The efficacy of buprenorphine on moderate traumatic brain injury in the rat model.

INTRODUCTION: Traumatic brain injury (TBI) is the leading cause of death, disability, and mental health disorders. A wide range of bioactive lipids, cytokines, and chemokines drives the inflammatory response. This study aimed to assess the efficacy of buprenorphine on moderate Trauma Brain Injury (mTBI) in rats. METHODS: In this study, 21 Wistar male rats weighing 230 ± 10 g were included. We trained cases by Morris water navigation task and mTBI induced by the pendulum. Then, buprenorphine treatment with 0.05 mg per kilogram of body weight continued from day 8 to 21. Finally, by Micro-Computed Tomography, behavioral evaluation by the Morris aqueous riddle test and biochemical factors of inflammation were assessed. RESULTS: Severe subdural inflammation was more in the treatment group than in the control group. The behavior of Rats showed that in the buprenorphine group, the mean duration of finding the platform increased compared to the control and Sham groups. However, the groups had no significant differences (P > 0.05). Biochemically, buprenorphine increased prolactin and decreased cortisol compared to the control and trauma groups (P < 0.05). CONCLUSION: These results suggest that buprenorphine causes fewer changes in behavioral functions in rats' models of mTBI and, because of their positive effect changes on inflammation biomarkers, biochemical behavioral tests, and CT scan images, could be ideal analgesic agents for pre-clinical responses after TBI.

The applications of machine learning techniques in medical data processing based on distributed computing and the Internet of Things.

Medical data processing has grown into a prominent topic in the latest decades with the primary goal of maintaining patient data via new information technologies, including the Internet of Things (IoT) and sensor technologies, which generate patient indexes in hospital data networks. Innovations like distributed computing, Machine Learning (ML), blockchain, chatbots, wearables, and pattern recognition can adequately enable the collection and processing of medical data for decision-making in the healthcare era. Particularly, to assist experts in the disease diagnostic process, distributed computing is beneficial by digesting huge volumes of data swiftly and producing personalized smart suggestions. On the other side, the current globe is confronting an outbreak of COVID-19, so an early diagnosis technique is crucial to lowering the fatality rate. ML systems are beneficial in aiding radiologists in examining the incredible amount of medical images. Nevertheless, they demand a huge quantity of training data that must be unified for processing. Hence, developing Deep Learning (DL) confronts multiple issues, such as conventional data collection, quality assurance, knowledge exchange, privacy preservation, administrative laws, and ethical considerations. In this research, we intend to convey an inclusive analysis of the most recent studies in distributed computing platform applications based on five categorized platforms, including cloud computing, edge, fog, IoT, and hybrid platforms. So, we evaluated 27 articles regarding the usage of the proposed framework, deployed methods, and applications, noting the advantages, drawbacks, and the applied dataset and screening the security mechanism and the presence of the Transfer Learning (TL) method. As a result, it was proved that most recent research (about 43%) used the IoT platform as the environment for the proposed architecture, and most of the studies (about 46%) were done in 2021. In addition, the most popular utilized DL algorithm was the Convolutional Neural Network (CNN), with a percentage of 19.4%. Hence, despite how technology changes, delivering appropriate therapy for patients is the primary aim of healthcare-associated departments. Therefore, further studies are recommended to develop more functional architectures based on DL and distributed environments and better evaluate the present healthcare data analysis models.

Comparison of the effects of human fetal umbilical cord-derived hyaluronic acid and fibroblast-derived exosomes on wound healing in rats.

INTRODUCTION: Exosomes and hyaluronic acid influence tissue regeneration and may be used as an alternative to more conventional wound treatment methods. This study compared how well hyaluronic acid from the human umbilical cord and exosomes from fibroblast cells heal burn wounds in a preclinical model. METHODS: Ninety-six male Westar rats were used and allocated into four groups: The treatment group received 10% hyaluronic acid (HA); the treatment group received 300 l of exosome solution (EX); the treatment group received phenytoin (PC); the negative control group received no treatment (NC). The wound healing process was evaluated after 3, 6, 9, and 12 days. Histopathological analysis was done on the skin biopsy taken from the wounds. Re-epithelialization, inflammatory cells (PMNs), lymphocytes (LYMs), granulation tissue, collagen maturation (fibrosis), and eschar formation parameters were assessed for histopathological evaluation. On a scale from 0 to 4, each parameter received a score. RESULTS: Compared to the PC and NC groups, the median score for re-epithelialization was greater in the HA and EX groups (P < 0.05). At three days, PMN abundance distinguished the PC and NC groups from the HA and EX groups (P < 0.01). Compared to the PC and NC groups, the HA and EX groups had a lower median LYM score (P < 0.01). We found no statistical difference between the four groups for granulation tissue and fibrosis (P > 0.05). The EX group had a lower average score for eschar formation than the PC, NC, and HA groups (P < 0.01). The HA and EX groups demonstrated faster healing in the clinical and microscopic examinations than the NC and PC groups. CONCLUSION: The results showed that hyaluronic acid and exosomes improved wound healing. Also, the study demonstrated that hyaluronic acid has better effects in the re-epithelization. The exosome was more effective than HA in eschar formation. Both compounds were more influential in the PMNs and LYMs parameters than other groups. The combination of both compounds should be assessed further to achieve better therapeutic effects on wound healing.

Effects of exosomes derived from fibroblast cells on skin wound healing in Wistar rats.

BACKGROUND: The role of exosomes in areas, such as skin wound healing, have been of consideratble interest recently. However, the effects of exosomes derived mainly from fibroblast cells on wound healing have yet to be documented well. The study aimed to evaluate the effects of exosomes derived from fibroblast cells on wound healing in Wistar rats. METHODS: Human fetal skin was isolated afterward centrifuge, and trypsin 0.1% was added to the cells after removing DPBS from the Falcon tube, and the trypsin was removed. The cells were moved to culture flasks. Then, the secondary culture of Human Fetal Skin Fibroblast was done. The pellets containing exosomes were suspended in PBS, and to achieve purified exosomes, the suspended Exosome were passed through a 0.22 µm filter. The exosome solution was kept at - 20 ºC. In the in vivo phase, 48 male Wistar rats were divided into four groups. Group I, low-dose exosome (LDE) solution (150 µl/day), group II high-dose exosome (HDE) solution (300 µl/day), group III commercially available ointment (positive control (PC)) was topically applied on wounds and group VI without treatment (negative control (NC)). A skin biopsy was taken for histopathological analysis. Wound area, depth of ulcer, degree of granulation, and inflammation were assessed. For histopathological assessment, re-epithelialization, inflammatory cells, granulation tissue, crust formation, and collagen maturation (fibrosis) parameters were evaluated. RESULTS: Forty-eight male Wistar rats were included. The HDE group's showed accelerated healing compared to the NC and PC groups at 9 and 12 days. Inflammation and granulation were higher in the HDE, LDE, and PC groups than in the NC group (p < 0.05). The onset of re-epithelialization and collagen deposition was higher in the LDE, HDE, and PC groups, then on nine and 12-day, gradually maturing and extending through the ulcer (p < 0.05). On day 12, in almost all parameters, the LDE and HDE groups showed improved results compared to NC cases (p < 0.05). CONCLUSIONS: The results showed that the utilization of fibroblast-Exo significantly promoted cutaneous wound healing in a rat full-thickness skin ulcer model. This is a potential innovation for cell-free therapy from fibroblast-Exo as a closed structure similar to human cells.

Evaluation of Associated Genes with Traumatic Pain: A Systematic Review.

OBJECTIVES: The knowledge about the molecular pathway of traumatic pain relief is less documented. This systematic review study aimed to identify the genes and molecular pathways associated with various traumatic pains. METHODS: The online databases such as EMBASE, MEDLINE, PubMed, Cochrane Library, International Clinical Trials Registry Platform, Clinical Trials, Google Scholar, Wiley, ISI Web of Knowledge, and Scopus were searched. Two review authors searched and screened all records' titles and abstracts, and the third expert reviewer author resolved their disagreement. The study's design, various trauma injuries, types of genes, and molecular pathways were recorded. The genes and molecular pathways data were obtained via GeneCards®: The Human Gene Database (https://www.genecards.org). RESULTS: Studies on a variety of trauma injuries regarding nerve and Spinal Cord Injuries (SCIs) (12 records), Hypertrophic scar with Severe Pain (one record), severe post-traumatic musculoskeletal pain (MSP) (one record), and orthopedic trauma (one record) were included. The main molecular pathways such as the immune system, apoptosis, and death receptor signaling, T-cell antigen receptor (TCR) signaling pathway, oxidative stress, interleukin(s) mediated signaling pathway, biological oxidations, metabolic pathways (especially amino acid metabolism and amino group), focal adhesion, the proliferation of vascular, epithelial, and connective tissue cells, angiogenesis and neural development were identified. CONCLUSION: The immune system, apoptosis, and metabolic pathways are crucial for understanding the roles of genes in traumatic pain. It is recommended that these identified pathways and related genes be considered therapeutical targets for pain management in patients with trauma injuries. In addition, different forms of trauma injuries require different pathways and related genes to be considered.

Evaluation of a single amino acid substitution at position 79 of human IFN-α2b in interferon-receptor assembly and activity.

Type I interferons (IFNs) are homologous cytokines that bind to a cell surface receptor and establish signaling pathways that motivate immune responses. The purpose of the current study is to assess the activity of a novel-engineered IFN-α2b. The crystallographic structure of IFN-α2b and its receptors was acquired from Protein Data Bank. Various amino acid substitutions were designed based on structural properties and other biological characteristics of residues to find the most effective amino acid on IFN affinity to advanced activities. The IFN-α2b mutants and receptors have been modeled and the interactions between two proteins have been studied as in silico by protein-protein docking for both mutants and native forms. The proper nucleic acid sequence IFN-α2 (T79Q) has been prepared based on the selected mutant. The modified IFN gene was cloned in pcDNA 3.1(-) and introduced to Chinese Hamster Ovary (CHO) cell line. Antiviral and antiproliferative assays of native and IFN-α2 (T79Q) proteins were performed in vitro. The results showed two-fold increasing in IFN-α2 (T79Q) activity (antiviral and antiproliferative activity) in comparison to native IFN-α2b. This engineered IFN-α2b may have significant novel therapeutic applications and in silico studies can be an influential method for practical research function and structure of these molecules.

Derivation of islet-like cells from mesenchymal stem cells using PDX1-transducing lentiviruses.

Pancreatic duodenum homeobox protein-1 (PDX1) is a master regulatory gene in pancreatic development. Reprogramming of mesenchymal stem cells (MSCs) is a promising tool for producing insulin-producing cells. In this study, lentivirus harboring PDX1 (LV-PDX1) has been used for persistence gene expression in MSCs. The objective of this study was to evaluate the potential of lentivirus to introduce the PDX1 gene into MSCs to produce insulin-secreting cells and apply it for treatment of hyperglycemia in diabetic rats. MSCs were isolated from rat bone marrow, characterized, and transduced by LV-PDX1. Significant expressions of PDX1, neurogenin3, glucagon, glucose transporter2 (Glut2), and insulin were detected by quantitative reverse transcription-polymerase chain reaction (P < 0.05). PDX1 and insulin were detected at the protein level by immunofluorescence analysis. PDX1 could trigger a gene expression cascade that involved pancreatic endocrine differentiation and also revealed the glucose sensing ability by expressing Glut2 in high-glucose medium. The insulin secretion of MSCs(PDX1+) in the high-glucose medium was 1.75-fold higher than that secreted in the low-glucose medium (P < 0.05). MSCs(PDX1+) implanted into diabetic rats could decrease the blood glucose level from 485 mg/dL to the normal level in 3 days. This study showed MSCs(PDX1+) have the potential to be used as a viable resource in cell-based gene therapy of type 1 diabetes.