Spectrodensitometric and ultra-performance liquid chromatographic quantification of dapagliflozin and saxagliptin in their dosage form and human plasma

Purpose: To simultaneously quantify dapagliflozin (DAPA) and saxagliptin (SAX) in a pharmaceutical product and human plasma. Methods: Separation and quantification of DAPA and SAX were performed on pre-coated TLC plates in TLC-densitometric method using a solvent system of chloroform, ethyl acetate and methanol at a volume ratio of 8:1:1 as the mobile phase. The developed spots were scanned at 225 and 210 nm in absorbance mode. Moreover, the studied drugs were concurrently determined in human plasma using ultra-performance liquid chromatography (UPLC). The separation process was carried out in WatersTM Acquity C18 BEH column using a solvent system of 0.02 M KH2PO4 buffer, pH 4; MeOH and acetonitrile (2:1:1, v:v:v) isocratically at a flow speed of 0.5 mL/min. The absorbance of each eluent was read at 220 nm. Results: Concurrent evaluation of DAPA and SAX was carried without separation using TLC-densitometric method, and it was successful in determination of DAPA and SAX in concentration ranges of 10 – 70 μg/band and 5 – 60 μg/band, respectively. In addition, retardation factor (Rf) values for SAX and DAPA were 0.17 and 0.31, respectively. Furthermore, the studied drugs were concurrently determined in human plasma using UPLC, which was sensitive enough to quantify DAPA and SAX in concentration ranges of 100 – 1000 and 20 – 200 ng/mL, respectively. Conclusion: These methods can be utilized for sensitive monitoring of DAPA and SAX in pharmacokinetic and bioequivalence studies

Paclobutrazol Improves Sesame Yield by Increasing Dry Matter Accumulation and Reducing Seed Shattering Under Rainfed Conditions

Several biotic and abiotic stresses significantly decrease the biomass accumulation and seed yield of sesame crops under rainfed areas. However, plant growth regulators (such as Paclobutrazol) can improve the total dry matter and seed production of the sesame crop. The effects of the paclobutrazol application on dry matter accumulation and seed yield had not been studied before in sesame under rainfed conditions. Therefore, a two-year field study during 2018 and 2019 was conducted with key objectives to assess the impacts of paclobutrazol on leaf greenness, leaf area, total dry matter production and partitioning, seed shattering, and seed yield of sesame. Two sesame cultivars (TS-5 and TS-3) were treated with four paclobutrazol concentrations (P0 = Control, P1 = 100 mg L-1, P2 = 200 mg L-1, P3 = 300 mg L-1). The experiment was executed in RCBD-factorial design with three replications. Compared with P0, treatment P3 improved the leaf greenness of sesame by 17%, 38%, and 60% at 45, 85, and 125 days after sowing, respectively. However, P3 treatment decreased the leaf area of sesame by 14% and 20% at 45 and 85 days after sowing than P0, respectively. Compared with P0, treatment P3 increased the leaf area by 46% at 125 days after sowing. On average, treatment P3 also improved the total biomass production by 21% and partitioning in roots, stems, leaves, capsules, and seeds by 23%, 19%, 23%, 22%, and 40%, respectively, in the whole growing seasons as compared to P0. Moreover, under P3 treatment, sesame attained the highest seed yield and lowest seed shattering by 27% and 30%, respectively, compared to P0. This study indicated that by applying the paclobutrazol concentration at the rate of 300 mg L-1 in sesame, the leaf greenness, leaf areas, biomass accumulation, partitioning, seed yield, and shatter resistance could be improved. Thus, the optimum paclobutrazol level could enhance the dry matter accumulation and seed production capacity of sesame by decreasing shattering losses under rainfed conditions

Preferential Solvation Study of Rosuvastatin in the {PEG400 (1) + Water (2)} Cosolvent Mixture and GastroPlus Software-Based In Vivo Predictions

Article claims that rosuvastatin (RST) is a poorly water-soluble drug responsible for limited in vivo dissolution and subsequently low oral systemic absorption (poor bioavailability). The results of inverse Kirkwood–Buff integrals showed the PS of RST by PEG400 as observed in all studied ratios of the binary mixture

Preferential Solvation Study of the Synthesized Aldose Reductase Inhibitor (SE415) in the {PEG 400 (1) + Water (2)} Cosolvent Mixture and GastroPlus-Based Prediction

This article presents evidence that the binary cosolvent system can be a promising approach for enhanced oral absorption in controlling diabetes mellitus (DM) and associated complications in humans

Can sulphur improve the nutrient uptake, partitioning, and seed yield of sesame?

Sulphur (S) is considered to improve the nutrient uptake of plants due to its synergistic relationship with other nutrients. This could ultimately enhance the seed yield of oilseed crops. However, there is limited quantitative information on nutrient uptake, distribution, and its associated impacts on seed yield of sesame under the S application. Thus, a two-year field study (2018 and 2019) was conducted to assess the impacts of different S treatments (S-0 = Control, S-20 = 20, S-40 = 40, and S-60 = 60 kg ha(-1)) on total dry matter production, nitrogen, phosphorus, potassium, S uptake and distribution at the mid-bloom stage and physiological maturity. Furthermore, treatment impacts were studied on the number of capsules per plant, number of seeds per capsule, thousand seed weight, and seed yield at physiological maturity in sesame. Compared to S-0, over the years, treatment S-40 significantly increased the total uptake of nitrogen, phosphorus, potassium, and S (by 13, 22, 11% and 16%, respectively) at physiological maturity, while their distribution by 13, 36, 14, and 24% (in leaves), 12, 15, 11, and 15% (in stems), 15, 42, 18, and 10% (in capsules), and 14, 22, 9, and 15% (in seeds), respectively. Enhanced nutrient uptake and distribution in treatment S-40 improved the total biomass accumulation (by 28%) and distribution in leaves (by 34%), stems (by 27%), capsules (by 26%), and seeds (by 28%), at physiological maturity, as compared to S-0. Treatment S-40 increased the number of capsules per plant (by 13%), number of seeds per capsule (by 11%), and thousand seed weight (by 6%), compared to S-0. Furthermore, over the years, relative to control, sesame under S-40 had a higher seed yield by 28% and enhanced the net economic returns by 44%. Thus, our results suggest that optimum S level at the time of sowing improves the nutrient uptake and distribution during the plant lifecycle, which ultimately enhances total dry matter accumulation, seed yield, and net productivity of sesame

The integrative bioinformatics approaches to predict the xanthohumol as anti-breast cancer molecule : targeting cancer cells signaling PI3K and AKT kinase pathway

DATA AVAILABILITY STATEMENT : The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.BACKGROUND : Breast cancer is the most common type of cancer in women, and vast research is being conducted throughout the world for the treatment of this malignancy by natural products using various computational approaches. Xanthohumol, a prenylated flavonoid, is known for its anticancer activity; however, the mechanism behind its action is still in the preliminary stage. METHODS : The current study aimed to analyze the efficacy of xanthohumol compared to the currently available anticancer drugs targeting phosphoinositide-3-kinase (PI3K), serine/threonine kinase (AKT) receptors, and human epidermal growth factor receptor 2 (HER2) for breast cancer treatment through in silico analysis. RESULTS : The result revealed that the target compound showed significant binding affinity to targets within the PI3K, AKT, and HER2 signaling pathways with a binding energy of −7.5, −7.9, and −7.9 kcal/mol, respectively. Further prediction studies were then made concerning this compound’s absorption, distribution, metabolism, and excretion (ADME) as well as drug-likeness properties, resulting in its oral bioavailability with only a single violation of Lipinski’s rule of five. CONCLUSIONS : The finding revealed the ability of xanthohumol to bind with multiple cancer cell signaling molecules including PI3K, AKT kinase, and HER2. The current novel study opened the door to advancing research into the management and treatment of breast cancer.Princess Nourah bint Abdulrahman University Researchers Supporting Project.https://www.frontiersin.org/journals/oncologyMedical OncologySDG-03:Good heatlh and well-bein

Enhanced drug delivery and wound healing potential of berberine-loaded chitosan–alginate nanocomposite gel: characterization and in vivo assessment

Berberine–encapsulated polyelectrolyte nanocomposite (BR–PolyET–NC) gel was developed as a long-acting improved wound healing therapy. BR–PolyET–NC was developed using an ionic gelation/complexation method and thereafter loaded into Carbopol gel. Formulation was optimized using Design-Expert® software implementing a three-level, three-factor Box Behnken design (BBD). The concentrations of polymers, namely, chitosan and alginate, and calcium chloride were investigated based on particle size and %EE. Moreover, formulation characterized in vitro for biopharmaceutical performances and their wound healing potency was evaluated in vivo in adult BALB/c mice. The particle distribution analysis showed a nanocomposite size of 71 ± 3.5 nm, polydispersity index (PDI) of 0.45, ζ–potential of +22 mV, BR entrapment of 91 ± 1.6%, and loading efficiency of 12.5 ± 0.91%. Percentage drug release was recorded as 89.50 ± 6.9% with pH 6.8, thereby simulating the wound microenvironment. The in vitro investigation of the nanocomposite gel revealed uniform consistency, well spreadability, and extrudability, which are ideal for topical wound use. The analytical estimation executed using FT-IR, DSC, and X-ray diffraction (XRD) indicated successful formulation with no drug excipients and without the amorphous state. The colony count of microbes was greatly reduced in the BR–PolyET–NC treated group on the 15th day from up to 6 CFU compared to 20 CFU observed in the BR gel treated group. The numbers of monocytes and lymphocytes counts were significantly reduced following healing progression, which reached to a peak level and vanished on the 15th day. The observed experimental characterization and in vivo study indicated the effectiveness of the developed BR–PolyET–NC gel toward wound closure and healing process, and it was found that >99% of the wound closed by 15th day, stimulated via various anti-inflammatory and angiogenic factors

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised