Non-coding RNAs and exosomal non-coding RNAs in pituitary adenoma.

Pituitary adenoma (PA) is the third most common primary intracranial tumor in terms of overall disease incidence. Although they are benign tumors, they can have a variety of clinical symptoms, but are mostly asymptomatic, which often leads to diagnosis at an advanced stage when surgical intervention is ineffective. Earlier identification of PA could reduce morbidity and allow better clinical management of the affected patients. Non-coding RNAs (ncRNAs) do not generally code for proteins, but can modulate biological processes at the post-transcriptional level through a variety of molecular mechanisms. An increased number of ncRNA expression profiles have been found in PAs. Therefore, understanding the expression patterns of different ncRNAs could be a promising method for developing non-invasive biomarkers. This review summarizes the expression patterns of dysregulated ncRNAs (microRNAs, long non-coding RNAs, and circular RNAs) involved in PA, which could one day serve as innovative biomarkers or therapeutic targets for the treatment of this neoplasia. We also discuss the potential molecular pathways by which the dysregulated ncRNAs could cause PA and affect its progression.

Quercetin modulates signal transductions and targets non-coding RNAs against cancer development.

In recent decades, various investigations have indicated that natural compounds have great potential in the prevention and treatment of different chronic disorders including different types of cancer. As a bioactive flavonoid, Quercetin (Qu) is a dietary ingredient enjoying high pharmacological values and health-promoting effects due to its antioxidant and anti-inflammatory characterization. Conclusive in vitro and in vivo evidence has revealed that Qu has great potential in cancer prevention and development. Qu exerts its anticancer influences by altering various cellular processes such as apoptosis, autophagy, angiogenesis, metastasis, cell cycle, and proliferation. In this way, Qu by targeting numerous signaling pathways as well as non-coding RNAs regulates several cellular mechanisms to suppress cancer occurrence and promotion. This review aimed to summarize the impact of Qu on the molecular pathways and non-coding RNAs in modulating various cancer-associated cellular mechanisms.

Potential of natural products in the treatment of myocardial infarction: focus on molecular mechanisms.

Although conventional drugs are widely used in the prevention and treatment of cardiovascular disease (CVD), they are being used less frequently due to concerns about possible side effects over the long term. There has been a renewed research interest in medicinal plant products, and their role in protecting the cardiovascular system and treating CVD, which are now being considered as potential alternatives to modern drugs. The most important mechanism causing damage to the myocardium after heart attack and reperfusion, is increased levels of free radicals and oxidative stress. Therefore, treatment approaches often focus on reducing free radicals or enhancing antioxidant defense mechanism. It has been previously reported that bioactive natural products can protect the heart muscle in myocardial infarction (MI). Since these compounds are readily available in fruits and vegetables, they could prevent the risk of MI if they are consumed daily. Although the benefits of a healthy diet are well known, many scientific studies have focused on whether pure natural compounds can prevent and treat MI. In this review we summarize the effects of curcumin, resveratrol, quercitin, berberine, and tanshinone on MI and CVD, and focus on their proposed molecular mechanisms of action.

The use of nanoparticles in the treatment of infectious diseases and cancer, dental applications and tissue regeneration: a review.

The emergence of nanotechnology as a field of study can be traced back to the 1980s, at which point the means to artificially produce, control, and observe matter on a nanometer level was made viable. Recent advancements in technology have enabled us to extend our reach to the nanoscale, which has presented an unparalleled opportunity to directly target biomolecular interactions. As a result of these developments, there is a drive to arise intelligent nanostructures capable of overcoming the obstacles that have impeded the progress of conventional pharmacological methodologies. After four decades, the gradual amalgamation of bio- and nanotechnologies is initiating a revolution in the realm of disease detection, treatment, and monitoring, as well as unsolved medical predicaments. Although a significant portion of research in the field is still confined to laboratories, the initial application of nanotechnology as treatments, vaccines, pharmaceuticals, and diagnostic equipment has now obtained endorsement for commercialization and clinical practice. The current issue presents an overview of the latest progress in nanomedical strategies towards alleviating antibiotic resistance, diagnosing and treating cancer, addressing neurodegenerative disorders, and an array of applications, encompassing dentistry and tuberculosis treatment. The current investigation also scrutinizes the deployment of sophisticated smart nanostructured materials in fields of application such as regenerative medicine, as well as the management of targeted and sustained release of pharmaceuticals and therapeutic interventions. The aforementioned concept exhibits the potential for revolutionary advancements within the field of immunotherapy, as it introduces the utilization of implanted vaccine technology to consistently regulate and augment immune functions. Concurrently with the endeavor to attain the advantages of nanomedical intervention, it is essential to enhance the unceasing emphasis on nanotoxicological research and the regulation of nanomedications' safety. This initiative is crucial in achieving the advancement in medicine that currently lies within our reach.

Curcumin and inflammatory bowel diseases: From in vitro studies to clinical trials.

Inflammatory bowel diseases (IBDs) may result from mutations in genes encoding for innate immunity, which can lead to exacerbated inflammatory response. Although some mono-targeted treatments have developed in recent years, IBDs are caused through several pathway perturbations. Therefore, targeting all these pathways is difficult to be achieved by a single agent. Moreover, those mono-targeted therapies are usually expensive and may cause side-effects. These limitations highlight the significance of an available, inexpensive and multi-targeted dietary agents or natural compounds for the treatment and prevention of IBDs. Curcumin is a multifunctional phenolic compound that is known for its anti-inflammatory and immunomodulatory properties. Over the past decades, mounting experimental investigations have revealed the therapeutic potential of curcumin against a broad spectrum of inflammatory diseases including IBDs. Furthermore, it has been reported that curcumin directly interacts with many signaling mediators implicated in the pathogenesis of IBDs. These preclinical findings have created a solid basis for the assessment of the efficacy of curcumin in clinical practice. In clinical trials, different dosages e.g., 550 mg /three times daily-1month, and 1 g /twice times daily-6month of curcumin were used for patients with IBDs. Taken together, these findings indicated that curcumin could be employed as a therapeutic candidate in the treatment of IBDs. Moreover, it seems that overcome to current limitations of curcumin i.e., poor oral bioavailability, and poor oral absorption with using nanotechnology and others, could improve the efficacy of curcumin both in pre-clinical and clinical studies.

Morphometric development of sheep (Ovis aries) lymph nodes in fetal period.

Immune system plays crucial role in body and lymph nodes are essential parts of this system for combating pathogens. However, no study has ever been conducted on morphometric development of sheep lymph nodes in fetal period. Thus, this study attempted to examine the morphometric characteristics of a number of important lymph nodes of some lymphocenters of sheep during fetal period. To this end, 60 pieces of sheep fetuses collected from Ahvaz slaughterhouse were fixated in 10% formalin and then divided into four categories based on crown-rump length (CRL) following gender and weight determinations. Mandibular, caudal superficial cervical (prescapular), caudal mediastinum, jejunal mesenteric and popliteal lymph nodes were evaluated in five lymphocenters of head, neck, thoracic cavity, abdominal viscera and pelvic limbs, respectively. In each sample, nodes formation was visually checked and in cases of nodes formation, they were measured in terms of weight, length, width and thickness and collected data were statistically analyzed. The longest and shortest fetal CRLs were found to be 48.50 cm and 3.50 cm, respectively. Gender had no effect on study parameters in 32 male and 28 female fetuses. Study of sheep fetuses' lymph nodes revealed no macroscopic lymph node development by day 45, while all nodes were observable after the day 59. The shortest lymph node was mandibular node and the longest one was caudal mediastinum. Based on the results, it seemed that although the size of lymph nodes grows by age, this increase is not the same for all nodes and groups.

Protective effect of quercetin on histomorphometric changes in kidney of retinoid acid-treated rat fetuses / Efecto protector de la quercetina sobre los cambios histomorfométricos en el riñón de fetos de rata tratados con ácido retinoico

SUMMARY: Retinoic acid, an active metabolite of vitamin A, plays essential signaling roles in mammalian embryogenesis. Prenatal rat fetuse exposure to retinoid induces some malformations in various organs, the most active and teratogenic metablolite is all-transretinoic acid (atRA). The teratogenic effects of some drugs can be prevented by the application of antioxidant drugs and stimulation of the maternal immune system. Also, quercetin, a naturally occurring flavonoid has excellent antioxidant properties. Therefore, the aim of this study was assess the protective effects of quercetin against atRA in fetuses of rat's kidney tissue. This study was performed on 40 pregnant rats that were divided into seven groups. Control group received normal saline and test groups received DMSO, quercetin (75 mg/kg), quercetin (200 mg/kg), atRA (25 mg/kg), atRA (25 mg/kg) plus quercetin (75 mg/kg) and atRA (25 mg/kg) plus quercetin (200 mg/kg), intraperitoneally at 8-10th days of gestation. Fetuses were collected at 20th day of gestation. Kidneys were collected and placed in 10 % buffered formalin solution. Then, kidneys were sectioned by routine method and stained by H&E and examined histologically. On histomorphomertrical examination, it was observed the priglomerular space and diameter of renal corpuscle in group which received only atRA were significantly (p≤0.05) greater than those received normal saline, dimethyl sulfoxide and quercetin, while these two indexes in group which received atRA plus quercetin significantly (p≤0.05) decreased by quercetin as dose dependent manner. Number of renal corpuscles were significantly (p≤0.05) decreased by atRA, but the quercetin could not affect the glomerular numbers. It is concluded that quercetin can protect fetuses against atRA damages and prevent their incidence probably via its antioxidant effect.

RESUMEN: El ácido retinoico, un metabolito activo de la vitamina A, desempeña un papel esencial de señalización en la embriogénesis de mamíferos. La exposición al ácido retinoico en fetos de ratas prenatales induce malformaciones en varios órganos, siendo el metabolito más activo y teratogénico el ácido transretinoico (ATRA). Los efectos teratogénicos de algunos medicamentos se pueden prevenir mediante la aplicación de medicamentos antioxidantes y la estimulación del sistema inmune materno. Además, la quercetina, un flavonoide de origen natural, tiene excelentes propiedades antioxidantes. Por lo tanto, el objetivo de este estudio fue evaluar los efectos protectores de quercetina contra ATRA en fetos de tejido de riñón de rata. Este estudio se realizó en 40 ratas preñadas que se dividieron en siete grupos. El grupo control recibió solución salina normal y los grupos de prueba recibieron DMSO, quercetina (75 mg / kg), quercetina (200 mg / kg), ATRA (25 mg / kg), ATRA (25 mg / kg) más quercetina (75 mg / kg) y ATRA (25 mg / kg) más quercetina (200 mg / kg), por vía intraperitoneal a los 8-10 días de gestación. Los fetos se recolectaron a los 20 días de gestación. Los riñones se recogieron y se colocaron en solución de formalina tamponada al 10 %. Luego, los riñones se seccionaron por método de rutina y se tiñeron con H & E y se examinaron histológicamente. En el examen histomorfométrico, se observó que el espacio periglomerular y el diámetro del corpúsculo renal en el grupo que recibió solo ATRA fueron significativamente (p≤0.05) mayores que los que recibieron solución salina normal, dimetilsulfóxido y quercetina, mientras que estos dos índices, en el grupo que recibió ATRA más quercetina, disminuyó significativamente (p≤0.05) en forma dependiente de la dosis. El número de corpúsculos renales disminuyó significativamente (p≤0.05) por el ATRA, pero la quercetina no pudo afectar el número de glomérulos. Se concluye que la quercetina puede proteger a los fetos contra daños de ATRA y prevenir su incidencia, probablemente, a través de su efecto antioxidante.

Protective effect of quercetin on skeletal and neural tube teratogenicity induced by cyclophosphamide in rat fetuses.

Cyclophosphamide (CP) is a drug commonly used to treat neoplastic disease and some autoimmune diseases. It is also a well-known and well-studied teratogen causing a variety of birth defects in fetuses of pregnant women treated with the drug. There are many reports that show the adverse effects of CP can be decreased by use of antioxidant drugs. It appears that, quercetin has antioxidant effect. The aim of this study was prevention or decrease of teratogenicity of CP in fetuses of rats by quercetin. This study was performed on 35 pregnant rats divided into six groups. Control group was received normal saline (5 mL kg(-1), intraperitoneally) and 2-6 groups received a single dose of CP (15 mg kg(-1)), a single dose of quercetin (75 or 200 mg kg(-1)), CP plus quercetin (75 or 200 mg kg(-1)) intraperitoneally at 9(th) day of gestation, respectively. Fetuses were collected at 20(th) day of gestation and after determination of weight and crown rump length were stained by alizarin red - alcian blue method and skeletal system were examined by stereomicroscope. The results showed that the cleft palate, exencephaly, spina bifida and omphalocele incidence were 55.56%, 27.77%, 33.34% and 11.11%, in fetuses of rat that received only CP, respectively. However, it decreased to 16.00%, 16.00%, 16.00% and 8.00% by quercetin (75 mg kg(-1)) and so to 12.90%, 12.90%, 6.45% and 3.28% by quercetin (200 mg kg(-1)), respectively. On the basis of results, quercetin significantly can decrease teratogenicity induced by CP.

L-Carnitine Protect against Cyclophosphamide Induced Skeletal and Neural Tube Malformations in Rat Fetuses.

Cyclophosphamide (CP) is a mustard alkylating agent used in the treatment of a number of neoplastic diseases and as an immunosuppressant for the prevention of xenograft rejection. There are many reports that the teratogenic effects of cyclophosphamide can be prevented by application of antioxidant drugs and stimulation of the maternal immune system. Also, there is some evidence that L-carnitine is antioxidant. Therefore, in this study, the prophylactic effect of L-carnitine on teratogenic effects of CP was evaluated. This study was performed on 31 pregnant rats divided into 5 groups. Control group received normal saline and test groups received L-carnitine (500 mg/kg), CP (15 mg/kg), CP (15 mg/kg) plus L-carnitine (250 mg/kg) and CP (15 mg/kg) plus L-carnitine (500 mg/kg) intraperitoneally at 9th day of gestation. Fetuses were collected at 20th day of gestation and after determination of weight and length; they were stained by Alizarin red-Alcian blue method. Cleft palate, spina bifida, and exencephaly incidence were 55.55%, 33.34% and 27.77% in fetuses of mice that received only CP. Cleft palate, spina bifida, exencephaly incidence were 21.42%, 4.76% and 9.52% in the group which received CP plus L-carnitine (250 mg/kg), respectively. However, cleft palate, spina bifida, and exencephaly incidence were 8%, 0% and 8% range in the group received CP plus L-carnitine (500 mg/kg), respectively. In addition, skeletal anomalies incidence including limbs, vertebrae, and sternum defects were decreased by L-carnitine. The mean of weight and length of animals' fetuses received L-carnitine were significantly greater than those received only CP. In conclusion, L-carnitine significantly decreased teratogenicity induced by CP; but this subject needs more detailed evaluation.

A case of conjoined twins (thoraco-omphalopygopagus tribrachius tetrapus) in lamb.

Nearly completed conjoined or fused symmetrical twins are generally called diplopagus. Sheep conjoined twins have been reported less than cow. An apparently female conjoined twin lambs was examined based on external and internal features. In radiology, two vertebral columns and two pairs of the ribs were seen. Only two heads and two necks were separated (thoraco-omphalopygopagus). There were three forelimbs (tribrachius), one of which grew on dorsal region as a notomelus. Teat buds of the monsters differed in number. Only one lamb had umbilicus, including one umbilical vein, and two umbilical arteries locating besides one urinary bladder. This lamb had also one uterus. Two-separated alimentary tracts were observed in a common abdomen. Common thorax and abdominal cavities were separated by a diaphragm. There were two esophageal hiatuses, and two caval foramina but only one aortic hiatus. Two pairs of lungs and two unequal and connected hearts in a common pericardium were observed. Abnormality of the circulatory system might have caused the death of the twins.

Prophylactic Effects of Levamisole and Vitamin E on Phenobarbital-induced Cleft Palate and Spina Bifida in Rat Embryos.

There are many reports that show the teratogenic effects of phenobarbital can be decreased by stimulation of maternal immune system. Therefore, in this study, the prophylactic effects of levamisole and vitamin E on teratogenic effects of phenobarbital were compared. This study was performed on 20 pregnant rats that were divided into four groups. Control group received normal saline and test groups received phenobarbital (120 mg/kg), phenobarbital (120 mg/kg) plus levamisole (10 mg/kg) and phenobarbital (120 mg/kg) plus vitamin E (100 mg/kg) intraperitoneally at 9-11th days of gestation, respectively. Fetuses were collected at 20th day of gestation and after determination of weight and length; they were stained by Alizarin red - Alcian blue method. Cleft palate and spina bifida incidence were 66.66% and 69.44% in fetuses of rats that had received only phenobarbital. Cleft palate and spina bifida incidence were 65.45% and 38.18% had in the group which had received phenobarbital plus levamisole. However, Cleft palate and spina bifida incidence were 54.54% and 27.27% in the group which had received phenobarbital plus vitamin E. The arithmetic means of the weight and length of fetuses the rats that had received levamisole and vitamin E were significantly greater than that of those that had received only phenobarbital. Vitamin E had a greater prophylactic effect than levamisole on the incidence of phenobarbital-induced cleft palate and spina bifida. However, the difference was not significant.