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PLoS Neglected Tropical Diseases May 2024Photobiomodulation has exhibited promise in mitigating the local effects induced by Bothrops snakebite envenoming; however, the mechanisms underlying this protection are...
BACKGROUND
Photobiomodulation has exhibited promise in mitigating the local effects induced by Bothrops snakebite envenoming; however, the mechanisms underlying this protection are not yet fully understood. Herein, the effectiveness of photobiomodulation effects on regenerative response of C2C12 myoblast cells following exposure to Bothrops jararacussu venom (BjsuV), as well as the mechanisms involved was investigated.
METHODOLOGY/PRINCIPAL FINDINGS
C2C12 myoblast cells were exposed to BjsuV (12.5 μg/mL) and irradiated once for 10 seconds with laser light of 660 nm (14.08 mW; 0.04 cm2; 352 mW/cm2) or 780 nm (17.6 mW; 0.04 cm2; 440 mW/ cm2) to provide energy densities of 3.52 and 4.4 J/cm2, and total energies of 0.1408 and 0.176 J, respectively. Cell migration was assessed through a wound-healing assay. The expression of MAPK p38-α, NF-Кβ, Myf5, Pax-7, MyoD, and myogenin proteins were assessed by western blotting analysis. In addition, interleukin IL1-β, IL-6, TNF-alfa and IL-10 levels were measured in the supernatant by ELISA. The PBM applied to C2C12 cells exposed to BjsuV promoted cell migration, increase the expression of myogenic factors (Pax7, MyF5, MyoD and myogenin), reduced the levels of proinflammatory cytokines, IL1-β, IL-6, TNF-alfa, and increased the levels of anti-inflammatory cytokine IL-10. In addition, PBM downregulates the expression of NF-kB, and had no effect on p38 MAKP.
CONCLUSION/SIGNIFICANCE
These data demonstrated that protection of the muscle cell by PBM seems to be related to the increase of myogenic factors as well as the modulation of inflammatory mediators. PBM therapy may offer a new therapeutic strategy to address the local effects of snakebite envenoming by promoting muscle regeneration and reducing the inflammatory process.
PubMed: 38814992
DOI: 10.1371/journal.pntd.0012227 -
Cell Reports May 2024Lipids have emerged as potent regulators of immune cell function. In the skin, adipocyte lipolysis increases the local pool of free fatty acids and is essential for...
Lipids have emerged as potent regulators of immune cell function. In the skin, adipocyte lipolysis increases the local pool of free fatty acids and is essential for coordinating early macrophage inflammation following injury. Here, we investigate G-protein-coupled receptor 84 (GPR84), a medium-chain fatty acid (MCFA) receptor, for its potential to propagate pro-inflammatory signaling after skin injury. GPR84 signaling was identified as a key component of regulating myeloid cell numbers and subsequent tissue repair through in vivo administration of a pharmacological antagonist and the MCFA decanoic acid. We found that impaired injury-induced dermal adipocyte lipolysis is a hallmark of diabetes, and lipidomic analysis demonstrated that MCFAs are significantly reduced in diabetic murine wounds. Furthermore, local administration of decanoic acid rescued myeloid cell numbers and tissue repair during diabetic wound healing. Thus, GPR84 is a readily targetable lipid signaling pathway for manipulating injury-induced tissue inflammation with beneficial effects on acute diabetic healing.
PubMed: 38814782
DOI: 10.1016/j.celrep.2024.114288 -
Clinical Ophthalmology (Auckland, N.Z.) 2024To report the outcomes of using a sutureless human amniotic membrane dehydrated matrix (HAMDM) in the management of a range of ocular surface conditions utilizing a...
Management of Ocular Surface Inflammation with Persistent Epithelial Defects Using a Sutureless Human Amniotic Membrane Dehydrated Matrix: A Prospective Study Utilizing a Digital Ocular Surface Assessment Tool.
PURPOSE
To report the outcomes of using a sutureless human amniotic membrane dehydrated matrix (HAMDM) in the management of a range of ocular surface conditions utilizing a digital ocular surface disease assessment tool.
METHODS
Two UK NHS Trusts - Queen Victoria Hospital Foundation Trust (East Grinstead and Maidstone) and Tunbridge Wells Trust (Kent) - prospectively treated patients with ocular surface disease with sutureless HAMDM. The patient cohort was assessed for resolution of epithelial defects, ocular surface inflammation, and best-corrected visual acuity pre- and posttreatment. Measurements of ocular surface inflammation and epithelial defect size were assessed using AOS digital imaging software, a validated tool for objective grading of bulbar conjunctival redness and measurement of corneal epithelial defects.
RESULTS
A total of 47 applications of sutureless HAMDM on 46 eyes of 46 patients (25 male, 21 female, age 9-94 years) were assessed across various etiologies for an average of 24.0±14.1 days. Patients with limbal stem-cell deficiency (n=17), persistent epithelial defects (n=16), neurotrophic corneal disease (n=7), filamentary keratitis (n=2), corneal erosion (n=1), corneal thinning (n=1), ocular surface inflammation (n=1), and traumatic corneal laceration (n=1) were included in the study. Across all patents, 63% of eyes showed complete healing of epithelial defects and 32.6% of eyes showed partial resolution. The average rate of healing (wound closure) was 0.36 mm per day across the overall patient cohort, and the rate of healing in cases with complete resolution of epithelial defects was 0.41 mm per day. Inflammation across all four quadrants of the ocular surface remained stable. Visual acuity across the patient cohort remained stable (61%) and improved in 26% of patients (0.06±0.51 logMAR).
CONCLUSION
Sutureless HAMDM application can be accomplished in just a few minutes and effectively treat a range of ocular surface disease in a clinical, nonsurgical setting. The AOS imaging software offered a quantitative methodology for measuring epithelial defect size and inflammation state.
PubMed: 38813539
DOI: 10.2147/OPTH.S456864 -
Turkish Journal of Medical Sciences 2023The common disease gastric adenocarcinoma (GAC) has a high morbidity and mortality, so there is an urgent need for research to explore new diagnostic markers and...
BACKGROUND/AIM
The common disease gastric adenocarcinoma (GAC) has a high morbidity and mortality, so there is an urgent need for research to explore new diagnostic markers and therapeutic targets. This investigation was carried out to investigate the expression of sphingomyelin phosphodiesterase acid-like 3b (SMPDL3B) in GAC and its effects on tumor progression.
MATERIALS AND METHODS
Samples were collected from patients who underwent radical gastrectomy from January 2021 to December 2022. Along with the normal gastric epithelial cell lines GES-1 and SGC-7901, the AGS, MGC-803, and MSN-45 human gastric cancer cell lines were used to confirm SMPDL3B expression. RT-qPCR, Western blot, immunohistochemical, cell proliferation, assay of wound healing, transwell migration assay, invasion assay, flow cytometry, and immune evaluation experiments were carried out.
RESULTS
SMPDL3B was found to be substantially expressed in GAC, and this condition has a bad prognosis. By establishing SMPDL3B knockdown and overexpression of GAC cell lines, this study confirmed that SMPDL3B promoted tumor cell proliferation, migration, and invasion. Additional bioinformatics research revealed a connection between SMPDL3B and immune cell infiltration in the GAC immunological microenvironment, which enhanced tumor cell proliferation by promoting the infiltration content of M2 macrophages.
CONCLUSION
This study determined the function of SMPDL3B for the clinical diagnosis, prediction, and novel management of GAC.
Topics: Humans; Stomach Neoplasms; Adenocarcinoma; Cell Proliferation; Cell Line, Tumor; Macrophages; Cell Movement; Sphingomyelin Phosphodiesterase; Disease Progression; Male; Female; Middle Aged; Tumor Microenvironment
PubMed: 38813495
DOI: 10.55730/1300-0144.5732 -
Heliyon May 2024The erector spinae plane block (ESPB) was proposed as a part of the postoperative multimodal analgesic regimen to improve pain management after posterior spinal surgery....
BACKGROUND
The erector spinae plane block (ESPB) was proposed as a part of the postoperative multimodal analgesic regimen to improve pain management after posterior spinal surgery. However, ESPB might cause more surgical incisional wound exudate and poor wound healing, which might be improved after topical lyophilized thrombin application.
MATERIALS AND METHODS
We performed a retrospective study on patients who received posterior spinal surgery between January 2018 and December 2021. These patients were assigned into three groups: group A (general anesthesia), group B (general anesthesia with ESPB), and group C (general anesthesia with ESPB and topical 1000-unit thrombin application). Postoperative outcomes, including times of dressing changes, duration of suture removal, and incisional wound healing, were compared among these groups.
RESULTS
Our study included 89 patients, with 48, 20, and 21 patients in groups A, B, and C, respectively. Baseline demographics, height, weight, comorbidities, and operation duration were comparable among the three groups. Group B required statistically significantly more dressing changes and had a prolonged duration of suture removal than group A (9.4 ± 4.7 versus 6.5 ± 2.0 times, 16.2 ± 3.7 versus 14.2 ± 1.4 days, respectively), which could be statistically significantly improved after the thrombin application in group C. Group B also had more frequent poor wound healing (25.0 %), which could also be improved after the thrombin application (0.0 %).
CONCLUSIONS
ESPB could cause more dressing changes and poor surgical wound healing after posterior spinal surgery, which could be improved by topical lyophilized thrombin powder application.
PubMed: 38813190
DOI: 10.1016/j.heliyon.2024.e31335 -
RSC Advances May 2024The Biginelli reaction, a three-component cyclocondensation reaction, is an important member of the multicomponent reaction (MCR) family. In this study, we conducted...
The Biginelli reaction, a three-component cyclocondensation reaction, is an important member of the multicomponent reaction (MCR) family. In this study, we conducted end-group modifications on a variety of biodegradable polyesters, including poly(1,4-butylene adipate) (PBA), poly(ε-caprolactone) (PCL), polylactic acid (PLA), and poly(-dioxanone) (PPDO), based on the precursor polyethylene glycol (PEG). By combining two polymers through the Biginelli multi-component reaction, four new biodegradable polyester copolymers, namely DHPM-PBA, DHPM-PCL, DHPM-PLA, and DHPM-PPDO, were formed. These Biginelli reactions demonstrated exceptional completeness, validating the efficiency of the synthesis strategy. Although the introduction of various polyesters lead to different properties, such as crystallinity and cytotoxicity, the newly synthesized 3,4-dihydro-2()-pyrimidinone compounds (DHPMs) exhibit enhanced hydrophilicity and can self-assemble in water and ,-dimethylformamide (DMF) solution to form micelles with a controllable size. Furthermore, DHPM-PPDO promotes cellular growth and has potential applications in wound healing and tissue engineering. In conclusion, this method demonstrates great universality and methodological significance and offers insights into the medical applications of polyethylene glycol.
PubMed: 38813120
DOI: 10.1039/d4ra02002b -
Hsa-circ-0006091 modulates the proliferation of hepatocellular carcinoma via the miR-622/CCNB1 axis.Turkish Journal of Medical Sciences 2023Hepatocellular carcinoma (HCC) is a common type of cancer. We hypothesize that circular RNA-0006091 (circ-0006091) affects the progression of HCC. The study aims to...
BACKGROUND/AIM
Hepatocellular carcinoma (HCC) is a common type of cancer. We hypothesize that circular RNA-0006091 (circ-0006091) affects the progression of HCC. The study aims to investigate the effect of circ-0006091 in HCC cells.
MATERIALS AND METHODS
The levels of circ-0006091, microRNA-622 (miR-622), and cyclin B1 (CCNB1) were assayed using qRT-PCR and western blotting. The metastasis of the HCC cells was measured with wound healing and transwell assays. The protein expression levels of MMP-2 and MMP-9 were assayed with western blotting. Dual-luciferase reporter and RNA-pulldown assays were used to determine the link between miR-622 and circ-0006091 or CCNB1. Mice-based tests were used to determine the effect of circ-0006091 on the proliferation of HCC cells.
RESULTS
The levels of circ-0006091 and CCNB1 were increased in the HCC cells, but miR-622 was down-regulated. Deficiency of circ-0006091 reduced the metastasis of the HCC cells, and silencing of circ-0006091 decreased the activities of MMP-2 and MMP-9 in the same cells. Circ-0006091 modulated the CCNB1 level in the HCC cells via miR-622. Silencing of circ-0006091 suppressed the proliferation of the HCC cells in vivo.
CONCLUSION
Circ-0006091 regulated HCC cell metastasis via the miR-622/CCNB1 axis, a possible therapeutic target in managing HCC.
Topics: Carcinoma, Hepatocellular; Liver Neoplasms; MicroRNAs; Cyclin B1; RNA, Circular; Humans; Cell Proliferation; Animals; Mice; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Matrix Metalloproteinase 9
PubMed: 38813026
DOI: 10.55730/1300-0144.5703 -
Turkish Journal of Medical Sciences 2023Curcumin may have potential as a therapy for wound healing, but the underlying mechanism remains unclear. It is not known whether curcumin can promote wound healing by...
BACKGROUND/AIM
Curcumin may have potential as a therapy for wound healing, but the underlying mechanism remains unclear. It is not known whether curcumin can promote wound healing by activating Nrf2 signaling pathway and inducing apoptosis. This study determined the role of Nrf2 signaling pathway and apoptosis in curcumin-promoting skin wound healing.
MATERIALS AND METHODS
The full-thickness skin defect model of mice was made and randomly divided into a control group and a curcumin group. The mice in the curcumin group and in the control group received respectively a daily topical treatment of Vaseline cream with or without 5 mg curcumin. The wound healing of mice was observed daily. The mice in two groups were killed respectively on postinjury days 3, 7, and 14, and the wound tissues were collected, with 5 mice in each group. Pathological change and formation of collagen fibers were observed by HE and Masson staining respectively. The expression of caspase-3 was observed by immunohistochemistry. Western blot was used to examine the protein levels of Nrf2 and HO-1, and ELISA assay and colorimetry assay were used to check the contents of ROS, MDA, SOD, and GSH.
RESULTS
The wound healing rates of curcumin group were higher than those of control group (p < 0.05), and the pathological changes were also significantly better than those in the control group (p < 0.05). Collagen fiber synthesis in curcumin group was higher than that in control group (p < 0.05). Moreover, the expression of caspase-3 in curcumin group was higher than that in control group on 7th day post wound (p < 0.05). Furthermore, the levels of ROS and MDA in curcumin were lower than those in control group (p < 0.05), and the level of Nrf2, HO-1, SOD and GSH were higher than those in control group (p < 0.05).
CONCLUSION
Curcumin improves skin wound healing by activating the Nrf2 signaling pathway and inducing apoptosis in mice.
Topics: Animals; Curcumin; Wound Healing; NF-E2-Related Factor 2; Apoptosis; Mice; Signal Transduction; Skin; Male; Disease Models, Animal
PubMed: 38812993
DOI: 10.55730/1300-0144.5678 -
Frontiers in Immunology 2024Adipose tissue mesenchymal stem/stromal cells (ASC) can be used as advanced therapy medicinal product in regenerative and cancer medicine. We previously demonstrated...
INTRODUCTION
Adipose tissue mesenchymal stem/stromal cells (ASC) can be used as advanced therapy medicinal product in regenerative and cancer medicine. We previously demonstrated Supernatant Rich in Growth Factors (SRGF) can replace fetal bovine serum (FBS) to expand ASC by a clinical grade compliant protocol. The therapeutic potential of ASC is based also on their homing capacity toward inflammatory/cancer sites: oriented cell migration is a fundamental process in this scenario. We investigated the impact of SRGF on ASC migration properties.
METHODS
The motility/migration potential of ASC expanded in 5% SRGF was analyzed, in comparison to 10% FBS, by standard wound healing, bidimensional chemotaxis and transwell assays, and by millifluidic transwell tests. Mechanisms involved in the migration process were investigated by transient protein overexpression.
RESULTS
In comparison to standard 10% FBS, supplementation of the cell culture medium with 5% SRGF, strongly increased migration properties of ASC along the chemotactic gradient and toward cancer cell derived soluble factors, both in static and millifluidic conditions. We showed that, independently from applied migratory stimulus, SRGF expanded ASC were characterized by far lower expression of α-smooth muscle actin (αSMA), a protein involved in the cell migration machinery. Overexpression of αSMA induced a significant and marked decrease in migration capacity of SRGF expanded ASC.
DISCUSSION
In conclusion, 5% SRGF addition in the cell culture medium increases the migration potential of ASC, reasonably through appropriate downregulation of αSMA. Thus, SRGF could potentially improve the therapeutic impact of ASC, both as modulators of the immune microenviroment or as targeted drug delivery vehicles in oncology.
Topics: Humans; Cell Movement; Intercellular Signaling Peptides and Proteins; Adipose Tissue; Mesenchymal Stem Cells; Blood Platelets; Cells, Cultured; Culture Media; Actins; Female
PubMed: 38812519
DOI: 10.3389/fimmu.2024.1404228 -
Frontiers in Bioscience (Landmark... May 2024Colorectal cancer (CRC) is a major cause of mortality and morbidity. A study proved that brexpiprazole, as a novel dopamine receptor partial agonist, can also prevent...
BACKGROUND
Colorectal cancer (CRC) is a major cause of mortality and morbidity. A study proved that brexpiprazole, as a novel dopamine receptor partial agonist, can also prevent CRC cell proliferation. Therefore, clarifying the molecular mechanism of brexpiprazole is vital to developing a novel therapeutic strategy for CRC.
METHODS
The effect of brexpiprazole on human colorectal cancer cell proliferation was measured with Cell Counting Kit-8 (CCK-8) kits. Cell migration capability was measured using wound healing and transwell. Cell apoptosis was evaluated with a flow cytometer. Western blots and immunohistochemical staining were used to evaluate protein expression. The effects observed were also confirmed in xenograft models.
RESULTS
Brexpiprazole remarkably inhibited the proliferation, suppressed the migration ability, and induced apoptosis of colorectal cancer cells. Mechanism study showed that brexpiprazole exerted these effects by inhibiting the EGFR pathway. Brexpiprazole enhanced HCT116 cells' sensitivity to cetuximab, and a combination of brexpiprazole and cetuximab inhibited xenograft tumor growth .
CONCLUSIONS
Our finding suggested that brexpiprazole inhibits proliferation, promotes apoptosis, and enhances CRC cells' sensitivity to cetuximab by regulating the EGFR pathway and it might be an efficacious treatment strategy for CRC.
Topics: Humans; Colorectal Neoplasms; Thiophenes; ErbB Receptors; Animals; Cell Proliferation; Apoptosis; Cetuximab; Mice, Nude; Xenograft Model Antitumor Assays; Quinolones; Cell Movement; Cell Line, Tumor; Mice; HCT116 Cells; Mice, Inbred BALB C; Disease Progression
PubMed: 38812296
DOI: 10.31083/j.fbl2905174