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Medical Oncology (Northwood, London,... May 2023Immunotherapy utilizing tumor-infiltrating lymphocytes (TILs) is a promising approach for cancer treatment. Pentoxifylline (PTXF), a xanthine derivative, exhibits...
Immunotherapy utilizing tumor-infiltrating lymphocytes (TILs) is a promising approach for cancer treatment. Pentoxifylline (PTXF), a xanthine derivative, exhibits antitumor properties. This study aimed to investigate the impact of PTXF on the phenotype and function of TILs and splenocytes in a triple-negative breast cancer (TNBC) mouse model. TNBC was subcutaneously induced in BALB/c mice, followed by nine intraperitoneal injections of 100 mg/kg PTXF. TILs were then isolated by enzymatic digestion of tumors and cocultured with 4T1 cells. The proportion of regulatory T cells (Tregs) and cytotoxic T cells in TILs and splenocytes was assessed using flow cytometry. Transforming growth factor (TGF)-β and interferon (IFN)-γ production in TILs and splenocytes cultures was measured by ELISA. Relative expression of t-bet, foxp3, gata-3, and ror-γt in TILs and splenocytes was evaluated using real-time PCR. Tumor growth in PTXF-treated mice was significantly lower than that in the controls (P < 0.01). The frequency of regulatory and cytotoxic TILs in PTXF-treated mice was approximately half (P < 0.01) and twice (P < 0.05) that of the control group, respectively. The level of TGF-β and IFN-γ in the supernatant of PTXF-treated TILs was decreased and increased, respectively (P < 0.05). The relative expression of t-bet and foxp3 in the PTXF-treated mice compared to controls was increased and decreased, respectively (P < 0.05). Changes in the immune cell balance were less significant in the spleen compared to the TILs. PTXF treatment could limit the tumor growth and modify the regulatory-to-cytotoxic TILs ratio, as well as cytokine balance of TILs, in favor of antitumor responses.
Topics: Humans; Mice; Animals; Lymphocytes, Tumor-Infiltrating; Pentoxifylline; Triple Negative Breast Neoplasms; T-Lymphocytes, Cytotoxic; Antineoplastic Agents; Forkhead Transcription Factors
PubMed: 37149505
DOI: 10.1007/s12032-023-02034-5 -
Pharmaceutics Mar 2023This study aimed to develop films of chitosan (CSF) associated with pentoxifylline (PTX) for healing cutaneous wounds. These films were prepared at two concentrations,...
This study aimed to develop films of chitosan (CSF) associated with pentoxifylline (PTX) for healing cutaneous wounds. These films were prepared at two concentrations, F1 (2.0 mg/mL) and F2 (4.0 mg/mL), and the interactions between the materials, structural characteristics, in vitro release, and morphometric aspects of skin wounds in vivo were evaluated. The formation of the CSF film with acetic acid modifies the polymeric structure, and the PTX demonstrates interaction with the CSF, in a semi-crystalline structure, for all concentrations. The release for all films was proportional to the concentration, with two phases: a fast one of ≤2 h and a slow one of >2 h, releasing 82.72 and 88.46% of the drug after 72 h, being governed by the Fickian diffusion mechanism. The wounds of the mice demonstrate a reduction of up to 60% in the area on day 2 for F2 when compared to CSF, F1, and positive control, and this characteristic of faster healing speed for F2 continues until the ninth day with wound reduction of 85%, 82%, and 90% for CSF, F1, and F2, respectively. Therefore, the combination of CSF and PTX is effective in their formation and incorporation, demonstrating that a higher concentration of PTX accelerates skin-wound reduction.
PubMed: 37111607
DOI: 10.3390/pharmaceutics15041122 -
Pharmaceuticals (Basel, Switzerland) Apr 2023COVID-19 is a fatal, fast-spreading pandemic, and numerous attempts are being made around the world to understand and manage the disease. COVID-19 patients may develop a...
COVID-19 is a fatal, fast-spreading pandemic, and numerous attempts are being made around the world to understand and manage the disease. COVID-19 patients may develop a cytokine-release syndrome, which causes serious respiratory diseases and, in many cases, death. The study examined the feasibility of employing legally available anti-inflammatory pentoxifylline (PTX), a low toxicity and cost medication, to mitigate the hyper-inflammation caused by COVID-19. Thirty adult patients who tested positive for SARS-CoV2 were hospitalized owing to the cytokine storm syndrome. They were given 400 mg of pentoxifylline orally TID according to the standard COVID-19 protocol of the Egyptian Ministry of Health. Besides this, a group of thirty-eight hospitalized COVID-19 patients who received the standard COVID-19 protocol was included in the study as a control group. The outcomes included laboratory test parameters, clinical improvements, and number of deaths in both groups. After receiving PTX, all patients showed a significant improvement in C reactive protein (CRP), and interleukin-6 (IL-6) levels at < 0.01 and = 0.004, respectively, while there was an increase in total leukocyte count (TLC) and neutrophil-to-leucocyte ratio (NLR) at < 0.01 compared to their baseline levels. The D-dimer level showed a significant increase in the treatment group at < 0.01, while showing no statistically significant difference in the control group. The median initial ALT (42 U/L) in the treatment group showed a decrease compared to the control group (51 U/L). No statistical significance was reported regarding clinical improvement, length of stay, and death percentages between the two groups. Our results showed no significant improvement of PTX over controls in clinical outcomes of hospitalized COVID-19 patients. Nevertheless, PTX displayed a positive effect on certain inflammatory biomarkers.
PubMed: 37111389
DOI: 10.3390/ph16040631 -
Antibiotics (Basel, Switzerland) Mar 2023Experimental reports have demonstrated that florfenicol (FFC) exerts potent anti-inflammatory effects, improving survival in a murine endotoxemia model. Considering the...
BACKGROUND
Experimental reports have demonstrated that florfenicol (FFC) exerts potent anti-inflammatory effects, improving survival in a murine endotoxemia model. Considering the anti-inflammatory and immunomodulatory properties of pentoxifylline (PTX) as an adjuvant to enhance the efficacy of antibiotics, the anti-inflammatory effects of the interaction FFC/PTX over the Lipopolysaccharide (LPS)-induced acute inflammatory response was evaluated in rabbits.
METHODS
Twenty-five clinically healthy New Zealand rabbits (3.8 ± 0.2 kg body weight: bw), were distributed into five experimental groups. Group 1 (control): treated with 1 mL/4 kg bw of 0.9% saline solution (SS) intravenously (IV). Group 2 (LPS): treated with an IV dose of 5 µg/kg of LPS. Group 3 (pentoxifylline (PTX) + LPS): treated with an oral dose of 30 mg/kg PTX, followed by an IV dose of 5 µg/kg of LPS 45 min after PTX. Group 4 (Florfenicol (FFC) + LPS): treated with an IM dose of 20 mg/kg of FFC, followed by an IV dose of 5 µg/kg of LPS 45 min after FFC administration. Group 5 (PTX + FFC + LPS): treated with an oral dose of 30 mg/kg of PTX, followed by an IM dose of 20 mg/kg of FFC, and, 45 min after an IV dose of 5 µg/kg of LPS was administered. The anti-inflammatory response was evaluated through changes in plasma levels of interleukins (TNF-α, IL-1β and IL-6), C-reactive protein (CRP), and body temperature.
RESULTS
It has been shown that each drug produced a partial inhibition over the LPS-induced increase in TNF-α, IL-1β, and CRP. When both drugs were co-administered, a synergistic inhibitory effect on the IL-1β and CRP plasma concentrations was observed, associated with a synergic antipyretic effect. However, the co-administration of PTX/FFC failed to modify the LPS-induced increase in the TNF-α plasma concentrations.
CONCLUSIONS
We concluded that the combination of FFC and PTX in our LPS sepsis models demonstrates immunomodulatory effects. An apparent synergistic effect was observed for the IL-1β inhibition, which peaks at three hours and then decreases. At the same time, each drug alone was superior in reducing TNF-α levels, while the combination was inferior. However, the peak of TNF-α in this sepsis model was at 12 h. Therefore, in rabbits plasma IL-1β and TNF-α could be regulated independently, thus, further research is needed to explore the effects of this combination over a more prolonged period.
PubMed: 37107001
DOI: 10.3390/antibiotics12040639 -
Scientific Reports Apr 2023To investigate the effect of pentoxifylline (PTX) on Chlorine (Cl)-induced acute lung injury (ALI) by single-cell RNA sequencing (scRNA-seq). Female BALB/c mice were...
To investigate the effect of pentoxifylline (PTX) on Chlorine (Cl)-induced acute lung injury (ALI) by single-cell RNA sequencing (scRNA-seq). Female BALB/c mice were exposed to Cl at 400 ppm for 15 min. H&E staining was used to observe the degree of lung injury. scRNA-seq was conducted to analysis of normal and Cl-exposed mice lung tissues. Immunofluorescence was used to observe genes of interest. Thirty-two mice were randomly divided into four groups: Control, Cl, Cl+Fer-1, Cl+PTX. TEM, WB and ELISA were used to detect ferroptosis-related indicators. The 5, 8, 10, 12, 16, 20 clusters were epithelial cells and 4, 15, 18, 19, 21 clusters were endothelial cells. Pseudo-time analysis revealed the differentiation trajectory of epithelial cells and key regulatory genes (Gclc, Bpifa1, Dnah5 and Dnah9) during the process of injury. Cell-cell communication analysis identified several important receptor-ligand complexes (Nrp1-Vegfa, Nrp2-Vegfa, Flt1-Vegfa and Flt4-Vegfa). Ferroptosis were found up-regulated in epithelial and endothelial cells by GSVA analysis. Highly expressed genes to which closely related ferroptosis were found by SCENIC analysis. PTX could significantly decrease the levels of MDA and abnormal high expression of solute carrier family 7 member 11 (SLC7A11, the key transporter of cystine) as well as increase the expression of GSH/GSSG and glutathione peroxidase 4 (GPX4) (p < 0.05). This study revealed novel molecular features of Cl-induced ALI. PTX may be a potential specific drug by inhibiting the process of ferroptosis in epithelial and endothelial cells.
Topics: Female; Animals; Mice; Chlorine; Ferroptosis; Pentoxifylline; Endothelial Cells; Transcriptome; Acute Lung Injury; Glycoproteins; Phosphoproteins
PubMed: 37100790
DOI: 10.1038/s41598-023-32093-7 -
Asian Journal of Andrology Apr 2023Phosphodiesterase (PDE) inhibitors can improve sperm motility in patients with asthenozoospermia. However, the most commonly reported nonselective PDE inhibitor...
Phosphodiesterase (PDE) inhibitors can improve sperm motility in patients with asthenozoospermia. However, the most commonly reported nonselective PDE inhibitor pentoxifylline and PDE5 inhibitor sildenafil have the disadvantages of requiring a high concentration and destroying sperm integrity. We examined the PDE10A inhibitor PF-2545920 to compare its ability to promote sperm motility with that of pentoxifylline and sildenafil. After seminal plasma was discarded, several semen samples were subjected to four treatments (control, PF-2545920, pentoxifylline, and sildenafil) to evaluate their ability to affect motility, viability, and spontaneous acrosome reactions. Intracellular calcium and adenosine triphosphate (ATP), mitochondrial membrane potential, and penetration through viscous medium were assessed by flow cytometry, luciferase, and hyaluronic acid after treatment with PF-2545920. Statistical analyses were performed using the analysis of variance statistical test. PF-2545920 elevated the percentage of motile spermatozoa compared to the control, pentoxifylline, and sildenafil groups at 10 µmol l -1 ( P < 0.01). It is less toxic to GC-2spd mouse spermatocytes cells and spermatozoa and causes fewer spontaneous acrosomal reactions ( P < 0.05). PF-2545920 also increased mitochondrial membrane potential ( P < 0.001) and altered intracellular calcium ( P < 0.05) in a dose-dependent manner, including increasing sperm hyaluronic acid penetrating ability ( P < 0.05). Therefore, PF-2545920 might be an excellent choice for stimulating the sperm motility.
PubMed: 37026191
DOI: 10.4103/aja2022117 -
SAGE Open Medical Case Reports 2023A 71-year-old woman presented with a persistent, intensely pruritic cutaneous eruption localized on the palmoplantar regions, lips and palate. The histological findings...
A 71-year-old woman presented with a persistent, intensely pruritic cutaneous eruption localized on the palmoplantar regions, lips and palate. The histological findings allowed to make the diagnosis of recurrent cutaneous eosinophilic vasculitis, a very rare cutaneous vasculitis characterized clinically by multiple erythematous or purpuric erythematous papules or plaques or angioedema with a relapsing course in the absence of systemic involvement and histologically by a necrotizing vasculitis of the dermal small vessels with a dominant eosinophilic infiltration. The patient was treated with oral methylprednisolone and pentoxifylline which led to a rapid resolution of the cutaneous lesions.
PubMed: 37009553
DOI: 10.1177/2050313X231163636 -
PLoS Neglected Tropical Diseases Mar 2023Chronic Chagas cardiomyopathy (CCC) is one of the leading causes of morbidity and mortality due to cardiovascular disorders in endemic areas of Chagas disease (CD), a...
Chronic Chagas cardiomyopathy (CCC) is one of the leading causes of morbidity and mortality due to cardiovascular disorders in endemic areas of Chagas disease (CD), a neglected tropical illness caused by the protozoan parasite Trypanosoma cruzi. CCC is characterized by parasite persistence and inflammatory response in the heart tissue, which occur parallel to microRNA (miRNA) alterations. Here, we investigated the miRNA transcriptome profiling in the cardiac tissue of chronically T. cruzi-infected mice treated with a suboptimal dose of benznidazole (Bz), the immunomodulator pentoxifylline alone (PTX), or the combination of both (Bz+PTX), following the CCC onset. At 150 days post-infection, Bz, PTX, and Bz+PTX treatment regimens improved electrocardiographic alterations, reducing the percentage of mice afflicted by sinus arrhythmia and second-degree atrioventricular block (AVB2) when compared with the vehicle-treated animals. miRNA Transcriptome profiling revealed considerable changes in the differential expression of miRNAs in the Bz and Bz+PTX treatment groups compared with the control (infected, vehicle-treated) group. The latter showed pathways related to organismal abnormalities, cellular development, skeletal muscle development, cardiac enlargement, and fibrosis, likely associated with CCC. Bz-Treated mice exhibited 68 differentially expressed miRNAs related to signaling pathways like cell cycle, cell death and survival, tissue morphology, and connective tissue function. Finally, the Bz+PTX-treated group revealed 58 differentially expressed miRNAs associated with key signaling pathways related to cellular growth and proliferation, tissue development, cardiac fibrosis, damage, and necrosis/cell death. The T. cruzi-induced upregulation of miR-146b-5p, previously shown in acutely infected mice and in vitro T. cruzi-infected cardiomyocytes, was reversed upon Bz and Bz+PTX treatment regimens when further experimentally validated. Our results further our understanding of molecular pathways related to CCC progression and evaluation of treatment response. Moreover, the differentially expressed miRNAs may serve as drug targets, associated molecular therapy, or biomarkers of treatment outcomes.
Topics: Animals; Mice; Chagas Cardiomyopathy; Pentoxifylline; Transcriptome; Disease Models, Animal; Trypanosoma cruzi; Chagas Disease; Nitroimidazoles; MicroRNAs; Fibrosis; Gene Expression Profiling; Trypanocidal Agents
PubMed: 36972298
DOI: 10.1371/journal.pntd.0011223 -
Journal of Oncology 2023Osteoradionecrosis (ORN) is described as a disease with exposed, nonviable bone that fails to heal spontaneously or by means of conservative treatment after radiotherapy... (Review)
Review
Osteoradionecrosis (ORN) is described as a disease with exposed, nonviable bone that fails to heal spontaneously or by means of conservative treatment after radiotherapy in at least 3 months. Though traditional theories in the early stage including hypoxic-hypocellular-hypovascular and fibro-atrophic in addition to new findings such as ferroptosis were put forward to explain the mechanisms of the osteoradionecrosis, the etiology of ORN is still unclear. With the high rate of occurrence in the head and neck area, especially in the mandible, this disease can disrupt the shape and function of the irradiated area, leading to a clinical presentation ranging from stable small areas of asymptomatic exposed bone to severe progressive necrosis. In severe cases, patients may experience pain, xerostomia, dysphagia, facial fistulas, and even a jaw defect. Consequently, sequence therapy and sometimes extensive surgery and reconstructions are needed to manage these sequelae. Treatment options may include pain medication, antibiotics, the removal of sequesters, hyperbaric oxygen therapy, segmental resection of the mandible, and free flap reconstruction. Microanastomosed free-flaps are considered to be promising choice for ORN reconstruction in recent researches, and new methods including three-dimensional (3-D) printing, pentoxifylline, and amifostine are used nowadays in trying increase the success rates and improve quality of the reconstruction. This review summarizes the main research progress in osteoradionecrosis and reconstruction treatment of osteoradionecrosis with mandibular defect.
PubMed: 36968640
DOI: 10.1155/2023/1440889 -
Journal of Clinical and Experimental... 2023Severe alcoholic hepatitis (SAH) is a grave condition, and the presence of acute kidney injury (AKI) further jeopardizes patient survival. However, the impact of AKI on...
BACKGROUND & AIMS
Severe alcoholic hepatitis (SAH) is a grave condition, and the presence of acute kidney injury (AKI) further jeopardizes patient survival. However, the impact of AKI on survival in SAH has not been assessed from this region of Asia.
MATERIALS AND METHODS
This study was conducted on consecutive alcohol-associated liver disease (ALD) patients hospitalized in Gastroenterology Department, SCB Medical College, Cuttack, India, between October 2016 and December 2018. On diagnosis of SAH (mDF score ≥32), demographic, clinical, and laboratory parameters were recorded, and survival was compared between patients with and without AKI (AKIN criteria). In addition, survival was compared among SAH patients defined by other criteria and prognostic models in the presence and absence of AKI.
RESULTS
309 (70.71%) of ALD patients had SAH, and 201 (65%) of them had AKI. SAH patients with AKI had higher total leucocyte count, total bilirubin, serum creatinine, serum urea, INR, MELD (UNOS), MELD (Na+), CTP score, mDF score, Glasgow score, ABIC score, and increased prevalence of acute on chronic liver failure (ACLF) as per EASL-CLIF Consortium criteria ( < 0.001). Further, they had prolonged hospital stay, and increased death during hospitalization, at 28 days as well as 90 days ( < 0.001). Significant differences in survival were also seen in SAH (as per MELD, ABIC, and GAHS criteria) patients above the marked cut offs in respect to AKI.
CONCLUSIONS
Over two-thirds of ALD patients had SAH, and about two-thirds had AKI. Patients with SAH and AKI had an increased prevalence of ACLF, longer hospital stay, and increased mortality during hospitalization at 28 days and 90 days.
LAY SUMMARY
SAH is a critical condition, and the presence of AKI negatively affects their survival. Hence, early identification of SAH and AKI, as well as early initiation of treatment, is crucial for better survival. Our study from the coastal part of eastern India is the first to demonstrate the prevalence of SAH among patients with ALD along with the prevalence of AKI among SAH patients in this region. This knowledge will be helpful in managing these patients from this region of world.
PubMed: 36950492
DOI: 10.1016/j.jceh.2022.11.008