Evaluation of Beclin1 and mTOR genes and p62 protein expression in breast tumor tissues of Iranian patients.

Autophagy is a cellular process that plays a major role in the fate of tumor cells. Understanding the role of autophagy in cancer therapy is a major challenge, particularly for breast cancer as the sole top cause of mortality among women. In this study, we evaluated the gene expression of mTOR and Beclin1 and the levels of p62 protein, in breast tumors and compared them to a control condition. To explore the role of autophagy in breast cancer, we acquired tumor biopsies from 41 new cases of breast cancer patients. We extracted total RNA from each biopsy and used real-time PCR to quantify Beclin1 and mTOR-specific RNA expression. In addition, we evaluated the expression of the p62 protein in paraffin-embedded tumor tissue using the immunohistochemistry technique. The data revealed an upregulation of Beclin1 and a downregulation of mTOR in tumor tissues compared to the control condition. The correlation between p62 expression and Beclin1/mTOR showed a negative and positive correlation, respectively, confirming autophagy activation in the tumor tissues. However, there was no correlation between autophagy markers and tumor size, grade and stage. The findings revealed that autophagy activation was found in breast tumor tissues, suggesting that autophagy can be a target for breast cancer therapy.

Neurosurgical Management of Cerebrospinal Tumors in the Era of Artificial Intelligence : A Scoping Review.

Central nervous system tumors are identified as tumors of the brain and spinal cord. The associated morbidity and mortality of cerebrospinal tumors are disproportionately high compared to other malignancies. While minimally invasive techniques have initiated a revolution in neurosurgery, artificial intelligence (AI) is expediting it. Our study aims to analyze AI's role in the neurosurgical management of cerebrospinal tumors. We conducted a scoping review using the Arksey and O'Malley framework. Upon screening, data extraction and analysis were focused on exploring all potential implications of AI, classification of these implications in the management of cerebrospinal tumors. AI has enhanced the precision of diagnosis of these tumors, enables surgeons to excise the tumor margins completely, thereby reducing the risk of recurrence, and helps to make a more accurate prediction of the patient's prognosis than the conventional methods. AI also offers real-time training to neurosurgeons using virtual and 3D simulation, thereby increasing their confidence and skills during procedures. In addition, robotics is integrated into neurosurgery and identified to increase patient outcomes by making surgery less invasive. AI, including machine learning, is rigorously considered for its applications in the neurosurgical management of cerebrospinal tumors. This field requires further research focused on areas clinically essential in improving the outcome that is also economically feasible for clinical use. The authors suggest that data analysts and neurosurgeons collaborate to explore the full potential of AI.

Inhibitory effects of fluoxetine on the secretion of inflammatory mediators and JAK/STAT3 and JNK/TLR4 gene expression.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are the most common class of medicines used for the treatment of major depression. Recent studies have reported an association between depression and inflammation and suggested the significant effects of SSRIs on inflammatory processes. METHODS: The current study aimed to evaluate the effects of fluoxetine, an SSRI, on the level of inflammatory cytokines, including interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in the rat serum and RAW264.7 mouse macrophage cell line, using ELISA sandwich assays. Also, the expression of inflammatory genes, including JAK/STAT3 and TLR4/JNK, was examined in macrophages, using real-time quantitative reverse transcription PCR to determine the potential mechanism of fluoxetine in inflammation. The rats received fluoxetine (10, 20, and 40 mg/kg) 30 min before lipopolysaccharide (LPS) treatment for 90 min. The cells received different doses of fluoxetine (5, 10, and 20 µg/mL) before stimulation with LPS for 24 or 48 h. RESULTS: The serum concentrations of IL-1ß, IL-6, and TNF-α were reduced in rats and cells treated with fluoxetine. Following fluoxetine administration, the expression of JAK/STAT3 and TLR4/JNK genes was significantly decreased in the RAW264.7 cells treated with LPS for 24 h. However, after 48 h of treatment with LPS, fluoxetine failed to diminish the elevated expression of JAK and JNK genes, while it significantly decreased the expression of STAT3 and TLR4 genes. CONCLUSION: The findings revealed that fluoxetine has anti-inflammatory properties, mainly due to the reduction of inflammatory cytokines and inhibition of JAK/STAT3 and TLR4/JNK gene expression in macrophages.

The ameliorative effects of Alpinia officinarum rhizome hydroalcoholic extract on cisplatin-induced testicular toxicity in rats.

OBJECTIVE: In this study we evaluated the influence of Alpinia officinarum rhizome extract (AO) on the alleviation of testicular damage induced by cisplatin in rats. METHODS: The study groups included the control group, AO-administered group, cisplatin-administered group, and three groups administered with cisplatin and AO (different concentrations of 100, 200, and 400 mg/kg). On the 14th day we removed the testes of the rats, and the testicular organ parameters were measured. Moreover, through the malondialdehyde concentration we assessed the oxidative stress and superoxide dismutase (SOD) activity of the testes and ran a histopathological analysis. RESULTS: The results demonstrated that cisplatin-induced oxidative stress and severe testicular damage on the AO-administered group showed no harm compared with the control group. AO- treatment in cisplatin-received rats led to the reduction of oxidative stress, enhancement of SOD activity, and prevention of testicular damage. The lowest testis damage was attributed to the group which received 400 mg/kg of AO compared to 100 and 200 mg/kg. CONCLUSIONS: Overall, the Cis+/AO+400 group had the best antioxidant effect. The findings could lead to changes in cancer care guidelines that incorporate phytochemicals, making cancer therapies safer.

Evaluation of maxillary arch width and palatal volume and depth in patients with maxillary impacted canine by CBCT.

Introduction: Canines are the second most common tooth in terms of impaction. Impacted teeth can be associated with some different indices of dental arch and dentoalveolar structures. The aim of this study was to evaluate maxillary arch width as well as volume and depth of palate in patients with maxillary impacted canine by cone beam computed tomography (CBCT). Methods: In this cross-sectional study, 45 CBCT images of patients with unilateral maxillary impacted canines were examined. All patients had palatally impacted canines. Three parameters of maxillary arch width, palatal volume and palatal depth were assessed using axial and sagittal incisions on the CBCT images. Then all the measurements on the impacted side were compared with the non-impacted side. Data were entered into SPSS software and paired sample t-test and Student's t-test were used to comparison. The significance level of 0.05 was considered. Results: The maxillary arch width on the impacted side was significantly less than the normal side (P < 0.001). The mean depth of the palate was 14.86 ± 3.53 mm. There was a significant correlation between canine impaction and Palatal volume (R = 0.728 and P-value< 0.001), but no significant correlation between canine impaction and Maxillary arch width was shown (R = 0.15 and p-value = 0.326). Conclusion: The impacted canine was significantly associated with a reduction in the width of the maxillary arch on the affected side, and it made no difference if the impacted side was left or right. Also, impacted canine teeth were significantly associated with volume reduction on the affected side.

Post-COVID-19 Pulmonary Fibrosis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions worldwide with a high mortality rate due to a lack of definitive treatment. Despite having a wide range of clinical features, acute respiratory distress syndrome (ARDS) has emerged as the primary cause of mortality in these patients. Risk factors and comorbidities like advanced age with limited lung function, pre-existing diabetes, hypertension, cardiovascular diseases, and obesity have increased the risk for severe COVID-19 infection. Rise in inflammatory markers like transforming growth factor ß (TGF-ß), interleukin-6 (IL-6), and expression of matrix metalloproteinase 1 and 7 (MMP-1, MMP-7), along with collagen deposition at the site of lung injury, results in extensive lung scarring and fibrosis. Anti-fibrotic drugs, such as Pirfenidone and Nintedanib, have emerged as potential treatment options for post-COVID-19 pulmonary fibrosis. A lung transplant might be the only life-saving treatment. Despite the current advances in the management of COVID-19, there is still a considerable knowledge gap in the management of long-term sequelae in such patients, especially concerning pulmonary fibrosis. Follow up on the current clinical trials and research to test the efficacy of various anti-inflammatory drugs is needed to prevent long-term sequelae early mortality in these patients.

A Green Approach for the Biosynthesis of Gold Nanoparticles Using Cuminum cyminum L. Seed and Its Application for Pain Management in Rats.

Background: This study investigated the antinociceptive effect of cumin and its biosynthesized gold nanoparticles (AuNPs). Methods: Cumin extract (E) and cumin-AuNPs (GN) were prepared and administered intraperitoneally at the concentrations of 200, 500, and 1000 mg/ml to 27 male rats. Ultraviolet-visible spectroscopy and atomic force microscopy were applied for AuNPs synthesis confirmation. The nociceptive behavior was assessed, and IL-6 serum levels were measured. Results: Cumin-AuNPs showed a peak absorption of 515 nm, and a size of about 40 nm. Three different concentrations of extract had no significant effect on acute and chronic nociceptive behavior. GN + E200 (46.00 ± 10.59) showed a significant acute anti-nociceptive effect compared to the control (98.66 ± 4.91; p = 0.029) and SS300 (98.33 ± 20.30; p = 0.029) groups. Also, GN + E500 (42.00 ± 11.84) significantly reduced acute nociceptive behavior compared to the control (98.66 ± 4.91; p = 0.019), SS300 (98.33 ± 20.30; p = 0.020), and GN + E1000 (91.00 ± 26.00; p = 0.040) groups. IL-6 serum levels reduced significantly in GN + E500 (24.65 ± 10.38; p = 0.002) and SS300 (33.08 ± 1.68; p = 0.039) compared to the controls (46.24 ± 3.02). Chronic nociceptive behavior was significantly lower in the SS300 (255.33 ± 26.30) compared to E200 (477.00 ± 47.29; p = 0.021), E500 (496.25 ± 46.29; p = 0.013), and GN + E500 (437.00 ± 118.03; p = 0.032) groups. Conclusion: Our findings suggest the potential effects of cumin-AuNPs on formalin-induced nociceptive behavior, which is independent of IL-6serum levels.

Risk Factors for Postpartum Depression During COVID-19 Pandemic: A Systematic Literature Review.

INTRODUCTION: The COVID-19 pandemic has had a devastating worldwide effect on mental health. Recent studies correlate the spreading of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with symptoms of depression, most prominent in postpartum women. Our systematic literature review scope is to identify the risk factors and predictors for postpartum depression (PPD) and describe the steps that should be taken to help postpartum women. This study will help clinicians, researchers, and policymakers to elucidate the predictors of PPD during this pandemic and prevent these adverse outcomes in future crises. METHODS: We conducted a systematic search by employing databases PubMed, Google Scholar, Scopus, and Embase to identify articles published before March 2021. About 463 publications were generated during our search process and from those, 36 were reviewed, summarized, and synthesized. Studies qualified the criteria if they (1) utilized qualitative or quantitative design, (2) explored the risk factors for PPD, and (3) were written in English. Quality evaluation of each study was achieved by using criteria set by Lincoln and Guba. RESULTS: Prevalence of depression symptoms ranged from 7% to 80.8% in postpartum women during the SARS-COV 2 pandemic. The risk factors for PPD were classified into 6 major categories: socio-demographic, psychological, pre-existing pathology, metabolic factors, previous events of miscarriage, and media misinformation. CONCLUSION: It is extremely vital to care for women's mental health during pregnancy and after childbirth during these unprecedented times. This review urges the need to design adequate interventions for this vulnerable population to prevent negative consequences of PPD.

Increased protein expression of ABCA1, HMG-CoA reductase, and CYP46A1 induced by garlic and allicin in the brain mouse and astrocytes-isolated from C57BL/6J.

OBJECTIVE: Regulation of cholesterol level is essential for the brain optimal function. The beneficial effect of garlic consumption on cholesterol homeostasis is well known; however, the molecular mechanism to support its properties is unclear. Here, we investigated the beneficial effect of aqueous extract of garlic and allicin on lipid profile and the main players involved in brain cholesterol homeostasis including ABCA1, HMG-CoA reductase, and CYP46A1 in both C57BL/6J mice brain and astrocytes. MATERIALS AND METHODS: Thirty mice were divided into control and garlic groups. Garlic group was fed with the aqueous extract of garlic. Serum lipids were measured and brain protein levels of ABCA1, HMGCR, and CYP46A1 were determined by western blotting. Changes in these proteins expression were also studied in the presence of allicin in cultured astrocytes. RESULTS: A moderate decrease in serum total cholesterol and a significant increase in plasma HDL-C levels (p<0.05) were detected. A significant increase in ABCA1, HMGCR, and CYP46A1 protein levels was observed in the garlic group and in the cultured astrocytes treated with allicin by western blotting (p<0.05). CONCLUSION: Our findings indicated that the main players involved in cholesterol turnover including HMGCR that is involved in cholesterol synthesis, ABCA1 that is important in cholesterol efflux, and CYP46A1 that is necessary in cholesterol degradation, were up regulated by garlic/allicin in both animal and cell culture model. We concluded that increasing cholesterol turnover is a possible mechanism for the beneficial effects of garlic in cholesterol homeostasis.

Use of Epoprostenol in the Treatment of Pulmonary Arterial Hypertension.

Pulmonary Hypertension (PH) is defined as a disorder in which the mean Pulmonary Arterial Pressure (mPAP) is greater than 20 mmHg at rest. Pulmonary Arterial Hypertension (PAH) is considered when mPAP is > 20 mmHg and pulmonary vascular resistance (PVR) is ⩾ 3 WU. PAH is a chronic progressive disease resulting in right heart failure and premature death. It is postulated to be due to an inactivating mutation of a gene named bone morphogenetic protein receptor type 2 (BMPR2), whose predominant function is halting vascular proliferation. It has a lamentable prognosis if not rapidly diagnosed and adequately treated. Treatment of PAH has evolved in the past few decades since many related pathways and potential therapeutic targets have been explored. Parenteral prostanoids are the most effective therapeutic options for PAH. Epoprostenol is a synthetic analog of prostacyclin and a potent vasodilator that was Food and Drug Administration (FDA)-approved in December 1995 for intravenous use to treat PAH. It has also been used to treat different PAH subtypes, including connective tissue-related PAH like lupus and systemic sclerosis, congenital heart disease, and drug-induced PAH. It is effective in reducing mortality rates and improving survival rates. Although the use of Epoprostenol for PAH is challenging, it has been one of the most successful therapies used. In this manuscript, we review the pathophysiology of PAH and the risk stratification tool. We also discuss the mechanism of action of PAH-targeted therapies while focusing on the role of epoprostenol that has been investigated in many clinical trials. Finally, we discuss two ongoing clinical trials which highlight some potential therapeutic options.

Efficacy of naproxen in the management of patients hospitalized with COVID-19 infection: A randomized, double-blind, placebo-controlled, clinical trial.

BACKGROUND AND AIMS: The current study was done to examine the efficacy of naproxen in the management of patients with COVID-19 infection. METHODS: This randomized, double-blind, placebo-controlled, clinical trial was done on hospitalized adult patients with confirmed COVID-19 infection. Patients were randomly assigned to receive either naproxen (two capsules per day each containing 500 mg naproxen sodium) or placebo (containing starch) for five days along with the routine treatment that was nationally recommended for COVID-19 infection. Clinical symptoms of COVID-19 infection, the time to clinical improvement, blood pressure, laboratory parameters, and death due to COVID-19 infection were considered as the outcome variables in the present study. RESULTS: Treatment with naproxen improved cough and shortness of breath in COVID-19 patients; such that, compared with placebo, naproxen intake was associated with 2.90 (95% CI: 1.10-7.66) and 2.82 (95% CI: 1.05-7.55) times more improvement in cough and shortness of breath, respectively. In addition, naproxen administration resulted in a significant increase in mean corpuscular volume (MCV) and had a preventive effect on the reduction of systolic blood pressure in COVID-19 patients. CONCLUSION: Treatment with naproxen can improve cough and shortness of breath in COVID-19-infected patients. Further studies are required to confirm our findings.

Evaluation of Oxidative Stress, Apoptosis, and Expression of MicroRNA-208a and MicroRNA-1 in Cardiovascular Patients.

BACKGROUND: MicroRNA expression signature and reactive oxygen species (ROS) production have been associated with the development of cardiovascular diseases (CVDs). This study aimed to evaluate oxidative stress, inflammation, apoptosis, and the expression of miRNA-208a and miRNA-1 in cardiovascular patients. METHODS: The study population included four types of patients (acute coronary syndromes (ACS), myocardial infarction (MI), arrhythmia, and heart failure (HF)), with 10 people in each group, as well as a control group. Quantitative real-time PCR was performed to measure mir-208 and miR-1 expression, the mRNAs of inflammatory mediators (TNFα, iNOS/eNOS), and apoptotic factors (Bax and Bcl2). XOX, MDA, and antioxidant enzymes (CAT, SOD, and GPx) were measured by ZellBio GmbH kits by an ELISA Reader. RESULTS: The results showed significant decreases in the activity of antioxidant enzymes (CAT, SOD, and Gpx) and a significant increase in the activity of the MDA and XOX in cardiovascular patients. Significant increases in IL-10, iNos, iNOS / eNOS, and TNF-α in cardiovascular patients were also observed. Also, a significant increase in the expression of miR-208 (HF> arrhythmia> ACS> MI) and a significant decrease in the expression of miR-1 (ACS> arrhythmia> HF> MI) were found in all four groups in cardiovascular patients. CONCLUSION: The results showed increases in oxidative stress, inflammation, apoptotic factors, and in the expression of miR-208a in a variety of cardiovascular patients (ACS, MI, arrhythmia, and HF). It is suggested that future studies determine the relationships that miR-1, miR-208, and oxidative stress indices have with inflammation and apoptosis.

Effect of Total Suspended Particulate Matter in the Air on Inflammation Factors and Apoptotic Markers in Diabetic Rats: The Protective Effect of Insulin and Crocin.

BACKGROUND: The effect of total suspended particulate matter (TSP) was investigated on the expression of inflammatory and apoptotic factors in diabetic rats, and the effect of crocin and insulin was examined on these factors. METHODS: Fifty-four adult male wistar rats were divided into nine experimental groups: control group, crocin group (received crocin, 50 mg/kg), diabetic group (received a single dose of alloxan at 120 mg/kg, IP), TSP group (5 mg/kg TSP instilled intratracheally), diabetic-crocin group (received crocin at 50 mg/kg after the induction of diabetes by alloxan (120 mg/kg)), diabetic-insulin group (received regular insulin (5 U/kg), crocin-TSP group (received crocin at 50 mg/kg, IP, and then 5 mg/kg TSP was instilled intratracheally), diabetic-TSP-insulin group (after receiving alloxan (120 mg/kg) and instilling TSP (5 mg/kg, intratracheally), a single dose (5 U/kg) of regular insulin), and diabetic-TSP-crocin group (after receiving alloxan (120 mg/kg) and instilling TSP (5 mg/kg, intratracheally), a single dose of crocin (50 mg/kg, IP)). Quantitative real-time PCR was performed to measure the expression of the mRNAs of apoptotic (Bax and Bcl2) and inflammatory mediators (TNFα, COX2, iNOS/eNOS) in Wistar rats. RESULTS: In diabetic and TSP groups the inflammatory factors and BAX/Bcl2 ratio significantly increased compared to the control group. In diabetic-TSP-insulin and diabetic-TSP-crocin, a significant decrease was observed in the rate of inflammatory factors and BAX/Bcl2 ratio. CONCLUSION: The results suggested that diabetes and exposure to TSP increase the rate of apoptosis and inflammation, and also demonstrated the anti-apoptotic and anti-inflammation role of insulin and crocin.

Cuminum cyminum L.-Mediated Synthesis of Silver Nanoparticles: Their Characterization and Effect on Formalin-Induced Nociceptive Response in Male Rats.

In this study, a simple, low-cost, rapid, and eco-friendly approach for the biosynthesis of silver nanoparticles (AgNPs) using the aqueous extract of Cuminum cyminum L. (cumin) seed (CcAgNPs) was developed. Also, the anti-nociceptive properties of these synthesized AgNPs were evaluated in vivo. The CcAgNPs characterized using Ultraviolet-visible (UV-Vis) spectrophotometer, X-ray diffraction analysis (XRD), Fourier transform infrared (FTIR) spectroscopy, atomic force microscopy (AFM), and transmission electron microscopy (TEM). The analysis of phytochemical components in the aqueous extract of cumin seeds showed high concentrations of total phenols and ascorbic acid and low concentrations of total flavonoids. The analysis of phytochemical components and FTIR spectroscopy confirmed the presence of functional groups responsible for the bioreduction of Ag+ to AgNPs. The UV-Vis absorbance spectrum of CcAgNPs showed a maximum wavelength at 442 nm. The analysis of TEM images showed a spherical shape with a size of less than 50 nm, while XRD spectra revealed the crystallinity of CcAgNPs. The analysis of anti-nociceptive properties of CcAgNPs showed that the first phase of formalin-induced pain was significantly reduced in the groups receiving 200, 500, and 1000 mg/kg CcAgNPs compared with the controls and the group receiving 300 mg/kg of sodium salicylate (SS300). The second phase of formalin pain was also significantly reduced in the groups receiving 200 and 500 mg/kg CcAgNPs compared to the controls and SS300 group. Overall, we introduced a new AgNPs synthesized from cumin seeds (CcAgNPs) and showed their anti-nociceptive properties in the formalin-induced pain.

Effect of Hydroalcoholic Ginger Extract on Brain HMG-CoA Reductase and CYP46A1 Levels in Streptozotocin-induced Diabetic Rats.

BACKGROUND: Patients with diabetes present with lipid disorders, including hypercholesterolemia, which can be a high-risk factor for atherosclerosis. Recently, increasing interest has been focused on anti-lipidemic function of herbal medicines, especially Zingiber officinale (known as ginger), in diabetes. However, the mechanism underlying the effect of ginger on some players involved in cholesterol homeostasis of Central Nervous System (CNS) among diabetic patients remains unclear. To our knowledge, this is the first study to investigate the effect of ginger on brain regulation of Hydroxymethylglutaryl-CoA Reductase (HMG-CoA reductase) and Cholesterol 24-hydroxylase (CYP46A1), which provides a rational model for understanding brain dyslipidemia mechanisms associated with diabetes. METHODS: Brains of rats were isolated from four groups: control, non-treated diabetic, and treated diabetic groups receiving 200 or 400 mg/kg of hydroalcoholic extracts of ginger for eight weeks. HMG-CoA reductase and CYP46A1 levels in brain homogenates were determined by western-blot technique. RESULTS: Ginger root extract caused a significant decrease in HMG-CoA reductase and an increase in CYP46A1 levels in treated diabetic groups compared to diabetic control. In comparison to diabetic group, these effects were more remarkable with 400 mg/kg concentration of ginger extract. CONCLUSION: The findings showed that ginger extract has a regulatory effect on proteins involved in cholesterol homeostasis in CNS by a significant down- and up-regulation of HMG-CoA reductase and CYP46A1 levels, respectively. It can be suggested that adding ginger to daily diet of diabetic patients has useful effects and may ameliorate diabetes complications.

Association of G/C (rs638405) Polymorphism in ß-secretase Gene with Alzheimer's Disease.

BACKGROUND: Alzheimer's Disease (AD) is a neurodegenerative disorder, which is the most common cause of dementia in the elderly. Accumulation of ß-amyloid plaques outside neurons is the most important pathological hallmark of AD, which is produced by cleavage of amyloid precursor protein by the Alzheimer's ß-secretase (BACE1). Since BACE1 is a key enzyme in the formation of ß-amyloid peptides, the purpose of this study was to assess the association between polymorphisms of G/C (rs638405) BACE1 gene with sporadic AD in Khuzestan, Isfahan and Fars provinces in Iran. METHODS: Genotypes were determined by the PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) technique in two groups including 89 sporadic AD patients and 73 healthy subjects. RESULTS: The findings of the BACE1 G/C (rs638405) polymorphism revealed that there was no significant difference between AD patients and controls in men group; however, there was a weak difference in the frequency of CC genotype between patients and controls in women group (χ 2=3.333, df=1, p=0.068). CONCLUSION: The results of this study suggest that the G/C (rs638405) polymorphism of BACE1 gene might not be related with sporadic AD in Khuzestan, Isfahan and Fars provinces in Iran. However, our results do not support a genetic risk factor of this polymorphism for developing AD in male group of this study.