Clinical Manifestations and Outcomes of Budd-Chiari Syndrome in Children: A Single-Centre Study.

Introduction Budd-Chiari syndrome (BCS) is a rare cause of ascites in children, and its clinical manifestation depends upon the extent and rapidity of the occlusion of hepatic veins. This study aimed to identify the clinical manifestations, causes, treatment options, and outcomes of BCS in children. Materials and methods A retrospective descriptive study of BCS in children under 15 years of age was conducted. This study was approved by the Pakistan Kidney and Liver Institute and Research Centre on June 23, 2023, with approval number 0128. The patients' medical records from December 2020 to July 2023 were obtained from Sisoft Healthcare Information System. In this study, we employ a set of predetermined questions to retrieve relevant data retrospectively and then organise it in Excel spreadsheets. SPSS version 26 (Armonk, NY: IBM Corp.) was used to analyse the data. Categorical variables are shown as frequencies (%), while continuous variables are reported as mean±SD. Results Of 37 (n) patients diagnosed with BCS, 19 (51.35%) were male and 18 (48.65%) were female. The mean age of presentation was 9.8±4.1 years. Ascites are the predominant clinical manifestation (100%), followed by hepatomegaly (37.8%). A total of 45.9% of patients had deranged liver function tests. Chronic BCS is the predominant mode of presentation. Protein C deficiency was present in nine patients (24.3%), two patients (5.4%) had protein S deficiency and two patients (5.4%) had antithrombin III deficiency. Hepatic veins exhibited the highest incidence of obstruction (73.0%). Liver biopsies were done in 15 (40.54%) patients to determine the staging of fibrosis. Eight patients (21.62%) had undergone radiological interventions, two patients had liver transplants and the rest were treated with medications, including anticoagulants. Conclusion BCS can present in acute, subacute or chronic forms. Ascites and hepatomegaly should raise the suspicion of BCS in children. Common radiological findings are non-visualisation of the hepatic veins. BCS has a wide range of aetiologies and treatment options. Protein C deficiency is the most predominant procoagulant disorder. Radiological interventions during the acute and subacute forms of BCS usually have excellent results. Liver transplant remains the definite treatment.

Synthesis of Porous Biochar Containing Graphitic Carbon Derived From Lignin Content of Forestry Biomass and Its Application for the Removal of Diclofenac Sodium From Aqueous Solution.

Porous biochar containing graphitic carbon materials have received great attention from various disciplines, especially for environmental pollutant treatment, due to their cost-effective and specific textural properties. This study exhibited a two-step strategy to compose lignin-porous biochar containing graphitic carbon (LPGC) from pitch pine sawdust and investigated its adsorptive removal for diclofenac sodium (DCF) from an aqueous solution. Sulfuric acid (H2SO4) was utilized to obtain lignin content from biomass and potassium ferrate (K2FeO4) and was adopted to fulfill the synchronous carbonization and graphitization of LPGC. Through slow pyrolysis in atmospheric N2 (900°C - 2 h), the structure of the as-prepared sample was successfully modified. Using SEM images, a stripped layer structure was observed on the H2SO4-treated sample for both one-step and two-step activated samples, indicating the pronounced effect of H2SO4 in the layering of materials. K2FeO4 acted as an activator and catalyst to convert biomass into the porous graphitic structure. The BET surface area, XRD and Raman spectra analyses demonstrated that LPGC possessed a micro/mesoporous structure with a relatively large surface area (457.4 m2 g-1) as well as the presence of a graphitic structure. Further adsorption experiments revealed that LPGC exhibited a high DCF adsorption capacity (qmax = 159.7 mg g-1 at 298 K, pH = 6.5). The effects of ambient conditions such as contact time, solution pH, temperature, ionic strength, electrolyte background on the uptake of DCF were investigated by a batch adsorption experiment. Results indicated that the experimental data were best fitted with the pseudo second-order model and Langmuir isotherm model. Furthermore, the adsorption of DCF onto the LPGC process was spontaneous and endothermic. Electrostatic interaction, H-bonding interaction, and π-π interaction are the possible adsorption mechanisms. The porous biochar containing graphitic carbon obtained from the lignin content of pitch pine sawdust may be a potential material for eliminating organic pollutants from water bodies.

Efficient Removal of Diclofenac from Aqueous Solution by Potassium Ferrate-Activated Porous Graphitic Biochar: Ambient Condition Influences and Adsorption Mechanism.

Porous graphitic biochar was synthesized by one-step treatment biomass using potassium ferrate (K2FeO4) as activator for both carbonization and graphitization processes. The modified biochar (Fe@BC) was applied for the removal of diclofenac sodium (DCF) in an aqueous solution. The as-prepared material possesses a well-developed micro/mesoporous and graphitic structure, which can strengthen its adsorption capacity towards DCF. The experimental results indicated that the maximum adsorption capacity (qmax) of Fe@BC for DCF obtained from Langmuir isotherm simulation was 123.45 mg·L-1 and it was a remarkable value of DCF adsorption in comparison with that of other biomass-based adsorbents previously reported. Thermodynamic quality and effect of ionic strength studies demonstrated that the adsorption was a endothermic process, and higher environmental temperatures may be more favorable for the uptake of DCF onto Fe@BC surface; however, the presence of NaCl in the solution slightly obstructed DCF adsorption. Adsorption capacity was found to be decreased with the increase of solution pH. Additionally, the possible mechanism of the DCF adsorption process on Fe@BC may involve chemical adsorption with the presence of H-bonding and π-π interaction. With high adsorption capacity and reusability, Fe@BC was found to be a promising absorbent for DCF removal from water as well as for water purification applications.

Kröhnke pyridines: Rapid and facile access to Mcl-1 inhibitors.

The tumorigenic activity of upregulated Mcl-1 is manifested by binding the BH3 α-helical death domains of opposing Bcl-2 family members, neutralizing them and preventing apoptosis. Accordingly, the development of Mcl-1 inhibitors largely focuses on synthetic BH3 mimicry. The condensation of α-pyridinium methyl ketone salts and α,ß-unsaturated carbonyl compounds in the presence of a source of ammonia, or the Kröhnke pyridine synthesis, is a simple approach to afford highly functionalized pyridines. We adapted this chemistry to rapidly generate low-micromolar inhibitors of Mcl-1 wherein the 2,4,6-substituents were predicted to mimic the i, i + 2 and i + 7 side chains of the BH3 α-helix.

Effects of calcium at toxic concentrations of cadmium in plants.

MAIN CONCLUSION: This review provides new insight that calcium plays important roles in plant growth, heavy metal accumulation and translocation, photosynthesis, oxidative damage and signal transduction under cadmium stress. Increasing heavy metal pollution problems have raised word-wide concerns. Cadmium (Cd), being a highly toxic metal, poses potential risks both to ecosystems and human health. Compared with conventional technologies, phytoremediation, being cost-efficient, highly stable and environment-friendly, is believed to be a promising green technology for Cd decontamination. However, Cd can be easily taken up by plants and may cause severe phytotoxicity to plants, thus limiting the efficiency of phytoremediation. Various researches are being done to investigate the effects of exogenous substances on the mitigation of Cd toxicity to plants. Calcium (Ca) is an essential plant macronutrient that involved in various plant physiological processes, such as plant growth and development, cell division, cytoplasmic streaming, photosynthesis and intracellular signaling transduction. Due to the chemical similarity between Ca and Cd, Ca may mediate Cd-induced physiological or metabolic changes in plants. Recent studies have shown that Ca could be used as an exogenous substance to protect plants against Cd stress by the alleviation of growth inhibition, regulation of metal uptake and translocation, improvement of photosynthesis, mitigation of oxidative damages and the control of signal transduction in the plants. The effects of Ca on toxic concentrations of Cd in plants are reviewed. This review also provides new insight that plants with enhanced Ca level have improved resistance to Cd stress.

Tracing the source of sedimentary organic carbon in the Loess Plateau of China: An integrated elemental ratio, stable carbon signatures, and radioactive isotopes approach.

Soil erosion, which will induce the redistribution of soil and associated soil organic carbon (SOC) on the Earth's surface, is of critically importance for biogeochemical cycling of essential elements and terrestrial carbon sequestration. Despite the importance of soil erosion, surprisingly few studies have evaluated the sources of eroded carbon (C). This study used natural abundance levels of the stable isotope signature (13C) and radioactive isotopes (137Cs and 210Pbex), along with elements ratio (C/N) based on a two end member mixing model to qualitatively and quantitatively identify the sources of sedimentary OC retained by check dam in the Qiaozigou small watershed in the Loess Plateau, China. Sediment profiles (0-200 cm) captured at natural depositional area of the basin was compared to possible source materials, which included: superficial Loess mineral soils (0-20 cm) from three land use types [i.e., grassland (Medicago sativa), forestland (Robinia pseudoacacia.), shrubland (Prunus sibirica), and gully land (Loess parent material.)]. The results demonstrated that SOC in sediments showed significantly negative correlation with pH (P < 0.01), and positive correlation with soil water content (SWC) (P < 0.05). The sedimentary OC was not derived from grasslands or gullies. Forestland and shrubland were two main sources of eroded organic carbon within the surface sediment (0-60 cm deep), except for that in the 20-40 cm soil layer. Radionuclides analyses also implied that the surface sediments retained by check-dams mainly originated from soils of forestland and shrubland. Results of the two end-member mixing model demonstrated that more than 50% SOC (mean probability estimate (MPE) 50.13% via 13C and 60.53% via C/N) in surface sediment (0-20 cm deep) derived from forestland, whereas subsurface sedimentary SOC (20-200 cm) mainly resulted from shrubland (MPE > 50%). Although uncertainties on the sources of SOC in deep soils exist, the soil organic δ13C and C/N is still an effective indicator for sources of sedimentary organic carbon in the deposition zone in the short term (<10 years).

The nanoparticulate Quillaja saponin KGI exerts anti-proliferative effects by down-regulation of cell cycle molecules in U937 and HL-60 human leukemia cells.

Cancer cells are characterized by uncontrolled replication involving loss of control of cyclin dependent kinases (CDKs) and cyclins, and by abolished differentiation. In this study we introduce KGI, which is a nanoparticle with a Quillaja saponin as an active molecule. By the use of RNA array analysis and confirmation at the protein level, we show that KGI affects myeloid leukemia cells (in particular, the U937 monoblast cancer cell) by the following mechanisms: (A) ceasing cell replication via proteasome degradation, (B) down-regulation of key molecules at check points between G1/S and G2/M phases, (C) reduction of thymidine kinase activity, followed by (D) exit to differentiation and production of interleukin-8 (IL-8), eventually leading to apoptosis. Leukemia cell lines (U937 and HL-60 cells) were exposed to KGI for 8 h, after which the drug was removed. The cancer cells did not revert to replication over the following 10 days. Thus our findings suggest that the nanoparticle KGI inhibits proliferation and promotes differentiation in leukemic cells by interfering with the cell cycle process.

Antitumor efficacy and acute toxicity of the novel dipeptide melphalanyl-p-L-fluorophenylalanine ethyl ester (J1) in vivo.

The novel alkylating dipeptide melphalanyl-p-L-fluorophenylalanine ethyl ester (J1) was evaluated for acute toxicity and antitumor activity in mice, with melphalan as a reference. To determine a safe and tolerable dose for efficacy studies the acute toxicity following intravenous injection in the tail vein was monitored using a 14-day schedule with up to four doses. The highest tested dose, 25 micromoles/kg, was considered close to this level, with minor effects on body weight gain but significant effects on hematological parameters. Melphalan and J1 appeared equitoxic with no statistically significant differences. Subsequently a mouse hollow fiber model was employed with subcutaneous implantation of fibers containing human tumor cells. Three different human tumor cell lines as well as two samples of primary human tumor cells (ovarian carcinoma and chronic lymphatic leukemia) were used as tumor models. At the dose level tested there was a marked and statistically significant decrease in both T-cell leukemia CCRF-CEM and small cell lung cancer NCI-H69 tumor cell growth and viability in response to J1 as compared with both placebo and melphalan treated groups. In primary ovarian carcinoma cells only J1 treatment resulted in significant tumor regression (net cell kill). In summary the results indicate that, despite an expected short half time in the blood circulation, the promising in vitro data from the previous studies of J1 seems translatable into the in vivo situation. At equal doses of alkylating units J1, compared to melphalan, was more active in the mouse hollow-fiber model, but showed similar general toxicity.

Tibial lengthening: does the fibula migrate?

A retrospective study of 32 patients who underwent tibial lengthening was performed in order to establish the need for distal tibio-fibular fixation. In 16 patients stabilization of the inferior tibio-fibular joint was carried out and in the other 16 no stabilization was performed. Three established and one new radiographic index of the tibio-fibular relationship at the ankle were used to assess proximal fibular migration. All patients showed proximal migration of the distal fibula, but those without stabilization demonstrated marked migration of the fibula associated with a valgus tendency. The difference between the groups was statistically significant ( <0.001), confirming the need for fibular fixation.

Activity of CHS 828 in primary cultures of human hematological and solid tumors in vitro.

CHS 828 is a pyridyl cyanoguanidine that has shown promising preclinical anticancer activity against various experimental tumor models and is presently being tested in a phase II trial in man. In the present study the fluorometric microculture cytotoxicity assay was used for in vitro evaluation of CHS 828 activity in primary cell cultures from hematological and solid tumors. In total, 156 samples from various diagnoses were tested with 72-h continuous drug exposure. CHS 828 showed high relative in vitro activity against tumor cells from chronic lymphocytic leukemia as well as from acute leukemia and high-grade lymphoma. Activity was also observed in several solid tumor cell samples, although the group as a whole appeared less responsive. CHS 828 was significantly more active against hematological malignancies compared to normal lymphocytes. Correlation analysis with standard drugs revealed low to moderate correlation coefficients. The results show that CHS 828 has potent antitumor activity against primary cultures of human tumor cells from patients and might have a unique mechanism of action.

Temporal effects of the novel antitumour pyridyl cyanoguanidine (CHS 828) on human lymphoma cells.

CHS 828, a novel pyridyl cyanoguanidine, has shown potent antitumour activity both in vitro and in vivo and is currently undergoing phase I evaluation in humans in collaboration with the European Organization for Research and Treatment of Cancer (EORTC). Here we study the temporal effects of CHS 828 on cytotoxicity, protein and DNA synthesis, cellular morphology and ultra structure using the lymphoma cell line U-937 GTB as the primary tumour model. In vitro analysis of tumour cell survival in response to CHS 828 revealed a cytotoxic effect progressively increased as a function of exposure time with maximum efficacy observed after 72 h. Activity of CHS 828 on U-937 GTB cells grown in vivo was also found. CHS 828 induced-cell death was dependent on intact protein synthesis and most cells appeared to lose their membrane integrity in the presence of a relatively well preserved nuclear structure. The results indicate that CHS 828 induced active and delayed cell death with a non-apoptotic morphology.