Nanotherapeutic approach to treat diabetic foot ulcers using tissue-engineered nanofiber skin substitutes: A review

Background and aimsDiabetes mellitus (DM) is a chronic metabolic disease associated with long-term multisystem complications, among which nonhealing diabetic foot ulcers (DFUs) are recognized as major cause of morbidity and mortality. Treating DFUs with surgical procedures such as synthetic or biological skin grafts or skin substitutes has several limitations, where none of the currently available skin substitutes is ideal.MethodsOVID/Medline and PubMed databases were searched using the Medical Subject Heading (MeSH) or Title/Abstract words (“diabetic foot ulcers”, “skin substitutes”, and “nanofibers”), to identify published research studies on DFUs and nanofibers.ResultsElectrospinning nanotechnology is being used in the biomedical field to produce polymeric nanofibers impregnated with drugs for wound healing, burns and diabetic ulcers. Those nanofibers also enable seeding of cells into them and culturing them in vitro to synthesize tissue-like structures. Knowing the advantages of generating patient-specific induced pluripotent stem cells (iPSCs) and organoids in three-dimension (3D), including skin organoids, it is worth mingling these technologies to develop tissue-engineered biological skin substitutes.ConclusionNanofiber-skin substitutes hold promise for treatment of patients suffering from DFUs and inspire novel strategies that could be applied to other organ systems as well, introducing a new era of “regenerative and personalized medicine”.     

The effect of induced joint restriction on plantar pressure during gait – a pilot study

BackgroundThe aim of this study was to analyse the effect of induced lower limb joint restriction on plantar pressures during gait. Focusing on restricting a single joint, without the effect of other co-morbidities, would provide better understanding as to the resultant plantar loadings during gait, which would be especially beneficial in patients requiring offloading procedures.Research QuestionDoes induced lower limb joint restriction affect plantar pressure distribution during gait?MethodsA prospective, quasi-experimental study was conducted, recruiting ten healthy, adult participants who were instructed to walk barefoot over a Tekscan HR Mat™. This procedure was repeated after separately inducing restriction of the hip, knee and ankle joints. Mean peak plantar pressure (MPP) and pressure-time integral (PTI) data were analysed to compare between unrestricted and restricted data.ResultsSignificant plantar pressure changes were observed in the heel and first metatarsal regions. Rearfoot PTIs were increased with restriction of the contralateral hip (left p <0.001) (right p =0.02) and knee joints (left p =0.01) (right p =0.04). Both MPPs (left p =0.01; right p =0.01) and PTIs (left p =0.004; right p =0.03) were increased in the first metatarsal when restricting the hip joint of the same limb. MPP was decreased in the left first metatarsal with induced knee (left p =0.01; right p =0.04) and ankle (left and right p <0.001) joint restriction. Finally, MPP was decreased in the right first metatarsal with knee (left and right p =0.01) and ankle (left p =0.04; right p =0.01) joint restriction.SignificanceLimited joint mobility may have a direct effect on plantar pressure, particularly with restriction in the hip and knee joints, hence careful attention should be given especially in patients with conditions involving plantar loadings. Results in this study also show that PTI changes during gait should be equally evaluated clinically along with peak plantar pressure analysis.     

Rubeosis faciei diabeticorum is not associated with oxidative stress and skin autofluorescence

BackgroundRubeosis faciei diabeticorum is a persistent facial erythema in patients with diabetes mellitus. The actual pathogenesis has not been studied. However, it is speculated to be a cutaneous diabetic microangiopathy.ObjectiveExamine the correlation between the severity of facial erythema and the possible causes of microvascular diabetic complications, namely oxidative stress, hyperglycemia, and cutaneous accumulation of advanced glycation end-products .MethodsPatients diagnosed with Type 2 diabetes mellitus (n = 32) were enrolled in the study. The facial erythema index was measured using the Mexameter MX18; cutaneous accumulation of advanced glycation end-products was estimated by measuring skin auto fluorescence with the AGE Reader (DiagnOptics Technologies B.V. – Groningen, Netherlands). Glycated haemoglobin, total antioxidant status, and malondialdehyde were measured in blood by TBARS assay. The correlation between the selected variables was assessed by Spearman's rank test; p ≤ 0.05 was considered statistically significant.ResultsThere was a statistically significant correlation between total antioxidant status and the facial erythema index (ρ = 0.398, p = 0.024). Malondialdehyde, skin autofluorescence, glycated haemoglobin, body mass index, duration of diabetes, and age did not demonstrate statistically significant correlation with the facial erythema index.Study limitationsThis is an observational study. Elevation of total antioxidant status could have been caused by several factors that might have also influenced the development of rubeosis faciei, including hyperbilirubinemia and hyperuricemia.ConclusionsThe results contradicted expectations. Total antioxidant status correlated positively with facial erythema index; however, there was no correlation with oxidative stress and skin autofluorescence. Further investigations should be conducted to reveal the cause of total antioxidant status elevation in patients with rubeosis faciei.     

New insights into bioelectronic medicines: A new approach to tackle diabetic peripheral neuropathy pain in clinics

Bioelectronic medicines are a newer way to treat and diagnose the diseases associated with biological systems. All vital organs of the body are innervated, commanding brain to regulate the homeostasis functions. Bioelectronic medicines rely on implications of electrical stimulations or signals associated with the nervous system for real-time treatment. Diabetic peripheral neuropathy (DPN) is a most prevalent micro-vascular complication associated with diabetes mellitus. Complex plexus of nerves were affected in this complication with impaired function. Bioelectronic medicines are future hope for effective treatment of DPN.     

至阳八阵穴隔附子饼灸治疗糖尿病胃轻瘫临床研究

目的观察至阳八阵穴隔附子饼灸治疗脾胃气虚型糖尿病胃轻瘫的疗效及对胃泌素(GAS)、胃动素(MTL)和血管活性肠肽(VIP)水平的影响。方法86例脾胃气虚型糖尿病胃轻瘫患者随机分为对照组和治疗组,每组43例。治疗组给予至阳八阵穴隔附子饼灸;对照组口服枸橼酸莫沙必利片。治疗12周后观察胃轻瘫主要症状指数量表症状积分改善情况、胃排空率及血清GAS、MTL、VIP水平。结果治疗组治疗后在胃轻瘫主要症状指数量表症状积分及胃排空率方面明显高于对照组,差异均有统计学意义(P<0.05)。治疗组治疗后血清GAS、MTL水平明显高于对照组,血清VIP水平明显低于对照组,差异均有统计学意义(P<0.05)。治疗组总有效率为90.7%,明显高于对照组的72.1%(P<0.05)。结论采用至阳八阵穴隔附子饼灸能快速促进糖尿病胃轻瘫患者胃功能的恢复,改善症状和体征,其作用机制可能与升高患者血清GAS和MTL水平,降低VIP水平有关。     

激光联合复方血栓通胶囊治疗糖尿病视网膜病变合并黄斑水肿的疗效观察

目的:分析糖尿病视网膜病变合并黄斑水肿联合采用激光与复方血栓通胶囊治疗的临床疗效。方法:选取我院2017年1月—2019年1月收治的200例糖尿病视网膜病变合并黄斑水肿患者为研究对象,随机分为两组。对照组单独行激光治疗,观察组于对照组基础上联合复方血栓通胶囊治疗,对比两组临床疗效、治疗前后IL-6(白介素-6)、VEGF(血管内皮生长因子)、NOS(血清一氧化氮合成酶)水平变化情况。结果:对照组总有效率(68.00%,68/100)较观察组总有效率(98.00%,98/100)更高(P<0.05);与对照组对比,观察组治疗后NOS水平更高,IL-6、VEGF水平更低(P<0.05)。结论:糖尿病视网膜病变合并黄斑水肿联合采用激光与复方血栓通胶囊治疗的临床疗效显著,值得推广。     

More studies are necessary to establish the effectiveness of Jinhuang powder in the treatment of diabetic foot

Diabetes mellitus is a common global public health problem that can cause serious illness and premature death. Diabetic foot ulcer, one of the complications of diabetes, is a major cause of morbidity and mortality and is associated with many other devastating complications. Previous study found that a group of traditional Chinese medicine (TCM) can be used for treating diabetic foot ulcers. More and more attention is being paid to the use of Chinese medicine to heal diabetic feet. Under the guidance of relevant theories of traditional Chinese medicine, more studies are needed to reveal the key active components and related signal pathways of TCM in the treatment of diabetic foot ulcer. One clinical study explored the treatment of diabetic foot with infection combined moist exposed burn ointment with Jinhuang powder. However, large-scale multi-center, double blind, randomized, placebo-controlled clinical trials and animal studies are necessary to establish the effectiveness of Jinhuang powder in the treatment of diabetic foot.     

Renin-angiotensin system blockers-SGLT2 inhibitors-mineralocorticoid receptor antagonists in diabetic kidney disease: A tale of the past two decades!

Several pharmacological agents to prevent the progression of diabetic kidney disease (DKD) have been tested in patients with type 2 diabetes mellitus (T2DM) in the past two decades. With the exception of renin-angiotensin system blockers that have shown a significant reduction in the progression of DKD in 2001, no other pharmacological agent tested in the past two decades have shown any clinically meaningful result. Recently, the sodium-glucose cotransporter-2 inhibitor (SGLT-2i), canagliflozin, has shown a significant reduction in the composite of hard renal and cardiovascular (CV) endpoints including progression of end-stage kidney disease in patients with DKD with T2DM at the top of renin-angiotensin system blocker use. Another SGLT-2i, dapagliflozin, has also shown a significant reduction in the composite of renal and CV endpoints including death in patients with chronic kidney disease (CKD), regardless of T2DM status. Similar positive findings on renal outcomes were recently reported as a top-line result of the empagliflozin trial in patients with CKD regardless of T2DM. However, the full results of this trial have not yet been published. While the use of older steroidal mineralocorticoid receptor antagonists (MRAs) such as spironolactone in DKD is associated with a significant reduction in albuminuria outcomes, a novel non-steroidal MRA finerenone has additionally shown a significant reduction in the composite of hard renal and CV endpoints in patients with DKD and T2DM, with reasonably acceptable side effects.