Evaluation of expression level of BANCR, MALAT1 and FER1L4 and their target genes in coumarin-treated AGS cell line.

Because long non-coding RNAs (lncRNAs) can affect several interconnected processes, its value as a predictive marker for gastric cancer has been demonstrated. Coumarin - a natural compound known to contain some beneficial antitumor qualities - was tested for its effects on AGS gastric cancer cells. In this study, we investigated the expression level of selected cellular lncRNAs (BANCR, MALAT1 and FER1L4) and their target genes (PTEN, p-PI3K and p-AKT) in coumarin-treated AGS cell line. The expressions of the three lncRNAs: BANCR, MALAT1 and FER1L4, as well as their specified targets, PTEN, PI3K and AKT, were measured by qRT-PCR. To gauge the impact of coumarin on the AGS cells, a MTT assay was utilized. A Western blot has been employed to assess variations in PTEN, p-PI3K, and p-AKT expression. The experiment's results showed that AGS viability diminished with increasing doses of coumarin. Compared to the control cells, the cells exposed to coumarin had showed reduced levels of mRNAs which are known targets of the lncRNA BANCR. At the same time, levels of lncRNAs MALAT1 and FER1L4 within coumarin group have been higher comparing to those within control group. Additionally, the Western blot analysis revealed that the coumarin-treated cells expressed lower levels of p-PI3K, PTEN as well as p-AKT compared to control group. This information points to coumarin being a possible option in a treatment regimen for gastric cancer due to its ability to affect lncRNAs and the molecules they target.

COVID-19 associated mucormycosis (CAM) in Kashan, Iran: clinical presentations, risk factors, management, and outcomes.

BACKGROUND: This study aimed to estimate the disease burden and describe the clinical presentation, risk factors, and outcome of CAM in a single centre in Iran. METHODS: A case of mucormycosis was defined as one that had clinical and radiological features consistent with mucormycosis along with demonstration of the fungus in tissue via KOH mount/culture/histopathological and molecular examination. RESULTS: We report 30 cases of COVID-19 associated mucormycosis (CAM). The results of this study showed the affected age group in the range of 40-79 years (median = 65.5; IQR = 5) with women (16/30, 53%) affected more than men (14/30, 47%). Among the fungi recovered, Rhizopus oryzae had the highest frequency (79%). Out of the 30 patients, 28 (93%) patients were diabetic with 24 (80%) patients having other co-morbidities. Headache followed by retro-orbital pain, proptosis/ptosis and rapid diminution of vision was a common sequence of symptoms reported by the majority of cases. Use of mechanical ventilation (58% vs. 6%, p = 0.003), O2 required (92% vs. 50%, p = 0.024), and development of renal dysfunction during hospital stay (17% vs. 0%, p = 0.041) was significantly higher in non-survivors than survivors. Temperature (C°), PR (pulse rate), mean levels of serum creatinine, BUN, troponin, and neutrophils were significantly higher in non-survivors (p < 0.05). Besides, Albumin and PO2 were also significantly higher in survivors than non-survivors. CONCLUSION: Despite medical and surgical treatment, the mortality rate among CAM patients is still high. Thus, concerted efforts of revamping surveillance, diagnosis and management, along with public awareness and patient education, are the requisites for managing COVID-19 and mucormycosis.

Invasive Fusarium rhinosinusitis in COVID-19 patients: report of three cases with successful management.

Invasive fungal rhinosinusitis (IFRS) is a life-threatening infection that can occur in immunocompromised patients, including those with COVID-19. Although Mucorales and Aspergillus species are the most common causes of IFRS, infections caused by other fungi such as Fusarium are rare. In this report, we present three cases of proven rhinosinusitis fusariosis that occurred during or after COVID-19 infection. The diagnosis was confirmed through microscopy, pathology, and culture, and species identification of the isolates was performed by DNA sequencing the entire ITS1-5.8 rRNA-ITS2 region and translation elongation factor 1-alpha (TEF-1α). Antifungal susceptibility testing was conducted according to CLSI guidelines. The causative agents were identified as Fusarium proliferatum, F. oxysporum + Aspergillus flavus, and F. solani/falciforme. Treatment involved the administration of antifungal medication and endoscopic sinus surgery to remove the affected mucosa, leading to the successful resolution of the infections. However, one patient experienced a recurrence of IFRS caused by A. flavus 15 months later. Early diagnosis and timely medical and surgical treatment are crucial in reducing mortality rates associated with invasive fusariosis. Additionally, the cautious use of corticosteroids in COVID-19 patients is highly recommended.

A case of COVID-19-associated mucormycosis due to Lichtheimia ramosa.

BACKGROUND: Mucormycosis is a life-threatening invasive fungal infection in immunocompromised and COVID-19 patients. CASE REPORT: Here, we report a fatal rhino-orbito-cerebral mucormycosis caused by Lichtheimia ramosa, in a 79-year-old diabetic female. She was initially admitted to the hospital for COVID-19 infection and received broad-spectrum antibiotics and corticosteroids. After 1 month, she was admitted again because of persistent headaches and decreased right eye movement when the computed tomography scan showed mucosal thickening and opacification of paranasal sinuses. Microbiological investigations, including culture and direct microscopy, and histopathological findings confirmed the diagnosis of proven mucormycosis. The isolated causal agent was identified as Lichtheimia ramosa by sequencing the entire ITS region of nuclear ribosomal DNA. Despite surgical debridement and administration of liposomal amphotericin B 5 mg/kg/day, the patient's level of consciousness suddenly deteriorated; she was intubated and mechanically ventilated in the ICU and died on the same day. CONCLUSION: To our knowledge, this is the first worldwide case of COVID-19-associated rhino-orbito-cerebral mucormycosis due to Lichtheimia ramosa.

Case report: COVID-19-associated mucormycosis co-infection with Lomentospora prolificans: The first case and review on multiple fungal co-infections during COVID-19 pandemic.

Along with the pandemic COVID-19 spreads, new clinical challenges have emerged in the health care settings, among which there is a high risk of secondary invasive fungal infections with significant mortality. Here, we report a case of invasive fungal rhino orbital sinusitis due to the simultaneous co-infection by Rhizopus oryzae and Lomentospora prolificans, both identified by sequencing, in a 70-year-old Afghanistanian female with COVID-19. The patient was subjected to surgical debridement as well as taking liposomal amphotericin B, voriconazole, and on discharge, her condition was good. As far as we know, this is the first case of co-infection of COVID-19-associated mucormycosis (CAM) and Lomentospora prolificans infection. Multiple fungal co-infections in COVID-19 patients are reviewed.

Microbial and clinical epidemiology of invasive fungal rhinosinusitis in hospitalized COVID-19 patients, the divergent causative agents.

Since COVID-19 spread worldwide, invasive fungal rhinosinusitis (IFRS) has emerged in immunocompromised patients as a new clinical challenge. In this study, clinical specimens of 89 COVID-19 patients who presented clinical and radiological evidence suggestive of IFRS were examined by direct microscopy, histopathology, and culture, and the isolated colonies were identified through DNA sequence analysis. Fungal elements were microscopically observed in 84.27% of the patients. Males (53.9%) and patients over 40 (95.5%) were more commonly affected than others. Headache (94.4%) and retro-orbital pain (87.6%) were the most common symptoms, followed by ptosis/proptosis/eyelid swelling (52.8%), and 74 patients underwent surgery and debridement. The most common predisposing factors were steroid therapy (n = 83, 93.3%), diabetes mellitus (n = 63, 70.8%), and hypertension (n = 42, 47.2%). The culture was positive for 60.67% of the confirmed cases, and Mucorales were the most prevalent (48.14%) causative fungal agents. Different species of Aspergillus (29.63%) and Fusarium (3.7%) and a mix of two filamentous fungi (16.67%) were other causative agents. For 21 patients, no growth was seen in culture despite a positive result on microscopic examinations. In PCR-sequencing of 53 isolates, divergent fungal taxons, including 8 genera and 17 species, were identified as followed: Rhizopus oryzae (n = 22), Aspergillus flavus (n = 10), A. fumigatus (n = 4), A. niger (n = 3), R. microsporus (n = 2), Mucor circinelloides, Lichtheimia ramosa, Apophysomyces variabilis, A. tubingensis, A. alliaceus, A. nidulans, A. calidoustus, Fusarium fujikuroi/proliferatum, F. oxysporum, F. solani, Lomentospora prolificans, and Candida albicans (each n = 1). In conclusion, a diverse set of species involved in COVID-19-associated IFRS was observed in this study. Our data encourage specialist physicians to consider the possibility of involving various species in IFRS in immunocompromised and COVID-19 patients. In light of utilizing molecular identification approaches, the current knowledge of microbial epidemiology of invasive fungal infections, especially IFRS, may change dramatically.

Invasive fungal rhinosinusitis (IFRS) may infect people with diabetes, cancer, or COVID-19. In this study, various types of fungi were identified from COVID-19-associated-IFRS, encouraging physicians to consider specific treatments.

The therapeutic effect of N-acetylcysteine as an add-on to methadone maintenance therapy medication in outpatients with substance use disorders: A randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVE: Patients with substance use disorders (SUD) under methadone maintenance therapy (MMT) are susceptible to a number of complications (psychological and metabolic disorders). Evidence studies have shown the roles of the glutamatergic system in addiction. N-Acetylcysteine (NAC) enhances extracellular glutamate, and is effective in the treatment of neuropsychiatric disorders. We assessed oral NAC as an add-on to MMT medication for the treatment of SUD. METHODS: In the current randomized, double-blind, placebo-controlled clinical trial, outpatients with SUD under MMT who were 18-60 years old received 2400 mg/day NAC (n = 30) or placebo (n = 30) for 12 weeks. Psychological status and metabolic biomarkers were assessed at baseline and the end of the trial. RESULTS: Compared with the placebo group, NAC treatment resulted in a significant improvement in depression score (ß -2.36; 95% CI, -3.97, -0.76; p = .005), and anxiety score (ß -1.82; 95% CI, -3.19, -0.44; p = .01). Furthermore, NAC treatment resulted in a significant elevation in total antioxidant capacity levels (ß 72.28 mmol/L; 95% CI, 11.36, 133.19; p = .02), total glutathione (GSH) levels (ß 81.84 µmol/L; 95% CI, 15.40, 148.28; p = .01), and a significant reduction in high-sensitivity C-reactive protein levels (ß -0.89 mg/L; 95% CI, -1.50, -0.28; p = .005), and homeostasis model of assessment-insulin resistance (ß -0.33; 95% CI, -0.65, -0.009; p = .04), compared with the placebo group. CONCLUSION: In the current study, improvement in depression and anxiety symptoms as well as some metabolic profiles with NAC treatment for 12 weeks in outpatients with SUD under MMT was detected.

Unmasking sarcoidosis following SARS-CoV-2 vaccination: A case report.

Sarcoidosis is an inflammatory and granulomatous disorder, developed due to dysregulation between immune response and certain environmental antigens. We hereby report an interesting case of sarcoidosis following COVID-19 vaccination (COVIran Barekat), which presented with inflammation of previous tattoo sites as well as the development of erythema nodosum and systemic lymphadenopathy, suggested a possible link between the COVID vaccination and dysregulation of the inflammatory process and served as a reminder for clinicians to have enough vigilance before proposing a vaccine booster to these patients.

The Effects of Probiotic Supplementation on Opioid-Related Disorder in Patients under Methadone Maintenance Treatment Programs.

Introduction: Patients under methadone maintenance treatment programs (MMTPs) are susceptible to numerous complications (e.g., mental and metabolic disorders). This study evaluated the effects of probiotics on clinical symptoms, biomarkers of oxidative stress, inflammation, insulin resistance, and serum lipid content in patients receiving MMTPs. Materials and Methods: A randomized, double-blind, placebo-controlled trial was conducted among 70 patients receiving MMTPs to receive either 1.8 × 109 CFU/day probiotics (n = 35) or placebo (n = 35) for 12 weeks. Clinical symptoms and metabolic profiles were measured before and after the intervention in patients receiving MMTPs. Results: Compared with the placebo group, probiotic supplementation resulted in a significant improvement in the severity of depression (P < 0.05). In addition, probiotic administration significantly decreased fasting plasma glucose (FPG), total cholesterol, and low-density lipoprotein cholesterol (LDL cholesterol) (P < 0.05). Furthermore, probiotics resulted in a significant reduction in high-sensitivity C-reactive protein (hs-CRP) and a significant elevation in total antioxidant capacity (TAC) and total glutathione (GSH) levels (P < 0.05). Conclusion: Treatment with probiotics for 12 weeks to patients receiving MMTPs had beneficial effects on symptoms of depression, as well as several metabolic profiles. Clinical Trial Registration: this study was registered in the Iranian website (https://www.irct.ir) for clinical trials registration (https://fa.irct.ir/trial/46363/IRCT20170420033551N9). The registration date is March 22, 2020.

Evaluation of Nestin and EGFR in Patients with Glioblastoma Multiforme in a Public Hospital in Iran.

INTRODUCTION: Glioblastoma multiforme (GBM) is a grade IV glioma and accounts for 15% of all primary brain tumors. This GBM has a median survival range of less than 2 years after diagnosis and it is highly vascularized by neoformed vessels. Neoangiogenesis is a crucial factor in the malignant tumoral behavior and prognosis of patients and Nestin protein belongs to class VI which is expressed in endothelial cells of neoformed vessels in GBM. Our study shows the correlation between EGFR mutation and Nestin expression in endothelial of neoformed vessels in GBM. METHODS: We analyzed 40 GBM samples by immunohistochemistry staining. The immunohistochemical expression of EGFR in tumoral cells and Nestin in endothelial cells in paraffin sections were analyzed. EGFR scoring was the based on staining intensity. Score 0 shows No staining, Score1, mild to moderate staining and score2 sever staining. Microvascular density (MVD) was evaluated with Nestin-immunoreactive. RESULTS: The mean of MVD was 14.6 ±8.25. Nestin-MVD was significantly higher in GBM with sever vascular prolifration (p-value=0.01). EGFR was expressed in 92.5% of samples. The EGFR scoring for tumoral tissue was 7.5%(score:0), 22.5% (score:1) and 70% (score:2). There was a significant relationship between EGFR expression and MVD (p-value=0.017). CONCLUSION: We suggest that some important mutations as like as EGFR in GBM is responsible for inducing angiogenesis and vascular proliferation. Nestin overexpression as a novel marker might reflect the extent of neoangiogenesis, thus target therapy against EGFR pathway and anti angiogenic may be useful for GBM treatment.

Association of ApaI and TaqI polymorphisms in VDR Gene with Breast Cancer.

BACKGROUND: Vitamin D inhibits cell proliferation via the vitamin D receptor (VDR), which may affect breast cancer risk. This study aimed to investigate the association of ApaI and TaqI polymorphisms of the VDR gene with breast cancer risk which followed by stratified analysis. MATERIALS AND METHODS: A case-control study was conducted on 150 breast cancer patients and 150 healthy controls. VDR ApaI and TaqI genotyping were performed by PCR-RFLP. Some demographic and pathologic features of patients were extracted from their archived files and then were analyzed by genotypes distributions. RESULTS: For ApaI polymorphism, our data showed a significant difference between the patient and healthy groups for mutant allele carriers compared with those with AA genotype. Besides, statistical analysis showed that there was a significant association between the C allele and the increased risk of breast cancer. For TaqI polymorphism, statistical analysis revealed that there was a significant association between CC genotype and increased risk of breast cancer. Also, there was a significant association between the C allele and the increased risk of breast cancer. In a preliminary study, stratified analysis based on the size of tumor and lymph node metastasis revealed no significant association between two ApaI and TaqI variations and these parameters. CONCLUSIONS: Based on our results, the VDR ApaI and TaqI variations could be considered as genetic risk factors for breast cancer. However, further studies with a larger sample size are required to obtain more accurate outcomes, especially in stratified analysis.