The importance of temperature monitoring in predicting wound healing.

CONCLUSION: Upon wound formation, the wound temperature rises in the first 3-4 days until reaching its peak. It then falls at about one week after wound formation. In the second week after wound formation, the wound temperature decreases steadily to the baseline indicating a good wound condition and progression towards healing. While a continuous high temperature is often a sign of excessive inflammation or infection, which indicates urgent need of intervention and treatment.

Impact of time in range during hospitalization on clinical outcomes in diabetic patients with toe amputation: a propensity score matching analysis.

PURPOSE: In recent years, time in range (TIR), defined as a percentage within a target time range, has attracted much attention. This study was aimed to investigate the short-term effects of Time in Rang on diabetic patients undergoing toe amputation in a more specific and complete manner. METHODS: A retrospective analysis on patients with diabetic foot ulcer (DFU) treated by toe amputation or foot amputation at the First Affiliated Hospital of Wenzhou Medical University between January 2015 and December 2019 were evaluated. A 1:1 match was conducted between the TIR < 70% group and the TIR ≥ 70% group using the nearest neighbor matching algorithm. Data were analyzed using Chi-squared, Fisher's exact, and Mann-Whitney U tests. RESULTS: Compared with patients in the TIR ≥ 70% group, patients in the TIR < 70% had a higher rate of re-amputation, and a higher rate of postoperative infection. Multivariate analysis revealed that smoking, lower extremity arterial disease and TIR < 70% were risk factors for surgery of re-amputation. The results of subgroup analysis found that the TIR < 70% was associated with a greater risk of re-amputation in patients with HbA1c < 7.5%, lower extremity arterial disease, and non-smokers. CONCLUSIONS: TIR can be used as a short-term glycemic control indicator in patients with DFUs and should be widely accepted in clinical practice. However, a future multicenter prospective study is needed to determine the relationship between TIR and toe re-amputation in diabetic foot patients.

Small extracellular vesicles derived from human mesenchymal stem cells prevent Th17-dominant neutrophilic airway inflammation via immunoregulation on Th17 cells.

Type 17 helper T cells (Th17)-dominant neutrophilic airway inflammation is critical in the pathogenesis of steroid-resistant airway inflammation such as severe asthma. Small extracellular vesicles (sEV) derived from human mesenchymal stem cells (MSCs) display extensive therapeutic effects and advantages in many diseases. However, the role of MSC-sEV in Th17-dominant neutrophilic airway inflammation and the related mechanisms are still poorly studied. Here we found that MSC-sEV significantly alleviated the infiltration of inflammatory cells in peribronchial interstitial tissues and reduced levels of inflammatory cells, especially neutrophils, in bronchoalveolar lavage fluids (BALF) of mice with neutrophilic airway inflammation. Consistently, MSC-sEV significantly decreased levels of IL-17A in BALF and Th17 in lung tissues. Furthermore, we found that labelled MSC-sEV were taken up by human CD4+ T cells most obviously at 12 h after incubation, and distributed mostly in mouse lungs. More importantly, potential signaling pathways involved in the MSC-sEV mediated inhibition of Th17 polarization were found using RNA sequencing. Using Western blot, JAK2-STAT3 pathway was identified as an important role in the inhibition of Th17 polarization by MSC-sEV. We found that proteins in MSC-sEV were mostly involved in the therapeutic effects of MSC-sEV. In total, our study suggested that MSC-sEV could be a potential therapeutic strategy for the treatment of neutrophilic airway inflammation.

Spatiotemporal expression of SKIP after rat sciatic nerve crush.

Ski-interacting protein (SKIP) is a highly conserved protein from yeast to Human. As an essential spliceosomal component and transcriptional co-regulator it plays an important role in preinitiation, splicing and polyadenylation. SKIP can also combine with Ski to overcome the G1 arrest and the growth-suppressive activities of pRb. Furthermore SKIP has the capacity to augment TGF-ß dependent transcription. While the distribution and function of SKIP in peripheral nervous system lesion and regeneration remain unclear. Here, we investigated the spatiotemporal expression of SKIP in an acute sciatic nerve crush model in adult rats. Western Blot analysis revealed that SKIP was expressed in normal sciatic nerves. It gradually increased, reached a peak at 1 week after crush, and then returned to the normal level at 4 weeks. Besides, we observed that up-regulation of SKIP was approximately in parallel with Proliferating cell nuclear antigen (PCNA), and numerous Schwann cells (SCs) expressing SKIP were PCNA and Ki-67 positive. Collectively, we hypothesized peripheral nerve crush induced up-regulation of SKIP in the sciatic nerve, which was associated with SCs proliferation.

The role of IL-6 in bone marrow (BM)-derived mesenchymal stem cells (MSCs) proliferation and chondrogenesis.

Rheumatoid arthritis (RA) is the most common degenerative arthritic cartilage and represents a disease where the prospect of stem cell therapy offers considerable hope. Currently, bone marrow (BM) represents the major source of mesenchymal stem cells (MSCs) for cell therapy. In the pathology of RA, the pro-inflammatory cytokines, such as interleukin 6 (IL-6) play a pivotal role. To investigate the direct role of IL-6 in the chondrogenic differentiation of murine MSCs (mMSCs), we isolate MSCs from the murine bone marrow, and induce MSCs chondrogenesis with different concentrations of IL-6 in vitro. Through detecting the histological and histochemical qualities of the aggregates, we demonstrate that IL-6 inhibited the differentiation of MSCs into chondrocytes in the dose-dependence manner. These findings suggest that possible strategies for improving the clinical outcome of cartilage repair procedures.

Neck circumference is an accurate and simple index for evaluating overweight and obesity in Han children.

BACKGROUND: The prevalence of obesity has reached alarming levels in recent years. Neck circumference (NC) has been shown to be an indicator of central adiposity. AIM: The purpose of this study was to analyse whether NC can be used to determine overweight and obesity in Han Chinese children. SUBJECTS AND METHODS: In 2011, anthropometric measurements were gathered in a cross-sectional, population-based study of 2847 Han children aged 7-12 years. Overweight and obesity were defined according to the 2004 Chinese obesity task force definition. Receiver operating characteristic curve analyses were conducted to assess the accuracy of NC as a diagnostic test for elevated body mass index (BMI) (overweight and obesity). RESULTS: The prevalence of overweight and obesity in boys was 18.0% and 26.0%, respectively, and 11.7% and 15.7%, respectively, for girls. The mean NC in boys was significantly greater than in girls (29.2 ± 3.1 cm vs 28.1 ± 2.8 cm, p < 0.001). NC was significantly correlated with age, BMI and waist circumference in both boys and girls (p < 0.001 for all comparisons). NC cut-off values for elevated BMI were between 27.4~31.3 cm in boys and 26.3~31.4 cm in girls. The sensitivities were 75.5~86.7% in boys and 80.0~92.5% in girls. The specificities were 73.9~91.7% in boys and 74.7~93.3% in girls. CONCLUSION: The present study demonstrates that NC is a simple, inexpensive and accurate measurement that may be used to identify overweight and obesity in Han children.

The compound losartan cream inhibits scar formation via TGF-ß/Smad pathway.

The role of angiotensin receptor blocker in wound healing and cutaneous fibrosis has become a hotspot in recent years. We have developed a losartan cream that is comparable to triamcinolone ointment in inhibiting scarring. Considering the effects of chitosan and asiaticoside on wound healing and scarring, we added them to the losartan cream this time and improved the formula, expecting to get a better anti-scarring effect. The effects of creams were investigated on mouse scar model with triamcinolone ointment, onion extract gel, and commercial asiaticoside cream set as positive controls. A preliminary exploration of the mechanism involved in TGF-ß/Smad pathway was performed in vivo and in vitro. With all results of anti-scarring, the compound losartan cream (containing chitosan, asiaticoside, and losartan) shows the best effect, followed by the chitosan asiaticoside cream. The treatment of the compound losartan cream inhibited expression of TGF-ß1, collagen, and Smads, and decreased phosphorylation of Smad in vivo. These inhibitory effects were also confirmed in vitro. Our findings indicated that the compound losartan cream could inhibit scarring via TGF-ß/Smad pathway. This cream might be an effective option for scar treatment.

Preclinical efficacy of stem cell therapy for skin flap: a systematic review and meta-analysis.

BACKGROUND: A skin flap is one of the most critical surgical techniques for the restoration of cutaneous defects. However, the distal necrosis of the skin flap severely restricts the clinical application of flap surgery. As there is no consensus on the treatment methods to prevent distal necrosis of skin flaps, more effective and feasible interventions to prevent skin flaps from necrosis are urgently needed. Stem therapy as a potential method to improve the survival rate of skin flaps is receiving increasing attention. METHODS: This review followed the recommendations from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statements. Twenty studies with 500 animals were included by searching Web of Science, EMBASE, PubMed, and Cochrane Library databases, up until October 8, 2020. Moreover, the references of the included articles were searched manually to obtain other studies. All analyses were conducted using Review Manager V.5.3 software. RESULTS: Meta-analysis of all 20 studies demonstrated stem cell treatment has significant effects on reducing necrosis of skin flap compared with the control group (SMD: 3.20, 95% CI 2.47 to 3.93). Besides, subgroup analysis showed differences in the efficacy of stem cells in improving the survival rate of skin flaps in areas of skin flap, cell type, transplant types, and method of administration of stem cells. The meta-analysis also showed that stem cell treatment had a significant effect on increasing blood vessel density (SMD: 2.96, 95% CI 2.21 to 3.72) and increasing the expression of vascular endothelial growth factor (VEGF, SMD: 4.34, 95% CI 2.48 to 6.1). CONCLUSIONS: The preclinical evidence of our systematic review indicate that stem cell-based therapy is effective for promoting early angiogenesis by up regulating VEGF and ultimately improving the survival rate of skin flap. In summary, small area skin flap, the administration method of intra-arterial injection, ASCs and MSCs, and xenogenic stem cells from humans showed more effective for the survival of animal skin flaps. In general, stem cell-based therapy may be a promising method to prevent skin flap necrosis.

Flexible electrical stimulation device with Chitosan-Vaseline® dressing accelerates wound healing in diabetes.

The healing process of diabetic wounds is typically disordered and prolonged and requires both angiogenesis and epithelialization. Disruptions of the endogenous electric fields (EFs) may lead to disordered cell migration. Electrical stimulation (ES) that mimics endogenous EFs is a promising method in treating diabetic wounds; however, a microenvironment that facilitates cell migration and a convenient means that can be used to apply ES are also required. Chitosan-Vaseline® gauze (CVG) has been identified to facilitate wound healing; it also promotes moisture retention and immune regulation and has antibacterial activity. For this study, we created a wound dressing using CVG together with a flexible ES device and further evaluated its potential as a treatment for diabetic wounds. We found that high voltage monophasic pulsed current (HVMPC) promoted healing of diabetic wounds in vivo. In studies carried out in vitro, we found that HVMPC promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs) by activating PI3K/Akt and ERK1/2 signaling. Overall, we determined that the flexible ES-chitosan dressing may promoted healing of diabetic wounds by accelerating angiogenesis, enhancing epithelialization, and inhibiting scar formation. These findings provide support for the ongoing development of this multidisciplinary product for the care and treatment of diabetic wounds.

Co-transfection with BMP2 and FGF2 via chitosan nanoparticles potentiates osteogenesis in human adipose-derived stromal cells in vitro.

OBJECTIVE: To investigate if co-transfection of human bone morphogenetic protein 2 (BMP-2, BMP2) and human fibroblast growth factor 2 (FGF2, FGF2) via chitosan nanoparticles promotes osteogenesis in human adipose tissue-derived stem cells (ADSCs) in vitro. MATERIALS AND METHODS: Recombinant BMP2 and/or FGF2 expression vectors were constructed and packaged into chitosan nanoparticles. The chitosan nanoparticles were characterized by atomic force microscopy. Gene and protein expression levels of BMP-2 and FGF2 in ADSCs in vitro were evaluated by real-time polymerase chain reaction (PCR), western blot, and enzyme-linked immunosorbent assay. Osteocalcin (OCN) and bone sialoprotein (BSP) gene expression were also evaluated by real-time PCR to assess osteogenesis. RESULTS: The prepared chitosan nanoparticles were spherical with a relatively homogenous size distribution. The BMP2 and FGF2 vectors were successfully transfected into ADSCs. BMP-2 and FGF2 mRNA and protein levels were significantly up-regulated in the co-transfection group compared with the control group. OCN and BSP mRNA levels were also significantly increased in the co-transfection group compared with cells transfected with BMP2 or FGF2 alone, suggesting that co-transfection significantly enhanced osteogenesis. CONCLUSIONS: Co-transfection of human ADSCs with BMP2/FGF2 via chitosan nanoparticles efficiently promotes the osteogenic properties of ADSCs in vitro.

Using Buck's Fascia as an Integral Covering in Urethroplasty to Restore the Anatomical Structure of the Penis in One-Stage Hypospadias Repair: A Multicenter Chinese Study Comprising 1,386 Surgeries.

Objectives: The objective of the study is to investigate the feasibility and efficacy of urethroplasty with a Buck's fascia integral-covering technique (BFIC) to wrap and restore the normal anatomical structure of the penis in one-stage hypospadias surgery. Methods: One-stage surgeries for hypospadias management were performed using BFIC from January 2016 to September 2020 at four high-volume medical centers in China. The technique integrates Buck's fascia with glans wings to mobilize and wrap the urethra and restore penile anatomical relationships. The clinical data, postoperative follow-up data, and complications were recorded, and the results were analyzed. Results: A total of 1,386 patients were included in the study: 1,260 cases of primary hypospadias and 126 cases of re-operations; distal in 382 cases (27.6%), mid-shaft in 639 (46.1%), proximal in 365 (26.3%); tubularized incised plate (TIP) in 748 cases, inlay-graft in 124, onlay-graft in 49, Mathieu in 28, free-tube graft urethroplasty in 406, and 31 of hybrid procedures. One thousand one hundred forty-two patients (82.4%) were found to have penile curvature (>10°) after artificial erection and all corrected by dorsal plication/s or transection of the urethra plate (UP) simultaneously. The median followed-up time was 27 months (6-62). A total of 143 (10.3%) complications were recorded: 114 (9.0%) in the primary operations and 29 (23%) in the re-operations, 15 (3.9%) in distal hypospadias, 61 (9.5%) in mid-shaft, and 67 (18.4%) in proximal. The complication rate in UP preservation and transection was 10.1 and 10.8%, respectively. Of all case complications, there were 73 (5.2%) of fistula, 10 (0.6%) of dehiscence, 22 (1.6%) of meatal stenosis, 21 (1.5%) of stricture, 6 (0.7%) of diverticulum, and resident curvature in 11 cases (1.2%). The overall complication rate in TIP and free-tube procedure was 9.8 and 9.9%, respectively, and fistula occurred in primary TIP of 33 cases (4.9%). Conclusions: Buck's fascia with the glans can be used as an integral covering technique in one-stage distal to proximal hypospadias and primary or re-operative hypospadias repair. It is safe, feasible, and effective for the repair of hypospadias.

Gene-activated dermal equivalents to accelerate healing of diabetic chronic wounds by regulating inflammation and promoting angiogenesis.

Diabetic chronic wound, characterized by prolonged inflammation and impaired angiogenesis, has become one of the most serious challenges in clinic and pose a significant healthcare burden worldwide. Although a great variety of wound dressings have been developed, few of encouraged achievements were obtained so far. In this study, the gene-activated strategy was applied to enhance sustained expression of vascular endothelial growth factor (VEGF) and achieve better healing outcomes by regulating inflammation and promoting angiogenesis. The gene-activated bilayer dermal equivalents (Ga-BDEs), which has good biocompatibility, were fabricated by loading the nano-sized complexes of Lipofectamine 2000/plasmid DNA-encoding VEGF into a collagen-chitosan scaffold/silicone membrane bilayer dermal equivalent. The DNA complexes were released in a sustained manner and showed the effective transfection capacities to up-regulate the expression of VEGF in vitro. To overcome cutaneous contraction of rodents and mimic the wound healing mechanisms of the human, a reformative rat model of full-thickness diabetic chronic wound was adopted. Under the treatment of Ga-BDEs, speeding wound healing was observed, which is accompanied by the accelerated infiltration and phenotype shift of macrophages and enhanced angiogenesis in early and late healing phases, respectively. These proved that Ga-BDEs possess the functions of immunomodulation and pro-angiogenesis simultaneously. Subsequently, the better regeneration outcomes, including deposition of oriented collagen and fast reepithelialization, were achieved. All these results indicated that, being different from traditional pro-angiogenic concept, the up-regulated expression of VEGF by Ga-BDEs in a sustained manner shows versatile potentials for promoting the healing of diabetic chronic wounds.

Smart Flexible Electronics-Integrated Wound Dressing for Real-Time Monitoring and On-Demand Treatment of Infected Wounds.

As the most frequent wound complication, infection has become a major clinical challenge in wound management. To overcome the "Black Box" status of the wound-healing process, next-generation wound dressings with the abilities of real-time monitoring, diagnosis during early stages, and on-demand therapy has attracted considerable attention. Here, by combining the emerging development of bioelectronics, a smart flexible electronics-integrated wound dressing with a double-layer structure, the upper layer of which is polydimethylsiloxane-encapsulated flexible electronics integrated with a temperature sensor and ultraviolet (UV) light-emitting diodes, and the lower layer of which is a UV-responsive antibacterial hydrogel, is designed. This dressing is expected to provide early infection diagnosis via real-time wound-temperature monitoring by the integrated sensor and on-demand infection treatment by the release of antibiotics from the hydrogel by in situ UV irradiation. The integrated system possesses good flexibility, excellent compatibility, and high monitoring sensitivity and durability. Animal experiment results demonstrate that the integrated system is capable of monitoring wound status in real time, detecting bacterial infection and providing effective treatment on the basis of need. This proof-of-concept research holds great promise in developing new strategies to significantly improve wound management and other pathological diagnoses and treatments.

Flexible wound healing system for pro-regeneration, temperature monitoring and infection early warning.

To break the "Black-Box" status of the wound healing process under traditional dressing, which cannot achieve satisfactory repair outcome of skin wounds, a wound healing system with the abilities of pro-regeneration and real-time monitoring of wound status has become a considerable necessity. Here, by integrating the emerging bioelectronics and software, we created a flexible wound healing system. The hardware system was designed as Band-Aid shaped with a double-layer structure; the upper is the flexible temperature-sensing layer comprising the temperature sensor STH21, power manager circuit and data processing circuit, and the lower is a collagen-chitosan dermal equivalent for skin regeneration. A customized software application (app) installed on a smartphone to receive data from the sensing layer by BLE4.0 can display and analyze real-time wound temperature. Our system had high monitoring sensitivity and stability, good stretchability, excellent reliability and biocompatibility. It was applied to a pig skin wound model to reveal temperature fluctuation during the entire wound regeneration process. As a credible reference and foundation for further early warning of an adverse event, three main phases of temperature fluctuation were found: the rising phase (below 39 °C), plateau phase (39-39.5 °C), and falling phase (below 39 °C), which were accompanied by significant wound biological events, including inflammatory cell infiltration, angiogenesis and wound healing. Furthermore, verified by wound infection models of different healing phases and wound Gram's staining, early warning ahead of serious infection was realized with the use of a customized app's alarm.

Current potential therapeutic strategies targeting the TGF-ß/Smad signaling pathway to attenuate keloid and hypertrophic scar formation.

Aberrant scar formation, which includes keloid and hypertrophic scars, is associated with a pathological disorganized wound healing process with chronic inflammation. The TGF-ß/Smad signaling pathway is the most canonical pathway through which the formation of collagen in the fibroblasts and myofibroblasts is regulated. Sustained activation of the TGF-ß/Smad signaling pathway results in the long-term overactivation of fibroblasts and myofibroblasts, which is necessary for the excessive collagen formation in aberrant scars. There are two categories of therapeutic strategies that aim to target the TGF-ß/Smad signaling pathway in fibroblasts and myofibroblasts to interfere with their cellular functions and reduce cell proliferation. The first therapeutic strategy includes medications, and the second strategy is composed of genetic and cellular therapeutics. Therefore, the focus of this review is to critically evaluate these two main therapeutic strategies that target the TGF-ß/Smad pathway to attenuate abnormal skin scar formation.

Development of a Chitosan-Vaseline Gauze Dressing with Wound-Healing Properties in Murine Models.

Wound dressings are always needed after skin injury; however, most of the dressings still leave room for improvement. Here, we would like to develop an effective dressing with the ability to improve wound healing. A chitosan-Vaseline gauze (CVG) dressing was developed by coating the chitosan mixture and Vaseline on sterile gauze with subsequent drying. Infrared spectroscopy and electron microscopy were used to investigate the miscibility and structure of the dressing. The cytotoxicity and antibacterial nature were evaluated in vitro. The studies of water retention rate, wound healing, and tissue compatibility were carried out over a period of 14 days on full-thickness skin wounds of male Sprague-Dawley rats. It was observed that the CVG dressing demonstrated functional structure by miscibility, non-cytotoxicity, and good antibacterial effects against both Gram-positive and Gram-negative bacteria. The water retention rate incresased up to 25% after applying CVG for 3 hours. Besides, CVG treatment increased angiogenesis and improved microvascular density in wounds. The wounds treated with CVG showed size deduction with new collagen aggregations similar to those in the normal dermis. All the aforementioned results suggest that CVG dressing could be a promising candidate for wound treatment.

Optimizing detergent concentration and processing time to balance the decellularization efficiency and properties of bioprosthetic heart valves.

Decellularization treatment has been widely used to decrease the potential immunogenicity and improve the anticalcification properties of bio-derived materials, which may be utilized as an alternative method for the preparation of bioprosthetic heart valves. However, the excessive decellularization treatments will deteriarate the properties of heart valves. Among the decellularizaton parameters, detergent concentration and processing time are considered as those of the most key factors. Therefore, it should be meaningful to balance the decellularization efficiency and properties of bioprosthetic heart valves by optimizing the detergent concentration and processing time. In this study, three groups of the decellularized heart valves treated by sodium deoxycholate (SD) with different concentration and processing time were investigated through histological, biochemical, and mechanical analysis. Similar decellularization efficiency can be concluded through histological staining, DNA and α-Gal quantification results. Extracellular matrix contents quantification and tensile test results revealed that there is no obvious difference among the three decellularized heart valves. in vitro cytotoxicity assay showed that the remnant detergent is not enough to cause cell death, which indicated that the decellularized porcine aortic heart valves may be suitable for further in vivo research. In conclusion, Triton X-100/SD may be a suitable protocol used for heart valves decellularization. And it is feasible to vary the detergent processing time by changing the detergent concentration without compromising the decellularization efficiency.

Stretchable Optical Sensing Patch System Integrated Heart Rate, Pulse Oxygen Saturation, and Sweat pH Detection.

OBJECTIVE: Continuous measurement of key physiological parameters, such as heart rate (HR), pulse oxygen saturation (SpO2), and sweat pH value, has very broad applications in healthcare, disease surveillance, and fitness and sports training. In this study, a stretchable optical sensing patch system was developed for real-time continuous noninvasive monitoring of the HR, SpO2, and sweat pH, and the sensing data were transmitted to a smartphone through Bluetooth. METHODS: The sensor patch system adopted serpentine stretchable interconnects between the optical sensor and microcontroller chip with wireless function on a flexible substrate. The pH sensing function was implemented by coating a pH sensitive organically modified silicate film on the surface of a commercial blood oxygen sensor, achieving simultaneous measurement of HR, SpO2, and sweat pH with a single sensor. RESULTS: Real-time on-body assessment was carried out to evaluate the sensor patch system, showing its excellent repeatability and applicability. The sensor patch system could withstand up to 35% extension and exhibited a pH sensitivity of 4.42 mV/pH from 4.0 to 8.0, while the accuracy of HR from 25 to 250 b/min and SpO2 from 70% to 100% sensing were ±1 b/min and ±2%, respectively. CONCLUSION: The triple sensing functions was achieved through a single optical sensor on a flexible substrate while holding excellent contact with the body. SIGNIFICANCE: The sensor patch system can be used for fitness guidance, skin disease detection, and wound monitoring and management by replacing related sensitive films.

Cyclocarya paliurus triterpenic acids fraction attenuates kidney injury via AMPK-mTOR-regulated autophagy pathway in diabetic rats.

BACKGROUD: Diabetic nephropathy is the most serious complication of diabetes. Cyclocarya paliurus (CP), an herbal plant in China, has been reported the biological activity of anti-hyperglycemia. However, its effects on the diabetic nephropathy (DN) remain unclear. PURPOSE: We aimed to investigate the potential role of CP and its underlying mechanisms on DN. STUDY DESIGN: In this study, the effects of triterpenic acids-enriched fraction from CP (CPT) on DN was evaluated in streptozotocin (STZ)-induced rats and high glucose (HG)-induced HK-2 cells models. METHODS: After oral administration with or without CPT for 10 weeks, body weight, glucose, microalbumin, serum creatinine and blood urea in STZ-induced rats were detected. Histological analysis was performed to evaluate renal function of mice. Moreover, the level of autophagy was detected by western blot or immunostaining. In vitro, HG-induced HK-2 cell was conducted to evaluate the renal protection and mechanism of CPT. RESULTS: CPT dramatically decreased the levels of microalbumin, serum creatinine and blood urea nitrogen and ameliorated increased mesangial matrix and glomerular fibrosis. In addition, we found the CPT prevented renal damage and cell apoptosis through the autophagy. Furthermore, CPT could increase the phosphorylation of AMPK and decrease its downstream effector phosphorylation of mTOR. Besides, the expression of LC3-II were locked by AMPK inhibitor dorsomorphin dihydrochloride (compound C), implying that the autophagy may be regulated with AMPK activation. CONCLUSION: These findings suggested that CPT might be a desired candidate against diabetes, potentially through AMPK-mTOR-regulated autophagy pathway.