Modern neurosurgery clearly relies on evidence-based medicine. The integrity, interpretation, and application of research depended on a solid understanding of the statistical methods used. This review highlights the important need for neurosurgeons and trainees to gain proficiency in basic statistical concepts. We emphasize this need throughout the research process—from forming hypotheses and defining variables to selecting tests, analyzing power, and interpreting key indices. Also, we provide practical guides for choosing suitable statistical tests and translating research findings into useful clinical metrics. We believe that statistical literacy is not an extra skill but a key part of clinical expertise and academic success. It allows neurosurgeons to evaluate literature, conduct valid research, and effectively apply evidence in patient care.

Glioblastoma multiforme (GBM) is a common central nervous system malignancy with poor survival despite new treatments. Although some evidence demonstrated the prognostic effects of metastasis-associated lung adenocarcinoma transcript 1 ( MALAT1 ) and urothelial carcinoma associated 1 ( UCA1 ) long non-coding RNAs (lncRNAs) in patients with GBM, a comprehensive study has not yet evaluated the clinical importance of these lncRNAs. Hence, this review aimed to predict the significance of expressions of MALAT and UCA1 lncRNAs in patients with GBM. Using proper keywords, a thorough literature search was performed via databases, including PubMed, Web of Knowledge, Scopus, and EMBASE until December 2024. The relationship between lncRNA expressions and overall survival (OS) in patients with GBM was assessed using hazard ratios (HR) and confidence intervals (95% CI), and the fixed and random effects models were used to estimate the pooled effect size. Also, the Newcastle-Ottawa Quality Assessment Scale was used as an appraisal tool. Among 1553 initially founded records, 13 studies were enrolled in the final analysis, consisting of 915 and 257 samples in the MALAT1 and UCA1 groups, respectively. Compared to the patients with low expression, those with high expression of MALAT1 had a mortality risk of 80% (HR = 1.8, 95% CI = [1.39, 2.33], p  = .001). Additionally, the impact of UCA1 expression on patient prognosis indicated that lower OS among patients was correlated with high expression of UCA1 ; however, the meta-analysis was not performed for UCA1 due to a lack of adequate studies. According to our findings, high expression of MALAT1 was correlated with poor prognosis in patients with GBM.

Background: Chlordiazepoxide is a benzodiazepine which is widely used as an anxiolytic, sedative and muscle-relaxant and its effects on neurodevelopment is yet to be identified. The aim of the current experimental study was to determine the effects of prenatal exposure to chlordiazepoxide on development of the prefrontal cortex (PFC). Materials and Methods: A total number of 9 pregnant Wister rats that were randomly assigned to three groups receiving standard rat food and drinking water ad libitum (n=3) or chlordiazepoxide (10 mg/kg) (n=3) and an equal volume of vehicle (0.9% NaCl) (n=3) intraperitoneal (i.p.) injection once daily from first to 21st day of gestation, respectively. At the end of the experiment, 14-day-old neonatal rat pups (n=8 per each group) were sacrificed and their PFC cells were extracted. Mitochondria were extracted from the PFC cells and their level of reactive oxygen species (ROS), protein density, Glutathione (GSH) content, mitochondrial membrane potential (MMP), swelling, cytochrome c release and ATP level was identified. We also performed the Nissl staining, DNA fragmentation assay and RNA extraction and real-time polymerase chain reaction (PCR) on PFC cells. Results: We found that isolated mitochondria from rat pups receiving chlordiazepoxide (E), had significantly higher ROS formation (P<0.001), decreased GSH (P<0.001), lower MMP (P<0.001), higher mitochondrial swelling (P<0.001), decreased ATP level (P<0.001), increased cytochrome c release (P<0.001) and higher Bax (P<0.001), p53 (P<0.001), cytochrome c (P<0.001) and caspase 8 mRNAs (P<0.001). The Nissle-stained neurons decreased while the apoptosis significantly increased (P<0.001). Conclusions: The results of this in vivo study provide evidence regarding negative effects of prenatal exposure to chlordiazepoxide on PFC.

BACKGROUND:Glioblastoma (GBM) is a malignant brain tumor that frequently occurs alongside other central nervous system (CNS) conditions. The secretome of GBM cells contains a diverse array of proteins released into the extracellular space, influencing the tumor microenvironment. These proteins can serve as potential biomarkers for GBM due to their involvement in key biological processes, exploring the secretome biomarkers in GBM research represents a cutting-edge strategy with significant potential for advancing diagnostic precision, treatment monitoring, and ultimately improving outcomes for patients with this challenging brain cancer. AIM:This study was aimed to investigate the roles of secretome biomarkers and their pathwayes in GBM through bioinformatics analysis. METHODS AND RESULTS:Using data from the Gene Expression Omnibus and the Cancer Genome Atlas datasets-where both healthy and cancerous samples were analyzed-we used a quantitative analytical framework to identify differentially expressed genes (DEGs) and cell signaling pathways that might be related to GBM. Then, we performed gene ontology studies and hub protein identifications to estimate the roles of these DEGs after finding disease-gene connection networks and signaling pathways. Using the GEPIA Proportional Hazard Model and the Kaplan-Meier estimator, we widened our analysis to identify the important genes that may play a role in both progression and the survival of patients with GBM. In total, 890 DEGs, including 475 and 415 upregulated and downregulated were identified, respectively. Our results revealed that SQLE, DHCR7, delta-1 phospholipase C (PLCD1), and MINPP1 genes are highly expressed, and the Enolase 2 (ENO2) and hexokinase-1 (HK1) genes are low expressions. CONCLUSION:Hence, our findings suggest novel mechanisms that affect the occurrence of GBM development, growth, and/or establishment and may also serve as secretory biomarkers for GBM prognosis and possible targets for therapy. So, continued research in this field may uncover new avenues for therapeutic interventions and contribute to the ongoing efforts to combat GBM effectively.

Study designA systematic review and meta-analysisObjectiveTo determine the global frequency of osteomyelitis in individuals with spinal cord injury who have pressure injuries (SCI-PI).MethodsA comprehensive search on PubMed, EMBASE, Scopus, and the Web of Science has been conducted until November 2023. The Cochrane Handbook for Systematic Reviews was followed. Cohort and cross-sectional studies included SCI-PI participants who reported the frequency of osteomyelitis without language restriction. Data extraction was performed by four reviewers in two groups. We used the Newcastle-Ottawa Quality Assessment Scale for quality assessment. The Chi-squared and I2 tests were applied to detect heterogeneity between studies. Also, a random-effects model was performed for the report data.ResultsTen out of 986 studies met our eligibility criteria, with 492 SCI-PI individuals. It was discovered that most SCIs were thoracolumbar injuries and male. There was a history of PI in more than half the patients. SCI was primarily caused by trauma. A meta-analysis revealed a significantly heterogeneous 43.0% osteomyelitis frequency. There was no evidence of publication bias. Subgroup analysis based on study quality revealed that the frequency of osteomyelitis in low-quality studies was 34.5%, whereas the frequency in high-quality research was 47.4%. Furthermore, the overall frequency of osteomyelitis was 29.0% in the subgroup analysis of research carried out in the USA.ConclusionsOur study highlights the significant burden of osteomyelitis among SCI-PI individuals. These findings underscore the pressing need for standardized diagnostic and management protocols to mitigate the morbidity associated with osteomyelitis in this vulnerable population.

The thalamic lesion is one of the most challenging tumors with significant mortality and morbidities. Current literature highlights the importance of individualized treatment strategies tailored to the specific characteristics of the lesion and the patient. In terms of efficacy, studies have demonstrated that maximal safe resection (MSR) of thalamic lesions can lead to better tumor control, prolonged progression-free survival, and improved overall survival rates compared to biopsy alone. However, the feasibility of achieving MSR is highly dependent on the location, size, and histology of the lesion, as well as the patient's functional status and overall health. Also, surgical interventions in the thalamus carry inherent risks of neurological deficits, including sensory, motor, and cognitive impairments, depending on the extent of surgical resection and proximity to eloquent neural structures. On the other hand, biopsy remains a valuable diagnostic tool for obtaining tissue samples and establishing a definitive histological diagnosis in cases where MSR is not feasible or poses a high risk of neurological complications. Indeed, biopsy is preferred in patients with advanced age, significant comorbidities, or lesions located in eloquent regions of the thalamus where aggressive surgical resection may result in considerable morbidity. Quality of life (QoL) outcomes, including functional status, symptom burden, and overall well-being, are important endpoints in evaluating the impact of treatment approaches for thalamic lesions on patients' daily activities. While MSR may offer potential long-term benefits in terms of tumor control and survival outcomes, it may also be associated with a higher risk of neurological deficits and functional impairments that can impact QoL postoperatively. Conversely, biopsy may involve less invasive procedures and shorter recovery times, resulting in better preserved functional status and improved QoL in selected patient populations.

Background: Brain metastases are serious complication of breast cancer (BC) that poses a critical management challenge. Hence, this study aimed to evaluate clinical findings, the status of hormonal receptors, and their correlation with brain metastasis among patients with BC. Materials and Methods: This cross-sectional study was performed on women with BC that was newly diagnosed with brain metastasis from 2020 to 2023. Also, hormonal receptor status (such as p53, estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor2 [HER2]), histopathological type of BC, duration of disease, type of treatment, local cerebral invasions, and initial presentations were recorded. A P-value less than 0.05 was considered as statistical significance. Results: Of a total of 302 patients, 49 (16.2%) patients had brain metastasis. The mean age of patients was 45.21±8.3 years, which was significantly lower in patients with metastasis (45.96±11.31 vs. 51.13±12.61 years, P=0.008). There was a significant association between the duration of disease in patients with and without brain metastasis (2.76±1.03 vs. 5.55±3.32 years, P=0.002). Also, the most prevalent histopathological type of BC was invasive ductal carcinoma (IDC). Headache was the most common clinical presentation among patients with brain metastasis. In addition, the most and the least common positive receptors among patients with metastasis were Ki-67 (93.87%) and PR (55.1%), respectively. Compared to patients without metastasis, HER2-positive and P53-positive receptors were markedly associated with brain metastasis (P=0.03 and P=0.021, respectively). However, there was no significant association between treatment methods and metastasis status.Conclusion: Patients with younger age, IDC, and positivity of HER2 and P53 receptors were at an increased risk of developing brain metastases.

IntroductionPenetrating neck trauma (PNT) due to gunshot injuries is one of the challenging conditions with the potential for both significant morbidities and mortality.Research questionThere are significant concerns in the approach to patients with spinal gunshot injuries. Surgery indications, methods of surgery, and management of CSF leaks are the main concerns of these patients.Methods and materialsAn 11-year-old boy was referred to our center with a single gunshot wound to the left side of the posterior cervical region 2 days ago with cerebrospinal fluid leakage and left arm weakness.ResultsThe patient underwent surgery, and the pellet was removed. His left arm weakness fully recovered after the operation, and no new symptoms developed during the 1-year follow-up.ConclusionTimely surgery could dramatically improve outcomes in PNT patients with mild symptoms and prevent worsening neurological defects.

Context: Planarians, zebrafish, and Xenopus laevis are able to mend damage to their spinal cords after they have been damaged. After undergoing metamorphosis, the X. laevis loses the ability to do this. This study examines the genes that are involved in the process of spinal cord regeneration in these animals, investigates the pattern of their expression at various stages after spinal cord injury (SCI), and compares them to animals that do not have the ability to regenerate their spinal cords. This study reviews gene-based studies in regenerative animals, such as zebrafish, X. laevis, and planarians, and compares their expression patterns and fold-change slopes to non-regenerative ones to identify SCI recovery milestones. Evidence Acquisition: A systematic search was carried out with the intention of including all of the studies that had been conducted on the gene expression of X. laevis, zebrafish, and planarians in the context of SCI. Studies have been transferred to Endnote 2019 software. The researchers used the software to remove duplicate studies. Two researchers then assessed the titles and abstracts. A neutral third party resolved the discrepancies and extracted the data to a predesigned Microsoft Excel Worksheet. The genes were retrieved, and the data from the genome-wide studies were also combined to identify genes whose expression patterns in non-regenerative and regenerative species were significantly comparable or disagreeing with one another. Results: This review included 45 original and 2 genome-wide studies. Overall, 112 genes and their pathways were extracted. A total of 238 genes were common in these studies, and 9 significant expression patterns were possible. Among these 238 common genes, genes 23, 9, and 4 followed 4, 5, and 6 of these significant patterns, respectively. Additionally, pooling the genome-wide studies yielded 15 significant genes, with similar patterns in zebrafish and regenerative X. laevis and conflicting patterns between them and non-regenerative X. laevis. Conclusions: The regeneration of the spinal cord involves several processes, including regulation of inflammation, promotion of glial cell proliferation, facilitation of neuroplasticity, and establishment of coordination between newly formed neurons. Genes such as FOXN4, STC1, HSPA5, EGFR, and PRTFDC1 are also important. MCAM and Dkkb genes must be timed to create the right microenvironment for SCI healing in regenerating X. laevis and zebrafish. However, humans and non-regenerative X. laevis share an insufficient microenvironment. In contrast to non-regenerative models of SCI, regenerative animals decrease early-phase agents and increase injury site neuroplasticity in the late phase. As they show parallel expression patterns in regenerative and non-regenerative animals but in competition with one another.

BACKGROUND: Glioblastoma is associated with low median survival time irrespective of maximal treatment. Previous in vitro studies have revealed tumor inhibitory effect of cyclosporine A. However, whether the addition of cyclosporine could improve survival among patients with glioblastoma is unknown. This study aimed to determine the impact of postoperation treatment with cyclosporine on the survival and performance status.METHODS: In this randomized, triple-blinded, placebo -controlled trial, 118 patients with glioblastoma who un-derwent surgery were treated with standard chemo-radiotherapy regimen. Patients were randomized to receive intravenous cyclosporine for 3 days postoperatively or placebo during the same period. The primary endpoint was the short-term effect of intravenous cyclosporine on sur-vival and Karnofsky performance scores. Secondary end-points were chemoradiotherapy toxicity and neuroimaging features.RESULTS: The overall survival (OS) in the cyclosporine (17.03 & PLUSMN; 5.8, 95% confidence interval: 11-17.37 months) group was statistically lower than in the placebo (30.53 & PLUSMN; 4.9, 95% confidence interval: 8-32.3 months) groups (P = 0.049). However, compared to the placebo group, a statistically higher percentage of patients in the cyclo-sporine group were alive at 12 months follow-up. Also, progression-free survival in the cyclosporine group was significantly prolonged than in the placebo group (6.3 & PLUSMN; 4.07 months vs. 3.4 & PLUSMN; 2.98 months, P < 0.001). In the multivariate analysis, age <50 years (P = 0.022) and gross total resection (P = 0.03) were significantly associated with OS.CONCLUSIONS: Our study results demonstrated that administering postoperative cyclosporine does not improve OS and functional performance status. Notably, the survival rate was significantly dependent on the patient age and the extent of glioblastoma resection.

Introduction: Breast cancer is the major leading cause of death from cancer among women. Given the drug resistance seen during the treatment of this disease, it is very important to identify new therapies and new anticancer drugs. Some studies indicate the cytotoxic effects of cyanidin 3-glycoside (C3G). Therefore, this study aims to evaluate the anticancer effect of C3G in the treatment of the MCF-7 cell line.Material and methods: In this study, the MCF-7 cell line was treated with different concentrations of C3G for 24 and 48 h. Assessment of cell death was performed by MTT assay. The cell apoptosis rate was measured using an Annexin V/propidium iodide assay through flow cytometry. The expression levels of p53, Bax, Caspase3, CYP1, CYP2, and Bcl2 genes were evaluated using polymerase chain reaction, and Western blotting was performed for CYP1 to confirm the results.Results: Our findings showed that C3G has dose-dependent cytotoxic effects on the MCF-7 cell line. According to flow cytometry results, the apoptosis of the cells 24 h after exposure to C3G was more than 51.5%. Moreover, after 24 h of exposure to the half-maximal inhibitory concentration of C3G, the expression of p53, Bax, Caspase3, CYP1, and CYP2 genes increased, and the expression of Bcl2 gene decreased. The Western blotting showed that CYP1 protein increased 2-fold compared to the control sample.Conclusions: The results of this study demonstrated that C3G has apoptotic and cytotoxic effects on breast cancer cells. Therefore, it is likely that this substance could be a suitable option for cancer therapy.

Background: Glioblastoma (GBM) is the most common primary central nervous system malignancy with a low survival without extra logistics. Currently, there is no definitive chemotherapy among the studied options. This study aims to evaluate the neuroprotective effects of dimethyl fumarate (DMF) on surgical brain injuries in patients treated for GBM. Materials and Methods: This randomized, phase II, placebo, triple-blinded, controlled trial was performed on 36 patients with a diagnosis of GBM. All the patients received DMF (240 mg, three-times per day) or placebo (with the same shape and administration route) one week before surgery. Also, patients in both groups after the operation received standard treatments (radiotherapy plus chemotherapy). In addition, Kanofsky's performance status (KPS) score was evaluated at baseline and one month later. Also, serum S100β was measured 48 hours before and after surgery. Results: There was no significant difference among DMF and control groups with regard to age, gender, and the extent of resections (P˃0.05). The most adverse event in both groups was a headache. Although the serum S100β level was not markedly changed after surgery, the mean KPS in the DMF group was higher than in the control group after surgery. Conclusion: The DMF could be a possible good regime for the treatment of GBM; however, questions are raised regarding its efficacy and application for the addition to standard treatment.

BACKGROUND:Atorvastatin is a member of statins, which has shown positive vascular effects, anti-oxidant, anti-platelet, and anti-apoptotic properties.OBJECTIVE:In this study, we hypothesized that atorvastatin could prevent the neurons lost in the hippocampal dentate gyrus region after transient global Ischemia/Reperfusion (I/R) through its anti- oxidant and anti-apoptotic activities.METHOD:Twenty-four male Wistar rats, 12-13 weeks old and weighing 250-300 g, were divided randomly into four groups: control, I/R, vehicle (I/R treated with NaCl) and experiment (I/R treated with atorvastatin, 10 mg/kg); rats were sacrificed 96 hours after I/R. Quantitative expression of genes (caspase 8, p53, bax, bcl2, cytochrome c) was studied. The MDA level, SOD, CAT, and GPx activities were measured with biochemical tests. To detect apoptotic cells, TUNEL and Nissl staining were performed. Mitochondria were prepared from the hippocampus rats and used for the quantification of mitochondrial ROS, ATP level, GSH content, membrane potential, cytochrome c release, and determination of mitochondrial swelling.RESULTS:Atorvastatin attenuated the overexpression of bax, cytochrome C, p53, and caspase8 mRNAs and induced expression of bcl-2 mRNA (P<0.001). Atorvastatin treatment increased anti-oxidant enzyme levels (P<0.01). Treatment with atorvastatin reduced the number of TUNEL-positive cells. It could decrease the cytochrome c release (P<0.01), inhibit the decrease of MMP (P<0.001) and increase the ATP level (P<0.001) in hippocampal mitochondria compared with the I/R group.CONCLUSION:Atorvastatin treatment in I/R rats decreases oxidative stress, production of ROS, apoptosis rate in neuronal cells, and improves the mitochondrial function. Hence, atorvastatin has a proper neuronal protective effect against the I/R injury in the brain.

Background: Multi-level spine surgeries are associated with high bleeding during and after surgery. A majority of studies have previously evaluated the effect of tranexamic acid (TXA) in reducing bleeding with a focus on intravenous (IV) administration. The aim of the study was to evaluate the efficacy of topical TXA in decreasing bleeding after laminectomy and spinal fusion. Methods: In this randomized, double-blinded, placebo-controlled clinical trial, 80 patients were enrolled from January 2017 to January 2019. The patients were eligible for laminectomy (2 or more levels) and posterolateral fusion with a pedicle screw. Patients were randomly divided into two equal groups; single-dose TXA (1 g/50 ml) and normal saline. Intergroup comparison was performed for the amount of bleeding during and after surgery, received packed cells, and the number of hospitalization days. Results: The mean age of the patients was 55.51 ± 10.27 years, and 50 of them were women. 18 and 20 patients in control and TXA groups had intraoperative bleeding more than 400 ml, respectively (P ˃0.05). The only significant difference was observed in the first and second 12 hours, and total bleeding after surgery in patients who had bleeding above 400 ml (P = 0.011, P = 0.039, P = 0.015, respectively). Conclusion: The application of topical TXA was effective in patients with high amount of hemorrhage during spine surgery for reducing the bleeding rate in the first and second 12 hours, as well as the mean total bleeding rate after surgery. It had no significant effect on total intraoperative hemorrhage, total packed cells, and total hospitalization length.

Macrophages play an important role in mediating damage after Spinal cord injury (SCI) by secreting macrophage migration inhibitory factor (MMIF) as a secondary injury mediator. We aimed to systematically review the role of MMIF as a therapeutic target after traumatic SCI. Our systematic review has been performed according to the PRISMA 2009 Checklist. A systematic search in the scientific databases was carried out for studies published before 20 February 2019 from major databases. Two researchers independently screened titles. The risk of bias of eligible articles was assessed, and data were extracted. Finally, we systematically analyzed and interpreted related data. 785 papers were selected for the title and abstract screening. 12 papers were included for data extraction. Eight animal studies were of high quality and the remaining two were of medium quality. One of the two human studies was of poor quality and the other was of fair quality. MMIF as a pro-inflammatory mediator can cause increased susceptibility to glutamate-related neurotoxicity, increased nitrite production, increased ERK activation, and increased COX2/PGE2 signaling pathway activation and subsequent stimulation of CCL5-related chemotaxis. Two human studies and six animal studies demonstrated that MMIF level increases after SCI. MMIF inhibition might be a potential therapeutic target in SCI by multiple different mechanisms (6/12 studies). Most animal studies demonstrate significant neurologic improvement after administration of MMIF inhibitors, but these inhibitors have not been studied in humans yet. Further clinical trials are need to further understand MMIF inhibitor utility in acute or chronic SCI. Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.

It is of great importance to find an effective approach that not only eliminates gastric cancer cells but also do exhibits significant side effect to normal cells. Some studies have shown the effectiveness of hypericin against cancer cells. In this study, we evaluated the anti-cancer effect of Hypericin in the treatment of gastric cancer. In this study, the AGS cell line was exposed to different concentrations of hypericin for 24 and 48 h. Evaluation of cell death was done by MTT assay. The rate of apoptosis was measured by flow cytometry assay using Annexin V/ Propidium Iodide. The expression rate of , and genes was evaluated by Real-time PCR test, and immunocytochemistry () analysis and western blotting was used for further evaluation of . MTT assay test showed that hyepricin induces 50% cell death in the concentration of 1 (µg/mL) and 0.5 (µg/mL) at 24 h and 48 h post-treatment, respectively, however no similar effect seen on fibroblast cells. Annexin/PI test revealed that cell apoptosis after exposure to hypericin for 24 h was 74%. Real-time PCR showed that expression level of , and Bax genes increases and gene decreases in AGS cell lines after treatment by hypericin. analysis and western blotting for confirmed these data. The results of this study indicated that hypericin has the potential to be introduced as an effective treatment for gastric cancer. Therefore, it seems that this substance has potential to be utilized as anti-cancer drug.

The prefrontal cortex is the largest lobe of the brain and is consequently involved in stroke. There is no comprehensive practical pharmacological strategy for ameliorating prefrontal cortex injury induced by cerebral ischemia. Therefore, we studied the neuroprotective properties of verapamil (Ver) on mitochondrial dysfunction and morphological features of apoptosis in transient global ischemia/reperfusion (I/R). Ninety-six Wistar rats were allocated into four groups: control, I/R, I/R+Ver (10 mg/kg twice 1 hour prior to ischemia and 1 hour after reperfusion phase), and I/R+NaCl (vehicle). Animals were sacrificed, and mitochondrial dysfunction parameters (i.e., mitochondrial swelling, mitochondrial membrane potential, ATP concentration, ROS production, and cytochrome c release), antioxidant defense (i.e., superoxide dismutase, malondialdehyde, glutathione peroxidase, catalase, and caspase-3 activation), and morphological features of apoptosis were determined. The results showed that mitochondrial damage, impairment of antioxidant defense system, and apoptosis were significantly more prevalent in the I/R group in comparison with the other groups. Ver decreased mitochondrial damage by reducing oxidative stress, augmented the activity of antioxidant enzymes in the brain, and decreased apoptosis in the I/R neurons. The current study confirmed the role of oxidative stress and mitochondrial dysfunction in I/R progression and indicated the possible antioxidative mechanism of the neuroprotective activities of Ver.

BACKGROUND:Breast cancer is the major cause of death from cancer among women around the world. Given the drug resistance in the treatment of this disease, it is very important to identify new therapies and anticancer drugs. Many studies demonstrated that hypericin could induce apoptosis in different cancer cell lines; however, the underlying mechanism is not well understood yet. Therefore, this study aimed to evaluate the anticancer effect of hypericin in two breast cancer cell lines, one with wild type P53 and the other with mutant P53.METHODS:In this study, the MDA-MB-231 and MDA-MB-175-VII cell lines were treated with different concentrations of hypericin for 24 and 48 hours. The measurement of cell death was performed by MTT assay. The cell apoptosis rate was measured using annexin V/propidium iodide assay through flow cytometry. The level of expression in P21 and P53 genes was evaluated by real time PCR. Immunocytochemistry (ICC) analysis was performed for P21 (direct target for P53 protein) to confirm the results.RESULTS:The results showed that hypericin could have dose-dependent cytotoxic effects on the MDA-MB-231 and MDA-MB-175-VII cell lines, and its cytotoxicity is much higher in the latter cells. According to flow cytometry results, 86% of MDA-MB-175-VII cells underwent apoptosis with IC50 dose of hypericin for MDA-MB-231 cells after 24 hours. Moreover, after 24 hours of exposure to hypericin with MDA- MB-231 IC50 concentration, the expression of P53 and P21 genes upregulated in MDA-MB-175-VII much more than MDA-MB-231 when both cell lines were treated with 24 hours IC50 dose of MDA-MB-231. The ICC analysis on P21 confirmed that by treating both cell lines with MDA-MB-231 IC50 dose of hypericin for 24 hours, this protein is overexpressed much more in MDA-MB-175-VII cells.CONCLUSION:The results of this study demonstrated that hypericin's apoptotic and cytotoxic effects on cancer cells may be mediated via P53 overexpression, cell cycle arrest and the subsequent apoptosis. Therefore, it is of great importance to consider that hypericin would have better impact on cells or tumors with wild type P53.

BACKGROUND: Central nervous system tuberculoma is the most severe manifestation of extrapulmonary tuberculosis with high mortality. Cavernous sinus tuberculoma (CST) is a very rare central nervous system tuberculoma with few cases reported in the literature. CASE DESCRIPTION: A 57-year-old woman was admitted to our clinic with acute diplopia and headache limited to the right side. There was no specific medical history except for migraine, depression, and anxiety, all of which were controlled by oral medications. Physical examination revealed ptosis and mydriasis in the right eye, which indicated right third and sixth cranial nerve palsies. Pituitary magnetic resonance imaging showed a right parasellar lesion at the cavernous sinus wall and ophthalmic nerve. Laboratory examinations and brain computed tomography scan showed negative findings. Initial differential diagnosis included meningioma, sarcoidosis, tuberculoma, and lymphoma. However, results of further studies, including blood and cerebrospinal fluid cultures and Mycobacterium tuberculosis DNA assay, were negative. Biopsy of the cerebral lesion was performed through the subfrontal approach, and histopathologic study confirmed CST. She was treated with a standard antituberculous regimen. After 12 months of follow-up, no cerebral or clinical findings were seen. CONCLUSIONS: CST is a rare presentation of M. tuberculosis, and the diagnosis is a difficult challenge. However, accurate diagnosis and timely treatment of CST can result in complete cure.