scholarly journals Mulberry Leaf and Radix Astragali Regulates Differentially Expressed Genes and Proteins in the Streptozotocin-Induced Diabetic Mice Liver

Processes ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1898
Author(s):  
Shu Zhang ◽  
Qi Ge ◽  
Liang Chen ◽  
Keping Chen

As a chronic non-infectious disease, severely affecting human quality and health of life, diabetes mellitus (DM) and its complications have gradually developed into a major global public health problem. Mulberry Leaf and Radix Astragali have been used as a traditional medicinal formulation in diabetic patients for a long time, whose combination is usually found in traditional Chinese medicine prescriptions. However, due to the unclear synergistic mechanism of them for DM, the changes of differential genes and proteins in the liver tissue of streptozotocin-induced diabetic mice were analyzed, and then the potential synergistic mechanism of them in anti-diabetes was investigated in our research. Compared with the diabetic model group, there were 699 differentially expressed genes and 169 differentially expressed proteins in the Mulberry Leaf and Radix Astragali treated group, and there were 35 common specific genes both in the transcriptome and the proteome. These common genes participated mainly in the pathways, such as retinol metabolism, steroid hormone biosynthesis, and arachidonic acid metabolism. Quantitative real-time PCR() and Western blot results speculated that the synergistic effect on anti-diabetes was mainly through regulating the expression of Tap1, Ncoa4, and Alas2, by down-regulating Fabp2 and Hmox1 and up-regulating Hmgcr, Cyp7a1. All these genes would affect bile acid secretion, alleviate the occurrence of iron death, promote the metabolism and synthesis of glycolipid substances, and ultimately maintain the body’s glucose homeostasis.

2018 ◽  
Author(s):  
Sang-Min Oh ◽  
Jin-Su Shin ◽  
Il-Koo Kim ◽  
Jae-Seung Moon ◽  
Jung-Ho Kim ◽  
...  

AbstractPatients with uncontrolled diabetes are susceptible to implant failure due to impaired bone metabolism. Hypoxia-Inducible Factor 1α (HIF-1α), a transcription factor that is up-regulated in response to reduced oxygen condition during the bone repair process after fracture or osteotomy, is known to mediate angiogenesis and osteogenesis. However, its function is inhibited under hyperglycemic conditions in diabetic patients. The aim of this study is to evaluate the effects of exogenous HIF-1α on bone formation around implants by applying HIF-1α to diabetic mice via a novel PTD-mediated DNA delivery system. Smooth surface implants (1mm in diameter; 2mm in length) were placed in the both femurs of diabetic and normal mice. HIF-1α and placebo gels were injected to implant sites of the right and left femurs, respectively: Normal mouse with HIF-1α gel (NH), Normal mouse with placebo gel (NP), Diabetic mouse with HIF-1α gel (DH), and Diabetic mouse with placebo gel (DP). RNA sequencing was performed 4 days after surgery. Based on RNA sequencing, Differentially Expressed Genes (DEGs) were identified and HIF-1α target genes were selected. Histologic and histomorphometric results were evaluated 2 weeks after the surgery. The results showed that bone-to-implant contact (BIC) and bone volume (BV) were significantly greater in the DH group than the DP group (p < 0.05). A total of 216 genes were differentially expressed in DH group compared to DP group. On the other hand, there were 95 DEGs in the case of normal mice. Twenty-one target genes of HIF-1α were identified in diabetic mice through bioinformatic analysis of DEGs. Among the target genes, NOS2, GPNMB, CCL2, CCL5, CXCL16 and TRIM63 were manually found to be associated with wound healing-related genes. In conclusion, local administration of HIF-1α via PTD may help bone formation around the implant and induce gene expression more favorable to bone formation in diabetic mice.


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Birhanu Ayelign ◽  
Markos Negash ◽  
Meaza Genetu ◽  
Tadelo Wondmagegn ◽  
Tewodros Shibabaw

The interaction between diabetes and major world infections like TB is a major public health concern because of rapidly rising levels of diabetes. The dual burden of tuberculosis (TB) and diabetes mellitus (DM) has become a major global public health problem. Diabetes mellitus is a major risk factor for the development of active and latent tuberculosis. Immune mechanisms contributing to the increased susceptibility of diabetic patients to TB are due to the defects in bacterial recognition, phagocytic activity, and cellular activation which results in impaired production of chemokines and cytokines. The initiation of adaptive immunity is delayed by impaired antigen-presenting cell (APC) recruitment and function in hyperglycemic host, which results in reduced frequencies of Th1, Th2, and Th17 cells and its secretion of cytokines having a great role in activation of macrophage and inflammatory response of tuberculosis. In addition, impaired immune response and killing of intracellular bacteria potentially increase bacterial load, chronic inflammation, and central necrosis that facilitate bacterial dissemination and miliary tuberculosis. Understanding of the immunological and biochemical basis of TB susceptibility in diabetic patients will tell us the rational development of implementation and therapeutic strategies to alleviate the dual burden of the diseases. Therefore, the aim of this review was focused on the association between diabetes and tuberculosis, focusing on epidemiology, pathogenesis, and immune dysfunction in diabetes mellitus, and its association with susceptibility, severity, and treatment outcome failure to tuberculosis.


2018 ◽  
Vol 3 (3) ◽  
pp. 2473011418S0046
Author(s):  
Kelly Stéfani ◽  
Vinicius Borges ◽  
Aldo Barbachan

Category: Diabetes Introduction/Purpose: Diabetes mellitus has become a global public health problem. Not only has its incidence remained high in developed countries such as Japan and the United States, but, also, the number of cases has been growing alarmingly in developing countries such as Brazil. The concept of detection and management of diabetes mellitus in primary care centers is widely practiced in Brazil by the general physician. The purpose of this study was to evaluate the efficacy of our educational diabetics program for patients with diabetes mellitus and to determine the predictors of compliance. Since our patient orientation protocols and the insensitive footwear we provide reduce our hospital admission costs. Methods: A prospective study (2005-2017) was performed in a quaternary hospital where patients with diabetes were referred to the outpatient clinic of the diabetic foot group. The epidemiological profile of these patients under treatment in a specialized multidisciplinary outpatient unit was evaluated. A specific protocol included notes on the age, body mass index, length of disease, use of insulin, degree of sensation as evaluated by the Semmes-Weinstein monofilament test, deformity in feet, palpation of peripheral pulses, cigarette smoking, and previous operative procedure in foot an ankle.The same specialist orthopedic doctors in foot and ankle completed the protocol and performed the specific physical examination (reports were made on deformities regarded as risky for the incursion of ulcers such as plantar callosities, alterations of the hallux and lesser toes, loss of the longitudinal plantar arch, and all those related to Charcot arthropathy) and performed the same a guidelines for foot care. Results: Out of the 578 diabetic patients, the mean age of was 67 years, 69% being of the female gender. There was 53% made use of insulin, the time of disease was 14 years, and 85% patients were obese. Evaluation of protective sensibility showed that 68% were significantly decreased (from the 4.0 g monofilament). The ulcers was found in 64 patients, 57% had degree 1 in the Wagner classification, and 63% was affected in the forefoot. Charcot neuroarthropathy was diagnosed in 54 patients, 52% had the phase 3 in the Eichenholz classification, and 61% was affected in the midfoot. Fifty-three patients had amputations at the time of their first appointment, 66% on toes. 127 patients required surgery resulted from clinical complications: ulcers, osteomyelitis, and Charcot arthropathy. Conclusion: The costs related to the disease increase greatly with the appearance of the complications, especially if there is need of hospitalization and surgical treatment. The prevention of injuries, with adequate glycemic control and supply of protective shoes is essential.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Avolio ◽  
A Thomas ◽  
Z Dang ◽  
A Faulkner ◽  
Y Gu ◽  
...  

Abstract Background Healthy longevity is the result of the interaction between favourable environment and unique genetic makeup. We showed that horizontal transfer of a longevity-associated gene variant (LAV-BPIFB4) improves endothelial function and accelerates the recovery from ischemia. Purpose To determine if the benefit of LAV-BPIFB4 gene therapy can be extended to diabetic cardiomyopathy. Methods and results We confirmed that human diabetic patients with heart failure (n=13) show a decreased cardiac expression of BPIFB4 compared with healthy subjects (n=10). Obese db/db mice received a systemic injection of adeno-associated viral vector (AAV9)-LAV-BPIFB4, AAV9-wild type (WT)-BPIFB4 (both 100 μL at 1×1012 GC/mL) or vehicle before the onset of cardiomyopathy, and were euthanised four weeks later for histological, metabolic and transcriptional analyses. Echocardiographic evaluation (n=8/group), performed at baseline and after gene therapy, showed that LAV-BPIFB4 treatment, despite not resolving hyperglycaemia, improved left ventricular function compared with the other groups. Histological analyses of the hearts (n=5 to 10/group) revealed that LAV-BPIFB4 reduced myocardial fibrosis and increased angiogenesis compared with vehicle and WT-hearts; moreover, LAV increased the expression of the alpha-isoform of the cardiac myosin heavy chain, which is associated with a superior cardiomyocyte contractility. Interestingly, LAV-BPIFB4 treatment induced an increase in cardiac SDF1 expression compared with WT and vehicle, despite the mechanism linking the two events is still unknown. The oral administration of the CXCR4 antagonist AMD-070, given at 2 mg/kg/day for four weeks, abolished several of the beneficial effects exerted by the LAV-BPIFB4 therapy in the obese diabetic mice, as assessed by echocardiography and histology (n=7/group). At the molecular level, next-generation RNA sequencing (n=3 to 4 /group) showed 8 genes were differentially expressed by LAV-BPIFB4-hearts compared with vehicle-hearts. These genes are associated with mitochondrial and metabolic functions. Among them, changes in the UCP3, HMGCS2, CS, ATPB and TOMM20 expression were also validated at the protein level by western blotting. Lipidomics using ultrahigh-performance liquid chromatography-mass spectrometry (n=6 or 7/group) showed 63 metabolites differentially expressed by LAV-BPIFB4- compared with vehicle-hearts, with only 3 (two cardiolipins and one glycerophospholipid) returning close to the non-diabetic phenotype following LAV-BPIFB4 treatment. Conclusions This study newly shows the possibility of transferring the benefit of salutary polymorphic gene variants to protect the cardiovascular system from metabolic pressure. Rather than combating pathogenic mechanisms, the strategy activates alternative pathways overriding disease risk factors. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): British Heart Foundation project grant “Longevity-associated BPIFB4 gene therapy for treatment of ischemic disease”


2019 ◽  
Vol 13 (Supl 1) ◽  
pp. S31
Author(s):  
Kelly Cristina Stéfani ◽  
Aldo Barbachan Rodrigues ◽  
Vinicius Quadros Borges ◽  
Gabriel Ferraz Ferreira ◽  
Leonardo Vinícius De Matos Moraes

Introduction: Diabetes mellitus (DM) has become a global public health problem. The concept of detection and management of diabetes mellitus in primary care centers is widely practiced in Brazil by the general practitioner. The aim of this study was to evaluate the efficacy of our educational program for diabetics for patients with diabetes mellitus and to determine the predictors of compliance. Methods: A cross-sectional prospective study was performed in a quaternary hospital where patients with diabetes were referred to the outpatient clinic of the diabetic foot group so that they were part of a multidisciplinary group (medical orthopedists specialists in foot and ankle, medical endocrinologists, physiotherapist and nurse) with a specific protocol for guidelines for foot care. Specialist orthopedic doctors of the foot and ankle completed the protocol and performed the specific physical examination. Results: Of the 578 diabetic patients, the mean age was 67 years, 69% were female, 53% used insulin to control the disease and the disease duration was 14 years. Obesity was diagnosed by calculation of the body mass index (BMI), and 85% patients were overweight. Evaluation of protective sensibility showed that 68% were significantly decreased, with sensation from the 4.0 g monofilament. One hundred and twenty seven patients required surgery resulting from clinical complications of the disease: 64 ulcers (Wagner classification 57% ulcers had a degree 1 Wagner classification, 63% affected forefoots), 54 Charcot arthropathies (52% Eichenholz in phase 3, 61% located in the mid-foot), and 9 cases of osteomyelitis. Fifty-three patients had one or more prior amputations at the time of their first appointment, mostly of the toes (66%). Conclusion: The costs related to the disease increased greatly with the appearance of complications, especially if there was a need for hospitalization and surgical treatment. The prevention of injuries with adequate glycemic control and the provision of protective shoes is essential.  


2019 ◽  
Vol 8 (1) ◽  
pp. 73 ◽  
Author(s):  
En-Shyh Lin ◽  
Wei-An Chang ◽  
Yang-Yi Chen ◽  
Ling-Yu Wu ◽  
Yi-Jen Chen ◽  
...  

Keratinocytes constitute the major cell type of epidermis, which participates in re-epithelialization during wound repair and the immune defense response to pathogens. The aim of the current study was to explore the differentially expressed genes and novel microRNA (miRNA) regulations that are potentially involved in diabetic keratinocytes through next-generation sequencing (NGS) and bioinformatics approaches. A total of 420 differentially expressed genes between normal and diabetic keratinocytes were identified, and systematic bioinformatics analyses indicated that these differentially expressed genes were functionally enriched in interferon-alpha signaling, viral defense response, and immune response. Additionally, the potential miR-340-3p-DTX3L interaction that has been systematically validated in miRNA prediction databases was proposed to participate in the disrupted skin homeostasis, altering the defense and immune response of diabetic skin. The findings may provide new insights into understanding the pathogenesis of epidermal pathologies in diabetic patients and targeting novel molecules to advance diabetic skin care in clinical practice.


F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1030
Author(s):  
Chudchawal Juntarawijit ◽  
Yuwayong Juntarawijit

Background: Type 2 diabetes mellitus (T2DM) is a global public health problem. To avoid disease complications, diabetic patients have to control their blood glucose and maintain a healthy lifestyle including a healthy diet, weight control, moderate exercise and smoking cessation. Methods: This study aimed to survey sleep, eating and exercise behaviors of diabetic patients in Bang Rakam district, a rural community in Phitsanulok province, Thailand. The data on sleep and other health behaviors were taken from 1,385 T2DM patients and 1,394 non-T2DM controls, who were aged 30 - 85 years and were free from other chronic diseases. The data were collected using a structured questionnaire. Results: Compared to the control group, the diabetic group had a significantly higher body mass index (BMI).  However, fewer of them were found to smoke cigarettes and drink alcohol. Most of the participants were ‘morning people’ who slept 7-9 hours per day. It was found that sleep ≥8 hours increased the risk of diabetes among women (OR = 1.27, 95% CI 1.03 - 1.56). The diabetic group reported eating chicken and vegetables more than the control group. They also avoided eating beef and eating more than a cup of rice per meal. However, the T2DM group did fewer physical activities, such as walking, biking or playing sports, during their leisure time. Conclusions: Compared to the control group, diabetic patients in a rural community of Thailand had healthier sleep, lifestyle and eating behaviors but not healthier exercise behaviors, especially among obese women. Diabetic prevention programs should emphasize and promote weight control and increasing levels of exercise.


Author(s):  
Angeliki Stamatopoulou ◽  
Tonia Vasilakou

Background: Diabetes mellitus is a global public health problem. The purposes of this study were: development of healthy eating habits, excellent glycemic control, maintenance ideal body weight, smoking cessation, regular physical exercise, prevention of complications.Methods: A sample of 100 diabetic patients (57% males and 43% females, aged 39-89 years old) was monitored in the Hospital of Tripolis. Patients completed a questionnaire about their eating habits. Body weight, height, waist circumference, body mass index (BMI) calculation and glycosylated hemoglobin were measured. Follow lifestyle intervention included dietary guidelines.Results: After the intervention significant differences were observed: increases in physical activity (58.95% from 41.0%, p-value = 0.002), duration of exercise (Q1 = 1.0 from 0.5, p-value = 0.023), consumption of breakfast (94.74% from 86.0%, p-value = 0.013 ), daily number of meals (median = 5 from 4, p-value = 0.002), average score of frequency in fats / oils / olive consumption (median = 2.8 from 2.5, p-value <0.001) average score of frequency in fruit consumption (median = 4.0 from 2.5, p-value <0.001), and decreases in weight (Q1 = 73.0 from 74.5, p-value = 0.002), BMI (median = 31.7 from 32.4, p-value = 0.002), waist circumference (median = 106 from 108, p-value <0.001), average score of frequency in grain / starchy / legumes consumption (Q1 = 2.6 from 2.8, p-value = 0.050).Conclusions: This study shows that even small interventions can have the desired results. But it needs perseverance and adaptation of programs to the specific characteristics and cultural beliefs of patients.


F1000Research ◽  
2021 ◽  
Vol 8 ◽  
pp. 1030
Author(s):  
Chudchawal Juntarawijit ◽  
Yuwayong Juntarawijit

Background: Type 2 diabetes mellitus (T2DM) is a global public health problem. To avoid disease complications, diabetic patients have to control their blood glucose and maintain a healthy lifestyle including a healthy diet, weight control, moderate exercise, and smoking cessation. Methods: This study aimed to survey sleep, eating, and exercise behaviors of diabetic patients in Bang Rakam district, a rural community in Phitsanulok province, Thailand. The data on sleep and other health behaviors were taken from 1,385 T2DM patients and 1,394 non-T2DM controls, who were aged 30 - 85 years and were free from other chronic diseases. The data were collected using a structured questionnaire. Results: Compared to the control group, the diabetes group had a significantly higher body mass index (BMI).  However, fewer of them were found to smoke cigarettes and drink alcohol. Most of the participants were ‘morning people’ who slept 7-9 hours per day. It was found that sleep ≥8 hours increased the risk of diabetes among women (OR = 1.27, 95% CI 1.03 - 1.56). The diabetes group reported eating chicken and vegetables more than the control group. They also avoided eating beef and eating more than a cup of rice per meal. However, the T2DM group did fewer physical activities, such as walking, biking, or playing sports, during their leisure time. Conclusions: Compared to the control group, diabetic patients in a rural community of Thailand had healthier sleep, lifestyle, and eating behaviors but not healthier exercise behaviors, especially among obese women. Diabetes prevention programs should emphasize and promote weight control and increasing levels of exercise.


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