Riboflavin-Induced DNA Damage and Anticancer Activity in Breast Cancer Cells under Visible Light: A TD-DFT and In Vitro Study.

Targeted treatments for breast cancer that minimize harm to healthy cells are highly sought after. Our study explores the potentiality of riboflavin as a targeted anticancer compound that can be activated by light irradiation. Here, we integrated time-dependent density functional theory (TD-DFT) calculations and an in vitro study under visible light. The TD-DFT calculations revealed that the electronic charge transferred from the DNA base to riboflavin, with the most significant excitation peak occurring within the visible light range. Guided by these insights, an in vitro study was conducted on the breast cancer cell lines MCF-7 and MDA-MB-231. The results revealed substantial growth inhibition in these cell lines when exposed to riboflavin under visible light, with no such impact observed in the absence of light exposure. Interestingly, riboflavin exhibited no/minimal growth-inhibitory effects on the normal cell line L929, irrespective of light conditions. Moreover, through EtBr displacement (DNA-EtBr) and the TUNEL assay, it has been illustrated that, upon exposure to visible light, riboflavin can intercalate within DNA and induce DNA damage. In conclusion, under visible light conditions, riboflavin emerges as a promising candidate with a selective and effective potent anticancer agent against breast cancer while exerting a minimal influence on regular cellular activity.

Biomedical applications of graphene-based nanomaterials: recent progress, challenges, and prospects in highly sensitive biosensors.

Graphene-based nanomaterials (graphene, graphene oxide, reduced graphene oxide, graphene quantum dots, graphene-based nanocomposites, etc.) are emerging as an extremely important class of nanomaterials primarily because of their unique and advantageous physical, chemical, biological, and optoelectronic aspects. These features have resulted in uses across diverse areas of scientific research. Among all other applications, they are found to be particularly useful in designing highly sensitive biosensors. Numerous studies have established their efficacy in sensing pathogens and other biomolecules allowing for the rapid diagnosis of various diseases. Considering the growing importance and popularity of graphene-based materials for biosensing applications, this review aims to provide the readers with a summary of the recent progress in the concerned domain and highlights the challenges associated with the synthesis and application of these multifunctional materials.

Deciphering the Lexicon of Protein Targets: A Review on Multifaceted Drug Discovery in the Era of Artificial Intelligence.

Understanding protein sequence and structure is essential for understanding protein-protein interactions (PPIs), which are essential for many biological processes and diseases. Targeting protein binding hot spots, which regulate signaling and growth, with rational drug design is promising. Rational drug design uses structural data and computational tools to study protein binding sites and protein interfaces to design inhibitors that can change these interactions, thereby potentially leading to therapeutic approaches. Artificial intelligence (AI), such as machine learning (ML) and deep learning (DL), has advanced drug discovery and design by providing computational resources and methods. Quantum chemistry is essential for drug reactivity, toxicology, drug screening, and quantitative structure-activity relationship (QSAR) properties. This review discusses the methodologies and challenges of identifying and characterizing hot spots and binding sites. It also explores the strategies and applications of artificial-intelligence-based rational drug design technologies that target proteins and protein-protein interaction (PPI) binding hot spots. It provides valuable insights for drug design with therapeutic implications. We have also demonstrated the pathological conditions of heat shock protein 27 (HSP27) and matrix metallopoproteinases (MMP2 and MMP9) and designed inhibitors of these proteins using the drug discovery paradigm in a case study on the discovery of drug molecules for cancer treatment. Additionally, the implications of benzothiazole derivatives for anticancer drug design and discovery are deliberated.

4″-Alkyl EGCG Derivatives Induce Cytoprotective Autophagy Response by Inhibiting EGFR in Glioblastoma Cells.

Epidermal growth factor receptor (EGFR)-targeted therapy has been proven vital in the last two decades for the treatment of multiple cancer types, including nonsmall cell lung cancer, glioblastoma, breast cancer and head and neck squamous cell carcinoma. Unfortunately, the majority of approved EGFR inhibitors fall into the drug resistance category because of continuous mutations and acquired resistance. Recently, autophagy has surfaced as one of the emerging underlying mechanisms behind resistance to EGFR-tyrosine kinase inhibitors (TKIs). Previously, we developed a series of 4″-alkyl EGCG (4″-Cn EGCG, n = 6, 8, 10, 12, 14, 16, and 18) derivatives with enhanced anticancer effects and stability. Therefore, the current study hypothesized that 4″-alkyl EGCG might induce cytoprotective autophagy upon EGFR inhibition, and inhibition of autophagy may lead to improved cytotoxicity. In this study, we have observed growth inhibition and caspase-3-dependent apoptosis in 4″-alkyl EGCG derivative-treated glioblastoma cells (U87-MG). We also confirmed that 4″-alkyl EGCG could inhibit EGFR in the cells, as well as mutant L858R/T790M EGFR, through an in vitro kinase assay. Furthermore, we have found that EGFR inhibition with 4″-alkyl EGCG induces cytoprotective autophagic responses, accompanied by the blockage of the AKT/mTOR signaling pathway. In addition, cytotoxicity caused by 4″-C10 EGCG, 4″-C12 EGCG, and 4″-C14 EGCG was significantly increased after the inhibition of autophagy by the pharmacological inhibitor chloroquine. These findings enhance our understanding of the autophagic response toward EGFR inhibitors in glioblastoma cells and suggest a potent combinatorial strategy to increase the therapeutic effectiveness of EGFR-TKIs.

Metastatic Primary Neuroendocrine Tumor of Ovary-A Rare Presentation.

Neuroendocrine tumors (NETs) occur more commonly in lungs, gastrointestinal tract, or pancreas. NETs in locations such as ovaries are rare, and they have been described mainly in case reports. Here we describe a patient with primary NET of ovary presenting with distant metastases to peritoneum, liver, lung, and mediastinal lymph nodes.

Structure-based design and synthesis of a novel long-chain 4''-alkyl ether derivative of EGCG as potent EGFR inhibitor: in vitro and in silico studies.

Herein, we report the discovery of a novel long-chain ether derivative of (-)-epigallocatechin-3-gallate (EGCG), a major green tea polyphenol as a potent EGFR inhibitor. A series of 4''-alkyl EGCG derivatives have been synthesized via regio-selectively alkylating the 4'' hydroxyl group in the D-ring of EGCG and tested for their antiproliferative activities against high (A431), moderate (HeLa), and low (MCF-7) EGFR-expressing cancer cell lines. The most potent compound, 4''-C14 EGCG showed the lowest IC50 values across all the tested cell lines. 4''-C14 EGCG was also found to be significantly more stable than EGCG under physiological conditions (PBS at pH 7.4). Further western blot analysis and imaging data revealed that 4''-C14 EGCG induced cell death in A431 cells with shrunken nuclei, nuclear fragmentation, membrane blebbing, and increased population of apoptotic cells where BAX upregulation and BCLXL downregulation were observed. In addition, autophosphorylation of EGFR and its downstream signalling proteins Akt and ERK were markedly inhibited by 4''-C14 EGCG. MD simulation and the MM/PBSA analysis disclosed the binding mode of 4''-C14 EGCG in the ATP-binding site of EGFR kinase domain. Taken together, our findings demonstrate that 4''-C14 EGCG can act as a promising potent EGFR inhibitor with enhanced stability.

Inflammatory Lesions Mimicking Chest Malignancy: CT, Bronchoscopy, EBUS, and PET Evaluation From an Oncology Referral Center.

Infective and inflammatory diseases can mimic malignancy of the lung. Granulomatous inflammations are common causes of pulmonary nodule, mass, or nodal disease. Systemic infection or inflammation also commonly involves the lung that may raise suspicion of a malignant process. Even in patients with a known malignancy, inflammatory diseases can simulate new metastasis or disease progression. Knowledge of the imaging features of these diseases is essential to prevent missed or overdiagnosis of malignancy. Radiologists also need to be familiar with the scope and limitations of bronchoscopy, endobronchial ultrasound, PET-CT, and biopsy to guide clinical management. In this review, we discuss the imaging features and diagnostic approach of common mimickers of chest malignancy that involve the chest wall, pleura, lung parenchyma, and mediastinal nodes.

Dorsal Vertebral Enhancement Mimicking Sclerosing Metastases in Lung Cancer.

We report cases of vertebral body enhancement in patients with superior vena cava and brachiocephalic venous obstruction appearing as sclerotic metastases in post-contrast CT.A 58-year-old male presented with right lung mass compressing the superior vena cava.Sclerotic areas seen involving few vertebrae in post-contrast scans.Another patient, 64-year-old female with right lung mass and narrowing of left brachiocephalic vein, sclerosis of lower cervical and upper dorsal vertebrae were seen in contrast studies. In both cases after resolution of pathology following treatment showed no enhancement in post contrast scan which was attributed to the collaterals arising due to obstruction, obviously not seen in metastases. Keywords: Brachiocephalic vein obstruction; computed tomography CT; superior vena cava SVC; vertebral enhancement; venous collaterals.

Accuracy of MRI without intracavernosal prostaglandin E1 injection in staging, preoperative evaluation, and operative planning of penile cancer.

PURPOSE: To evaluate the performance of non-erectile MRI in staging and preoperative evaluation of penile carcinomas, compared to postoperative histopathology. METHODS: In this retrospective study, MRI scans of patients who had undergone surgery for penile carcinoma (n = 54) between January 2012 and April 2018 were read by two radiologists; and disagreement was solved in the presence of a third experienced radiologist. Data necessary for preoperative evaluation and staging were collected and compared with final postoperative histology and the type of surgery performed. All MRI had been performed without intracavernosal injection of prostaglandin E1 and with IV Gadolinium, as per local protocol. RESULTS: 54 patients were included in the study (mean age 57.52 ± 12.78). The number of patients with T1, T2, and T3 staging in histopathology were 32, 14, and 8. Moderate interobserver agreement was found for staging, disease-free penile length, and all subsites except urethra, which had weak agreement. Strong agreement of consensus MRI with final histopathological staging was found (49/54, weighted κ = 0.85), with high sensitivity and specificity. Sensitivity and specificity for involvement of corpus spongiosum, corpora cavernosa, and urethra were 95.5% and 93.8%, 87.5% and 97.8%, and 90.9% and 86.1%, respectively. Sensitivity (89.6%) and specificity (100%) of MRI for predicting adequate disease-free penile length were high. CONCLUSION: There were acceptable interobserver agreement and good diagnostic performance of MRI for staging and preoperative assessment without intracavernosal injection, especially for higher stages and higher degrees of invasion which require more extensive surgery.

Multidisciplinary corroboration in differentiation syndrome: a case report.

BACKGROUND: Differentiation syndrome (DS) is a life-threatening complication that may be seen in patients with acute promyelocytic leukaemia undergoing induction therapy with all-trans retinoic acid or arsenic trioxide. It can lead to severe inflammatory response syndrome and shock if adequate measures are not taken immediately. The radiological features of lung nodules with changes in ground-glass opacity can represent DS. The principal unique feature of the case reported here is that the diagnosis of DS was based on imaging results in the absence of a low total leukocyte count. CASE PRESENTATION: A 14-year-old Indian girl diagnosed with acute promyelocytic leukaemia currently undergoing a chemotherapy regimen that included all-trans retinoic acid/arsenic trioxide was sent to the radiology department for investigation of respiratory distress which she had developed soon after the initiation of chemotherapy. Her chest radiograph showed bilateral lower zone lung infiltrates. Computed tomography (CT) revealed changes in ground-glass opacity in the lower lobes with multiple lung nodules. Differential diagnosis included bacterial, viral or fungal infections, leukemic infiltrates, drug toxicity, pulmonary haemorrhage or leukostasis. She was started on dexamethasone immediately after stopping the chemotherapy with all-trans retinoic acid/arsenic trioxide and given ventilatory support. Her condition subsequently improved and her follow-up chest radiograph and CT scan showed a significant reduction of abnormal lung findings. Based on the clinical improvement and the resolution of findings on imaging following the withdrawal of all-trans retinoic acid/arsenic trioxide, we made the diagnosis of DS. CONCLUSIONS: Though a rather unusual possibility, the treatment history of the patient enabled a rather crucial diagnosis in the nick of time and imaging played a pivotal role. This case further iterates the importance of keeping DS in mind when dealing with similar patients in the future.

Circulation of oxytetracycline- and ciprofloxacin-resistant commensal Escherichia coli strains in broiler chickens and farm environments, Bangladesh.

BACKGROUND AND AIM: The emergence of antimicrobial resistance (AMR) in commensal organism, such as Escherichia coli of food animals, is an alarming issue for global health. It increases the possibility of transmitting AMR determinant(s) to human bacterial pathogens by transferable genetic materials, particularly by plasmids. Hence, it is important to know which resistant genes are being carried by commensal organisms in food chain in a country and their level of temporal loads. As a result, pre-emptive measures can be advocated with an aim to reduce their risks in their primary source of circulation which consequently would benefit the public health. MATERIALS AND METHODS: Commensal E. coli strains from broiler chickens on randomly selected 30 farms and the farm environments were examined for the frequencies of isolation of resistant strains to oxytetracycline and ciprofloxacin. Five birds were randomly selected from each farm to collect cloacal swab samples (total of 150 samples). Furthermore, a total of 150 environmental samples comprising one each from feed, water, soil, litter, and litter damping site of each farm were screened for the isolation of commensal E. coli strains. Strains thus obtained were initially tested for their resistance to oxytetracycline and ciprofloxacin by Kirby-Bauer disk diffusion method. Oxytetracycline-resistant strains were further screened for the presence of resistance determining genes, namely, tetA, tetB, and tetC by uniplex polymerase chain reactions. Risks associated with the isolation frequency of oxytetracycline- and ciprofloxacin-resistant E. coli were also assessed by univariable logistic regression analysis. RESULTS: The results revealed that all E. coli isolates, regardless of the source of origin, were resistant to oxytetracycline, while 78.4% (95% confidence interval [CI] 69.1-85.5%) showed resistance to ciprofloxacin. All the randomly selected (20) oxytetracycline-resistant strains harbored the tetA gene, whereas tetB and tetC were reported in three and two isolates, respectively. After univariable analysis, only one variable, that is, strain 1 of broiler chickens compared to two other strains was found to be positively associated with the isolation of ciprofloxacin-resistant E. coli (odds ratio 12.75 [95% CI 1.0-157.1], p=0.047). CONCLUSION: Resistance emerged against oxytetracycline and ciprofloxacin in commensal E. coli strains circulating in live poultry and farm environments in Bangladesh seems to be very high. Thus, human infection with drug-resistant E. coli strains through food chain will critically compromise the therapeutic measures currently available.

Centrally inserted tunnelled peripherally inserted central catheter: Off-label use for venous access in oncology patients.

PURPOSE: Vascular access in oncology patients can often be challenging, especially after a few cycles of chemotherapy through peripheral lines which can cause veins to become attenuated. We evaluated the feasibility of centrally placed non-cuffed tunnelled peripherally inserted central catheter in the chest as an alternative to conventional peripherally inserted central catheter. METHOD: Patients referred for peripherally inserted central catheter found to have inadequate peripheral venous access in their arms due to prior chemotherapy, and therefore they were offered placement of the non-cuffed tunnelled peripherally inserted central catheter in the chest. Adult patients were subjected to the procedure under local anaesthesia, while paediatric patients underwent this procedure under general anaesthesia. Ultrasound guidance was used for venous access, and fluoroscopy was used for tip positioning. Using internal jugular vein access, BARD Groshong-valved 4F peripherally inserted central catheter was placed with its tip in the cavo-atrial junction. Proximal end of the catheter was brought out through the subcutaneous tunnel, so that the exit point of the peripherally inserted central catheter lies over the upper chest. Extra length of the catheter was trimmed, and extensions were attached. The device was stabilized with adhesive and sutures. RESULTS: Out of 19 patients, 18 patients were male (4-72 years). Technical success was achieved in 100% cases. No catheter-related bloodstream infection was noted within 30 days of peripherally inserted central catheter. Overall, during 1966 catheter days, no catheter-related bloodstream infection was observed. The purpose of peripherally inserted central catheter was achieved in 15 patients (78.9%) either in the form of completion of chemotherapy (8/15) or maintained peripherally inserted central catheter line till death (7/15). Partial or complete pullout was observed in four patients (20.1%), which required cuffed tunnelled catheter or implantable port. External fracture was noted in one patient, which was successfully corrected using repair kit. No exit site infection, bleeding, catheter occlusion, catheter dysfunction, venous thrombosis, venous stenosis or catheter embolizations were noted in our series. CONCLUSION: Centrally placed tunnelled peripherally inserted central catheter is a promising alternative method, when conventional arm peripherally inserted central catheter placement is not feasible. It is an easy and safe procedure that can be performed under local anaesthesia.

Imaging Approach to Sinonasal Neoplasms.

The neoplastic lesions that can be found in the sinonasal space are numerous and varied. This article describes a general approach to narrowing down the differential diagnosis and provides the treating physician sufficient information to choose and deliver the best treatment modality. Computed tomography and MR imaging together provide complete radiologic assessment of sinonasal neoplasms.

Sinonasal Tumors: Computed Tomography and MR Imaging Features.

This article describes the computed tomography and MR imaging features of the neoplasms of the sinonasal space. Although a pathologic diagnosis may not always be possible, knowledge of the features may help in narrowing down the differentials and establishing a malignant pathology.

Complete duplication of the urinary bladder: An extremely rare congenital anomaly.

A case of complete bladder duplication with urethra duplication, diphallus, anorectal malformation and rightsided renal agensis with ipsilateral gonadal agenesisis was reported because of its rarity. Possible deranged embryology resulting in these anomalies has been reviewed with relevant hypothesis. The patient underwent several investigations and undergoing multistage surgical intervention.

Lewis acid mediated intramolecular C-C bond formation of alkyne-epoxide leading to six-membered nitrogen and oxygen heterocycles.

Intramolecular C-C bond formation of oxygen- and nitrogen-tethered alkynes and epoxide mediated by Lewis acid under ambient conditions is described. A simple procedure for the synthesis of 3,6- and 5,6-dihydropyrans and 3,4-dehydropiperidines from acyclic building blocks in good yields without using any transition metal is shown.

Diastereoselective synthesis of substituted dihydropyrans via an oxonium-ene cyclization reaction.

Substituted dihydropyrans can be efficiently synthesized in good yields with excellent diastereoselectivity from the reaction of aldehydes or epoxides and ethyl 3-alkyl-3-hydroxy-5-methylhex-5-enoate via an oxonium-ene cyclization reaction catalyzed by trimethylsilyl trifluoromethanesulfonate (TMSOTf) under mild conditions.