Synergistic Effect In Treatment Research Articles

A mechanistic study of the synergistic and counter effects of ultrasonic and solvent treatment on the rheology and asphaltene structure of heavy crude oil

Production from heavy oil reservoirs faces challenges, such as accumulating heavy hydrocarbon materials like asphaltenes near the wellbore, resulting in low recovery rates. To enhance recovery and prevent formation damage, methods often focus on reducing oil viscosity. Solvents and ultrasonic waves have proven effective in this regard, though challenges related to asphaltene aggregation and structural changes persist. This study explores the impact of simultaneously applying ultrasonic radiation and solvents on crude oil's viscosity and asphaltene structure. Toluene and n-heptane, representing aromatic and paraffinic solvents, were employed. Viscosity measurements and Fourier transform infrared spectroscopy tests were conducted on sonicated crude oil diluted with solvents and solvent-diluted crude oil subjected to sonication. Results were compared to untreated and separately treated crude oil samples. The study found that the most effective viscosity reduction method involved blending sonicated oil with toluene under optimal radiation time and concentration conditions. Two primary mechanisms for viscosity reduction were identified. Firstly, there was the dissolution and aggregation of asphaltene clusters. Secondly, chemical changes in asphaltene molecular structure were observed, altering the ratio of aromatic rings to aliphatic chains. This research offers potential insights into how ultrasonication and solvation interact to modify crude oil structure.

Synergistic effect of CaCO3 addition and cold atmospheric plasma treatment on the surface evolution, mechanical properties, and in-vitro degradation behavior of FDM-printed PLA scaffolds

The ease of processing and biocompatibility of polylactic acid (PLA) have made it a widely used material for fused deposition modeling (FDM)-based 3D printing. In spite of this, PLA suffers from some limitations for its extensive use in tissue engineering applications, including poor wettability, low degradation rate, and insufficient mechanical properties. To address the previously mentioned limitations, this study examined how combining in-process cold atmospheric plasma treatment with the inclusion of CaCO3 influences the properties of FDM-printed PLA scaffolds. Differential scanning calorimetry results showed that by incorporating CaCO3 micro-particles into the PLA matrix, heterogeneous nucleation promoted the matrix's crystalline content. Scanning electron microscopy analysis revealed that the surface of the PLA-CaCO3 scaffold exhibited increased roughness and improved interlayer bonding after undergoing plasma treatment. Atomic force microscopy revealed a significant (up to 80-fold) increase in the roughness value of PLA scaffolds after the incorporation of CaCO3 and subsequent cold plasma treatment. Furthermore, X-ray photoelectron spectroscopy analysis indicated that atmospheric plasma treatment substantially increased the presence of oxygen-containing bonds, leading to a significant reduction in the water contact angle, which decreased from 89° to 37°. According to the tensile test, the tensile modulus (634.1 MPa) and ultimate tensile strength (25.4 MPa) of PLA were markedly increased and reached 914.3 and 37.2 MPa, respectively, for the plasma-treated PLA-CaCO3 (PT-PLA-CaCO3). Additionally, the in-vitro degradation test showed that PT-PLA-CaCO3 scaffold exhibited higher degradation rate compared to the PLA-CaCO3 sample. Based on the obtained results, it appears that in-process cold atmospheric plasma treatment could serve as an efficient and straightforward method to enhance the properties of 3D-printed composite parts, particularly for tissue engineering applications.

BIBR1532 inhibits proliferation and enhances apoptosis in multiple myeloma cells by reducing telomerase activity

Background Multiple myeloma (MM) is a rare haematological disorder with few therapeutic options. BIBR1532, a telomerase inhibitor, is widely used in cancer treatment and has promising outcomes. In this study, we investigated the efficacy and mechanism of action of BIBR1532 in MM. Methods K562 and MEG-01 cells were cultured with BIBR1532 at different concentrations. After 24 and 48 h, cell survival was analyzed. Next, these cells were cultured with 25 and 50 µM BIBR1532 for 48 h, then, cell proliferation, apoptosis, and the expression of the telomerase activity related markers were tested by 5-Ethynyl-2′-deoxyuridine (EdU) staining, flow cytometric analysis, western blot and quantitative real-time PCR (qRT-PCR), respectively. Expression of Bcl-xL, Bad, Survivin, phosphorylation of PI3K, AKT, mTOR, ERK1/2, and MAPK were tested via western blotting. Further experiments were conducted to evaluate the synergistic effects of BIBR1532 and doxorubicin (Dox) or bortezomib (Bor). Results BIBR1532 inhibited K562 and MEG-01 cell survival in a dose- and time-dependent manner. In addition, BIBR1532 hindered cell proliferation while promoting apoptosis, and this effect was enhanced by increasing the BIBR1532 concentration. Moreover, BIBR1532 inhibited TERT and c-MYC expression, PI3K, AKT, mTOR phosphorylation, and facilitated ERK1/2 and MAPK phosphorylation. Additionally, BIBR1532 combined with Dox or Bor showed synergistic effects in MM treatment. Conclusion BIBR1532 inhibits proliferation and promotes apoptosis in MM cells by inhibiting telomerase activity. Additionally, BIBR1532 combined with Dox or Bor exhibited synergistic effects, indicating that BIBR1532 may be a novel medicine for the treatment of MM.

Catalytic hydrothermal co-liquefaction of sewage sludge and agricultural biomass for promoting advanced biocrude production

Conventional hydrothermal liquefaction (HTL) technology is inhibited by the complicated feedstock properties, low biocrude yield, and poor biocrude quality. Herein, this work aimed to propose a novel catalytic hydrothermal co-liquefaction (catalytic co-HTL) route for enhancing high-quality biocrude production. Four representative biowastes were applied to determine the synergistic effects in co-HTL treatment. Binary sewage sludge (SS)/wheat straw (WS) presented the highest synergistic effect (14.05%) on biocrude production. Furthermore, homogenous and heterogeneous catalysts (i.e., Na2CO3, HY, SSB, CSB, and Ni@CSB) were comprehensively tested during catalytic co-HTL of binary SS/WS. Biocrude produced over Ni@CSB revealed the highest carbon content at 75.5% and HHV at 36.96 MJ/kg, due to the deoxygenation and desulfurization reactions enhanced by Ni@CSB. Thermalgravimetric behaviors and kinetic studies of biocrude degradation were further analyzed. Moreover, the byproducts (hydrochar and gaseous phase) were characterized. Overall, this study provides an effective and promising route to valorize biowastes into green high-quality biocrude.

Ear keloids: An innovative 3-steps combined treatment.

An excessive proliferation of fibroblasts and collagen synthesis after an injury may lead to a benign fibrous tumor, known as keloid, which does not regress spontaneously. Earlobes are a very frequent site of onset, since after a trauma (i.e., piercing) keloids may develop either on the helix and on the anterior or posterior lobe, from a few months up to several years after the injury. To report the effectiveness of a combined protocol of CO2 laser + Dye laser + a portable Blue LED Light medical device for Photobiomodulation Therapy (EmoLED®). Fifty-two patients with a total of 56 ear keloids have been treated in the same session with a single CO2 laser procedure + a pulsed Dye laser procedure with an adjunctive EmoLED® procedure for 3 up to 6 min. A monthly follow-up has been performed with an adjunctive EmoLED® session in case of signs of inflammation. Among 56 treated keloids, 89.3% of them (50/56) did not recur during a follow-up period (from 6 up to 24 months, mean 16.3 months) while six keloids recurred (6/56, 10.7%) with mild thickening of the scar, thus requiring further treatments. Even if an excellent outcome obtained by the synergistic effect of combined laser treatments has already been described (i.e., CO2 laser + Dye Laser), the present study showed the adjuvant procedure with EmoLED® can reduce significantly the risk of keloids recurrences.

Glutathione promotes the synergistic effects of venetoclax and azacytidine against myelodysplastic syndrome‑refractory anemia by regulating the cell cycle.

Azacitidine is a DNA methyltransferase inhibitor that has been used as a singular agent for the treatment of myelodysplastic syndrome-refractory anemia with excess blast-1 and -2 (MDS-RAEB I/II). However, recurrence and overall response rates following this treatment remain unsatisfactory. The combination of azacitidine and venetoclax has been used for the clinical treatment of a variety of hematological diseases due to the synergistic killing effect of the two drugs. Venetoclax is a BCL-2 inhibitor that can inhibit mitochondrial metabolism. In addition, azacitidine has been shown to reduce the levels of myeloid cell leukemia 1 (MCL-1) in acute myeloid leukemia cells. MCL-1 is an anti-apoptotic protein and a potential source of resistance to venetoclax. However, the mechanism underlying the effects of combined venetoclax and azacitidine treatment remains to be fully elucidated. In the present study, the molecular mechanism underlying the impact of venetoclax on the efficacy of azacitidine was investigated by examining its effects on cell cycle progression. SKM-1 cell lines were treated in vitro with 0-2 µM venetoclax and 0-4 µM azacytidine. After 24, 48 and 72 h of treatment, the impact of the drugs on the cell cycle was assessed by flow cytometry. Following drug treatment, changes in cellular glutamine metabolism pathways was analyzed using western blotting (ATF4, CHOP, ASCT2, IDH2 and RB), quantitative PCR (ASCT2 and IDH2), liquid chromatography-mass spectrometry (α-KG, succinate and glutathione) and ELISA (glutamine and glutaminase). Venetoclax was found to inhibit mitochondrial activity though the alanine-serine-cysteine transporter 2 (ASCT2) pathway, which decreased glutamine uptake. Furthermore, venetoclax partially antagonized the action of azacitidine through this ASCT2 pathway, which was reversed by glutathione (GSH) treatment. These results suggest that GSH treatment can potentiate the synergistic therapeutic effects of venetoclax and azacitidine combined treatment on a myelodysplastic syndrome-refractory anemia cell line at lower concentrations.

Recombinant Prevotella melaninogenica α-1,3 glucanase and Capnocytophaga ochracea α-1,6 glucanase as enzymatic tools for in vitro degradation of S. mutans biofilms.

Dental biofilms represent a serious oral health problem playing a key role in the development of caries and other oral diseases. In the present work, we cloned and expressed in E. coli two glucanases, Prevotella melaninogenica mutanase (PmGH87) and Capnocytophaga ochracea dextranase (CoGH66), and characterized them biochemically and biophysically. Their three-dimensional structures were elucidated and discussed. Furthermore, we tested the capacity of the enzymes to hydrolyze mutan and dextran to prevent formation of Streptococcus mutans biofilms, as well as to degrade pre- formed biofilms in low and abundant sugar conditions. The percentage of residual biofilm was calculated for each treatment group in relation to the control, as well as the degree of synergism. Our results suggest that both PmGH87 and CoGH66 are capable of inhibiting biofilm formation grown under limited or abundant sucrose conditions. Degradation of pre-formed biofilms experiments reveal a time-dependent effect for the treatment with each enzyme alone. In addition, a synergistic and dose-dependent effects of the combined enzymatic treatment with the enzymes were observed. For instance, the highest biomass degradation was 95.5% after 30min treatment for the biofilm grown in low sucrose concentration, and 93.8% after 2h treatment for the biofilm grown in sugar abundant condition. Strong synergistic effects were observed, with calculated degree of synergism of 5.54 and 3.18, respectively and their structural basis was discussed. Jointly, these data can pave the ground for the development of biomedical applications of the enzymes for controlling growth and promoting degradation of established oral biofilms.

Conductive Passivator and Dipole Layer Mixture Enabling High‐Performance Stable Perovskite Photoelectrode‐Based Solar Water Splitting

AbstractRecently, lead halide perovskites have attracted significant attention as promising absorber materials for photoelectrochemical (PEC) solar water splitting. However, charge‐accumulation‐induced ion migration at the interface causes perovskite degradation and efficiency loss. To suppress the charge accumulation and improve the PEC performance of the perovskite photoanode, a simple interface engineering is proposed by decorating the SnO2/perovskite interface with a mixture of polyethylenimine ethoxylated (PEIE) and chlorobenzenesulfonic acid (CBSA). The mixed CBSA+PEIE treatment effectively passivates the oxygen vacancies in SnO2 and adjusts the band alignment between SnO2 and the perovskite. The synergistic effects of the mixture treatment facilitate an effective carrier extraction at the SnO2/perovskite interface, enhance the PEC performance, and improve the stability of the device. The perovskite photoanode exhibits an impressive applied bias photon‐to‐current efficiency of 12.9% with an outstanding durability for 225 h. Furthermore, an unbiased solar water splitting is achieved using all the perovskite photoelectrodes, resulting in a remarkable unassisted solar‐to‐hydrogen efficiency of 10.9% and a continuous 22 h stable operation.

E2F8 exerts cancer-promoting effects by transcriptionally activating RRM2 and E2F8 knockdown synergizes with WEE1 inhibition in suppressing lung adenocarcinoma

Ribonucleotide reductase (RR) is a rate-limiting enzyme that facilitates DNA replication and repair by reducing nucleotide diphosphates (NDPs) to deoxyribonucleotide diphosphates (dNDPs) and is thereby crucial for cell proliferation and cancer development. The E2F family of transcription factors includes key regulators of gene expression involved in cell cycle control. In this study, E2F8 expression was significantly increased in most cancer tissues of lung adenocarcinoma (LUAD) patients and was correlated with the expression of RRM2 through database and clinical samples analysis. The protein expression of E2F8 and RRM2 were positively correlated with tumor–node–metastasis (TNM) pathological stage, and high expression of E2F8 and RRM2 predicted a low 5-year overall survival rate in LUAD patients. Overexpression and knockdown experiments showed that E2F8 was essential for LUAD cell proliferation, DNA synthesis, and cell cycle progression, which were RRM2-dependent. Reporter gene, ChIP-qPCR, and DNA pulldown–Western blot assays indicated that E2F8 activated the transcription of the RRM2 gene by directly binding with the RRM2 promoter in LUAD cells. Previous studies indicated that inhibition of WEE1 kinase can suppress the phosphorylation of CDK1/2 and promote the degradation of RRM2. We further showed here that the combination of E2F8 knockdown with MK-1775, an inhibitor of WEE1 being evaluated in clinical trials, synergistically suppressed proliferation and promoted apoptosis of LUAD cells in vitro and in vivo. Thus, this study reveals a novel role of E2F8 as a proto-oncogenic transcription activator by activating RRM2 expression in LUAD, and targeting both the transcription and degradation mechanisms of RRM2 could produce a synergistic inhibitory effect for LUAD treatment in addition to conventional inhibition of RR enzyme activity.

Effect of sequential release of sirolimus and rosuvastatin using silk fibroin microneedle to prevent intimal hyperplasia

Intimal hyperplasia (IH) is a major cause of vascular restenosis after bypass surgery, which progresses as a series of processes from the acute to chronic stage in response to endothelial damage during bypass grafting. A strategic localized drug delivery system that reflects the pathophysiology of IH and minimizes systemic side effects is necessary. In this study, the sequential release of sirolimus, a mechanistic target of rapamycin (mTOR) inhibitor, and statin, an HMG-COA inhibitor, was realized as a silk fibroin-based microneedle device in vivo. The released sirolimus in the acute stage reduced neointima (NI) and vascular fibrosis through mTOR inhibition. Furthermore, rosuvastatin, which was continuously released from the acute to chronic stage, reduced vascular stiffness and apoptosis through the inactivation of Yes-associated protein (YAP). The sequential release of sirolimus and rosuvastatin confirmed the synergistic treatment effects on vascular inflammation, VSMC proliferation, and ECM degradation remodeling through the inhibition of transforming growth factor (TGF)-beta/NF-κB pathway. These results demonstrate the therapeutic effect on preventing restenosis with sufficient vascular elasticity and significantly reduced IH in response to endothelial damage. Therefore, this study suggests a promising strategy for treating coronary artery disease through localized drug delivery of customized drug combinations.

Synergistic effects of sequential light treatment with 222-nm/405-nm and 280-nm/405-nm wavelengths on inactivation of foodborne pathogens.

Light-based technologies of different wavelengths can inactivate pathogenic microorganisms, but each wavelength has its limitations. This work explores the potential of sequential treatments with different wavelengths for enhancing the disinfection performance of individual treatments by employing various bactericidal mechanisms. The effectiveness, inactivation kinetics, and bactericidal mechanisms of treatments with 222/405, 280/405, and 405 nm alone against Escherichia coli O157:H7, Listeria monocytogenes, Staphylococcus aureus, Salmonella Typhimurium, and Pseudomonas aeruginosa were evaluated. Inactivation experiments were performed in thin liquid bacterial suspensions that were treated either individually with 48 h of 405-nm light or sequentially with (i) 30 s of 222-nm far-UV-C light, followed by 48 h of 405-nm light, or (ii) 30 s of 280-nm far-UV-C light, followed by 48 h of 405-nm light. Survivors were recovered and enumerated by standard plate counting. All inactivation curves were non-linear and followed the Weibull model (0.99 ≥ R2 ≥ 0.70). Synergistic effects were found for E. coli, L. monocytogenes, and S. Typhimurium, with maximum inactivation level increases of 2.9, 3.3, and 1.1 log CFU after the sequential treatments, respectively. Marginal synergy was found for S. aureus, and an antagonistic effect was found for P. aeruginosa after sequential treatments. Significant differences in reactive oxygen species accumulation were found (P < 0.05) after various treatment combinations, and the performance of sequential treatments was correlated with cellular oxidative damage. The sequential wavelength treatments proposed demonstrate the potential for enhanced disinfection of multiple foodborne pathogens compared with individual wavelength treatments, which can have significant food safety benefits. IMPORTANCE Nonthermal light-based technologies offer a chemical-free method to mitigate microbial contamination in the food and healthcare industries. However, each individual wavelength has different limitations in terms of efficacy and operating conditions, which limits their practical applicability. In this study, bactericidal synergism of sequential treatments with different wavelengths was identified. Pre-treatments with 280 and 222 nm enhanced the disinfection performance of follow-up 405-nm treatments for multiple foodborne pathogens by inducing higher levels of cellular membrane damage and oxidative stress. These findings deliver useful information for light equipment manufacturers, food processors, and healthcare users, who can design and optimize effective light-based systems to realize the full potential of germicidal light technologies. The results from the sequential treatments offer practical solutions to improve the germicidal efficacy of visible light systems, as well as provide inspiration for future hurdle disinfection systems design, with a positive impact on food safety and public health.

Effects of slightly acidic electrolysed water spraying and ultraviolet C light-emitting diode irradiation combination on the inactivation kinetics of Escherichia coli biofilms on food contact surfaces

In this study, we aimed to quantitatively investigate the effect of ultraviolet C (UVC)-light-emitting diode (LED) irradiation and slightly acidic electrolysed water (SAEW) treatment, alone or in combination, on elimination and inactivation mechanisms and the inactivation kinetics of E. coli O157:H7 biofilms formed on stainless-steel coupons. Although E. coli biofilms were inactivated significantly up to 2.36 log and 3.23 log, respectively, by both SAEW and UVC-LED disinfection treatment alone, a lesser reduction was seen with sprayed SAEW droplet treatment than with UVC-LED irradiation, possibly due to the interactions between extracellular polymeric substances and the constituents of biofilms and the chemical composition of SAEW. The inactivation kinetics of E. coli O157:H7 biofilms were evaluated using mathematical models to fit nonlinear reduction curves (Mean Sum of Squared Error (MSSE): 0.055–0.245; Root-mean-square deviation (RMSE): 0.236–0.495; R2: 0.943–0.985). For disinfection by a combination of spraying SAEW droplets and UVC-LED irradiation, inactivation synergy effect values and synergy ratios were calculated, where synergy effect values and synergy ratios were not time-dependent. The synergistic effect of the combined treatment showed the highest value of 1.2 log10 in the 14-min treatment condition, whereas the synergistic effect value of the 19-min treatment condition, which was the longest treatment time, was 0.9 log10. Our results established that the combination of sprayed SAEW droplets and UVC-LED irradiation could have a more efficient synergistic effect in biofilm reduction on SUS food contact surface materials than sprayed SAEW droplets or UVC-LED treatment alone. Further studies are required to simulate typical commercial conditions to develop reliable combined applications of SAEW and UVC-LEDs for food safety management.

Tumor Regression with 5-Aminolevulinic Acid (5-ALA)-Mediated Radiodynamic Therapy (RDT) Using Different Megavoltage Energies

5-aminolevulinic acid (5-ALA) accumulates in target tumor cells, where it is metabolized to a photosensitizer - protoporphyrin IX (PpIX). Cherenkov light induced by high-energy photon beams effectively activates the PpIX due to the Soret band. The activated photosensitizers lead to cellular toxicities to kill malignant tumor cells by converting surrounding tissue oxygens into singlet oxygens. Radiodynamic therapy (RDT) utilizes cellular damage caused by both radiation dose and activated photosensitizer. The emission of Cherenkov light was observed higher with higher energy irradiation in phantom and ex-vivo tissues. Therefore, using an in-vivo mouse model, this study aimed to investigate the efficacy and energy dependency of RDT combined with 5-ALA and different ranges of megavoltage photon irradiation. In order to investigate individual and synergistic effects of 5-ALA administration and radiation treatment, the tumors (n = 344) were randomized into eight groups: control (untreated), 5-ALA only, 6-, 15-, and 45-MV conventional radiation treatment (RT) only, 6-, 15-, and 45-MV RDT. 4 Gy in a single fraction was delivered to the tumors using three different energy photons for RT only and RDT groups. 5-ALA was systemically injected into 5-ALA only and RDT groups at 100 mg/kg by tail-vein 4 hours before irradiation for endogenous PpIX accumulation in the tumor. Tumor growth was measured using a 1.5 T MR scanner on the day of treatment (prior to the treatment), 3, 7, and 14 days post-treatment. Two-way repeated ANOVA with Bonferroni correction was used to compare each treatment group to determine the statistically significant difference in tumor growth. A total of 45 MV RDT resulted in the most significant decrease in tumor growth by 58.8 ± 3.4 %, 58.0 ± 3.0 %, and 55.0 ± 3.0 % compared to 5-ALA, 45 MV RT, and control group on 7 days post-treatment (P<0.001), respectively. Moreover, a synergistic effect of 45 MV RDT causes a 47.1-54.1 % additional decrease in tumor growth toward the effective treatment outcome. Compared to the different energies, 45 MV RDT resulted in a 52.2 ± 3.1 % and 19.7 ± 7.2 % decrease in tumor growth compared to 6 MV RDT and 15 MV RDT on 7 days post-treatment, respectively (P<0.001), whereas the conventional RT was not. Radiodynamic therapy using 5-ALA administration and 45MV photon beam irradiation resulted in the most significant tumor growth control. A photon energy dependency was observed in radiodynamic therapy. 45MV photon beams showed greater in activating PpIX, improving the synergistic effects of radiation dose and activated photosensitizer than the other energies. The preliminary results provide a foundation for new innovative treatment strategies that have the potential to improve cancer treatment.

Microwave and dielectric barrier discharge atmospheric plasma interaction on guava industrial biomass for biomaterial production

AbstractThis research helps to develop a novel and economical method for improving the extraction efficiency of oil and fully valorizing guava fruit processing industrial waste into biomaterial. Dielectric barrier discharge atmospheric (DBDA) plasma is a novel non‐thermal technology that has been widely used in the food processing field of research. In this study, the synergistic effect of microwave (MW) and DBDA plasma treatment under different treatment combinations on the modification of morphological and biochemical properties of the guava pomace powder on improving the efficiency of extraction of biomaterials has been investigated. The response surface model (RSM) model was then constructed using the experimental results of Box–Behnken Design (BBD) to obtain the optimal extraction conditions. The predicted optimal extraction conditions for the microwave power level of 600 W for a treatment time of 90 s under solvent extraction at 420 min; DBDA plasma treatment as 35 kV for 15 min and solvent extraction conditions were determined as 80°C for 360 min causing an increment of the oil yield up to 16.19% when extracted using solvent extractor with ethanol as a solvent. These results indicate that the DBDA plasma treatment previous to the extraction step extraction process can contribute to reducing the duration of extraction by 120 min. The obtained data indicate that the MW and DBDA plasma pre‐treatment before the extraction can reduce the extraction duration, increase the yield, and improve the nutritional quality and functional properties.

Synergistic Effect of L-cycloserine and Capecitabine on Human Colon Cancer Cell Line

Introduction: Colon cancer comes in second place in the list of cancers in developed countries. Drug resistance is one of the causes of colorectal cancer therapeutic failure that usually occurs in most patients in advanced stage of colon cancer. This study investigates the effect of adding L-cycloserine to capecitabine in the HCT-116 colon cancer cell line. Materials and methods: We compared the combined L-cycloserine-capecitabine effect with each of the two drugs alone on the HCT-116 colon cancer cell line as a positive control group. The growth rate inhibition was examined by crystal violet assay. Results: The growth inhibition effect of L-cycloserine-capecitabine, L-cycloserine and capecitabine on HCT-116 cells was assessed with crystal violet assay, different concentrations including 3.12, 6.25, 12.5, 25, 50, and 100 μg/mL were used for L-cycloserine-capecitabine combination, and for both L-cycloserine and capecitabine. After incubation for 24 hours, results appeared that the combination of L-cycloserine and capecitabine increased the effect of both drugs alone as seen by a significant increase (p &lt;0.05) of the growth inhibition percentages in the L-cycloserine-capecitabine combination as compared with the positive control groups. Conclusion: From the result, we can conclude that the L-cycloserine combination with capecitabine has a synergistic effect for colon cancer treatment that could be a more effective regimen.

Removal of trichlorfon and phoxim from pak choi (Brassica campestris ssp. chinensis) by combined ultrasonic and ozone treatment and their effects on quality

AbstractThe effect of ultrasound, ozone, and their combination treatment on the removal of two common pesticides (trichlorfon and phoxim) in pak choi samples was studied in this work. The results showed that both ultrasound and ozone treatment alone can significantly remove trichlorfon and phoxim residues in pak choi (&gt;90%), but they reduced the quality of pak choi (such as vitamin C and color). Ultrasound and ozone had a synergistic effect on the removal of pesticide residues in pak choi. The synergistic effect of combined treatment was evaluated from the perspective of pesticide removal speed, and found that their combination significantly accelerated the removal of pesticides. Compared with ultrasound or ozone alone, the removal rate constant of trichlorfon by the combined treatment increased by 121% and 347%, and that of phoxim increased by 159% and 367%, respectively. In addition, the combined treatment of ultrasound and ozone can well maintain the vitamin C and color of pak choi while removing pesticides. Therefore, the combined treatment of ultrasound and ozone can be used as an effective cleaning method to remove pesticide residues in vegetables.Practical applicationsReducing pesticide residues in vegetables is of great significance to human health, and how to maintain the quality of vegetables as much as possible while removing pesticides is a key issue. In this study, the combination of ultrasound and ozone significantly accelerated the removal of pesticides, and retained the vitamin C and color of pak choi well. Therefore, the combined application of ultrasound and ozone has the potential to be an industrial cleaning method for removing pesticide residues in fruits and vegetables without compromising quality.

Drug repurposing based on differentially expressed genes suggests drug combinations with possible synergistic effects in treatment of lung adenocarcinoma

ABSTRACT Lung adenocarcinoma is one of the leading causes of cancer-related mortality globally. Various treatment approaches and drugs had little influence on overall survival; thus, new drugs and treatment strategies are needed. Drug repositioning (repurposing) seems a favorable approach considering that developing new drugs needs much more time and costs. We performed a meta-analysis on 6 microarray datasets to obtain the main genes with significantly altered expression in lung adenocarcinoma. Following that, we found major gene clusters and hub genes. We assessed their enrichment in biological pathways to get insight into the underlying biological process involved in lung adenocarcinoma pathogenesis. The L1000 database was explored for drug perturbations that might reverse the expression of differentially expressed genes in lung adenocarcinoma. We evaluated the potential drug combinations that interact the most with hub genes and hence have the most potential to reverse the disease process. A total of 2148 differentially expressed genes were identified. Six main gene clusters and 27 significant hub genes mainly involved in cell cycle regulation have been identified. By assessing the interaction between 3 drugs and hub genes and information gained from previous clinical investigations, we suggested the three possible repurposed drug combinations, Vorinostat – Dorsomorphin, PP-110 – Dorsomorphin, and Puromycin – Vorinostat with a high chance of success in clinical trials.

Accessible approach of fabricating pH‐responsive nanofibrous membranes with photothermal effect as antibacterial wound dressings

AbstractThe synergistic antibacterial effect of photothermal and drug treatments is a promising therapeutic method for treating the persistent bacterial infection of chronic wounds. In this study, we used electrospinning to fabricate functionalized poly(ε‐caprolactone) (PCL) nanofiber membranes as antibacterial wound dressings after incorporating tannic acid (TA) and ferric ion (Fe3+). The abilities of pH‐responsive controlled release TA and the photothermal effect of the membrane were obtained by introducing the TA/Fe3+ complexes. Additionally, the membrane had a defined nanofibrous network structure, excellent mechanical properties, hydrophilicity, and water uptake ability. While the controlled release of TA endowed the membrane with high antibacterial properties at different pH values, the antibacterial ratio was further enhanced by approximately 10% under the photothermal synergistic effect. These results indicate that the PCL/TA/Fe3+ nanofiber membranes could be regarded as an ideal candidate for treating bacterial infection of chronic wounds.

Synergistic anti-cancer effect of sodium pentaborate pentahydrate, curcumin and piperine on hepatocellular carcinoma cells

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in the world. Poor prognosis of HCC patients is a major issue, thus, better treatment options for patients are required. Curcumin (Cur), hydrophobic polyphenol of the plant turmeric, shows anti-proliferative, apoptotic, and anti-oxidative properties. Boron is a trace element which is essential part of human nutrition. Sodium pentaborate pentahydrate (NaB), a boron derivative, is an effective agent against cancer. In the current study, we performed in vitro experiments and transcriptome analysis to determine the response of NaB, Cur, piperine (Pip) and their combination in two different HCC cell lines, HepG2 and Hep3B. NaB and Cur induced cytotoxicity in a dose and time dependent manner in HepG2 and Hep3B, whereas Pip showed no significant toxic effect. Synergistic effect of combined treatment with NaB, Cur and Pip on HCC cells was observed on cytotoxicity, apoptosis and cell cycle assay. Following in vitro studies, we performed RNA-seq transcriptome analysis on NaB, Cur and Pip and their combination on HepG2 and Hep3B cells. Transcriptome analysis reveals combined treatment of NaB, Cur and Pip induces anti-cancer activity in both of HCC cells.

Neoadjuvant chemoradiation therapy combined with immunotherapy for microsatellite stable ultra-low rectal cancer (CHOICE II): study protocol of a multicentre prospective randomised clinical trial

IntroductionNeoadjuvant chemoradiotherapy (nCRT) could bring tumour shrinking and downstaging and increase the probability of organ preservation for patients with low rectal cancer. But for ultra-low rectal cancer, there is little...