Distinct immunometabolic signatures in circulating immune cells define disease outcome in acute-on-chronic liver failure.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a complication of cirrhosis characterized by multiple organ failure and high short-term mortality. The pathophysiology of ACLF involves elevated systemic inflammation leading to organ failure, along with immune dysfunction that heightens susceptibility to bacterial infections. However, it is unclear how these aspects are associated with recovery and nonrecovery in ACLF. APPROACH AND RESULTS: Here, we mapped the single-cell transcriptome of circulating immune cells from patients with ACLF and acute decompensated (AD) cirrhosis and healthy individuals. We further interrogate how these findings, as well as immunometabolic and functional profiles, associate with ACLF-recovery (ACLF-R) or nonrecovery (ACLF-NR). Our analysis unveiled 2 distinct states of classical monocytes (cMons). Hereto, ACLF-R cMons were characterized by transcripts associated with immune and stress tolerance, including anti-inflammatory genes such as RETN and LGALS1 . Additional metabolomic and functional validation experiments implicated an elevated oxidative phosphorylation metabolic program as well as an impaired ACLF-R cMon functionality. Interestingly, we observed a common stress-induced tolerant state, oxidative phosphorylation program, and blunted activation among lymphoid populations in patients with ACLF-R. Conversely, ACLF-NR cMon featured elevated expression of inflammatory and stress response genes such as VIM , LGALS2 , and TREM1 , along with blunted metabolic activity and increased functionality. CONCLUSIONS: This study identifies distinct immunometabolic cellular states that contribute to disease outcomes in patients with ACLF. Our findings provide valuable insights into the pathogenesis of ACLF, shedding light on factors driving either recovery or nonrecovery phenotypes, which may be harnessed as potential therapeutic targets in the future.

Direct Versus Indirect Revascularization for Moyamoya: a Large Multicenter Study.

BACKGROUND: Moyamoya is a chronic occlusive cerebrovascular disease of unknown etiology causing neovascularization of the lenticulostriate collaterals at the base of the brain. Although revascularization surgery is the most effective treatment for moyamoya, there is still no consensus on the best surgical treatment modality as different studies provide different outcomes. OBJECTIVE: In this large case series, we compare the outcomes of direct (DR) and indirect revascularisation (IR) and compare our results to the literature in order to reflect on the best revascularization modality for moyamoya. METHODS: We conducted a multicenter retrospective study in accordance with the Strengthening the Reporting of Observational studies in Epidemiology guidelines of moyamoya affected hemispheres treated with DR and IR surgeries across 13 academic institutions predominantly in North America. All patients who underwent surgical revascularization of their moyamoya-affected hemispheres were included in the study. The primary outcome of the study was the rate of symptomatic strokes. RESULTS: The rates of symptomatic strokes across 515 disease-affected hemispheres were comparable between the two cohorts (11.6% in the DR cohort vs 9.6% in the IR cohort, OR 1.238 (95% CI 0.651 to 2.354), p=0.514). The rate of total perioperative strokes was slightly higher in the DR cohort (6.1% for DR vs 2.0% for IR, OR 3.129 (95% CI 0.991 to 9.875), p=0.052). The rate of total follow-up strokes was slightly higher in the IR cohort (8.1% vs 6.6%, OR 0.799 (95% CI 0.374 to 1.709) p=0.563). CONCLUSION: Since both modalities showed comparable rates of overall total strokes, both modalities of revascularization can be performed depending on the patient's risk assessment.

Protein C and S activities in COVID-19: A systematic review and meta-analysis.

COVID-19 has been associated with alterations in coagulation. Recent reports have shown that protein C and S activities are altered in COVID-19. This may affect the complications and outcome of the disease. However, their exact role in COVID-19 remains uncertain. The aim of the current study was therefore to analyze all papers in the literature on protein C and S activities in COVID-19. We searched three medical electronic databases. Of the 2442 papers, 28 studies were selected for the present meta-analysis. For the meta-analysis, means ± standard deviations with 95% confidence intervals (CI) for protein C and S activities were extracted. Pooled p values were calculated using STATA software. Protein C and S activities were significantly lower in COVID-19 patients than in healthy controls (pooled p values: 0.04 and 0.02, respectively). Similarly, protein C activities were considerably lower in nonsurviving patients (pooled p value = 0.00). There was no association between proteins C or S and thrombosis risk or ICU admission in COVID-19 patients (p value > 0.05). COVID-19 patients may exhibit lower activities of the C and S proteins, which might affect disease outcome; however, additional attention should be given when considering therapeutic strategies for these patients.

Eye-Related Adverse Events After I-131 Radioiodine Therapy: A Systematic Review of the Current Literature.

OBJECTIVE: Although I-131 is relatively safe, there is limited focus on probable eye-related side effects after radioactive iodine (RAI) therapy. Thus, we aimed to provide evidence for the adverse outcomes of I-131, exclusively in patients with thyroid cancer. METHODS: A systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was designed to examine the ocular complications of RAI therapy. Databases including PubMed, Scopus, and Web of Science were searched until October 2023 with specific thyroid neoplasms, ophthalmology and iodine terms. After thorough screening and review, relevant data were extracted. RESULTS: The database search yielded 3434 articles, which resulted in the final 28 eligible studies. These studies investigated ophthalmic symptoms following RAI therapy, classifying them as obstructive diseases (for example, nasolacrimal duct obstruction; median incidence rate: 6.8%), inflammatory symptoms (median incidence rate: 13%), and cataracts (median incidence rate: 2.5 and 5%). The most common time interval between RAI therapy and the onset of symptoms was within the first 12 months and then declined in the preceding years. A strong positive correlation was observed between higher I-131 doses of more than 100 to 150 mCi (3.7-5.55 GBq) and the risk of symptom development. Ages older than 45 also showed a significant association with nasolacrimal duct obstruction. CONCLUSION: The risk of ophthalmic complications is associated with various factors, including the administration of high I-131 doses, age of more than 45 years, and time to event within the first 12 months. Considering these conditions may help enhance patient care and prevent adverse outcomes that may limit patients' quality of life.

Stereotactic radiosurgery versus combined stereotactic radiosurgery and bevacizumab for recurrent glioblastoma; a systematic review and meta-analysis of survival.

Recurrent glioblastoma (rGBM) is a brain tumor that is resistant to standard treatments. Although stereotactic radiosurgery (SRS) is a non-invasive radiation technique, it cannot fully prevent tumor recurrence and progression. Bevacizumab blocks tumor blood supply and has been approved for rGBM. However, the best way to combine SRS and bevacizumab is still unclear. We did a systematic review and meta-analysis of studies comparing SRS alone and SRS plus bevacizumab for rGBM. We searched three databases for articles published until June 2023. All statistical analysis was performed by STATA v.17. Our meta-analysis included 20 studies with 926 patients. We found that the combination therapy had a significantly lower rate of overall survival (OS) than SRS alone at 6-month 0.77[95%CI:0.74-0.85] for SRS alone and (100%) for SRS plus bevacizumab. At 1-year OS, 0.39 [95%CI: 0.32-0.47] for SRS alone and 0.61 [95%CI:0.44-0.77] for SRS plus bevacizumab (P-value:0.02). However, this advantage was not seen in the long term (18 months and two years). Additionally, the combination therapy had lower chances of progression-free survival (PFS) than SRS alone at the 6-month and 1-year time points, but the differences were insignificant. Our study indicates that incorporating bevacizumab with SRS may lead to a short-term increase in OS for rGBM patients but not long-term. Additionally, the PFS rate did not show significant improvement in the group receiving combination therapy. Further clinical trials are necessary to validate the enhanced overall survival with combination therapy for rGBM.

Powered single hip joint exoskeletons for gait rehabilitation: a systematic review and Meta-analysis.

BACKGROUND: Gait disorders and as a consequence, robotic rehabilitation techniques are becoming increasingly prevalent as the population ages. In the area of rehabilitation robotics, using lightweight single hip joint exoskeletons are of significance. Considering no prior systematic review article on clinical outcomes, we aim to systematically review powered hip exoskeletons in terms of gait parameters and metabolic expenditure effects. METHODS: Three databases of PubMed, Scopus, and Web of science were searched for clinical articles comparing outcomes of gait rehabilitation using hip motorized exoskeleton with conventional methods, on patients with gait disorder or healthy individuals. Of total number of 37 reviewed articles, 14 trials were quantitatively analyzed. Analyses performed in terms of gait spatiotemporal parameters like speed (self-speed and maximum speed), step length, stride length, cadence, and oxygen consumption. RESULTS: Improved clinical outcomes of gait spatiotemporal parameters with hip joint exoskeletons are what our review's findings show. In terms of gait values, meta-analysis indicates that rehabilitation with single hip joint exoskeleton enhanced parameters of maximum speed by 0.13 m/s (0.10-0.17) and step length by 0.06 m (0.05-0.07). For the remaining investigated gait parameters, no statistically significant difference was observed. Regarding metabolic parameters, oxygen consumption was lower in individuals treated with hip exoskeleton (- 1.23 ml/min/kg; range - 2.13 to - 0.32). CONCLUSION: Although the analysis demonstrated improvement with just specific gait measures utilizing powered hip exoskeletons, the lack of improvement in all parameters is likely caused by the high patient condition heterogeneity among the evaluated articles. We also noted in patients who rehabilitated with the hip exoskeleton, the oxygen cost was lower. More randomized controlled trials are needed to verify both the short- and long-term clinical outcomes, including patient-reported measures. LEVEL OF EVIDENCE: Level I (systematic review and meta-analysis).

Differential expression levels of ß-catenin are associated with invasive behavior of both functional and non-functional pituitary neuroendocrine tumor (PitNET).

BACKGROUND: Although research continues to elucidate the molecular mechanism underlying pituitary tumor pathogenesis, limited information is available on the potential role and expression profile of ß-catenin in functional and non-functional pituitary neuroendocrine tumors (PitNETs). METHODS AND RESULTS: In the current study, 104 pituitary samples (tumors and cadaveric healthy pituitary tissues) were included and the gene and protein expression levels of ß-catenin were assessed by Real-Time PCR and immunohistochemistry, respectively. The correlation between expression level of ß-catenin and tumor invasive feature and size as well as patient age, gender, and hormonal level was measured. The data showed that PitNET samples expressed higher levels of the ß-catenin gene and protein compared to healthy pituitary tissues. Although there was no difference in ß-catenin expression level between non-functioning (NF-PitNETs) and growth hormone-producing tumors (GH-PitNETs), both tumor types showed significantly elevated ß-catenin levels compared to healthy pituitary tissues. The high level of ß-catenin in the invasive functional and non-functional tumors is indicative of the association of ß-catenin with PitNETs invasion. The expression pattern of the ß-catenin gene and protein was consistently and significantly associated with these tumor types. The correlation between ß-catenin and insulin-like growth factor 1 (IGF-1) in GH-PitNETs indicates the potential relevance of ß-catenin and IGF-1 for GH-PitNETs. CONCLUSIONS: The simultaneous increase in the expression of ß-catenin gene and protein level in PitNET tissues and their relationship to the tumor severity indicates the possible contributing role of ß-catenin and its underlying signaling mediators in PitNET pathogenesis.

Successful microvascular decompression surgery for dolichoectatic vertebral artery compression of medulla oblongata in a patient with hypersomnia disorder.

INTRODUCTION: Hypersomnia is a condition in which a person has trouble staying awake during the day. There are several potential causes of it, including sleep apnea and sleep disorders. CASE PRESENTATION: A 43 year old male was referred to our practice with complaints of hypersomnia, snoring, slurred speech and sleep apnea for more diagnostic and therapeutic interventions. His brain MRI was significant for a vascular loop compression on medulla oblongata. The patient underwent microvascular decompression surgery subsequently and showed improvement in all of his symptoms. CONCLUSION: One of the rare causes of sleep apnea is medulla oblongata compression by a vascular loop. Vertebrobasilar dolichoectasia may cause this phenomenon probably and should be reviewed in imaging examinations more precisely. Microvascular decompression by using a synthetic Teflon patch may be helpful in management of these patients.

Traumatic iatrogenic dissecting anterior cerebral artery aneurysms: conservative management as a therapeutic option.

INTRODUCTION: Traumatic iatrogenic intracranial aneurysms (TICAs) are rare, but are important due to their risk of intracranial hemorrhage and complexity of management. METHODS: Two adult patients, one with history of chronic sinusitis and nasal cavity polyposis undergoing functional endoscopic sinus surgery (FESS), and second during rhinoplasty, suffered subarachnoid hemorrhage (SAH) due to anterior cerebral artery (ACA) injury during the procedures. RESULTS: Two women patients aged 17 and 38 years with SAH after nasal surgery were referred to our institute. Three small dissecting aneurysms were seen involving A2 segment of ACA of two patients. Both were managed conservatively. Follow-up angiography (after 2 months) demonstrated complete occlusion of the aneurysms. There was no rebleeding and the patients had a good outcome at the last follow-up. CONCLUSIONS: Conservative management of traumatic iatrogenic dissecting cerebral aneurysms is a reasonable therapeutic option that can lead to favorable angiographic and clinical outcomes.

Electromagnetic Field Exposure and Abortion in Pregnant Women: A Systematic Review and Meta-Analysis.

This study examined the effects of exposure to electromagnetic fields (EMF) on pregnancy and the risk of miscarriage. We performed a systematic search for relevant studies published to August 2021 in the medical databases of PubMed, CINAHL, Scopus, Web of Science, Google Scholar and Cochrane Library. The following key terms were used: 'electromagnetic field,' 'mobile phones,' 'mobile phone base stations,' 'watching TV,' 'using Internet,' 'miscarriage,' 'abortions,' 'spontaneous abortion,' 'early abortion' and 'late abortion'. All case-control and cohort studies that investigated the effect of EMF exposure on the risk of miscarriage were included without any restriction of language or time. Statistical analyses were done using Comprehensive Meta-Analysis software (version 2.0). A random-effects model was performed to calculate the overall effect size. A primary search revealed a total of 982 relevant studies; six articles (N = 3,187 participants) met the inclusion criteria for the meta-analysis. The results of the random-effects meta-analysis indicated that EMF exposure had a significant effect on miscarriage: rate ratio (RR) = 1.699; 95% confidence interval (CI): 1.121, 2.363 (P < 0.001); and heterogeneity (I2) = 84.55% (P < 0.001). The findings showed that pregnant woman who were exposed to high levels of EMF had an increased risk of miscarriage.

Molecular analysis of dominant paranasal sinus bacteria in patients with and without chronic rhinosinusitis.

Recent studies have established the possible role of microbiota in developing various diseases. In this regard, attention has shifted to the evaluation of microbiota changes in the paranasal sinuses and its relationship to chronic rhinosinusitis (CRS), especially CRS with nasal polyposis (CRSwNP). This study aimed to examine the bacterial communities of the sphenoidal sinus in Iranian patients with and without CRS. The investigation included 36 subjects, including 18 patients with CRSwNP who underwent Functional Endoscopic Sinus Surgery (FESS) and 18 non-CRS patients who underwent Endoscopic Endonasal Approach (EEA) for pituitary adenoma. The surgeries were performed under general anesthesia, and the sphenoidal sinus was sampled using sterile rayon-tipped swabs coated with a sheet. TaqMan quantitative real-time polymerase chain reaction (qPCR) method (the 16S rDNA gene from bacteria) was used for detection of bacterial communities in different samples. Staphylococcus haemolyticus and Pseudomonas aeruginosa were significantly more prevalent in CRS patients than non-CRS patients (P value ≤ 0.05). However, no significant difference in the frequency of Corynebacterium spp. and Staphylococcus aureus was observed between the two groups, and no Streptococcus pneumoniae or Haemophilus influenza species were isolated from any of the samples. The current study's findings indicated a significant difference in the frequency of certain bacterial species in patients with CRS vs. non-CRS patients. By establishing a link between microbial burden and CRS, it is possible to develop effective treatments or even prevent disorders in this body area.

International controlled study of revascularization and outcomes following COVID-positive mechanical thrombectomy.

BACKGROUND AND PURPOSE: Previous studies suggest that mechanisms and outcomes in patients with COVID-19-associated stroke differ from those in patients with non-COVID-19-associated strokes, but there is limited comparative evidence focusing on these populations. The aim of this study, therefore, was to determine if a significant association exists between COVID-19 status with revascularization and functional outcomes following thrombectomy for large vessel occlusion (LVO), after adjustment for potential confounding factors. METHODS: A cross-sectional, international multicenter retrospective study was conducted in consecutively admitted COVID-19 patients with concomitant acute LVO, compared to a control group without COVID-19. Data collected included age, gender, comorbidities, clinical characteristics, details of the involved vessels, procedural technique, and various outcomes. A multivariable-adjusted analysis was conducted. RESULTS: In this cohort of 697 patients with acute LVO, 302 had COVID-19 while 395 patients did not. There was a significant difference (p < 0.001) in the mean age (in years) and gender of patients, with younger patients and more males in the COVID-19 group. In terms of favorable revascularization (modified Thrombolysis in Cerebral Infarction [mTICI] grade 3), COVID-19 was associated with lower odds of complete revascularization (odds ratio 0.33, 95% confidence interval [CI] 0.23-0.48; p < 0.001), which persisted on multivariable modeling with adjustment for other predictors (adjusted odds ratio 0.30, 95% CI 0.12-0.77; p = 0.012). Moreover, endovascular complications, in-hospital mortality, and length of hospital stay were significantly higher among COVID-19 patients (p < 0.001). CONCLUSION: COVID-19 was an independent predictor of incomplete revascularization and poor functional outcome in patients with stroke due to LVO. Furthermore, COVID-19 patients with LVO were more often younger and had higher morbidity/mortality rates.

Evaluation of the expression of necroptosis pathway mediators and its association with tumor characteristics in functional and non-functional pituitary adenomas.

BACKGROUND: Pituitary adenomas impose a burden of morbidity on patients and characterizing the molecular mechanisms underlying its pathogenesis received remarkable attention. Despite the appealing role of necroptosis as an alternative cell death pathway in cancer pathogenesis, its relevance to pituitary adenoma pathogenesis has yet to be determined that is perused in the current study. METHODS: The total number of 109 specimens including pituitary adenomas and cadaveric healthy pituitary tissues were enrolled in the current study. Tumor and healthy pituitary tissues were subjected to RNA extraction and gene analysis using Real-Time PCR. The expression levels of necroptosis markers (RIP1K, RIP3K and, MLKL) and their association with the patient's demographic features were evaluated, also the protein level of MLKL was assessed using immunohistochemistry in tissues. RESULTS: Based on our data, the remarkable reduction in RIP3K and MLKL expression were detected in nonfunctional and GH-secreting pituitary tumors compared to pituitary normal tissues. Invasive tumors revealed lower expression of RIP3K and MLKL compared to non-invasive tumors, also the attenuated level of MLKL was associated with the tumor size in invasive NFPA. The simultaneous down-regulation of MLKL protein in pituitary adenoma tissues was observed which was in line with its gene expression. While, RIP1K over-expressed significantly in both types of pituitary tumors which showed no significant correlation with patient's age, gender and tumor size in GHPPA and NFPA group. Notably, MLKL and RIP3K gene expression was significantly correlated in the GHPPA group. CONCLUSIONS: According to our data, the reduced expression of necroptosis mediators (RIP3K, MLKL) in pituitary adenoma reinforces the hypothesis that the necroptosis pathway can be effective in regulating the proliferation and growth of pituitary tumor cells and tumor recurrence.

Improving bactericidal performance of implant composite coatings by synergism between Melittin and tetracycline.

Methicillin resistance Staphylococcus aureus bacteria (MRSA) are serious hazards of bone implants. The present study was aimed to use the potential synergistic effects of Melittin and tetracycline to prevent MRSA associated bone implant infection. Chitosan/bioactive glass nanoparticles/tetracycline composite coatings were deposited on hydrothermally etched titanium substrate. Melittin was then coated on composite coatings by drop casting method. The surfaces were analyzed by FTIR, XRD, and SEM instruments. Tetracycline in coatings revealed multifunctional behaviors include bone regeneration and antibacterial activity. Releasing ALP enzyme from MC3T3 cells increased by tetracycline, so it is suitable candidate as osteoinductive and antibacterial agent in orthopedic implants coatings. Melittin increased the proliferation of MC3T3 cells. Composite coatings with combination of tetracycline and Melittin eradicate all MRSA bacteria, while coatings with one of them could no t eradicate all of the bacteria. In conclusion, chitosan/bioactive glass/tetracycline/Melittin coating can be suggested as a multifunctional bone implant coating because of its osteogenic and promising antibacterial activity. Graphical abstract.

Post-treatment heterogeneity of cardiometabolic risk in patients with acromegaly: The impact of GH and IGF-1.

BACKGROUND: Metabolic abnormalities are frequently seen in patients with acromegaly. However, it is not clear to what extent growth hormone/insulin-like growth factor-1 (GH/IGF-1) contributes to the development of these abnormalities. OBJECTIVE: This study aimed to explore the impact of postoperative GH/IGF-1 on different aspects of metabolic abnormalities in patients with acromegaly. METHODS: This retrospective, registry-based study conducted on 102 patients with acromegaly. The impact of GH/IGF-1 on the cardiometabolic risk factors at 3-12 months after surgery has been investigated using linear and logistic regression models. RESULTS: In this study, each 1 ng/ml increase in the level of GH was significantly associated with a 2 mg/dl increase in the level of fasting blood glucose (FBG), a 0.5 mmHg increase in the level of systolic blood pressure (SBP), and a 0.9 mmHg increase in the level of diastolic blood pressure (DBP). Upon multivariate analysis, GH, but not IGF-1, significantly increased the odds of diabetes mellitus (DM) (OR; 1.2, 95% CI; 1.0-1.4, p = .025). CONCLUSIONS: Our findings indicated at early postoperative stage, GH is significantly associated with the levels of FBG, SBP, and DBP. Moreover, GH, but not IGF-1, appears as a predictive factor for the presence of DM. However, neither GH nor IGF-1 could predict the presence of hypertension HTN, or dyslipidemia in this study. ABBREVIATIONS: CVD: Cardiovascular disease; GH: Growth hormone; IGF-1: Insulin-like growth factor 1; BMI: Body mass index; HTN: hypertension; IPTR: Iran Pituitary Tumor Registry; WC: Waist circumference; MRI: Magnetic resonance imaging; FBG: Fasting blood glucose; HbA1C: Glycated hemoglobin; TG: Triglyceride; LDL: Low density lipoprotein; HDL: High density lipoprotein; SBP: Systolic blood pressure; DBP: Diastolic blood pressure.

Dural arteriovenous fistulas as a relative contraindication for lumbar puncture: brief report and literature review.

We report three patients who deteriorated after lumbar puncture (LP). Two patients were later found to have type іі (a + b) dural arteriovenous fistulas (DAVF) with high flow retrograde venous drainage on cerebral angiography. The third had a type II (a) DAVF. All patients recovered at least partially after DAVF treatment. In patients with signs and symptoms of increased intracranial pressure (ICP) but no evidence of focal mass lesion on cranial imaging, we suggest an evaluation for a DAVF before performing an LP.

Endoscopic cystoventriculostomy of an arachnoid cyst using a neuroendovascular stent to maintain patency.

INTRODUCTION: Cystoventriculostomy is a surgical treatment for arachnoid cysts. We present a case using a neuroendovascular stent to maintain ostomy patency. CASE REPORT: A 6½-year-old male with symptomatic arachnoid cyst underwent endoscopic fenestration and Wingspan stent insertion. CONCLUSION: Neuroendovascular stent placement may be an adjunct to maintain patency in cystoventriculostomy.

Increasing Antioxidant Activity in Food Waste Extracts by ß-Glucosidase.

Research background: Food by-products such as onion peels and olive leaves are rich in bioactive compounds applicable as natural and low-cost sources of antioxidants. Still, these compounds mainly exist in glycosylated form. Often, hydrolysis of glycoside compounds increases their antioxidant activity and health benefits. However, not many studies have been done concerning the ß-glucosidase effect, specifically from Aspergillus niger, on glycosylated compounds within these by-products. Also, changes in the antioxidant activity of the mentioned by-products under the effect of ß-glucosidase have not been reported yet. Therefore, this study considers the effect of A. niger ß-glucosidase on glucoside compounds and the antioxidant activity of onion peel and olive leaf extracts. Experimental approach: The antioxidant activity of the extracts was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Also, glucose, total phenolic and flavonoid contents were measured. Moreover, TLC and HPLC analyses were performed before and after the enzymatic hydrolysis. Results and conclusions: The obtained results showed an increase in the extract antioxidant activity after treatment. Also, ß-glucosidase increased the glucose content of the extracts. The thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) results showed the ß-glucosidase efficacy to hydrolyze quercetin glucosides in onion peel extract, and the quercetin concentration increased from (0.48±0.04) mg/mL in the untreated extract to (1.26±0.03) mg/mL in the treated extract (0.5% m/V) after 3 h of enzymatic hydrolysis at 45 °C. Also, the content of quercetin-3-O-glucoside increased considerably from (1.8±0.1) to (54±9) µg/mL following the enzyme treatment. Moreover, oleuropein in olive leaf extract (1% m/V) was hydrolyzed completely from (0.382±0.016) to 0 mg/mL by ß-glucosidase for 24 h at 50 °C. Novelty and scientific contribution: This study showed that A. niger ß-glucosidase, as a stable enzyme, hydrolyzed quercetin and oleuropein glycosides in onion peel and olive leaf extracts. Thus, A. niger ß-glucosidase is a good candidate for processing the food waste and extracting valuable bioactive compounds. Also, the treated extracts with higher antioxidant and biological activity, and without bitter taste can be applicable as potent, natural and cost-effective antioxidants in the food industry.

Up-regulation of sex-determining region Y-box 9 (SOX9) in growth hormone-secreting pituitary adenomas.

BACKGROUND: Pituitary adenomas are benign brain tumors that cause considerable morbidity and neurological symptoms. SOX9 as a regulatory transcriptional mediator affects normal and tumor cell growth with an undefined role in pituitary adenomas pathogenesis. Thus, in the present study, the expression pattern of SOX9 in GH-secreting pituitary tumors and normal pituitary tissues is investigated. METHODS: The SOX9 gene expression level was evaluated in 60 pituitary tissues including different types of GH-secreting adenomas and normal pituitary tissues through Real-Time PCR. The protein level of SOX9 was assessed using immunohistochemistry. The correlations of SOX9 gene and protein expression level with the patient's clinical and pathological features were considered. RESULTS: The SOX9 over-expression was detected in GH-secreting adenomas tumor tissues compared to normal pituitary tissues which were accompanied by overexpression of SOX9 protein in tumor tissues. The over-expression of SOX9 had a significant impact on GH-secreting adenomas tumor incidence with the odds ratio of 8.4 and the diagnostic value of SOX9 was considerable. The higher level of SOX9 expression was associated with invasive and macro tumors in GH-secreting pituitary adenoma patients. The positive correlation of SOX9 gene and protein level was observed and the tumor size and tumor invasive features were valuable in predicting SOX9 expression level in GH-producing pituitary tumors. CONCLUSION: The study provided the first shreds of evidence regarding the expression pattern of SOX9 in the GH- secreting pituitary adenomas at both gene and protein levels which may emphasize the possible involvement of SOX9 as a mediator in pituitary adenoma tumor formation also open up new intrinsic molecular mechanism regarding pituitary adenoma pathogenesis.

Aspergillosis of central nervous system in patients with leukemia and stem cell transplantation: a systematic review of case reports.

BACKGROUND: Aspergillosis of Central Nervous System (CNS) is a highly lethal infection in patients with leukemia and Stem Cell Transplantation (SCT). METHODS: Case reports of CNS aspergillosis in patients with leukemia and SCT published between 1990 and August 2020 were gathered using a structured search through PubMed/Medline. RESULTS: Sixty-seven cases were identified over the searches of the PubMed bibliographic database and then, 59 cases were included in the final analysis. Europe had the largest share of cases at 57.6% (34 reports), followed by Americas and Asia. Affected patients were predominantly males (58.6%) and the mean age of the patients was 36.1 years, while 62.7% of the patients were under the age of 50 years. The most common leukemia types include Acute Lymphoblastic Leukemia (ALL), Chronic Lymphocytic Leukemia (CLL), and Acute Myeloid Leukemia (AML) at 43.4%, 27.4%, and 23.5%, respectively. Furthermore, stem cell transplantation was reported in 11 cases. The overall mortality was 33%; however, the attributable mortality rate of CNS aspergillosis was 24.5%. Altered mental status, hemiparesis, cranial nerve palsies, and seizures were the clearest manifestations of infection and lung involvement reported in 57% of the patients. Histopathologic examination led to the diagnosis of infection in 57% of the patients followed by culture (23.7%), galactomannan assay (8.5%), and molecular method (3.3%). Amphotericin B and voriconazole were the most frequently used drugs for infection treatment. Good results were not obtained in one-third of the patients treated by voriconazole. Finally, neurosurgical intervention was used for 23 patients (39%). CONCLUSION: CNS aspergillosis is a rapidly progressive infection in leukemic patients. Thus, these patients should be followed up more carefully. Furthermore, management of induction chemotherapy, use of different diagnostic methods, and use of appropriate antifungal can lead to infection control.