Malignancy prediction among tissues from Oral SCC patients including neck invasions: a 1H HRMAS NMR based metabolomic study.

INTRODUCTION: Oral cancer is a sixth commonly occurring cancer globally. The use of tobacco and alcohol consumption are being considered as the major risk factors for oral cancer. The metabolic profiling of tissue specimens for developing carcinogenic perturbations will allow better prognosis. OBJECTIVES: To profile and generate precise 1H HRMAS NMR spectral and quantitative statistical models of oral squamous cell carcinoma (OSCC) in tissue specimens including tumor, bed, margin and facial muscles. To apply the model in blinded prediction of malignancy among oral and neck tissues in an unknown set of patients suffering from OSCC along with neck invasion. METHODS: Statistical models of 1H HRMAS NMR spectral data on 180 tissues comprising tumor, margin and bed from 43 OSCC patients were performed. The combined metabolites, lipids spectral intensity and concentration-based malignancy prediction models were proposed. Further, 64 tissue specimens from twelve patients, including neck invasions, were tested for malignancy in a blinded manner. RESULTS: Forty-eight metabolites including lipids have been quantified in tumor and adjacent tissues. All metabolites other than lipids were found to be upregulated in malignant tissues except for ambiguous glucose. All of three prediction models have successfully identified malignancy status among blinded set of 64 tissues from 12 OSCC patients with an accuracy of above 90%. CONCLUSION: The efficiency of the models in malignancy prediction based on tumor induced metabolic perturbations supported by histopathological validation may revolutionize the OSCC assessment. Further, the results may enable machine learning to trace tumor induced altered metabolic pathways for better pattern recognition. Thus, it complements the newly developed REIMS-MS iKnife real time precession during surgery.

Alteration in lipid composition differentiates breast cancer tissues: a 1H HRMAS NMR metabolomic study.

INTRODUCTION: Breast cancer is the most frequent diagnosed cancer among women with a mortality rate of 15% of all cancer related deaths in women. Breast cancer is heterogeneous in nature and produces plethora of metabolites allowing its early detection using molecular diagnostic techniques like magnetic resonance spectroscopy. OBJECTIVES: To evaluate the variation in metabolic profile of breast cancer focusing on lipids as triglycerides (TG) and free fatty acids (FFA) that may alter in malignant breast tissues and lymph nodes from adjacent benign breast tissues by HRMAS 1H NMR spectroscopy. METHODS: The 1H NMR spectra recorded on 173 tissue specimens comprising of breast tumor tissues, adjacent tissues, few lymph nodes and overlying skin tissues obtained from 67 patients suffering from breast cancer. Multivariate statistical analysis was employed to identify metabolites acting as major confounders for differentiation of malignancy. RESULT: Reduction in lipid content were observed in malignant breast tissues along with a higher fraction of FFA. Four small molecule metabolites e.g., choline containing compounds (Chocc), taurine, glycine, and glutamate were also identified as major confounders. The test set for prediction provided sensitivity and specificity of more than 90% excluding the lymph nodes and skin tissues. CONCLUSION: Fatty acids composition in breast cancer using in vivo magnetic resonance spectroscopy (MRS) is gaining its importance in clinical settings (Coum et al. in Magn Reson Mater Phys Biol Med 29:1-4, 2016). The present study may help in future for precise evaluation of lipid classification including small molecules as a source of early diagnosis of invasive ductal carcinoma by employing in vivo magnetic resonance spectroscopic methods.

Novel Imbricatolic acid derivatives as protein tyrosine phosphatase-1B inhibitors: Design, synthesis, biological evaluation and molecular docking.

Protein tyrosine phosphatase (PTP-1B) antagonizes insulin signaling and is a potential therapeutic target for insulin resistance associated with obesity and type 2 diabetes. To find potential PTP-1B inhibitors, derivatives of Imbricatolic acid (1) have been synthesized by introducing various nitrogenous functionalities at C-15 and C-19 positions. They were evaluated for PTP-1B enzyme inhibition activity. Compounds 3, 6, 14, and 15 exhibited promising PTP-1B inhibitory activity at 10 µM concentrations with IC50 6.3, 6.8, 7.0 and 7.8 values, respectively. Structure activity relationship and molecular docking studies of these derivatives demonstrated that the integrity of the polar substituents were important for significant PTP-1B inhibitory activity. The Imbricatolic acid and active derivatives in this study might represent a starting point for development of new potential PTP-1B inhibitors.

Dual evaluation of some novel 2-amino-substituted coumarinylthiazoles as anti-inflammatory-antimicrobial agents and their docking studies with COX-1/COX-2 active sites.

Synthesis of total eighteen 2-amino-substituted 4-coumarinylthiazoles including sixteen new compounds (3a-o and 5b) bearing the benzenesulfonamide moiety is described in the present report. All the synthesized target compounds were examined for their in vivo anti-inflammatory (AI) activity and in vitro antimicrobial activity. Results revealed that six compounds (3 d, 3 f, 3 g, 3 h, 3 j and 3 n) exhibited pronounced anti-inflammatory activity comparable to the standard drug indomethacin. AI results were further confirmed by the docking studies of the most active (3n) and the least active compound (3a) with COX-1 and COX-2 active sites. In addition, most of the compounds exhibited moderate antimicrobial activity against Gram-positive bacteria as well as fungal yeast, S. cervisiae. Comparison between 3 and 5 indicated that incorporation of additional substituted pyrazole nucleus into the scaffold significantly enhanced AI activity.

Regional Anaesthesia, Contemporary Techniques, and Associated Advancements: A Narrative Review.

In particular, the application of regional anaesthesia techniques in existing medicine can be characterized as experiencing regular changes in recent decades. It is useful for obtaining accurate and efficient pain management solutions, from the basic spinal and epidural blocks to the novel ultrasound nerve blocks and constant catheter procedures. These advancements do enhance not only the value of the perioperative period but also the patient's rated optimization as enhancing satisfaction, better precision, and the safety of nerve block placement. The use of ultrasound technology makes it even easier to determine the proper positioning of the needle and to monitor nerve block placement. Moreover, the duration and efficiency of regional anaesthesia are being enhanced by state-of-the-art approaches, which come in the form of liposomal bupivacaine, and better recovery plans and protocols, which shorten recovery time and decrease the number of hospital days. As these methods develop further, more improvements in the safety, efficacy, and applicability of regional anaesthesia in contemporary medicine are anticipated through continued research and innovation.

The Use of Point-of-Care Ultrasound (POCUS) in Anesthesiology: A Narrative Review.

Point-of-care ultrasound (POCUS) has become an essential tool in modern anesthesiology, offering real-time imaging that aids in diagnosis, treatment, and procedural guidance. Its applications have expanded significantly, from routine assessments to complex perioperative management, enhancing patient care across various domains. This study aimed to review and summarize the current literature on the applications of POCUS in anesthesiology, focusing on its utility in airway management, cardiac assessment, lung ultrasound (LUS), and abdominopelvic evaluations. Additionally, it discusses the challenges and strategies for overcoming barriers to its widespread adoption. A narrative literature review was conducted, encompassing studies on using POCUS in anesthesiology. Key databases were searched for relevant articles ("Point-of-care ultrasound," "Focused cardiac ultrasound," "Lung ultrasound"), and studies were selected based on their relevance to the main topics of interest: airway management, cardiac ultrasound, LUS, and abdominopelvic and gastric ultrasound. Both observational studies and randomized controlled trials were included. POCUS improves the safety and accuracy of regional anesthesia and airway procedures, enhancing patient outcomes by providing real-time visualization. Focused cardiac ultrasound is valuable in preoperative, intraoperative, and postoperative care, allowing for tailored anesthesia plans and timely interventions based on cardiac function. The US is an effective diagnostic tool for assessing pulmonary conditions, with specific signs and artifacts aiding in identifying pathologies such as pneumothorax, pleural effusions, and pulmonary congestion. Despite its benefits, POCUS faces barriers such as limited access to training, the need for standardized protocols, and the high equipment cost, especially in low-resource settings. While its integration into clinical practice continues to grow, overcoming challenges related to training, standardization, and equipment access is essential to realize its full potential. Continued efforts in education and research are needed to support the widespread adoption of POCUS in anesthesiology.

The suburban-city divide: an evaluation of emergency department mental health presentations across two centres.

OBJECTIVE: To evaluate the characteristics of mental health presentations to the emergency department in two different hospital settings. METHODS: This was a retrospective cross-sectional study examining ED referrals to psychiatry in an inner-city and suburban centre. The authors collected data on gender, age, employment, housing, clinical presentation, time of assessment and admissions, over a 1-month period. RESULTS: The total number referred was 213: inner-city n = 109 and suburban n = 104. The inner-city saw a younger population; 47/109 (43%) were aged between 20 and 29 years, compared with 28/104 (27%) of suburban presenters (P value 0.0134). A higher number of presenters were aged over 60 in the suburban centre n = 13/104 (12.5%) versus the inner-city centre 3/109 (2.8%) (P value 0.0084). In the inner-city, the proportion of homeless presenters was significantly higher at 30/109 (28%) versus 5/104 (4.8%) in the suburban setting (P < 0.0001). Presentations related to substances were highest, a total of 73 (34.3%) across both centres, with no significant difference in clinical presentations across the two centres. The majority were seen in the on-call period, 74/109 (67.9%) in the inner-city centre and 66/104 (63.5%) in the suburban centre. The psychiatric admission rate was significantly different between the two centres, with 33/109 (30.3%) patients admitted in the inner-city centre and 13/104 (12.5%) patients admitted in the suburban centre (P value 0.002). CONCLUSIONS: A large proportion of ED referrals to psychiatry constitute patients with unmet social and addiction needs, who are seen out of hours. This prompts consideration of expanding both ED and community services to comprise a more multidisciplinary-resourced, 24/7 care model.

Specioside (SS) & verminoside (VS) (Iridoid glycosides): isolation, characterization and comparable quantum chemical studies using density functional theory (DFT).

Two biologically important molecules specioside (SS) and verminoside (VS) have been isolated from the ethanolic extract of stem bark of Kigelia pinnata. We have explored the electronic and spectroscopic properties of these two molecules on the basis of the Density Function Theory (DFT) quantum chemical calculations along with the correlations of biological efficacies and the results are presented in this paper. The structures of the molecules were established with the help of spectroscopic techniques (1H, 13C NMR, UV-VIS, FTIR) and chemical reactivity was compared by computed DFT theory using Becke3-Lee-Yang-Parr (B3LYP)/6-31G (d,p) data basis set. UV-Visible spectrum was obtained using Time Dependent DFT method. Electric dipole moment, polarizability, first static hyper polarizability and hyper conjugative interactions were also studied with the aid of natural bond orbital (NBO) analysis of these two compounds. The thermodynamic parameters of these compounds were determined at various temperatures. The HOMO, LUMO, chemical hardness (η), chemical potential (µ), electronegativity (χ), electrophilicity power (ω), the gap energy and NBO analysis of both the compounds have been discussed in this paper. Local reactivity was evaluated through the Fukui function i.

Synthesis, SAR and docking studies of substituted aryl phenylthiazolyl phenylcarboxamide as potential protein tyrosine phosphatase 1B (PTP1B) inhibitors.

In our continued effort to discover novel PTP1B inhibitor with improved in vivo activity, we attempted to optimize our previously discovered lead compound by replacing the sulfonyl group with benzoyl group to yield compound II. Additional structural modifications were performed on compound II to yield a series of 24 aryl phenylthiazolyl phenylcarboxamides as potential PTP1B inhibitors. Of the 24 tested, 6 compounds showed good PTP1B inhibitory activity while compound 38 as the most promising one. The plausible PTP1B-binding site interaction of compound 38 showed favourable binding similar to known PTP1B binders and suggests its selectivity towards PTP1B. Compound 38 also showed promising antihyperglycaemic, antidyslipidaemic and insulin resistant reversal activities in vivo in STZ model and db/db mice model. Altogether, the compound 38 presents an excellent candidate for future PTP1B targeted drug discovery.

A combined experimental (IR, Raman and UV-Vis) and quantum chemical study of canadine.

Plant based natural products cover a major sector of the medicinal field, as such focus on plant research has been increased all over the world. As an attempt to aid that research, we have performed structural and spectroscopic analysis of a natural product, an alkaloid: canadine. Both ab initio Hartree-Fock (HF) and density functional theory (DFT) employing B3LYP using 6-311++G(d,p) basis set were used for the calculations. The calculated vibrational frequencies were scaled and compared with the experimental infrared and Raman spectra. The complete vibrational assignments were made using potential energy distribution. The structure-activity relation has also been interpreted by mapping electrostatic potential surface and evaluating the reactivity descriptors, which are valuable information for quality control of medicines and drug-receptor interactions. Natural bond orbital analysis has also been performed to understand the stability and hyperconjugative interactions of the molecule. Furthermore, UV-Vis spectra have been recorded in an ethanol solvent (EtOH) and the electronic property has been analyzed employing TD-DFT for both gaseous and solvent phase. The HOMO and LUMO calculation with their energy gap show that charge transfer occurs within the molecule. Additionally, the nonlinear optical properties of the title compound have been interpreted that predicts it's the best candidate for the NLO materials.

Lipid Lowering Oxopropanylindole Hydrazone Derivatives with Antioxidant and Anti-hyperglycemic Activity.

A series of substituted oxopropanylindole hydrazone derivatives was synthesized and evaluated for anti-oxidant and anti-dyslipidemic activity. Of the 12 tested, 3 compounds (6c, 7b and 7d) showed good anti-oxidant activity, compound 6c attenuated LDL oxidation by 32%. The compounds 6c and 7d also showed good anti-dyslipidemic activity by reducing serum levels of total cholesterol (TC), phospholipids (PL) and triglycerides (TG). These two compounds were further evaluated for antiadipogenic and anti-hyperglycemic activity, where 6c showed 44% reduction in lipid accumulation and 20.5% and 24.3% reduction in blood glucose at 5h and 24h respectively, as compared to standard drug metformin. Thus, compounds 6c and 7d with balanced anti-oxidant and anti-dyslipidimic activities may be excellent candidates for lead optimization and drug development for the treatment of metabolic disorders.

Determination of pesticide and phthalate residues in tea by QuEChERS method and their fate in processing.

In this study, the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method was applied for the analysis of the multiclass pesticide residues of 12 organochlorines (OCs), 9 organophosphates (OPs), 11 synthetic pyrethroids (SPs), 4 herbicides, 6 phthalates in raw tea (loose tea, branded tea and herbal tea), and tea infusion in 4 different containers (glass cup, earthen cup, plastic bag and disposal cup). In loose tea and branded tea residues, malathion (0.257 and 0.118 mg kg-1), cypermethrin (0.065 and 0.030 mg kg-1), and fenvalerate (0.032 and 0.030 mg kg-1) were detected, respectively. In herbal tea, residues of only cypermethrin (0.053 mg kg-1) and fenvalerate (0.045 mg kg-1) were detected. Tea infusion samples contained in a plastic bag were found to be contaminated with only dibutyl phthalate (DBP) (0.038 mg kg-1). Disposable cup was found to be contaminated with DBP (0.026 mg kg-1) and diethyl phthalate (DEP) (0.004 mg kg-1). Further, to know the processing behavior of pesticides, the spiked raw tea was subjected to tea infusion at different brewing times (2, 5, 10 min). The analysis demonstrated that dimethoate, dichlorvos, and malathion had shown more than 10 % of translocation at 5 min of brewing time. Further brewing for 10 min revealed the reduction in concentration of pesticides. Leaching of phthalate residues from different plastic containers was also studied at 10, 30, and 60 min. DBP, benzyl butyl phthalate (BzBP), and di-2-(ethylhexyl) phthalate (DEHP) were leached in the tea infusion samples packed in plastic bags. On the other hand, in disposable cups, leaching of DBP, DEP, and dimethyl phthalate were found. The concentration of phthalate residues increased with retention time. Pesticide and phthalate contaminants were recorded at low quantities in few samples only.

Glomangiopericytoma of nasal cavity.

Glomangiopericytoma/sinonasal type hemangiopericytoma is a rare sinonasal neoplasm arising from the pericytes surrounding capillaries and accounts for less than 0.5% of all sinonasal tumors. This tumor differs from conventional soft tissue hemangiopericytoma in location, biologic behaviour and histologic features. Glomangiopericytoma is a borderline low malignancy tumor with a good prognosis after complete surgical resection. We report a case of 60-year-old woman who presented with progressive nasal obstruction and frequent nasal bleeding and was diagnosed as glomangiopericytoma on histopathological and immunohistochemistry findings. Histological characteristics, differential diagnosis and prognosis of this tumor are discussed in this article. This case has been reported because of its rarity and an array of differential diagnosis.

FT-IR spectroscopy, intra-molecular C-H⋯O interactions, HOMO, LUMO, MESP analysis and biological activity of two natural products, triclisine and rufescine: DFT and QTAIM approaches.

The present study deals with two natural products, triclisine and rufescine which are extracted from the Amazonian wines but ubiquitous in nature. The quantum chemical density functional method at B3PW91/6-311+G(d,p) level is used to obtain the equilibrium geometries of these molecules. The quantum theory of atoms-in-molecule approach is employed to study various intra-molecular C-H⋯O interactions within these molecules. We have also performed vibrational analyses of triclisine and rufescine at their equilibrium geometries and presented the complete assignments of the significant vibrational modes. The calculated vibrational frequencies are shown to be in perfect agreement with the experimentally observed FTIR spectra of molecules under study. In addition, the electronic properties of these molecules are also discussed with the help of HOMO-LUMO and MESP surfaces and a number of electronic as well as thermodynamic parameters are calculated which are closely related to their chemical reactivity and reaction paths. The biological activities of both molecules have also been predicted which highlight their pharmacological importance.

The biosynthesis of beta-carboline and quinolizidine alkaloids of Alangium lamarckii.

The incorporation of tryptamine, dopamine, N-deacetylisoipecoside, N-deacetylipecoside into alangimarckine, deoxytubulosine and ankorine and of strictosidine and vincoside into alangimarckine and deoxytubulosine in young Alangium lamarckii Thw. (Alangiaceae) has been studied and specific utilisation of N-deacetylisoipecoside demonstrated. Parallel experiments with nordeoxytubulosine and deoxytubulosine suggested that O-methylation precedes condensation of protoemetine with tryptamine and further the reduction of ethylene side chain takes place before condensation. Hydroxylation at C-8 in the trans-quinolizidine moiety is the terminal step in the biosynthesis of alangimarckine.

Quantum chemical and experimental studies on the structure and vibrational spectra of an alkaloid--Corlumine.

The study concentrates on an important natural product, phthalide isoquinoline alkaloid Corlumine (COR) [(6R)-6-[(1S)-1,2,3,4-Tetrahydro-6,7-dimethoxy-2-methylisoquinolin-1-yl] furo [3,4-e]-1,3-benzodioxol-8(6H)-one] well known to exhibit spasmolytic and GABA antagonist activity. It was fully characterized by a variety of experimental methods including vibrational spectroscopy (IR and Raman), thermal analysis (DSC), UV and SEM. For a better interpretation and analysis of the results quantum chemical calculations employing DFT were also performed. TD-DFT was employed to elucidate electronic properties for both gaseous and solvent environment using IEF-PCM model. Graphical representation of HOMO and LUMO would provide a valuable insight into the nature of reactivity and some of the structural and physical properties of the title molecule. The structure-activity relationship have been interpreted by mapping electrostatic potential surface (MEP), which is valuable information for the quality control of medicines and drug-receptor interactions. Stability of the molecule arising from hyper conjugative interactions, charge delocalisation has been analyzed using natural bond orbital (NBO) analysis. Computation of thermodynamical properties would help to have a deep insight into the molecule for further applications.

Spectroscopic and quantum chemical study of an alkaloid aristolochic acid I.

Aristolochic acids (AAs) (Aristolochiaceae) are used in the traditional Chinese herb medicine. We have presented the geometry optimization, electrostatic potential surface, frontier orbital energy gap and vibrational wavenumbers of aristolochic acid I (AA I) using ab initio Hartree-Fock (HF) and density functional theory (DFT/B3LYP) method employing 6-311G(d,p) basis set. A complete vibrational assignment has been done on the basis of calculations on monomer and dimer of AA I. The UV-vis absorption spectrum has been recorded in ethanol solvent and compared with the calculated one in the gas phase as well as in solvent environment (integral-equation formalism polarizable continuum model; IEF-PCM) using TD-DFT/6-31G basis set. A short outline of the NBO analysis segment with their structural meaning has been presented. The variation of thermodynamic properties with temperature was calculated theoretically and the thermal response of the compound has been recorded with the help of differential scanning calorimetry (DSC) in N2 environment.

Molecular structure, vibrational spectra and HOMO, LUMO analysis of yohimbine hydrochloride by density functional theory and ab initio Hartree-Fock calculations.

Yohimbine hydrochloride (YHCl) is an aphrodisiac and promoted for erectile dysfunction, weight loss and depression. The optimized geometry, total energy, potential energy surface and vibrational wavenumbers of yohimbine hydrochloride have been determined using ab initio, Hartree-Fock (HF) and density functional theory (DFT/B3LYP) method with 6-311++G(d,p) basis set. A complete vibrational assignment is provided for the observed Raman and IR spectra of YHCl. The UV absorption spectrum was examined in ethanol solvent and compared with the calculated one in gas phase as well as in solvent environment (polarizable continuum model, PCM) using TD-DFT/6-31G basis set. These methods are proposed as a tool to be applied in the structural characterization of YHCl. The calculated highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) with frontier orbital gap are presented.

Antagonistic properties of a natural product-Bicuculline with the gamma-aminobutyric acid receptor: studied through electrostatic potential mapping, electronic and vibrational spectra using ab initio and density functional theory.

(+)-Bicuculline (hereinafter referred to as bicuculline), a phthalide isoquinoline alkaloid is of current interest as an antagonist of gamma-aminobutyric acid (GABA). Its inhibitor properties have been studied through molecular electrostatic potential (MEP) mapping of this molecule and GABA receptor. The hot site on the potential surface of bicuculline, which is also isosteric with GABA receptor, has been used to interpret the inhibitor property. A systematic quantum chemical study of the possible conformations, their relative stabilities, FT-Raman, FT-IR and UV-vis spectroscopic analysis of bicuculline has been reported. The optimized geometries, wavenumber and intensity of the vibrational bands of all the conformers of bicuculline have been calculated using ab initio Hartree-Fock (HF) and density functional theory (DFT) employing B3LYP functional and 6-311G(d,p) basis set. Mulliken atomic charges, HOMO-LUMO gap ΔE, ionization potential, dipole moments and total energy have also been obtained for the optimized geometries of both the molecules. TD-DFT method is used to calculate the electronic absorption parameters in gas phase as well as in solvent environment using integral equation formalism-polarizable continuum model (IEF-PCM) employing 6-31G basis set and the results thus obtained are compared with the UV absorption spectra. The combination of experimental and calculated results provides an insight into the structural and vibrational spectroscopic properties of bicuculline.