An Experimental and Computational Study of 2-(3-Oxo-3H-benzof chromen-1-ylmethoxy)-Benzoic Acid Methyl Ester

The various methods for studying polarities are based on the use of probe molecules, whose molecular spectral profile is significantly affected by the polarity of the medium. The absorption and emission spectra and dipole moments (µg and µe) of 2-(3-oxo-3H-benzofchromen-1-ylmethoxy)-benzoic acid methyl ester (2BME) are studied in solvents of different polarities at room temperature. The determination of dipole moments by solvatochromic shift using various relations and the change in dipole moment (�µ) were determined using Stokes shift with the variation of the solvent polarity parameter (ET N). The value of µe greater than µg indicating that the probe is more polar in the higher state. DFT and TDDFT theoretical analysis of dipole moment in the vacuum and with solvent, solvent accessible surface (SAS) and molecular electrostatic potential (MEP) are also performed. © 2017, Springer Science+Business Media, LLC

InCl3-​assisted synthesis and cytotoxic studies of some novel heteroaryl thiazoles

Heteroaryl thiazoles were synthesized by the Hantzsch reaction of various α-​bromoketones with aryl thioureas using InCl3 as a catalyst in a shorter reaction time. The synthesized compds. were characterized and screened for their in-​vitro cytotoxic activity against DAL and EAC cells. Compd. I was found to be most effective against DAL cell lines with IC50 value of 15.76 μg​/mL. Compd. II was found to be most effective against EAC cells with IC50 value of 28.73 μg​/mL

Mesenchymal stromal cells’ therapy for polyglutamine disorders: where do we stand and where should we go?

Polyglutamine (polyQ) diseases are a group of inherited neurodegenerative disorders caused by the expansion of the cytosine-adenine-guanine (CAG) repeat. This mutation encodes extended glutamine (Q) tract in the disease protein, resulting in the alteration of its conformation/physiological role and in the formation of toxic fragments/aggregates of the protein. This group of heterogeneous disorders shares common molecular mechanisms, which opens the possibility to develop a pan therapeutic approach. Vast efforts have been made to develop strategies to alleviate disease symptoms. Nonetheless, there is still no therapy that can cure or effectively delay disease progression of any of these disorders. Mesenchymal stromal cells (MSC) are promising tools for the treatment of polyQ disorders, promoting protection, tissue regeneration, and/or modulation of the immune system in animal models. Accordingly, data collected from clinical trials have so far demonstrated that transplantation of MSC is safe and delays the progression of some polyQ disorders for some time. However, to achieve sustained phenotypic amelioration in clinics, several treatments may be necessary. Therefore, efforts to develop new strategies to improve MSC's therapeutic outcomes have been emerging. In this review article, we discuss the current treatments and strategies used to reduce polyQ symptoms and major pre-clinical and clinical achievements obtained with MSC transplantation as well as remaining flaws that need to be overcome. The requirement to cross the blood-brain-barrier (BBB), together with a short rate of cell engraftment in the lesioned area and low survival of MSC in a pathophysiological context upon transplantation may contribute to the transient therapeutic effects. We also review methods like pre-conditioning or genetic engineering of MSC that can be used to increase MSC survival in vivo, cellular-free approaches-i.e., MSC-conditioned medium (CM) or MSC-derived extracellular vesicles (EVs) as a way of possibly replacing the use of MSC and methods required to standardize the potential of MSC/MSC-derived products. These are fundamental questions that need to be addressed to obtain maximum MSC performance in polyQ diseases and therefore increase clinical benefits.Portuguese Foundation for Science and Technology: SFRH/BD/148877/2019; CENTRO01-0145-FEDER-000008 CENTRO-01-0145FEDER-022095 POCI-01-0145-FEDER-016719 POCI-01-0145-FEDER-029716 POCI01-0145-FEDER-016807 POCI-01-0145-FEDER016390 UID4950/2020 CENTRO-01-0145-FEDER-022118info:eu-repo/semantics/publishedVersio

Solvent influence on the photophysical properties of 4-(2-Oxo-2H-benzo[h]chromen-4-ylmethoxy)-benzaldehyde

Steady-state absorption and the fluorescence properties of the synthesized Benzofuran derivatives were studied. Absorption and fluorescence spectra of 4-(2-Oxo-2H-benzo[h]chromen-4-ylm ethoxy)-benzaldehyde (4-OBCM) have been recorded at room temperature in extensive variety of solvents of various polarities. 4-OBCM Fluorescence band maxima of the solvents are small amount spectral shifted to hypsochromic when the solvent polarity will increase, compared to absorption band under the identical circumstance. This suggests an increase in dipole moment of excited state compared to ground state. The ground-state dipole moment of 4-OBCM was found from quantum mechanical methods and the excited state dipole moment of 4-OBCM was evaluated from Lippert-Mataga Bakhshiev’s, Kawski-Chamma-Viallet’s and Reichardt conditions by methods for solvatochromic shift. Kamlet-Taft coefficients which affect this absorption profiles

Clostridium Difficile and COVID-19: Novel Risk Factors for Acute Portal Vein Thrombosis

The COVID-19 pandemic has created an unprecedented global health care crisis. COVID-19 patients are found to have increased thrombotic risk. Despite being on prophylactic anticoagulation, many develop serious arterial and venous thromboembolic events. Emerging reports indicate COVID-19 may be considered a novel risk factor for portal vein thrombosis. Although, intra-abdominal infections are identified as risk factors, clostridium difficile colitis has not been typically seen as a risk factor for PVT. We report a case of an elderly female with a recent diagnosis of COVID-19 and no prior history of cirrhosis or malignancy who presented with diarrhea due to clostridium difficile infection. She developed sudden onset severe abdominal pain during the course of hospitalization. Acute portal vein thrombosis was identified on CT imaging of the abdomen, and she improved well with therapeutic anticoagulation. Acute portal vein thrombosis usually results from a combination of local and systemic prothrombotic risk factors. The combination of local infection by clostridium difficile and COVID-19 coagulopathy led to development of portal vein thrombosis in our patient. To the best of our knowledge, this is the first case of portal vein thrombosis reported in a patient with clostridium difficile infection in the setting of COVID-19 coagulopathy. During the current pandemic, clinicians should strongly consider abdominal imaging in patients presenting with abdominal pain due to clostridium difficile infection in the setting of COVID-19 to rule out complications such as portal vein thrombosis. Early diagnosis and treatment of portal vein thrombosis prevent complications of portal hypertension and intestinal infarctions

Rational Design of Donor–Acceptor Based Semiconducting Copolymers with High Dielectric Constants

The low dielectric constant of organic semiconductors limits the efficiency of organic solar cells (OSCs). In an attempt to improve the dielectric constant of conjugated polymers, we report the synthesis of three semiconducting copolymers by combining the thiophene-substituted diketopyrrolopyrrole (TDPP) monomer with three different monomeric units with varying electron donating/accepting strengths: benzodithiophene (BBT-3TEG-TDPP), TDPP (TDPP-3TEG-TDPP), and naphthalene diimide (P(gNDI-TDPP)). Among the series, BBT-3TEG-TDPP and P(gNDI-TDPP) exhibited the highest dielectric constants (∼5) at 1 MHz frequency, signifying the contribution of dipolar polarization from TEG side-chains. Furthermore, transient absorption spectroscopic studies performed on these polymers indicated low exciton diffusion length as observed in common organic semiconducting polymers. Our findings suggest that utilizing the polar side-chains enhances the dielectric constant in a frequency regime of megahertz. However, it is not sufficient to reduce the Coulombic interaction between hole and electron in excitonic solar cells

The flavonoid hesperidin methyl chalcone as a potential therapeutic agent for cancer therapy: Molecular docking, in vitro cytotoxicity, and in vivo antitumor activity

Hesperidin methyl chalcone (HMC) is a methylation product of the flavanone hesperidin, a flavonoid derived from citrus fruits. Many reports have emphasized the analgesic, anti-inflammatory and antioxidant properties of HMC. However, the anticancer potential of HMC has not been fully elucidated. The objective of this study was to assess the possible anticancer potential of HMC. MTT assay was carried out to assess the in vitro cytotoxicity of HMC against using A549 cancer cell line. In addition, the in vivo antitumor activity of HMC was screened against murine Ehrlich ascites carcinoma (EAC) model, in terms of tumor volume, tumor weight, life span, hematological and biochemical parameters, and compared with that of the anticancer agent, hesperetin. HMC was efficient to suppress the cell viability of A549 cancer cells with an IC50 value of 51.12 µM, which was comparable to that of the anticancer agent hesperetin (IC50 = 49.12 µM). Similarly, in Ehrlich ascites carcinoma model, HMC significantly inhibited the growth of Ehrlich ascites carcinoma with mutual increase in the life span of HMC-treated mice, compared to EAC control. Most importantly, HMC showed a good safety profile as evidenced by restoring hematological profile count of RBCs, WBCs, and hemoglobin to the normal levels. HMC also efficiently reduced the oxidative stress in EAC-bearing mice via increasing the levels of GSH, SOD and Catalase. Collectively, HMC exerted a potent anticancer activity and data presented in this work suggest the usefulness of HMC as a promising candidate in cancer therapy

MSCs: science and trials

Although the field of regenerative medicine is rife with unsubstantiated claims of benefit and is often biased by strong commercial interests, it is important that the legitimate scientific enterprise does not allow this noise to overshadow meaningful advances in the field. By providing a skeletal system\u2013centric view of MSCs, the Perspective by Bianco et al. relegates the rapidly growing body of literature dedicated to exploring nonprogenitor functions of MSCs, including immunomodulation, to obscurity and undermines the efforts of legitimate and dedicated scientists to understand these functions and exploit them to achieve a therapeutic benefit in human patients. Indeed, our committee believes that the existing scientific data are sufficiently mature to warrant MSC-based clinical trials for disease indications beyond the skeletal system. However, we acknowledge that the sound establishment of MSC-based therapies requires controlled, randomized, prospective clinical trials that incorporate mechanistic-based studies to fully assess the pharmaceutical underpinnings of such therapy