The Spectrum of Central Nervous System Tumors at a Tertiary Care Center Primarily Serving a Rural Population.

Background Central nervous system (CNS) tumors cause significant mortality and morbidity in all age groups. There was no data about the histological spectrum of all CNS tumors in the tertiary care center serving primarily the rural population of Uttar Pradesh. Aims and objectives The present study aimed to describe the histopathological spectrum of all CNS tumors reported in a rural tertiary care center at Saifai, Uttar Pradesh. It also aimed to provide an overview of the descriptive epidemiology of CNS tumors. Material and methods This was a retrospective, cross-sectional study. The study duration was three years. A total of 115 cases of CNS tumors were studied during that period. Cases were classified according to their histological types, and results were analyzed. Results The most common histological group was neuroepithelial tumors, with 53 cases (46.08%). This group had 36 cases of astrocytic tumors (31.3%), three cases of oligodendroglial tumors (2.6%), five cases of oligoastrocytic tumors (4.34%), five cases of ependymal tumors (4.34%), and four cases of embryonal tumors (3.47%). The second most common tumor was meningeal tumors, with 32 cases (27.82%). The male/female ratio (M/F) ratio was 0.7. Females were found to be more affected by almost all histologic categories. Most meningiomas (89.6%) were of World Health Organization (WHO) grade I (26 cases out of 29). Astrocytic tumors showed WHO grade I, II, III, and IV tumors in two cases (5.5%), twelve cases (33.3%), four cases (11.1%), and eighteen cases (50%), respectively. In the younger age group (0-20 years), ependymoma and medulloblastoma were most common, followed by pilocytic astrocytoma and schwannoma. Conclusion In this region, neuroepithelial tumors were seen more commonly than meningioma. Females were found to be more affected by CNS tumors. This study has provided relevant data, which can be used for research and better patient management. Further studies with the incorporation of advanced radiological investigation and immunohistochemistry have been recommended.

Markers of Oxidative Stress and Tyrosinase Activity in Melasma Patients: A Biochemical Investigation.

BACKGROUND: Melasma is a skin hyperpigmentary disorder that develops over time. Genetic factors, oxidative stress, female sex hormones, and UV light may all play a role in the disorder's progression. AIMS: To compare the levels of oxidative stress and tyrosinase activity in melasma patients with healthy volunteers. METHODS: After written consent, 130 patients were enrolled in a case-control study. 65 cases were of melasma disorder, and 65 were served as control. Homogenized skin tissues were taken and used to estimate superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx) (antioxidants), malondialdehyde (MDA) and tyrosine hydroxylase (TH). RESULTS: Melasma patients had lower basal levels of systemic antioxidants than healthy subjects. Tyrosinase activity was shown to be greater in lesional skin than in non-lesional skin. In controls, there was a good positive relationship between TH and MDA and an excellent negative relationship between GPx and GSH. In melasma patients, there were significant associations between CAT, GPx, SOD and MDA. CONCLUSIONS: Increased oxidative stress may affect tyrosinase activity and eumelanin synthesis via the anabolic pathway of melanin synthesis, according to our findings. In conclusion, we discovered a negative relationship between antioxidants and tyrosinase activity.

Uncemented Total Hip Arthroplasty in an Adult without Osteotomy for Neglected Developmental Dysplasia of Hip.

Introduction: Developmental dysplasia of hip (DDH) is an abnormal development of hip joint which when neglected in early age group can lead to joint pain and secondary osteoarthritic changes. Crowe types III and IV neglected DDH joint is widely managed with total hip arthroplasty with subtrochanteric shortening. Case Report: A 52-year-old female presented with neglected DDH joint which was managed in two stages with femoral lowering followed by uncemented total hip arthroplasty without osteotomy. Conclusion: With the two-stage procedure, subtrochanteric shortening which is widely accepted management for neglected DDH and the related complications were avoidable with a satisfactory Harris hip score.

A Multi-target Drug Designing for BTK, MMP9, Proteasome and TAK1 for the Clinical Treatment of Mantle Cell Lymphoma.

BACKGROUND: Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma characterized by the mutation and overexpression of the cyclin D1 protein by the reciprocal chromosomal translocation t(11;14)(q13:q32). AIM: The present study aims to identify potential inhibition of MMP9, Proteasome, BTK, and TAK1 and determine the most suitable and effective protein target for the MCL. METHODOLOGY: Nine known inhibitors for MMP9, 24 for proteasome, 15 for BTK and 14 for TAK1 were screened. SB-3CT (PubChem ID: 9883002), oprozomib (PubChem ID: 25067547), zanubrutinib (PubChem ID: 135565884) and TAK1 inhibitor (PubChem ID: 66760355) were recognized as drugs with high binding capacity with their respective protein receptors. 41, 72, 102 and 3 virtual screened compounds were obtained after the similarity search with compound (PubChem ID:102173753), PubChem compound SCHEMBL15569297 (PubChem ID:72374403), PubChem compound SCHEMBL17075298 (PubChem ID:136970120) and compound CID: 71814473 with best virtual screened compounds. RESULT: MMP9 inhibitors show commendable affinity and good interaction profile of compound holding PubChem ID:102173753 over the most effective established inhibitor SB-3CT. The pharmacophore study of the best virtual screened compound reveals its high efficacy based on various interactions. The virtual screened compound's better affinity with the target MMP9 protein was deduced using toxicity and integration profile studies. CONCLUSION: Based on the ADMET profile, the compound (PubChem ID: 102173753) could be a potent drug for MCL treatment. Similar to the established SB-3CT, the compound was non-toxic with LD50 values for both the compounds lying in the same range.

Structural Insights into the Molecular Design of ROS1 Inhibitor for the Treatment of Non-Small Cell Lung Cancer (NSCLC).

BACKGROUND: Non-Small Cell Lung Cancer (NSCLC) alone is the leading cause of deaths worldwide. ROS1 is a receptor tyrosine kinase (RTK), eminently recognized as the stereotyped oncogenic driver. These RTKs trigger an array of physiological regulations via cellular signal transduction pathways, which are crucial for cancer development. This attributed ROS1 as an appealing and potential target towards the targeted cancer therapy. The present research aims to propound out an effective contemporary inhibitor for targeting ROS1 with a high affinity. METHODS: Molegro Virtual Docker (MVD) provided a flexible docking platform to find out the bestestablished drug as an inhibitor for targeting ROS1. A similarity search was accomplished against the PubChem database to acquire the corresponding inhibitor compounds regarding the Entrectinib (Pub- Chem ID: 25141092). These compounds were docked to procure the high-affinity inhibitor for the target protein via virtual screening. A comparative study between the control molecule (PubChem ID: 25141092)and the virtual screened compound(PubChem ID-25175866) was performed for the relative analysis of their salient features, which involved pharmacophore mapping, ADMET profiling, and BOILED-Egg plot. RESULTS: The virtual screened compound (PubChem ID-25175866) possesses the lowest rerank score (-126.623), and the comparative ADMET analysis also shows that it is a potential and effective inhibitor for ROS1 among the selected inhibitors. CONCLUSION: The present study provided a scope for the ROS1 inhibitor as significant prevention for nonsmall cell lung cancer (NSCLC). It can be upheld for future studies as a promising support via in vivo studies.

Advances and perspective in bioremediation of polychlorinated biphenyl-contaminated soils.

In recent years, microbial degradation and bioremediation approaches of polychlorinated biphenyls (PCBs) have been studied extensively considering their toxicity, carcinogenicity and persistency potential in the environment. In this direction, different catabolic enzymes have been identified and reported for biodegradation of different PCB congeners along with optimization of biological processes. A genome analysis of PCB-degrading bacteria has led in an improved understanding of their metabolic potential and adaptation to stressful conditions. However, many stones in this area are left unturned. For example, the role and diversity of uncultivable microbes in PCB degradation are still not fully understood. Improved knowledge and understanding on this front will open up new avenues for improved bioremediation technologies which will bring economic, environmental and societal benefits. This article highlights on recent advances in bioremediation of PCBs in soil. It is demonstrated that bioremediation is the most effective and innovative technology which includes biostimulation, bioaugmentation, phytoremediation and rhizoremediation and acts as a model solution for pollution abatement. More recently, transgenic plants and genetically modified microorganisms have proved to be revolutionary in the bioremediation of PCBs. Additionally, other important aspects such as pretreatment using chemical/physical agents for enhanced biodegradation are also addressed. Efforts have been made to identify challenges, research gaps and necessary approaches which in future, can be harnessed for successful use of bioremediation under field conditions. Emphases have been given on the quality/efficiency of bioremediation technology and its related cost which determines its ultimate acceptability.

Investigating the folding pathway and substrate induced conformational changes in B. malayi Guanylate kinase.

Guanylate kinase is one of the key enzymes in nucleotide biosynthesis. The study highlights the structural and functional properties of Brugia malayi Guanylate kinase (BmGK) in the presence of chemical denaturants. An inactive, partially unfolded, dimeric intermediate was observed at 1-2M urea while GdnCl unfolding showed monomer molten globule like intermediate at 0.8-1.0M. The results also illustrate the protective role of substrates in maintaining the integrity of the enzyme. The thermo stability of protein was found to be significantly enhanced in the presence of the substrates. Furthermore, binding of the substrates, GMP and ATP to BmGK changed its GdnCl induced unfolding pattern. Docking and molecular dynamic simulation performed for native BmGK, BmGK bound to GMP and GMP+ATP showed change in the fluctuation in the region between 130 and 150 residues. Arg134 lost its interaction with GMP and Arg145 interaction shifted to ATP after 40ns simulation upon binding of ATP to BmGK-GMP complex. We, thus, propose the importance of specific rearrangements contributed by binding of substrates which participate in the overall stability of the protein. The work here emphasizes on detailed biophysical characterization of BmGK along with the significant role of substrates in modulating the structural and functional properties of BmGK.

Comparative analysis of various electrostatic potentials on docking precision against cyclin-dependent kinase 2 protein: a multiple docking approach.

The fundamental of molecular modeling is the interaction and binding to form a complex, because it explains the action of most drugs to a receptor active site. In the present study, different semiempirical (RM1, AM1, PM3, MNDO) and ab initio (HF, DFT) charge models were investigated for their performance in prediction of docking pose against CDK2 proteins with their respective inhibitor. Further, multiple docking approaches and Prime/MM-GBSA calculations were applied to predict the binding mode with respective charge model against CDK2 inhibitors. A reliable docking result was obtained using RRD, which showed significance improvement on ligand binding poses and docking score accuracy to the IFD. The combined use of RRD and Prime/MM-GBSA method could give a high correlation between the predicted binding free energy and experimental biological activity. The preliminary results point out that AM1 could be a precious charge model for design of new drugs with enhanced success rate. As a very similar result was also found for a different system of the protein-ligand binding, the suggested scoring function based on AM1 method seems to be applicable in drug design. The results from this study can provide insights into highest success rate for design of potent and selective CDK2 inhibitors.

Degradation of Di- Through Hepta-Chlorobiphenyls in Clophen Oil Using Microorganisms Isolated from Long Term PCBs Contaminated Soil.

Present work describes microbial degradation of selected polychlorinated biphenyls (PCBs) congeners in Clophen oil which is used as transformer oil and contains high concentration of PCBs. Indigenous PCBs degrading bacteria were isolated from Clophen oil contaminated soil using enrichment culture technique. A 15 days study was carried out to assess the biodegradation potential of two bacterial cultures and their consortium for Clophen oil with a final PCBs concentration of 100 mg kg(-1). The degradation capability of the individual bacterium and the consortium towards the varying range of PCBs congeners (di- through hepta-chlorobiphenyls) was determined using GCMS. Also, dehydrogenase enzyme was estimated to assess the microbial activity. Maximum degradation was observed in treatment containing consortium that resulted in up to 97 % degradation of PCB-44 which is a tetra chlorinated biphenyl whereas, hexa chlorinated biphenyl congener (PCB-153) was degraded up to 90 % by the consortium. This indicates that the degradation capability of microbial consortium was significantly higher than that of individual cultures. Furthermore, the results suggest that for degradation of lower as well as higher chlorinated PCB congeners; a microbial consortium is required rather than individual cultures.

Skull metastasis in papillary carcinoma of thyroid: A case report.

Papillary thyroid carcinoma with metastasis to the skull is extremely rare. We report a case of unsuspected papillary thyroid carcinoma with skull metastasis. A 48-year-old female patient presenting with painless, pulsatile, progressively increasing swelling in the occipitoparietal region of the scalp approached for an X-ray of the skull. Ultrasound of palpable swelling in the neck revealed a heteroechoic lesion with increased vascularity. Foci of calcification were seen involving both lobes of the thyroid. Ultrasound of scalp showed a destructive mass in the skull with increased vascularity. Biopsy of thyroid lesions revealed branching papillae having a dense fibrovascular core covered by cuboidal epithelial cells with nuclei having a clear ground glass appearance. This case illustrates how isolated extensive skull metastasis can be found in papillary carcinoma patients without causing significant morbidity. Therefore, in the clinical course of thyroid papillary carcinoma, skull metastasis should be considered, and the patients should be meticulously investigated and followed up.