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Monitoring the concentration of Fludarabine phosphate, a standard chemotherapeutic drug widely used in cancer treatment, is vital for ensuring the drug's safety and effectiveness, tailoring treatments to individual needs, and consequently improving overall patient outcomes. Regarding the limitations of conventional techniques in terms of complexity, large time measurements, and a high cost, there is an urgent need to develop simple, rapid, and cost-effective devices. In this paper, we report the design of an aptasensor for the specific and selective detection of Fludarabine. Systematic evolution of ligands by exponential enrichment (SELEX) protocol was performed to select a specific aptamer for Fludarabine. Eleven rounds were carried out, and nine sequences were selected. Based on the dissociation constant (Kd), Ful-3, exhibiting the highest affinity (18.86 nM), was chosen and integrated into a simple electrochemical aptasensing platform for Fludarabine detection. Electrochemical results demonstrated good performance of the selected aptamer in detecting Fludarabine within the analytical range of 1 to 150 pg/mL and with LOD and LOQ in the order of 0.11 pg/mL (0.31 fM) and 0.39 pg/mL (1.06 fM), respectively. The developed platform also showed good selectivity against different analogous molecules and high applicability in serum-spiked samples, with recovery percentages ranging from 96.81 to 99.04%. Considering the encouraging results, this research presents an excellent alternative in terms of simplicity, stability, ease of use, reduction of sample volume, and low cost. [ABSTRACT FROM AUTHOR]

Malignant tumors are among the most important causes of death worldwide. The pathogenesis of a malignant tumor is complex and has not been fully elucidated. Studies have shown that such pathogenesis is related to abnormal cell cycle progression. The expression levels of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors as well as functions of the cell cycle checkpoints determine whether the cell cycle progression is smooth. Cell-cycle-targeting drugs have the advantages of high specificity, low toxicity, low side effects, and low drug resistance. Identifying drugs that target the cell cycle and applying them in clinical treatments are expected to promote chemotherapeutic developments against malignant tumors. This article aims to review drugs targeted against the cell cycle and their action mechanisms. [ABSTRACT FROM AUTHOR]

Background: Programmed cell death (PCD) has been widely investigated in various human diseases. The present study aimed to identify a novel PCD‐related genetic signature in cervical squamous cell carcinoma (CESC) to provide clues for survival, immunotherapy and drug sensitization prediction. Methods: Single‐sample gene set enrichment analysis (ssGSEA) was used to quantify the PCD score and assess the distribution of PCD in clinicopathological characteristics in The Cancer Genome Atlas (TCGA)‐CESC samples. Then, the ConsensusClusterPlus method was used to identify molecular subtypes in the TCGA‐CESC database. Genomic mutation analysis, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment, as well as tumor microenvironment (TME) infiltration analysis, were performed for each molecular subtype group. Finally, a prognostic model by Uni‐Cox and least absolute shrinkage and selection operator‐Cox analysis was established based on differentially expressed genes from molecular subtypes. ESTIMATE (i.e. Estimation of STromal and Immune cells in MAlignantTumours using Expression data) and ssGSEA were performed to assess the correlation between the model and TME. Drug sensitization prediction was carried out with the oncoPredict package. Results: Preliminary analysis indicated that PCD had a potential association clinical characteristics of the TCGA‐CESC cohort, and PCD‐related genes mutated in 289 (70.59%) CESC patients. Next, four groups of CESC molecular typing were clustered based on 63 significantly prognostic PCD‐related genes. Among four subtypes, C1 group displayed the worst prognosis combined with over expressed PCD genes and enriched cell cycle‐related pathways. C4 group exhibited the best prognosis accompanied with high degree of immune infiltration. Finally, a five‐gene (SERPINE1, TNF, CA9, CX3CL1 and JAK3) prognostic model was constructed. Patients in the high‐risk group displayed unfavorable survival. Immune infiltration analysis found that the low‐risk group had significantly higher levels of immune cell infiltration such as T cells, Macrophages_M1, relative to the high‐risk group, and were significantly enriched in apoptosis‐associated pathways, which predicted a higher level of immunity. Drug sensitivity correlation analysis revealed that the high‐risk group was resistant to conventional chemotherapeutic drugs and sensitive to the Food and Drug Administration‐approved drugs BI.2536_1086 and SCH772984_1564. Conclusions: In the present study, we first found that PCD‐related gene expression patterns were correlated with clinical features of CESC patients, which predicts the feasibility of subsequent mining of prognostic features based on these genes. The five‐PCD‐associated‐gene prognostic model showed good assessment ability in predicting patient prognosis, immune response and drug‐sensitive response, and provided guidance for the elucidation of the mechanism by which PCD affects CESC, as well as for the clinical targeting of drugs. [ABSTRACT FROM AUTHOR]

Lung cancer is the main cause of cancer-related deaths throughout the world. Its treatment involves intensive cycles of chemotherapy and radiotherapy, which are associated with serious adverse effects. EGCG, an active component of green tea/white tea, regulates cell molecular pathways of apoptosis, angiogenesis, proliferation, differentiation, and self-renewal ability of cancer stem cells. It also acts as a pro-oxidant that can cause cell death in cancer cells via apoptosis. It can control lung carcinogenesis by altering the molecules involved in multiple signal transduction pathways like Ras-GTPase, ERK, COX2, VEGF, and protein kinases. Moreover, it can also affect other signalling molecules or pathways such as DNMT1, MAPK, NF-κB, Bcl/Bax, HIF-1α, EGFR, Akt/PI3, Wnt/β-catenin, caspases, NEAT1, TGF-β, HDGF, and CLOCK. Recent studies on cell lines and animals have focused on the role of EGCG in enhancing the efficacy of chemotherapeutic drugs and reducing their adverse effects. The low bioavailability and rapid metabolism of EGCG can act as a hurdle in the translation of this agent from lab to bedside. The uses of synthetic agents such as COMT inhibitors and nano-drug delivery tools have been shown to enhance the plasma levels of EGCG and its cancer preventive and therapeutic ability.

Anthracyclines, a class of drugs considered as most effective anticancer drugs, used in the various regimens of cancer chemotherapy, induce long-term impairment of mitochondrial respiration, increase reactive oxygen species, and induce other mechanisms potentially leading to neurotoxicity. According to literature findings, one drug of this class - doxorubicin used to treat e.g. breast cancer, bladder cancer, lymphoma, and acute lymphocytic leukemia may induce such effects in the nervous system. Doxorubicin has poor penetration into the brain due to the lack of drug penetration through the blood-brain barrier, thus the toxicity of this agent is the result of its peripheral action. This action is manifested by cognitive impairment and anatomical changes in the brain and peripheral nervous system found in both preclinical and clinical studies in adult patients. Furthermore, more than 50% of children with cancer are treated with anthracyclines including doxorubicin, which may affect their nervous system, and lead to lifelong damage in many areas of their life. Despite ongoing research into the side effects of this drug, the mechanism of its neurotoxicity action on the central and peripheral nervous system is still not well understood. This review aims to summarize the neurotoxic effects of doxorubicin in preclinical (in vitro and in vivo) research and in clinical studies. Furthermore, it discusses the possible mechanisms of the toxic action of this agent on the nervous system. [ABSTRACT FROM AUTHOR]

Regarding applicative, facile, green chemical research, a bio-inspired approach is being reported for the synthesis of CuO nanoparticles by pectin (PEC) as a natural reducing and stabilizing agentin alkaline medium without using any toxic reducing agent. The biosynthesized CuO NPs@Pectin were characterized by advanced physicochemical techniques like ultraviolet–visible (UV–Vis), Fourier Transformed Infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-ray spectroscopy (EDX) and X-ray Diffraction (XRD) study. It has been established that pectin-stabilized copper nanoparticles have a spherical shape with a mean diameter from approximately 10 nm. To survey the cytotoxicity and anti-human cervical cancer effects of CuO NPs@Pectin, MTT assay was used on C-33 A [c-33a], SiHa, Ca Ski, DoTc2 4510, HT-3 and LM-MEL-41 cell lines. The resulting IC50 values of the CuO NPs@Pectin against C-33 A [c-33a], SiHa, Ca Ski, DoTc2 4510, HT-3 and LM-MEL-41 cell lines were 231, 214, 243, 376, 315 and 169 µg/mL, respectively. Antioxidant properties of CuO NPs@Pectin were surveyed through the DPPH test in presence of butylated hydroxytoluene as the positive control. The CuO NPs@Pectin inhibited half of the DPPH molecules in the concentration of 98 µg/mL. The cell viability of the treated cell lines was found to reduce dose-dependently over the CuO NPs@Pectin nanocomposite. After approving the above results in the clinical trial studies, the CuO NPs@Pectin can be used as a chemotherapeutic drug for the treatment of several types of cervical cancers.

5-Fluorouracil (5-FU) is a conventional chemotherapeutic drug widely used in clinics worldwide, but development of resistance that compromises responsiveness remains a major hurdle to its efficacy. The mechanism underlying 5-FU resistance is conventionally attributed to the disruption of nucleotide synthesis, even though research has implicated other pathways such as RNA processing and chromatin dysregulation. Aiming to clarify resistance mechanisms of 5-FU, we tested the response of a collection of fission yeast (Schizosaccharomyces pombe) null mutants, which confer multiple environmental factor responsiveness (MER). Our screen identified disruption of membrane transport, chromosome segregation and mitochondrial oxidative phosphorylation to increase cellular susceptibility towards 5-FU. Conversely, we revealed several null mutants of Ino80 complex factors exhibited resistance to 5-FU. Furthermore, attenuation of Ino80 function via deleting several subunit genes reversed loss of chromosome-segregation fidelity in 5-FU in the loss-of-function mutant of the Argonaute protein, which regulates RNA interference (RNAi)-dependent maintenance of pericentromeric heterochromatin. Our study thus uncovered a critical role played by chromatin remodeling Ino80 complex factors in 5-FU resistance, which may constitute a possible target to modulate in reversing 5-FU resistance. [ABSTRACT FROM AUTHOR]

As traditional strategies for cancer treatment, some chemotherapy agents, such as doxorubicin, oxaliplatin, cyclophosphamide, bortezomib, and paclitaxel exert their anti-tumor effects by inducing immunogenic cell death (ICD) of tumor cells. ICD induces anti-tumor immunity through release of, or exposure to, damage-related molecular patterns (DAMPs), including high mobility group box 1 (HMGB1), calreticulin, adenosine triphosphate, and heat shock proteins. This leads to activation of tumor-specific immune responses, which can act in combination with the direct killing functions of chemotherapy drugs on cancer cells to further improve their curative effects. In this review, we highlight the molecular mechanisms underlying ICD, including those of several chemotherapeutic drugs in inducing DAMPs exposed during ICD to activate the immune system, as well as discussing the prospects for application and potential role of ICD in cancer immunotherapy, with the aim of providing valuable inspiration for future development of chemoimmunotherapy. [ABSTRACT FROM AUTHOR]

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Malignant bone tumors are usually treated by resection of tumor tissue followed by filling of the bone defect with bone graft substitutes. Polymethylmethacrylate (PMMA) cement is the most commonly used bone substitute in clinical orthopedics in view of its reliability. However, the dense nature of PMMA renders this biomaterial unsuitable for local delivery of chemotherapeutic drugs to limit the recurrence of bone tumors. Here, we introduce porosity into PMMA cement by adding carboxymethylcellulose (CMC) to facilitate such local delivery of chemotherapeutic drugs, while retaining sufficient mechanical properties for bone reconstruction in load-bearing sites. Our results show that the mechanical strength of PMMA-based cements gradually decreases with increasing CMC content. Upon incorporation of ≥3% CMC, the PMMA-based cements released up to 18% of the loaded cisplatin, in contrast to cements containing lower amounts of CMC which only released less than 2% of the cisplatin over 28 days. This release of cisplatin efficiently killed osteosarcoma cells in vitro and the fraction of dead cells increased to 91.3% at day 7, which confirms the retained chemotherapeutic activity of released cisplatin from these PMMA-based cements. Additionally, tibias filled with PMMA-based cements containing up to 3% of CMC exhibit comparable compressive strengths as compared to intact tibias. In conclusion, we demonstrate that PMMA cements can be rendered therapeutically active by introducing porosity using CMC to allow for release of cisplatin without compromising mechanical properties beyond critical levels. As such, these data suggest that our dual-functional PMMA-based cements represent a viable treatment option for filling bone defects after bone tumor resection in load-bearing sites.

Bacterial cancer therapies aim to manipulate bacteria to effectively deploy therapeutic payloads to tumors. Attenuated bacteria alone often cannot eradicate solid tumors. Attenuated Salmonella can be engineered to deliver cytotoxic drugs to either trigger an immune response or increase antitumor efficacy when combined with chemotherapeutic drugs. However, the extracellular matrix (ECM) surrounding cancer cells forms a barrier that often limits the ability of chemotherapeutic and cytotoxic drugs to penetrate and eliminate tumors. To overcome this limitation, we developed a strategy to combine chemotherapy with an attenuated Salmonella typhimurium strain engineered to secrete HysA protein (from Staphylococcus aureus ; Hyaluronidase, HAase) in tumors. The engineered Salmonella effectively degraded hyaluronan (HA), which is a major ECM constituent in tumors, and suppressed tumor growth in mouse models of pancreatic adenocarcinoma (ASPC-1) and breast cancer (4T1). Furthermore, it prolonged survival when combined with chemotherapeutic drugs (doxorubicin or gemcitabine). Upon bacterial colonization, the HAase-mediated ECM degradation decreased interstitial fluid pressure (IFP) in the tumor microenvironment. Additionally, HA degradation using HAase-expressing bacteria in vivo led to decreased binding to the receptor, CD44, expressed in tumors. This may modulate proliferation- and apoptosis-related signal pathways. Therefore, ECM-targeting bacteria can be used as a synergistic anticancer therapeutic agent to maximize chemotherapeutic drug delivery into highly invasive tumors. [Display omitted] • Attenuated S. typhimurium suppresses tumor growth by proliferating within tumors. • S. typhimurium (SLlux/HAase) HAase degrades HA of tumor ECM and decreases IFP. • Lower IFP facilitates penetration of chemotherapeutic drugs into the tumors. • SLlux/HAase enhances tumor suppression by increasing drug penetration. • SLlux/HAase inhibits CD44 and HA interaction and proliferation of tumor cells. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aims to reveal the oxidant and antioxidant status in nurses with chemotheropathic drug exposure and radiology unit workers exposed to ionizing radiation (IR). METHODS: Nineteen radiology unit workers, 14 nurses, and 15 controls were included the study. All of the participants using antioxidants, vitamin supplements, smokers, any therapeutic drugs, and exposed therapeutic or diagnostic X-ray or chemotherapeutic drugs in 12 months were excluded from the study. Total and native thiols, disulfide/native thiol percent ratios (SS/SH), disulfide/total thiol percent ratios, disulfide amounts, and native thiol/total thiol percent ratios, ischemia-modified albumin (IMA) were determined. RESULTS: Disulfide levels, disulfide/total thiol ratio, and disulfide/native thiol ratio of serum samples of both radiology unit workers and nurses were significantly higher and ratio of native thiol/total thiol was lower than the control group. The radiation dose in radiology unit workers was mean±SD: 0.02±0.009, median (min-max): 0.02 (0.001-0.04). Thiol-disulfide homeostasis was disturbed and the balance shifted in the direction of oxidant damage, even at low-dose IR exposure and normal range. CONCLUSION: As far as we know, the current findings first demonstrate an apparent chronic oxidative stress in the subjects who were occupationally exposed to antineoplastic drugs and radiation even if annual radiation exposure dose measurements are normal. [ABSTRACT FROM AUTHOR]

Regarding applicative, facile, green chemical research, a bio-inspired approach is being reported for the synthesis of CuO nanoparticles by pectin (PEC) as a natural reducing and stabilizing agentin alkaline medium without using any toxic reducing agent. The biosynthesized CuO NPs@Pectin were characterized by advanced physicochemical techniques like ultraviolet–visible (UV–Vis), Fourier Transformed Infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-ray spectroscopy (EDX) and X-ray Diffraction (XRD) study. It has been established that pectin-stabilized copper nanoparticles have a spherical shape with a mean diameter from approximately 10 nm. To survey the cytotoxicity and anti-human cervical cancer effects of CuO NPs@Pectin, MTT assay was used on C-33 A [c-33a], SiHa, Ca Ski, DoTc2 4510, HT-3 and LM-MEL-41 cell lines. The resulting IC50 values of the CuO NPs@Pectin against C-33 A [c-33a], SiHa, Ca Ski, DoTc2 4510, HT-3 and LM-MEL-41 cell lines were 231, 214, 243, 376, 315 and 169 µg/mL, respectively. Antioxidant properties of CuO NPs@Pectin were surveyed through the DPPH test in presence of butylated hydroxytoluene as the positive control. The CuO NPs@Pectin inhibited half of the DPPH molecules in the concentration of 98 µg/mL. The cell viability of the treated cell lines was found to reduce dose-dependently over the CuO NPs@Pectin nanocomposite. After approving the above results in the clinical trial studies, the CuO NPs@Pectin can be used as a chemotherapeutic drug for the treatment of several types of cervical cancers. [ABSTRACT FROM AUTHOR]

The nitrogen mustard alkylating agent chlorambucil (CBL) is a critical component of chemotherapeutic regimens used in the treatment of chronic lymphocytic leukemia. The cancer cell-killing actions of CBL are limited by glutathione (GSH) conjugation, a process catalyzed by the GSH transferase hGSTA1-1 that triggers CBL efflux from cells. In the cancer cell microenvironment, intracellular GSH levels are elevated to counterbalance oxidative stress generated due to the high glycolytic demand. As many chemotherapeutic drugs trigger cell death through mechanisms that depend on reactive oxygen species (ROS), antioxidant capacity in cancer cells also represents a barrier to anticancer therapies. Here, we demonstrate that a heightened GSH content in cancer cells can also be exploited for cell-selective drug delivery. We successfully synthesized a malononitrile conjugate terpyridine-based derivative L1 , which specifically reacts with GSH in the presence of other biologically relevant amino acids including cysteine (Cys) and homocysteine (Hcy). The significant change in the electronic spectra of L1 in the presence of GSH confirmed GSH detection, which was further corroborated by density functional theory calculations. We next encapsulated CBL into L1 -containing, anthracene-functionalized, and 10,12-pentacosadiynoic acid (PCDA)- and 1,2-dimyristoyl- sn -glycero-3-phosphocholine (DMPC)-based liposomes ( Lip-CBL-L1 ). We established successful CBL encapsulation and release from L1 -containing liposomes in GSH-enriched cancer cells in vitro. Both Lip-CBL-L1 and the L1 -lacking Lip-CBL control displayed cell-killing activity. However, human triple-negative breast cancer cells MDAMB231, human lung cancer cells A549, and murine leukemic WEHI cells were more sensitive to the cytotoxic effects of Lip-CBL-L1 compared to the nonmalignant cells (AC16 and HEK293). Indeed, in these cancer cell lines, Lip-CBL-L1 induced greater ROS generation compared to that of Lip-CBL . Together, our results provide initial evidence of the feasibility of exploiting the unique oxidant environment of cancer cells for optimized drug delivery.

Background: The persistently high mortality and morbidity rates of hepatocellular carcinoma (HCC) remain a global concern. Notably, the disruptions in mitochondrial cholesterol metabolism (MCM) play a pivotal role in the progression and development of HCC, underscoring the significance of this metabolic pathway in the disease's etiology. The purpose of this research was to investigate genes associated with MCM and develop a model for predicting the prognostic features of patients with HCC., Methods: MCM-related genes (MCMGs) were identified through The Cancer Genome Atlas (TCGA), The Molecular Signatures Database (MsigDB), and the Mitocarta3.0 databases. Differential gene expression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression analysis were performed using R software to construct a MCM-related model. This model underwent further analysis for somatic mutations, single sample gene set enrichment analysis (ssGSEA), stromal and immune cell estimation, immune checkpoint evaluation, and drug susceptibility prediction to assess the tumor microenvironment (TME) and therapeutic responses. The mRNA expression levels of the genes associated with the model were quantified using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR)., Results: The model, which included six MCMGs ( ACADL , ACLY , TXNRD1 , DTYMK , ACAT1 , and FLAD1 ), divided all patients (age ≤65 vs. >65 years, P<0.001; male vs. female, ns) into a high-risk group and a low-risk group. The high-risk group showed a higher mortality rate and lower survival rate with AUC of 0.785, 0.752, 0.756, 0.774 and 0.759 for the 1-, 2-, 3-, 4-, and 5-year respectively. A nomogram based on risk score, stage, T, and M had a better prognostic accuracy, with AUC of 0.808, 0.796, 0.811, 0.824 and 0.795 for the 1-, 2-, 3-, 4-, and 5-year respectively. The high-risk group showed enrichment in cell cycle, cell division, and chromosome processes, and a significantly higher tumor mutation burden (TMB) value compared to the low-risk group. Further immune infiltration analysis indicated a significantly reduction in the abundances of some immune cells (activated CD4 T cells, type 2 helper T cells, and neutrophils) and significantly higher expression levels of some immune checkpoint ( CD80 , CTLA4 , HAVCR2 , and TNFRSF4 ) in the high-risk group. Moreover, the risk score was associated with the response to immune checkpoint inhibitors (ICIs) therapy and efficiencies of multiple chemotherapy drugs., Conclusions: This study developed a prognostic model based on MCMGs, which can predict the prognosis of liver cancer patients and their response to immunotherapy and chemotherapy. The model may provide new strategies to enhance the prognosis and treatment of HCC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-1153/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

In the present study, iron nanoparticles were green-synthesized using the aqueous extract of Alhagi maurorum leaf aqueous extract. The synthesized FeNPs were characterized by analytical techniques including EDX, FE-SEM, XRD, UV–vis and FT-IR. The anti-human lung cancer activity of FeNPs was evaluated using MTT assay. The nanoparticles were formed in a spherical shape in the average size of 60.11 nm. In the cellular and molecular part of the recent study, the treated cells with FeNPs were assessed by MTT assay for 48 h about the cytotoxicity and anti-human lung cancer properties on normal (HUVEC) and lung cancer cell lines i.e. HLC-1 and PC-14. The viability of malignant lung cell line reduced dose-dependently in the presence of FeNPs. The IC50 of FeNPs was 195 and 181 µg/mL against HLC-1 and PC-14 cell lines, respectively. In the antioxidant test, the IC50 of FeNPs and BHT against DPPH free radicals was 214 and 62 µg/mL, respectively. After the clinical study, iron nanoparticles containing A. maurorum leaf aqueous extract may be used to formulate a new chemotherapeutic drug or supplement to treat several types of human lung cancer.

Abstract Background Tuberculosis (TB) caused Mycobacterium tuberculosis (M.tb) is one of infectious disease that lead a large number of morbidity and mortality all over the world. Although no reliable evidence has been found, it is considered that combining chemotherapeutic drugs with Chinese herbs can significantly improves the cure rate and the clinical therapeutic effect. Methods Multi-drug resistant pulmonary tuberculosis (MDR-PTB, n = 258) patients with Qi-yin deficiency syndrome will be randomly assigned into a treatment group (n = 172) or control/placebo group (n = 86). The treatment group will receive the chemotherapeutic drugs combined with Chinese herbs granules (1 + 3 granules), while the control group will receive the chemotherapeutic drugs combined with Chinese herbs placebo (1 + 3 placebo granules). In addition, MDR-PTB (n = 312) patients with Yin deficiency lung heat syndrome will be randomly assigned to a treatment (n = 208) or control/placebo (n = 104) group. The treatment group will receive the chemotherapeutic regimen combined with Chinese herbs granules (2 + 4 granules), while the control group will receive the chemotherapeutic drugs and Chinese herbs placebo (2 + 4 placebo granules). The primary outcome is cure rate, the secondary outcomes included time to sputum culture conversion, lesion absorption rate and cavity closure rate. BACTEC™ MGIT™ automated mycobacterial detection system will be used to evaluate the M.tb infection and drug resistance. Chi-square test and Cox regression will be conducted with SAS 9.4 Statistical software to analyze the data. Discussion The treatment cycle for MDR-PTB using standardized modern medicine could cause lengthy substantial side effects. Chinese herbs have been used for many years to treat MDR-PTB, but are without high-quality evidence. Hence, it is unknown whether Chinese herbs enhances the clinical therapeutic effect of synthetic drugs for treating MDR-PTB. Therefore, this study will be conducted to evaluate the clinical therapeutic effect of combining Chinese herbs and chemotherapeutic drugs to treat MDR-PTB cases. It will assist in screening new therapeutic drugs and establishing treatment plan that aims to improve the clinical therapeutic effect for MDR-PTB patients. Trial registration This trial was registered at ClinicalTrials.gov (ChiCTR1900027720) on 24 November 2019 (prospective registered). Graphical Abstract

The vestibule of the inner ear is susceptible to certain chemotherapeutic agents in clinical practice. Therefore, it is of great significance to discover molecular pathways and targets that can protect the vestibule from chemotherapeutic drugs. The Notch signaling pathway is closely related to hair cell regeneration in the inner ear. However, the role of Notch signaling in chemotherapeutic drug-induced vestibular injury still remains unclear. The aim of this study was first to evaluate the role of Notch signaling in chemotherapy-induced vestibular injury. Cisplatin-induced vestibular injury of mice was evaluated by the swimming test. Changes of vestibular hair cells and the expression levels of Notch1, Jagged1, and Hes1 in Notch signaling were observed by immunofluorescence. The results showed that Notch signaling was found activated in cisplatin-induced injured vestibular cells, while, DAPT (Notch signaling inhibitor) could reversed this effect. In conclusion, the Notch signaling pathway may play a critical role in chemotherapeutic drug-induced vestibular injury and, therefore, serves as a promising therapeutic target for vestibular injury. [ABSTRACT FROM AUTHOR]

(1) Background: Gastric cancer (GC) is the fourth leading cause of cancer death worldwide. Silver nanoparticles (Ag-NPs) have been increasingly used in the diagnosis and treatment of cancer due to their physicochemical properties. This study investigated the role of a kind of biosynthetic silver nanoparticle (b-Ag) in the development of GC, the enhancement of 5-fluorouracil (5F), and its mechanism. (2) Methods: X-ray, transmission electron microscopy (TEM), and UV absorbance were used to detect the characterizations of AgNPs. CCK8, Colony formation and a Transwell assay were performed to confirm the malignant behaviors of GC. DCFH-DA and DHE were used to detect intracellular reactive oxygen species (ROS). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression of apoptosis-related genes. (3) Results: Compared with the chemosynthetic silver nanoparticles (c-Ag), b-Ag had a stronger cytokilling effect, and it had a better inhibition on the malignant phenotype of GC when combined with 5F. The b-Ag increased the expression of Bax and P53 while decreasing the expression of Bcl2. It also promoted the generation of intracellular ROS. (4) Conclusions: By promoting cell apoptosis and increasing intracellular ROS, b-Ag inhibited the development of GC and enhanced the inhibition of 5F on GC. [ABSTRACT FROM AUTHOR]

The essential oils from the stem of Etlingera velutina was obtained by a Clevenger-apparatus and the chemical composition of the volatile oil was identified using GC-FID and GC-MS methods. the oil consists of sesquiterpene hydrocarbon. α-Cubebene (29.98%) and 2-undecanone (20.04%) were the main components for the rhizome oil. In the cellular and molecular part of this study, the MTT assay was run to treat of the cell lines by EO for evaluation of the cytotoxicity and anti-human gastric cancer properties of EO. The results revealed a dose-dependently on the viability of malignant gastric cell line. The IC50 of EO were 376 and 371 μg/mL against NCI-N87 and MKN45 cell lines, respectively. For antioxidant analysis, the IC50 of 192 μg/mL was obtained for radical scavenging activity of EO against DPPH. [ABSTRACT FROM AUTHOR]

Purpose: This retrospective study evaluated the efficacy, safety, and factors affecting the prognosis of transarterial chemoembolisation with irinotecan-eluting beads with CalliSpheres (DEB-TACE) for intrahepatic cholangiocarcinoma (ICC). Materials and Methods: We retrospectively collected data on 39 patients with unresectable ICC who received DEB-TACE therapy. We assessed the indicators of tumour response, progression-free survival (PFS), overall survival (OS), and the incidence of adverse events. PFS and OS were analysed using Kaplan–Meier curves, while Cox analysis was used to identify factors affecting the prognosis. Results: The 3-month objective response rate (ORR) and disease control rate (DCR) of the 39 patients with unresectable ICC were 35.9% and 56.4%, respectively, while the 6-month ORR and DCR were 23.0% and 40.9%, respectively. The median OS and PFS were 11.0 months and 8.0 months, respectively. Cox analysis demonstrated that combined therapy (adjuvant sorafenib after DEB-TACE) and a low cancer antigen (CA) 125 level (≤ 35 U/ml) were independent favourable prognostic factors. Transient elevation of the aminotransferase level, nausea, vomiting, abdominal pain, fever, and hyper-bilirubinaemia were common adverse events in patients with unresectable ICC treated with DEB-TACE with CalliSphere beads (CBs). Hepatic abscess was the most serious complication, observed in one patient. Conclusions: DEB-TACE with CBs is a safe and well-tolerated therapy in patients with unresectable ICC with a low incidence of adverse events and relatively prolonged survival. Combined therapy and low CA125 are prognostic factors associated with longer survival. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX), a valuable anti-cancer drug can cause multi-organ toxicities. Among several suggested mechanisms, the role of oxidative stress remains obscure, though it is the most probable mechanism for its cardiotoxic effect. The main focus of this study is to analyze the mechanism of renal toxicity caused by this chemotherapeutic drug. As reactive oxygen species are significant regulators of transcription factors and gene expression, this study was aimed at analyzing the expression levels of genes that are induced in response to oxidative stress following DOX administration to rats. DOX was administered to rats intraperitoneally at 3 mg/kg at alternate days for two weeks. Kidney tissues were harvested and the mRNA levels of glutathione peroxidase-1(Gpx1), NAD(P)H quinone dehydrogenase 1 (Nqo1), 24-dehydrocholesterol reductase (Dhcr24), dual oxidase 2 (Duox2), and isocitrate dehydrogenase-1 (Idh1) were analyzed in the kidney tissues by RT-PCR. Extent of injury was analyzed by the change in expression of kidney injury biomarkers, kidney injury molecule-1 (KIM-1) and osteopontin (OPN), while the effect of DOX was also analyzed in terms of changes in the anti-inflammatory cytokine, interleukin-10 (IL10). Of the oxidative stress induced genes analyzed, the expression of Gpx1 was found to be increased significantly. Significant increase was also observed in case of IL10 gene, while kidney injury biomarker level was not increased in response to DOX. It is concluded from this study that DOX treatment can modulate the expression levels of Gpx1 and IL10, while injury markers may have differential expression depending upon the duration following toxicity. [ABSTRACT FROM AUTHOR]

Rutin is a bioactive compound that possesses anti-tumor activities through triggering apoptosis. Triple-negative breast cancer (TNBC) is insensitive to targeted anti-tumoral drugs, and drug resistance in TNBC poses a challenge for a successful cure. The accumulation of misfolded proteins in the lumen of the endoplasmic reticulum (ER) results in cellular stress that initiates a specialized response designated as the unfolded protein response. This study aimed to find potential ER stress targets in triple-negative breast cancer. The viability of cells was evaluated using an MTT assay. Cell migration and proliferation were done by wound scratch and colony formation assay. Cell cycle detection, measurement of ER stress, mitochondrial membrane potential disruption, and cell death identification was performed using flow cytometry. The interaction of rutin with ER stress proteins is predicted using in silico docking. The pattern of gene expression was determined by qRT-PCR. The elevated rate of cell viability, cell cycle arrest, ER stress, MMP, and apoptotic induction was observed in combination treatment. Rutin exhibited the highest glide score with ASK1 and JNK. The results of qRT-PCR showed that rutin induced apoptosis through upregulation of ASK1 and JNK. The present study provides strong evidence supporting an important role of the ER stress response in mediating rutin-induced apoptosis in triple-negative breast cancer.

Background: Super-paramagnetic iron oxide nanoparticles (SPION) contain a chemotherapeutic drug and are regarded as a promising technique for improving targeted delivery into cancer cells. Results: In this study, the fabrication of 5-fluorouracil (5-FU) was investigated with loaded Dextran (DEX-SPION) using the co-precipitation technique and conjugated by folate (FA). These nanoparticles (NPs) were employed as carriers and anticancer compounds against liver cancer cells in vitro. Structural, magnetic, morphological characterization, size, and drug loading activities of the obtained FA-DEX-5-FU-SPION NPs were checked using FTIR, VSM, FESEM, TEM, DLS, and zeta potential techniques. The cellular toxicity effect of FA-DEX-5-FU-SPION NPs was evaluated using the MTT test on liver cancer (SNU-423) and healthy cells (LO2). Furthermore, the apoptosis measurement and the expression levels of NF-1, Her-2/neu, c-Raf-1, and Wnt-1 genes were evaluated post-treatment using flow cytometry and RT-PCR, respectively. The obtained NPs were spherical with a suitable dispersity without noticeable aggregation. The size of the NPs, polydispersity, and zeta were 74 ± 13 nm, 0.080 and −45 mV, respectively. The results of the encapsulation efficiency of the nano-compound showed highly colloidal stability and proper drug maintenance. The results indicated that FA-DEX-5-FU-SPION demonstrated a sustained release profile of 5-FU in both phosphate and citrate buffer solutions separately, with higher cytotoxicity against SNU-423 cells than against other cells types. These findings suggest that FA-DEX-SPION NPs exert synergistic effects for targeting intracellular delivery of 5-FU, apoptosis induction, and gene expression stimulation. Conclusions: The findings proved that FA-DEX-5-FU-SPION presented remarkable antitumor properties; no adverse subsequences were revealed against normal cells.How to cite: Mahdia SA, Kadhimb AA, Albukhaty S, et al. Gene expression and apoptosis response in hepatocellular carcinoma cells induced by biocompatible polymer/magnetic nanoparticles containing 5-fluorouracil. Electron J Biotechnol 2021;52. https://doi.org/10.1016/j.ejbt.2021.04.001

Malaysia is the world's major producer and exporter of ornamental fish, contributing 9% to the global trade and taking the second position after Singapore. Because of their artistic appeal and tremendous commercial value for international trade, ornamental fish recently gain rapid importance for foreign exchange and as a source of employment. While ornamental fish production is growing, there is an increase in infectious diseases, resulting in high fish mortality with significant economic loss. Bacterial disease is a serious problem for ornamental fish industry. Bacterial species surveillance in diseased freshwater ornamental fish from an aquarium shop reveals that Aeromonas hydrophila is the most dominant bacteria isolated. Consequently, Malaysia is stepping up its efforts by implementing the Economic Transformation Program and other biosecurity steps to address the aquaculture issues and encourage the regrowth of the ornamental fish market. Chemotherapeutic medications, phytobiotics, probiotics, yeast extracts, vaccines, and disinfectants can be used in controlling bacteria. Further studies should be done to find new antibacterial agents from natural sources to combat bacterial fish diseases and reduce fish mortality rate in sustainable aquaculture farms. This review summarizes the literature on ornamental fish industries and aquaculture production in relation to A. hydrophila-associated diseases and ornamental fish health management in Malaysia.

[Display omitted] • AgNPs were characterized using XRD, TEM, UV–Vis, and FE-SEM. • To examine the antioxidant characteristics of AgNPs, the DPPH assay was employed with BHT serving as the positive control. • The HOS revealed the most effective outcome regarding anti-human bone tumor efficacies when treated with AgNPs. Several studies have recently uncovered the ability of plants to enhance the therapeutic efficacies of Ag NPs on various carcinoma cells, particularly those associated with human bone tumors. Developing and formulating novel chemotherapy supplements or medications for the management of bone tumors in humans is a top research focus for both developing and developed nations. Our current study involved the development of a contemporary chemotherapeutic medication utilizing silver nanoparticles (AgNPs) combined with an aqueous extract of Allium sativum L. for the purpose of treating bone tumors in humans. AgNPs were characterized using XRD, TEM, UV–Vis, and FE-SEM. The peaks detected at 2θ values of 77.4, 65.1, and 37.8 were associated with the crystal planes 311, 220, and 111, respectively. To examine the antioxidant characteristics of AgNPs, the DPPH assay was employed with BHT serving as the positive control. The MTT assay was employed to examine the anti-human bone tumor and cytotoxicity properties of AgNPs on bone cancer cells, including A-673 and HS-729 (rhabdomyosarcoma), MHH-ES1 and CADO-ES1 (Ewing's sarcoma), MG-63 and HOS (osteosarcoma), as well as CH-3573 and SW-1353 (chondrosarcoma). The DPPH assay demonstrated comparable antioxidant capacities among AgNPs, and butylated hydroxytoluene. The anti-human bone tumor properties and cell viability of silver nanoparticles exhibited a dose-dependent decrease against CH-3573, SW-1353, MG-63, HOS, MHH-ES1, CADO-ES1, HS-729, and A-673 cells, while showing no cytotoxic effects on the normal cell line. The viability of the cells and their response to the nanoparticles varied based on the dosage administered. The silver nanoparticles exhibited IC 50 values of 154, 67, 129, 110, 124, 107, 70, and 81 µg/ml against H-3573, SW-1353, MG-63, HOS, MHH-ES1, CADO-ES1, HS-729, and A-673 cell lines, respectively. The HOS revealed the most effective outcome regarding anti-human bone tumor efficacies when treated with AgNPs, surpassing the results observed in other cell lines. Based on the aforementioned results, it is possible to utilize the silver nanoparticles with A. sativum extract for the management of various human bone tumors, particularly human bone rhabdomyosarcoma, human bone chondrosarcoma, human bone osteosarcoma, and human bone Ewing's sarcoma. [ABSTRACT FROM AUTHOR]

In recent years, silver nanoparticles have been used as modern chemotherapeutic drugs to treat several cancers such as pancreatic, breast, prostate, and blood cancers. No previous reports demonstrated the in vitro anti‐human pancreatic cancer effects of the novel chemotherapeutic drug formulated by silver nanoparticles containing Berberis thunbergii leaf (AgNPs). The synthesized AgNPs were characterized using different techniques including UV–vis. and FT‐IR spectroscopy, X‐ray diffraction, scanning electron microscopy (SEM), and TEM. All techniques approved the synthesized silver nanoparticles. The SEM and TEM exhibited a uniform spherical morphology and an average size of about 15 nm for the biosynthesized nanoparticles, respectively. The 4‐(dimethylamino)benzaldehyde,2,2‐diphenyl‐1‐ pikrilhydrazil (DPPH) test revealed similar antioxidant potentials for B. thunbergii leaf aqueous extract, AgNPs, and butylated hydroxytoluene. AgNPs inhibited half of the DPPH molecules in the concentration of 108 μg/mL. To survey the anti‐human pancreatic cancer activities of AgNO3, B. thunbergii leaf aqueous extract, and AgNPs, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay was used on common human pancreatic cancer cell lines. AgNPs had very low cell viability and anti‐human pancreatic cancer effects dose‐dependently against PANC‐1, AsPC‐1, and MIA PaCa‐2. The IC50 values of the AgNPs were 259, 268, and 141 μg/mL against PANC‐1, AsPC‐1, and MIA PaCa‐2 cell lines, respectively. It is thought that the AgNPs obtained can be used as an anticancer drug for the diagnosis of pancreatic cancer in humans after acceptance of the above findings in clinical study trials. [ABSTRACT FROM AUTHOR]

In the recent research, we investigated the application of gold nanoparticles green-synthesized by Alhagi maurorum aqueous extract in the treatment of several types of leukemia, i.e. acute T cell leukemia, acute lymphoblastic leukemia, and acute myeloid leukemia. Different techniques such as transmission electron microscopy (TEM), fourier-transform infrared spectroscopy (FTIR), and ultraviolet–visible spectroscopy analysis were used to characterize AuNPs. The TEM images show a spherical morphology for AuNPs with the range size of 21 to 59 for the synthetic nanoparticles. In the antioxidant test, the IC50 of AuNPs and butylated hydroxytoluene (BHT) against DPPH free radicals were 117 and 87 µg/mL, respectively. In the oncological part of the recent study, the treated cells with AuNPs and Cytarabine were assessed by MTT assay for 48 h about the cytotoxicity and anti-leukemia properties on normal (HUVEC) and leukemia cell lines i.e., acute myeloid leukemia (Human HL-60/vcr and 32D-FLT3-ITD), acute lymphoblastic leukemia (MOLT-3 and TALL-104), and acute T cell leukemia (J.RT3-T3.5 and Jurkat, Clone E6-1). The IC50 of AuNPs were 242, 297, 383, 207, 234, and 218 µg/mL against acute myeloid leukemia (Human HL-60/vcr and 32D-FLT3-ITD), acute lymphoblastic leukemia (MOLT-3 and TALL-104), and acute T cell leukemia (J.RT3-T3.5 and Jurkat, Clone E6-1) cell lines, respectively. In addition, the IC50 of Cytarabine were 117, 113, 145, 119, 131, and 135 µg/mL against acute myeloid leukemia (Human HL-60/vcr and 32D-FLT3-ITD), acute lymphoblastic leukemia (MOLT-3 and TALL-104), and acute T cell leukemia (J.RT3-T3.5 and Jurkat, Clone E6-1) cell lines, respectively. The viability of malignant leukemia cell line reduced dose-dependently in the presence of AuNPs and Cytarabine.

The diversity of small molecules formed via plant diterpene metabolism offers a rich source of known and potentially new biopharmaceuticals. Among these, the microtubule-destabilizing activity of pseudolaric acid B (PAB) holds promise for new anticancer agents. PAB is found, perhaps uniquely, in the coniferous tree golden larch (Pseudolarix amabilis, Pxa). Here we describe the discovery and mechanistic analysis of golden larch terpene synthase 8 (PxaTPS8), an unusual diterpene synthase (diTPS) that catalyzes the first committed step in PAB biosynthesis. Mining of the golden larch root transcriptome revealed a large TPS family, including the monofunctional class I diTPS PxaTPS8, which converts geranylgeranyl diphosphate into a previously unknown 5,7-fused bicyclic diterpene, coined "pseudolaratriene." Combined NMR and quantum chemical analysis verified the structure of pseudolaratriene, and co-occurrence with PxaTPS8 and PAB in P amabilis tissues supports the intermediacy of pseudolaratriene in PAB metabolism. Although PxaTPS8 adopts the typical three-domain structure of diTPSs, sequence phylogeny places the enzyme with two-domain TPSs of mono- and sesqui-terpene biosynthesis. Site-directed mutagenesis of PxaTPS8 revealed several catalytic residues that, together with quantum chemical calculations, suggested a substantial divergence of PxaTPS8 from other TPSs leading to a distinct carbocation-driven reaction mechanism en route to the 5,7-trans-fused bicyclic pseudolaratriene scaffold. PxaTPS8 expression in microbial and plant hosts provided proof of concept for metabolic engineering of pseudolaratriene.

In this study, iron nanoparticles were prepared and synthesized in aqueous medium using Cinnamomum verum as stabilizing and reducing agents. We determined the anti-acute leukemia potentials of FeNPs against acute T cell leukemia and acute lymphoblastic leukemia cell lines. FeNPs inhibited half of the DPPH molecules in the concentration of 139 µg/mL. MTT assay was used on J.RT3-T3.5 (Acute T cell leukemia cell line), Jurkat, Clone E6-1 (Acute T cell leukemia cell line), MOLT-3 (Acute lymphoblastic leukemia cell line), TALL-104 (Acute lymphoblastic leukemia cell line), and HUVEC (Normal cell line) for analyzing of cytotoxicity and anti-acute leukemia effects of FeNPs. These nanoparticles had high cell death and anti-acute leukemia effects against J.RT3-T3.5, Jurkat, Clone E6-1, MOLT-3, and TALL-104 cell lines. Among the above cell lines, the best result of anti-acute leukemia properties of composite was gained in the cell line of Jurkat, Clone E6-1. All result showed the iron nanoparticles may be used as a chemotherapeutic treatment drug of leukemia in humans. [ABSTRACT FROM AUTHOR]

We present a mathematical analysis of a mixed ODE-PDE model describing the spatial distribution and temporal evolution of tumor and normal cells within a tissue subject to the effects of a chemotherapeutic drug. The model assumes that the influx of chemotherapy is restricted to a limited region of the tissue, mimicking a blood vessel passing transversely. We provide results on the existence and uniqueness of the model solution and numerical simulations illustrating different model behaviors.

In the recent study, we decided to survey the capacities of metallic nanoparticles formulated by Allium monanthum (AgNPs) as a novel chemotherapeutic drug in the treatment of several types of breast cancers. Characterization of AgNPs was done by UV–Visible Spectroscopy (UV–Vis), Fourier Transformed Infrared Spectroscopy (FT‐IR), Transmission Electron Microscopy (TEM), and Field Emission Scanning Electron Microscopy (FE‐SEM). For investigating the antioxidant properties of AgNO3, Allium monanthum, and AgNPs, the DPPH test was used in the presence of butylated hydroxytoluene as the positive control. To survey the cytotoxicity and anti-breast cancer effects of AgNO3, Allium monanthum, and AgNPs, MTT assay was used on the breast adenocarcinoma (MCF7), breast carcinoma (Hs 578Bst), infiltrating ductal cell carcinoma (Hs 319.T), infiltrating lobular carcinoma of breast (UACC-3133), inflammatory carcinoma of the breast (UACC-732), and metastatic carcinoma (MDA-MB-453) cell lines. DPPH test revealed similar antioxidant potentials for Allium monanthum, AgNPs, and butylated hydroxytoluene. Silver nanoparticles had very low cell viability and anti-breast cancer properties dose-dependently against MCF7, Hs 578Bst, Hs 319.T, UACC-3133, UACC-732, and MDA-MB-453 cell lines without any cytotoxicity on the normal cell line. The best result of anti-breast cancer properties of AgNPs against the above cell lines was seen in the case of the UACC-3133 cell line. According to the above findings, the silver nanoparticles containing Allium monanthum aqueous extract can be administrated in humans for the treatment of several types of breast cancer especially breast adenocarcinoma, breast carcinoma, infiltrating ductal cell carcinoma, infiltrating lobular carcinoma of breast, inflammatory carcinoma of the breast, and metastatic carcinoma.

Gold nanoparticles as one of the productions of the chemistry field have a special place in the cure of many diseases. Many experiences in medicinal researches have indicated that the plants enhance the anticancer effects of gold nanoparticles. According to the above contents, we investigated the capacities of Spinacia oleracea L. leaf aqueous extract green-mediated gold nanoparticles (AuNPs) as a modern chemotherapeutic material in treating endometrial cancer. The physicochemical characterization tests including UV–Visible Spectroscopy (UV–Vis), Field Emission Scanning Electron Microscopy (FE‐SEM), Fourier Transformed Infrared Spectroscopy (FT‐IR), and Transmission Electron Microscopy (TEM) were used for investigating the physicochemical properties of AuNPs. To survey the antioxidant potentials of AuNPs, one of the common antioxidant techniques i.e., DPPH was used. Determination of anti-endometrial cancer effects of AuNPs was carried out by the MTT assay and against Ishikawa, KLE, HEC-1-A, and HEC-1-B cell lines. The physicochemical characterization analyses revealed that the AuNPs had been formulated as the best possible. The results of the DPPH test confirmed excellent antioxidant properties of AuNPs in comparison to the butylated hydroxytoluene. The AuNPs IC50 was 194 µg/mL in the antioxidant test. The results of the MTT assay confirmed removing Ishikawa, KLE, HEC-1-A, and HEC-1-B cell lines after treating with low concentrations of AuNPs. The IC50 of the AuNPs was 341, 335, 316, and 325 µg/mL against Ishikawa, KLE, HEC-1-A, and HEC-1-B cell lines, respectively. The best finding of anti-endometrial cancer potentials was determined in the HEC-1-A cell line. According to the above results, significant anti-endometrial cancer effects of Au nanoparticles green-mediated by S. oleracea leaf extract are confirmed. It is offered that the studies of the clinical trial are performed for approving the above findings in humans.

Chemotherapeutics drugs play a pivotal role in the treatment of cancer. However, many issues generate by chemotherapy drugs, including unfavorable harm to healthy cells and multidrug resistance (MDR), persist and have a negative impact on therapeutic outcomes. When compared to monotherapy, combination cancer therapy has many advantages, like improving efficacy through synergistic effects and overcoming drug resistance. Combination treatment may comprise several chemotherapeutics drugs and combinations of chemotherapeutic drugs with some other therapeutic options such as surgery or radiation. Cancer treatment that utilizes co-delivery strategies with siRNA and chemotherapeutic drugs has been shown to have highly effective antitumor effects in the treatment of many cancers. However, the highly complex mechanisms of chemotherapeutic drugs-siRNA pairs during the co-delivery process have received little attention. The ideal combination of chemotherapeutic drugs with siRNA is very crucial for producing the desirable anticancer effects that would greatly enhance therapeutic efficiency. This review puts an emphasis on the logic for choosing suitable chemotherapeutic drug-siRNA combinations, which may open the way for the co-delivery of chemotherapeutic drugs and siRNA for treating cancer in the clinic. This review summarizes recent breakthrough in the area of diverse mechanism-based chemotherapeutic drugs-siRNA combinations in cancer treatment.

Piperine (PIP) is an alkaloid found primarily in Piper longum, and this natural compound has been shown to exert effects on proliferation and survival against various types of cancer. In particular, PIP has potent inhibitory effects on breast cancer (BC), the most prevalent type of cancer in women worldwide. PIP targets numerous signaling pathways associated with the therapy of BC cells through the following mechanisms: (a) induction of arrest of the cell cycle and apoptosis; (b) alteration of the signaling protein expression; (c) reduction in transcription factors; and (d) inhibition of tumor growth. BC cells have the ability to resist conventional drugs, so one of the strategies is the combination of PIP with other phytochemicals such as paclitaxel, thymoquinone, hesperidin, bee venom, tamoxifen, mitoxantrone, piperlongumin, and curcumin. Nanotechnology‐based drug encapsulation systems are currently used to enhance the release of PIP. This includes polymer nanoparticles, carbon nanotubes, and liposomes. In the present review, the chemistry and bioavailability of PIP, its molecular targets in BC, and nanotechnological strategies are discussed. Future research directions are also discussed to further understand this promising natural product. [ABSTRACT FROM AUTHOR]

In the present study, iron nanoparticles were green-synthesized using the aqueous extract of Alhagi maurorum leaf aqueous extract. The synthesized FeNPs were characterized by analytical techniques including EDX, FE-SEM, XRD, UV–vis and FT-IR. The anti-human lung cancer activity of FeNPs was evaluated using MTT assay. The nanoparticles were formed in a spherical shape in the average size of 60.11 nm. In the cellular and molecular part of the recent study, the treated cells with FeNPs were assessed by MTT assay for 48 h about the cytotoxicity and anti-human lung cancer properties on normal (HUVEC) and lung cancer cell lines i.e. HLC-1 and PC-14. The viability of malignant lung cell line reduced dose-dependently in the presence of FeNPs. The IC50 of FeNPs was 195 and 181 µg/mL against HLC-1 and PC-14 cell lines, respectively. In the antioxidant test, the IC50 of FeNPs and BHT against DPPH free radicals was 214 and 62 µg/mL, respectively. After the clinical study, iron nanoparticles containing A. maurorum leaf aqueous extract may be used to formulate a new chemotherapeutic drug or supplement to treat several types of human lung cancer. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) caused Mycobacterium tuberculosis (M.tb) is one of infectious disease that lead a large number of morbidity and mortality all over the world. Although no reliable evidence has been found, it is considered that combining chemotherapeutic drugs with Chinese herbs can significantly improves the cure rate and the clinical therapeutic effect. Methods: Multi-drug resistant pulmonary tuberculosis (MDR-PTB, n = 258) patients with Qi-yin deficiency syndrome will be randomly assigned into a treatment group (n = 172) or control/placebo group (n = 86). The treatment group will receive the chemotherapeutic drugs combined with Chinese herbs granules (1 + 3 granules), while the control group will receive the chemotherapeutic drugs combined with Chinese herbs placebo (1 + 3 placebo granules). In addition, MDR-PTB (n = 312) patients with Yin deficiency lung heat syndrome will be randomly assigned to a treatment (n = 208) or control/placebo (n = 104) group. The treatment group will receive the chemotherapeutic regimen combined with Chinese herbs granules (2 + 4 granules), while the control group will receive the chemotherapeutic drugs and Chinese herbs placebo (2 + 4 placebo granules). The primary outcome is cure rate, the secondary outcomes included time to sputum culture conversion, lesion absorption rate and cavity closure rate. BACTEC™ MGIT™ automated mycobacterial detection system will be used to evaluate the M.tb infection and drug resistance. Chi-square test and Cox regression will be conducted with SAS 9.4 Statistical software to analyze the data. Discussion: The treatment cycle for MDR-PTB using standardized modern medicine could cause lengthy substantial side effects. Chinese herbs have been used for many years to treat MDR-PTB, but are without high-quality evidence. Hence, it is unknown whether Chinese herbs enhances the clinical therapeutic effect of synthetic drugs for treating MDR-PTB. Therefore, this study will be conducted to evaluate the clinical therapeutic effect of combining Chinese herbs and chemotherapeutic drugs to treat MDR-PTB cases. It will assist in screening new therapeutic drugs and establishing treatment plan that aims to improve the clinical therapeutic effect for MDR-PTB patients. Trial registration: This trial was registered at ClinicalTrials.gov (ChiCTR1900027720) on 24 November 2019 (prospective registered). [ABSTRACT FROM AUTHOR]

The title iron(II) complex, [Fe(C16H12NO2)2], crystallizes in the ortho-rhom-bic space group Pbca with the Fe(2+) cation positioned on an inversion center. The cyclo-penta-dienyl (Cp) rings adopt an anti conformation in contrast with other substituted ferrocenes in which the Cp rings appear in a nearly eclipsed conformation. The Cp and the aromatic rings are positioned out of the plane, with a twist angle of 70.20 (12)°, and the C(Cp)-C(CO) bond length is shorter than a typical C-C single bond, which suggests a partial double-bond character and delocalization with the Cp π system. The structure of the complex is compared to other functionalized ferrocenes synthesized in our laboratory.

Chemotherapeutic drugs could cause cardiovascular complications. Previous studies focused on the left ventricle, ignoring the right ventricle. Recent studies have shown that chemotherapeutic drug-induced heart in jury usually synchronously involves both the right ventricle and the left ventricle, and therefore right ventricular re modeling should not be ignored. Anthracyclines, trastuzumab, etc. could significantly affect the structure and function of the right ventricle. The mechanism of right ventricular remodeling caused by chemotherapeutic drugs is not completely clear at present. It may be related to the direct myocardial injury, oxidative stress, endothelial dysfunetion and pulmonary circulation damage caused by chemotherapeutic drugs. This article reviews on the effects of chemotherapeutic drugs on right ventricular remodeling. [ABSTRACT FROM AUTHOR]

• Mesoporous silica nanospheres (MSN) were produced by a template-assisted base-catalysed sol-gel methodology. • A surface coating shell of pH-reponsive polydopamine (PDA) was in situ formed around MSN. • PDA was in situ formed by oxidative self-polymerization of dopamine monomers under milde alkaline conditions. • TEM and XPS confirmed the presence of PDA coating shell (about 10 nm in thickness) around MSN surface. • The PDA surface coating shell protected metformin drug leakage under physiological-like conditions (pH 7.4). • The PDA surface coating shell allowed pH-responsive metformin drug release under acidic conditions (pH 4.5 - pH 5.5). A recent attention has been paid to the repurposing potential of metformin drug for cancer chemotherapy. Herein, pH-responsive metformin drug delivery nanocarriers were achieved using sol-gel synthesized mesoporous silica nanospheres (MSN) uniformly coated with polydopamine (PDA) shell. The PDA coating shell around the MSN surface was in situ formed through oxidative self-polymerization of dopamine monomers in an alkaline solution at room temperature. The microstructure, structural and textural characteristics of PDA@MSN were examined and compared to uncoated MSN. Furthermore, PDA coated metformin (MET) drug-loaded MSN were used to study the pH-responsive MET drug release behaviour under neutral and acidic conditions. The in vitro release test showed that the PDA coating shell not only protects MET drug leakage under normal physiological conditions (pH 7.4) but also allows for its controlled/sustained release in acidic conditions (pH 4.5 and pH 5.5) which closely mimic the intracellular acidity (pH 4.5–5.5) of endosomes/lysosomes formed around drug-loaded nanocarriers after their endocytosis by cancer cells. [Display omitted] [ABSTRACT FROM AUTHOR]

Every year, many people die due to cancer in all of the world. So, the preparation and formulation of new chemotherapeutic supplements and drugs with remarkable effects for the treatment of cancer are in the priority of both developing and developed countries. Recently, gold nanoparticles have been used as modern chemotherapeutic drugs for the treatment of several cancers such as leukemia, lung cancer, breast cancer, prostate cancer, etc. According to the above explanations, we tried to prepare and formulate a chemotherapeutic drug (gold nanoparticles in aqueous medium using Rhus coriaria L. fruit aqueous extract) for the treatment of several types of esophageal cancer including human esophageal squamous cell carcinoma, human Caucasian esophageal carcinoma, adenocarcinoma of the gastroesophageal junction, and distal esophageal adenocarcinoma. The organometallic chemistry tests such as Fourier Transformed Infrared Spectroscopy (FT‐IR), UV–Visible Spectroscopy (UV–Vis), Field Emission Scanning Electron Microscopy (FE‐SEM), and Transmission Electron Microscopy (TEM) were used for characterizing of gold nanoparticles. For investigating the antioxidant properties of HAuCl4, R. coriaria aqueous extract, and gold nanoparticles, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test was used in the presence of butylated hydroxytoluene as the positive control. To survey the cytotoxicity and anti-esophageal cancer effects of HAuCl4, R. coriaria aqueous extract, and gold nanoparticles, dye compound 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromidefor (MTT) assay was used on the human esophageal squamous cell carcinoma (KYSE-270), human Caucasian esophageal carcinoma (OE33), adenocarcinoma of the gastroesophageal junction (ESO26), and distal esophageal adenocarcinoma (FLO-1) cell lines. In the FT-IR test, the presence of many antioxidant compounds with related bonds caused the excellent condition for reducing of gold in the gold nanoparticles. In UV–Vis, the clear peak in the wavelength of 527 nm indicated the formation of gold nanoparticles. Also, in the FE-SEM and TEM images, the gold nanoparticles were spherical with an average size of 19–24 nm. The gold nanoparticles inhibited half of the DPPH molecules in the concentration of 196 µg/mL. The IC50 of the gold nanoparticles was 226, 213, 267, and 294 µg/mL against KYSE-270, OE33, ESO26, and FLO-1 cell lines, respectively. As mentioned, the gold nanoparticles had significant anti-esophageal cancer effects against the above cancers especially human Caucasian esophageal carcinoma. After approving the above results in the clinical trial studies, these gold nanoparticles can be used as a chemotherapeutic drug for the treatment of several types of esophageal cancer such as human esophageal squamous cell carcinoma, human Caucasian esophageal carcinoma, adenocarcinoma of the gastroesophageal junction, and distal esophageal adenocarcinoma.

Mesenchymal stem/stromal cell (MSC)-based therapy has become an attractive and advanced scientific research area in the context of cancer therapy. This interest is closely linked to the MSC-marked tropism for tumors, suggesting them as a rational and effective vehicle for drug delivery for both hematological and solid malignancies. Nonetheless, the therapeutic application of the MSCs in human tumors is still controversial because of the induction of several signaling pathways largely contributing to tumor progression and metastasis. In spite of some evidence supporting that MSCs may sustain cancer pathogenesis, increasing proofs have indicated the suppressive influences of MSCs on tumor cells. During the last years, a myriad of preclinical and some clinical studies have been carried out or are ongoing to address the safety and efficacy of the MSC-based delivery of therapeutic agents in diverse types of malignancies. A large number of studies have focused on the MSC application as delivery vehicles for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), chemotherapeutic drug such as gemcitabine (GCB), paclitaxel (PTX), and doxorubicin (DOX), prodrugs such as 5-fluorocytosine (5-FC) and ganciclovir (GCV), and immune cell-activating cytokines along with oncolytic virus. In the current review, we evaluate the latest findings rendering the potential of MSCs to be employed as potent gene/drug delivery vehicle for inducing tumor regression with a special focus on the in vivo reports performed during the last two decades.

In this study, V2O5 nanoparticles were synthesized in an aqueous medium using Calendula officinalis extract as stabilizing and reducing agents. The synthesized nanoparticles (VNPs@C.officinalis) were characterized using different techniques including UV–Vis. and FT-IR Spectroscopy, X‐ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and Energy Dispersive X-ray Spectrometry (EDS). According to the XRD analysis, 28.83 nm was measured for VNPs@C.officinalis crystal size. SEM images exhibited a uniform spherical morphology in size of 38.14 nm for the biosynthesized nanoparticles. To survey the cytotoxicity and anti-human cervical cancer effects of C. officinalis aqueous extract and vanadium nanoparticles, MTT assay was used on C-33 A [c-33a], SiHa, Ca Ski, DoTc2 4510, HT-3, and LM-MEL-41 cell lines. The IC50 of the vanadium nanoparticles were237, 259, 226, 409, 335, and 192 µg/mL against C-33 A [c-33a], SiHa, Ca Ski, DoTc2 4510, HT-3, and LM-MEL-41 cell lines, respectively. To survey the antioxidant properties of Calendula officinalis aqueous extract and vanadium nanoparticles, the DPPH test was used. The vanadium nanoparticles inhibited half of the DPPH molecules in a concentration of 125 µg/mL. As mentioned, the vanadium nanoparticles had significant antioxidant and anti-human cervical cancer effects.

The chemoresistance of lung cancer is a significant contributor to its high mortality and morbidity rate. There is an urgent need to identify differentially expressed genes in lung cancer patients with a poor prognosis to develop effective means to overcome drug resistance in subsequent treatment. In this study, we identified the secreted phosphoprotein 1 (SPP1) as a potential gene associated with a poor diagnosis of lung cancer patients using the Cancer Genome Atlas analysis, which suggested that the expression of SPP1 in tumor tissues was significantly higher than normal tissues. The high expression of SPP1 was also correlated with tumor grade and poor clinical prognosis. To understand the roles of SPP1 and the DNA methyltransferase 1 (DNMT1), which regulated SPP1 expression, in affecting cell viability, migration and invasion, SPP1 and DNMT1 were overexpressed in the human lung cancer A549 and NCI-446 cells, followed by analyzing cell viability, migration and invasion. We showed that SPP1 promoted the proliferation, migration and invasion of lung cancer cells, and increased the resistance of lung cancer to the chemotherapeutic drug cisplatin. Knocking down SPP1 in cells restored sensitivity to cisplatin. Further, A549 cells without SPP1 overexpression demonstrated lower tumor growth rate than SPP1 overexpression cells using the xenograft tumor mouse model. High expression of SPP1 in lung cancer tumor tissue was caused by the reduced methylation level of its promoter region mediated by DNMT1. Our data suggested that SPP1 can be used as a marker for highly malignant lung cancer and targeting SPP1 may be a potential lung cancer treatment strategy.

In recent years, silver nanoparticles (AgNPs) have been used as key chemotherapeutic drugs to treat various cancers like prostate, breast, ovarian, and blood cancers. No previous reports demonstrated the in vitro anti-human pancreatic cancer properties of the novel chemotherapeutic drug formulated by silver nanoparticle compounds including Zingiber officinale leaf. To survey the anti-human pancreatic cancer activities of AgNO3, Zingiber officinale leaf aqueous extract, and silver nanoparticles, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used on common human pancreatic cancer cell lines. According to the Field Emission Scanning Electron Microscopes (FE-SEM) and Transmission electron microscopy (TEM) images, the silver nanoparticles were in an average size of 18.93 nm with a spherical shape. 2,2-diphenyl-1-picrylhydrazyl (DPPH) test revealed similar antioxidant potentials for Zingiber officinale leaf aqueous extract, silver nanoparticles, and butylated hydroxytoluene. Silver nanoparticles inhibited half of the DPPH molecules in the concentration of 172 µg/mL. Silver nanoparticles had very low cell viability and anti-human pancreatic cancer properties dose-dependently against AsPC-1, PANC-1, and MIA PaCa-2. The IC50 values of the silver nanoparticles were 295, 312, and 220 µg/mL against AsPC-1, PANC-1, and MIA PaCa-2 cell lines, respectively. It is thought that the silver nanoparticles obtained can be used as an anticancer drug for the diagnosis of pancreatic cancer in humans after acceptance of the above findings in clinical study trials.

In recent days, novel biomolecule stabilized nanocomposites have come into prominence as featured next generation materials. In this article we have green synthesized Au nanoparticles being deposited and stabilized over chitosan (CS) molecules. The electron rich polar functional groups of chitosan have been exploited to cap the Au NPs. The structural and physical features of Au NPs-CS nanocomposite was analyzed with different techniques like Ultraviolet–Visible Spectroscopy, Fourier Transform Infrared Spectroscopy, Field Emission Scanning Electron Microscope, Transmission Electron Microscopy, and Energy-Dispersive X-Ray Spectroscopy techniques. Recently, noble metal nanoparticles have been used in the treatment of different cancers. This has prompted us to use our nanocomposite in the treatment of acute myeloid leukemia (AML) both in vitro and in vivo. Initially, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay was performed to study the excellent antioxidant properties of Au NPs-CS nanocomposite. For in vitro cytotoxicity studies, HUVEC normal cell line, 32D-FLT3-ITD and Murine C1498 cancer cell lines were used and the nanocomposite was found of comparable potential as the standard AML drug Daunorubicin. For in vivo studies, 7,12-Dimethylbenz[a]anthracene (DMBA) was injected for inducing AML over 50 mice and then the drug as well as the nanocomposite was administered. Subsequently, comparison of different immunological, hematological, biochemical, stereological parameters and S1PR1 and S1PR5 mRNA expressions were ascertained. By quantitative real-time polymerase chain reaction, S1PR1 and S1PR5 mRNA expression in lymphocytes were significantly (p ≤ 0.05) raised by treating the leukemic mice with the nanocomposite. Also, nanocomposite significantly (p ≤ 0.05) decreased the weight and volume of liver and spleen, the pro-inflammatory cytokines, and the total white blood cells, blast, neutrophil, monocyte, eosinophil, and basophil counts, increased the anti-inflammatory cytokines and the lymphocyte, platelet and red blood cells parameters, and regulated the biochemical parameters as compared to the untreated mice. An extensive study was done on these biological experiments using the Au NPs-CS nanocomposite and we achieved fascinating results such that it could be used as an alternative prospective chemotherapeutic drug for the treatment of acute myeloid leukemia.

Background: Aurora kinase A (AURKA) is a potent oncogene that is often aberrantly expressed during tumorigenesis, and is associated with chemo-resistance in various malignancies. However, the role of AURKA in chemo-resistance remains largely elusive. Methods: The cleavage of AURKA upon viral infection or apoptosis stimuli was assesed by immunoblotting assays in several cancer cells or caspase deficient cell line models. The effect of AURKA cleavage at Asp 132 on mitosis was explored by live cell imaging and immunofluorescence staining experiments. The role of Asp132-cleavage of AURKA induced by the chemotherapy drug paclitaxel was investigated using TUNEL, immunohistochemistry assay in mouse tumor xenograft model and patient tissues. Results: The proteolytic cleavage of AURKA at Asp 132 commonly occurs in several cancer cell types, regardless of viral infection or apoptosis stimuli. Mechanistically, caspase 3/7/8 cleave AURKA at Asp 132 , and the Asp 132 -cleaved forms of AURKA promote cell apoptosis by disrupting centrosome formation and bipolar spindle assembly in metaphase during mitosis. The AURKA D132A mutation blocks the expression of cleaved caspase 3 and EGR1, which leads to reduced therapeutic effects of paclitaxel on colony formation and malignant growth of tumor cells in vitro and in vivo using a murine xenograft model and cancer patients. Conclusions: This study reveals that caspase-mediated AURKA D132 proteolysis is essential for paclitaxel to elicit cell apoptosis and indicates that AURKA D132 is a potential key target for chemotherapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)