Prevalent Complication Of Diabetes Research Articles

Total flavonoids of Astragalus protects glomerular filtration barrier in diabetic kidney disease

BackgroundDiabetic kidney disease (DKD) is a prevalent complication of diabetes and the leading cause of end-stage renal disease. Recent evidence suggests that total flavonoids of Astragalus (TFA) has promising effects on diabetes; however, its influence on DKD and the underlying mechanism remains unclear.MethodsIn this study, we induced the DKD model using streptozotocin (STZ) in male C57BL/6J mice and utilized glomerular endothelial cell (GEC) lines for in vitro investigations. We constructed a network pharmacology analysis to understand the mechanism of TFA in DKD. The mechanism of TFA action on DKD was investigated through Western blot analysis and multi-immunological methods.ResultsOur findings revealed that TFA significantly reduced levels of urinary albumin (ALB). Network pharmacology and intracellular pathway experiments indicated the crucial involvement of the PI3K/AKT signaling pathway in mediating these effects. In vitro experiments showed that TFA can preserve the integrity of the glomerular filtration barrier by inhibiting the expression of inflammatory factors TNF-alpha and IL-8, reducing oxidative stress.ConclusionOur findings demonstrated that TFA can ameliorates the progression of DKD by ameliorating renal fibrosis and preserving the integrity of the kidney filtration barrier. These results provide pharmacological evidence supporting the use of TFA in the treatment of kidney diseases.

Experience of humanistic nursing in hemodialysis nursing for patients with diabetic kidney disease.

Diabetic kidney disease (DKD) is a prevalent complication of diabetes that often requires hemodialysis for treatment. In the field of nursing, there is a growing recognition of the importance of humanistic care, which focuses on the holistic needs of patients, including their emotional, psychological, and social well-being. However, the application of humanistic nursing in the context of hemodialysis for DKD patients remains relatively unexplored. To explore the experience of humanistic nursing in hemodialysis nursing for DKD patients. Ninety-six DKD patients treated with hemodialysis from March 2020 to June 2022 were included in the study and divided into the control cluster (48 cases) and the study cluster (48 cases) according to different nursing methods; the control cluster was given routine nursing and the study cluster was given humanized nursing. The variances of negative emotion mark, blood glucose, renal function, the incidence of complications, life mark and nursing satisfaction before and after nur-sing were contrasted between the two clusters. No significant difference in negative emotion markers between the two clusters were observed before nursing (P > 0.05), and the negative emotion markers of the two clusters decreased after nursing. The Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale markers were lower in the study cluster than the control cluster. The healing rate of patients in the study cluster was significantly higher than the control cluster (97.92% vs 85.42%, P < 0.05). Blood glucose parameters were not significantly different between the groups prior to nursing (P > 0.05). However, after nursing, blood urea nitrogen and serum creatinine (SCr) levels in the study cluster were lower than those in the control cluster (P < 0.05). The incidence rate of complications was significantly lower in the study group compared to the control cluster (6.25% vs 20.83%, P < 0.05). There was no significant difference in the life markers between the two clusters before nursing. While the life markers increased after nursing for both groups, the 36-item health scale markers in the study cluster were higher than those within the control cluster (P < 0.05). Finally, the nursing satisfaction rate was 93.75% in the study cluster, compared to 75% in the control cluster (P < 0.05). In hemodialysis for DKD patients, the implementation of humanistic nursing achieved ideal results, effectively reducing patients' psychological negative emotion markers so that they can actively cooperate with the diagnosis and nursing, facilitate the control of blood glucose and the maintenance of residual renal function, reduce the occurrence of complications, and finally enhance the life quality and nursing satisfaction of patients. It is worthy of being widely popularized and applied.

Spectrum of Diabetic Neuropathy: New Insights in Diagnosis and Treatment.

Diabetic neuropathy is a highly prevalent complication of diabetes. It consists of a broad range of neuropathic conditions, such as distal symmetric polyneuropathy and various forms of autonomic neuropathies involving the cardiovascular, gastrointestinal, and urogenital systems. Prevention or diagnosis in early stages of disease is crucial to prevent symptomatic onset and progression, particularly in the absence of current disease-modifying therapies. In this review, we describe the four main types of diabetic neuropathy. We review current understanding with respect to diagnosis and treatment while highlighting knowledge gaps and future directions.

SIPA1 promotes angiogenesis by regulating VEGF secretion in Müller cells through STAT3 activation

Diabetic retinopathy (DR) is a prevalent complication of diabetes that can lead to vision loss. The chronic hyperglycemia associated with DR results in damage to the retinal microvasculature. Müller cells, as a kind of macroglia, play a crucial role in regulating the retinal vascular microenvironment. The objective of this study was to investigate the role of signal-induced proliferation-associated protein 1 (SIPA1) in regulating angiogenesis in Müller cells. Through proteomics, database analysis, endothelial cell function tests, and Western blot detection, we observed an up-regulation of SIPA1 expression in Müller cells upon high glucose stimulation. SIPA1 expression contributed to VEGF secretion in Müller cells and regulated the mobility of retinal vascular endothelial cells. Further investigation of the dependence of SIPA1 on VEGF secretion revealed that SIPA1 activated the phosphorylation STAT3, leading to its translocation into the nucleus. Overexpression of SIPA1 combined with the STAT3 inhibitor STATTIC demonstrated the regulation of SIPA1 in VEGF expression, dependent on STAT3 activation. These findings suggest that SIPA1 promotes the secretion of pro-angiogenic factors in Müller cells by activating the STAT3 signaling pathway, thereby highlighting SIPA1 as a potential therapeutic target for DR.

Fluorescent pH‐sensing bandage for point‐of‐care wound diagnostics

AbstractDiabetic foot ulcers (DFUs) are a serious and prevalent complication of diabetes. Current diagnostic options are limited to macroscopic wound analysis such as wound size, depth, and infection. Molecular diagnostics promise to improve DFU diagnosis, staging, and assessment of treatment response. Here, we developed a rapid and easy‐to‐use fluorescent pH‐sensing bandage for wound diagnostics. In a fluorescent dye screen, we identified pyranine as the lead compound due to its suitable pH‐sensing properties in the clinically relevant pH range of 6–9. To minimize the release of this dye into the wound bed, we screened a library of ionic microparticles and found a strong adhesion of the anionic dye to a cationic polymeric microparticle. These dye‐loaded microparticles showed a strong fluorescence response in the clinically relevant pH range of 6–9 and a dye release below 1% after 1 day in biological media. The dye‐loaded microparticles were subsequently encapsulated in a calcium alginate hydrogel to minimize the interaction of the microparticles with the wound tissue. This pH‐sensing diagnostic wound dressing was tested on full thickness dorsal wounds of mice, and a linear fluorescence response (R2 = 0.9909) to clinically relevant pH values was observed. These findings encourage further development of this pH‐sensing system for molecular diagnostics in DFUs.

Scutellarin Alleviates Diabetic Retinopathy via the Suppression of Nucleotide-Binding Oligomerization Domain (NOD)-Like Receptor Pyrin Domain Containing Protein 3 Inflammasome Activation

Purpose Diabetic retinopathy, a prevalent complication of diabetes, represents the leading cause of vision loss and blindness among middle-aged and elderly populations. Recent research has demonstrated the ameliorating effects of scutellarin on diabetes-associated complications such as diabetic retinopathy and type 2 diabetic cardiomyopathy. However, investigations into its protective impact and underlying mechanisms on diabetic retinopathy are scant. This study aims to explore the therapeutic potential of scutellarin in diabetic retinopathy treatment. Methods Diabetic retinopathy was induced in rats through intraperitoneal injections of streptozotocin (STZ, 60 mg/kg) administered daily for three consecutive days. Following this, diabetic retinopathy rats received daily intragastric administration of scutellarin (40 mg/kg) for 42 days. Results Our findings suggest that scutellarin alleviates histological damage in the retinal tissues of streptozotocin-challenged rats. Furthermore, scutellarin effectively enhances total retinal thickness and increases the number of ganglion cell layer (GCL) cells in the retinal tissues of streptozotocin-treated rats. Scutellarin also demonstrated anti-inflammatory and antioxidant effects in the retinal tissues of STZ-induced rats, as indicated by reduced levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6, and elevated levels of glutathione peroxidase, superoxide dismutase, and catalase. Additionally, scutellarin effectively inhibited the expression of NOD-like receptor pyrin domain containing protein 3 inflammasome-related markers in the retinal tissues of streptozotocin-administered rats. Conclusions Collectively, our results indicate that scutellarin significantly reduces streptozotocin-induced retinal inflammation, an effect that may be partially attributed to the suppression of NLRP3 inflammasome activation.

Comparing Local Binary Pattern and Gray Level Co-occurrence Matrix for Feature Extraction in Diabetic Retinopathy Classification

Diabetic retinopathy, a condition characterized by retinal damage and vision loss, is a prevalent complication of diabetes arising from elevated blood sugar levels. With a growing number of individuals affected, efficient and accurate diagnosis is crucial. This study aims to implement and compare the Local Binary Pattern (LBP) and Gray Level Co-occurrence Matrix (GLCM) feature extraction techniques, which have demonstrated success in prior research. The comparison will provide a comprehensive under- standing of the image features, extract relevant data, and improve the performance of the image analysis pipeline for diabetic retinopathy classification. The result showed that from three scenarios the best accuracy provided by Support Vector Machine with the accuracy score between 73% until 74%, however, other algorithm have little difference which the result on 73%.

The ideal treatment timing for diabetic retinopathy: the molecular pathological mechanisms underlying early-stage diabetic retinopathy are a matter of concern.

Diabetic retinopathy (DR) is a prevalent complication of diabetes, significantly impacting patients' quality of life due to vision loss. No pharmacological therapies are currently approved for DR, excepted the drugs to treat diabetic macular edema such as the anti-VEGF agents or steroids administered by intraocular route. Advancements in research have highlighted the crucial role of early intervention in DR for halting or delaying disease progression. This holds immense significance in enhancing patients' quality of life and alleviating the societal burden associated with medical care costs. The non-proliferative stage represents the early phase of DR. In comparison to the proliferative stage, pathological changes primarily manifest as microangiomas and hemorrhages, while at the cellular level, there is a loss of pericytes, neuronal cell death, and disruption of components and functionality within the retinal neuronal vascular unit encompassing pericytes and neurons. Both neurodegenerative and microvascular abnormalities manifest in the early stages of DR. Therefore, our focus lies on the non-proliferative stage of DR and we have initially summarized the mechanisms involved in its development, including pathways such as polyols, that revolve around the pathological changes occurring during this early stage. We also integrate cutting-edge mechanisms, including leukocyte adhesion, neutrophil extracellular traps, multiple RNA regulation, microorganisms, cell death (ferroptosis and pyroptosis), and other related mechanisms. The current status of drug therapy for early-stage DR is also discussed to provide insights for the development of pharmaceutical interventions targeting the early treatment of DR.

Optimizing diabetic kidney disease animal models: Insights from a meta-analytic approach.

Diabetic kidney disease (DKD) is a prevalent complication of diabetes, often leading to end-stage renal disease. Animal models have been widely used to study the pathogenesis of DKD and evaluate potential therapies. However, current animal models often fail to fully capture the pathological characteristics of renal injury observed in clinical patients with DKD. Additionally, modeling DKD is often a time-consuming, costly, and labor-intensive process. The current review aims to summarize modeling strategies in the establishment of DKD animal models by utilizing meta-analysis related methods and to aid in the optimization of these models for future research. A total of 1215 articles were retrieved with the keywords of "diabetic kidney disease" and "animal experiment" in the past 10 years. Following screening, 84 articles were selected for inclusion in the meta-analysis. Review manager 5.4.1 was employed to analyze the changes in blood glucose, glycosylated hemoglobin, total cholesterol, triglyceride, serum creatinine, blood urea nitrogen, and urinary albumin excretion rate in each model. Renal lesions shown in different models that were not suitable to be included in the meta-analysis were also extensively discussed. The above analysis suggested that combining various stimuli or introducing additional renal injuries to current models would be a promising avenue to overcome existing challenges and limitations. In conclusion, our review article provides an in-depth analysis of the limitations in current DKD animal models and proposes strategies for improving the accuracy and reliability of these models that will inspire future research efforts in the DKD research field.

AR/PCC herb pair inhibits osteoblast pyroptosis to alleviate diabetes-related osteoporosis by activating Nrf2/Keap1 pathway.

Osteoporosis is a prevalent complication of diabetes, characterized by systemic metabolic impairment of bone mass and microarchitecture, particularly in the spine. Anemarrhenae Rhizoma/Phellodendri Chinensis Cortex (AR/PCC) herb pair has been extensively employed in Traditional Chinese Medicine to manage diabetes; however, its potential to ameliorate diabetic osteoporosis (DOP) has remained obscure. Herein, we explored the protective efficacy of AR/PCC herb pair against DOP using a streptozotocin (STZ)-induced rat diabetic model. Our data showed that AR/PCC could effectively reduce the elevated fasting blood glucose and reverse the osteoporotic phenotype of diabetic rats, resulting in significant improvements in vertebral trabecular area percentage, trabecular thickness and trabecular number, while reducing trabecular separation. Specifically, AR/PCC herb pair improved impaired osteogenesis, nerve ingrowth and angiogenesis. More importantly, it could mitigate the aberrant activation of osteoblast pyroptosis in the vertebral bodies of diabetic rats by reducing increased expressions of Nlrp3, Asc, Caspase1, Gsdmd and IL-1β. Mechanistically, AR/PCC activated antioxidant pathway through the upregulation of the antioxidant response protein Nrf2, while concurrently decreasing its negative feedback regulator Keap1. Collectively, our in vivo findings demonstrate that AR/PCC can inhibit osteoblast pyroptosis and alleviate STZ-induced rat DOP, suggesting its potential as a therapeutic agent for mitigating DOP.

Microalbuminuria as the Tip of Iceberg in Type 2 Diabetes Mellitus: Prevalence, Risk Factors, and Associated Diabetic Complications.

Background Microalbuminuria (MA) is an important clinical marker for the early detection of kidney damage in patients with type 2 diabetes (T2DM). Urine albumin-to-creatinine ratio (ACR), also known as urine microalbumin, is a sign of diabetic nephropathy (DN), which is a prevalent complication of diabetes and can result in end-stage renal disease (ESRD) if not managed. The prevalence of MA in T2DM has been steadily increasing worldwide, making it a significant public health concern. The goal of this study was to estimate the prevalence of MA and its relationship to hypertension and other diabetic complications among people with T2DM. Methodology This descriptive cross-sectional study was conducted from February 5, 2022, to February 10, 2023, to analyse data from T2DM patients who visited the outpatient diabetic clinic of Sheikh Zayed Medical College and Hospital, Rahim Yar Khan, Pakistan. This study included a total of 640 patients, aged 35-60 years, who had been diagnosed with T2DM for at least five years and fulfilled the inclusion criteria. Data on demographic and clinical characteristics, blood pressure (BP) measurements, and laboratory investigations were collected. MA was assessed based on the ACR in a spot urine sample of more than 30 mg/l. Blood pressure greater than 140/90 or already taking anti-hypertensives was taken to constitute hypertension. Factors associated with MA like hypertension, gender, mode of diabetes treatment, duration of diabetes, glycosylated haemoglobin (HbA1c), dyslipidemia, and other diabetic complications such as retinopathy and neuropathy were also recorded. Results The prevalence of MA in this study of T2DM patients study was 39.1%. The mean age of the participants with MA was 53.9 with a standard deviation (SD) of 6.1 years, and the mean duration of diabetes was 10.1 years (SD 6.2 years); 101 (33.4%) males (n=302) and 103 (30.5%) females (n=338) had MA. There was a statistically significant correlation between MA > 30mg/d and hypertension (p = <0.001), diabetes duration since diagnosis (p=0.04), HbA1C level (p = <0.001), dyslipidemia (p=0.001), therapy type (p = <0.001), triglyceridemia (p = 0.03), history of diabetes retinopathy (p= <0.002), and peripheral neuropathy (p= <0.001). However, there was no statistically significant correlation between MA and age (p = 0.56), female gender (p = 0.08), low- and high-density lipids, or statin use (p = 0.06). Conclusion The prevalence of microalbuminuria among T2DM patients is significantly high (39.1%) and is positively correlated with various factors such as male gender, hypertension, suboptimal control of diabetes mellitus, high HbA1c levels, longer disease duration, dyslipidemia with high triglycerides,treatment modalities of T2DM, and other diabetic complications like neuropathy and retinopathy. As diabetes is very prevalent in our country, the number of patients with diabetic kidney disease will rise significantly in the near future, leading to ESRD and other diabetic complications, and immediate intervention is needed to prevent this. Further research is warranted to explore potential interventions and evaluate their impact on patient outcomes.

Rolipram and pentoxifylline combination ameliorates the morphological abnormalities of dorsal root ganglion neurons in experimental diabetic neuropathy by reducing mitochondrial dysfunction and apoptosis.

Diabetic neuropathy (DN) is the most prevalent complication of diabetes. Pharmacological treatments for DN are often limited in efficacy, so the development of new agents to alleviate DN is essential. The aim of this study was to evaluate the effects of rolipram, a selective phosphodiesterase-4 inhibitor(PDE-4I), and pentoxifylline, a general PDE inhibitor, using a rat model of DN. In this study, a diabetic rat model was established by i.p. injection of STZ (55 mg/kg). Rats were treated with rolipram (1 mg/kg), pentoxifylline (100 mg/kg), and combination of rolipram (0.5 mg/kg) and pentoxifylline (50 mg/kg), orally for 5 weeks. After treatments, sensory function was assessed by hot plate test. Then rats were anesthetized and dorsal root ganglion (DRG) neurons isolated. Cyclic adenosine monophosphate (cAMP), adenosine triphosphate (ATP, adenosine diphosphate and mitochondrial membrane potential (MMP) levels, Cytochrome c release, Bax, Bcl-2, caspase-3 proteins expression in DRG neurons were assessed by biochemical and ELISA methods, and western blot analysis. DRG neurons were histologically examined using hematoxylin and eosin (H&E) staining method. Rolipram and/or pentoxifylline significantly attenuated sensory dysfunction by modulating nociceptive threshold. Rolipram and/or pentoxifylline treatment dramatically increased the cAMP level, prevented mitochondrial dysfunction, apoptosis and degeneration of DRG neurons, which appears to be mediated by inducing ATP and MMP, improving cytochrome c release, as well as regulating the expression of Bax, Bcl-2, and caspase-3 proteins, and improving morphological abnormalities of DRG neurons. We found maximum effectiveness with rolipram and pentoxifylline combination on mentioned factors. These findings encourage the use of rolipram and pentoxifylline combination as a novel experimental evidence for further clinical investigations in the treatment of DN.

Regenerative antibacterial hydrogels from medicinal molecule for diabetic wound repair.

Hydrogel products for chronic diabetic wounds, a serious and prevalent complication of diabetes, show limited effects on disability and remain nonspecific. Thus, improvements in the usage of pharmaceutical molecule in the hydrogels are highly desirable to increase the therapeutic effect of hydrogels. In this study, thioctic acid (a common medicine molecule in diabetes treatment) is used for preparing regenerative antibacterial hydrogels (RAH) which contains in situ synthesized silver nanoparticles (AgNPs). The RAH shows regenerative, self-healing and injectable ability, because of the reversible hydrogen and coordination bonds. With good regenerative capacity, RAH can be stored as powder to avoid the water loss and facilitate storage availability. Owing to the antioxidant properties of thioctic acid, the RAH can decrease the oxidative damage and retain cell proliferation efficiency. Due to the in situ synthesized AgNPs, the RAH also exhibits extraordinary antimicrobial capacities against MDR bacteria. All of these superiorities enable RAH to be a promising therapy for chronic diabetic wounds.

Interference of periostin attenuates pathological changes, proinflammatory markers and renal fibrosis in diabetic kidney injury.

Diabetic nephropathy (DN) is a prevalent complication of diabetes, in which inflammation and fibrosis are the significant pathogenesis. Periostin is a matricellular protein that functions on stabilizing the extracellular matrix by binding to integrins during development. This study aimed to explored the role of periostin in DN. The animal and cell models of DN were constructed in streptozocin (STZ)-induced mice and high glucose-challenged human mesangial cells (HMCs). The role of periostin in pathological changes, inflammation and fibrosis in DN was investigated through biochemical detection, HE and Masson staining and scores, western blot, enzyme‑linked immunosorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) assays. Knockdown of periostin counteracted the STZ-induced the ratio of kidney weight and body weight, and the concentrations of urine albumin excretion (UAE), serum creatinine (Scr), urine albumin/creatinine ratio (UACR) and blood urea nitrogen (BUN) in mice. Moreover, silencing of periostin alleviated the pathological manifestations and reduced the concentrations of IL-6, TNF-α and IL-1β in mice kidney tissues and sera. Also, downregulation of periostin decreased the relative protein expression of fibronectin, collagen IV and α-SMA in kidney tissues. Meanwhile, interference of periostin attenuated the levels of pro-inflammation factors and the expressions of fibrosis markers in HG-induced HMCs. Interference of periostin resisted DN via attenuating the pro-inflammatory cytokines release and renal fibrosis in diabetic kidney injury. Our study establishes a basis for its further study and underlying application in clinical practice in diagnosing and treating diabetic kidney injury or other relevant diseases.

The mechanisms of NLRP3 inflammasome/pyroptosis activation and their role in diabetic retinopathy.

In the working-age population worldwide, diabetic retinopathy (DR), a prevalent complication of diabetes, is the main cause of vision impairment. Chronic low-grade inflammation plays an essential role in DR development. Recently, concerning the pathogenesis of DR, the Nod-Like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome in retinal cells has been determined as a causal factor. In the diabetic eye, the NLRP3 inflammasome is activated by several pathways (such as ROS and ATP). The activation of NPRP3 leads to the secretion of inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18), and leads to pyroptosis, a rapid inflammatory form of lytic programmed cell death (PCD). Cells that undergo pyroptosis swell and rapture, releasing more inflammatory factors and accelerating DR progression. This review focuses on the mechanisms that activate NLRP3 inflammasome and pyroptosis leading to DR. The present research highlighted some inhibitors of NLRP3/pyroptosis pathways and novel therapeutic measures concerning DR treatment.

Relationship between deep and superficial sensitivity assessments and gait analysis in diabetic foot patients.

Peripheral neuropathy is a prevalent complication of diabetes that can lead to gait impairment and its adverse consequences. This study explored the potential utility of different parameters of gait analysis using a single sensor unit as a simple tool to detect peripheral neuropathy in 85 diabetic patients (DP) with diabetic foot in whom different somato-sensitivity tests in the feet were performed. Gait spatiotemporal parameters were examined by sensor inertial measurement placed in the lumbar area, while the superficial sensitivity pathway was assessed by nociception tests and deep sensitivity was examined by light touch-pressure and vibration sensitivity tests. Correlations between each sensory test and gait parameters were analysed in a logistic regression model in order to assess if gait parameters are associated with two different sensory pathways. Impaired deep sensory pathways were significantly (P < .05) correlated with lower gait speed, reduced cadence, smaller stride length, longer stance periods, and a higher risk of falling on the Tinetti Scale, while all gait parameters were significantly (P < .01) correlated with the superficial sensory pathway. Type 2 diabetics have significantly (P < .05) higher impairment in vibratory sensitivity than type 1 diabetics, and the years with diabetes mellitus (DM) diagnosis have a significant (P < .05) association with reduced vibration sensitivity. These findings indicate relationships between the deep sensory pathway and gait impairments in DP measured by inertial sensors, which could be a useful tool to diagnose gait alterations in DP and to evaluate the effect of treatments to improve gait and thus the risk of falls in diabetic patients.

Lean adipose tissue macrophage derived exosome confers immunoregulation to improve wound healing in diabetes

Chronic non-healing wounds, a prevalent complication of diabetes, are associated with increased mortality in diabetic patients. Excessive accumulation of M1 macrophages in diabetic wounds promotes inflammation and results in dysregulated tissue repair. Adipose tissue macrophages (ATMs) derived from healthy lean donors have the ability to improve glucose tolerance and insulin sensitivity, as well as modulate inflammation. MicroRNAs (miRs), which can be packaged into exosomes (Exos) and secreted from cells, serve as essential regulators of macrophage polarization. Here, we revealed that ATMs isolated from lean mice secrete miRs-containing Exos, which modulate macrophage polarization and promote rapid diabetic wound healing when administered to diabetes-prone db/db mice. The miRs sequence of tissue samples from wounds treated with Exos secreted by lean ATMs (ExosLean) revealed that miR-222-3p was up-regulated. Further analyses showed that inhibiting miR-222-3p using a miR inhibitor impaired the macrophage-reprogramming effect of ExosLean. In the excisional skin wound mouse model, locally inhibiting miR-222-3p disrupted healing dynamics and failed to modulate macrophage polarization. Mechanistic studies revealed a connection between miR-222-3p, Bcl2l11/Bim, an inflammatory response effector, macrophage polarization, and diabetic wound healing. In summary, ExosLean act as positive regulators of macrophage polarization by regulating miR levels in wounds and accelerating wound healing, and thus have important implications for wound management in diabetes.Graphic

Effectiveness and safety of traditional Chinese medicine decoction for diabetic gastroparesis: A network meta-analysis.

Diabetic gastroparesis (DGP) is a prevalent complication of diabetes that impairs people's quality of life and places a significant financial burden on them. The gastrointestinal symptoms of DGP patients can be improved by several Traditional Chinese Medicine (TCM) decoctions that have been shown to be effective in treating the disease. There are still many unanswered questions regarding the identification of appropriate therapeutic agents for the treatment of DGP in clinical practice. To analyze the efficacy of several TCM decoctions in the treatment of DGP using Bayesian network meta-analysis for reference. PubMed, EMBASE, Cochrane Library, Web of Science, China National Kno-wledge Infrastructure, The China Biology Medicine DVD, Wanfang, and CQVIP were searched from inception to September 17, 2022, to collect randomized controlled trials (RCTs) about TCM decoctions for DGP. Clinical effects and symptom scores were the primary outcomes. Additionally, we assessed motilin (MOT), somatostatin (SS), gastrin (GAS), gastric emptying rate, gastric emptying time, and adverse drug events as secondary outcomes. A total of 67 eligible RCTs involving 4790 DGP patients and 7 TCM decoctions were included. The results of network meta-analysis (NMA) and surface under the cumulative ranking curve showed that with western medicine (WM) as a common control, the Banxia Xiexin Decoction (BXXD) + WM was most effective in clinical effects and enhancing early satiety scores; the Simo decoction (SMD) + WM was most effective in improving nausea and vomiting scores and anorexia scores, bloating scores; the Chaishao Liujunzi Decoction (CSLJD) was most effective in MOT, the Zhishi Xiaopi Decoction (ZSXPD) was most effective in SS and upgrading emptying rate; the Jianpi Xiaozhi Decoction was most effective in GAS; the CSLJD + WM was most effective in improving gastric emptying time. These NMA results suggest that the BXXD + WM and SMD + WM may be one of the potential optimal treatments. Due to various limitations, further large-sample, double-blind, multi-center randomized RCTs are needed.

Prevalence of Complications Associated with Diabetes among Pakistani Patients: A Questionnaire-based Survey.

The rate of mortality is increasing in diabetic patients due to diabetes-associated complications. The common complications include neuropathy, nephropathy, retinopathy, foot ulcer, slow wound healing, kidney dysfunction, amputation, dysfunction of organs, frequent infections, sepsis, skin diseases, hearing impairment, cardiovascular disorders, etc. These complications can be diagnosed following some common symptoms such as increased thirst, frequent urination, extreme hunger, unexplained weight loss, fatigue, irritability, blurred vision, slow-healing sores, etc. This survey was designed to study the prevalence of various complications in a group of diabetic patients so that effective treatment options could be developed against the most prevalent complications. This cross-sectional study was conducted in 2019 in a tertiary care hospital of Karachi after the approval of the ethical committee of the hospital as well as in the University of Karachi. To perform this study, a questionnaire was designed comprised of different questions related to diabetic complications. The consent form was attached to each questionnaire in which the patient agreed to participate voluntarily in this survey. The diabetic patients who visited the General Physician OPD were the subjects of this survey. All designed questions included in the questionnaire were asked either directly from the patients or their attendants. A total of 160 diabetic subjects were part of the study range between the ages of 11 to 90 years. Out of 160 patients, 52 were males, and 108 were females. Among all subjects, 124 (78 %) patients were type 2 while 57 (36 %) were type 1 diabetic patients. 117 (73 %) showed confusion of mind, 104 (65 %) complained of blood pressure, 105 (66 %) had hypertension, 106 (66 %) had eye damage (retinopathy), 96 (60 %) were facing trouble focusing vision, and 70 (44 %) were experiencing seizures, 63 (39 %) patients had laser treatment, 68 (43 %) showed wounds on foot and slow wounds healing, 49 (31 %) were having kidney damage (nephropathy), 79 (49 %) had pain in legs or knee, 35 (22 %) and 26 (16 %) complained of heart problems and liver damage respectively. Some patients were found to deal with more hunger, i.e., 99 (62 %) patients, 118 (74 %) were experiencing frequent urine desire, 138 (86 %) showed fatigue, 123 (77 %) complained of thirst, 35 (22 %) had nausea, 30 (19 %) had a frequent cold, 36 (23 %) had skin problems, 17 (11 %) patients showed frequent vomiting, 19 (12 %), 13 (8 %) and 16 (10 %) were experiencing acne formation, stroke and nerve damage (neuropathy) respectively. All age groups showed diabetes-associated complications and different abnormal body conditions. However, the age groups ranging from thirty to eighty years showed more complications. The most prevalent complications reported were retinopathy, nephropathy, diabetic wounds on the foot, slow wound healing, seizures, hypertension, neuropathy, skin infections, cardiovascular disorders, liver damage, and stroke in both types of diabetic patients. Our survey may aid in pointing out the most prevalent diabetic complications prevailing in our population so that effective treatment options could be developed to reduce these life-threatening complications.

Next-Generation Diagnostic Wound Dressings for Diabetic Wounds.

Chronic lower extremity wounds (diabetic foot ulcers) are a serious and prevalent complication of diabetes. These wounds exhibit low healing rates and present a high risk of amputation. Current diagnostic options for foot ulcers are limited to macroscopic wound analysis such as wound depth, implicated tissues, and infection. Molecular diagnostics promises to improve foot ulcer diagnosis, staging, and assessment of the treatment response. In this perspective, we report recent progress in understanding the pathophysiology of diabetic wound healing and point to recently emerged novel molecular targets for wound diagnostics. We discuss selected diagnostic wound dressings under preclinical development that detect one or several inflammatory markers, bacterial secretions, hyperglycemia, and mechanical stress. We also highlight key translational challenges of investigational diagnostic bandages for diabetic foot ulcers.