-
Investigative Ophthalmology & Visual... Nov 2023The purpose of this study was to determine the role of nuclear factor kappa B (NF-κB) c-Rel during acute corneal transplant rejection and whether targeting c-Rel can...
PURPOSE
The purpose of this study was to determine the role of nuclear factor kappa B (NF-κB) c-Rel during acute corneal transplant rejection and whether targeting c-Rel can reduce corneal transplant rejection.
METHODS
Allogeneic corneal transplantation was performed in wild-type and c-Rel-deficient mice. Corneal graft survival rate, opacity, neovascularization, and edema were evaluated by slit-lamp microscopy. Adeno-associated virus 6 (AAV6) expressing c-Rel-specific small hairpin RNA (AAV6-shRel) and the small-molecule compound pentoxifylline (PTXF) were used to reduce c-Rel expression. Enzyme-linked immunosorbent assay was used to determine the expression of inflammatory cytokines. c-Rel expression was determined by quantitative RT-PCR and western blot. The effect of c-Rel inhibition on corneal transplant rejection was examined using a mouse model of acute allogeneic corneal transplantation. Tear production and corneal sensitivity were measured to determine the potential toxicity of AAV6-shRel and PTXF.
RESULTS
The expression of c-Rel and its inflammatory targets was increased in both mice and patients with corneal transplant rejection. Loss of c-Rel reduced corneal transplant rejection in mouse. Both AAV6-shRel and PTXF were able to downregulate the expression of c-Rel and its inflammatory targets in vitro. Treatment with AAV6-shRel or PTXF reduced corneal transplant rejection in mouse and downregulated the expression of inflammatory cytokines in peripheral blood mononuclear cells from patients with corneal transplant rejection. Treatment with AAV6-shRel or PTXF displayed no side effects on tear production or corneal sensitivity.
CONCLUSIONS
Increased expression of c-Rel is a risk factor for acute corneal transplant rejection, and targeting c-Rel can efficiently reduce corneal transplant rejection.
Topics: Humans; Animals; Mice; NF-kappa B; Leukocytes, Mononuclear; Cornea; Corneal Transplantation; Cytokines
PubMed: 37962530
DOI: 10.1167/iovs.64.14.16 -
Pharmaceuticals (Basel, Switzerland) Oct 2023The involvement of NK and other cytotoxic cells is considered the first defense line against cancer. However, a significant lack of information prevails on the possible...
The involvement of NK and other cytotoxic cells is considered the first defense line against cancer. However, a significant lack of information prevails on the possible roles played by factors considered characteristic of primitive cells, such as c-kit and Sca-1, in activating these cells, particularly in melanoma models subjected to treatments with substances under investigation, such as the case of norcantharidin. In this study, B16F1 murine melanoma cells were used to induce tumors in DBA/2 mice, estimating the proportions of NK and iNKT cells; the presence of activation (CD107a+) and primitive/activation (c-kit+/Lya6A+) markers and some tumor parameters, such as the presence of mitotic bodies, nuclear factor area, NK and iNKT cell infiltration in the tumor, infiltrated tumor area, and infiltrating lymphocyte count at 10x and 40x in specimens treated with pentoxifylline, norcantharidin, and the combination of both drugs. Possible correlations were estimated with Pearson's correlation analysis. It should be noted that, despite having demonstrated multiple correlations, immaturity/activation markers were related to these cells' activation. At the tumor site, iNKT cells are the ones that exert the cytotoxic potential on tumor cells, but they are confined to specific sites in the tumor. Due to the higher number of interactions of natural killer cells with tumor cells, it is concluded that the most effective treatment was PTX at 60 mg/kg + NCTD at 0.75 mg/kg.
PubMed: 37895943
DOI: 10.3390/ph16101472 -
Biomedicines Oct 2023Chronic kidney disease (CKD) is a progressive and incurable disease that impairs kidney function. Its prevalence is estimated to affect up to 800 million individuals... (Review)
Review
Chronic kidney disease (CKD) is a progressive and incurable disease that impairs kidney function. Its prevalence is estimated to affect up to 800 million individuals within the general population, and patients with diabetes and hypertension are particularly at risk. This disorder disrupts the physiological mechanisms of the body, including water and electrolyte balance, blood pressure regulation, the excretion of toxins, and vitamin D metabolism. Consequently, patients are exposed to risks such as hyperkalemia, hyperphosphatemia, metabolic acidosis, and blood pressure abnormalities. These risks can be reduced by implementing appropriate diagnostic methods, followed by non-pharmacological (such as physical activity, dietary, and lifestyle adjustment) and pharmacological strategies after diagnosis. Selecting the appropriate diet and suitable pharmacological treatment is imperative in maintaining kidney function as long as possible. Drugs such as finerenone, canakinumab, and pentoxifylline hold promise for improved outcomes among CKD patients. When these interventions prove insufficient, renal replacement therapy becomes essential. This is particularly critical in preserving residual renal function while awaiting renal transplantation or for patients deemed ineligible for such a procedure. The aim of this study is to present the current state of knowledge and recent advances, providing novel insights into the treatment of chronic kidney disease.
PubMed: 37893119
DOI: 10.3390/biomedicines11102746 -
Advances in Respiratory Medicine Oct 2023Cardiogenic pulmonary edema (CPE) is characterized by the development of acute respiratory failure associated with the accumulation of fluid in the lung's alveolar... (Review)
Review
Cardiogenic pulmonary edema (CPE) is characterized by the development of acute respiratory failure associated with the accumulation of fluid in the lung's alveolar spaces due to an elevated cardiac filling pressure. All cardiac diseases, characterized by an increasing pressure in the left side of the heart, can cause CPE. High capillary pressure for an extended period can also cause barrier disruption, which implies increased permeability and fluid transfer into the alveoli, leading to edema and atelectasis. The breakdown of the alveolar-epithelial barrier is a consequence of multiple factors that include dysregulated inflammation, intense leukocyte infiltration, activation of procoagulant processes, cell death, and mechanical stretch. Reactive oxygen and nitrogen species (RONS) can modify or damage ion channels, such as epithelial sodium channels, which alters fluid balance. Some studies claim that these patients may have higher levels of surfactant protein B in the bloodstream. The correct approach to patients with CPE should include a detailed medical history and a physical examination to evaluate signs and symptoms of CPE as well as potential causes. Second-level diagnostic tests, such as pulmonary ultrasound, natriuretic peptide level, chest radiograph, and echocardiogram, should occur in the meantime. The identification of the specific CPE phenotype is essential to set the most appropriate therapy for these patients. Non-invasive ventilation (NIV) should be considered early in the treatment of this disease. Diuretics and vasodilators are used for pulmonary congestion. Hypoperfusion requires treatment with inotropes and occasionally vasopressors. Patients with persistent symptoms and diuretic resistance might benefit from additional approaches (i.e., beta-agonists and pentoxifylline). This paper reviews the pathophysiology, clinical presentation, and management of CPE.
Topics: Humans; Pulmonary Edema; Lung; Heart Failure; Oxygen; Vasodilator Agents; Emergency Medicine
PubMed: 37887077
DOI: 10.3390/arm91050034 -
Annals of Dermatology May 2023Livedoid vasculopathy (LV) is a chronic coagulation disorder characterized by recurrent, painful ulcers on the lower extremities. Methylene tetrahydrofolate reductase ()...
Livedoid vasculopathy (LV) is a chronic coagulation disorder characterized by recurrent, painful ulcers on the lower extremities. Methylene tetrahydrofolate reductase () gene polymorphism is associated with coagulopathy. Therapeutic options usually include anti-inflammatory or immunosuppressive agents. However, the condition is still highly challenging to manage and no consensus over the first-line treatment for LV exists. Furthermore, when LV is accompanied with gene polymorphism, clinical presentations could be more severe and resistant to treatment. We report a case of refractory LV accompanied by gene polymorphism, which was successfully treated with hyperbaric oxygen therapy (HBOT). A 63-year-old female patient presented with multiple painful ulcers, atrophie blanches, and retiform purpura on both lower legs and feet. Histopathologic findings were compatible with LV. LV was diagnosed based on these clinicopathological findings. Following the diagnosis, we treated the patient with pentoxifylline, aspirin, systemic corticosteroid, antihistamine, and antibiotics. In spite of six-month treatment, the skin lesions did not improve; hence, HBOT was performed. It was performed at 2.0 absolute atmosphere for 120 minutes each time, three times a week. After 4 sessions, the ulcers began to heal and after 13 sessions, the skin lesions almost healed. During the eight-month follow-up period, the skin ulcers did not recur and the symptoms remained stable. Additionally, it was confirmed that she had gene polymorphism after a genetic test. In conclusion, we wish to provide evidence regarding the effectiveness of HBOT and suggest that HBOT might be a considerable treatment option in refractory LV.
PubMed: 37853867
DOI: 10.5021/ad.20.330 -
Cureus Sep 2023Raynaud's phenomenon (RP) is a vasospastic disorder characterized by an exaggerated vasoconstrictive response to cold or emotional stress. It can be classified as...
Raynaud's phenomenon (RP) is a vasospastic disorder characterized by an exaggerated vasoconstrictive response to cold or emotional stress. It can be classified as primary (PRP) or secondary (SRP) depending on its association with an underlying condition. We present a case of a young female with severe RP, with trophic changes and abnormal capillaroscopy. After a detailed investigation, a diagnosis of secondary RP due to solvent exposure was made. The patient was treated with calcium channel blocker in low doses, due to hypotension, without improvement of symptoms. Vitamin C and pentoxifylline were added with an unsatisfactory response. Given the progressive worsening of RP and the appearance of trophic lesions, the patient's treatment was reviewed, and continuous intravenous iloprost infusion through an elastomeric pump was started. This resulted in significant symptom improvement and normalization on the capillaroscopic examination.
PubMed: 37829986
DOI: 10.7759/cureus.45004 -
BMC Oral Health Oct 2023The aim of this review is to evaluate the different medicinal interventions available for the management of oral submucous fibrosis (OSF). (Review)
Review
OBJECTIVE
The aim of this review is to evaluate the different medicinal interventions available for the management of oral submucous fibrosis (OSF).
MATERIALS AND METHODS
We conducted a comprehensive electronic search on PubMed, Web of Science, and Cochrane Library databases for articles related to OSF patients treated with medications from December 2011 to September 2022. GRADE system was used to evaluate the evidence quality. The reporting of the systematic review is in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The main outcomes were the improvement of maximum mouth opening, burning sensation, cheek flexibility, and tongue protrusion.
RESULTS
Twenty-nine randomized controlled trials (RCTs), five clinical trials (CCTs) were included, and the use of drugs for OSF treatment were evaluated. Drugs like steroids, hyaluronidase, pentoxifylline, lycopene, curcumin, dpirulina, aloe vera, omega3, oxitard, allicin, colchicine have been used. It was found that drugs with evidence high quality were salvia miltiorrhiza combined with triamcinolone acetonide, lycopene, pentoxifylline, curcumin, and aloe vera, and those with evidence moderate quality were allicin, colchicine, omega 3, and oxitard.
CONCLUSION
Based on the results of our comprehensive analysis, for long-term treatment, we found lycopene with low side effects, whereas for relieving the symptoms of severe burning sensation, aloe vera is the most effective. Although the recent review has made some progress, drug therapy for OSF remains unclear, and more high-quality RCTs are needed to identify better treatments for OSF.
Topics: Humans; Oral Submucous Fibrosis; Lycopene; Curcumin; Pentoxifylline; Colchicine
PubMed: 37828490
DOI: 10.1186/s12903-023-03488-9 -
Communications Chemistry Oct 2023Hydrogen transfer biocatalysts to prepare optically pure alcohols are in need, especially when it comes to sterically demanding ketones, whereof the bioreduced products...
Hydrogen transfer biocatalysts to prepare optically pure alcohols are in need, especially when it comes to sterically demanding ketones, whereof the bioreduced products are either essential precursors of pharmaceutically relevant compounds or constitute APIs themselves. In this study, we report on the biocatalytic potential of an anti-Prelog (R)-specific Lactobacillus kefir ADH variant (Lk-ADH-E145F-F147L-Y190C, named Lk-ADH Prince) employed as E. coli/ADH whole-cell biocatalyst and its characterization for stereoselective reduction of prochiral carbonyl substrates. Key enzymatic reaction parameters, including the reaction medium, evaluation of cofactor-dependency, organic co-solvent tolerance, and substrate loading, were determined employing the drug pentoxifylline as a model prochiral ketone. Furthermore, to tap the substrate scope of Lk-ADH Prince in hydrogen transfer reactions, a broad range of 34 carbonylic derivatives was screened. Our data demonstrate that E. coli/Lk-ADH Prince exhibits activity toward a variety of structurally different ketones, furnishing optically active alcohol products at the high conversion of 65-99.9% and in moderate-to-high isolated yields (38-91%) with excellent anti-Prelog (R)-stereoselectivity (up to >99% ee) at substrate concentrations up to 100 mM.
PubMed: 37828252
DOI: 10.1038/s42004-023-01013-1 -
Neurotoxicity Research Dec 2023Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by behavioral, cognitive, and progressive memory impairments. Extensive neuronal...
Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by behavioral, cognitive, and progressive memory impairments. Extensive neuronal loss, extracellular accumulation of insoluble senile amyloid-β (Aβ) plaques, and intracellular neurofibrillary tangles (NFTs) are the major pathological features. The present study aimed to investigate the therapeutic effect of donepezil (DON) and pentoxifylline (PTX) in combination to combat the neurodegenerative disorders (experimental AD) induced by CuSO intake in experimental rats. Thirty adult male Wistar rats (140-160 g) were used in this study. AD was first induced in rats by CuSO supplement to drinking water (10 mg/L) for 14 weeks. The AD group received no further treatment. Oral treatment with DON (10 mg/kg/day), PTX (100 mg/kg/day), or DON + PTX for the other three groups was started from the 10th week of CuSO intake for 4 weeks. Cortex markers like acetylcholine (ACh), acetylcholinesterase (AChE), total antioxidant capacity (TAC), and malondialdehyde (MDA) and hippocampus markers like β-amyloid precursor protein cleaving enzyme 1 (BACE1), phosphorylated Tau (p-tau), Clusterin (CLU), tumor necrosis factor-α (TNF-α), caspase-9 (CAS-9), Bax, and Bcl-2 were measured. The histopathology studies were done by using hematoxylin and eosin and Congo red stains as well as immunohistochemistry for neurofilament. CuSO induced adverse histological and biochemical changes. The histological injury in the hippocampus was inhibited following the administration of the DON and PTX. The brain tissue levels of AChE, MDA, BACE1, p-tau, CLU, CAS-9, Bax, and TNF-α were significantly increased, while brain tissue levels of ACh, TAC, and Bcl-2 were significantly decreased in CuSO-treated rats as compared with the untreated control group. The effects induced by either DON or PTX on most studied parameters were comparable. Combined treatment of DON and PTX induced remarkable results compared with their individual use. However, more clinical and preclinical studies are still required to further confirm and prove the long-term efficacy of such combination.
Topics: Rats; Male; Animals; Alzheimer Disease; Donepezil; Amyloid Precursor Protein Secretases; Copper Sulfate; Pentoxifylline; bcl-2-Associated X Protein; Acetylcholinesterase; Tumor Necrosis Factor-alpha; Rats, Wistar; Aspartic Acid Endopeptidases; Amyloid beta-Peptides; Antioxidants; Proto-Oncogene Proteins c-bcl-2; Disease Models, Animal
PubMed: 37821782
DOI: 10.1007/s12640-023-00672-1 -
SAGE Open Medicine 2023The objective of this study was to assess the effectiveness of triamcinolone in combination with pentoxifylline and vitamin E in the treatment of patients with level two...
OBJECTIVE
The objective of this study was to assess the effectiveness of triamcinolone in combination with pentoxifylline and vitamin E in the treatment of patients with level two and three oral submucous fibrosis.
METHODS
The study aimed to compare the efficacy of corticosteroid injections (triamcinolone) versus pentoxifylline and vitamin E in the therapy of patients with stage two and three oral submucous fibrosis. A total of 42 participants with indications and features of oral submucous fibrosis were enrolled between January 2020 and September 2021. The patients' age and mouth opening were evaluated, and descriptive statistics and paired -test were used for analytical investigation.
RESULTS
The study showed a statistically significant improvement in both treatment groups ( = 0.001) concerning pre- and post-treatment deviations. However, when comparing the standard differences in treatment outcomes between the two study groups, only mouth opening exhibited a statistically significant difference ( = 0.001).
CONCLUSIONS
The findings indicate that a treatment regimen combining pentoxifylline and triamcinolone can significantly alleviate oral submucous fibrosis symptoms, including mouth opening, pain, and flaring agitation, thereby enhancing the affected individual's quality of life.
PubMed: 37786898
DOI: 10.1177/20503121231200757