ABSTRACT
Recent research indicated that ulcers and peripheral vascular disease resulting from drug-resistant bacterial infections are the main causes of delayed healing in chronic diabetic wounds. 5-Aminolevulinic acid (ALA) is a second-generation endogenous photosensitizer. The therapeutic effect and mechanism of ALA-mediated photodynamic therapy (ALA-PDT) on methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds in diabetic rats were investigated in this study. The results revealed the promising antibacterial effects of ALA-PDT MRSA in vitro, with a minimum inhibitory concentration and minimum bactericidal concentration of 250 and 500⯵M, respectively. ALA-PDT also changed the permeability and structural integrity of bacterial cell membranes by producing reactive oxygen species. Meanwhile, ALA-PDT accelerated wound healing in MRSA-infected diabetic rats, with 5â¯% ALA-PDT achieving complete sterilization in 14 days and wound closure in 21 days. Treatment with 5â¯% ALA-PDT additionally improved the histopathological appearance of skin tissue, as well as fibrosis, inflammatory cytokine release, and angiogenesis-related protein expression. These findings indicated that ALA-PDT significantly promoted the healing of MRSA-infected wounds in diabetic rats by eliminating bacteria, inhibiting inflammation, generating granulation tissues, promoting neovascularization, and restoring damaged nerves. In addition, the healing mechanism was related to the activation of inflammatory and angiogenesis pathways through the regulation of tumor necrosis factor-alpha and interleukin-6 expression and upregulation of CD206, CD31, and VEGF. These findings underscored the potential role of ALA-PDT in promoting the healing of chronic diabetic wounds.
Subject(s)
Aminolevulinic Acid , Diabetes Mellitus, Experimental , Methicillin-Resistant Staphylococcus aureus , Photochemotherapy , Rats, Sprague-Dawley , Wound Healing , Wound Infection , Animals , Aminolevulinic Acid/pharmacology , Photochemotherapy/methods , Wound Infection/drug therapy , Wound Infection/microbiology , Wound Infection/pathology , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/complications , Male , Methicillin-Resistant Staphylococcus aureus/drug effects , Wound Healing/drug effects , Rats , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Chronic Disease , Staphylococcal Infections/drug therapy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Microbial Sensitivity Tests , Reactive Oxygen Species/metabolismABSTRACT
We investigate the efficacy of photodynamic antimicrobial chemotherapy (PACT) and its combination with an antibiotic in the treatment of diabetic foot ulcers (DFUs) in rats using a novel cationic amino acid porphyrin-based photosensitizer. The research findings demonstrate that the combination of novel cationic photosensitizer-mediated PACT and an antibiotic exhibits significant therapeutic efficacy in treating deep ulcers in a rat model of DFUs. Moreover, the PACT + Antibiotic group displays enhanced angiogenesis, improved tissue maturation, and superior wound healing effect. Micro-computed tomography examination showed that the periosteal reaction was most obvious in the PACT + Antibiotic group. The cortical bone volume ratio (BV/TV), the bone mineral density, and trabecular thickness were significantly higher in the PACT + Antibiotic group than in the model group (p < 0.05). The combination of PACT and antibiotic plays a sensitizing therapeutic role, which provides a new idea for the clinical treatment of DFUs.
Subject(s)
Diabetic Foot , Photochemotherapy , Photosensitizing Agents , Rats, Sprague-Dawley , Wound Healing , Animals , Rats , Diabetic Foot/drug therapy , Diabetic Foot/diagnostic imaging , Diabetic Foot/pathology , Male , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Wound Healing/drug effects , Anti-Bacterial Agents/pharmacology , X-Ray MicrotomographyABSTRACT
The plateau environment impacts male reproductive function, causing decreased sperm quality and testosterone levels. L-carnitine can improve the semen microenvironment. However, the role of L-carnitine in a high-altitude environment remains unclear. In our study, we investigated the effects of L-carnitine administration in a male Wistar rat reproductive system injury model in the context of a simulated high-altitude environment. Rats were randomly divided into a normal control group (group A1, A2-low dose and A3-high dose) and high-altitude model groups (group B, C-low dose and D-high dose) with 20 rats in each group. With the exception of the normal control group exposed to normoxic conditions, the other groups were maintained in a hypobaric oxygen chamber that simulated an altitude of 6000 m for 28 days. In the experimental period, the low-dose groups (A2 and C) were administered 50 mg/kg L-carnitine via intraperitoneal injection once a day, and the high-dose groups (A3 and D) were given 100 mg/kg. After the feeding period, blood samples were collected to assess blood gas, serum hormone levels and oxidative stress. Sperm from the epididymis were collected to analyse various sperm parameters. After obtaining the testicular tissue, the morphological and pathological changes were observed under a light microscope and transmission electron microscopy (TEM). The impact of the simulated high-altitude environment on the rat testis tissue is obvious. Specifically, a decreased testicular organ index and altered indices of arterial blood gas and serum sex hormone levels caused testicular tissue morphological damage, reduced sperm quality, increased sperm deformity rate and altered malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) concentrations. The results demonstrate that L-carnitine can be administered as a preventive intervention to reduce the reproductive damage caused by high-altitude hypobaric and hypoxic environments and improve semen quality in a rat model.
Subject(s)
Carnitine , Semen Analysis , Male , Rats , Animals , Rats, Wistar , Carnitine/pharmacology , Altitude , Semen , Spermatozoa , Testis/metabolism , Oxidative Stress , Hypoxia/metabolism , Gonadal Steroid Hormones/metabolism , Sperm MotilityABSTRACT
Background and purpose: Circular RNAs (circRNAs) are a big group of members of the noncoding RNA family following long non-coding RNA and microRNA. They play a regulatory role in many biological processes. Analyzing their current research status and future development trends is conducive to a more comprehensive understanding of circRNAs and contributes to the dedication to the biological field. Methods: The literature on circRNA from 2000 to 2021 in the Web of Science Core Collection of the Web of Science database with "circular RNA" as the subject was searched. R Studio's Bibliometrix package and biblioshiny software were used for publication trend analysis, citation analysis, keyword analysis, author analysis, research institution analysis, source analysis, country analysis, and collaboration analysis for all documents and highly cited documents. Results: From 2000 to 2021, 3,186 circRNA-related articles were published worldwide, of which 193 were highly cited. The number of published articles had shown an explosive increase after 2013. These articles were mainly from Chinese research institutions and authors, but the country with the highest average number of citations per year in highly cited documents was Germany. Scientific research institutions came from countries represented by Germany, USA, China, Australia and Canada all had different degrees of cooperation. The theme and key points of the research had evolved over time from expression to the role and mechanism of circRNA in diseases, especially in cancer. CDR1as, circFOXO3, circHIPK3, circITCH, circMTO1, circSMARCA5 and circZNF609 are circRNAs that are mainly studied currently, their studies mainly involve cell biology, biological functions and cancer. The future research direction and trend would still be the application of circRNA in diseases. Conclusion: The basic situation and development trend of circRNA related research we described provide a direction for future research.
ABSTRACT
Circular RNA (circRNA) molecules are noncoding RNAs with unique circular covalently closed structures that contribute to gene expression regulation, protein translation and act as microRNA sponges. circRNAs also have important roles in human disease, particularly tumorigenesis and antitumor processes. Methylation is an epigenetic modification that regulates the expression and roles of DNA and coding RNA and their interactions, as well as of noncoding RNA molecules. Previous studies have focused on the effects of methylation modification on circRNA expression, transport, stability, translation and degradation of circRNAs, as well as how circRNA methylation occurs and the influence of circRNAs on methylation modification processes. circRNA and methylation can also regulate disease pathogenesis via these interactions. In the present study, we define the relationship between circRNAs and methylation, as well as the functions and mechanisms of their interactions during disease progression.
Subject(s)
MicroRNAs , RNA, Circular , Carcinogenesis , Gene Expression Regulation , Humans , Methylation , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Circular/geneticsABSTRACT
OBJECTIVE: To establish a model of reproductive system injury in male rats at high altitude using the low-pressure hypoxic animal laboratory and study the changes in the testicular tissue, semen parameters, blood gas and oxidative stress in male rats at different altitudes. METHODS: Sixty male Wistar rats were randomly assigned to be raised on the plains (the plains group, n = 20), at an altitude of 4 000 m (the plateau model group â , n = 20), or at an altitude of 6 000 m (the plateau model group â ¡, n = 20) for a spermatogenic cycle of 14 days. After establishment of the model of high-altitude reproductive system injury, the testis tissues of the rats were harvested for HE staining and observed for histopathological changes under the light microscope, and their epididymedes collected for preparation of sperm suspension and detection of sperm motility, sperm count and the percentage of morphologically abnormal sperm (MAS). The blood gas level and oxidative stress-related indexes in different groups were also measured using the serological test. RESULTS: With the elevation of altitude, the levels of pH and PO2 were decreased, those of PCO2, Hct, K+, Clï¼ and Hb increased markedly, while that of Na+ exhibited no significant change. The model rats also showed folded spermatogenic tubule walls, thinned spermatogenic epithelia, disorderly arranged and reduced number of spermatogenic cells, and increased vascuolization in the spermatogenic epithelia, with decreased sperm motility and count, increased percentage of MAS, elevated concentration of malondialdehyde (MDA) and reduced activity of superoxide dismutase (SOD). CONCLUSIONS: A model of reproductive system injury was successfully established in male rats at a simulated altitude of 4 000 m. With increasing of the altitude to 6000 m, oxidative damage to the testicular tissue was aggravated, sperm motility decreased, and the percentage of MAS increased, indicating that an altitude of 6 000 m may cause serious damage to the rat reproductive system.