DNA binding and cleavage, BRCA1 gene interaction, antiglycation and anticancer studies of transition metal complexes of sulfonamides.

A series of 4-((4-methylphenylsulfonamido)methyl)cyclohexanecarboxylic acid (NaMSCCA) transition metal complexes [Cu(II), Zn(II), Ni(II), Mn(II), and Co(II)] have been synthesized by precipitation method. The characterization was done by physical techniques, FT-IR spectroscopy, mass spectrometry, and NMR spectroscopy. The molecular structures of nickel (II) AZ-3 and cobalt (II) AZ-5 complexes were determined by the X-ray diffraction technique and found to crystallize in the triclinic space group P-1. The coordination geometry around the central nickel (AZ-3) and cobalt (AZ-5) atoms was square planar bipyramidal. Molecular docking was performed with duplex DNA of sequence d(CGCGAATTCGCG)2 DNA to determine the probable binding mode of compounds. Then these synthesized compounds were used to perform DNA cleavage activity through the agarose gel electrophoresis method. Among the compounds, compounds AZ-1 and AZ-2 exhibited good nuclease activity. The DNA sequence of breast-cancer suppressor gene 1 (BRCA1) was amplified through PCR and interaction studies of compounds AZ-1 and AZ-2 were performed through gel electrophoresis and fluorescence emission spectroscopy. The expression analysis of the BRCA1 gene was also performed to quantify the expression relative fold change (2^-(∆∆CT)) after treatment with compounds. All synthesized compounds were evaluated for their antioxidant and antiglycation activities and AZ-2 exhibited excellent results. The molecular docking study of these compounds was performed against the protein structure of advanced glycation end products to support the experimental results. Anticancer activity of compounds was performed through MTT assay. Copper and zinc complexes depicted the highest anticancer activity against human breast adenocarcinoma (MCF7) and human corneal epithelial cell (HCEC) cell lines.

Non-pharmacological therapies for pain management in Parkinson's disease: A systematic review.

Among the various non-motor symptoms of Parkinson's disease (PD), pain is often cited as the most common and debilitating feature. Currently, the literature contains gaps in knowledge with respect to the various forms of treatment available, particularly non-pharmacological therapies. Thus, the purpose of this systematic review is to provide an examination of the literature on non-pharmacological therapies for pain in PD. We compared the findings of research articles indexed within various literature databases related to non-pharmacological treatments of pain in PD patients. Our review identified five major non-pharmacological methods of pain therapy in PD: acupuncture, hydrotherapy, massage therapy, neuromodulation, and exercise. Treatments such as exercise therapy found a reduction in pain perception due to various factors, including the analgesic effects of neurotransmitter release during exercise and increased activity leading to a decrease in musculoskeletal rigidity and stiffness. By the same token, hydrotherapy has been shown to reduce pain perception within PD patients, with authors often citing a combined treatment of exercise and hydrotherapy as an effective treatment for pain management. Multiple methods of neurostimulation were also observed, including deep brain stimulation and spinal cord stimulation. Deep brain stimulation showed efficacy in alleviating certain pain types (dystonic and central), while not others (musculoskeletal). Hence, patients may consider deep brain stimulation as an additive procedure for their current treatment protocol. On the other hand, spinal cord stimulation showed significant improvement in reducing VAS scores for pain. Finally, although the literature on massage therapy and acupuncture effectiveness on pain management is limited, both have demonstrated a reduction in pain perception, with common reasons such as tactile stimulation and release of anti-nociceptive molecules in the body. Although literature pertaining to non-pharmacological treatments of pain in PD is sparse, there is copious support for these treatments as beneficial to pain management. Further exploration in the form of clinical trials is warranted to assess the efficacy of such therapies.

Oxygen-vacancy-induced magnetism in anti-perovskite topological Dirac semimetal Ba3SnO.

The thermodynamic, structural, magnetic and electronic properties of the pristine and intrinsic vacancy-defect-containing topological Dirac semimetal Ba3SnO are studied using first-principles density functional theory calculations. The thermodynamic stability of Ba3SnO has been evaluated with reference to its competing binary phases Ba2Sn, BaSn and BaO. Subsequently, valid limits of the atomic chemical potentials derived from the thermodynamic stability were used for assessing the formation of Ba, Sn and O vacancy defects in Ba3SnO under different synthesis environments. Based on the calculated defect-formation energies, we find that the charge-neutral oxygen vacancies are the most favourable type of vacancy defect under most chemical environments. The calculated electronic properties of pristine Ba3SnO show that inclusion of spin-orbit coupling in exchange-correlation potentials computed using generalized gradient approximation yields a semimetallic band structure exhibiting twin Dirac cones along the Γ-X path of the Brillouin zone. The effect of spin-polarization and spin-orbit coupling on the physical properties of intrinsic vacancy defects containing Ba3SnO has been examined in detail. Using Bader charges, electron localization function (ELF), electronic density of states (DOS) and spin density, we show that the isolated oxygen vacancy is a magnetic defect in anti-perovskite Ba3SnO. Our results show that the origin of magnetism in Ba3SnO is the accumulation of unpaired charges at the oxygen vacancy sites, which couple strongly with the 5d states of the Ba atom. Owing to the metastability observed in earlier theoretically predicted magnetic topological semimetals, the present study reveals the important role of intrinsic vacancy defects in giving rise to magnetism and also provides opportunities for engineering the electronic structure of a Dirac semimetal.

Synchronous primary diffuse large B-cell lymphoma and papillary thyroid carcinoma: A case report highlighting "Lymphoma first approach".

Papillary thyroid carcinoma (PTC) is the most common type of all thyroid carcinomas and accounts for up to 90% of all thyroid malignancies. It is the most indolent form of the disease and has an excellent prognosis. On the other hand, Primary thyroid lymphoma (PTL) is a rare entity accounting for only about 1% to 5% of all thyroid malignancies and only 2% of extranodal lymphomas. Synchronous PTC and PTL is a very rare condition and only a few cases have been reported in the literature up till now. We report one such case in a 52-year-old lady who was referred to us with goiter and progressively increasing difficulty in breathing.

Adenoid cystic carcinoma of external auditory canal: A rare disease.

External auditory canal, like other epithelialized surfaces is predisposed to malignancies such as Squamous cell carcinomas (SCC), melanomas and adenocarcinomas. In this background, malignancies like adenoid cystic carcinoma (ACC) are a rare occurrence and need to be thoroughly evaluated both locally and for distant extension. The malignancy needs to be addressed with an aggressive approach surgically with adequate marginal clearance. The role of radiation is debatable considering the outcomes in the limited data. Here we present the case of a 35-year-old female who came in with otalgia and otorrhea associated with a mass in the external auditory canal. After biopsy and imaging, a diagnosis of adenoid cystic carcinoma was made and the patient was managed accordingly.

Development, characterization and optimization of methotrexate-olive oil nano-emulsion for topical application.

The chronic inflammatory conditions like psoriasis has an increased prevalence and is linked with various associated life threatening disease conditions. The main objective of this project was to developed a methotrexate-olive loaded nano emulsion. The formulation was assessed for various parameters including Thermodynamic Stability, physico-chemically characterization, drug release kinetics and entrapment efficiency and in vitro/ in vivo skin permeation analysis. Final optimized formulation had a particle size 18.27±5.78 nm with a PDI of 0.25±0.01, whereas the average entrapment efficiency of formulation was 74.68±2.1%. The release kinetics suggested 97.72% drug release at pH 5 after 20 hrs. The FTIR data confirmed that the chemical structure of drug is retained with efficient loading into the formulation. Permeation data showed that an average of 79.23±3.6µg/cm2 of methotrexate was permeated from the nano emulsion with an average flux of 2.326±0.45µg/cm2/h after 24 hrs. Finally in vivo studies on rabbit skin confirmed that the structural changes of intercellular lipid layers in the stratum corneum are not responsible for enhanced skin permeation of methotrexate loaded nano emulsion. It was concluded that olive oil based MTX-NE is suitable for topical application and can be used for management of psoriasis.

Non-recurrent laryngeal nerve: a case report and review of literature.

Right recurrent laryngeal nerve can take a "Non-Recurrent" course and can present as a Non Recurrent Laryngeal nerve which is a rare entity. Such anomalies can lead to difficulty in locating the laryngeal nerve during thyroid surgeries and there are higher chances of it being injured. Therefore, surgeons should be mindful of this entity. We report the case of a 53-year-old lady who underwent thyroid surgery and a right Non Recurrent Laryngeal Nerve was identified intra-operatively.

Management of Laryngotracheal trauma: A review of current trends and future Directions.

Laryngotracheal trauma is rare but can pose serious threats to one's life. Presenting symptoms vary according to the severity of injury. Immediate Airway control is first step in the management, intubation should be considered by a senior member of the trauma team if the injury is minor while tracheostomy should be reserved for more severe injuries. Evaluation by a fibre-optic laryngoscopy and CT scan should be done whenever possible. Reconstruction is done according to the site involved using suture, titanium miniplates and stents. Tissue engineering has added a new horizon in this management but up till now complete laryngotracheal regeneration is very far-fetched, but tissue regeneration at individual sites have shown some positive results. More work needs to be done in this less explored field including laryngeal transplantation.

Metabolomics and marker-based stability studies of methanol extract of seeds of Syzygium cumini L.

Though, herbal medicines are prone to deterioration upon storage due to their complex nature, but less attention has been paid to investigating stability of such products to assign shelf-life. Therefore, the present study aimed to assess the accelerated stability of methanolic extract of seeds of Syzygium cumini. The extract was kept at three different storage conditions (30oC/60% RH, 40oC/75% RH and 60oC/85% RH) for a period of 6 months. The samples withdrawn at 0 (before starting the study), 1, 2, 3, 4 and 6 months were analyzed to get UV-Visible metabolomics fingerprints and determine caffeic acid contents using RP-HPLC. The comparison of metabolomics fingerprints indicated that the extract was stable for 1 month at all the three storage conditions. However, caffeic acid contents were found to be intact for a longer period of time. Following the zero order degradation, caffeic acid was predicted to be stable for more than 3 years, if kept at 25oC. The results of the present study indicate that metabolomes of methanol extract of seeds of Syzygium cumini change very fast, suggesting the development of stable formulations.

Evaluation of antioxidant and antimicrobial activities of Bergenia ciliata Sternb (Rhizome) crude extract and fractions.

Biologically, screening of medicinal plants extracts have been since pre-historic to determine the antioxidants and antimicrobial profile. The present study was aimed to investigate and evaluate crude extract and different fractions of Bergenia ciliata Sternb (rhizome) for bioactivity which is most considerable medicinal plants. The chloroform fraction was found to be highly anti-oxidative with the IC50 value (4.15±0.82) as compare to ethyl acetate and n-hexane fraction. In addition, neither crude extract nor any fraction showed inhibition against fungal strains, i.e. Aspergillus flavus and Aspergillus niger. Furthermore, the crude extract and fractions of B. ciliata (rhizome) exhibiting promising activities against Bacillus atrophoeus, Bacillus subtilis, Kleibsiella pneumonia and Pseudomonas aeruginosa strains. In summary, B. ciliata is recommended as a source of bioactive compounds which might be used against oxidative stress and drug resistance bacteria.

Benzene oxidation by Fe(III)-catalyzed sodium percarbonate: matrix constituent effects and degradation pathways.

Complete degradation of benzene by the Fe(III)-activated sodium percarbonate (SPC) system is demonstrated. Removal of benzene at 1.0 mM was seen within 160 min, depending on the molar ratios of SPC to Fe(III). A mechanism of benzene degradation was elaborated by free-radical probe-compound tests, free-radical scavengers tests, electron paramagnetic resonance (EPR) analysis, and determination of Fe(II) and H2O2 concentrations. The degradation products were also identified using gas chromatography-mass spectrometry method. The hydroxyl radical (HO.) was the leading species in charge of benzene degradation. The formation of HO. was strongly dependent on the generation of the organic compound radical (R.) and superoxide anion radical (O.). Benzene degradation products included hydroxylated derivatives of benzene (phenol, hydroquinone, benzoquinone, and catechol) and aliphatic acids (oxalic and fumaric acids). The proposed degradation pathways are consistent with radical formation and identified products. The investigation of selected matrix constituents showed that the Cl and HCO3 had inhibitory effects on benzene degradation. Natural organic matter (NOM) had accelerating influence in degrading benzene. The developed system was tested with groundwater samples and it was found that the Fe(III)-activated SPC has a great potential in effective remediation of benzene-contaminated groundwater while more further studies should be done for its practical application in the future because of the complex subsurface environment.

Development of cetyl dimethicone based water-in-oil emulsion containing botanicals: Physical characteristics and stability.

The aim of current research was to develop a water-in-oil emulsion containing grape seed extract for application in cosmeceuticals. Finally grinded dried grape seeds powder was extracted with hydro alcoholic mixture. Emulsions consisting of different concentrations of cetyl dimethicone (Abile EM90), the nonionic emulsifier, liquid paraffin as oily phase and water as aqueous phase were developed. Color, odor, pH, viscosity, liquefaction, phase separation, centrifugation and thermal stability of the formulated emulsions were observed at various storage temperatures i.e. 8±0.5°C, 25±0.5°C, 40±0.5°C and 40°C±0.5°C with 70% RH. The stable formulation consist of 16% mineral oil, 4% of ABIL EM 90(®), 4% grape seeds extract, 1% rose oil and 75% distilled water. All the results derived from this study showed good stability over the three months study period which indicates w/o emulsion can be used as carrier of 4% grape seeds extract to enhance desired effects when applied topically.

Antioxidant and antiacetylcholine esterase potential of aerial parts of Conocarpus erectus, Ficus variegata and Ficus maclellandii.

The current study was designed to check the antioxidant and enzyme inhibition potential of various extracts/ fractions of three selected plants. The aerial parts of Conocarpus erectus (Combretaceae), Ficus variegata (Moraceae) and Ficus maclellandii (Moraceae) were extracted with ethanol (95%) and the resulting crude extracts were partitioned with n-hexane, chloroform and n-butanol successively. Folin-Ciocalteu reagent was used to calculate the total phenolic contents, flavonoids contents were calculated with aluminum chloride while antioxidant and enzyme studies were carried out through standard protocols. All extracts/fractions contained reasonable amount of phenolic compounds ranging from 0.58-58.23 mg CE/g of DW and 0.43-30.56 mg GAE/g of DW. Total flavonoids were determined using rutin and quercetin standards, ranging from 2.65-18.2 mg rutin equivalent/g of dry weight and 0.92-5.41 mg quercetin equivalent/g of dry weight. Antioxidant studies such as DPPH inhibition FRAP and total antioxidant capacity (TAC) was checked. The crude ethanolic extract of C. erectus showed maximum antiradical scavenging power (90.43%; IC50=7 µg) and ferric reducing antioxidant power (16.5 µM eq.FeSO4.7H2O), respectively while leave extract of F. variegata (chloroform) was the most active (0.6577) in TAC among other extracts of the selected medicinal plants. Butanolic leave extract of C. erectus exhibited maximum enzyme inhibition activity (91.62% with IC50 40 µg/ml) while other extracts showed significant activity. It was observed from results that all extracts/fractions of under consideration plants, exhibited significant bioactivities especially ethanolic and butanolic fractions, which may be the richest source of such type of activities.

Enhancement effects of chelating agents on the degradation of tetrachloroethene in Fe(III) catalyzed percarbonate system.

The performance of Fe(III)-based catalyzed sodium percarbonate (SPC) for stimulating the oxidation of tetrachloroethene (PCE) for groundwater remediation applications was investigated. The chelating agents citric acid monohydrate (CIT), oxalic acid (OA), and Glutamic acid (Glu) significantly enhanced the degradation of PCE. Conversely, ethylenediaminetetraacetic acid (EDTA) had a negative impact on PCE degradation, which may due to its strong Fe chelation and HO• scavenging abilities. However, excessive SPC or chelating agent will retard PCE degradation. In addition, investigations using free radical probe compounds and radical scavengers revealed that PCE was primarily degraded by HO• radical oxidation in both the chelated and non-chelated systems, while O2•- also participated in the non-chelated system and the OA and Glu modified systems. According to the electron paramagnetic resonance (EPR) studies, the presence of HO• in the Fe(III)/SPC system was maintained much longer than that in the Fe(II)/SPC system. The results indicated that the addition of CIT, OA or Glu indeed enhanced the generation of HO• in the first 10 min and promoted degradation efficiency by increasing the amount of Fe(III) and maintaining the concentration of HO• radicals in solution. In conclusion, chelated Fe(III)-based catalyzed SPC oxidation is a promising method for the remediation of PCE-contaminated groundwater.

Analytical, nutritional and biological evaluation of various brands of fortified and non-fortified wheat flour.

In Pakistan, a funded flour fortification program was launched for malnourished population, residing mainly in rural low income areas, but the urban population having comparatively better nutritional as well as economic status was focused wherein excessive intake of fortificants might cause complications. Therefore, the present study describes the physicochemical properties, elemental composition, nutritional components and hemoglobin/ferritin increasing potential of fortified and non-fortified flour. Domesticated chicken (Gallus gallus domesticus), either sex, age one month, weight 380 ± 18.28 g, were randomly segregated into 4 groups (n=6). The group I, II and III were fed on fortified flour, whereas group IV was fed on non-fortified flour for 30 days. The birds were weighed and blood samples of each of the birds were analyzed for determination of markers of iron status, hemoglobin (Hb) and serum ferritin (SF). Moisture, ash and iron contents were found to be lower in non-fortified flour than that of the fortified samples. Hb and SF levels in groups fed on fortified flour were significantly higher than the one received non-fortified flour (P < 0.05). The consumption of iron-fortified flour increases iron stores in the body without any further complication but long-term usage needs to be monitored.

A generalized Gompertz promotion time cure model and its fitness to cancer data.

The cure models based on standard distributions like exponential, Weibull, lognormal, Gompertz, gamma, are often used to analyze survival data from cancer clinical trials with long-term survivors. Sometimes, the data is simple, and the standard cure models fit them very well, however, most often the data are complex and the standard cure models don't fit them reasonably well. In this article, we offer a novel generalized Gompertz promotion time cure model and illustrate its fitness to gastric cancer data by three different methods. The generalized Gompertz distribution is as simple as the generalized Weibull distribution and is not computationally as intensive as the generalized F distribution. One detailed real data application is provided for illustration and comparison purposes.

Predictive modeling and regression analysis of diverse sulfonamide compounds employed in cancer therapy.

Topological indices (TIs) have rich applications in various biological contexts, particularly in therapeutic strategies for cancer. Predicting the performance of compounds in the treatment of cancer is one such application, wherein TIs offer insights into the molecular structures and related properties of compounds. By examining, various compounds exhibit different degree-based TIs, analysts can pinpoint the treatments that are most efficient for specific types of cancer. This paper specifically delves into the topological indices (TIs) implementations in forecasting the biological and physical attributes of innovative compounds utilized in addressing cancer through therapeutic interventions. The analysis being conducted to derivatives of sulfonamides, namely, 4-[(2,4-dichlorophenylsulfonamido)methyl]cyclohexanecarboxylic acid (1), ethyl 4-[(naphthalene-2-sulfonamido)methyl]cyclohexanecarboxylate (2), ethyl 4-[(2,5-dichlorophenylsulfonamido)methyl]cyclohexanecarboxylate (3), 4-[(naphthalene-2-sulfonamido)methyl]cyclohexane-1-carboxylic acid (4) and (2S)-3-methyl-2-(naphthalene-1-sulfonamido)-butanoic acid (5), is performed by utilizing edge partitioning for the computation of degree-based graph descriptors. Subsequently, a linear regression-based model is established to forecast characteristics, like, melting point and formula weight in a quantitative structure-property relationship. The outcomes emphasize the effectiveness or capability of topological indices as a valuable asset for inventing and creating of compounds within the realm of cancer therapy.

Computational modeling of imines based anti-oxidant and anti-esterases compounds: Synthesis, single crystal and In-vitro assessment.

Molecular modeling strategy was adopted to check the biological potential of the imine based molecules against free radical, acetylcholine esterase and butyrylcholine esterase. Three Schiff based compounds as (E)-2-(((4-bromophenyl)imino)methyl)-4-methylphenol (1), (E)-2-(((3-fluorophenyl)imino)methyl)-4-methylphenol (2) and (2E,2E)-2-(2-(2-hydroxy-5-methylbenzylidene)hydrazono)-1,2-diphenylethanone (3) were synthesized with high yield. The synthesized compounds were characterized with the help of modern techniques such as UV, FTIR and NMR while exact structure was depicted with Single Crystal X-Ray diffraction technique which disclosed that compound 1 is orthorhombic, while 2 and 3 are monoclinic. A hybrid functional (B3LYP) method with general basis set of 6-31 G(d,p) were applied to optimize synthesized Schiff bases. The contribution of in-between molecular contacts within a crystalline assembly of compounds were studied using Hirshfeld surface analysis (HS). In order to check the ability of the synthesized compounds toward free radical and enzyme inhibition, in vitro models were used to assess the radical scavenging and enzyme inhibition potential which depicted that compound 3 showed highest potential (57.43 ± 1.0%; DPPH, 75.09 ± 1.0%; AChE and 64.47 ± 1.0%; BChE). The ADMET assessments suggested the drug like properties of the synthesized compounds. It was concluded from results (in vitro and in silico) that synthesized compound have ability to cure the disorder related to free radical and enzyme inhibition. Compound 3 was shown to be the most active compared to other compounds.

Docetaxel-Loaded Methoxy poly(ethylene glycol)-poly (L-lactic Acid) Nanoparticles for Breast Cancer: Synthesis, Characterization, Method Validation, and Cytotoxicity.

This study aimed to synthesize and characterize DTX-mPEG-PLA-NPs along with the development and validation of a simple, accurate, and reproducible method for the determination and quantification of DTX in mPEG-PLA-NPs. The prepared NPs were characterized using AFM, DLS, zetasizer, and drug release kinetic profiling. The RP-HPLC assay was developed for DTX detection. The cytotoxicity and anti-clonogenic effects were estimated using MTT and clonogenic assays, respectively, using both MCF-7 and MDA-MB-231 cell lines in a 2D and 3D culture system. The developed method showed a linear response, high precision, accuracy, RSD values of ≤2%, and a tailing factor ≤2, per ICH guidelines. The DTX-mPEG-PLA-NPs exhibited an average particle size of 264.3 nm with an encapsulation efficiency of 62.22%. The in vitro drug kinetic profile, as per the Krosmeyers-Peppas model, demonstrated Fickian diffusion, with initial biphasic release and a multistep sustained release over 190 h. The MTT assay revealed improved in vitro cytotoxicity against MCF-7 and MDA-MB-231 in the 2D cultures and MCF-7 3D mammosphere cultures. Significant inhibitions of the clonogenic potential of MDA-MB-231 were observed for all concentrations of DTX-mPEG-PLA-NPs. Our results highlight the feasibility of detecting DTX via the robust RP-HPLC method and using DTX-mPEG-PLA-NPs as a perceptible and biocompatible delivery vehicle with greater cytotoxic and anti-clonogenic potential, supporting improved outcomes in BC.

Ethyl 2-benzene-sulfonamido-4-methyl-penta-noate.

In the title compound, C(14)H(21)NO(4)S, the O-S-O angle is 120.06 (11)°, with the S atom adopting a distorted tetra-hedral geometry. In the crystal, N-H⋯O hydrogen bonds connect the mol-ecules along the a axis, generating an infinite chain. The disordered C atoms of the isobutyl group were refined with the C-C distances restrained to 1.52 (1) Šand the occupancy ratio refined to 0.504 (3):0.496 (3).