Vascular endothelial growth factor levels in diabetic peripheral neuropathy: a systematic review and meta-analysis

ObjectiveVascular endothelial growth factors (VEGFs, including VEGF-A, VEGF-B, VEGF-C, VEGF-D and PLGF) have important roles in the development and function of the peripheral nervous system. Studies have confirmed that VEGFs, especially VEGF-A (so called VEGF) may be associated with the diabetic peripheral neuropathy (DPN) process. However, different studies have shown inconsistent levels of VEGFs in DPN patients. Therefore, we conducted this meta-analysis to evaluate the relationship between cycling levels of VEGFs and DPN.MethodsThis study searched 7 databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, WanFang Database, and Chinese Biomedical Literature (CBM), to find the target researches. The random effects model was used to calculate the overall effect.Results14 studies with 1983 participants were included, among which 13 studies were about VEGF and 1 was VEGF-B, so only the effects of VEGF were pooled. The result showed that there were obviously increased VEGF levels in DPN patients compared with diabetic patients without DPN (SMD:2.12[1.34, 2.90], p<0.00001) and healthy people (SMD:3.50[2.24, 4.75], p<0.00001). In addition, increased circulating VEGF levels were not associated with an increased risk of DPN (OR:1.02[0.99, 1.05], p<0.00001).ConclusionCompared with healthy people and diabetic patients without DPN, VEGF content in the peripheral blood of DPN patients is increased, but current evidence does not support the correlation between VEGF levels and the risk of DPN. This suggests that VEGF may play a role in the pathogenesis and repairment of DPN

Prevalence of gastroparesis in diabetic patients: a systematic review and meta-analysis

Abstract Although there was no significant heterogeneity in the meta-publication, sensitivity analyses revealed significant heterogeneity. Overall, the prevalence was higher in women (N = 6, R = 4.6%, 95% CI 3.1%, 6.0%, and I2 = 99.8%) than in men (N = 6, R = 3.4%, 95% CI 2.0%, 4.7%, and I2 = 99.6the %); prevalence of type 2 diabetes (N = 9, R = 12.5%, 95% CI 7.7%, 17.3%, and I2 = 95.4%) was higher than type 1 diabetes (N = 7, R = 8.3%, 95% CI 6.4%, 10.2%, and I2 = 93.6%); the prevalence of DGP was slightly lower in DM patients aged over 60 years (N = 6, R = 5.5%, 95% CI 3.3%, 7.7%, and I2 = 99.9%) compared to patients under 60 years of age (N = 12, R = 15.8%, 95% CI 11 15.8%, 95% CI 11.4%, 20.2%, and I2 = 88.3%). In conclusion, our findings indicate that the combined estimated prevalence of gastroparesis in diabetic patients is 9.3%. However, the sensitivity of the results is high, the robustness is low, and there are significant bias factors. The subgroup analysis revealed that the prevalence of DM-DGP is associated with factors such as gender, diabetes staging, age, and study method

Potential effects of bisphenol A on diabetes mellitus and its chronic complications: A narrative review

Diabetes mellitus (DM) is a metabolic disease caused by multiple factors such as genetics, environment, and lifestyle. Bisphenol A (BPA), as one of the most common endocrine-disrupting chemicals (EDCs), has been strongly implicated in the development of type 2 diabetes mellitus (T2DM). BPA exposure is associated with target organ damage in DM and may exacerbate the progression of some chronic complications of DM. This paper reviews relevant epidemiological, in vivo, and in vitro studies to better understand BPA's potential risk associations and pathological mechanisms in several chronic diabetic complications

The Herbal Medicine Scutellaria-Coptis Alleviates Intestinal Mucosal Barrier Damage in Diabetic Rats by Inhibiting Inflammation and Modulating the Gut Microbiota

Recent studies have confirmed that increased intestinal permeability and gut-origin lipopolysaccharide (LPS) translocation are important causes of metabolic inflammation in type 2 diabetes (T2D), but there are no recognized therapies for targeting this pathological state. Scutellaria baicalensis and Coptis chinensis are a classic herbal pair often used to treat diabetes and various intestinal diseases, and repair of intestinal barrier damage may be at the core of their therapeutic mechanism. This study investigated the effects of oral administration of Scutellaria-Coptis (SC) on the intestinal mucosal barrier in diabetic rats and explored the underlying mechanism from the perspective of anti-inflammatory and gut microbiota-modulatory effects. The main results showed that, in addition to regulating glycolipid metabolism disorders and inhibiting serum inflammatory factors, SC could also upregulate the expression levels of the tight junction proteins claudin-1, occludin, and zonula occludens (ZO-1), significantly improve intestinal epithelial damage, and inhibit excessive LPS translocation into the blood circulation. Furthermore, it was found that SC could reduce the levels of the inflammatory factors interleukin-1β (IL-1β), IL-6, and tumour necrosis factor-α (TNF-α) in intestinal tissue and that the anti-inflammatory effects involved the TLR-4/TRIF and TNFR-1/NF-κB signalling pathways. Moreover, SC had a strong inhibitory effect on some potential enteropathogenic bacteria and LPS-producing bacteria, such as Proteobacteria, Enterobacteriaceae, Enterobacter, Escherichia-Shigella, and Enterococcus, and could also promote the proliferation of butyrate-producing bacteria, such as Lachnospiraceae and Prevotellaceae. Taken together, the hypoglycaemic effects of SC were related to the protection of the intestinal mucosal barrier, and the mechanisms might be related to the inhibition of intestinal inflammation and the regulation of the gut microbiota

Gut Microbiota, a Potential New Target for Chinese Herbal Medicines in Treating Diabetes Mellitus

The gut microbiota, as an important factor affecting host health, plays a significant role in the occurrence and development of diabetes mellitus (DM), and the mechanism may be related to excessive endotoxins, altered short-chain fatty acids (SCFAs), and disordered bile acid metabolism. Traditional Chinese medicine (TCM) has a long history of treating DM, but its mechanism is not very clear. Recent research has suggested that Chinese herbal medicine can improve glucose metabolism by remodeling the gut microbiota, which opens new avenues for further research on hypoglycemic mechanisms. This review presents the recent progress of Chinese herbs, herbal extracts, and herbal compound preparations in treating DM through regulating the gut microbiota and summarizes the main mechanisms involved, namely, anti-inflammatory and antioxidative effects, protecting the intestinal barrier and inhibiting lipotoxicity. In addition, some suggestions for improvement are also proposed

N-Phenyl-2-Pyridone-Derived Endoperoxide Exhibiting Dual Activity by Suppressing both Lung Cancer and Idiopathic Pulmonary Fibrosis

Conventional light-driven photodynamic therapy (PDT) to generate toxic singlet oxygen are potential for cancer therapeutics but limited by the light penetrability and hypoxia tumor. PDT-involved combinational therapy could enhance overall therapeutic effects and reduce drug resistance, while disadvantages such as diverse pharmacokinetics among different ingredients, low active-ingredient loading, inevitably utilization of non-functional components need to be addressed. Here we report an endoperoxide E5 synthesized via ‘in vitro’ PDT could spontaneously deliver singlet oxygen, triplet oxygen and 3-methyl-N-phenyl-2-pyridone as an analogue of pirfenidone (Approved drug for treatment of idiopathic pulmonary fibrosis), showing great potential for treating non-small cell lung cancer and idiopathic pulmonary fibrosis. In aqueous solution, E5 could undergo a clear cycloreversion to afford three components with a half-life time of 8.3 hours and it efficiently suppress the migration and invasion of lung cancer cell as well as the TGF-b1 induced fibrosis in vitro. In vivo experiments suggest that E5 not only efficiently inhibits tumor growth, decreases the HIF-1α protein levels, relieves idiopathic pulmonary fibrosis, but shows good biocompatibility. Many evidence reveal that both singlet oxygen and 3-methyl-N-phenyl-2-pyridone are therapeutic ingredients, and triplet oxygen could relieve tumor hypoxia which is an inevitable issue in conventional PDT. Our study validates that endoperoxides as single active components containing multiple ingredients including singlet oxygen are of exceptionally therapeutic potential