25-hydroxyvitamin D is a predictor of COVID-19 severity of hospitalized patients.

OBJECTIVES: Studies investigating the association between vitamin D and severity of COVID-19 have mixed results perhaps due to immunoassay assessment of total 25-hydroxyvitamin D (tD) (the sum of 25-hydroxyvitamin-D2 [25-OH-D2] and 25-hydroxyvitamin-D3 [25-OH-D3]). Liquid chromatography tandem mass spectrometry (LC-MS/MS) has high analytical specificity and sensitivity for 25-OH-D2 and 25-OH-D3, and thus enables a more accurate assessment of impact on COVID-19 outcomes. METHODS: We established reference intervals for 25-OH-D3 and tD using LC-MS/MS. 25-OH-D2, 25-OH-D3 and tD were quantitated for 88 COVID-19 positive and 122 COVID-19 negative specimens. Chi-square or Fisher's exact tests were used to test associations in binary variables. T-Tests or Wilcoxon rank sum tests were used for continuous variables. Cox proportional hazards were used to test associations between 25-OH-D3 or tD levels and length of stay (LOS). For mortality and ventilation, logistic regression models were used. RESULTS: COVID-19 patients with deficient (<20 ng/mL) levels of 25-OH-D3 had significantly longer LOS by 15.3 days. COVID-19 P patients with deficient (<20 ng/mL) and insufficient (<30 ng/mL) of tD had significantly longer LOS by 12.1 and 8.2 days, respectively. Patients with insufficient levels of tD had significantly longer LOS by 13.7 days. COVID-19 patients with deficient serum 25-OH-D3 levels had significantly increased risk-adjusted odds of in-hospital mortality (OR [95% CI]: 5.29 [1.53-18.24]); those with insufficient 25-OH-D3 had significantly increased risk for requiring ventilation during hospitalization was found at LCMS insufficient cutoff (OR [95% CI]: 2.75 [1.10-6.90]). CONCLUSIONS: There is an inverse relationship of 25-hydroxyvitamin D levels and hospital LOS for COVID-19 patients. Vitamin D status is a predictor for severity of outcomes. LCMS results are useful for assessing the odds of mortality and the need for ventilation during hospitalization.

ß-cell Smad2 null mice have improved ß-cell function and are protected from diet-induced hyperglycemia.

Understanding signaling pathways that regulate pancreatic ß-cell function to produce, store, and release insulin, as well as pathways that control ß-cell proliferation, is vital to find new treatments for diabetes mellitus. Transforming growth factor-beta (TGF-ß) signaling is involved in a broad range of ß-cell functions. The canonical TGF-ß signaling pathway functions through intracellular smads, including smad2 and smad3, to regulate cell development, proliferation, differentiation, and function in many organs. Here, we demonstrate the role of TGF-ß/smad2 signaling in regulating mature ß-cell proliferation and function using ß-cell-specific smad2 null mutant mice. ß-cell-specific smad2-deficient mice exhibited improved glucose clearance as demonstrated by glucose tolerance testing, enhanced in vivo and ex vivo glucose-stimulated insulin secretion, and increased ß-cell mass and proliferation. Furthermore, when these mice were fed a high-fat diet to induce hyperglycemia, they again showed improved glucose tolerance, insulin secretion, and insulin sensitivity. In addition, ex vivo analysis of smad2-deficient islets showed that they displayed increased glucose-stimulated insulin secretion and upregulation of genes involved in insulin synthesis and insulin secretion. Thus, we conclude that smad2 could represent an attractive therapeutic target for type 2 diabetes mellitus.

Prostate Cancer Cellular Uptake of Ternary Titanate Nanotubes/CuFe2O4/Zn-Fe Mixed Metal Oxides Nanocomposite.

BACKGROUND: Certainly, there is a demand for stronger recognition of how nanoparticles can move through the cell membrane. Prostate cancer is one of the forcing sources of cancer-relevant deaths among men. AIM OF THE WORK: The current research studied the power of prostate cancer cells to uptake a ternary nanocomposite TNT/CuFe2O4/Zn-Fe mixed metal oxides (MMO). METHODOLOGY: The nanocomposite was synthesized by a chemical method and characterized by a High-resolution transmission electron microscope, Field emission scanning electron microscope, X-ray diffraction, Fourier transmission infra-red, X-ray photoelectron spectroscopy, dynamic light scattering. Besides, it was implemented as an inorganic anticancer agent versus Prostate cancer PC-3 cells. RESULTS: The results revealed cellular uptake validity, cell viability reduction, ultra-structures alterations, morphological changes and membrane damage of PC-3 cells. CONCLUSION: The prepared ternary nanocomposite was highly uptake by PC-3 cells and possessed cytotoxicity that was dose and time-dependent. To conclude, the study offered the potential of the investigated ternary nanocomposite as a promising prostate anticancer agent.

New Approach in Ulcer Prevention and Wound Healing Treatment using Doxycycline and Amoxicillin/LDH Nanocomposites.

Doxycycline (DOX) and amoxicillin (AMOX) are important Broad-spectrum antibiotics used in treating multiple human and animal diseases. For the sake of exploring novel medical applications, both antibiotics were loaded into magnesium aluminium layer double hydroxide (Mg-Al)/LDH nanocomposite through the co-precipitation method. The synthesized materials were characterized by XRD, FT-IR, particle size analysis, FESEM and HRTEM. Acute toxicological studies were conducted using median lethal dose LD50, where a total number of 98 rats (200-150 gm) of both sexes were used. An experimental wound was aseptically incised on the anterior-dorsal side of each rat, while 98% of pure medical ethanol was used for ulcer induction. Acute toxicity, wound closure rate, healing percentages, ulcer index, protective rate and histopathological studies were investigated. Antibiotic Nanocomposites has significantly prevented ulcer formation and improved wound healing process to take shorter time than that of the typical processes, when compared with that of same drugs in microscale systems or commercial standard drugs. These results were confirmed by the histopathological findings. By converting it into the Nanoform, which is extremely important, especially with commonly used antibiotics, novel pharmacological properties were acquired from the antibiotics. The safe uses of DOX/LDH and AMOX/LDH Nanocomposites in this study were approved for biomedical applications.

Synthesis and evaluation of layered double hydroxide/doxycycline and cobalt ferrite/chitosan nanohybrid efficacy on gram positive and gram negative bacteria.

The current study tested the antibacterial activity of layered double hydroxide (LDH), LDH-Doxycycline nanohybrid, Cobalt ferrite nanoparticles (NPs) and Cobalt ferrite-Chitosan nanohybrid against Gram-negative bacteria Escherichia coli. In addition, the study investigated the Cobalt ferrite NPs and Cobalt ferrite-Chitosan nanohybrids against Gram-positive bacteria Staphylococcus aureus. The nanoparticles and nanohybrids were synthesized by a chemical method and characterized by high resolution transmission electron microscope (HRTEM), X-ray diffraction (XRD), and Fourier transformation Infra-red Spectroscopy (FTIR). Multi-point Brunauer-Emmet-Teller (BET) method determined the specific surface area while Barrett-Joyner-Halenda for (BJH) figured the corresponding specific pore volume and pore size and Zetasizer ranked the particle size distribution. Minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) measurements besides agar well diffusion method showed the antimicrobial activity of the nanoparticles. The results revealed no antibacterial activity of the LDH and Cobalt ferrite NPs alone. Meanwhile, the Cobalt ferrite-Chitosan nanohybrid and LDH-Doxycycline showed a high activity antibacterial effect.