The protective effect of hydroalcoholic extract of Ephedra pachyclada leaves on ovarian damage induced by cyclophosphamide in rat: An experimental study.

Background: Cyclophosphamide (CP) is an anticancer drug that acts as an alkylation agent after metabolism in the liver. CP has toxic effects on the body's cells, especially the reproductive system's function, and causes infertility. Moreover, medicinal plants have few side effects and are psychologically acceptable to patients. Objective: This study aimed to investigate the impact of Ephedra pachyclada hydroalcoholic extract (EPHE) on ovarian tissue and hypothalamic-pituitary-gonadal axis in rats treated with CP. Materials and Methods: In this experimental study, 48 adult female Wistar rats (180-200 gr, 9-10 wk) were randomly assigned to 6 experimental groups (n = 8/each): (a) control; (b) sham; (c) CP; (d) CP+250 mg/kg EPHE; (e) CP+500 mg/kg EPHE; (f) CP+1000 mg/kg EPHE. On the 29th day of the experiment, serum was collected; serum concentration of the luteinizing hormone, follicle-stimulating hormone, estrogen, progesterone, and antioxidant activity were measured. The number of ovarian follicles were also counted. Results: In the CP groups, serum concentrations of follicle-stimulating hormone and luteinizing hormone significantly increased, and estrogen and progesterone significantly decreased (p ≤ 0.05). EPHE significantly compensated for the complications caused by CP and 1000 mg/kg had the greatest effect. Antioxidant reduction by CP was significantly enhanced by EPHE, especially at higher doses (p ≤ 0.05). The number of primordial, primary, secondary, and Graafian follicles showed a significant decrease in CP groups and EPHE groups showed a significant increase compared to the CP. EPHE showed that the concentration of 1000 mg/kg was more effective than other doses (p ≤ 0.05). Conclusion: In addition to proving the effect of EPHE on the hypothalamic-pituitary-gonadal axis, our investigation showed antioxidant properties, which can be an effective factor in CP-treated rats.

Resveratrol in breast cancer treatment: from cellular effects to molecular mechanisms of action.

Breast cancer (BC) is one of the most common cancers in females and is responsible for the highest cancer-related deaths following lung cancer. The complex tumor microenvironment and the aggressive behavior, heterogenous nature, high proliferation rate, and ability to resist treatment are the most well-known features of BC. Accordingly, it is critical to find an effective therapeutic agent to overcome these deleterious features of BC. Resveratrol (RES) is a polyphenol and can be found in common foods, such as pistachios, peanuts, bilberries, blueberries, and grapes. It has been used as a therapeutic agent for various diseases, such as diabetes, cardiovascular diseases, inflammation, and cancer. The anticancer mechanisms of RES in regard to breast cancer include the inhibition of cell proliferation, and reduction of cell viability, invasion, and metastasis. In addition, the synergistic effects of RES in combination with other chemotherapeutic agents, such as docetaxel, paclitaxel, cisplatin, and/or doxorubicin may contribute to enhancing the anticancer properties of RES on BC cells. Although, it demonstrates promising therapeutic features, the low water solubility of RES limits its use, suggesting the use of delivery systems to improve its bioavailability. Several types of nano drug delivery systems have therefore been introduced as good candidates for RES delivery. Due to RES's promising potential as a chemopreventive and chemotherapeutic agent for BC, this review aims to explore the anticancer mechanisms of RES using the most up to date research and addresses the effects of using nanomaterials as delivery systems to improve the anticancer properties of RES.

Comparison of the prevalence of perforated appendicitis during and before COVID19 pandemic.

Objective: Coronavirus disease 2019 has significantly impacted the rate of emergency department visits among patients with the non-repository disease. Patients with acute appendicitis are also likely to delay their visit to the health care center, which can lead to complications including perforated appendicitis. The aim of this study was to compare the prevalence of perforated appendicitis during the COVID19 and pre-pandemic periods. Methods: This retrospective study was performed on all appendectomies performed during COVID-19, Group A, and one year earlier, Group B. A questionnaire comprising demographic variables (age, gender, occupation, education), clinical variables (white blood cell count, fever), location and type of appendicitis, the status of appendectomy, and duration of hospitalization was completed for all the patients included in the study. Results: The demographic variables were not significantly different among the two groups. The perforation appendicitis rate during the COVID19 pandemic increased compared to the previous year, The difference was not statistically significant. The number of negative appendectomy in group A was significantly less compared to group B. The mean time from the onset of pain to the time of referral was significantly lesser in group A. The mean length of hospital stay in group B was longer than in group A. In terms of fever, patients with perforated appendicitis in group B had a higher fever than in group A, which was statistically significant. Conclusion: A non-significant increase in the number of perforated appendicitis cases during the pandemic period. Duration of hospitalization and fever was significantly greater in pre-pandemic perforated appendicitis cases.

Long non-coding RNA (lncRNA) H19 in human cancer: From proliferation and metastasis to therapy.

Initiation and development of cancer depend on multiple factors that mutations in genes and epigenetic level can be considered as important drivers. Epigenetic factors include a large family of members and understanding their function in cancer has been a hot topic. LncRNAs are RNA molecules with no capacity in synthesis of proteins, and they have regulatory functions in cells. LncRNAs are localized in nucleus and cytoplasm, and their abnormal expression is related to development of tumor. This manuscript emphasizes on the role of lncRNA H19 in various cancers and its association with tumor hallmarks. The function of lncRNA H19 in most tumors is oncogenic and therefore, tumor cells increase its expression for promoting their progression. LncRNA H19 contributes to enhancing growth and cell cycle of cancers and by EMT induction, it is able to elevate metastasis rate. Silencing H19 induces apoptotic cell death and disrupts progression of tumors. LncRNA H19 triggers chemo- and radio-resistance in cancer cells. miRNAs are dually upregulated/down-regulated by lncRNA H19 in increasing tumor progression. Anti-cancer agents reduce lncRNA H19 in impairing tumor progression and increasing therapy sensitivity. A number of downstream targets and molecular pathways for lncRNA H19 have been detected in cancers including miRNAs, RUNX1, STAT3, ß-catenin, Akt2 and FOXM1. Clinical studies have revealed potential of lncRNA H19 as biomarker and its association with poor prognosis. LncRNA H19 can be transferred to cancer cells via exosomes in enhancing their progression.

Association of different pathologic subtypes of growth hormone producing pituitary adenoma and remission in acromegaly patients: a retrospective cohort study.

BACKGROUND: Regarding the inconclusive results of previous investigations, this study aimed to determine the association between pathology, as a possible predictor, with remission outcomes, to know the role of pathology in the personalized decision making in acromegaly patients. METHODS: A retrospective cohort study was performed on the consecutive surgeries for growth hormone (GH) producing pituitary adenomas from February 2015 to January 2021. Seventy-one patients were assessed for granulation patterns and prolactin co-expression as dual staining adenomas. The role of pathology and some other predictors on surgical remission was evaluated using logistic regression models. RESULTS: Among 71 included patients, 34 (47.9%) patients had densely granulated (DG), 14 (19.7%) had sparsely granulated (SG), 23 (32.4%) had dual staining pituitary adenomas. The remission rate was about 62.5% in the patients with SG and DG adenomas named single staining and 52.2% in dual staining groups. Postoperative remission was 1.53-folds higher in the single staining adenomas than dual staining-one (non-significant). The remission rate was doubled in DG group compared to two other groups (non-significant). By adjusting different predictors, cavernous sinus invasion and one-day postoperative GH levels decreased remission rate by 91% (95% CI: 0.01-0.67; p = 0.015) and 64% (95% CI: 0.19-0.69; p < 0.001), respectively. Responses to the medications were not significantly different among three groups. CONCLUSION: Various pathological subtypes of pituitary adenomas do not appear to have a predictive role in estimating remission outcomes. Cavernous sinus invasion followed by one-day postoperative GH is the strongest parameter to predict biochemical remission.

Recurrence of a neuroendocrine tumor of adrenal origin: a case report with more than a decade follow-up.

BACKGROUND: Neuroendocrine tumor (NET) with adrenocorticotropic hormone (ACTH) secretion are very rare. To our knowledge, no follow-up study is published for ACTH-secreting NET, regardless of the primary site, to show second occurrence of tumor after a long follow-up, following resection of primary tumor. CASE PRESENTATION: Here, we describe a 49-year-old-man with cushingoid feature, drowsiness and quadriparesis came to emergency department at December 2005. Laboratory tests revealed hyperglycemia, metabolic alkalosis, severe hypokalemia, and chemical evidence of an ACTH-dependent hypercortisolism as morning serum cortisol of 57 µg /dL without suppression after 8 mg dexamethasone suppression test, serum ACTH level of 256 pg/mL, and urine free cortisol of > 1000 µg /24 h. Imaging showed only bilateral adrenal hyperplasia, without evidence of pituitary adenoma or ectopic ACTH producing tumors. Importantly, other diagnostic tests for differentiating Cushing disease (CD) from ectopic ACTH producing tumor, such as inferior petrosal sinus sampling (IPSS), corticotropin releasing hormone (CRH) stimulation test, octreotide scan or fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan were not available in our country at that time. Therefore, bilateral adrenalectomy was performed that led to clinical and biochemical remission of hypercortisolism and decreased ACTH level to < 50 pg/mL, findings suggestive of a primary focus of NET in adrenal glands. After 11 years uncomplicated follow up, the ACTH level elevated up to 341 pg/mL and re-evaluation showed a 2 cm nodule in the middle lobe of the right lung. Surgical excision of the pulmonary nodule yielded a carcinoid tumor with positive immunostaining for ACTH; leading to decrease in serum ACTH level to 98 pg/mL. Subsequently after 7 months, serum ACHT levels rose again. More investigation showed multiple lung nodules with metastatic bone lesions accompanied by high serum chromogranin level (2062 ng/mL), and the patient managed as a metastatic NET, with bisphosphonate and somatostatin receptor analogues. CONCLUSION: This case of surgically-treated NET showing a secondary focus of carcinoid tumor after one decade of disease-free follow-up emphasizes on the importance of long-term follow-up of ACTH-secreting adrenal NET.

Hydralazine induces stress resistance and extends C. elegans lifespan by activating the NRF2/SKN-1 signalling pathway.

Nuclear factor (erythroid-derived 2)-like 2 and its Caenorhabditis elegans ortholog, SKN-1, are transcription factors that have a pivotal role in the oxidative stress response, cellular homeostasis, and organismal lifespan. Similar to other defense systems, the NRF2-mediated stress response is compromised in aging and neurodegenerative diseases. Here, we report that the FDA approved drug hydralazine is a bona fide activator of the NRF2/SKN-1 signaling pathway. We demonstrate that hydralazine extends healthy lifespan (~25%) in wild type and tauopathy model C. elegans at least as effectively as other anti-aging compounds, such as curcumin and metformin. We show that hydralazine-mediated lifespan extension is SKN-1 dependent, with a mechanism most likely mimicking calorie restriction. Using both in vitro and in vivo models, we go on to demonstrate that hydralazine has neuroprotective properties against endogenous and exogenous stressors. Our data suggest that hydralazine may be a viable candidate for the treatment of age-related disorders.

A Significant Breakthrough in the Incidence of Childhood Cancers and Evaluation of its Risk Factors in Southern Iran.

BACKGROUND AND OBJECTIVE: This study investigates epidemiologic and practical information about the incidence and risk factors of childhood cancer in a population of Southern Iranian children. MATERIALS AND METHODS: A total number of 300 cancer patients along with 600 age- and gender-matched healthy control were interviewed by a trained physician regarding their demographic characteristics, and major family-associated risk factors, childhood malignancies. RESULTS: The average annual percentage change for cancers in the studied population is calculated as 45%. Our study indicated that possible risk factors which could contribute to the development of childhood cancer are maternal oral contraceptive pill use during pregnancy, exposure to radiation during pregnancy, parental smoking, residence near high voltage electricity lines, exposure to pesticides and fertilizers, patient allergy, contact with domestic animals and father's educational degree. Furthermore, new ecological risk factors such as air pollution due to nonstandard petroleum or toxic inhalant particles, nonhealthy food consumption, and satellite jamming are other predisposing factors. CONCLUSION: Our study reported a higher average annual percentage change of childhood cancers in our area, compared to the existing literature. In conclusion, detection and prevention of the consistent and possible new environmental risk factors such as nonstandard petroleum or satellite jamming from all around the country should be taking into consideration.