antibody causes transferable tolerance to discordant human xenogenic islets.

BACKGROUND: The treatment of diabetes by islet cell transplantation has become an accepted therapy, with transplantation of xenogeneic islet cells an attractive alternative to the problem. Previous studies in mice have demonstrated that anti-CD45RB induce immune tolerance in human pancreatic islet cells. The current study was to define the mechanism of action of anti-CD45RB induced nonspecific immune tolerance to heteroantigens. METHODS: A total of 1500 IEQ human islets were transplanted to diabetic B6µMT-/- mice, B6 mice, and µMT-/- diabetic mice undergoing thymectomy. These mice were treated short-term with doses of anti-CD45RB. CD4+Foxp3+Tregs were detected in the blood, peripheral lymphatic organs by flow cytometry, and immunohistochemistry. In addition, anti-CD25 mAb was administered to tolerant human islet cells B6µMT-/-mice. Mice then were transplanted with other human islet cells and received CD4+CD25+Tregs isolated from tolerant human islets mice to observe islet destruction. RESULTS: Anti-CD45RB treatment-induced tolerance to islets in both immunocompetent and B-cell-deficient mice (µMT-/- mice) by processes that were dependent on CD25+ Tregs, but not B cells. Anti-CD45RB treatment increased the number of CD4+Foxp3+Tregs cells. Anti-CD45RB treatment-induced immune tolerance that was antigen nonspecific, with Tregs playing an important role. Anti-CD45RB treatment-induced tolerance generated Tregs that could be transferred to another individual to manifest nonspecific immune tolerance. CONCLUSION: The results of the experiment suggest that anti-CD45RB induced tolerance to human islet xenografts is mediated by the proliferation of Tregs. These tolerogenic Tregs can be transferred to other mice and induce nonspecific immune tolerance.

Properties of regulatory B cells regulating B cell targets.

Regulatory B cells (Bregs) have shown promise as anti-rejection therapy applied to organ transplantation. However, less is known about their effect on other B cell populations that are involved in chronic graft rejection. We recently uncovered that naïve B cells, stimulated by TLR ligand agonists, converted into B cells with regulatory properties (Bregs-TLR) that prevented allograft rejection. Here, we examine the granular phenotype and regulatory properties of Breg-TLR cells suppressing B cells. Cocultures of Bregs-TLR with LPS-activated B cells showed a dose-dependent suppression of targeted B cell proliferation. Adoptive transfers of Bregs-TLR induced a decline in antibody responses to antigenically disparate skin grafts. The role of Breg BCR specificity in regulation was assessed using B cell-deficient mice replenished with transgenic BCR (OB1) and TCR (OT-II) lymphocytes of matching antigenic specificity. Results indicated that proliferation of OB1 B cells, mediated through help from CD4+ OT-II cells, was suppressed by OB1 Bregs of similar specificity. Transcriptomic analyses indicated that Bregs-TLR suppression is associated with a block in targeted B cell differentiation controlled by PRDM1 (Blimp1). This work uncovered the regulatory properties of a new brand of Breg cells and provided mechanistic insights into potential applications of Breg therapy in transplantation.

Strategies to halt 2019 novel coronavirus (SARS-CoV-2) spread for organ transplantation programs at the Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, China.

During the 2019 novel coronavirus (SARS-CoV-2) outbreak in China (from January 24 to March 11, 2020), our center performed 16 organ transplants (10 kidney, 4 liver, and 2 lung transplants) harvested from deceased donors. Regarding the strategies to prevent infections of SARS-CoV-2, we implemented specific measures for the donor and recipient management, as well as prevention of hospital-acquired infections. All 16 organ recipients had a favorable outcome without SARS-CoV-2 infection. Our approaches aiming to interrupt the spread of SARS-CoV-2 within the transplantation wards were successful, and allowed us to maintain the transplantation program for deceased liver, kidney, and lung organ recipients.

Regulatory changes in China on xenotransplantation and related products.

BACKGROUND: Given the persistence and the worldwide shortage of organs from both the deceased and living donors for clinical transplantation, pig organs or tissues hold immense promises for the patients on the waiting list, and xenotransplantation is deemed as one of the solutions to the organ shortage crisis. Indeed, the emerging gene editing technologies, such as CRISPR/Cas9, have led to tremendous progress in the generation of genetically modified pigs to overcome many barriers associated. METHOD: We presented a description of the xenotransplantation regulations in China and the related products. RESULT: Several groups in China have successfully generated transgenic pigs with the elimination of immune rejection or coagulation-related genes, and both pre-clinical and clinical studies have been reported. However, the pre-clinical evaluation and clinical application of porcine xenotransplantation raises ethical and regulatory considerations. Herein, in this review, we will summarize and discuss the progress in xenotransplantation in China and xenotransplantation-related products from the regulatory perspective. CONCLUSION: There has been remarkable progress in both the genetically modified pigs and pre-clinical studies in China, and China will be the first country to successfully fulfill the xenotransplantation from pig organ to human in the near future.

Epidemiological and clinical based study on four passages of COVID-19 patients: intervention at asymptomatic period contributes to early recovery.

BACKGROUND: With the worldwide spread of the 2019 novel coronavirus, scarce knowledge is available on the clinical features of more than two passages of patients. Further, in China, early intervention policy has been enacted since February. Whether early intervention contributes to swift recovery is still unknown. Hence, in this study, we focused on the patients from an isolated area, investigated the epidemiological and clinical characteristics of four serial passages of the virus. METHODS: From January 25 to February 29, 2020, all patient data on the SARS-CoV-2 passages in this isolated area were traced, and the patients were grouped according to the passaging of SARS-CoV-2. Clinical characteristics of patients, including laboratory, radiology, treatment and outcomes, were collected and analyzed. RESULTS: A total of 78 patients with four passages of virus transmission were included in this study. One patient transmitted SARS-CoV-2 to 8 patients (passage 2, P2), who next infected 23 patients (passage 3, P3), and then 46 patients (passage 4, P4). P2 received antiviral treatment when they had symptom, whereas P4 received antiviral treatment during their asymptomatic period. The incubation periods for P2, P3 and P4 patients were 7 days (IQR:2-12), 8 days (IQR:4-13) and 10 days (IQR:7-15), respectively. P2 patients showed lymphocytopenia (0.79 × 109/L), decreased lymphocyte percentages (12.15%), increased white blood cell count (6.51 × 109/L), increased total bilirubin levels (25% of P2 patients), increased C-reactive protein levels (100% of P2 patients) and abnormal liver function. By chest CT scans, all P2 patients (100%), 15 of P3 patients (65.22%) and 16 of P4 patients (34.78%) showed abnormality with typical feature of ground glass opacity. All of P2 patients (100%) received oxygen therapy, and in contrast, 19 of P4 patients (41.3%) received oxygen therapy. Further, significant decreased nucleic acid positive periods was found in P4 group (16 days, IQR: 10-23), compared with that of P2 group (22 days, IQR: 16-27). Moreover, the severity ratios were sharply decreased from 50% (P2 patients) to 4.35% (P4 patients), and the case fatality rate is zero. CONCLUSIONS: Judged from four passages of patients, early intervention contributes to the early recovery of COVID-19 patients.

Artificial sweeteners affect the glucose transport rate in the Caco-2/NCI-H716 co-culture model.

BACKGROUND: Artificial sweeteners have been used widely as substitutes for sugar for several decades. In recent years they have been reported to be harmful to human health - especially to glucose absorption. However, as conclusions from previous studies using a single Caco-2 cell model were not consistent, further studies with a more suitable cell model are needed. RESULTS: We established a co-culture model with enterocyte Caco-2 and enteroendocrine NCI-H716 cell lines cultured in transwell inserts. The effects of artificial sweeteners, enhancing the glucose transport rate, lasted for 60 min and then began to diminish. Most importantly, different artificial sweeteners with the same sweetness intensity had similar effects on glucose transport. The sodium / glucose co-transporter member 1 (SGLT1) mRNA expression levels increased significantly with an initial glucose concentration of 20 mM, while glucose transporter 2 (GLUT2) mRNA expression significantly increased with initial glucose concentrations of 20 mM and 60 mM. CONCLUSION: Based on the Caco-2/NCI-H716 co-culture model, SGLT1 and GLUT2 mediated the enhancing effects of artificial sweeteners on glucose transport, depending on the sweetness intensity and initial glucose concentration.

Xenotransplantation in China: Present status.

The main obstacle to organ transplantation is the shortage of organs from deceased individuals. Especially in China, the ratio of patients on the waiting list versus the transplant recipients is 30:1. Therefore, there is an urgent need for organ donors. Genetically modified pig organs have proved to be a new source for xenotransplantation, and Chinese scientists have made considerable progress in this area during recent years. In this paper, we review four important aspects of the xenotransplantation field in China. First, a large variety of genetically modified pigs have been generated by Chinese scientists: all these genetically modified pigs and the purpose of these modifications will be summarized. Second, the preclinical research in pig-to-nonhuman primate xenotransplantation is outlined. The survival time and major biochemical parameters for the xenografts are summarized. Third, regarding the bench-to-bed approach, more suitable organs have been developed for xenotransplantation in humans, and in particular, pig islet transplantation into diabetic patients as well as pig-to-human cornea and skin transplantation. Fourth, we briefly address the regulations and prospects for recruiting xenotransplantation experts in China. Based on recent progress, we anticipate that genetically modified pigs will offer suitable organs for the treatment of end-stage organ diseases in humans in the near future. Given the recent influx of world-renowned scientists in xenotransplantation to China, our country will definitely become one of the major centers of xenotransplantation research and development in the world.

Promising potentials of Tibetan macaques in xenotransplantation.

Organ transplantation is a crucial medical procedure, as it is often the only treatment for patients suffering from end-stage organ failure. Unfortunately, the shortage of donor organs limits the number of patients whose lives can be saved. Carrying out research on xenotransplantation with the aim of eventually replacing human organ transplants with those of animals is very promising, as it could effectively bridge the shortfall in donor organs. Thanks to the success of cloned pigs and to the emergence of gene-editing techniques, genetically modified pigs have come to be considered ideal animal donors for human xenotransplantation and have been widely used in basic research. Such research focuses on pig-to-nonhuman primates transplantation, as the recipients are suitable for preclinical studies because both their genes and organ sizes are similar to those of humans. Chinese transplantation scientists have carried out several experiments on Tibetan macaques, including successful preclinical transplants of material from genetically modified pigs, as well as research on such topics as intraocular pressure, Parkinson's disease, advanced cancer, islet transplantation, and liver transplantation. This article reviews basic and applied research on Tibetan macaques in xenotransplantation, as well as the issues of immune rejection and ethical concerns. We aim to demonstrate the various advantages of Tibetan macaques as transplant recipients compared to other nonhuman primate species and to provide a perspective for the future establishment of Tibetan macaques as principal recipients in preclinical studies of xenotransplantation.

Xenotransplantation in Asia.

The organ shortage crisis affects most of the world today. In Asia, rates of deceased organ donation are extremely low due to sociocultural factors. In this context, implementing new organ donation policies is not enough; xenotransplantation remains the most promising way to solve the organ crisis. Most of the early research on xenotransplantation was conducted in the US and Europe. Today, however, Asia has caught up on its Western counterparts partly due to the increasing demand for organ transplants. Given the growing influence of countries such as China, South Korea, and Japan in xenotransplantation, this article provides the reader with an essential global understanding of the scientific and ethical issues currently at stake. Furthermore, it sheds light on the beliefs and values that shape the response of the Asian public to both organ donation and xenotransplantation.

Progress in multiple genetically modified minipigs for xenotransplantation in China.

Pig-to-human organ transplantation provides an alternative for critical shortage of human organs worldwide. Genetically modified pigs are promising donors for xenotransplantation as they show many anatomical and physiological similarities to humans. However, immunological rejection including hyperacute rejection (HAR), acute humoral xenograft rejection (AHXR), immune cell-mediated rejection, and other barriers associated with xenotransplantation must be overcome with various strategies for the genetic modification of pigs. In this review, we summarize the outcomes of genetically modified and cloned pigs achieved by Chinese scientists to resolve the above-mentioned problems in xenotransplantation. It is now possible to knockout several porcine genes associated with the expression of sugar residues, antigens for (naturally) existing antibodies in humans, including GGTA1, CMAH, and ß4GalNT2, and thereby preventing the antigen-antibody response. Moreover, insertion of human complement- and coagulation-regulatory transgenes, such as CD46, CD55, CD59, and hTBM, can further overcome effects of the humoral immune response and coagulation dysfunction, while expression of regulatory factors of immune responses can inhibit the adaptive immune rejection. Furthermore, transgenic strategies have been developed by Chinese scientists to reduce the potential risk of infections by endogenous porcine retroviruses (PERVs). Breeding of multi-gene low-immunogenicity pigs in China is also presented in this review. Lastly, we will briefly mention the preclinical studies on pig-to-non-human primate xenotransplantation conducted in several centers in China.

Rapamycin inhibits activation of AMPK-mTOR signaling pathway-induced Alzheimer's disease lesion in hippocampus of rats with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is strongly correlated with Alzheimer's disease (AD). Rapamycin has important uses in oncology, cardiology and transplantation medicine. This study aims to investigate effects of rapamycin on AD in hippocampus of T2DM rat by AMPK/mTOR signaling pathway. METHODS: Morris water maze test was applied to evaluate the learning and memory abilities. The fasting plasma glucose (FBG), glycosylated haemoglobin, total cholesterol, triglyceride and serum insulin level were measured. RT-qPCR and Western blot analysis were performed to test expression of AMPK and mTOR. Immunohistochemistry was used to detect the Aß deposition and immunoblotting to test the total tau, p-tau and Aß precursor APP expressions. RESULTS: After treated with rapamycin, T2DM rats and rats with T2DM and AD showed increased learning-memory ability, and decreased levels of FBG, glycosylated hemoglobin, total cholesterol, triglyceride and serum insulin, decreased expression of APP and p-tau, increased AMPK mRNA expression and p-AMPK and decreased Aß deposition, mTOR mRNA expression and p-mTOR. CONCLUSION: The study demonstrated that rapamycin reduces the risk of AD in T2DM rats and inhibits activation of AMPK-mTOR signaling pathway, thereby improving AD lesion in hippocampus of T2DM rats.

Low intake of digestible carbohydrates ameliorates duodenal absorption of carbohydrates in mice with glucose metabolism disorders induced by artificial sweeteners.

BACKGROUND: Long-term artificial sweetener consumption has been reported to induce glucose intolerance, and the intestinal microbiota seems as an important target. While the impacts of artificial sweeteners on energy balance remain controversial, this work aimed to evaluate the protective effects in mice of a low digestible carbohydrate (LDC) diet on plasma glucose, plasma fasting insulin, sweet taste receptors, glucose transporters, and absorption of carbohydrates, together with consumption of acesulfame potassium (AK) or saccharin (SAC). RESULTS: Artificial sweetener was administered to mice for 12 weeks to induce glucose metabolism disorders; mice were treated with an LDC diet for the final 6 weeks. The experimental groups were treated with an LDC diet that had the same energy as the normal-diet group. Prolonged administration of artificial sweeteners led to metabolic dysfunction, characterized by significantly increased plasma glucose, insulin resistance, sweet taste receptors, glucose transporters, and absorption of carbohydrates. Treatment with an LDC diet positively modulated these altered parameters, suggesting overall beneficial effects of an LDC diet on detrimental changes associated with artificial sweeteners. CONCLUSIONS: Reducing digestible carbohydrates in the diet can significantly reduce the absorption of carbohydrates and improve glucose metabolism disorders caused by dietary factors. These effects may be due to the fact that reducing the amount of digestible carbohydrates in the feed can reduce the number of intestinal sweet receptors induced by exposure to artificial sweeteners. © 2019 Society of Chemical Industry.

[Mechanism of hsa-miR-302a-3p-targeted VEGFA in the Inhibition of Proliferation of Gastric Cancer Cell].

OBJECTIVE: To explore the role mechanism of hsa-miR-302a-3p overexpression in the inhibition of proliferation of gastric cancer cell SGC-7901 by targeted-regulating vascular endothelial growth factor A (VEGFA). METHODS: The cell transfection was used to transfect hsa-miR-302a-3p mimic into miR mimic group and transfect pc-VEGFA into VEGFA group, and the two genes were co-transfected into miR+VEGFA group. The transfection efficiency was detected by RT-PCR and Western blot. The bioinformatics targeting prediction and fluorescein assay were used to verify the targeting relationship between the two genes. Cell proliferation was detected by CCK-8 test, and Transwell assay was used to detect the invasion ability of each group, and scratch assay was used to detect the migration ability of each group. The morphology changes of epithelial-mesenchymal transition (EMT) in cells were observed under microscope. Western blot was used to detect the protein expression levels of survival-related proteins Ki67 and Caspase-3, EMT-related proteins E-cadherin, Vimentin, N-cadherin and Snail and VEGFA downstream target genes p-P38, p-MAPKAPK and p-Hsp27. RESULTS: VEGFA was the predicted target site of miR-302a-3p. Compared with control group, the number of cells, the invasion and migration rates were also reduced ( P<0.05) in miR mimic group, and the number of cells was increased ( P<0.05) as well as the invasion and migration rates in VEGFA group. Compared with VEGFA group, the number of cells, the invasion and migration rates were also decreased ( P<0.05) in miR+VEGFA group. The protein expression level of E-cadherin was up-regulated ( P<0.05) while the protein expression levels of Vimentin, N-cadherin and Snail were down-regulated ( P<0.05), and the protein expression levels of p-P38, p-MAPKAPK and p-Hsp27 were also down-regulated ( P<0.05). CONCLUSION: hsa-miR-302a-3p overexpression can inhibit the proliferation and promote apoptosis of gastric cancer cell SGC-7901 by targeting negative regulation of VEGFA expression.

Comparisons of Effects on Intestinal Short-Chain Fatty Acid Concentration after Exposure of Two Glycosidase Inhibitors in Mice.

Acarbose and voglibose are the most widely used diabetes drugs as glycosidase inhibitors. In this study, the use of these two inhibitors significantly increased the content of starch in large intestine, and altered the concentration of short-chain fatty acids (SCFAs) by affecting the intestinal microbiota. However, there are some differences in the intestinal microbiome of the two groups of mice, mainly in bacteria such as Bacteroidaceae bacteroides and Desulfovibrionaceae desulfovibrio. The productions of acetate and propionate in caecum in voglibose group were significantly higher than those in acarbose group and two kinds of glycosidase inhibitors were close in the production of butyrate in caecum. The Tax4Fun analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) data indicated that different productions of acetate and propionate between acarbose group and voglibose group may be related to 2-oxoisovalerate dehydrogenase and pyruvate oxidase. In addition, in-vitro experiments suggested that voglibose had less effect on epithelial cells than acarbose after direct stimulation. According to the recent researches of SCFAs produced by intestinal microbiota, our comparative study shown higher concentration of these beneficial fatty acids in the lumen of voglibose-treated mice, which implied a lower level of inflammation.

Diagnostic Significance of Serum Levels of Nerve Growth Factor and Brain Derived Neurotrophic Factor in Diabetic Peripheral Neuropathy.

BACKGROUND Our study aimed to explore the levels of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) in healthy participants, type 2 diabetes mellitus (T2DM) patients, and diabetic peripheral neuropathy (DPN) patients in order to find their effects on DPN. MATERIAL AND METHODS The clinical data of 110 healthy participants (age: 57.3±8.2 year, height: 165.4±5.5 cm, weight: 64.1±7.5 kg), 83 T2DM patients (age: 56.5±7.9 year, height: 164.8±6.2 cm, and weight: 63.6±6.6 kg), and 65 DPN patients (age: 58.2±7.3 year, height: 166.7±6.7 cm, weight: 63.1±5.8 kg) were observed. ELISA was applied to detect serum NGF and BDNF levels. Receiver operating characteristic (ROC) curve analysis was performed to evaluate diagnostic value of serum NGF and BDNF levels in DPN. Logistic regression analysis was performed to analyze risk factors for DPN. RESULTS Serum NGF and BDNF levels decreased most in DPN patients. Subsequently, we determined that serum NGF and BDNF levels were correlated with: the course of disease for patients, fasting C-peptide (FCP), 2-hour postprandial C-peptide level (2-h PCP), glycosylated hemoglobin level (HbAlc), and 24-hour urinary microalbumin excretion (24-h UME). ROC curve analysis identified high sensitivity, specificity, and accuracy of NGF and BDNF levels on DPN. Serum levels of NGF and BDNF, course of disease, 2-h PCP level, and postprandial blood glucose level were determined to be risk factors for DPN. CONCLUSIONS Our study highlights that serum levels of NGF and BDNF might be associated with the occurrence and development of DPN.