Quality of New Domestic Hand Sanitizer Drug Product Manufacturers During COVID-19.

The FDA initiated a cross-sectional, statistically based sampling and testing study to characterize the quality of marketed alcohol-based hand sanitizer (ABHS) by evaluating the alcohol content and impurities present in ABHS products manufactured by establishments that registered with the FDA during March-April 2020. A stratified sampling design divided the population of manufacturers into independent groups based on each establishment's level of experience with FDA oversight and its geographic location. ABHS products were collected and analyzed by spatially offset Raman spectroscopy and gas chromatography with mass spectrometry (GC-MS).

Old Polymorph, New Technique: Assessing Ritonavir Crystallinity Using Low-Frequency Raman Spectroscopy.

Two decades ago, postmarket discovery of a second crystal form of ritonavir with lower solubility had major implications for drug manufacturers and patients. Since then, ritonavir has been reformulated via the hot-melt-extrusion process in an amorphous form. Here, quantitative low- and mid-frequency Raman spectroscopy methods were developed to characterize polymorphs, form I and form II, in commercial ritonavir 100 mg oral tablets as an alternate analysis approach compared to X-ray powder diffraction (XRPD).

Through-container quantitative analysis of hand sanitizers using spatially offset Raman spectroscopy.

The COVID-19 pandemic created an increased demand for hygiene supplies such as hand sanitizers. In response, a large number of new domestic or imported hand sanitizer products entered the US market. Some of these products were later found to be out of specification.

TRIP13 promotes metastasis of colorectal cancer regardless of p53 and microsatellite instability status.

Overexpression of TRIP13, a member of the AAA-ATPase family, is linked with various cancers, but its role in metastasis is unknown in colorectal cancer (CRC). In the current study, we investigated the role TRIP13 in experimental metastasis and its involvement in regulation of WNT/β-catenin and EGFR signaling pathways. Evaluation of formalin-fixed paraffin-embedded (FFPE) and frozen tissues of adenomas and CRCs, along with their corresponding normal samples, showed that TRIP13 was gradually increased in its phenotypic expression from adenoma to carcinoma and that its overexpression in CRCs was independent of patient's gender, age, race/ethnicity, pathologic stage, and p53 and microsatellite instability (MSI) status.

PAICS, a De Novo Purine Biosynthetic Enzyme, Is Overexpressed in Pancreatic Cancer and Is Involved in Its Progression.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with an extremely poor prognosis. There is an urgent need to identify new therapeutic targets and also understand the mechanism of PDAC progression that leads to aggressiveness of the disease. To find therapeutic targets, we analyzed data related to PDAC transcriptome sequencing and found overexpression of the de novo purine metabolic enzyme phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS).

PAICS, a Purine Nucleotide Metabolic Enzyme, is Involved in Tumor Growth and the Metastasis of Colorectal Cancer.

The identification of colorectal cancer (CRC) molecular targets is needed for the development of drugs that improve patient survival. We investigated the functional role of phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), a de novo purine biosynthetic enzyme involved in DNA synthesis, in CRC progression and metastasis by using cell and animal models. Its clinical utility was assessed in human CRC samples.

Targeting P4HA1 with a Small Molecule Inhibitor in a Colorectal Cancer PDX Model.

Deposition, remodeling, and signaling of the extracellular matrix facilitate tumor growth and metastasis. Here, we demonstrated that an enzyme, collagen prolyl 4-hydroxylase, alpha polypeptide I (P4HA1), which is involved in collagen synthesis and deposition, had elevated expression in colorectal cancers (CRCs) as compared to normal colonic tissues. The expression of P4HA1 in CRCs was independent of patient's age, race/ethnicity, gender, pathologic stage and grade, tumor location, and microsatellite instability (MSI) and p53 status.

Shape Recovery of Spherical Hydrogen-Bonded Multilayer Capsules after Osmotically Induced Deformation.

The mechanical properties of microparticles intended for in vivo applications as drug delivery vehicles are among important parameters that influence their circulation in the blood and govern particle biodistribution. We report on the synthesis of soft but mechanically robust spherical capsules via a hydrogen-bonded multilayer assembly of (poly(-vinylpyrrolidone), = 10 000 g mol) with (poly(methacrylic acid) = 100 000 g mol)) (PVPON/PMAA) in methanol using 4 μm nonporous silica microparticles as sacrificial templates, where = 5 and 10 and represents the bilayer number. The mechanical properties of (PVPON/PMAA) spherical capsules were assessed using the osmotic pressure difference method and resulted in an elasticity modulus of 97 ± 8 MPa, which is in the range of Young's modulus for elastomeric networks.

Encapsulation and Ultrasound-Triggered Release of G-Quadruplex DNA in Multilayer Hydrogel Microcapsules.

Nucleic acid therapeutics have the potential to be the most effective disease treatment strategy due to their intrinsic precision and selectivity for coding highly specific biological processes. However, freely administered nucleic acids of any type are quickly destroyed or rendered inert by a host of defense mechanisms in the body. In this work, we address the challenge of using nucleic acids as drugs by preparing stimuli responsive poly(methacrylic acid)/poly(-vinylpyrrolidone) (PMAA/PVPON) multilayer hydrogel capsules loaded with ~7 kDa G-quadruplex DNA.

Design of 2-Nitroimidazooxazine Derivatives as Deazaflavin-Dependent Nitroreductase (Ddn) Activators as Anti-Mycobacterial Agents Based on 3D QSAR, HQSAR, and Docking Study with In Silico Prediction of Activity and Toxicity.

Deazaflavin-dependent nitroreductase (Ddn) is an emerging target in the field of anti-tuberculosis agents. In the present study, 2-nitroimidazooxazine derivatives as Ddn activators were aligned for CoMFA, CoMSIA and HQSAR analysis. The best CoMFA and CoMSIA model were generated with leave-one-out correlation coefficients (q) of 0.

Honokiol inhibits the growth of head and neck squamous cell carcinoma by targeting epidermal growth factor receptor.

Here, we report the chemotherapeutic effect of honokiol, a phytochemical from Magnolia plant, on human head and neck squamous cell carcinoma (HNSCC). Treatment of HNSCC cell lines from different sub-sites, SCC-1 (oral cavity), SCC-5 (larynx), OSC-19 (tongue) and FaDu (pharynx) with honokiol inhibited their cell viability, which was associated with the: (i) induction of apoptosis, (ii) correction of dysregulatory cell cycle proteins of G0/G1 phase. Honokiol decreased the expression levels of epidermal growth factor receptor (EGFR), mTOR and their downstream signaling molecules.

Design, synthesis and docking studies of some novel (R)-2-(4'-chlorophenyl)-3-(4'-nitrophenyl)-1,2,3,5-tetrahydrobenzo[4,5] imidazo [1,2-c]pyrimidin-4-ol derivatives as antitubercular agents.

Filamenting temperature-sensitive mutant (FtsZ) is a novel target for the treatment of tuberculosis. A series of (R)-2-(4'-chlorophenyl)-3-(4'-nitrophenyl)-1,2,3,5-tetrahydrobenzo[4,5] imidazo[1,2-c]pyrimidin-4-ol derivatives were designed and docked on the FtsZ protein crystal structure (PDB Id: 1RLU, resolution 2.08 Å).