Synthesis, Characterization, and In Vivo Anti-Cancer Activity of New Metal Complexes Derived from Isatin-N(4)antipyrinethiosemicarbazone Ligand Against Ehrlich Ascites Carcinoma Cells

The current study aimed to synthesize new metal coordination complexes with potential biomedical applications. Metal complexes were prepared via the reaction of isatin-N(4)anti- pyrinethiosemicarbazone ligand 1 with Cu(II), Ni(II), Co(II), Zn(II), and Fe(III) ions. The obtained metal complexes 2–12 were characterized using elemental, spectral (1H-NMR, EPR, Mass, IR, UV-Vis) and thermal (TGA) techniques, as well as magnetic moment and molar conductance measurements. In addition, their geometries were studied using EPR and UV–Vis spectroscopy. To evaluate the in vivo anti-cancer activities of these complexes, the ligand 1 and its metal complexes 2, 7 and 9 were tested against solid tumors. The solid tumors were induced by subcutaneous (SC) injection of Ehrlich ascites carcinoma (EAC) cells in mice. The impact of the selected complexes on the reduction of tumor volume was determined. Also, the expression levels of vascular endothelial growth factor (VEGF) and cysteine aspartyl-specific protease-7 (caspase-7) in tumor and liver tissues of mice bearing EAC tumor were determined. Moreover, their effects on alanine transaminase (ALT), aspartate transaminase (AST), albumin, and glucose levels were measured. The results revealed that the tested compounds, especially complex 9, reduced tumor volume, inhibited the expression of VEGF, and induced the expression of caspase-7. Additionally, they restored the levels of ALT, AST, albumin, and glucose close to their normal levels. Taken together, our newly synthesized metal complexes are promising anti-cancer agents against solid tumors induced by EAC cells as supported by the inhibition of VEGF and induction of caspase-7

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Using Biochar and Nanobiochar of Water Hyacinth and Black Tea Waste in Metals Removal from Aqueous Solutions

The treatment of heavy metal-contaminated water is challenging. The use of nanomaterials from many environmental wastes is promising for removing metals and contaminants from aqueous solutions. This study is novel in using nanobiochar of water hyacinth (WH) and black tea waste (TW) as a promising approach to water decontamination owing to its unique properties that play an effective role in metal adsorption. The mono- and multi-adsorption systems of cadmium (Cd), chromium (Cr), and nickel (Ni) on biochar and nanobiochar of water hyacinths (BWH and NBWH) and black tea waste (BTW and NBTW) were investigated in this study as potential low-cost and environmentally friendly absorbents for the removal of previously mentioned heavy metals (HMs) from aqueous solutions. The WH and TW were collected from the locality, prepared, and kept until used in the experiment. Nanobiochar was prepared by grinding, characterizing, and storing in airtight containers until used. A batch experiment was designed in mono- and competitive systems to study the adsorption equilibrium behavior of HMs on biochar and nanobiochars. The Freundlich and Langmuir isotherm models were fitted to the mono- and competitive-adsorption equilibrium results. The Freundlich isotherm model provided a better fit. Furthermore, it was noticed that NBWH and NBWT efficiently removed the Cd in the mono-system by ≥99.8, especially in the smaller concentration, while NBWT and BTW removed ≥99.8 and 99.7% in the competitive system, respectively. In the mono- and competitive systems, the nanobiochars of NBTW removed more than 98.8 of Cr. The sorbents were less efficient in Ni removal compared to Cd and Cr. However, their effectiveness was very high also. The results revealed that Cd was the highest metal removed by sorbents, nanobiochars were better than biochars to remove the HMs, and the results also indicated that co-occurrence of multi-metals might fully occupy the adsorption sites on biochars and nanobiochars

Using Biochar and Nanobiochar of Water Hyacinth and Black Tea Waste in Metals Removal from Aqueous Solutions

The treatment of heavy metal-contaminated water is challenging. The use of nanomaterials from many environmental wastes is promising for removing metals and contaminants from aqueous solutions. This study is novel in using nanobiochar of water hyacinth (WH) and black tea waste (TW) as a promising approach to water decontamination owing to its unique properties that play an effective role in metal adsorption. The mono- and multi-adsorption systems of cadmium (Cd), chromium (Cr), and nickel (Ni) on biochar and nanobiochar of water hyacinths (BWH and NBWH) and black tea waste (BTW and NBTW) were investigated in this study as potential low-cost and environmentally friendly absorbents for the removal of previously mentioned heavy metals (HMs) from aqueous solutions. The WH and TW were collected from the locality, prepared, and kept until used in the experiment. Nanobiochar was prepared by grinding, characterizing, and storing in airtight containers until used. A batch experiment was designed in mono- and competitive systems to study the adsorption equilibrium behavior of HMs on biochar and nanobiochars. The Freundlich and Langmuir isotherm models were fitted to the mono- and competitive-adsorption equilibrium results. The Freundlich isotherm model provided a better fit. Furthermore, it was noticed that NBWH and NBWT efficiently removed the Cd in the mono-system by ≥99.8, especially in the smaller concentration, while NBWT and BTW removed ≥99.8 and 99.7% in the competitive system, respectively. In the mono- and competitive systems, the nanobiochars of NBTW removed more than 98.8 of Cr. The sorbents were less efficient in Ni removal compared to Cd and Cr. However, their effectiveness was very high also. The results revealed that Cd was the highest metal removed by sorbents, nanobiochars were better than biochars to remove the HMs, and the results also indicated that co-occurrence of multi-metals might fully occupy the adsorption sites on biochars and nanobiochars

Development of canagliflozin nanocrystals sublingual tablets in the presence of sodium caprate permeability enhancer: formulation optimization, characterization, in-vitro, in silico, and in-vivo study

AbstractCanagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor (SGLT2) that lowers albuminuria in type-2 diabetic patients, cardiovascular, kidney, and liver disease. CFZ is classified as class IV in the Biopharmaceutical Classification System (BCS) and is characterized by low permeability, solubility, and bioavailability, most likely attributed to hepatic first-pass metabolism. Nanocrystal-based sublingual formulations were developed in the presence of sodium caprate, as a wetting agent, and as a permeability enhancer. This formulation is suitable for children and adults and could enhance solubility, permeability, and avoid enterohepatic circulation due to absorption through the sublingual mucosa. In the present study, formulations containing various surfactants (P237, P338, PVA, and PVP K30) were prepared by the Sono-homo-assisted precipitation ion technique. The optimized formula prepared with PVP-K30 showed the smallest particle size (157 ± 0.32 nm), Zeta-potential (−18 ± 0.01), and morphology by TEM analysis. The optimized formula was subsequently formulated into a sublingual tablet containing Pharma burst-V® with a shorter disintegration time (51s) for the in-vivo study. The selected sublingual tablet improved histological and biochemical markers (blood glucose, liver, and kidney function), AMP-activated protein kinase (AMPK), and protein kinase B (AKT) pathway compared to the market formula, increased CFZ’s antidiabetic potency in diabetic rabbits, boosted bioavailability by five-fold, and produced faster onset of action. These findings suggest successful treatment of diabetes with CFZ nanocrystal-sublingual tablets