Proteomic characterization and cytotoxic potential of proteins from Cuscuta (Cuscuta epithymum (L.) crude herbal product against MCF-7 human breast cancer cell line.

BACKGROUND: The burden of breast cancer, the second leading cause of death worldwide, is increasing at an alarming rate. Cuscuta, used in traditional medicine for different ailments, including cancer, is known for containing phytochemicals that exhibit anticancer activity; however, the bioactivities of proteins from this plant remain unexplored. This study aimed to screen the cytotoxic potential of proteins from the crude herbal product of Cuscuta epithymum(L.) (CE) harvested from the host plants Alhagi maurorum and Medicago sativa. METHODS: The proteins from CE were extracted using a salting-out method, followed by fractionation with a gel filtration chromatography column. Gel-free shotgun proteomics was subsequently performed for protein characterization. The viability assay using MTT was applied to deduce the cytotoxic potential of proteins against MCF-7 breast cancer cells, with further exploration of the effect of treatment on the expression of the apoptotic mediator BCL2-associated X protein (BAX) and B-cell lymphoma protein 2 (BCL-2) proteins, using western blotting to strengthen the findings from the in vitro viability assay. RESULTS: The crude proteins (CP) of CE were separated into four protein peaks (P1, P2, P3, and P4) by gel filtration chromatography. The evaluation of potency showed a dose-dependent decline in the MCF-7 cell line after CP, P1, P2, and P3 treatment with the respective IC50 values of 33.8, 43.1, 34.5, and 28.6 µg/ml. The percent viability of the cells decreased significantly upon treatment with 50 µg/ml CP, P1, P2, and P3 (P < 0.001). Western-blot analysis revealed upregulation of proapoptotic protein BAX in the cells treated with CP, P3 (P < 0.01), and P2 (P < 0.05); however, the antiapoptotic protein, BCL-2 was downregulated in the cells treated with CP and P3 (P < 0.01), but no significant change was detected in P2 treated cells. The observed cytotoxic effects of proteins in the CP, P1, P2, and P3 from the in vitro viability assay and western blot depicted the bioactivity potential of CE proteins. The database search revealed the identities of functionally important proteins, including nonspecific lipid transfer protein, superoxide dismutase, carboxypeptidase, RNase H domain containing protein, and polyribonucleotide nucleotidyltransferase, which have been previously reported from other plants to exhibit anticancer activity. CONCLUSION: This study indicated the cytotoxic activity of Cuscuta proteins against breast cancer MCF-7 cells and will be utilized for future investigations on the mechanistic effect of active proteins. The survey of CE proteins provided substantial data to encourage further exploration of biological activities exhibited by proteins in Cuscuta.

Predicting FFAR4 agonists using structure-based machine learning approach based on molecular fingerprints.

Free Fatty Acid Receptor 4 (FFAR4), a G-protein-coupled receptor, is responsible for triggering intracellular signaling pathways that regulate various physiological processes. FFAR4 agonists are associated with enhancing insulin release and mitigating the atherogenic, obesogenic, pro-carcinogenic, and pro-diabetogenic effects, normally associated with the free fatty acids bound to FFAR4. In this research, molecular structure-based machine-learning techniques were employed to evaluate compounds as potential agonists for FFAR4. Molecular structures were encoded into bit arrays, serving as molecular fingerprints, which were subsequently analyzed using the Bayesian network algorithm to identify patterns for screening the data. The shortlisted hits obtained via machine learning protocols were further validated by Molecular Docking and via ADME and Toxicity predictions. The shortlisted compounds were then subjected to MD Simulations of the membrane-bound FFAR4-ligand complexes for 100 ns each. Molecular analyses, encompassing binding interactions, RMSD, RMSF, RoG, PCA, and FEL, were conducted to scrutinize the protein-ligand complexes at the inter-atomic level. The analyses revealed significant interactions of the shortlisted compounds with the crucial residues of FFAR4 previously documented. FFAR4 as part of the complexes demonstrated consistent RMSDs, ranging from 3.57 to 3.64, with minimal residue fluctuations 5.27 to 6.03 nm, suggesting stable complexes. The gyration values fluctuated between 22.8 to 23.5 nm, indicating structural compactness and orderliness across the studied systems. Additionally, distinct conformational motions were observed in each complex, with energy contours shifting to broader energy basins throughout the simulation, suggesting thermodynamically stable protein-ligand complexes. The two compounds CHEMBL2012662 and CHEMBL64616 are presented as potential FFAR4 agonists, based on these insights and in-depth analyses. Collectively, these findings advance our comprehension of FFAR4's functions and mechanisms, highlighting these compounds as potential FFAR4 agonists worthy of further exploration as innovative treatments for metabolic and immune-related conditions.

A Comparative Study of the Treatment of Oral Premalignant Lesions with Surgical Excision and Medical Therapy.

Introduction: Potentially malignant oral epithelial lesions are a group of oral conditions with an altered morphological state of the normal mucosal lining and include different lesions such as leukoplakia, erythroplakia, submucosal fibrosis, and lichen planus. Aim: To compare the outcome of premalignant oral lesions after medical therapy consisting of submucosal intralesional injection of triamcinolone with hyaluronidase and surgical excision. Materials and Methods: This was a comparative prospective interventional study and the study was conducted among 50 patients presented to the Department of Otorhinolaryngology with premalignant oral lesions from the year 2020 to 2022. Patients were divided into two groups by random allocation, group A was treated with medical therapy, and Group B was treated with surgical excision and followed for a minimum of 6 months and the outcome has been categorized. Results: All patients were divided into two groups-group A and group B, group A consisted of 22 (44%) patients who were given medical therapy, and group B consisted of 28 (56%) patients who underwent surgical excision. In group A, the clinical response was seen in 8 (36.36%) and in group B, the clinical response was seen in 18 (64.29%) patients. Conclusion: Surgical excision was found to be better with more cases of clinical response (64.29%) when compared to medical treatment (36.36%) with a p value of 0.0497 which is significant whereas malignant transformation was almost equal in medical therapy and surgical treatment which was 13.64% and 14.28%, respectively.

Preoperative anxiety management in pediatric patients: a systemic review and meta-analysis of randomized controlled trials on the efficacy of distraction techniques.

Background: This study addresses the pervasive issue of heightened preoperative anxiety in healthcare, particularly among pediatric patients. Recognizing the various sources of anxiety, we explored both pharmacological and nonpharmacological interventions. Focusing on distraction techniques, including active and passive forms, our meta-analysis aimed to provide comprehensive insights into their impact on preoperative anxiety in pediatric patients. Methods: Following the PRISMA and Cochrane guidelines, this meta-analysis and systematic review assessed the efficacy of pharmaceutical and distraction interventions in reducing pain and anxiety in pediatric surgery. This study was registered on PROSPERO (CRD42023449979). Results: This meta-analysis, comprising 45 studies, investigated pharmaceutical interventions and distraction tactics in pediatric surgery. Risk of bias assessment revealed undisclosed risks in performance and detection bias. Distraction interventions significantly reduced preoperative anxiety compared to control groups, with notable heterogeneity. Comparison with Midazolam favored distraction techniques. Subgroup analysis highlighted varied efficacies among distraction methods, with a notable reduction in anxiety levels. Sensitivity analysis indicated stable results. However, publication bias was observed, suggesting a potential reporting bias. Conclusion: Our study confirms distraction techniques as safe and effective for reducing pediatric preoperative anxiety, offering a valuable alternative to pharmacological interventions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=449979, PROSPERO [CRD42023449979].

A Prospective Clinical Study of Bacteriological Profile and their Antibiotic Susceptibilty Profile in Patients with Chronic Rhinosinusitis: The Recent Scenario in Northern India.

Objectives: 1. To determine the prevailing scenario of the bacteriological profile of patients with CRS, 2. To identify their antibiotic susceptibility profile. Material and methods: The study was conducted on 100 patients in the Department of ENT and Microbiology from December 2020-2022. Patients above the age of 12 years were evaluated. Those who received antibiotics in the last 12 months. and age < 12 years were excluded. Patients were subjected to a detailed history, clinical and radiological examination. After the informed consent of patients and ethical cleareance, samples were taken from the middle meatus area and studied for antibiotics sensitivity: levofloxacin, vancomycin, amikacin, amoxicillin-clavulanic acid and azithromycin. Results: The study was male predominance (71%), with the maximum of patients in the age group 21-30 years (38%). The most common clinical features were nasal obstruction ( 96%) and mucopurulent discharge (100%). The most common isolate was Staphylococcus aureus (45.16%). In Gram-positive, the maximum resistance was shown to azithromycin and amoxicillin-clavulanic acid and the maximum sensitivity to vancomycin, levofloxacin and amikacin. Conclusions: Antibiotic resistance seems to be emerging for azithromycin and amoxicillin-clavulanic acid at a higher rate. MRSA ( 19.35%) maintains a significant presence with associated increased levels of antibiotic resistance.

Comparative evaluation of ethylene oxide, electron beam and gamma irradiation treatments on commonly cultivated red chilli cultivars (Kunri and Hybrid) of Sindh, Pakistan.

Chillies are considered a universal ingredient for imparting flavor and pungency to foods. Pakistan stood in the top twenty countries worldwide by producing 82 thousand Tons of chillies during 2022-23. Chilli fungal contamination and aflatoxin production during drying is a common problem during post-harvest process. Gasses treatment and Ionizing radiations are efficient methods for reducing toxigenic and pathogenic microbial growth in food items. The current study was designed to compare the effects of ethylene oxide (ETO), gamma (GB) & electron beam (EB) treatments on two red chilli local cultivars (Kunri and Hybrid) of Pakistan. After treatment, the chilli samples were analyzed for aflatoxins, physicochemical, quality & safety attributes. All results were subjected to Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA), dendrogram and ANOVA to check the correlations, grouping and level of significance within the varieties and treatments. The results showed that moisture and water activity mainly designated PC-2 directions and are slightly positively correlated. Conversely, both fat and proteins have a negative correlation with moisture, ash and water activity. Besides, carotenoids and ABTS assay mainly designated PC-2 directions and are slightly positively correlated. Color, flavonoids and TPC also possess positive correlations among them. ETO depicts effectiveness in the reduction of E. coli but is not effective in saving antioxidant potential such as total flavonoids. Similarly, gamma irradiations showed strong reduction trends in fungal and pathogenic count, however same trend was observed in ascorbic acid too. Besides, the electron beam with dosage levels of 12 and 15 kGy has shown effectiveness against Aspergillus spp., aflatoxins and pathogenic microbial load in addition to saving antioxidant potential (phenolics and flavonoids), physicochemical parameters and color values compared to other applied methods especially in Kunri variety. It was evident from the research that varietal combination in addition to applied treatment must be specially considered while designing a treatment for chillies.

Computational Exploration of Fluorocyclopentenyl-purines and-pyrimidines Derivatives as Potential Inhibitors of Epidermal Growth Factor Receptor (EGFR) for the Treatment of Breast Cancer.

The Epidermal Growth Factor Receptor (EGFR) is an important therapeutic target for the treatment of a variety of epithelial malignancies, including breast cancer, in which EGFR is aberrantly expressed.The fluorocyclopentenyl-purine-pyrimidines derivatives, which have previously been described as powerful compounds against breast cancer, were selected to investigate their potential against EGFR using computational tools in an effort to obtain potent inhibitors with fewer adverse effects. The molecule's chemical reactivity and stability were assessed by determining the HOMO-LUMO energy gap using density functional theory (DFT) calculations. Among all the selected compounds, PU4 displayed a HOMO-LUMO gap of 0.191 eV. Additionally, molecular docking analysis was performed to assess the binding affinities of PU4 within the active pocket of EGFR-TK. The compound PU4 showed potent interactions with EGFR exhibiting -32.3 kJ/mol binding energy which was found best as compared to gefitinib i. e., -27.4 kJ/mol which was further validated by molecular dynamics simulations and ADMET analysis. The results of these analyses indicate that the top hits obtained from the virtual screening possess the ability to act as effective EGFR inhibitor. Therefore, it is recommended to further investigate the inhibitory potential of these identified compounds using in vitro and in vivo approaches.

Repurposing of Strychnine as the Potential Inhibitors of Aldo-keto Reductase Family 1 Members B1 and B10: Computational Modeling and Pharmacokinetic Analysis.

AKR1B1 and AKR1B10 are important members of aldo-keto reductase family which plays a significant role in cancer progression by modulating cellular metabolism. These enzymes are involved in various metabolic processes, including the synthesis and metabolism of hormones, detoxification of reactive aldehydes, and the reduction of various endogenous and exogenous compounds. This study aimed to explore the potential of strychnine as an anticancer agent by targeting AKR1B1 and AKR1B10 via drug repurposing approach. To assess the drug-like properties of strychnine, a physiologically based pharmacokinetic (PKPB) model and High Throughput Pharmacokinetics (HTPK) approach were employed. The obtained results fell within the expected range for drug molecules, confirming its suitability for further investigation. Additionally, density functional theory (DFT) studies were conducted to gain insight into the electronic properties contributing to the drug molecule's reactivity. Building upon the promising DFT results, molecular docking analysis using the AutoDock tool was performed to examine the binding interactions between strychnine and the proposed targets, AKR1B1 and AKR1B10. Findings from the molecular docking studies suggested a higher probability of strychnine acting as an inhibitor of AKR1B1 and AKR1B10 with docking scores of - 30.84 and - 29.36 kJ/mol respectively. To validate the stability of the protein-ligand complex, Molecular Dynamic Simulation (MDS) studies were conducted, revealing the formation of a stable complex between the enzymes and strychnine. This comprehensive approach sheds light on the potential effectiveness of strychnine as a treatment for breast, lung, liver, and pancreatic cancers, as well as related malignancies. The novel insights gained from the physiologically based pharmacokinetic modeling, density functional theory, molecular docking, and molecular dynamics simulations collectively support the prospect of strychnine as a promising molecule for anticancer therapy. Further investigations are warranted to validate these findings and explore the therapeutic potential of strychnine in preclinical and clinical settings.

A rare concurrent incidence of adult-onset acute disseminated encephalomyelitis and antiphospholipid antibody syndrome: A case report.

INTRODUCTION: Acute disseminated encephalomyelitis (ADEM) is a demyelinating immune-mediated condition of the central nervous system, whereas antiphospholipid antibody syndrome (APLA) is an autoimmune disorder accompanied by thrombosis and pregnancy-related problems. We present a unique case of a 30-year-old female with ADEM coexisting with APLA, highlighting the importance of early identification and specialized care. PRESENTATION OF CASE: We present a case of a 30-year-old woman with a history of hypertension, multiple miscarriages, and non-compliance with medication, who presented with altered consciousness and weakness in all four limbs. Laboratory tests revealed positive anti-cardiolipin and lupus anticoagulant antibodies, confirming APLA. A neurological examination revealed increased limb tone, heightened reflexes, and extensor plantar responses. MRI revealed confluent white matter lesions that were consistent with ADEM. The patient received prompt treatment with intravenous methylprednisolone and then received oral prednisone, leading to a rapid improvement in neurological status. DISCUSSION: The intricate interaction between ADEM and APLA remains enigmatic. The plausible connection between "molecular mimicry" and weakened blood-brain barrier, substantiated by antiphospholipid antibodies, may help explain their concurrent occurrence. CONCLUSION: This case highlights the significance of early diagnosis and management of the rare and complex coexistence of ADEM and APLA to attain optimal outcomes, as well as the significance of careful examination for simultaneous autoimmune markers in individuals presenting with neurological disturbances.

Cancer Stem Cells and Treatment of Cancer: An Update and Future Perspectives.

Cancer stem cells (CSCs) play an essential role in tumour progression and metastasis. These cells have the unique ability to self-renew and differentiate into specific tissue cell types. Their capacity for self-renewal enables CSCs to persist over time, thereby contributing to cancer relapse and therapy resistance. Therefore, targeting CSCs has emerged as a promising cancer treatment strategy. CSCs exhibit differentiation, self-renewal, and plasticity, and they contribute to multiple aspects of malignant tumours, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. While conventional treatments predominantly target cancer cells that are not CSCs, CSCs frequently survive, resulting in tumour recurrence and relapse. This article concentrates on the development of novel therapeutic strategies that combine conventional treatments with CSC inhibitors to eradicate cancer cells and CSCs, thereby treating cancer and preventing its recurrence. However, the diversity of CSCs poses a significant obstacle to the development of CSC-targeted therapies, necessitating extensive research for a better understanding and exploration of therapeutic approaches. Future development of CSC-targeted therapies will rely heavily on overcoming this obstacle.

A comprehensive review on the impact of calcium and vitamin D insufficiency and allied metabolic disorders in females.

Calcium is imperative in maintaining a quality life, particularly during later ages. Its deficiency results in a wide range of metabolic disorders such as dental changes, cataracts, alterations in brain function, and osteoporosis. These deficiencies are more pronounced in females due to increased calcium turnover throughout their life cycle, especially during pregnancy and lactation. Vitamin D perform a central role in the metabolism of calcium. Recent scientific interventions have linked calcium with an array of metabolic disorders in females including hypertension, obesity, premenstrual dysphoric disorder, polycystic ovary syndrome (PCOS), multiple sclerosis, and breast cancer. This review encompasses these female metabolic disorders with special reference to calcium and vitamin D deficiency. This review article aims to present and elaborate on available data regarding the worldwide occurrence of insufficient calcium consumption in females and allied health risks, to provide a basis for formulating strategies and population-level scientific studies to adequately boost calcium intake and position where required.

The structural characterization and bioactivity assessment of nonspecific lipid transfer protein 1 (nsLTP1) from caraway (Carum carvi) seeds.

BACKGROUND: Carum carvi (caraway) of the Apiaceae family has been used in many cultures as a cooking spice and part of the folk medicine. Previous reports primarily focus on the medicinal properties of caraway seed essential oil and the whole seeds extract. However, no effort has been made to study caraway proteins and their potential pharmacological properties, including nonspecific lipid transfer protein (nsLTP), necessitating further research. The current study aimed to characterize nonspecific lipid transfer protein 1 (nsLTP1) from caraway seed, determine its three-dimensional structure, and analyze protein-ligand complex interactions through docking studies. We also evaluated nsLTP1 in vitro cytotoxic effect and antioxidant capacity. Additionally, nsLTP1 thermal- and pH- stability were investigated. METHODS: Caraway nsLTP1 was purified using two-dimensional chromatography. The complete amino acid sequence of nsLTP1 was achieved by intact protein sequence for the first 20 residues and the overlapping digested peptides. The three-dimensional structure was predicted using MODELLER. Autodock Vina software was employed for docking fatty acids against caraway nsLTP1. Assessment of nsLTP1 cytotoxic activity was achieved by MTS assay, and the Trolox equivalent antioxidant capacity (TAC) was determined. Thermal and pH stability of the nsLTP1 was examined by circular dichroism (CD) spectroscopy. RESULTS: Caraway nsLTP1 is composed of 91 residues and weighs 9652 Da. The three-dimensional structure of caraway nsLTP1 sequence was constructed based on searching known structures in the PDB. We chose nsLTP of Solanum melongena (PDB ID: 5TVI) as the modeling template with the highest identity among all other homologous proteins. Docking linolenic acid with caraway protein showed a maximum binding score of -3.6 kcal/mol. A preliminary screening of caraway nsLTP1 suppressed the proliferation of human breast cancer cell lines MDA-MB-231 and MCF-7 in a dose­dependent manner with an IC50 value of 52.93 and 44.76 µM, respectively. Also, nsLTP1 (41.4 µM) showed TAC up to 750.4 µM Trolox equivalent. Assessment of nsLTP1 demonstrated high thermal/pH stability. CONCLUSION: To the best of our knowledge, this is the first study carried out on nsLTP1 from caraway seeds. We hereby report the sequence of nsLTP1 from caraway seeds and its possible interaction with respective fatty acids using in silico approach. Our data indicated that the protein had anticancer and antioxidant activities and was thermally stable.

Differential Protein Expression in Response to Varlitinib Treatment in Oral Cancer Cell Line: an In Vitro Therapeutic Approach.

Epidermal growth factor receptor (EGFR) is the most frequently overexpressed receptor histologically exhibited by oral squamous cell carcinoma (OSCC) patients. Aberrated EGFR signaling may lead to recurrence and metastasis, thus laying the foundation of targeted therapy. Deactivating EGFR is likely to prevent downstream signaling thus resulting in apoptosis. Tyrosine kinase inhibitors (TKIs) have come into play to revert aggressiveness of OSCC. We exploited comparative proteomic analyses based on anti-EGFR potential of varlitinib, using cellular proteomes from treated and untreated groups of oral cancer cells to identify protein players functional during oral carcinogenesis. Following separation by two-dimensional electrophoresis, differentially expressed cellular proteins (varlitinib-treated and untreated cells) were analyzed and later identified using QTOF mass spectrometer. In silico analysis for protein-protein interaction was carried out using STRING. Six differentially expressed proteins were identified as binding immunoglobulin protein (BiP), heat shock protein 7 C (HSP7C), protein disulfide isomerase 1 A (PDIA1), vimentin (VIME), keratin type I cytoskeletal 14 (K1C14), and ß-Actin (ACTB). Relative expression of five proteins was found to be downregulated upon varlitinib treatment, whereas only K1C14 was upregulated in treated cells compared to control. Protein network analysis depicts the interaction between BiP, PDIA1, VIME, etc. indicating their role in oral carcinogenesis. Oral cancer cells show proteome shift based on varlitinib treatment compared to corresponding controls. Our data suggest candidature of varlitinib as a potent therapeutic agent and BiP, PDIA1, HSP7C, VIME, and ß-Actin as complementary/prognostic markers of OSCC.

Mucoepidermoid Carcinoma of the Parotid Gland Mimicking Pleomorphic Adenoma on Cytology: A Case Report.

Salivary gland tumors most commonly involve the parotid gland. Among all the tumors, 80% are benign and of all the benign tumors 80% originate from the parotid gland. The pleomorphic adenoma is the most common benign tumor whereas the mucoepidermoid carcinoma is the most prevalent malignant tumor. Mucoepidermoid carcinoma is a diagnostic challenge on FNAC with a high false negative rate. A 17-year-old female presented with slow-growing painless swelling below the right ear for two years. The history and clinical examination appeared to be benign parotid swelling. The further investigation proceeded and fine needle aspiration cytology was performed. A case of the parotid lump which has shown the pleomorphic adenoma of the parotid gland on cytology. Surgical resection was done and a post-operative specimen of the parotid gland showed mucoepidermoid carcinoma on histopathology. FNAC is not always reliable in the case of mucoepidermoid carcinoma of the parotid gland, especially in the low-grade type. The confirmatory diagnosis can be made only after the histopathological examination.

A Large Facial Nerve Schwannoma Presenting as a Swelling in Parotid Region-A Rare Case Report.

Extratemporal facial nerve schwannomas are rare entity. Pre-operative assessment is mostly inconclusive with differential diagnosis of parotid tumors. We hereby report a case of 28 years female who presented with painless swelling in right parotid region with normal facial nerve function. Ultrasonography was suggestive well circumscribed and homogenous mass arising from the deep lobe of parotid gland. The Fine-needle aspiration cytology came out to be inconclusive. For further characterization of the tumor contrast enhanced MR imaging was performed. The MR imaging revealed well-defined cystic, heterogeneous, pear-shaped mass lesion situated near the stylomastoid foramen. Post operatively the mass came out to be schwannoma on histopathological examination.

New Insight into the Pharmacological Importance of Atropine as the Potential Inhibitor of AKR1B1 via Detailed Computational Investigations: DFTs, ADMET, Molecular Docking, and Molecular Dynamics Studies.

The aim of this research is to investigate the quantum geometric properties and chemical reactivity of atropine, a pharmaceutically active tropane alkaloid. Using density functional theory (DFT) computations with the B3LYP/SVP functional theory basis set, the most stable geometry of atropine was determined. Additionally, a variety of energetic molecular parameters were calculated, such as the optimized energy, atomic charges, dipole moment, frontier molecular orbital energies, HOMO-LUMO energy gap, molecular electrostatic potential, chemical reactivity descriptors, and molecular polarizability. To determine atropine's inhibitory potential, molecular docking was used to analyze ligand interactions within the active pockets of aldo-keto reductase (AKR1B1 and AKR1B10). The results of these studies showed that atropine has greater inhibitory action against AKR1B1 than AKR1B10, which was further validated through molecular dynamic simulations by analyzing root mean square deviation (RMSD) and root mean square fluctuations (RMSF). The results of the molecular docking simulation were supplemented with simulation data, and the ADMET characteristics were also determined to predict the drug likeness of a potential compound. In conclusion, the research suggests that atropine has potential as an inhibitor of AKR1B1 and could be used as a parent compound for the synthesis of more potent leads for the treatment of colon cancer associated with the sudden expression of AKR1B1.

Rapid Cytological Diagnosis With Evaluation of Pre- and Post-Therapeutic Fungal Morphological Characteristics in Mucormycosis.

Background: Mucormycosis necessitates rapid diagnosis and treatment. Microscopy and culture have been considered the gold standard for diagnosis but both take time of 3 - 5 days. KOH mount is another method for fungal identification that takes 1 - 2 h, but it has its own limitations. This study evaluated crush smear as a means of rapid cytological diagnosis. Methods: Biopsy tissue (pre-treatment) from clinically suspicious mucormycosis patients (n = 52) was received in normal saline and crush/imprint smears were prepared; the remaining tissue was processed as routine biopsy specimen. After the rapid initial cytological identification, the patients were managed according to the standard clinical protocol. Random post-therapeutic biopsy samples of some of these patients (n = 19) were also obtained and again evaluated cytologically. Results: Crush smears showed sensitivity/specificity of 77.7%/75.0% with histopathology and 72.2%/62.5% with culture, respectively, while KOH mount had values of 71.4%/70.5% with histopathology and 79.3%/69.5% with culture, respectively. Degenerative fungal morphological characteristics and cellular inflammatory infiltrate (predominantly neutrophilic) in the vicinity of fungal hyphae were compared in pre- and post-treatment groups, and we found a statistically significant difference (P < 0.05) between them. Conclusion: Our preliminary results suggest that crush smear cytology is a simple, rapid, cost-effective and easily available method for diagnosing mucormycosis. Moreover, crush smears also demonstrated morphological alteration in hyphal structure and accompanying immune cell infiltration which may provide valuable insights into mechanism of therapy/host immune response against fungal pathogen.

Novel Synergistic Combination of Pamidronate and Temozolomide for Breast Cancer Therapeutics.

OBJECTIVE: Human breast cancer is among one major health concerns with high prevalence and mortality among women worldwide. Various cellular signaling pathways are implicated in carcinogenesis. One of the major pathways that affect the downstream cellular growth cascades is Mevalonate pathway (MVA). The inhibition of MVA is therapeutically beneficial for various cancers. Pamidronate (PAM) (MVA inhibitor), a nitrogen-containing bisphosphosphonate, is an antiresorptive FDAapproved drug. The objective of our study was to explore adjuvant therapy using a combination of PAM and an alkylating agent, Temozolomide (TMZ) against breast cancer. METHODS: We have examined the differential gene and protein expression in response to the combination treatment strategy. For gene expression analysis RT-qPCR and for proteomic study, twodimensional gel electrophoresis and mass spectrometry techniques were utilized. RESULTS: Combination treatment (PAM+TMZ) showed more pronounced cytotoxic effect as compared to single agent treatment. Our results indicate that MVA pathway regulatory genes (FDFT1, FDPS, KRAS) are significantly (p<0.05) downregulated in combination-treated breast cancer cells. The differential proteomic analysis showed lower expression of GFAP, PPA1 and TRIM68 proteins after synergistic treatment whereas, these proteins are found to be up-regulated in multiple cancers. CONCLUSION: The present study reveals that a combination of PAM and TMZ produces an effective anti-cancerous effect on breast cancer cells. Therefore, this novel therapeutic regimen is likely to provide a better treatment strategy for breast cancer.

A Rare Presentation of a Branchial Cleft Cyst: Can It Cause Syncope in a Pediatric Patient?

Branchial cleft cysts (BCCs) are a congenital malformation most commonly seen in children and adolescents. BCCs are usually incidental findings and are benign in nature. In this report, we present a case of a 13-year-old female with syncope as a rare complication of a fluid-filled second BCC. The patient initially presented with a unilateral non-tender swelling on the right side of the neck and submandibular region, which was suspicious of an inflammatory process. After initial lab investigations came back negative, imaging studies of the neck with computed tomography (CT) with intravenous contrast revealed a hypodense lesion with a uniform density, which lay beneath the sternocleidomastoid muscle and abutted the carotid sheath. The cyst was surgically excised, and histopathological studies of the cyst wall and the analysis of the fluid contained within the cyst confirmed that it was indeed a branchial cleft cyst. We propose that the syncopal episodes she experienced most likely occurred due to the proximity of the cyst wall to the carotid sheath, which caused a mass effect leading to carotid sinus syndrome (CSS). This is the first case of CSS due to a BCC to be reported in the pediatric population.

A rare case of gastric duplication cyst in a male paediatric Caucasian patient: a case report.

Anywhere in the alimentary canal, you can find a gastric duplication cyst, a spherical muscle formation lined by mucosal membrane. It is an uncommon example of a group of congenital intestinal abnormalities. Gastric cysts typically develop on the stomach's greater curvature. A Caucasian 4-year-old boy came in with his family after experiencing colicky central stomach pain for 2 days, along with vomiting for 4 days, decreased oral intake, a temperature of up to 38.5°C and regular bowel movements. A region of the transverse colon with degraded and inflammatory serosa covered in omentum with black necrotic sections was seen during the procedure.