Discussion on the mechanism of Danggui Sini decoction in treating diabetic foot based on network pharmacology and molecular docking and verification of the curative effect by meta-analysis.

Objective: The main active components and mechanism of Danggui Sini decoction (DSD) in treating diabetic foot (DF) were studied and verified by network pharmacology and molecular docking. Evidence-based medicine was used to prove its efficacy. Methods: The TCMSP systematic pharmacology platform screened out DSD's practical components and targets-screening disease targets in GeneCards database, using Cytoscape 3.7.2 to draw DSD-active ingredient-target network diagram, and drawing the protein interaction network diagram through STRING database. The Metascape platform was used to analyze the GO function enrichment and KEGG signal pathway. The molecular docking experiment was carried out by using Auto Dock vina 4.2. The related literature on DSD in treating DF in China Zhiwang, Wanfang, Weipu, and China Biomedical Literature Database was searched. The literature was screened, data was extracted, and quality was evaluated according to the inclusion and exclusion criteria. Then, a meta-analysis was performed using RevMan 5.3 software. Results: A total of 256 targets of all effective components of DSD were obtained. Among 1,272 disease targets, there are 113 common targets. The GO analysis received 6,179 entries, and the KEGG pathway enrichment analysis found 251 related pathways. The molecular docking results of the main targets of diabetic foot and the active substances of DSD all showed a high docking activity. The meta-analysis included six literature, all of which were randomized controlled experiments. The quality grade of the literature was C, and the results showed that the total effective rate of clinical efficacy in the experimental group was significantly higher than that in the control group. Conclusions: DSD may treat DF by participating in biological processes such as cell proliferation regulation, inflammatory reaction, oxidative stress reaction, and promotion of angiogenesis. DSD treats DF through AKT1, TP53, IL6, TNF, VEGFA, and other targets. DSD plays a role in treating DF mainly through the AGE-RAGE signaling pathway and PI3K-AKT signaling pathway. The molecular docking results of AKT1, TP53, IL-6, TNF, and VEGFA with the active substances of DSD show that they all have a high docking activity; among them, VEGFA has a higher docking activity. Compared with conventional treatment, DSD has a high effective rate, short wound healing time, large wound healing area, and high ABI index.

Grb2 Expression in Acute Spinal Cord Injury After Methylprednisolone Intrathecal Injection in Rats.

OBJECTIVE: This study aims to investigate the effect of methylprednisolone (MP) intrathecal injection on a rat model of acute spinal cord injury (ASCI). METHODS: Allen's frame was used to establish a rat model of ASCI. MP and normal saline were intrathecally injected to Sprague-Dawley rats at 0, 3, 6, 8, 12, and 24 hours after ASCI, and injured spinal cord tissues were sterilely extracted after 24 hours of treatment. Isobaric tags for relative and absolute quantitation (iTRAQ) were coupled with 2-dimensional liquid chromatography tandem mass spectrometry to separate and identify differentially expressed proteins. RESULTS: The expression of growth factor receptor-bound protein 2 (Grb2) was downregulated in the MP groups at 0 hours (iTRAQ ratio = 0.996), 3 hours (iTRAQ ratio = 0.737), 8 hours (iTRAQ ratio = 0.763), and 24 hours (iTRAQ ratio = 0.908) after injury compared with that in the control groups. No significant difference in Grb2 expression was observed between the control groups at 6 and 12 hours after ASCI. CONCLUSIONS: Standardized MP intrathecal injection after ASCI treatment reduces Grb2 activation in a rat ASCI model. Further studies should determine whether or not the same effect can be observed in human ASCIs.

Antimicrobial photodynamic therapy against oral biofilm: influencing factors, mechanisms, and combined actions with other strategies.

Oral biofilms are a prominent cause of a wide variety of oral infectious diseases which are still considered as growing public health problems worldwide. Oral biofilms harbor specific virulence factors that would aggravate the infectious process and present resistance to some traditional therapies. Antimicrobial photodynamic therapy (aPDT) has been proposed as a potential approach to eliminate oral biofilms via in situ-generated reactive oxygen species. Although numerous types of research have investigated the effectiveness of aPDT, few review articles have listed the antimicrobial mechanisms of aPDT on oral biofilms and new methods to improve the efficiency of aPDT. The review aims to summarize the virulence factors of oral biofilms, the progress of aPDT in various oral biofilm elimination, the mechanism mediated by aPDT, and combinatorial approaches of aPDT with other traditional agents.

Experimental and theoretical investigations of dispersion of ultrasonic waves in the low-temperature and low-pressure nitrogen gas.

Temperature has a complex effect on acoustic dispersion in dilute gases. In this paper, the effect of temperature on the acoustic dispersion of dilute gases is analyzed theoretically and experimentally. Theoretically, the Navier-Stokes (NS) equation and the Greenspan's theory, which includes the rotational-relaxation correction, are applied to calculate the dispersive sound speed. It is concluded that the temperature affects the molecular translational relaxation and the rotational relaxation by influencing the average molecular collision frequency and the relaxation collision number, respectively, and thus, change the amplitude of the acoustic dispersion. Numerical calculations led to the conclusion that both translational and rotational dispersions weakened as the temperature decreased. Experimentally, sound speed measurements of 21-40 kHz acoustic waves were also carried out in gaseous nitrogen at temperatures ranging from -70 °C to 20 °C and pressures of 150-105 Pa. Theoretical predications indicate that the speed of sound should increase with decreasing pressure at all temperatures, and the degree of dispersion should diminish at lower temperatures. The experimental observation of dispersion is consistent with theory within experimental error (1%) but was not able to distinguish the small (0.01%) increase in sound speed expected at 150 Pa.

The progress and challenges of circRNA for diabetic foot ulcers: A mini-review.

Since the Human Genome Project was successfully completed, humanity has entered a post-genome era, and the second-generation sequencing technology has gradually progressed and become more accurate. Meanwhile, circRNAs plays a crucial role in the regulation of diseases and potential clinical applications has gradually attracted the attention of physicians. However, the mechanisms of circRNAs regulation at the cellular and molecular level of diabetic foot ulcer (DFU) is still not well-understood. With the deepening of research, there have been many recent studies conducted to explore the effect of circRNAs on DFU. In this mini-review, we discuss the potential role of circRNAs as therapeutic targets and diagnostic markers for DFU in order to gain a better understanding of the molecular mechanisms that underlie the development of DFU and to establish a theoretical basis for accurate treatment and effective prevention.

Efficacy and safety of tibial cortex transverse transport for diabetic foot: A protocol for systematic review and meta-analysis.

INTRODUCTION: Diabetic foot (DF) is one of the most serious chronic complications of diabetes. In recent years, the use of the tibial cortex transverse transport (TTT) technique has enabled great progress in microcirculation reconstruction and achievement of good outcomes in DF treatment. The objective of this systematic review protocol is to evaluate the efficacy and safety of TTT for DF. METHODS: Literature search was conducted using the Cochrane Library, Embase, PubMed, Web of Science, China Science Technology Journal Database (VIP), Wanfang Data, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Service System (SinoMed), and Chinese Biomedical Literature Service System (CBM) from inception until March, 1st 2022. In addition, our reviewers will retrieve dissertations, grey literature, systematic reviews, and reference lists of the relevant studies. Randomized controlled trials (RCTs) which compared the TTT for DF with conventional treatment will be included. Our reviewers will perform subgroup analysis, sensitivity analysis, and publication bias analysis to evaluate the heterogeneity and robustness. RevMan 5.3 software and Stata V.16.0 software will be used to analyze the available data. ETHICS AND DISSEMINATION: Ethical approval was not required because this protocol neither collected private information, nor involved animal experiments. The research was disseminated by academic journals or related meetings. PROSPERO REGISTRATION NUMBER: CRD42021279717.

Effect of tibial transverse transport on chronic lower extremity angiopathy: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Chronic lower extremity angiopathy is a peripheral vascular disease that can result in disability and death. The tibial transverse transport (TTT) technique has been used to treat this disease in recent years. TTT's effect remains unclear owing to the lack of large samples and high-quality evidence. Therefore, this study aims to assess TTT's effectiveness and safety in chronic lower extremity angiopathy treatment. METHODS AND ANALYSIS: Relevant studies were acquired by searching the following databases: Cochrane Library, Embase, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), China Science Technology Journal Database (VIP), Wanfang Data and Chinese Biomedical Literature Service System (CBM) until 20 September 2021. All randomised controlled trials and cohort studies on TTT for chronic lower extremity angiopathy will be included in this review. The primary outcomes will include the healing time and healing rate. The additional outcomes will include the Ankle Brachial Index, amputation rate, ankle skin temperature, Visual Analogue Scale, hospitalisation time, vascular endothelial growth factor, effective rate and complications. We will use Stata V.16.0 software and Review Manager V.5.3 software for meta-analysis. Subgroup and sensitivity analyses will be conducted, if necessary. ETHICS AND DISSEMINATION: This study was based on previous data. The medical ethics committee of Inner Mongolia People's Hospital, located in China waived the need for formal approval of this research, as this study did not fall under the principles of the Declaration of Helsinki. The results will be disseminated through peer-reviewed journals or relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42021281124.

Identification and validation of key modules and hub genes associated with the pathological stage of oral squamous cell carcinoma by weighted gene co-expression network analysis.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a major lethal malignant cancer of the head and neck region, yet its molecular mechanisms of tumourigenesis are still unclear. PATIENTS AND METHODS: We performed weighted gene co-expression network analysis (WGCNA) on RNA-sequencing data with clinical information obtained from The Cancer Genome Atlas (TCGA) database. The relationship between co-expression modules and clinical traits was investigated by Pearson correlation analysis. Furthermore, the prognostic value and expression level of the hub genes of these modules were validated based on data from the TCGA database and other independent datasets from the Gene Expression Omnibus (GEO) database and the Human Protein Atlas database. The significant modules and hub genes were also assessed by functional analysis and gene set enrichment analysis (GSEA). RESULTS: We found that the turquoise module was strongly correlated with pathologic T stage and significantly enriched in critical functions and pathways related to tumourigenesis. PPP1R12B, CFD, CRYAB, FAM189A2 and ANGPTL1 were identified and statistically validated as hub genes in the turquoise module and were closely implicated in the prognosis of OSCC. GSEA indicated that five hub genes were significantly involved in many well-known cancer-related biological functions and signaling pathways. CONCLUSION: In brief, we systematically discovered a co-expressed turquoise module and five hub genes associated with the pathologic T stage for the first time, which provided further insight that WGCNA may reveal the molecular regulatory mechanism involved in the carcinogenesis and progression of OSCC. In addition, the five hub genes may be considered candidate prognostic biomarkers and potential therapeutic targets for the precise early diagnosis, clinical treatment and prognosis of OSCC in the future.

Isopsoralen regulates PPAR­Î³/WNT to inhibit oxidative stress in osteoporosis.

The present study aimed to examine the effects of isopsoralen against postmenopausal osteoporosis in an ovariectomized rat model. The ovariectomized rats were treated with three days 10 mg/kg isopsoralen or with three days 20 mg/kg isopsoralen. Alkaline phosphatase, the oxidative stress indicators and caspase­3/9 were measured using ELISA assay kits. Reverse transcription­quantitative polymerase chain reaction was used to measure collagen type I (Col I), osteocalcin and osteoprotegerin mRNA levels. Wnt, ß­catenin and peroxisome proliferators­activated receptor γ (PPAR­Î³) were analyzed using western blot analysis. Isopsoralen suppressed mature adipocyte differentiation of C2C12 cells, inhibited serum calcium and urinary calcium levels, and reduced the structural scores of articular cartilage and cancellous bone in the proximal tibia metaphysis of mice with postmenopausal osteoporosis. Isopsoralen also promoted the activity of alkaline phosphatase and the mRNA expression levels of Col 1, osterix and osteopontin in mice with postmenopausal osteoporosis. Oxidative stress and activities of caspase­3/9 in the mice with postmenopausal osteoporosis were effectively suppressed by isopsoralen treatment, which upregulated the protein expression of Wnt/ß­catenin and downregulated the protein expression of PPAR­Î³. These findings demonstrated that isopsoralen prevented osteoporosis through the regulation of PPAR­Î³/WNT, inhibiting oxidative stress by targeting the PPAR­Î³/WNT pathway. These results provide evidence of the potential targeted therapy for isopsoralen in the clinical treatment of postmenopausal osteoporosis.

HIF-1α-induced microRNA-210 reduces hypoxia-induced osteoblast MG-63 cell apoptosis.

To better understand the ischemic-hypoxia-induced fracture healing impairment, we determined in this study the microRNA-210 expression in broken bone specimens and in osteoblasts under hypoxia and then determined the influence of microRNA-210 overexpression on the osteoblast cell proliferation and apoptosis. Results demonstrated that microRNA-210 expression was upregulated with an association with HIF-1α overexpression in clinical human catagmatic tissues and was upregulated HIF-1α-dependently in response to hypoxia in osteoblast MG-63 cells. CCK-8 assay indicated that microRNA-210 upregulation by microRNA-210 mimics reduced the chemotherapeutic 5-FU-induced osteoblast cell death, and colony formation assay demonstrated that microRNA-210 mimics promoted osteoblast cells growth. Moreover, the microRNA-210 mimics transfection inhibited the hypoxia-induced MG-63 cell apoptosis via inhibiting the activation of caspase 3 and caspase 9. Therefore, our research indicated a protective role of microRNA-210 in response to hypoxia. And microRNA-210 might serve as a protective role in bone fracture healing.