Secretome analysis of breast cancer cells to identify potential target proteins of Ipomoea turpethum extract-loaded nanoparticles in the tumor microenvironment.

Background: Breast cancer is the leading cause of frequent malignancy and morbidity among women across the globe, with an increment of 0.5% incidences every year. The deleterious effects of traditional treatment on off-target surrounding cells make it difficult to win the battle against breast cancer. Hence, an advancement in the therapeutic approach is crucial. Nanotechnology is one of the emerging methods for precise, targeted, and efficient drug delivery in cells. The previous study has demonstrated the cytotoxic effect of Ipomoea turpethum extract on breast cancer cells delivered via NIPAAM-VP-AA nanoparticles (NVA-IT). Manipulating the tumor microenvironment (TME) to inhibit cancer progression, invasion, and metastasis seems to be very insightful for researchers these days. With the help of secretome analysis of breast cancer cells after treatment with NVA-IT, we have tried to find out the possible TME manipulation achieved to favor a better prognosis of the disease. Method: MCF-7 and MDA MB-231 cells were treated with the IC50 value of NVA-IT, and the medium was separated from the cells after 24 h of the treatment. Nano LCMS/MS analysis was performed to identify the secretory proteins in the media. Further bioinformatics tools like GENT2, GSCA, GeneCodis 4, and STRING were used to identify the key proteins and their interactions. Result: From the nano LCMS/MS analysis, 70 differentially expressed secretory proteins in MCF-7 and 191 in MDA MB-231 were identified in the cell's media. Fifteen key target proteins were filtered using bioinformatics analysis, and the interaction of proteins involved in vesicular trafficking, cell cycle checkpoints, and oxidative stress-related proteins was prominent. Conclusion: This study concluded that I. turpethum extract-loaded NIPAAM-VP-AA nanoparticles alter the secretory proteins constituting the TME to cease cancer cell growth and metastasis.

Secretome profiling of Artemisia absinthium extract-loaded polymeric nanoparticle-treated MCF-7 and MDA-MB-231 revealed perturbation in microtubule assembly and cell migration.

Introduction: Artemisia absinthium (wormwood) exhibits anticancer properties by inhibiting proliferation and causing cell death in breast cancer. Targeted drug delivery of A. absinthium nanoformulation using N-isopropyl acrylamide, N-vinyl pyrrolidone, and acrylic acid-based polymeric nanoparticles (NVA-AA NPs) was ensured by utilizing features of the tumor microenvironment, although their mechanism of action involved in cytotoxicity remains unknown. Methods: The present study employed nano LC-MS/MS to identify differences in secretory protein expression associated with the treatment of breast cancer cell lines (MCF-7; MDA-MB-231) by NVA-AA NPs for the determination of affected pathways and easily accessible therapeutic targets. Different bioinformatics tools were used to identify signature differentially expressed proteins (DEPs) using survival analysis by GENT2 and correlation analysis between their mRNA expressions and sensitivity toward small-molecule drugs as well as immune cell infiltration by GSCA. Results: Analysis by GENT2 revealed 22 signature DEPs with the most significant change in their expression regulation, namely, gelsolin, alpha-fetoprotein, complement component C3, C7, histone H2B type 1-K, histone H2A.Z, H2AX, heat shock cognate 71 kDa protein, heat shock 70 kDa protein 1-like, cytochrome c somatic, GTP-binding nuclear protein Ran, tubulin beta chain, tubulin alpha-1B chain, tubulin alpha-1C chain, phosphoglycerate mutase 1, kininogen 1, carboxypeptidase N catalytic chain, fibulin-1, peroxiredoxins 4, lactate dehydrogenase C, SPARC, and SPARC-like protein 1. Correlation analysis between their mRNA expressions versus immune cell infiltrates showed a positive correlation with antitumor immune response elicited by these NPs as well as a correlation with drug response shown by the GDSC and CTRP drugs in different cancer cells. Discussion: Our results suggest that NVA-AA NPs were able to invade the tumor microenvironment; transformed the communication network between the cancer cells; affected potential drivers of microtubular integrity, nucleosome assembly, and cell cycle; and eventually caused cell death.

Evaluation of acute oral toxicity of Ipomoea turpethum extract loaded polymeric nanoparticles in Wistar rats.

Introduction: The amalgamation of novel drug delivery techniques and potential drugs is considered the most promising tool for the treatment of diseases. In our study, we have employed N-isopropyl acrylamide, N-vinyl pyrrolidone, and acrylic acid (NIPAAM-VP-AA) copolymeric nanoparticles for delivering Ipomoea turpethum root extract. I. turpethum is a perennial herb (Convolvulaceae family) and has been used as medicine for ages. The present study was conducted to evaluate the safety of I. turpethum root extract-loaded NIPAAM-VP-AA polymeric nanoparticles (NVA-IT) in Wistar rats. Methods: An acute oral toxicity study was conducted in accordance with OECD guidelines 423 for the testing of chemicals. Different doses of NVA-IT i.e., 5 mg/kg, 50 mg/kg, 300 mg/kg, and 2000 mg/kg were administered to female Wistar rats in a stepwise manner using oral gavage. The toxicity signs were thoroughly observed for the next 14 days. At the end of the study, the blood and vital organs were harvested for hematological, biochemical, and histopathological studies. Result: No mortality or pathological anomalies were observed even at the highest dose which exemplifies that the lethal dose would be more than 2000 mg/kg body weight (GSH category 5). Behavioral changes, biochemical parameters, and histopathology of vital organs were normal after NVA-IT administration. Conclusion: This study demonstrated that NVA-IT nanoparticles are non-toxic and can be considered for therapeutic use in different diseases, such as inflammation, CNS diseases, Cancer, etc.

Identification of a survival associated gene trio in chemical induced breast cancer.

Sporadic cases of breast cancer being more prevalent than the hereditary cases, can be largely attributed to environmental pollutants like polycyclic aromatic hydrocarbons (PAHs). The aim of the present study was to identify gene dysregulations and the associations in DMBA (a PAH) induced breast cancer. A breast cancer model was developed in Wistar rats (n = 40), using DMBA. Serum proteomics (2D electrophoresis and MALDI-TOF MS) followed by relative gene expression analysis in mammary glands were conducted to reach to the differential gene signatures. The candidate genes were subjected to survival analysis (by GEPIA2 and KM plotter) and infiltration analysis (by ImmuCellAI) for correlating gene expression with patient survival and immune cell infiltration respectively. Further, the regulatory network investigation (by Cytoscape) was performed to find out the transcription factors (TFs) and miRNAs of the concerned genes. A gene trio (ANXA5, MTG1, PPP2R5B), expressing differentially in early mammary carcinogenesis at 4 months (precancerous stage) till full-fledged cancerous stage (post 6 months) was identified. The altered gene expression was associated with less survival among breast cancer patients (n = 4019). The dysregulated expression also has a correlation with enhanced mammary infiltration of immune cells. Moreover, a regulatory network (comprising of 77 transcription factors and 50 miRNAs) involved in the regulation of candidate genes was also deciphered. The deregulated target genes can therefore be explored for reregulation via identified TFs and miRNAs, and survival thereby improved.

Elevated expression of ISY1, APOA-1, SYNE1, MTG1, and MMP10 at HCC initiation: HCC specific protein network involving interactions of key regulators of lipid metabolism, EGFR signaling, MAPK, and splicing pathways.

Identification of molecular regulators of hepatocellular carcinoma (HCC) initiation and progression is not well understood. We chemically induced HCC in male Wistar rats by administration of diethyl nitrosamine (DEN) and 2-acetylaminofluorene (2-AFF). Using 2D-electrophoresis and MALDI-TOF-MS/MS analyses, we characterized differentially expressed proteins in liver tissues at early stage of HCC progression. Using RT-PCR analysis, we quantified the mRNA expression of the characterized proteins and validated the transcript expression with tumor tissues of clinically confirmed HCC patients. Using bioinformatic tools, we analyzed a network among the introduced proteins that identified their interacting partners and analyzed the molecular mechanisms associated with signaling pathways during HCC progression. We characterized a protein, namely, pre-mRNA splicing factor 1 homolog (ISY1), which is upregulated at both transcriptome and proteome levels at HCC initiation, progression, and tumor stages. We analyzed the interacting partners of ISY1, namely, APOA-1, SYNE1, MMP10, and MTG1. Real-time PCR analysis confirmed elevated expression of APOA-1 mRNA at HCC initiation, progression, and tumor stages in animals undergoing tumorigenesis. The mRNA expression of the interacting partners was validated with tumor tissues of clinically confirmed liver cancer patients; the analysis revealed significant elevation in expression of transcripts. The transcriptome and proteome analyses complement each other and dysregulation in mRNA and protein expression of these regulators may play critical role in HCC initiation and progression.

Chemokines and cytokines: Axis and allies in prostate cancer pathogenesis.

Chemokines are recognized as the major contributor to various tumorigenesis, tumor heterogeneity, and failures of current cancer therapies. The tumor microenvironment (TME) is enriched with chemokines and cytokines and plays a pivotal role in cancer progression. Chronic inflammation is also considered an instructive process of cancer progression, where chemokines are spatiotemporally secreted by malignant cells and leukocyte subtypes that initiate cell trafficking into the TME. In various cancers, prostate cancer (PCa) is reported as one of the leading cancers in the worldwide male population. The chemokines-mediated signaling pathways are intensively involved in PCa progression and metastasis. Emerging evidence suggests that chemokines and cytokines are responsible for the pleiotropic actions in cancer, including the growth, angiogenesis, endothelial mesenchymal transition, leukocyte infiltration, and hormone escape for advanced PCa and therapy resistance. Chemokine's system and immune cells represent a promising target to suppress tumorigenic environments and serve as potential therapy/immunotherapy for the PCa. In this review, an attempt has been made to shed light on the alteration of chemokine and cytokine profiles during PCa progression and metastasis. We also discussed the recent findings of the diverse molecular signaling of these circulating chemokines and their corresponding receptors that could become future targets for therapeutic management of PCa.

Mechanism of phthalate esters in the progression and development of breast cancer.

Phthalate esters are produced widely for their use as plasticizer in consumer products such as cosmetics, PVC, deodorants etc. Their use is considered harmless but they are known to induce cancer and work as endocrine disruptors. In this review, we try to emphasize the ubiquitous presence of phthalate esters and the pathways they affect to induce, metastasizes cancer or to prompt drug resistance in cancer cells. We reviewed the literature from the last one decade on PubMed. The keywords used were 'Phthalates' 'Breast cancer' 'endocrine disruptors' 'environmental carcinogens' 'Phthalates and reproductive health' etc. In conclusion, the phthalates are able to mimic estrogen, to prompt proliferation, metastasis and drug resistance in breast cancer cells. The data for its dosage exposure to induce ill-effects remains largely inconsistent. The only well researched molecular target of phthalate is Aryl hydrocarbon receptor (AhR) which is a ligand activated transcription factor. Being an interesting and important problem of research this aspect had not been touched in the way as it has to be.

Assessment of insulin resistance and metabolic syndrome in young reproductive aged women with polycystic ovarian syndrome: analogy of surrogate indices.

BACKGROUND: Polycystic ovarian syndrome has emerged as a cardiometabolic disorder and aim of this study was to evaluate various surrogate indices and their diagnostic potential to determine the most convenient and cost-effective marker of IR, CVD, and MetS in these women. MATERIALS AND METHODS: Ninety-five PCOS women and 45 age matched healthy women were enrolled. Measures included anthropometric and biochemical parameters, BMI, WHR, WHtR, BAI, VAI, LAP, HOMA-IR, and lipid profile. RESULTS: LAP has highest AUC value 0.781 with cut-off value = 39.73 (sensitivity = 75% and specificity = 79.5%) for predicting IR and AUC value 0.83 with cut-off value = 35.63 (sensitivity = 94.4% and specificity = 77.3%) for predicting MetS in women with PCOS. LAP had statistically strong positive correlation with WC, BMI, WHR, fasting glucose, fasting insulin, HOMA-IR, TC, TG, and SBP. CONCLUSIONS: LAP is a powerful and reliable marker for assessment of IR, CVD, and MetS risk in young Indian women with PCOS.

Emerging role of metabolomics in protein conformational disorders.

Introduction: Metabolomics focuses on interactions among different metabolites associated with various cellular functions in cells, tissues, and organs. In recent years, metabolomics has emerged as a powerful tool to identify perturbed metabolites, pathways influenced by the environment, for protein conformational diseases (PCDs) and also offers wide clinical application.Area Covered: This review provides a brief overview of recent advances in metabolomics as applied to identify metabolic variations in PCDs, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, prion disease, and cardiac amyloidosis. The 'PubMed' and 'Google Scholar' database search methods have been used to screen the published reports with key search terms: metabolomics, biomarkers, and protein conformational disorders.Expert opinion: Metabolomics is the large-scale study of metabolites and is deemed to overwhelm other omics. It plays a crucial role in finding variations in diseases due to protein conformational changes. However, many PCDs are yet to be identified. Metabolomics is still an emerging field; there is a need for new high-resolution analytical techniques and more studies need to be carried out to generate new information.

Secretome Profiling and Computational Biology of Human Leiomyoma Samples Unravel Molecular Signatures with Potential for Diagnostic and Therapeutic Interventions.

In recent years, significant advancements have been made in the way the complex proteome samples are compared but the ultimate goal of routine biomarker discovery has yet to be achieved. Based on reverse genetic strategy, our study involved the spotting of genes showing expressional variability in uterine leiomyoma females. Serum samples were taken from uterine leiomyomas subjects (n=6) and healthy control subjects (n=6) for proteomic studies. Additionally, leiomyoma tissue samples (n=25) and normal myometrium samples (n=25) were taken for validation studies. In this study, we profiled the proteomes of uterine leiomyoma patient's serum and healthy control, along with relative quantification using Nano LC-MS/MS analysis. A total of 146 proteins were reported to be significantly differentially expressed (P value less than 0.05) in case and control sample. Statistical analysis identified a number of molecular signatures distinguishing healthy from diseased serum. Among these, five proteins lumican, ficolin, MASP2, EMSY, and kallistatin were further chosen according to their function for validation. Kallistatin was downregulated while ficolin, MASP2, lumican, and EMSY were found to be upregulated in the diseased sample. The expression modulations in the identified genes were further validated in twenty-five cases. Interactions among the differentially expressed proteins were identified followed with network analysis. Network analysis emphasized important pathways that are highly deregulated in myoma, and functional significance of these pathways in the pathology of the disease was discussed. Comparative expression analysis reveals distinct molecular signatures and their probable role in diagnosis of the disease.

Elevated expression of sepiapterin reductase, regulator of G protein signaling 1, hypothetical protein CXorf58 homolog, and zinc finger and BTB domain-containing protein 21 isoform X2 is associated with progression of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers associated with high mortality rate. Understanding of events leading to HCC pathophysiology is essential for its better management. We earlier reported development of a novel rodent model by administrating chemical carcinogens, DEN, and 2-AAF for study of HCC at very early stage. 2D-Electrophoresis analysis of total serum proteins identified several differentially expressed proteins in animals undergoing tumorigenesis. MALDI-TOF-MS/MS analyses were performed to characterize the differentially expressed proteins. Further real-time PCR analyses were taken place to quantify the transcript expression for the identified proteins at HCC initiation and tumor stages. Considering protein-protein interactions among the experimentally identified proteins and their interacting neighbors, a protein network has been analyzed that provided further insight into molecular events taking place during HCC development. Histological changes confirmed HCC initiation and hepatotumorigenesis at 1 and 4 months post carcinogen treatment, respectively. Four differentially expressed proteins were identified which were further characterized as regulator of G protein signaling 1 (RGS1), sepiapterin reductase (SPR), similar to zinc finger and BTB domain-containing protein 21 isoform X2 (ZNF295), and a hypothetical protein CXorf58 homolog. Quantification of transcripts for these proteins revealed elevation in their expression both at initiation and tumorigenesis stages. The study deciphers the regulatory role of these proteins during HCC progression.

Differential levels of CHMP2B, LLPH, and SLC25A51 proteins in secondary renal amyloidosis.

OBJECTIVES: Renal amyloidosis (RA) is a rare disease, typically manifested with proteinuria, nephrotic syndrome, and ultimately leads to renal failure. The present study aims to profile the proteomes of renal amyloidosis patient's serum and healthy controls, along with relative quantification to find out robust markers for RA. METHODS: In this study, 12 RA patients and their corresponding age and gender-matched healthy controls were recruited from the Nephrology department of Max Super Specialty Hospital, New Delhi. We employed gel-based proteomic approach coupled with MALDI-TOF MS to compare protein expression patterns in RA patients and controls. Furthermore, validation of differential proteins (selected) was done using bio-layer interferometry. RESULTS: Eleven proteins showed remarkably altered expression levels. Moreover, expression modulation of three proteins (LLPH, SLC25A51, and CHMP2B) was validated which corroborated with two-dimensional gel electrophoresis (2-DE) results showing significant upregulation (p < 0.05) in RA patients followed by ROC analysis which demonstrated the diagnostic potential of these proteins. A protein-protein master network was generated implicating the above identified proteins along with their interactors, fishing out the routes leading to amyloidosis. CONCLUSION: This study indicates that the identified serum proteomic signatures could improve early diagnosis and lead to possible therapeutic targets in RA.

Mechanism of tumour microenvironment in the progression and development of oral cancer.

Oral cancer has been a major problem all across the globe, majorly in the developing countries. With a growing emphasis in the field of cancer research, the contribution of the tumour microenvironment has been gaining a lot of importance in identifying the role of components other than the tumour cells that cause the development of cancer, thus changing the outlook. The review will shed light on the studies that describe the role of microenvironment, its components as well as summarize the studies related to their mechanism in the progression of oral cancer. The literature for the review was derived mainly from Google Scholar and PubMed, in particular concentrating on the most recent papers published in 2019 and 2020, by using the keywords "Cancer, Oral Cancer, Metastasis, OSCC, Tumour microenvironment, CAFs, ECM, Cytokines, Hypoxia, Therapeutics targeting the microenvironment". The study provides insight into the world of micro-environmental regulation of oral cancer, the mechanism by which they interact and how to exploit it as a potential therapeutic haven for treating the disease. The components Cancer-Associated Fibroblasts (CAFs), Tumour-associated Macrophages (TAMs), Tumour-associated neutrophils (TANs), Hypoxic environment, myeloid-derived stem cells (MDSCs) and T regulatory (Tregs) cells and underlying mechanisms that control them will be the targets of study to understand the microenvironment.

Mechanism of WASP and WAVE family proteins in the progression of prostate cancer.

Prostate cancer (PCa) is the second most commonly diagnosed and third lethal cause of death from cancer in men worldwide. Despite the availability of vast treatment procedures, still the high occurrence of invasion and metastasis of PCa are reported in cancer patients. The WASP (Wiskott-Aldrich syndrome protein) and WAVE (WASP family verprolin homologous protein) family of proteins are actin cytoskeleton regulatory proteins, reported to enhance cancer cell invasion and migration in prostate cancer. Hence, this review sheds light on the studies that explored the potential role of WASP and WAVE family of proteins in invasion and metastasis of prostate cancer. The research articles explored for the completion of this review were mostly from PubMed and Google Scholar by using the appropriate keywords for indexing. The conserved function of WASP and WAVE protein family is to receive the upstream signals from the Rho GTPase family and transmit them to activate the Arp2/3 complex that leads to rapid actin polymerization at leading edge of cells, which is crucial for PCa metastasis. Therefore, targeting these proteins could reflect a very interesting therapeutic opportunity to combat prostate cancer.

Herbal Based Polymeric Nanoparticles as a Therapeutic Remedy for Breast Cancer.

BACKGROUND: The currently available anti breast cancer agents as well as conventional drug delivery methods have some limitations. OBJECTIVE: In view of these limitations, researchers used phytochemicals/herbal extracts as anti-breast cancer agents together with the polymeric nanoparticles to provide an effective way of targeted drug delivery with lesser /no side effects. METHODS: The literature for this review was searched during the year 2015 to 2019, using the keywords, ' 'breast cancer', 'breast cancer and its current treatments', 'plants against the breast cancer', 'polymeric nanoparticles', 'herbal based polymeric nanoparticles'. The databases i.e., PubMed, Science Direct, and Google Scholar, were used for collecting the information. RESULTS: In the present review, an attempt was made to summarize the potential of herbal-based nanoformulation as a specific and high efficacy therapeutic strategy in order to pave the way for future research involving screening and use of herbal nanoparticles for the treatment of breast cancer. CONCLUSION: The encapsulation of the herbal extract in the polymeric nanoparticles is the prominent, effective, and emerging way of targeted drug delivery for cancer. It may serve as a safer way of targeted drug delivery and maybe the answer to the complications related to the currently available anti-breast cancer agents as well as limitations of the conventional method of drug delivery.

Differential expression of Lumican, Mimecan, Annexin A5 and Serotransferrin in ectopic and matched eutopic endometrium in ovarian endometriosis: a case-control study.

AIM: Endometriosis is a debilitating disease marked by recurrent gynecological proliferations. The present study aimed at performing differential proteomic analysis of matched eutopic and ectopic endometrium from women with ovarian endometriosis. MATERIALS AND METHODS: Proteomes were resolved using nano LC-MS and further identified and quantified using ProteinLynx Global SERVER (PLGS) software. Selected proteins were further chosen for validation by real time-polymerase chain reaction (RT-PCR). RESULTS: The protein profiles uncovered several differentially expressed proteins in the diseased sample (ectopic endometrium) as compared to the reference sample (eutopic endometrium). The study involved an advanced proteomic approach, nano LC-MS, and validates for the first time the upregulation of Mimecan and Lumican proteins in endometriosis. CONCLUSIONS: These proteins may hence prove as potentially useful tools in the search for diagnostic markers for early detection of the disease.

Exosome vesicle as a nano-therapeutic carrier for breast cancer.

Breast cancer (BC) is one of the most common lethal diseases found in women; in which shortcomings of currently used treatment procedures and efficiency to target disease contribute to the increment in mortality. Despite other factors, exosomes, a major class of EVs (extracellular vesicles) also play a regulatory role in normal physiological processes and have a major function in proliferation, metastases, and resistance in BC. Interestingly, despite their role in the progression of BC, exosomes also showed their importance as a drug carrier in the targeted drug delivery. The present review aims to shed light on the role of exosomes as a potential nano-therapeutic vehicle in the targeted drug delivery for BC. Information for this review was searched from PubMed and Google Scholar mostly during the year 2019-2020 by using appropriate keywords. The exosomes have been efficiently used in cancer therapeutics where these nano vehicles having specific markers help in efficient targeted delivery of therapeutics including proteins, nucleic acid, and anti-cancer drugs to BC cells. The properties of exosomes as an efficient delivery system can be explored in the future and holds the potential to be used in other forms of cancer as well.

Differential expression of MAP3K7 and TROPONIN C proteins and related perturbations in renal amyloidosis.

OBJECTIVES: Renal amyloidosis (RA) is a rare protein misfolding disorder that prompts progressive renal insufficiency. This study aimed to decipher proteomic changes in human sera to understand the pathophysiology and molecular mechanisms underlying the disease development, hence assisting in the diagnosis of RA. METHODS: Serum proteomic analysis was performed using a gel-based approach followed by MALDI-TOF MS. RA patients with age and sex matched healthy volunteers were recruited from Max Super Speciality Hospital, New Delhi, India. RESULTS: Proteome profiles of serum revealed eight differentially expressed proteins namely, Zinc finger protein 624, Protein FAM183A, Calcium-binding mitochondrial carrier protein Scamc-3, V-type proton ATPase 116 kDa subunit A isoforms 2, Protein TXNRD3NB, ATP - dependent RNA helicase, Troponin C and Mitogen-activated protein kinase kinase kinase 7. These proteins were reported first time in RA. The increased levels of MAP3K7 and TROPONIN C were validated by bio-layer interferometry and their diagnostic accuracy was evaluated by ROC curve analysis. The differentially expressed proteins were predominantly associated with vesicular trafficking, transcriptional regulation, metabolic processes, apoptotic process and mitochondrial metabolism. CONCLUSION: The results indicate that these proteomic signatures may be considered as potential molecular targets for RA diagnostics and therapeutics subject to validation on large sample size. Abbreviations: AßP= Amyloid-beta protein, Aß=Amyloid-beta, AL= Light chain amyloidosis, AA= Amyloid A, ALECT2= LECT2 amyloidosis, APS= Ammonium persulfate CKD= Chronic Kidney Diseases, EBRT= external beam radiation therapy, ESRD= End-Stage Kidney Disease, Glis2= Gli-similar 2, JNK= c-Jun NH 2-terminal kinase, MAPK= Mitogen-Activated Protein Kinase, MM=Multiple Myeloma, PHD= Prolyl hydroxylase, RA = Renal Amyloidosis, SAA= Serum Amyloid A, SD= Standard Deviation, Sepp= Selenoprotein, SCC= Squamous cell carcinoma, SDS= Sodium dodecyl sulfate, TEMED = tetramethyl ethylenediamine, TGF-Beta-1=Transforming growth factor- Beta-1, Trx = Thioredoxin, TrxR= Thioredoxin reductase.

Cytotoxic potential of Artemisia absinthium extract loaded polymeric nanoparticles against breast cancer cells: Insight into the protein targets.

Targeted drug delivery system in the form of herbal based nano-formulations is the new ray of hope for minimizing the side effects related to the anti-cancer drugs as well as conventional drug delivery system. In view of this, the present study was designed to evaluate the cytotoxic potential of A. absinthium extract loaded polymeric nanoparticles (NVA-AA) against the breast cancer cell lines (MCF-7 and MDA MB-231) and to identify the protein targets for the caused cytotoxicity. The polymeric nanoparticles (PNPs) were prepared by free radical mechanism and loaded with the whole plant extract. The cytotoxicity of these NVA-AA were evaluated on the breast cancer cell lines via different cytotoxic parameters viz. MTT assay, CFSE proliferation assay, apoptosis assay, cell cycle study. The protein targets and the interaction among them were identified by nano-LCMS/MS analysis and STRING online tool respectively, which were further validated by qPCR and BLI. The LCMS/MS analysis suggests that the caused cytotoxicity was due to the alteration of proteins involved in vesicular trafficking, apoptosis, proliferation and metastasis. Further, interactome analysis identified UBA52 in MCF-7 and TIAL1, PPP1CC in MDA MB-231 cells as the central molecule in the vesicular trafficking and apoptosis networking connection.

Effects of Tobacco on Biochemical Parameters in Healthy and Type 2 Diabetic Subjects.

Diabetes and tobacco use are two of the largest public health challenges of our time. We aim to investigate the association between the two by comparing biochemical profiles of diabetic tobacco users (TUs) and tobacco nonus-ers (TNUs) to provide insight into the joint effect of tobacco and diabetes on body systems. This case-controlled study included 265 subjects, aged 18-60 yr, from the suburban population of Delhi, India. With the help of a questionnaire, participants are interviewed regarding their history of tobacco use. Results show association of tobacco use with elevated body-mass index, blood glucose levels, and insulin resistance in otherwise healthy and diabetic TUs. Even without previous history of coronary heart disease, total cholesterol and triglycerides are significantly further increased in TUs rather than in TNUs, indicative of initiation of lipid metabolism disorders. Tobacco use is also seen as a cause of oxidant/antioxidant imbalance in the body. Low serum albumin coupled with increased markers of inflammation and globulin levels is an indicator of generalized inflammation caused by tobacco's toxic effects. Creatinine levels are significantly higher in diabetic TUs, posing a threat to nephropathy progression. Evidence sufficiently infers that tobacco activates multiple biological pathways, through which the risk of metabolic disease increases. These factors may work in conjunction to increase risk of certain microvascular and macrovascular complications.