Recurrent acromegaly: a systematic review on therapeutic approaches.

BACKGROUND AND OBJECTIVE: Management of recurrent acromegaly is challenging for both neurosurgeons and endocrinologists. Several treatment options including repeat surgery, medical therapy, and radiation are offered for such patients. The efficacy of these modalities for the treatment of recurrence has not been studied previously in the literature. In this study, we aim to systematically review the existing cases of recurrence and come to a conclusion regarding the appropriate treatment in such cases. METHOD: A systematic review was performed through PubMed, Scopus, Web of Science, and Cochrane database to identify studies reporting the treatment outcome of recurrent acromegaly patients. Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, the included studies were reviewed for primary and secondary treatment, complications, and outcomes of the secondary treatment. RESULTS: The systematic review retrieved 23 records with 95 cases of recurrent acromegaly. The mean time of recurrence was 4.16 years after the initial treatment. The most common primary treatment was surgery followed by radiotherapy. The remission rate was significantly higher in medical and radiotherapy compared to surgical treatment. CONCLUSION: In cases of recurrent acromegaly, the patient may benefit more from radiotherapy and medical therapy compared to surgery. As the quality of evidence is low on this matter feature studies specifically designed for recurrent patients are needed.

Emerging role of extracellular vesicles in the pathogenesis of glioblastoma.

While brain tumors are not extremely frequent, they cause high mortality due to lack of appropriate treatment and late detection. Glioblastoma is the most frequent type of primary brain tumor. This malignant tumor has a highly aggressive behavior. Expression profile of different types of transcripts, methylation status of a number of genomic loci and chromosomal aberrations have been found to affect course of glioblastoma and propensity for recurrence and metastasis. Recent studies have shown that glioblastoma cells produce extracellular vesicles whose cargo can affect behavior of neighboring cells. Several miRNAs such as miR-301a, miR-221, miR-21, miR-16, miR-19b, miR-20, miR-26a, miR-92, miR-93, miR-29a, miR-222, miR-221 and miR-30a have been shown to be transferred by glioblastoma-derived extracellular vesicles and enhance the malignant behavior of these cells. Other components of glioblastoma-derived extracellular vesicles are EGFRvIII mRNA/protein, Ndfip1, PTEN, MYC ssDNA and IDH1 mRNA. In the current review, we discuss the available data about the molecular composition of glioblastoma-derived extracellular vesicles and their impact on the progression of this malignant tumor and its resistance to therapeutic modalities.

Complete Loss of Myelin protein zero (MPZ) in a patient with a late onset Charcot-Marie-Tooth (CMT).

Charcot-Marie-Tooth (CMT) comprises a group of hereditary neuropathies with clinical, epidemiological, and molecular heterogeneity in which variants in more than 80 different genes have been reported. One of the important genes which cause 5% of all CMT cases is Myelin protein zero (P0, MPZ). Variants in this gene have been reported in association with different forms of CMT including classical CMT1, severe DSS (CMT3B), DI-CMT, CMT2I and CMT2J with autosomal dominant (AD) inheritance. To our knowledge, MPZ variants have not been described in autosomal recessive (AR) form of CMT in previous studies. Moreover, its complete deletion has not been reported in human. Here, we described clinical characteristics of a patient with CMT symptoms who demonstrated manifestations of the disease late in his life. We performed exome sequencing for identifying CMT subtype and its associated gene, and follow that co-segregation analysis has been done to characterize inheritance pattern of the disorder. Through using exome sequencing, we identified a novel 4074 bp homozygote deletion which encompasses all 6 exons of the MPZ gene in this patient. After identifying the alteration, variant confirmation and co-segregation analysis have been performed by using specific primers. Our result revealed that the patient's parents were heterozygous for the alteration and they did not show any symptoms of CMT. Although most MPZ variants have been described with early onset CMT with AD pattern of inheritance, the reported patient in our study had late onset form and his parents did not show any symptoms. Considering substantial role of MPZ protein in the biogenesis of peripheral nervous system (PNS) myelin, we proposed that there should be another protein in PNS that compensates for lack of MPZ protein. Taken together, our finding is the first report of MPZ association with AR form of CMT with late onset features. Moreover, our results propose the presence of another protein in PNS myelin biogenesis and its assembly. However, functional studies alongside with other molecular studies are needed to confirm our results and identify the proposed protein.

Effect of sustained release bolus oral administration on body condition change, blood parameters, and uterine health in primiparous cows under heat stress.

The transition period is very stressful for primiparous cows due to their first calving experience and will be more challenging if it occurs under heat stress conditions. Heat stress reduces the feed intake of dairy cows. Therefore, it reduces the consumption of minerals and vitamins. Oral administration of boluses through the provision of mineral-vitamin compounds can reduce metabolic abnormalities after calving. The present study aimed to evaluate effect of sustained-release bolus on body condition score (BCS) change, serum metabolites, uterine health, and reproductive status in primiparous cows. Heifers were selected at the beginning of the close-up period (n = 60, BCS = 3.35 ± 0.12). There were 2 experimental treatments at the time of calving: (1) heifers without bolus oral administration (H - Bo, n = 30); (2) heifers with bolus oral administration (H + Bo, n = 30). The results showed that although the rate of BCS loss was lower in the group receiving bolus, the effect of bolus was not significant. The effect of bolus on blood level of glucose, non-esterified fatty acids (NEFA), and beta-hydroxybutyrate (BHBA) was not significant; however, the highest concentration of albumin (P = 0.05) was observed in the H + Bo group on day 42 after calving. The concentration of aspartate transaminase (AST) tended to increase (P = 0.06) on day 14 after calving and entire the study. Total antioxidant capacity (TAC) was affected (P < 0.05) by bolus throughout the period of study, and the highest (P < 0.05) concentration of glutathione peroxidase (GPX) and superoxide dismutase (SOD) was observed in H + Bo group on day 42 after calving. The H + Bo group had the lowest (P < 0.05) vaginal discharge score (VDS). In general, oral administration of the sustained-release bolus in heifers significantly affected the antioxidant factors and uterine health, as well as had positive effects on liver function, body condition, and reproduction status.

Effect of sustained-release antioxidant bolus on body condition score, blood parameters, uterine health, and some reproductive parameters in transition dairy cows under heat stress condition.

The transition period for dairy cows is stressful, and if this occurs during heat stress conditions, it will become more challenging for them. This study aimed to evaluate the effect of sustained-release bolus (Each bolus consisted of a mixture of mineral salts including copper sulfate (8 g), sodium selenite (0.17 g), manganese sulfate (3.9 g), zinc sulfate (2.4 g), and vitamin A (0.47 g) on body condition score (BCS) change, serum metabolites, uterine health, and some reproductive parameters in transition cows with moderate or high pre-calving BCS. Four experimental treatments were (1) moderate BCS without bolus consumption (MB-Bo, n = 35), (2) moderate BCS with bolus consumption (MB + Bo, n = 35), (3) high BCS without bolus consumption (HB-Bo, n = 35), and (4) high BCS with bolus consumption (HB + Bo, n = 35). Results showed that after calving, negative energy balance occurred in all experimental groups. However, cows with high BCS (HB-Bo and HB + Bo) had greater (P = 0.02) BCS change during the postpartum period (0-40 days). Bolus administration decreased white blood cells count 14 days after calving (P = 0.02). Cows with moderate BCS (MB-BO and MB + Bo) had higher (P < 0.01) red blood cell count than cows with high BCS (HB-Bo and HB + Bo) on 14 days after calving. The cows in MB + Bo group had higher (P < 0.05) serum glucose and albumin and lower (P < 0.01) non-esterified fatty acids and beta-hydroxybutyrate. Moreover, this group of cows had higher (P < 0.05) serum total antioxidant capacity, glutathione peroxidase and superoxide dismutase, and lower malondialdehyde (P = 0.03) than other groups. In this regard, the increase in antioxidant capacity with the consumption of blues caused the HB-Bo group to have more incidence of metritis (P = 0.08) and endometritis (P = 0.08). The HB-Bo group had about 12 days longer (P < 0.01) days open than MB + Bo group. It was concluded that consumption of slow-release bolus containing antioxidant elements had positive effect on the metabolic and reproductive status of high-producing dairy cows under heat stress condition.

A review on the role of MCM3AP-AS1 in the carcinogenesis and tumor progression.

Minichromosome Maintenance Complex Component 3 Associated Protein Antisense 1 (MCM3AP-AS1) is an RNA gene located on 21q22.3. The sense transcript from this locus has dual roles in the pathogenesis of solid tumors and hematological malignancies. MCM3AP-AS1 has been shown to sequester miR-194-5p, miR-876-5p, miR-543-3p, miR-28-5p, miR-93, miR-545, miR-599, miR-193a-5p, miR-363-5p, miR-204-5p, miR-211-5p, miR-15a, miR-708-5p, miR-138, miR-138-5p, miR-34a, miR-211, miR-340-5p, miR-148a, miR-195-5p and miR-126. Some cancer-related signaling pathway, namely PTEN/AKT, PI3K/AKT and ERK1/2 are influenced by this lncRNA. Cell line studies, animal studies and clinical studies have consistently reported oncogenic role of MCM3AP-AS1 in different tissues except for cervical cancer in which this lncRNA has tumor suppressor role. In the current manuscript, we collected evidence from these three sources of evidence to review the impact of MCM3AP-AS1 in the carcinogenesis.

A review on the role of mir-16-5p in the carcinogenesis.

miR-16-5p is microRNA with important roles in the development of diverse malignancies including neuroblastoma, osteosarcoma, hepatocellular carcinoma, cervical cancer, breast cancer, brain tumors, gastrointestinal cancers, lung cancer and bladder cancer. This miRNA has 22 nucleotides. hsa-miR-16-5p is produced by MIR16-1 gene. First evidence for its participation in the carcinogenesis has been obtained by studies reporting deletion and/or down-regulation of these miRNAs in chronic lymphocytic leukemia. Subsequent studies have shown down-regulation of miR-16-5p in a variety of cancer cell lines and clinical samples. Besides, tumor suppressor role of miR-16-5p has been verified in animal models of different types of cancers. Studies in these models have shown that over-expression of this miRNA or modulation of expression of lncRNAs that sponge this miRNA can block carcinogenic processes. In the current review, we summarize function of miR-16-5p in the development and progression of different cancers.

A review on the role of DANCR in the carcinogenesis.

DANCR is an RNA gene located on chr4. This gene has several splice variants. Up-regulation of DANCR has been reported in many types of cancers. This lncRNA is mainly located in the cytoplasm and regulates genes expression at post-transcriptional level. In fact, it acts as a molecular sponge for a variety of miRNAs, including miR-874-3P, miR-335, miR-149, miR-4319, miR-758-3p, miR-216a-5p, miR-874-3p, miR-33a-5p, miR-335-5p, miR-145-3p, miR-665, miR-345-5p and miR-125b-5p. DANCR also regulates activity of PI3K/AKT/NF-κB, Wnt/ß-catenin, ERK/SMAD, MAPK, IL-6/JAK1/STAT3, Smad2/3, p53, FAK/PI3K/AKT/GSK3ß/Snail pathways. In the current narrative review article, we summarize the roles of DANCR in the carcinogenesis, with an especial emphasis on its role in the development of osteosarcoma and lung, liver, pancreatic and colorectal cancers.

Role of long non-coding RNAs (LncRNAs) in multiple sclerosis: a brief review.

Multiple sclerosis (MS) as chronic autoimmune inflammatory neurological disease of the central nervous system (CNS) occurs due to several environmental and genetic factors, whose pathogenesis is associated with genes with regulatory role in the immune system. Long non-coding RNAs (LncRNAs) are able to reportedly regulate responses of immune systems and expression of genes, and show the tissue specificity and complexity of biofunctions. Various studies have suggested that the aberrant LncRNA expression is an underlying factor involved in the incidence of MS and that the analysis of the expression profile of these molecules can be a specific biomarker of MS for preventing the course of the disease or responding to treatment. The purpose of this research was to review the recent studies for exploring the functions of LncRNAs in the processes leading to MS disease.

Short communication: Test of the relationship between prepartum milk leakage and blood calcium concentration in Holstein cows-An observational study.

Prepartum milk leakage happens in some pregnant dairy cows close to calving. It has been hypothesized that low blood Ca is a cause of this event. To investigate the possible reason(s) of milk leakage, 137 multiparous pregnant Holstein cows were enrolled in the experiment and categorized by the presence (72 cows; leak group) or lack (65 cows; control group) of milk leakage before calving. The concentrations of Ca and P and the length of the teat were measured for all cows. Data showed that Ca concentration was not different between cows in the leak group (7.90 mg/dL) and those in the control group (7.99 mg/dL). Moreover, neither P concentration (4.62 vs. 4.54 mg/dL) nor teat length (4.28 vs 4.10 cm) differed between leak and control groups. Milk yield was greater for the leak group (53.6 kg/d) compared with the control group (50.1 kg/d) through 4 mo in milk. The leakage did not affect the odds of postpartum disorders such as retained placenta, metritis, mastitis, displaced abomasum, or lameness occurrence. The current results show that hypocalcemia is not a reason for observed prepartum leakage and that cows in the leak group produced more milk in the subsequent lactation period.

ATP2B1 rs2681472 and STK39 rs35929607 polymorphisms and risk of Hypertension in Iranian Population.

Background: ATP2B1 and STK39 have been introduced as essential hypertension candidate genes. The association of these genes' variations have not been studied in Iranian population yet. Here we aimed to investigate the association of ATP2B1 rs2681472 and STK39 rs35929607 polymorphisms with the risk of hypertension in an Iranian population. Methods: We included 400 individuals in our case-control study: 200 cases with essential hypertension and 200 healthy sex and age matched controls. All subjects were genotyped for rs2681472 and rs35929607 using a PCR-RFLP method. Genotype and allele frequencies were compared between the two groups using chi-squared test. The association was further assessed under log-additive, dominant and recessive genetic models. Results: There was no association between rs2681472 and rs35929607 polymorphisms and risk of essential hypertension in our population (p>0.05). There was also no association between the studied polymorphisms and hypertension under different genetic models. Conclusion: Our study indicated that rs2681472 of ATP2B1 and rs35929607 of STK39 may not have a significant effect on the risk of essential hypertension in Iranian population. More studies are still needed to validate our results.

Spontaneous complete regression of hypothalamic pilocytic astrocytoma after partial resection in a child, complicated with Stevens-Johnson syndrome: a case report and literature review.

Pilocytic astrocytoma (PA) is the most common pediatric central nervous system glial neoplasm and the most common pediatric cerebellar tumor. The spontaneous regression that occurs after partial/subtotal resection is multifactorial, depending on multiple factors, as for the case of humoral and cell-mediated immune responses of the host to the implanted tumor. A 7-year-old boy was referred to a neurosurgery clinic with headache. Further imaging workup revealed hypothalamic PA. Partial resection of the lesions was performed with right-side pterional approach. The patient developed a severe panmucositis [Stevens-Johnson syndrome (SJS)] and respiratory failure plus conjunctivitis, due to phenytoin allergy. During the patient's 6-month follow-up, postoperative magnetic resonance imaging (MRI) revealed a residual tumor, and about 9 months later (at 15 months postoperatively), the MRI showed total regression of the tumor. Clinically, symptomatic PA may undergo spontaneous regression after partial resection. We report a well-documented case of spontaneous regression hypothalamic PA after partial resection that complicated with SJS. Immune system reaction in SJS may have a role in tumor behavior and spontaneous regression. Multiple studies confirmed spontaneous regression in PA after partial/subtotal resection. This phenomenon occurs due to humoral and cell-mediated host immune responses to the implanted tumor. The immune system reaction in SJS may have a role in tumor behavior and spontaneous regression.

The significance of N6-methyladenosine-modified non-coding RNAs in different disorders.

N6-methyladenosine (m6A) is the most widespread endogenous modification affecting the expression of eukaryotic mRNA transcripts. Recent studies have shown that the m6A marks within non-coding RNAs can affect their functions and expression in a manner similar to that of mRNA-coding genes. Since non-coding RNAs are involved in the pathophysiology of several disorders, identification of the role of m6A marks in the regulation of expression of non-coding RNAs can open a new era for identifying underlying mechanisms of several disorders and designing novel therapeutic modalities for a variety of disorders, particularly cancers. Moreover, a number of non-coding RNAs can affect m6A levels. In the current review, we discuss the impacts of m6A marks on the expression of non-coding RNAs in the context of different disorders, such as bone, gastrointestinal, neurologic, renal, pulmonary, hepatic and other disorders.

Interactions between non-coding RNAs and HIF-1α in the context of cancer.

Hypoxia-inducible factor 1α (HIF-1α) is a subunit of the HIF-1 transcription factor which is encoded by the HIF1A gene. This transcription factor is the main modulator of the cell response to hypoxia. Hypoxia-induced up-regulation of HIF-1α is involved in the pathogenesis of cancer. Recently, the interactions of several long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) with HIF-1α have been reported. These ncRNAs regulate the expression of HIF-1α through different mechanisms. The regulatory roles of ncRNAs on HIF-1α are involved in the response of cancer cells to a wide range of anticancer drugs such as sorafenib, cisplatin, propofol, doxorubicin, and paclitaxel. Therefore, identification of the complex network between ncRNAs and HIF-1α not only facilitates the design of novel therapies but also promotes the efficacy of conventional anticancer treatments. This review aims to explain the interactions between these classes of ncRNAs and HIF-1α in the context of cancer.

A review on the role of ZEB1-AS1 in human disorders.

ZEB1 Antisense RNA 1 (ZEB1-AS1) is a type of RNA characterized as long non-coding RNA (lncRNA). This lncRNA has important regulatory roles on its related gene, Zinc Finger E-Box Binding Homeobox 1 (ZEB1). In addition, role of ZEB1-AS1 has been approved in diverse malignancies such as colorectal cancer, breast cancer, glioma, hepatocellular carcinoma and gastric cancer. ZEB1-AS1 serves as a sponge for a number of microRNAs, namely miR-577, miR-335-5p, miR-101, miR-505-3p, miR-455-3p, miR-205, miR-23a, miR-365a-3p, miR-302b, miR-299-3p, miR-133a-3p, miR-200a, miR-200c, miR-342-3p, miR-214, miR-149-3p and miR-1224-5p. In addition to malignant conditions, ZEB1-AS1 has functional role in non-malignant conditions like diabetic nephropathy, diabetic lung, arthrosclerosis, Chlamydia trachomatis infection, pulmonary fibrosis and ischemic stroke. This review outlines different molecular mechanisms of ZEB1-AS1 in a variety of disorders and highlights its importance in their pathogenesis.

Abnormal expression of MAPK14-related lncRNAs in the peripheral blood of patients with multiple sclerosis.

Introduction: Contribution of MAPK14 in the pathogenesis of multiple sclerosis (MS) has been proposed by several studies. Long non-coding RNA (lncRNA) have been suggested to be functionally linked with Mitogen-activated protein kinase 14 (MAPK14). Methods: Expression levels of MAPK14 and its associated lncRNAs were measured in the circulation of MS patients compared with control subjects. Results: Expression levels of NORAD and RAD51-AS1 were higher in total patients compared with controls (Expression ratio (95% CI) = 1.4 (1.04-1.89), P value = 0.015 and Expression ratio (95% CI) = 1.91 (1.43-2.6), P value = 0.0001, respectively). Conversely, ZNRD1ASP was under-expressed in cases compared with controls (Expression ratio (95% CI) = 0.61 (0.41-0.8), P value = 0.0005). In spite of the observed abnormal expression levels of these lncRNAs in the circulation of MS patients, their expressions were not correlated with Expanded Disability Status Scale (EDSS) score, disease duration or age at disease onset. Conclusion: To sum up, the current investigation shows dysregulation of MAPK14-related lncRNAs in MS patients.

The Sensorineural Hearing Loss Related to a Rare Infratentorial Developmental Venous Angioma: A Case Report and Review of Literature.

BACKGROUND: Developmental venous anomaly (DVA) is a benign venous abnormality draining normal brain parenchyma. It is mostly asymptomatic; however, rare complications such as hemorrhage may lead to symptomatic conditions. Headache and seizure are the most common symptoms. Hearing loss is an extremely rare presentation of DVA. To our knowledge, only five cases of DVA, presenting with hearing loss, had been reported so far. CASE PRESENTATION: We report the case of a 27-year-old woman who presented with a sensorineural hearing loss followed by facial paresis. Magnetic resonance imaging (MRI) and computed tomography (CT) angiography revealed hematoma with adjacent converging veins showing a typical "caput medusa" sign in the left middle cerebellar peduncle, in favor of DVA. Due to the compression effect of hematoma, she underwent surgery. Hearing loss and facial paresis improved significantly during the postoperative follow-up. CONCLUSION: Although DVA is mostly benign and asymptomatic, complications such as hemorrhage rarely occur. Hearing loss is an extremely rare presentation that can be attributable to the compression effect on the cranial nerve VII to VIII complex. In the case of compression effect or progression of symptoms, surgical intervention is necessary. A good clinical outcome could be expected postoperatively.

A rare case of iatrogenic intracranial hypotension due to a minor CSF leakage.

Intracranial hypotension (IH) represents a rare complication, mainly following cerebrospinal fluid (CSF) leakage at the thoracic or cervicothoracic junction level. Iatrogenic IH may be expected secondary to the previous surgery or other procedures invading the patient's dura. Magnetic resonance imaging (MRI), computerized tomography (CT) scan images, CT cisternography, and magnetic resonance cerebrospinal fluid flow (MR CSF) remains the modality of choice to establish the diagnosis. The patient is in her late sixth decade, reflecting a history of progressive headaches, nausea, and vomiting. Once a diagnosis of foramen magnum meningioma was established using MRI, total microscopic resection was applied. Brain sagging and subdural fluid collection were identified on postoperative day three, suggesting intracranial hypotension due to cerebrospinal fluid leakage. Diagnosing IH following the CSF leak during the postoperative phase remains challenging. Although rare, early clinical suspicion must be considered to establish the diagnosis.

Expression of Linear and Circular lncRNAs in Alzheimer's Disease.

Alzheimer's disease is a neurodegenerative disorder of the elderly described by progressive cognitive debility. Recent studies have displayed the significance of linear and circular long non-coding RNAs (lncRNAs) in the pathobiology of Alzheimer's disease. These studies have reported the downregulation of MALAT1, while the upregulation of NEAT1, RP11-543N12.1, SOX21-AS1, BDNF-AS, BACE1-AS, ANRIL, XIST, and some other linear lncRNAs in clinical samples are obtained from these patients or animal models of Alzheimer's disease. A number of circRNAs such as ciRS-7, ciRS-7, circNF1-419, circHDAC9, circ_0000950,and circAß-a have been shown to partake in the pathogenesis of this disorder. In the present manuscript, we provide a review of the impact of linear and circular lncRNAs in the pathobiology of Alzheimer's disease and their potential application as markers for this neurodegenerative condition.

DLX6-AS1: A Long Non-coding RNA With Oncogenic Features.

Long non-coding RNAs (lncRNAs) are a heterogeneous group of ncRNAs with characteristic size of more than 200 nucleotides. An increasing number of lncRNAs have been found to be dysregulated in many human diseases particularly cancer. However, their role in carcinogenesis is not precisely understood. DLX6-AS1 is an lncRNAs which has been unveiled to be up-regulated in various number of cancers. In different cell studies, DLX6-AS1 has shown oncogenic role via promoting oncogenic phenotype of cancer cell lines. Increase in tumor cell proliferation, migration, invasion, and EMT while suppressing apoptosis in cancer cells are the effects of DLX6-AS1 in development and progression of cancer. In the majority of cell experiment, mediator miRNAs have been identified which are sponged and negatively regulated by DLX6-AS1, and they in turn regulate expression of a number of transcription factors, eventually affecting signaling pathways involved in carcinogenesis. These pathways form axes through which DLX6-AS1 promotes carcinogenicity of cancer cells. Xenograft animal studies, also have confirmed enhancing effect of DLX6-AS1 on tumor growth and metastasis. Clinical evaluations in cancerous patients have also shown increased expression of DLX6-AS1 in tumor tissues compared to healthy tissues. High DLX6-AS1 expression has shown positive association with advanced clinicopathological features in cancerous patients. Survival analyses have demonstrated correlation between high DLX6-AS1 expression and shorter survival. In cox regression analysis, DLX6-AS1 has been found as an independent prognostic factor for patients with various types of cancer.