Empty sella in somatotropic pituitary adenomas; a series of 23 cases.

Purpose: We aimed to investigate empty sella syndrome in somatotrophic pituitary adenoma for possible etiology, complications, and treatment options. Method: Among over 2,000 skull base masses that have been managed in our center since 2013, we searched for growth hormone-producing adenomas. Clinical, surgical, and imaging data were retrospectively collected from hospital records to check for sella that lacked pituitary tissue on routine imaging. Result: In 220 somatotrophic adenomas, 23 patients had an empty sella with surgical and follow-up data. The mean age of the sample was 46 years with the same male-to-female ratio. Five cases had partial empty sella and the rest were complete empty sellas. The most common simultaneous hormonal disturbance was high prolactin levels. Six had adenoma invasion into the clivus or sphenoid sinus and 10 had cavernous sinus intrusion. Peri-operative low-flow and high-flow cerebrospinal fluid (CSF) leaks were encountered in one and two patients, respectively, which were successfully sealed by abdominal fat. The majority of cases required growth hormone replacement therapy while it was controlled without any replacement therapy in nine patients. No pituitary hormonal disturbance occurred after transsphenoidal surgery except for hypothyroidism in one patient. Conclusion: An empty sella filled with fluid can be detected frequently in pituitary adenomas, especially in the setting of acromegaly. The pituitary gland may be pushed to the roof of the sella and might be visible as a narrow rim on imaging or may be detected in unusual places out of the sella. The pathophysiology behind such finding originates from soft and hard tissue changes and CSF pressure alternations during abundant growth hormone production.

Vertical triband flag sign for differential diagnosis of Rathke's cleft cyst.

Background: The Rathke cleft cyst (RCC) is a type of cystic growth that is benign, circular, and well-defined with an incidence rate of 4 %. This study aims to identify a useful diagnostic imaging sign that can aid in the differentiation of RCC from other cystic lesions. Methods: We retrospectively analyzed the records of 42 symptomatic RCC patients who were referred to our facility between 2016 and 2023. The data for the study were obtained from our electronic database. All magnetic resonance imaging (MRI) studies were performed using a 1.5-T superconducting magnetic scanner. All patients underwent endonasal transsphenoidal surgical resection. All MRIs were reviewed and evaluated by a neurosurgeon and a neuroradiologist. Results: There were 8 (19 %) males and 34 (81 %) females with a mean age of 37.2-years. Our study identified a distinct imaging characteristic in 38 of the cases, which we have named the "vertical triband flag sign", due to the growth of the cyst developing a specific appearance. The flag sign was mostly observed only in the T1-images (71.5 %), while in four cases the sign was spotted only in T2-images, and in four cases it appeared in both T1 and T2. In 4 cases, the flag sign was not observed in which further investigations revealed that these cases were suprasellar or small sellar RCCs. The dot sign, which is a characteristic finding in RCCs was only observed in one of our cases. Conclusion: Early diagnosis of RCCs may be facilitated by utilizing the vertical triband flag sign.

Role of miR-424 in the carcinogenesis.

Recent studies have revealed the impact of microRNAs (miRNAs) in the carcinogenic process. miR-424 is a miRNA whose role in this process is being to be identified. Experiments in the ovarian cancer, cervical cancer, hepatocellular carcinoma, neuroblastoma, breast cancer, osteosarcoma, intrahepatic cholangiocarcinoma, prostate cancer, endometrial cancer, non-small cell lung cancer, hemangioma and gastric cancer have reported down-regulation of miR-424. On the other hand, this miRNA has been found to be up-regulated in melanoma, laryngeal and esophageal squamous cell carcinomas, glioma, multiple myeloma and thyroid cancer. Expression of this miRNA is regulated by methylation status of its promoter. Besides, LINC00641, CCAT2, PVT1, LIN00657, LINC00511 and NNT-AS1 are among lncRNAs that act as molecular sponges for miR-424, thus regulating its expression. Moreover, several members of SNHG family of lncRNAs have been found to regulate expression of miR-424. This miRNA is also involved in the regulation of E2F transcription factors. The current review aims at summarization of the role of miR-424 in the process of cancer evolution and its impact on clinical outcome of patients in order to find appropriate markers for malignancies.

A bioinformatics-based approach and expression assay for identification of dysregulated genes in pituitary adenoma.

Non-functioning pituitary adenomas (NFPAs) are a group of pituitary neuroendocrine tumors that are associated with morbidity. The exact pathophysiological process leading to this pathology is not known. Nerve growth factor (NGF) is a neurotropic factor that might be involved in this process. We used bioinformatics tools to analyze expression of genes in NFPA samples. Our analyses led to identification of NGF-related genes, namely ARC, ID1, and SH3GL3 - as well as one long non-coding RNA (lncRNA) called myocardial infarction associated transcript (MIAT). Then, we assessed their expression in NFPAs and their adjacent non-cancerous samples. While expression levels of SH3GL3 and MIAT were different between NFPA samples and control samples, expressions of ARC and ID1 were not meaningfully different between these two groups of specimens. SH3GL3 was over-expressed in NFPA samples compared with control samples (expression ratio (95% CI)= 8.22 (1.51-44.6), P value= 0.03). Similarly, expression of MIAT was higher in NFPAs compared with controls (expression ratio (95% CI)= 7.7 (1.7-33.6), P value= 0.009). Taken together, we validated the bioinformatics results regarding the expression of SH3GL3 and MIAT. This study provides a deeper understanding of the involvement of these genes in the pituitary tumorigenesis.

Dysregulation of PVT1 and NEAT1 lncRNAs in pituitary adenomas.

Pituitary adenomas are slow-growing tumors originated from the anterior part of pituitary gland. These tumors are associated with dysregulation of a number of long non-coding RNAs (lncRNAs). PVT1, TUG1, MALAT1, NEAT1 and GAS5 are among lncRNAs with important roles in the regulation of cell proliferation, cell apoptosis, cell differentiation and cell cycle transition. In the current study, we assessed expression levels of PVT1, TUG1, MALAT1, NEAT1 and GAS5 in the pituitary adenoma samples compared with adjacent non-cancerous samples to find their relevance with this type of tumors and their potential as diagnostic markers in these tumors. Expression of NEAT1 was significantly higher in total adenoma tissues (Expression ratio (95% CI)= 7.06 (2.31-21.4), P value= 0.02) and in non-functioning pituitary adenoma (NFPA) samples (Expression ratio (95% CI)= 8.5 (2.17-33.12), P value= 0.04) compared with corresponding controls. Although both lncRNAs had appropriate sensitivity values for discrimination of NFPAs from adjacent non-cancerous tissues (0.84 and 0.90 for PVT1 and NEAT1, respectively), the calculated AUC values were not adequate for either lncRNAs (0.63 ± 0.04 and 0.58 ± 0.04 for PVT1 and NEAT1, respectively). Therefore, NEAT1 and PVT1 lncRNAs are dysregulated in NFPA. The current study suggests the role of NEAT1 and PVT1 in the pathogenesis of NFPA.

Emerging functions and clinical applications of exosomal microRNAs in diseases.

Exosomes are an important group of extracellular vesicles that transfer several kinds of biomolecules and facilitate cell-cell communication. The content of exosomes, particularly the amounts of microRNA (miRNAs) inside these vesicles, demonstrates a disease-specific pattern reflecting pathogenic processes and may be employed as a diagnostic and prognostic marker. miRNAs may enter recipient cells through exosomes and generate a RISC complex that can cause degradation of the target mRNAs or block translation of their corresponding proteins. Therefore, exosome-derived miRNAs constitute an important mechanism of gene regulation in recipient cells. The miRNA content of exosomes can be used as an important tool in the detection of diverse disorders, particularly cancers. This research field has an important situation in cancer diagnosis. In addition, exosomal microRNAs offer a great deal of promise in the treatment of human disorders. However, there are still certain challenges to be resolved. The most important challenges are as follow: the detection of exosomal miRNAs should be standardized, exosomal miRNAs-associated studies should be conducted in large number of clinical samples, and experiment settings and detection criteria should be consistent across different labs. The goal of this article is to present an overview of the effects of exosome-derived microRNAs on a variety of diseases, including gastrointestinal, pulmonary, neurological, and cardiovascular diseases, with a particular emphasis on malignancies.

A review on the role of LINC00173 in human cancers.

Long intergenic non-protein coding RNA 173 (LINC00173) is a long non-coding RNA with especial function in the tumorigenic process. Studies in different types of cancers support an oncogenic role for LINC00173 except for studies in B-cell precursor acute lymphoblastic leukemia, cervical cancer, pancreatic cancer and gastric cancer. In breast and lung cancers, both oncogenic and tumor suppressor roles have been reported for LINC00173. LINC00173 can serve as a molecular sponge for miRNAs. miR-218/Etk, miR-511-5p/VEGFA, miR-182-5p/AGER, miR-765/NUTF2, miR-765/PLP2, miR-182-5p/FBXW7, miR-338-3p/Rab25, miR­641/RAB14 and miR-1275/BCL2 are examples of the miRNA/mRNA axes being regulated by LINC00173 in the context of cancer. The current review provides a summary of different studies on the role of LINC00173 in these cancers.

Arachnoid prolapse in endoscopic transsphenoidal surgery of pituitary adenoma, technical note.

PURPOSE: An arachnoid prolapse after endoscopic transsphenoidal surgery for a pituitary adenoma is an uncommon, but important, phenomenon which should be managed. We have evaluated the efficacy of a new simple technique to correct the prolapsed arachnoid following endoscopic surgery of pituitary adenomas. METHODS: A total of 1352 patients with pituitary adenomas, 24-76 years old, who underwent full endoscopic transsphenoidal surgeries between February 2014 and February 2019 in Erfan and Loghman Hakim hospitals. 46 patients with arachnoid prolapse participated in this study and41 patients completed the study. Arachnoid prolapse was repaired by bipolar cauterization with either autologous fat grafts (36 patients) or without autologous fat grafts (5patients). RESULTS: Of 41 patients who completed the study, all except one, had large adenomas with significant suprasellar extension and enlarged diaphragma sellae. All patients had arachnoid prolapse at the end of the tumor removal stage and 13 patients had very minor intraoperative CSF leakage. Prolapsed arachnoid was repaired using a bipolar cautery with or without the autologous fat graft. During the postoperative follow-up period, none of the patient experienced early or delayed postoperative CSF leakage, meningitis, visual deterioration, delayed epistaxis, cranial nerve palsy, recurrence, or death. CONCLUSION: Bipolar cauterization is a safe, effective technique to repair a suprasellar arachnoid prolapse during reconstruction of the sellar floor following endoscopic transsphenoidal pituitary surgery.

Role of lncRNAs and circRNAs in epilepsy.

Epilepsy is a chronic disorder of with a high prevalence and extensive health burden in almost all age groups of the population. This condition is resulted from disturbance in the balance between excitatory and inhibitory factors in the brain. Genetic elements that affect synaptic connectivity, receptors functions or ion channels have been shown to predispose individuals to the epilepsy. More recently, a body of evidence points to the role of non-coding part of the transcriptome in the pathology of epilepsy. Expression levels of NEAT1, H19, PVT1, ILF3-AS1, GAS5, ZFAS1, UCA1, MALAT1 and SNHG1 have been changed in epileptic patients or animal models of epilepsy. Moreover, circ_ANKMY2, circRNA-0067835 and circHivep2 are among circRNAs which are involved in the pathogenesis of epilepsy. Although the mechanistical impact of these transcripts in the pathogenesis of epilepsy has not been fully explored, disturbances in neuron plasticity, apoptosis or differentiation might be implicated in this process. Expression levels of lncRNAs can be used for discrimination of epileptic patients from normal controls or refractory patients from non-refractory ones. JAK/STAT, Wnt, PI3K/AKT and NF-κB signaling pathways are among the regulated pathways by lncRNAs in the context of epilepsy. In the present review, we summarize the role of lncRNAs and circRNAs in the pathogenesis of epilepsy.

A review on the role of PTENP1 in human disorders with an especial focus on tumor suppressor role of this lncRNA.

PTENP1 is a long non-coding RNA which has been regarded as a pseudogene of the PTEN tumor suppressor gene. However, it has been shown to be a biologically active transcript that can function as a competing endogenous RNA and enhance expression of PTEN protein. This lncRNA has two transcripts, namely PTENP1-202 and PTENP1-202 with sizes of 3996 and 1215 bps, respectively. PTENP1 acts as a sponge for some PETN-targeting miRNAs, such as miR-17, miR-20a, miR-19b, miR-106b, miR-200c, miR-193a-3p, miR-499-5p and miR-214. Besides, it can affect miR-20a/PDCD4, miR-27a-3p/EGR1, miR-17-5p/SOCS6 and miR-19b/TSC1 axes. This long non-coding RNA participates in the pathoetiology of several types of cancers as well as non-malignant conditions such as alcohol-induced osteopenia, insulin resistance, osteoporosis, sepsis-associated cardiac dysfunction and spinal cord injury. In the current review, we elucidate the role of PTENP1 in human disorders, particularly malignant conditions based on evidence acquired from cell line assays, animal studies and investigations on human samples.

Tumor invasion to the spinal region after primary surgery: A case report.

BACKGROUND: It is believed that pituitary carcinoma is a rare disorder and arise from the transformation of benign invasive macroadenomas, and the process of this transformation takes place slowly. CASE PRESENTATION: A 51-year-old man presented with the clinical features of Cushing syndrome and walking impairment who was diagnosed with metastatic corticotroph pituitary carcinoma to the spine region, 6 years after the initial resection of a primary invasive pituitary adenoma. He made a visit to neurosurgery and endocrinology clinic with the chief complaint of weight gain, facial and extremities swelling, paresthesia, weakness, motion and speaking impairments, and HTN which all appeared through the last 1 year; hormonal laboratory tests showed urine free cortisol (UFC) 197.8 and 367. 30 ug/24hrs (36-137), cortisol 8 am after 1 mg overnight dexamethasone test 375 ng/mL (50-250) and ACTH 59 pg/mL. MRI study revealed a mass in the brainstem with the compression effect on spinal region, pituitary imagine does not differ from the last MRI. He underwent a neurosurgery for spinal mass resection, which was successful and the total mass was resected. After surgery, the patient's condition became better. CONCLUSION: Pituitary carcinoma is a rare entity impossible to recognize as a primary tumor because its diagnosis by definition requires the presence of metastasis. Clinical awareness of the rare possibility for aggressive adenomas will progress, to metastasize is essential to appropriately monitor patients for possible early detection and treatment of pituitary carcinoma.

Role of miRNA and lncRNAs in organ fibrosis and aging.

Fibrosis is the endpoint of pathological remodeling. This process contributes to the pathogenesis of several chronic disorders and aging-associated organ damage. Different molecular cascades contribute to this process. TGF-ß, WNT, and YAP/TAZ signaling pathways have prominent roles in this process. A number of long non-coding RNAs and microRNAs have been found to regulate organ fibrosis through modulation of the activity of related signaling pathways. miR-144-3p, miR-451, miR-200b, and miR-328 are among microRNAs that participate in the pathology of cardiac fibrosis. Meanwhile, miR-34a, miR-17-5p, miR-122, miR-146a, and miR-350 contribute to liver fibrosis in different situations. PVT1, MALAT1, GAS5, NRON, PFL, MIAT, HULC, ANRIL, and H19 are among long non-coding RNAs that participate in organ fibrosis. We review the impact of long non-coding RNAs and microRNAs in organ fibrosis and aging-related pathologies.

Inflammatory Response Leads to Neuronal Death in Human Post-Mortem Cerebral Cortex in Patients with COVID-19.

The recent coronavirus disease of 2019 (COVID-19) pandemic has adversely affected people worldwide. A growing body of literature suggests the neurological complications and manifestations in response to COVID-19 infection. Herein, we explored the inflammatory and immune responses in the post-mortem cerebral cortex of patients with severe COVID-19. The participants comprised three patients diagnosed with severe COVID-19 from March 26, 2020, to April 17, 2020, and three control patients. Our findings demonstrated a surge in the number of reactive astrocytes and activated microglia, as well as low levels of glutathione along with the upregulation of inflammation- and immune-related genes IL1B, IL6, IFITM, MX1, and OAS2 in the COVID-19 group. Overall, the data imply that oxidative stress may invoke a glial-mediated neuroinflammation, which ultimately leads to neuronal cell death in the cerebral cortex of COVID-19 patients.

Functional roles of non-coding RNAs in atrophy.

Atrophy is defined as a reduction in cell, organ, or tissue size after reaching their normal mature sizes because of loss of organelles, cytoplasmic compartments, and proteins. This process is also involved in the pathogenesis of human disorders. Inadequate nourishment, poor circulation, inadequate hormonal support, defects in nerve supply of the tissue, disproportionate induction of apoptosis in the tissue, and absence of exercise are some underlying causes of atrophy. Recently, several non-coding RNAs (ncRNAs) have been identified that regulate atrophy, thus participating in the pathobiology of related disorders such as neurodegenerative/ neuromuscular diseases, age-related muscle atrophy, and cardiac tissue atrophy. In the current review, we have focused on two classes of ncRNAs namely long ncRNAs (lncRNAs) and microRNAs (miRNAs) to unravel their participation in atrophy-associated disorders.

The contributory role of long non-coding RNAs (lncRNAs) in head and neck cancers: Possible biomarkers and therapeutic targets?

Along with the developments in techniques for genome study, our understanding of its sequences has completely changed. The non-coding sequences of the human genome are no longer considered as "junk" but are rather known to be the source of high-functioning molecules. Some of the most fascinating transcripts in this regard are long non-coding RNAs (lncRNAs) ___RNA molecules that exceed 200 nucleotides and are not transcribed from protein-coding regions of the genome. These transcripts are capable of gene regulation by various mechanisms, from epigenetic changes and chromosomal arrangements to post-transcription modulation of messenger RNAs. Furthermore, lncRNAs interact with other non-coding transcripts such as microRNAs that further affects gene expression. Considering the fact that cancer is a disease of deregulated expression, recent studies have identified lncRNAs acting as either oncogene or tumor suppressor in a wide range of human malignancies. Head and neck cancer (HNC), with a high incidence rate and unfavorable survival, is no exception in this matter and many investigations have introduced lncRNAs involved in its tumor progression and drug response, as well as those acting as promising diagnostic or prognostic markers. The present study reviews the vital regulatory roles of lncRNAs and further introduces their role in progression of HNC subtypes.

Emerging role of microRNAs in the pathogenesis of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a deadly motor neuron disease (MND) and the most frequent MND in adults. ALS is recognized by degenerative alterations in both upper and lower motor neurons. This disorder is classified to familial and sporadic classes. Disease-causing mutations in SOD1, C9ORF72, FUS, and TARDBP have been recognized in familial ALS cases. However, in spite of conduction of several genetic association studies, heritable genetic risk elements in sporadic have not been identified completely. Several miRNAs have been dysregulated in the serum samples or brain tissues of ALS patients. Moreover, a number of miRNAs have been suggested as putative biomarkers for sporadic ALS. In the current manuscript, we review of miRNAs in the development of ALS.

The gene expression of long non-coding RNAs (lncRNAs): MEG3 and H19 in adipose tissues from obese women and its association with insulin resistance and obesity indices.

BACKGROUND: There is evidence regarding the role of two lncRNAs: MEG3 and H19 the pathomechanism of obesity and related disorders. Here, we aimed to evaluate the expression of MEG3 and H19 in visceral adipose tissues (VAT) and subcutaneous adipose tissues (SAT) of obese women (n = 18), as compared to normal-weight women (n = 17). Moreover, we sought to identify the association of expression of MEG3 and H19 in SAT and VAT with obesity parameters, insulin resistance, and the mRNA expression of possible target genes involved in adipogenesis and lipogenesis including peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). METHODS: Real-time PCR was performed to investigate the mRNA expression of the above-mentioned genes in VAT and SAT from all participants. RESULTS: The results showed lower mRNA levels of H19 in SAT of obese women, compared to normal-weight women, while MEG3 expression was significantly higher in the SAT of the obese group rather than controls. Correlation analysis indicated that the transcript level of H19 had an inverse correlation with obesity indices and HOMA-IR values. However, MEG3 expression displayed a positive correlation with all the indicated parameters in all participants. Interestingly, a positive correlation was found between transcript level of MEG3 in SAT with FAS and PPARγ. However, there was an inverse correlation between SAT expression of H19 and FAS. CONCLUSIONS: It appears that lncRNAs, MEG3 and H19, are involved in obesity-related conditions. However, more clinical studies are still required to clarify the relationships between lncRNAs with obesity and related abnormalities.

The PI3K/Akt/mTORC signaling axis in head and neck squamous cell carcinoma: Possibilities for therapeutic interventions either as single agents or in combination with conventional therapies.

The latest advances in the sequencing methods in head and neck squamous cell carcinoma (HNSCC) tissues have revolutionized our understanding of the disease by taking off the veil from the most frequent genetic alterations in the components of the oncogenic pathways. Among all the identified alterations, aberrancies in the genes attributed to the phosphoinositide 3-kinases (PI3K) axis have attracted special attention as they were altered in more than 90% of the tissues isolated from HNSCC patients. In fact, the association between these aberrancies and the increased risk of cancer metastasis suggested this axis as an "Achilles Heel" of HNSCC, which may be therapeutically targeted. The results of the clinical trials investigating the therapeutic potential of the inhibitors targeting the components of the PI3K axis in the treatment of HNSCC patients, either alone or in a combined-modal strategy, opened a new chapter in the treatment strategy of this malignancy. The present study aimed to review the importance of the PI3K axis in the pathogenesis of HNSCC and also provide a piece of information about the breakthroughs and challenges of PI3K inhibitors in the therapeutic strategies of the disease.

The Prognostic Value of Thrombocytopenia in COVID-19 Patients; a Systematic Review and Meta-Analysis.

INTRODUCTION: Multiple lines of evidence have attested that decreased numbers of platelets may serve as a surrogate marker for poor prognosis in a wide range of infectious diseases. Thus, to provide a well-conceptualized viewpoint demonstrating the prognostic value of thrombocytopenia in COVID-19, we performed a meta-analysis of pertinent literature. METHODS: The keywords "platelet" OR "thrombocytopenia" AND "COVID-19" OR "coronavirus 2019" OR "2019-nCoV" OR "SARS-CoV-2" were searched in National Library of Medicine Medline/PubMed and Scopus between December 30, 2019, and May 9, 2020 in English without any restriction. The initial search results were first screened by title and abstract, and then full texts of relevant articles representing information on the platelet count (main outcome) with a clinically validated definition of COVID-19 severity were finally selected. To assess the existence of bias in the included studies, the funnel plot and egger plot along with egger tests were used. Also, the heterogeneity among the included studies was tested using the Chi-square test. RESULTS: The results of our meta-analysis of 19 studies, totaling 3383 COVID-19 patients with 744 (21.9%) severe cases, revealed that non-severe cases have a significantly higher number of platelets and showed that the probability of the emergence of thrombocytopenia is significantly higher in the severe cases with the pooled mean difference of -21.5 (%95 CI: -31.57, -11.43). CONCLUSION: Decreased number of platelets more commonly associates with severe COVID-19; however, whether the emergence of thrombocytopenia may result in diseases severity or the severity of the disease may decrease platelets, is open to debate.

Proinflammatory Cytokines in the Olfactory Mucosa Result in COVID-19 Induced Anosmia.

Studies have found increased rates of dysosmia in patients with Novel Coronavirus disease 2019 (COVID-19). However, the mechanism that causes olfactory loss is unknown. The primary objective of this study was to explore local proinflammatory cytokine levels in the olfactory epithelium in patients with COVID-19. Biopsies of the olfactory epithelium were taken from patients with confirmed COVID-19 as well as uninfected controls. Levels of tumor necrosis factor α (TNF-α) and interleukin-1-beta (IL-1ß) were assessed using ELISA and compared between groups. Average TNF-α levels were significantly increased in the olfactory epithelium of the COVID-19 group compared to the control group (P < 0.05). However, no differences in IL-1ß were seen between groups. Elevated levels of the proinflammatory cytokine TNF-α were seen in the olfactory epithelium in patients with COVID-19. This suggests that direct inflammation of the olfactory epithelium could play a role in the acute olfactory loss described in many patients with COVID-19.