BACKGROUND: One of the promising methods of influencing the wound process is photobiomodulation (PBM) therapy. The optimal parameters of PBM therapy have not yet been found because the molecular mechanisms of light interaction with tissue are not fully understood.
OBJECTIVE: Studying the influence of PBM of various parameters on the regulation of reparative process- es of chronic wounds using the example of indicators of aggregation activity of platelets, platelet-derived growth factor (PDGF), interleukin-8 (IL-8), and amino-terminal propeptide of type III procollagen (PIIINP) at the remodeling stage. And also the study of the structural and functional features of chronic wound heal- ing in an experiment under various parameters of PBM therapy.
METHODS: Experiments were carried out on Wistar rats. Chronic wounds were simulated. Experimental animals were exposed to PBM at a wavelength of 660 nm and an energy density of 1 J/cm2. In serum, PDGF, IL-8, and PIIINP levels were measured by enzyme-linked immunosorbent assay. The functional activity of platelets was measured using the turbidimetric method. Histological analysis was performed.
RESULTS: The work noted the dose-dependent effect of PBM using the example of platelet aggregation at the remodeling stage during the healing of chronic wounds. The use of PBM therapy resulted in increased serum PDGF levels. Histological examination data indicate a positive effect of PBM therapy on the wound healing process.
CONCLUSIONS: The effectiveness of the use of PBM therapy for the healing of chronic wounds to regulate reparative processes has been proven.

Pulmonary arterial hypertension (PAH) is an obstructive vasculopathy that, if not promptly treated, culminates in right heart failure. Therefore, pre-clinical studies are needed to support and optimize therapeutic approaches of PAH. Here, we explore a prospective function of sevoflurane in experimental PAH through regulating TRAF6. Monocrotaline (MCT)-induced PAH rats were subjected to sevoflurane inhalation and intratracheal instillation of lentivirus overexpressing TRAF6. Platelet-derived growth factor (PDGF)-treated pulmonary artery smooth muscle cells (PASMCs) were exposed to sevoflurane and genetically manipulated for TRAF6 overexpression. It was found that MCT and PDGF challenge upregulated the levels of TRAF6 in rat lung tissues and PASMCs, but sevoflurane treatment led to reduced TRAF6 expression. Sevoflurane inhalation in MCT-induced rats resulted in alleviative pulmonary vascular remodeling, mitigated right ventricular dysfunction and hypertrophy, improved mitochondrial function and dynamics, and inactivation of NF-κB pathway. In vitro studies confirmed that exposure to sevoflurane repressed PDGF-induced proliferation, migration, and phenotype switching of PASMCs, and suppressed mitochondrial dysfunction and NF-κB activation in PDGF-stimulated PASMCs. The beneficial impact of sevoflurane on pathological changes of lung and cell phenotype of PASMCs were reversed by overexpression of TRAF6. In summary, our study suggested the protective properties of sevoflurane in targeting PAH by downregulating TRAF6 expression, providing a novel avenue for the management of PAH.

UNASSIGNED: Applying autologous growth factors and diode laser in periodontal therapy enhances fibroblast-mediated new attachment and osteoblastic differentiation. Hence, this study compared and evaluated the effectiveness of concentrated growth factor (CGF) alone and with diode laser application in managing intrabony periodontal defects.
UNASSIGNED: Ten patients with stage III periodontitis were included in this study. All the patients underwent an open flap debridement (OFD) procedure followed by CGF membrane placement in the intrabony defect in site A, whereas, in site B, after OFD, all the patients underwent diode laser irradiation before CGF membrane placement. Plaque and gingival bleeding index (PI & GBI), PPD, and clinical attachment level (CAL) were evaluated at baseline and 3 and 6 months later. Bone fill (BF), BF%, bone crest changes (BCC), and BCC% were assessed radiographically at six months postoperatively.
UNASSIGNED: Significant reductions in PI and GBI scores, probing pocket depth (PPD), and CAL gain were observed at both sites 3 and 6 months from baseline. A significant reduction in PPD and CAL gain was noted between sites, which were higher in site B than in site A with a mean difference of 0.70±0.05 mm and 1.30±0.18 mm, 0.90±1.89 mm at 3 and 6 months, respectively. Radiographic measurement showed better BF, BF%, BCC, and BCC% at both sites at six months, which were higher at site B than at site A but statistically insignificant.
UNASSIGNED: The combination of CGF and diode laser application has demonstrated successful and promising results in terms of regeneration, improving the clinical and radiographic parameters.

OBJECTIVE: Aim: The aim of the work was to study the ef f ect of photobiomodulation therapy on the regulation of disorders in the healing of chronic wounds at the remodeling stage using indicators of platelet aggregation activity, reactive oxygen species, platelet-derived growth factor, and interleukin-1β.
METHODS: Materials and Methods: The study included 3 groups of Wistar rats: intact animals and animals of the control and experimental groups, for which chronic wounds were simulated. Rats in the experimental group received photobiomodulation therapy once a day for 5 days. Wound defects of animals in the control group were fictitiously irradiated. The levels of reactive oxygen species, platelet-derived growth factor, and interleukin-1β in the blood serum of animals were studied by enzyme immunoassay. The functional activity of platelets was measured on a computerized platelet aggregation analyzer using the turbidimetric method. Histological studies were carried out.
RESULTS: Results: Changes in the expression of the studied indicators were found in the blood serum of animals with chronic wounds when using photobiomodulation therapy: an increase in platelet-derived growth factor concentrations, the levels of reactive oxygen species and interleukin-1β did not have statistically signif i cant differences compared to the corresponding indicators of animals in the control group. There were no significant differences in the indicators of platelet aggregation activity in the control and experimental groups of animals.
CONCLUSIONS: Conclusions: The findings suggest that photobiomodulation therapy may promote wound healing by increasing platelet-derived growth factor levels. Histological studies have shown that using photobiomodulation therapy helps reduce inflammation and better organization of collagen fibers in animals of the experimental group.

Yohimbine (YHB) has been reported to possess anti-inflammatory, anticancer, and cardiac function-enhancing properties. Additionally, it has been reported to inhibit the proliferation, migration, and neointimal formation of vascular smooth muscle cells (VSMCs) induced by platelet-derived growth factor (PDGF) stimulation by suppressing the phospholipase C-gamma 1 pathway. However, the transcriptional regulatory mechanism of YHB controlling the behavior of VSMCs is not fully understood. In this study, YHB downregulated the expression of cell cycle regulatory proteins, such as proliferating cell nuclear antigen (PCNA), cyclin D1, cyclin-dependent kinase 4 (CDK4), and cyclin E, by modulating the transcription factor FOXO3a in VSMCs induced by PDGF. Furthermore, YHB decreased p-38 and mTOR phosphorylation in a dose-dependent manner. Notably, YHB significantly reduced the phosphorylation at Y397 and Y925 sites of focal adhesion kinase (FAK), and this effect was greater at the Y925 site than Y397. In addition, the expression of paxillin, a FAK-associated protein known to bind to the Y925 site of FAK, was significantly reduced by YHB treatment in a dose-dependent manner. A pronounced reduction in the migration and proliferation of VSMCs was observed following co-treatment of YHB with mTOR or p38 inhibitors. In conclusion, this study shows that YHB inhibits the PDGF-induced proliferation and migration of VSMCs by regulating the transcription factor FOXO3a and the mTOR/p38/FAK signaling pathway. Therefore, YHB may be a potential therapeutic candidate for preventing and treating cardiovascular diseases such as atherosclerosis and vascular restenosis.

UNASSIGNED: Haemorrhoidal disease is one of the most common nowadays. It is often associated with a sedentary lifestyle. The leading cause of its development is also a functional disorder of the intestine and chronic constipation. To date, there is a steady growth rate of this disease, leading to its \"rejuvenation\". The current stage of development indicates the need for further improvement of surgical treatment and optimisation of patient management methods and the creation of uniform standards of care for this contingent of patients.
UNASSIGNED: To evaluate the clinical effectiveness of the use of platelet-rich plasma therapy and the biologically active substance \"ozoyl\" in the treatment of haemorrhoidal disease.
UNASSIGNED: The main group included 100 patients with chronic haemorrhoids who were operated on in the period from March 2021 to March 2022. For this group, autoplasma was used during surgery, and an ozoyl-based drug in the postoperative period. The remaining 100 participants of this study, assigned to the control group, underwent a conventional haemorrhoidectomy operation and standard patient management using a hydrophilic ointment based on chloramphenicol.
UNASSIGNED: After the conducted clinical studies, it was established that in the main group, the pain syndrome decreased by about 30%, considering the period from the first day of the postoperative period compared to the control group. The postoperative wound healed in the main group in the third week after the operation, unlike the control group, in which this event was noted in the fourth week. The patients did not complain during the examination 3 months later.
UNASSIGNED: This study is of practical significance because haemorrhoidal disease today has a high prevalence, and an integrated approach is required for the treatment of such patients. Ozoyl is a powerful cell and tissue repairer.

Introduction Diabetic foot complications leading to limb amputations pose a global health concern. Platelet-rich plasma (PRP) gel has emerged as a promising method for ulcer healing, leveraging the growth factors provided by autologous PRP to enhance tissue healing. Therefore, we aimed to assess the frequency of the success of PRP therapy in the treatment of non-healing diabetic foot ulcers. Methods This quasi-experimental study, conducted in Lahore, Pakistan, from April 2021 to October 2022, enrolled 80 eligible individuals with non-responsive diabetic foot ulcers using a consecutive sampling technique. Inclusion criteria involved patients of both genders, aged 45-75 years, with unhealed diabetic foot ulcers, and exclusion criteria considered factors such as recurrent ulcers at the same site, smoking, and immunosuppressive or anticoagulant drug therapy. Baseline demographic details, ulcer measurements using a scale, and AutoCAD (Autodesk, Inc., San Francisco, California, United States)-assisted quantification of ulcer base were recorded. Autologous PRP injections were administered following strict aseptic protocols, with dressing changes and assessments performed at specified intervals over four weeks. Treatment success, defined as >90% healing after four weeks, was the primary outcome. Data analysis utilized IBM SPSS Statistics for Windows, Version 26.0 (Released 2019; IBM Corp., Armonk, New York, United States), employing post-stratification chi-square and t-tests where appropriate for significant differences. Results The mean age of the patients was 60.40 ± 9.72 years, the mean duration of diabetes was 9.48 ± 2.21 years, and the mean ulcer duration was 11.41 ± 1.63 months. The treatment success rate was 63.7%. Age, gender, and disease duration showed no significant impact on treatment success. However, patients with a normal BMI and shorter ulcer duration exhibited a significantly higher success rate (p <0.001 and p = 0.002, respectively). Conclusions This study reaffirms the efficacy of PRP in treating non-healing diabetic foot ulcers, aligning with previous research. Despite a slightly lower success rate compared to literature reports, PRP remains a promising agent for managing diabetic foot ulcers.

OBJECTIVE: The present study aims to investigate the specific protective effects and underlying mechanisms of Ganshuang granule (GSG) on dimethylnitrosamine (DMN)-induced hepatic fibrosis in rat models.
METHODS: Hepatic fibrosis was experimentally evoked in rats by DMN administration, and varying dosages of GSG were employed as an intervention. Hepatocellular damage was assessed by measuring serum levels of aminotransferase and bilirubin, accompanied by histopathological examinations of hepatic tissue. The hepatic concentrations of platelet-derived growth factor (PDGF) and transforming growth factor-β1 (TGF-β1) were quantitated via enzyme-linked immunosorbent assay (ELISA). The expression of α-smooth muscle actin (α-SMA) within hepatic tissue was evaluated using immunohistochemical techniques. The levels of hepatic interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and a spectrum of interleukins (IL-2, IL-4, IL-6, IL-10) were quantified by quantitative real-time PCR (qRT-PCR). Additionally, hepatic stellate cells (HSCs) were cultured in vitro and exposed to TNF-α in the presence of naringin, a principal component of GSG. The gene expression levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metallopeptidase-1 (MMP-1) in these cells were also quantified by qRT-PCR. Proliferative activity of HSCs was evaluated by the Cell Counting Kit-8 assay. Finally, alterations in Smad protein expression were analyzed through Western blotting.
RESULTS: Administration of GSG in rats with fibrosis resulted in reduced levels of serum aminotransferases and bilirubin, along with alleviation of histopathological liver injury. Furthermore, the fibrosis rats treated with GSG exhibited significant downregulation of hepatic TGF-β1, PDGF, and TNF-α levels. Additionally, GSG treatment led to increased mRNA levels of IFN-γ, IL-2, and IL-4, as well as decreased expression of α-SMA in the liver. Furthermore, treatment with naringin, a pivotal extract of GSG, resulted in elevated expression of MMP-1 and decreased levels of TIMP-1 in TNF-α-stimulated HSCs when compared to the control group. Additionally, naringin administration led to a reduction in Smad expression within the HSCs.
CONCLUSIONS: GSG has the potential to mitigate fibrosis induced by DMN in rat models through the regulation of inflammatory and fibrosis factors. Notably, naringin, the primary extract of GSG, may exert a pivotal role in modulating the TGF-β-Smad signaling pathway.

Airway remodelling in lung diseases can be treated by inhibiting excessive smooth muscle cell proliferation. Zedoarondiol (Zed) is a natural compound isolated from the Chinese herb Curcuma longa. The caveolin-1 (CAV-1) is widely expressed in lung cells and plays a key role in platelet-derived growth factor (PDGF) signalling and cell proliferation. This study aims to investigate the effect of Zed on human bronchial smooth muscle cell (HBSMC) proliferation and explore its potential molecular mechanisms. We assessed the effect of Zed on the proliferation of PDGF-stimulated HBSMCs and performed proteomic analysis to identify potential molecular targets and pathways. CAV1 siRNA was used to validate our findings in vitro. In PDGF-stimulated HBSMCs, Zed significantly inhibited excessive proliferation of HBSMCs. Proteomic analysis of zedoarondiol-treated HBSMCs revealed significant enrichment of differentially expressed proteins in cell proliferation-related pathways and biological processes. Zed inhibition of HBSMC proliferation was associated with upregulation of CAV1, regulation of the CAV-1/PDGF pathway and inhibition of MAPK and PI3K/AKT signalling pathway activation. Treatment of HBSMCs with CAV1 siRNA partly reversed the inhibitory effect of Zed on HBSMC proliferation. Thus, this study reveals that zedoarondiol potently inhibits HBSMC proliferation by upregulating CAV-1 expression, highlighting its potential value in airway remodelling and related diseases.

Achieving precise spatiotemporal control over the release of proangiogenic factors is crucial for vasculogenesis, the process of de novo blood vessel formation. Although various strategies have been explored, there is still a need to develop cell-laden biomaterials with finely controlled release of proangiogenic factors at specific locations and time points. We report on the developed of a near-infrared (NIR) light-responsive collagen hydrogel comprised of gold nanorods (GNRs)-conjugated liposomes containing proangiogenic growth factors (GFs). We demonstrated that this system enables on-demand dual delivery of GFs at specific sites and over selected time intervals. Liposomes were strategically formulated to encapsulate either platelet-derived growth factor (PDGF) or vascular endothelial growth factor (VEGF), each conjugated to gold nanorods (GNRs) with distinct geometries and surface plasmon resonances at 710 nm (GNR710) and 1064 nm (GNR1064), respectively. Using near infrared (NIR) irradiation and two-photon (2P) luminescence imaging, we successfully demonstrated the independent release of PDGF from GNR710 conjugated liposomes and VEGF from GNR1064-conjugated liposomes. Our imaging data revealed rapid release kinetics, with localized PDGF released in approximately 4 min and VEGF in just 1 and a half minutes following NIR laser irradiation. Importantly, we demonstrated that the release of each GF could be independently triggered using NIR irradiation with the other GF formulation remaining retained within the liposomes. This light-responsive collagen hydrogels holds promise for various applications in regenerative medicine where the establishment of a guided vascular network is essential for the survival and integration of engineered tissues. STATEMENT OF SIGNIFICANCE: In this study, we have developed a light-responsive system with gold nanorods (GNRs)-conjugated liposomes in a collagen hydrogel, enabling precise dual delivery of proangiogenic growth factors (GFs) at specific locations and timepoints. Liposomes, containing platelet-derived growth factor (PDGF) or vascular endothelial growth factor (VEGF), release independently under near- infrared irradiation. This approach allows external activation of desired GF release, ensuring high cell viability. Each GF can be triggered independently, retaining the other within the liposomes. Beyond its application in establishing functional vascular networks, this dual delivery system holds promise as a universal platform for delivering various combinations of two or more GFs.