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Long non-coding RNA (lncRNA) H19 has gained significant recognition as a pivotal contributor to the initiation and advancement of gynecologic cancers, encompassing ovarian, endometrial, cervical, and breast cancers. H19 exhibits a complex array of mechanisms, demonstrating dualistic effects on tumorigenesis as it can function as both an oncogene and a tumor suppressor, contingent upon the specific context and type of cancer being investigated. In ovarian cancer, H19 promotes tumor growth, metastasis, and chemoresistance through modulation of key signaling pathways and interaction with microRNAs. Conversely, in endometrial cancer, H19 acts as a tumor suppressor by inhibiting proliferation, inducing apoptosis, and regulating epithelial-mesenchymal transition. Additionally, H19 has been implicated in cervical and breast cancers, where it influences cell proliferation, invasion, and immune evasion. Moreover, H19 has potential as a diagnostic and prognostic biomarker for gynecologic cancers, with its expression levels correlating with clinical parameters and patient outcomes. Understanding the functional roles of H19 in gynecologic cancers is crucial for the development of targeted therapeutic strategies and personalized treatment approaches. Further investigation into the intricate molecular mechanisms underlying H19's involvement in gynecologic malignancies is warranted to fully unravel its therapeutic potential and clinical implications. This review aims to elucidate the functional roles of H19 in various gynecologic malignancies.
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Neoplasias de la Mama , Neoplasias de los Genitales Femeninos , MicroARNs , ARN Largo no Codificante , Femenino , Humanos , Neoplasias de la Mama/genética , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias de los Genitales Femeninos/genética , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND: One of the major complications associated with random-pattern skin flaps is distal necrosis. Cannabidiol (CBD) has recently gained much attention as a therapeutic anti-inflammatory agent. We aimed to evaluate the efficacy of CBD on the random-pattern skin flap survival (SFS) in rats and to explore the possible involvement of cannabinoid type-2 (CB2) receptors. METHODS: In this controlled experimental study, we randomly divided male Wistar rats into seven study groups (six rats each). We performed a random-pattern skin flap model in each rat following pretreatment with vehicle (control) or multiple doses of CBD (0.3, 1, 5, or 10 mg/kg). In a separate group, we injected SR144528 (2 mg/kg), a high affinity and selective CB2 inverse agonist, before the most effective dose of CBD (1 mg/kg). A sham nontreated and nonoperated group was also included. Seven days after surgeries, the percentage of necrotic area (PNA) was calculated. Histopathological microscopy, CB2 expression level, and interleukin (IL)-1ß and tumor necrosis factor (TNF)-α concentrations were also investigated in the flap tissue samples. RESULTS: A PNA of 72.7 ± 7.5 (95% confidence interval [CI]: 64.8-80.6) was captured in the control group. Following treatment with CBD 0.3, 1, 5, and 10 mg/kg, a dose-dependent effect was observed with PNAs of 51.0 ± 10.0 (95% CI: 40.5-61.5; p <0.05), 15.4 ± 5.8 (95% CI: 9.3-21.5; p <0.001), 37.1 ± 10.2 (95% CI: 26.3-47.8; p <0.001), and 46.4 ± 14.0 (95% CI: 31.7-61.1; p <0.001), respectively. Histopathologically, tissues enhanced significantly. Besides, CB2 expression surged remarkably, IL-1ß and TNF-α concentrations decreased considerably after treatment with CBD of 1 mg/kg compared with the control (p <0.05 and <0.001, respectively). Administering SR144528 reversed the favorable effects of CBD of 1 mg/kg, both macroscopically and microscopically. CONCLUSION: Pretreatment with CBD of 1 mg/kg improved SFS considerably in rats and exerted desirable anti-inflammatory effects which were possibly mediated by CB2 receptors.
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Cannabidiol , Ratas , Masculino , Animales , Cannabidiol/farmacología , Receptores de Cannabinoides , Ratas Wistar , Agonismo Inverso de DrogasRESUMEN
BACKGROUND/AIMS: Colitis is a main presentation of inflammatory bowel disease (IBD) and yet, has no definitive cure. Currently, corticosteroids, anti-tumor necrosis factor (anti-TNF) agents and 5-aminosalicylic acid derivatives are prescribed for management of colitis. Except their failure rate, they are not always tolerated because of their severe adverse effects. Additive formulas with fewer adverse effects may improve the treatment of colitis. METHODS: In this study, colitis was induced with intra-rectal injection of three concentrations of acetic acid (4, 6 and 8 v/v). Each group received sodium selenite (0.5 mg/kg) or saline, gavaged on days 0 and 1 for treatment. Two days after induction of colitis, rats were sacrificed and the end part of their colons were resected for macroscopic and microscopic evaluation and molecular measurement. RESULTS: Sodium selenite improved macroscopic and microscopic view of the colon, decreased cryptitis, crypt abscess and inflammatory cells infiltration and partly maintained mucosal structure. Sodium selenite markedly reduced tissue levels of malondialdehyde (MDA), TNF-α and interferon γ (INF-γ) and decreased myeloperoxidase (MPO) activity. Treatment with sodium selenite also significantly downregulated IL17, IL22, indoleamine 2,3-dioxygenase (IDO1), and kynurenine levels. Western blotting revealed that sodium selenite prevented apoptosis by increasing bcl2/Bax ratio. Furthermore, our findings showed that sodium selenite significantly downregulated the upstream inflammatory molecules such as nuclear factor kappa B (NF-κB) and toll-like receptor 4 (TLR4) in colitis. CONCLUSION: These findings show that sodium selenite alleviates inflammatory response and oxidative stress and protects against colitis.
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Colitis , FN-kappa B , Ácido Acético/toxicidad , Animales , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Colon/metabolismo , Quinurenina/metabolismo , Quinurenina/farmacología , Quinurenina/uso terapéutico , FN-kappa B/metabolismo , Ratas , Transducción de Señal , Selenito de Sodio/metabolismo , Selenito de Sodio/farmacología , Selenito de Sodio/uso terapéutico , Receptor Toll-Like 4/metabolismo , Inhibidores del Factor de Necrosis TumoralRESUMEN
Neurological disorders result in disability and morbidity. Neuroinflammation is a key factor involved in progression or resolution of a series of neurological disorders like Huntington disease (HD), Parkinson's disease (PD), Alzheimer's disease (AD), Spinal Cord Injury (SCI), and Seizure. Thereby, anti-inflammatory drugs have been developed to improve the neurodegenerative impairments. Licofelone is an approved osteoarthritis drug that inhibits both the COX (cyclooxygenase) and 5-LOX (lipoxygenase) pathways. Licofelone has pain-relieving and anti-inflammatory effects and it was shown to have neuroprotective properties in the central nervous system, which is implicated in its regulatory effect on the COX/5-LOX pathway, inflammatory cytokines, and immune responses. In this study, we briefly review the various features of neurological disorders and the function of COX/LOX in their flare up and current pharmacological products for their management. Moreover, this review attempts to summarize potential therapeutics that target the immune responses within the central nervous system. A better understanding of the interactions between Licofelone and the nervous systems will be crucial to demonstrate the possible efficacy of Licofelone in neurological disorders.
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Inhibidores de la Lipooxigenasa , Enfermedades del Sistema Nervioso , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa/farmacología , Humanos , Inhibidores de la Lipooxigenasa/farmacología , Inhibidores de la Lipooxigenasa/uso terapéutico , Enfermedades del Sistema Nervioso/tratamiento farmacológico , PirrolesRESUMEN
Previously, some allergic conditions involving pruritus have been linked to migraine, raising the possibility that migraine and itching may be governed by similar underlying mechanisms. We aimed to investigate the efficacy of Lasmiditan, a highly selective agonist of the 5-hydroxytryptamine 1F (5-HT1F) receptor and a recently approved medication for the treatment of migraine headaches, in ameliorating serotonergic itching. Forty animals were employed in the present study (n = 40). Eight animals were randomly assigned to each of the following study groups (n = 8, in each group): (1) "Normal Saline": This group was given intradermal injections of normal saline (2) "5-HT": The animals were injected with intradermal 5-HT, which was used to induce itching. (3) "Lasmiditan 0.3", "Lasmiditan 1", and "Lasmiditan 3" groups: injected with 5-HT as well as intraperitoneal Lasmiditan at different dose levels (0.3, 1, and 3 mg/kg, respectively). Scratching behavior was recorded for 60 min, and the skin tissue of three mice was sampled at the end of the behavioral experiment to assess the levels of TLR-4, IL-31, 5-HT1F receptor, CGRP & TRPV4. In the present study, we found that Lasmiditan when administered at 1 mg/kg effectively reduced serotonin-induced itching compared to the "5-HT" group (P < 0.0001). Following the administration of Lasmiditan (1 mg/kg), the expression levels of the 5-HT1F receptor significantly increased (P < 0.01). Further, the levels of TLR-4, IL-31, CGRP & TRPV4 were substantially reduced upon the administration of Lasmiditan (1 mg/kg). We found that Lasmiditan is effective in reducing serotonergic itch in mice through its interaction with the 5-HT1F receptor in the skin tissue of mice.
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INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung condition that produces symptoms including coughing which may cause by excessive accumulation of scar tissue inflammatory and oxidative stress exacerbation. Sumatriptan, utilized for migraine treatment as a selective 5-HT1B/1D receptor agonist, has demonstrated significant anti-inflammatory and antioxidant properties in multiple preclinical investigations. Operating primarily on serotonin receptors, sumatriptan leverages the diverse physiological functions of serotonin, playing a pivotal role in regulating both inflammation and oxidative stress which is particularly relevant in the context of IPF. MATERIALS & METHODS: Thirty-five male Wistar rats were divided to five group, including: Sham (without IPF induction), control (BLM 5â¯mg/kg, intraperitoneally), and three fibrosis group with sumatriptan (0.5, 1, and 3â¯mg/kg, i.p. for 2 weeks) administration. IPF was induced by injection of BLM (single dose, 5â¯mg/kg intratracheally). Lung tissues were separated for measurement of myeloperoxidase (MPO) as an oxidative stress hallmark, and tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-ß), and transforming growth factor-ß (TGF-ß) as inflammatory markers as well as alpha smooth muscle actin (α-SMA). Also, for histological investigations, tissue damages were assessed by Hematoxylin-eosin (H&E) and Masson's trichrome staining method. RESULTS: BLM-induced fibrosis could increase α-SMA, MPO, TNF-α, IL-1ß, and TGF-ß, while treatment with sumatriptan has reversed the α-SMA, MPO, and IL-1ß levels. Moreover, the results of H&E and Masson's trichrome staining indicated that sumatriptan (1 and 3â¯mg/kg) reduced tissue damages, alveolar wall thickness, collagen accumulation, and pulmonary fibrosis induced by BLM. CONCLUSION: According to the data achieved from this study, Sumatriptan appears to have therapeutic benefits in IPF, possibly via reducing α-SMA as well as inflammation and the toxicity caused by oxidative stress.
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Actinas , Bleomicina , Inflamación , Estrés Oxidativo , Fibrosis Pulmonar , Ratas Wistar , Sumatriptán , Animales , Bleomicina/toxicidad , Estrés Oxidativo/efectos de los fármacos , Masculino , Sumatriptán/farmacología , Ratas , Actinas/metabolismo , Inflamación/patología , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/inducido químicamente , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/metabolismoRESUMEN
The incorporation of skin flaps in wound closure management with its cosmetic implications has appeared as a gleam of hope in providing desirable outcomes. Given the influence of extrinsic and intrinsic factors, skin flaps are prone to several complications, including ischemia-reperfusion injury (IRI). Numerous attempts have been undertaken to enhance the survival rate of skin flaps entailing pre/post-conditioning with surgical and pharmacological modalities. Various cellular and molecular mechanisms are employed in these approaches in order to reduce inflammation, promote angiogenesis and blood perfusion, and induce apoptosis and autophagy. With the emerging role of multiple stem cell lineages and their ability to improve skin flap viability, these approaches are increasingly being used to develop even more translationally applicable methods. Therefore, this review aims at providing current evidence around pharmacological interventions for improving skin flap survival and discussing their underlying mechanism of action.
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Daño por Reperfusión , Colgajos Quirúrgicos , Humanos , Daño por Reperfusión/prevención & control , Apoptosis , Piel , Supervivencia de InjertoRESUMEN
BACKGROUND: Many drugs have been explored for their role in improving skin flap survival. 1-deamino-8-D-arginine vasopressin (DDAVP or desmopressin) is a synthesized form of anti-diuretic hormone (ADH) and a selective agonist for vasopressin type-2 receptors (V2 receptors). Desmopressin has been shown to improve endothelial function, induce vasodilation, and reduce inflammation. We aimed to evaluate its efficacy in enhancing flap survival and assess the role of vasopressin receptors in this process. MATERIALS AND METHODS: We randomly assigned six male Wistar rats to each study group. Different doses of desmopressin were injected intraperitoneally to find the most effective amount (8 µg/rat). SR-49059, a selective V1a receptor antagonist, was given at 2µg/rat before providing the most effective dose of desmopressin (8µg/rat). Histopathological assessments, quantitative measurements of interleukin-1ß (IL-1ß), Tumor necrosis factor-alpha (TNF-α), and Nuclear Factor-κB (NF-κB), optical imaging, and measurement of the expression levels of V2 receptor in the rat skin tissue were performed. RESULTS: Desmopressin (8µg/rat) significantly reduced the mean percentage of necrotic area compared to the control group (19.35% vs 73.57%). Histopathological evaluations revealed a notable reduction in tissue inflammation, edema, and degeneration following administration of desmopressin (8). The expression of the V2 receptor was increased following desmopressin administration. It also led to a reduction in IL-1ß, TNF-α, and NF-κB levels. The protective effect of desmopressin on flap survival was reversed upon giving SR-49059. The optical imaging revealed enhanced blood flow in the desmopressin group compared to the control group. CONCLUSIONS: Desmopressin could be repurposed to improve flap survival. V1a and V2 receptors probably mediate this effect.
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Desamino Arginina Vasopresina , Receptores de Vasopresinas , Ratas , Masculino , Animales , Desamino Arginina Vasopresina/farmacología , Receptores de Vasopresinas/fisiología , FN-kappa B , Factor de Necrosis Tumoral alfa , Ratas Wistar , Antagonistas de los Receptores de Hormonas Antidiuréticas , Vasopresinas/farmacología , InflamaciónRESUMEN
Background: Oral mucositis (OM) is a common adverse effect of radiation to the head and neck. Recent research has shown that extra oral photobiomodulation (EO-PBM) reduces the severity of OM. However, appropriate EO-PBM therapy parameters for OM severity reduction have not been documented. Objective: This work aims to optimize EO-PBM radiation parameters for lowering the severity of radiation-induced OM in rats by establishing a photobiomodulation (PBM) treatment system based on light-emitting diode arrays with top-hat beam profile. Methods: The 36 rats are separated into 2 control groups and 4 groups receiving PBM treatment. The PBM groups are exposed to irradiance between 4 and 24 J/cm2 at 660 nm. The cheek pouch mucosa is removed after scarification for biochemical and histological examination. Student's t-test, and one-way analysis of variance (ANOVA) followed by Tukey's Multiple were applied to compare the statistical significance of differences between control groups and PBM treatment groups. Results: Statistical analysis reveals that PBM irradiation at 12 J/cm2 (200 sec) with a flatness of 0.8 and a diameter of 3 cm substantially decreased the level of inflammatory cytokines compared with the positive control group. Conclusions: Our results indicate that the designed treatment PBM system is capable of delivering the optical parameters necessary for therapeutic treatment.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Terapia por Luz de Baja Intensidad , Estomatitis , Ratas , Animales , Estomatitis/etiología , Estomatitis/radioterapia , Terapia por Luz de Baja Intensidad/métodos , CitocinasRESUMEN
This study was designed to investigate the involvement of opioidergic/nitrergic systems in the anticonvulsant effect of mefloquine, compared with chloroquine, in mice. Seizures were induced by pentylenetetrazol and maximal electroshock. Mice were randomly subjected to receive mefloquine or chloroquine thirty minutes in advance. The role of opioidergic/nitrergic systems was shown by coadministration of pharmacological intervention and nitrite levels measurement in mice hippocampi. Results indicated that mefloquine (40 mg/kg) and chloroquine (5 mg/kg) significantly decreased the occurrence of tonic hindlimb extension. Also, mefloquine 120 mg/kg and chloroquine 5 mg/kg significantly increased seizure latency and decreased mortality rate. Mefloquine decreased seizure frequency too. Besides, mefloquine (20 mg/kg) and chloroquine (5, 10 mg/kg) significantly increased seizure threshold. Interestingly, LNAME, 7NI and naltrexone pretreatment reversed the anticonvulsant effects of both mefloquine (20 mg/kg) and chloroquine (5 mg/kg). Moreover, coadministration of minimaleffective doses of morphine with mefloquine/chloroquine (both 1 mg/kg) potentiated anticonvulsant effects, which was reversed by naltrexone and endorsed the involvement of opioid receptors. Also, nitrite levels in mice hippocampi remarkably increased after treatment with both mefloquine (20 mg/kg) and chloroquine (5 mg/kg). To conclude, mefloquine could protect the central nervous system against seizures in PTZ/MESinduced models through opioidergic/nitrergic pathways, with similarity to chloroquine effects.
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Anticonvulsivantes , Pentilenotetrazol , Convulsiones , Animales , Anticonvulsivantes/farmacología , Cloroquina/farmacología , Modelos Animales de Enfermedad , Electrochoque , Mefloquina/farmacología , Ratones , Naltrexona , Nitritos , Pentilenotetrazol/toxicidad , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológicoRESUMEN
BACKGROUND: Preterm labor (PTL) is one of the most important factors in neonatal mortality. Some studies have revealed a reverse relationship between cervical length (CL) and PTL, however, further evidence is needed to confirm it. OBJECTIVE: To investigate the predictive value of CL in spontaneous and in vitro fertilization (IVF) pregnancies. MATERIALS AND METHODS: This prospective cohort study was performed on 154 pregnant women from 16-26 wk of gestation with singleton fetus in spontaneous delivery (n = 77) and IVF pregnancies (n = 77) and followed up until delivery. Women with multiple pregnancy, placenta previa, cerclage, and congenital anomalies were excluded from study. The cut-off determination was done according to the Roc analysis. RESULTS: The mean CL in term delivery and PTL groups were 37 ± 7 mm and 31 ± 6 mm, respectively (p < 0.001). The frequency of PTL in spontaneous and IVF pregnancies were 7.8% and 23.27%, respectively (p = 0.007). According to the Roc analysis, the best cut-off for normal pregnancy was ≤ 36 mm with the negative predictive value of 97.9%, the positive predictive value of 11.4%, sensitivity 83.3%, and specificity of 46.5%. While for the IVF group, the cut off was ≤ 30 mm, with a negative predictive value of 88.4%, positive predictive value of 57.8%, sensitivity of 63.2%, and specificity of 86%. CONCLUSION: In this study, IVF had a significant direct correlation with PTL. CL also had a significant indirect relationship with PTL.
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Diabetes and osteoporosis are two common diseases with different complications. Despite different therapeutic strategies, managing these diseases and reducing their burden have not been satisfactory, especially when they appear one after the other. In this review, we aimed to clarify the similarity, common etiology and possible common adjunctive therapies of these two major diseases and designate the known molecular pattern observed in them. Based on different experimental findings, we want to illuminate that interestingly similar pathways lead to diabetes and osteoporosis. Meanwhile, there are a few drugs involved in the treatment of both diseases, which most of the time act in the same line but sometimes with opposing results. Considering the correlation between diabetes and osteoporosis, more efficient management of both diseases, in conditions of concomitant incidence or cause and effect condition, is required.
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Diabetes Mellitus , Osteoporosis , Diabetes Mellitus/epidemiología , Diabetes Mellitus/terapia , Humanos , Incidencia , Osteoporosis/epidemiología , Osteoporosis/terapiaRESUMEN
INTRODUCTION: Increased plasma homocysteine may be associated with adverse pregnancy outcomes, such as preeclampsia. The aim of this study was to determine the plasma homocysteine, serum folate, and vitamin B12 levels in preeclamptic pregnant women. METHODS: This case-control study was conducted in 2016 in Ahwaz on 51 pregnant women with preeclampsia and 51 healthy pregnant women of the same gestational age, who served as controls. The case group also was subdivided into severe and non-severe preeclampsia. Patients' data were collected through a questionnaire and medical records. Serum homocysteine, folic acid, and vitamin B12 were analyzed using chemiluminescent assay. The results were compared between two groups. Statistical analyses were done using IBM-SPSS 20.0. A Kolmogorov-Smirnov test, independent samples t-test, Mann-Whitney test, and Chi-square test were used for data analysis. RESULTS: No different demographic characteristics were found among the groups. Pregnant women complicated with preeclampsia displayed significantly higher serum homocysteine levels (p < 0.001) and lower serum folate (p = 0.005) and vitamin B12 levels (p < 0.001) compared to controls. A statistically significant inverse correlation was evident between serum homocysteine and serum folate levels in preeclamptic patients (p = 0.005; r = -0.389). In addition, an inverse correlation was identified between homocysteine and serum vitamin B12, but it was not statistically significant (p = 0.160; r = -0.200). Significant differences occurred in serum homocysteine and folate levels between the severe and non-severe subgroups (p < 0.001, p < 0.001). CONCLUSION: Women complicated with preeclampsia displayed higher maternal serum homocysteine and lower serum folate and vitamin B12. Further studies are needed to confirm if the prescription of folic acid and vitamin B12 in women with a deficiency of these vitamins could decrease the level of serum homocysteine and, therefore, reduce the risk of preeclampsia or, if it occurred, its severity.