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Conclusions Knowledge about the lacrimal glands in health and disease has improved tremendously since its discovery in the mid-eighteenth century. Today we stand at the cusp of exploring potential regenerative approaches for the treatment of lacrimal gland damage in dry eye disease.Tracking the excitation of water molecules in the homogeneous liquid is challenging due to the ultrafast dissipation of rotational excitation energy through the hydrogen-bonded network. Here we demonstrate strong transient anisotropy of liquid water through librational excitation using single-color pump-probe experiments at 12.3 THz. We deduce a third-order response of χ3 exceeding previously reported values in the optical range by 3 orders of magnitude. Using a theory that replaces the nonlinear response with a material property amenable to molecular dynamics simulation, we show that the rotationally damped motion of water molecules in the librational band is resonantly driven at this frequency, which could explain the enhancement of the anisotropy in the liquid by the external terahertz field. By addition of salt (MgSO4), the hydration water is instead dominated by the local electric field of the ions, resulting in reduction of water molecules that can be dynamically perturbed by THz pulses.The photochemical products of dinucleotides 5′-TpG/5′-GpT with a photoactivatable anticancer Pt(IV) complex (trans,trans,trans-[Pt(N3)2(OH)2(py)2], py = pyridine; 1) were characterized by electrospray ionization mass spectrometry. The primary MS showed the main products were monoplatinated and diplatinated adducts for both the dinucleotides accompanied by the formation of minor triplatinated dinucleotides, indicating that T-N3 and G-N1 may be platination sites additional to the well-known G-N7 site. Surprisingly, a series of minor platinated adducts with oxidation of guanine and/or thymine were observed. Although guanine is more sensitive to oxidation than thymine, thymine can compete with guanine for complex 1-induced oxidation, of which the oxidation adducts were identified as cis- and trans-diastereomers of 5,6-dihydroxy-5,6-dihydrothymidine (cis,trans-ThdGly), 5-formyl-2′-deoxyuridine (5-FormdUrd), and 5-(hydroxymethyl)-2′-deoxyuridine (5-HMdUrd), respectively. While for guanine, apart from 8-hydroxyguanine (8-OH-G) and N-formylamidoiminohydantoin (RedSp), other guanine oxidized adducts such as spiroiminodihydantoin (Sp), dehydroguanidinohydantoin (DGh), and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) were also identified. MS/MS analysis showed that unique fragments with a Pt moiety [Pt(N3)(py)] cross-linking the G and T bases were formed during the fragmentation of monoplatinated dinucleotides. Such binding mode to and oxidative damages on DNA bases imposed by the diazido Pt(IV) complex are apparently distinct from those of cisplatin, perhaps accounting for its unique mechanism of action.Accuracy of protein-ligand binding free energy calculations utilizing implicit solvent models is critically affected by parameters of the underlying dielectric boundary, specifically, the atomic and water probe radii. Here, a global multidimensional optimization pipeline is developed to find optimal atomic radii specifically for protein-ligand binding calculations in implicit solvent. The computational pipeline has these three key components (1) a massively parallel implementation of a deterministic global optimization algorithm (VTDIRECT95), (2) an accurate yet reasonably fast generalized Born implicit solvent model (GBNSR6), and (3) a novel robustness metric that helps distinguish between nearly degenerate local minima via a postprocessing step of the optimization. A graph-based “kT-connectivity” approach to explore and visualize the multidimensional energy landscape is proposed local minima that can be reached from the global minimum without exceeding a given energy threshold (kT) are considered to be connected. As an illustration of the capabilities of the optimization pipeline, we apply it to find a global optimum in the space of just five radii four atomic (O, H, N, and C) radii and water probe radius. The optimized radii, ρW = 1.37 Å, ρC = 1.40 Å, ρH = 1.55 Å, ρN = 2.35 Å, and ρO = 1.28 Å, lead to a closer agreement of electrostatic binding free energies with the explicit solvent reference than two commonly used sets of radii previously optimized for small molecules. At the same time, the ability of the optimizer to find the global optimum reveals fundamental limits of the common two-dielectric implicit solvation model the computed electrostatic binding free energies are still almost 4 kcal/mol away from the explicit solvent reference. The proposed computational approach opens the possibility to further improve the accuracy of practical computational protocols for binding free energy calculations.Colorectal cancer is the third most common cancer in the world, affecting both men and women, and it is one of the leading causes of cancer related deaths worldwide. Current treatment modalities employed for colorectal cancer management have their own share of drawbacks, such as toxicity due to nonspecific action and chemoresistance that may develop during treatment. The quest and pursuit for newer drugs which can overcome these drawbacks has led to extensive research on plant derived phytoconstituents. Tiplaxtinin cell line Herbal molecules are known to have promising therapeutic efficacy and less toxicity as compared to the current chemotherapeutic drugs of allopathic regimen. However most of these herbal molecules have low bioavailability as a result their therapeutic efficacy gets compromised. Integration of modern delivery approaches with these herbal molecules and presenting them in the form of nanocarriers will help alleviate these drawbacks. This review describes herbal drugs that have potential for treatment of colorectal cancer and nanotechnology strategies widely investigated for the delivery of these herbal molecules. Targeted delivery methods include use of such components as polymeric nanoparticles, liposomes, dendrimers, magnetic nanoparticles, solid lipid nanoparticles, and nanoemulsions. The paper also discusses in detail the formulation aspects of herbal nanocarriers, their design development, and preclinical assessment.