In-silico method for elucidation of prodigiosin as PARP-1 inhibitor a prime target of Triple-negative breast cancer.

Triple-Negative Breast Cancer (TNBC) is found to be one of the life-threatening cancer. Poly (ADP-Ribose) Polymerase-1 (PARP-1) is overexpressed by those tumour cells, which become resistant to chemotherapies. Inhibition of PARP-1 has a considerable effect on treating TNBC. Prodigiosin is a valuable pharmaceutical compound that exhibits anticancer properties. The present study aims to virtually evaluate prodigiosin as a potent PARP-1 inhibitor using Molecular docking and Molecular Dynamics (MD) simulation studies. The PASS (Prediction of Activity Spectra for Substances) prediction tool evaluated the biological properties of prodigiosin. Then the drug-likeness and pharmacokinetic properties of prodigiosin were determined using Swiss-ADME software. It was suggested that prodigiosin obeyed Lipinski's rule of five and thus could act as a drug with good pharmacokinetic properties. Moreover, molecular docking was done with AutoDock 4.2 to identify the critical amino acids of the protein-ligand complex. It was indicated that prodigiosin has a docking score of -8.08 kcal/mol, which showed its effective interaction with crucial amino acid, His201A of PARP-1 protein. Further, MD simulation was performed using Gromacs software to validate the stability of the prodigiosin-PARP-1 complex. Prodigiosin was found to have good structural stability and affinity at the active site of PARP-1 protein. Additionally, PCA and MM-PBSA were calculated for the prodigiosin-PARP-1 complex, which revealed that prodigiosin has an excellent binding affinity towards PARP-1 protein. Prodigiosin can possibly be used as oral drug due to its PARP-1 inhibition through high binding affinity, structural stability, and receptor flexibility towards crucial amino acid residue His201A of PARP-1 protein. In-addition, in-vitro cytotoxicity, and apoptosis analysis of prodigiosin-treated TNBC cell line-MDA-MB-231 revealed that prodigiosin exhibited significant anticancer activity in 101.1 µg/mL concentration, when compared to commercially available synthetic drug cisplatin. Thus, prodigiosin could act as a potential candidate for treatment of TNBC than the commercially available synthetic drugs.

Radiographic, clinical, and magnetic resonance imaging analysis of insertional Achilles tendinopathy.

The surgical correction of insertional Achilles tendinopathy (IAT) repair typically involves tendon debridement, osteophyte removal, lengthening of the gastroc-soleus complex, and resection of the posterior superior calcaneal eminence. Limited evidence has supported decompression of the superior calcaneal prominence, because this step has had a pronounced association with the surgical treatment of Haglund's syndrome. To appreciate the posterior calcaneal abnormality, 20 lateral weightbearing radiographs of asymptomatic patients were compared with 20 lateral weightbearing radiographs of patients with symptomatic IAT. The radiographs were evaluated for the calcaneal inclination angle, Fowler-Philip angle, total angle, parallel pitch lines, Chauveaux-Liet angle, and the presence or absence of retrocalcaneal enthesiophytes. Patients with IAT were also examined clinically and using magnetic resonance imaging to determine the incidence of Haglund's syndrome within the symptomatic population. A comparison of the radiographs revealed minimal differences in calcaneal morphology between the 2 populations. Of the analyzed variables, only an elevated Chauveaux-Liet angle and the presence of a retrocalcaneal enthesiophytes were characteristic of patients with IAT. The results of the present study have confirmed the absence of morphologic calcaneal variation and the presence of altered calcaneal angulations in symptomatic patients. Both the clinical examination and magnetic resonance imaging revealed a 25% frequency of Haglund's syndrome within the IAT population. Because these 2 diagnosis are clinically and radiographically divergent, their surgical interventions warrant distinct goals using separate methods. By understanding the abnormality, the surgeon can taper the correction precisely and specifically toward patients with IAT.

Combined arthroscopic and fluoroscopic guidance in the atraumatic treatment of posterior ankle impingement syndrome.

Posterior ankle impingement syndrome can result from chronic overuse or acute trauma. When coupled with the presence of an anatomic bony anomaly, the patient can present with significant pain with maximal plantarflexion. Treatment involves resection of the site of bony impingement (e.g., os trigonum or fractured Steida's process) and circumferential fibrosis and inflammation. The presented technique involves a stepwise approach incorporating focused arthroscopic release of the surrounding fibrosis and atraumatic fluoroscopic resection of the bony source of impingement. Thus, a minimal amount of trauma is incurred to the patient, and fragment resection is performed in an efficient manner.

Transosseous fixation in insertional Achilles tendonitis.

The surgical approach of severe insertional Achilles tendonitis involves debridement, repair, and reattachment. Previously described techniques for bone-tendon reattachment involved the use of suture anchors in the sparsely trabeculated calcaneus. The following technique tip is a reintroduction of bicortical transosseous fixation previously used in rotator cuff repairs. Bone tunnels are a viable option in the treatment of insertional Achilles tendonitis; however, additional research is necessary to validate its efficacy in this application.

Central nervous system tubercular abscess masquerading as intracranial space-occupying lesion.

This is a case report of patient suffering from multiple central nervous system tuberculoma which progressed to tubercular abscess. Patient developed signs and symptoms of mass effect and compression. Computed tomography of brain and magnetic resonance spectroscopy confirmed the diagnosis. Patient underwent left temporal craniotomy with evacuation of pus. The abscess wall and the pus sent for histopathological and microbiological examination which confirmed the etiological agent - Mycobacterium tuberculosis. Appropriate treatment was started and discharged. Hence, early diagnosis and treatment of intracranial tuberculoma are pivotal in preventing morbidity and mortality of the condition.

Broad-Spectrum Antimicrobial, Antioxidant, and Anticancer Studies of Leaf Extract of Simarouba glauca DC In Vitro.

The current study aimed to screen the preliminary phytochemicals in the leaf extract of the medicinal plant Simarouba glauca and to analyze its potential antimicrobial, antioxidant and anticancer properties. The phytochemical profile of the methanol extract was analyzed, and bioactive compounds were identified using chromatography, FTIR and GCMS. Antimicrobial activity and Minimum Inhibitory Concentration (MIC) were determined against 14 bacterial and 6 fungal strains. Moreover, the synergistic effect of a plant extract with commercially available antibiotics was also evaluated using the checkerboard method. The ethanolic and methanolic extracts showed exclusive activity against S. aureus and profound activity against E. coli and S. marcescens. Upon comparing breakpoints, methanolic extract demonstrated higher antimicrobial activity with a MIC value of 3.2 mg/mL against the test pathogens. Furthermore, the extracts demonstrated potential antioxidant activity; methanol extract had higher antioxidant potential compared to the ethanol extract. The major proactive bioactive compound with maximum antioxidant capacity was observed to be terpenoids. The methanol extract of S. glauca showed significant cytotoxicity against the MCF-7 breast cancer cell line with an IC50 value of 16.12 µg/mL. The overall results of our work provide significant evidence for the usage of methanolic extract of S. glauca as an efficient ethnomedicinal agent and a potential candidate for relieving many human ailments.