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Modern nanostructures must fulfill a wide range of functions to be valuable, leading to the combination of various nano-objects into hierarchical assemblies. Hybrid Nanoparticles (HNPs), comprised of multiple types of nanoparticles, are emerging as nanoscale structures with versatile applications. HNPs offer enhanced medical benefits compared to basic combinations of distinct components. They address the limitations of traditional nanoparticle delivery systems, such as poor water solubility, nonspecific targeting, and suboptimal therapeutic outcomes. HNPs also facilitate the transition from anatomical to molecular imaging in lung cancer diagnosis, ensuring precision. In clinical settings, the selection of nanoplatforms with superior reproducibility, cost-effectiveness, easy preparation, and advanced functional and structural characteristics is paramount. This study aims toextensively examine hybrid nanoparticles, focusing on their classification, drug delivery mechanisms, properties of hybrid inorganic nanoparticles, advancements in hybrid nanoparticle technology, and their biomedical applications, particularly emphasizing the utilization of smart hybrid nanoparticles. PHNPs enable the delivery of numerous anticancer, anti-leishmanial, and antifungal drugs, enhancing cellular absorption, bioavailability, and targeted drug delivery while reducing toxic side effects.

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BACKGROUND: Resveratrol has demonstrated its ability to regulate BRCA1 gene expression in breast cancer cells, and previous studies have established the binding of MBD proteins to BRCA1 gene promoter regions. However, the molecular mechanism underlying these interactions remains to be elucidated. The aimed to evaluate the impact of MBD proteins on the regulation of BRCA1, BRCA2, and p16 genes and their consequential effects on breast cancer cells. METHODS: Efficacy of resveratrol was assessed using the MTT assay. Binding interactions were investigated through EMSA, ChIP, & MeIP assay. Expression analyses of MBD genes and proteins were conducted using qRT-PCR and western blotting, respectively. Functional assays, including clonogenic, migratory, and sphere formation assays were used to assess cancer cells' colony-forming, metastatic, and tumor-forming abilities. The cytotoxicity of resveratrol on cancer cells was also tested using an apoptosis assay. RESULTS: The study determined an IC50 of 30µM for resveratrol. MBD proteins were found to bind to the BRCA1 gene promoter. Resveratrol exhibited regulatory effects on MBD gene expression, subsequently impacting BRCA1 gene expression and protein levels. Higher concentrations of resveratrol resulted in reduced colony and sphere formation, decreases migration of cancer cells, and an increases number of apoptotic cells in breast cancer cells. Impact Identification of MBD2-BRCA1 axis indicates their significant role in the induction of apoptosis and reduction of metastasis and proliferation in breast cancer cells. Further therapy can be designed to target these MBD proteins and resveratrol could be used along with other anticancer drugs to target breast cancer. CONCLUSIONS: In conclusion MBD2 protein interact to the BRCA1 gene promoter, and resveratrol modulates MBD2 gene expression, which in turn regulates BRCA1 gene expression, and inhibits cell proliferation, migration, and induces apoptosis in ER+, PR+ & Triple negative breast cancer cells.

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ß-carotene is obtained from both plants and animals and has been the subject of intense research because of its provitamin-A, antioxidant, and anticancer effects. Its limited absorption and oxidative degradation significantly reduce its antitumor efficacy when taken orally. In our study, we utilize a central composite design to develop "bio-safe and highly bio-compatible" solid lipid nanoparticles (SLNs) by using only the combination of palmitic acid and poloxamer-407, a block co-polymer as a surfactant. The current research aim to develop and characterize SLNs loaded with ß-carotene to improve their bioavailability and therapeutic efficacy. In addition, the improved cytotoxicity of solid lipid nanoparticles loaded with ß-carotene was screened in-vitro in human breast cancer cell lines (MCF-7). The nanoparticles exhibits good stability, as indicated by their mean zeta potential of -26.3 ± 1.3 mV. The particles demonstrated high drug loading and entrapment capabilities. The fabricated nanoparticle's prolonged release potential was shown by the in-vitro release kinetics, which showed a first-order release pattern that adhered to the Higuchi model and showed a slow, linear, and steady release over 48 h. Moreover, a diffusion-type release mechanism was used to liberate ß-carotene from the nanoparticles. For six months, the nanoparticles also showed a notable degree of physical stability. Lastly, using the MTT assay, the anti-cancer properties of ß-carotene-loaded solid lipid nanoparticles were compared with intact ß-carotene on MCF-7 cell lines. The cytotoxicity tests have shown that the encapsulation of ß-carotene in the lipid bilayers of the optimized formulation does not interfere with the anti-cancer activity of the drug. When compared to standard ß-carotene, ß-carotene loaded SLNs showed enhanced anticancer efficacy and it is a plausible therapeutic candidate for enhancing the solubility of water-insoluble and degradation-sensitive biotherapeutics like ß-carotene.

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India contributed approximately 66% of the malaria cases in the WHO South-East Asia region in 2022. In India, approximately 44% of cases have been reported to be disproportionately contributed by approximately 27 districts. A comparative analysis of reported malaria cases between January 2017 and December 2022 was performed in Mandla district, which is the site of a model malaria elimination demonstration project (MEDP) in Madhya Pradesh (MP), India. Compared to 2017, the decrease in malaria cases in Mandla from 2018 to 2022 was higher than MP and the rest of the country. The reduction of cases was significant in 2018, 2019, and 2021 (p < 0.01) (Mandla vs. MP) and was highly significant during 2018-2022 (p < 0.001) (Mandla vs. India). Robust surveillance and real-time data-based decisions accompanied by appropriate management, operational controls, and independent reviews, all designed for resource optimisation, were the reasons for eliminating indigenous malaria in Mandla district. The increase in infection rates during the months immediately following rains suggests that surveillance, vector control, and case management efforts should be specifically intensified for eliminating imported and indigenous cases in the near-elimination districts to work towards achieving the national elimination goal of 2030.

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OBJECTIVE/BACKGROUND: Benign prostatic hyperplasia (BPH) is increasing substantial burden on health care systems. Men with high body mass index (BMI) have bigger prostate volumes (PV) with subsequent increase in lower urinary tract symptoms (LUTS) than men with normal BMI. The purpose of this research was to investigate the correlation between Obesity and PV in patients with BPH. METHOD: The study included 560 patients (50-80 years) with BPH. Weight and height measured to calculate BMI. TRUS was used to measure PV. Patient demographics such as IPSS score and prostate specific antigen (PSA) were also noted. RESULTS: Patients in the study had a mean age of 65.3 ± 9.45 years and the mean BMI was 23.97 ± 4.89 kg/m2. The mean PV of each BMI group were 37.45 ± 0.81, 57.89 ± 1.52 and 77.94 ± 2.17 (ml) for normal, overweight and obese groups, respectively, and the average PV score was 57.76 ± 1.50 ml. The mean PSA score was 3.26 ± 0.94 (ng/dl) with a range of 0.6-10.4. There was significant correlation between BMI and PV (p = 0.001) as well as between BMI with PSA and IPSS (p = 0.02, 0.001, respectively). CONCLUSION: The results showing strong correlation between BMI and PV also BMI with PSA and IPSS. Therefore reducing weight may lead to a lower prostate volume in the elderly stage, making LUTS less noticeable and improving quality of life.

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The purpose of the current research is to formulate a smart drug delivery system for solubility enhancement and sustained release of hydrophobic drugs. Drug solubility-related challenges constitute a significant concern for formulation scientists. To address this issue, a recent study focused on developing PEG-g-poly(MAA) copolymeric nanogels to enhance the solubility of olmesartan, a poorly soluble drug. The researchers employed a free radical polymerization technique to formulate these nanogels. Nine formulations were formulated. The newly formulated nanogels underwent comprehensive tests, including physicochemical assessments, dissolution studies, solubility evaluations, toxicity investigations, and stability examinations. Fourier transform infrared (FTIR) investigations confirmed the successful encapsulation of olmesartan within the nanogels, while thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) studies verified their thermal stability. Scanning electron microscopy (SEM) images revealed the presence of pores on the surface of the nanogels, facilitating water penetration and promoting rapid drug release. Moreover, powder X-ray diffraction (PXRD) studies indicated that the prepared nanogels exhibited an amorphous structure. The nanogel carrier system led to a significant enhancement in olmesartan's solubility, achieving a remarkable 12.3-fold increase at pH 1.2 and 13.29-fold rise in phosphate buffer of pH 6.8 (NGP3). Significant swelling was observed at pH 6.8 compared to pH 1.2. Moreover, the formulated nexus is nontoxic and biocompatible and depicts considerable potential for delivery of drugs and protein as well as heat-sensitive active moieties.

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BACKGROUND: Resistance against artemisinin-based combination therapy is one of the challenges to malaria control and elimination globally. Mutations in different genes (Pfdhfr, Pfdhps, Pfk-13 and Pfmdr1) confer resistance to artesunate and sulfadoxine-pyrimethamine (AS + SP) were analysed from Mandla district, Madhya Pradesh, to assess the effectiveness of the current treatment regimen against uncomplicated Plasmodium falciparum. METHODS: Dried blood spots were collected during the active fever survey and mass screening and treatment activities as part of the Malaria Elimination Demonstration Project (MEDP) from 2019 to 2020. Isolated DNA samples were used to amplify the Pfdhfr, Pfdhps, Pfk13 and Pfmdr1 genes using nested PCR and sequenced for mutation analysis using the Sanger sequencing method. RESULTS: A total of 393 samples were subjected to PCR amplification, sequencing and sequence analysis; 199, 215, 235, and 141 samples were successfully sequenced for Pfdhfr, Pfdhps, Pfk13, Pfmdr1, respectively. Analysis revealed that the 53.3% double mutation (C59R, S108N) in Pfdhfr, 89.3% single mutation (G437A) in Pfdhps, 13.5% single mutants (N86Y), and 51.1% synonymous mutations in Pfmdr1 in the study area. Five different non-synonymous and two synonymous point mutations found in Pfk13, which were not associated to artemisinin resistance. CONCLUSION: The study has found that mutations linked to SP resistance are increasing in frequency, which may reduce the effectiveness of this drug as a future partner in artemisinin-based combinations. No evidence of mutations linked to artemisinin resistance in Pfk13 was found, suggesting that parasites are sensitive to artemisinin derivatives in the study area. These findings are a baseline for routine molecular surveillance to proactively identify the emergence and spread of artemisinin-resistant parasites.

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[This corrects the article DOI: 10.3389/fimmu.2023.1229667.].

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The present investigation highlights a rhodamine-B- and coumarin-based efficient probe that selectively detects Ga3+ over other metal ions. The active pocket of the ligand for trapping the metal ions and the binding stoichiometry of its Ga3+ complex were discovered by single-crystal X-ray diffraction (SC-XRD) analysis. This binding stoichiometry was further confirmed in the solution state by mass spectrometry and Job's plot. The detection limit was found to be at the nanomolar level. Pyrophosphate being a well-known quencher could easily quench the fluorescence intensity of the RC in the presence of Ga3+ and reversibly recognize Ga3+ in the solution. The spiro ring opening of the ligand after Ga3+ insertion is proposed to be the principal mechanism for the turn-on fluorescence response. This ring opening was confirmed by SC-XRD data and nuclear magnetic resonance (NMR) titration experiments. Both ground- and excited-state calculations of the ligand and complex have been carried out to obtain information about their energy levels and to obtain the theoretical electronic spectra. Furthermore, the live-cell imaging of the probe only and the probe after the addition of Ga3+ have been carried out in HaCaT cells and satisfactory responses were observed. Interestingly, with the help of this probe, Ga3+ can be tracked inside the intracellular organelle such as lysosomes along with other regions of the cell. The article highlights a rhodamine-coumarin-based probe for the detection of Ga3+ over other metal ions with a nanomolar level detection limit. Structural characterization of the ligand and its Ga3+ complex was investigated by SC-XRD. Density functional theory (DFT) and time-dependent DFT (TD-DFT) studies were carried out to explore the excited-state energies and electronic spectra. The application of the probe for the detection of Ga3+ in live cells has been explored, and positive responses were observed.

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The diabetic wound is excessively vulnerable to infection because the diabetic wound suggests delayed and incomplete healing techniques. Presently, wounds and ulcers related to diabetes have additionally increased the medical burden. A diabetic wound can impair mobility, lead to amputations, or even death. In recent times, advanced drug delivery systems have emerged as promising approaches for enhancing the efficacy of wound healing treatments in diabetic patients. This review aims to provide an overview of the current advancements in drug delivery systems in managing chronic diabetic wound healing. This review begins by discussing the pathophysiological features of diabetic wounds, including impaired angiogenesis, elevated reactive oxygen species, and compromised immune response. These factors contribute to delayed wound healing and increased susceptibility to infection. The importance of early intervention and effective wound management strategies is emphasized. Various types of advanced drug delivery systems are then explored, including nanoparticles, hydrogels, transferosomes, liposomes, niosomes, dendrimers, and nanosuspension with incorporated bioactive agents and biological macromolecules are also utilized for chronic diabetes wound management. These systems offer advantages such as sustained release of therapeutic agents, improved targeting and penetration, and enhanced wound closure. Additionally, the review highlights the potential of novel approaches such as antibiotics, minerals, vitamins, growth factors gene therapy, and stem cell-based therapy in diabetic wound healing. The outcome of advanced drug delivery systems holds immense potential in managing chronic diabetic wound healing. They offer innovative approaches for delivering therapeutic agents, improving wound closure, and addressing the specific pathophysiological characteristics of diabetic wounds.

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The increasing prevalence of food allergies worldwide and the subsequent life-threatening anaphylactic reactions often have sparse treatment options, providing only symptomatic relief. Great strides have been made in research and in clinics in recent years to offer novel therapies for the treatment of allergic disorders. However, current allergen immunotherapy has its own shortcomings in terms of long-term efficacy and safety, due to the local side effects and the possibility of anaphylaxis. Allergen-specific immunotherapy is an established therapy in treating allergic asthma, allergic rhinitis, and allergic conjunctivitis. It acts through the downregulation of T cell, and IgE-mediated reactions, as well as desensitization, a process of food tolerance without any allergic events. This would result in a protective reaction that lasts for approximately 3 years, even after the withdrawal of therapy. Furthermore, allergen-specific immunotherapy also exploits several routes such as oral, sublingual, and epicutaneous immunotherapy. As the safety and efficacy of allergen immunotherapy are still under research, the exploration of newer routes such as intra-lymphatic immunotherapy would address unfulfilled needs. In addition, the existence of nanoparticles can be exploited immensely in allergen immunotherapy, which would lead to safer and efficacious therapy. This manuscript highlights a novel drug delivery method for allergen-specific immunotherapy that involves the administration of specific allergens to the patients in gradual increasing doses, to induce desensitization and tolerance, as well as emphasizing different routes of administration, mechanism, and the application of nanoparticles in allergen-specific immunotherapy.

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A highly stereoselective, efficient and facile route was achieved for the synthesis of novel and biochemically potent sugar fused pyrano[3,2-c]pyranone derivatives starting from inexpensive, naturally occurring d-galactose and d-glucose. First, ß-C-glycopyranosyl aldehydes were synthesized from these d-hexose sugars in six steps, with overall yields 41-55%. Next, two different 1-C-formyl glycals were synthesized from these ß-C-glycopyranosyl aldehydes by treatment in basic conditions. The optimization of reaction conditions was carried out following reactions between 1-C-formyl galactal and 4-hydroxycoumarin. Next, 1-C-formyl galactal and 1-C-formyl glucal were treated with nine substituted 4-hydroxy coumarins at room temperature (25 °C) in ethyl acetate for ∼1-2 h in the presence of l-proline to obtain exclusively single diastereomers of pyrano[3,2-c]pyranone derivatives in excellent yields. Four compounds were found to be active for the MCF-7 cancer cell line. The MTT assay, apoptosis assay and migration analysis showed significant death of the cancer cells induced by the synthesized compounds.

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The pathetic malignant mesothelioma (MM) is a extremely uncommon and confrontational tumor that evolves in the mesothelium layer of the pleural cavities (inner lining- visceral pleura and outer lining- parietal pleura), peritoneum, pericardium, and tunica vaginalis and is highly resistant to standard treatments. In mesothelioma, the predominant pattern of lesions is a loss of genes that limit tumour growth. Despite the worldwide ban on the manufacture and supply of asbestos, the prevalence of mesothelioma continues to increase. Mesothelioma presents and behaves in a variety of ways, making diagnosis challenging. Most treatments available today for MM are ineffective, and the median life expectancy is between 10 and 12 months. However, in recent years, considerable progress has already been made in understanding the genetics and molecular pathophysiology of mesothelioma by addressing hippo signaling pathway. The development and progression of MM are related to many important genetic alterations. This is related to NF2 and/or LATS2 mutations that activate the transcriptional coactivator YAP. The X-rays, CT scans, MRIs, and PET scans are used to diagnose the MM. The MM are treated with surgery, chemotherapy, first-line combination chemotherapy, second-line treatment, radiation therapy, adoptive T-cell treatment, targeted therapy, and cancer vaccines. Recent clinical trials investigating the function of surgery have led to the development of innovative approaches to the treatment of associated pleural effusions as well as the introduction of targeted medications. An interdisciplinary collaborative approach is needed for the effective care of persons who have mesothelioma because of the rising intricacy of mesothelioma treatment. This article highlights the key findings in the molecular pathogenesis of mesothelioma, diagnosis with special emphasis on the management of mesothelioma.

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The present investigation highlights a quinoline-based small molecule probe (DEQ) for the detection of Cd2+ among other metal ions in near-aqueous media. The probe DEQ and its Cd2+ complex (DEQ-Cd) have been synthesized and characterized by all possible spectroscopic methods. The weakly emissive DEQ showed its strong emission in the presence of Cd2+, which is attributed to the photoinduced electron transfer (PET) along with the chelation-enhanced fluorescence (CHEF) mechanism. The 1:1 binding mode between ligand and Cd2+ is confirmed by single crystal XRD analysis, which is further supported by Job's plot and HRMS. The detection limit of the probe to recognize Cd2+ was found to be as low as 89 nM. Furthermore, DEQ can act as a reversible fluorescence probe with the off-on-off mechanism by the alternative addition of Cd2+ and EDTA. DFT and TD-DFT studies exposed the proposed mechanism after Cd2+ insertion and the obtained results for electronic spectra are in line with the experimental results. The response towards pH was quite interesting and allowed us to study its application in live cell imaging. With all the positive results, the proposed ligand DEQ can be used as a potential probe for the detection of Cd2+ in real-life applications.

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The objective of this investigation was to fabricate nanoparticles consisting of Imatinib mesylate-poly sarcosine-loaded chitosan/carrageenan in order to attain prolonged drug release and efficacious therapy for colorectal cancer. The study involved the synthesis of nanoparticles through the utilisation of ionic complexation and nanoprecipitation techniques. The subsequent nanoparticles were subjected to an assessment of their physicochemical characteristics, anti-cancer efficacy using HCT116 cell line, and acute toxicity. The present study examined two distinct nanoparticle formulations, namely IMT-PSar-NPs and CS-CRG-IMT-NPs, with respect to their particle size, zeta potential, and morphology. Both formulations demonstrated satisfactory characteristics, as they displayed consistent and prolonged drug release for a duration of 24 h, with the highest level of release occurring at a pH of 5.5. The efficacy and safety of IMT-PSar-NPs and CS-CRG-IMT-PSar-NPs nanoparticles were evaluated through various tests including in vitro cytotoxicity, cellular uptake, apoptosis, scratch test, cell cycle analysis, MMP & ROS estimate, acute toxicity, and stability tests. The results suggest that these nanoparticles were well fabricated and have promising potential for in vivo applications. The prepared polysaccharide nanoparticles have great potential for active targeting and could potentially reduce dose-dependent toxicity in the treatment of colon cancer.

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The outbreak of COVID-19 has caused great havoc and affected many parts of the world. It has imposed a great challenge to the medical and health fraternity with its ability to continue mutating and increasing the transmission rate. Some challenges include the availability of current knowledge of active drugs against the virus, mode of delivery of the medicaments, its diagnosis, which are relatively limited and do not suffice for further prognosis. One recently developed drug delivery system called nanoparticles is currently being utilized in combating COVID-19. This article highlights the existing methods for diagnosis of COVID-19 such as computed tomography scan, reverse transcription-polymerase chain reaction, nucleic acid sequencing, immunoassay, point-of-care test, detection from breath, nanotechnology-based bio-sensors, viral antigen detection, microfluidic device, magnetic nanosensor, magnetic resonance platform and internet-of-things biosensors. The latest detection strategy based on nanotechnology, biosensor, is said to produce satisfactory results in recognizing SARS-CoV-2 virus. It also highlights the successes in the research and development of COVID-19 treatments and vaccines that are already in use. In addition, there are a number of nanovaccines and nanomedicines currently in clinical trials that have the potential to target COVID-19.

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Lung cancer is a fatal disease caused by an abnormal proliferation of cells in the lungs. Similarly, chronic kidney disorders affect people worldwide and can lead to renal failure and impaired kidney function. Cyst development, kidney stones, and tumors are frequent diseases impairing kidney function. Since these conditions are generally asymptomatic, early, and accurate identification of lung cancer and renal conditions is necessary to prevent serious complications. Artificial Intelligence plays a vital role in the early detection of lethal diseases. In this paper, we proposed a modified Xception deep neural network-based computer-aided diagnosis model, consisting of transfer learning based image net weights of Xception model and a fine-tuned network for automatic lung and kidney computed tomography multi-class image classification. The proposed model obtained 99.39% accuracy, 99.33% precision, 98% recall, and 98.67% F1-score for lung cancer multi-class classification. Whereas, it attained 100% accuracy, F1 score, recall and precision for kidney disease multi-class classification. Also, the proposed modified Xception model outperformed the original Xception model and the existing methods. Hence, it can serve as a support tool to the radiologists and nephrologists for early detection of lung cancer and chronic kidney disease, respectively.

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Head and neck squamous cell carcinoma is a disease that most commonly produce tumours from the lining of the epithelial cells of the lips, larynx, nasopharynx, mouth, or oro-pharynx. It is one of the most deadly forms of cancer. About one to two percent of all neo-plasm-related deaths are attributed to head and neck squamous cell carcinoma, which is responsible for about six percent of all cancers. MicroRNAs play a critical role in cell proliferation, differentiation, tumorigenesis, stress response, triggering apoptosis, and other physiological process. MicroRNAs regulate gene expression and provide new diagnostic, prognostic, and therapeutic options for head and neck squamous cell carcinoma. In this work, the role of molecular signaling pathways related to head and neck squamous cell carcinoma is emphasized. We also provide an overview of MicroRNA downregulation and overexpression and its role as a diagnostic and prognostic marker in head and neck squamous cell carcinoma. In recent years, MicroRNA nano-based therapies for head and neck squamous cell carcinoma have been explored. In addition, nanotechnology-based alternatives have been discussed as a promising strategy in exploring therapeutic paradigms aimed at improving the efficacy of conventional cytotoxic chemotherapeutic agents against head and neck squamous cell carcinoma and attenuating their cytotoxicity. This article also provides information on ongoing and recently completed clinical trials for therapies based on nanotechnology.

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A brain tumor is an uncontrolled cell proliferation, a mass of tissue composed of cells that grow and divide abnormally and appear to be uncontrollable by the processes that normally control normal cells. Approximately 25,690 primary malignant brain tumors are discovered each year, 70% of which originate in glial cells. It has been observed that the blood-brain barrier (BBB) limits the distribution of drugs into the tumour environment, which complicates the oncological therapy of malignant brain tumours. Numerous studies have found that nanocarriers have demonstrated significant therapeutic efficacy in brain diseases. This review, based on a non-systematic search of the existing literature, provides an update on the existing knowledge of the types of dendrimers, synthesis methods, and mechanisms of action in relation to brain tumours. It also discusses the use of dendrimers in the diagnosis and treatment of brain tumours and the future possibilities of dendrimers. Dendrimers are of particular interest in the diagnosis and treatment of brain tumours because they can transport biochemical agents across the BBB to the tumour and into the brain after systemic administration. Dendrimers are being used to develop novel therapeutics such as prolonged release of drugs, immunotherapy, and antineoplastic effects. The use of PAMAM, PPI, PLL and surface engineered dendrimers has proven revolutionary in the effective diagnosis and treatment of brain tumours.

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Abemaciclib (Ab) and palbociclib (Pb) are CDK4/6 inhibitors used to cure advanced breast cancer (BC). However, acquired resistance is a major challenge. The molecular mechanisms and signature proteins of therapy resistance for Ab and Pb drugs need to be explored. Here we developed resistant cells for Ab and Pb drugs in MCF-7 cell lines and explored the mechanisms and signature proteins of therapy resistance in BC. Proteome profiling was performed using the label-free proteome-orbitrap-fusion-MS-MS technique. Gene ontology (GO)-terms, KEGG pathways and network analysis were performed for the proteome data. Drug-resistant cells showed increased drug tolerance, enhanced colony formation potential and an increased gap-healing tendency for the respective drug. Up-regulation of survival genes (BCL-2 and MCL-1) and down-regulation of apoptosis inducers were observed. Drug-resistance markers (MDR-1 and ABCG2 (BCRP)) along with ESR-1, CDK4, CDK6, and cyclin-D1 genes were up-regulated in resistant cells. A total of 237 and 239 proteins were found to be differentially expressed in the Ab and Pb-resistant cells, respectively. Down-regulated proteins induce apoptosis signalling and nucleotide metabolisms and restrict EGFR signalling; however, up-regulated proteins induce Erk, wnt-ß-catenin, VEGFR-PI3K-AKT, glucose transportation, and hypoxia signalling pathways and regulate hydrogen peroxide signalling pathways. The panel of identified proteins associated with these pathways might have characteristics of molecular signature and new drug targets for overcoming drug resistance in breast cancer.

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