Antioxidant and anti-aging role of silk sericin in D-galactose induced mice model.

The main purpose was to elucidate the potential anti-aging impact of sericin, due to its anti-oxidant potential in D-galactose induced mice model. To induce natural aging in mice, a solution of 0.9 % saline containing D-galactose (250 mg/kg b.w.) was injected intraperitoneally for a period of 60 days. In this experiment, 56 male mice were arbitrarily categorized into 8 groups (1: control; 2: D-Galactose (250 mg/kg b.w), Group 3: Sericin (150 mg/kg b.w), Group 4: Metformin (150 mg/kg), Group 5: sericin (P), Group 6; sericin (T), Group 7; Met (P), Group 8; Met (T). The level of Glutathione reductase (2.1 ± 0.2 µmol/L), CAT (0.5 ± 0.0 mmol/mL), Superoxide dismutase (65.4 ± 1.7 U/mL), GSHPx (69.2 ± 1.7 U/l), T3 (3.1 ± 0.7 ng/mL), IL-2 (68.8 ± 1.5 Pg/mL), IL-4 (71.4 ± 4.2 Pg/mL), IgG (0.6 ± 0.0 mg/mL) and IgM (0.6 ± 0.0 mg/mL) were significantly (P < 0.05) decreased whereas the cortisol (22.0 ± 1.5 µg/L), and total cholesterol (229.4 ± 4.2 mg/dL)) were significantly elevated in D-galactose-treated /aged mice. However, administration of sericin significantly reduced the level of oxidative stress in aged mice. Real-time qPCR data showed that the level of telomere length- gene TERT significantly downregulated (10.43 ± 0.1) in the D-Gal-treated mice with respect to control (21.97 ± 0.5). The highest significant upregulation was found in the TERT gene when D-Gal-induced aged mice were treated with sericin (24.74 ± 0.3). Our outcomes showed that sericin gradually recovered the organ indices, and improved the histological changes of the brain, kidney, and liver in D-Gal-induced aging mice. Therefore, concluded that sericin possesses anti-aging effect against D-Gal-induced aging by diminishing oxidative stress, restoring the immune system, and enhancing the antioxidant defense system.

Regulatory role of circular RNAs in oral squamous cell carcinoma.

OSCC is a genomically complicated disease and advancements in the modern era of molecular oncology have enabled researchers to portray near-to-complete resolution of signaling landscape. Over the last two decades, overwhelming proof-of-concept has established mechanistic regulatory role of non-coding RNAs in carcinogenesis, including OSCC. Circular RNAs demonstrate a burgeoning facet of oncology research and molecular biologists are only beginning to appreciate and recognize the significance of circRNAs in the pathogenesis of OSCC. Regulatory roles of non-coding RNAs in the re-shaping of signaling pathways offer plausible strategies for prevention/inhibition of OSCC. Circular RNAs have mechanistic roles in OSCC and "sponge effects" mediated by a wider variety of circRNAs need to be rationally targeted for effective cancer prevention. Phenomenal and cutting-edge research works in different types of animal models will further refine our knowledge for selection of most promising circRNAs as pharmacologically valuable targets.

Tauroursodeoxycholic Acid (TUDCA) Regulates Inflammation and Hypoxia in Autonomic Tissues of Rats with Seizures.

Inflammation and hypoxia have an effect on the molecular mechanism of cardiovascular and respiratory pathologies accompanying seizures. Against this, Tauroursodeoxycholic Acid (TUDCA) can regulate oxidative stress, inflammation and cellular survival by suppressing endoplasmic reticulum (ER) stress. We evaluated the expression changes of NF-κB p65, TNF-α, HIF1α and Kir6.2 proteins associated with seizures in brain stem, heart and lung tissues representing the autonomous network. Additionally, we examined the protective effects of TUDCA administration against damage caused by seizures in terms of immunohistochemistry and pathology. 4 groups of Wistar Albino male rats (250-300 g, n=32) were formed as control, pentylenetetrazole (PTZ), TUDCA and PTZ+TUDCA. The epilepsy kindling model was created by intraperitoneal (i.p.) injection of PTZ chemical (35 mg/kg, every 2 days) for one month. TUDCA (500 mg/kg; every 2 days) treatment was given intraperitoneally 30 minutes before seizures for 1 month. Brain stem, heart (atria, ventricle) and lung tissues of rats were isolated. NF-κB p65, TNF-α, HIF1α and Kir6.2 proteins in the obtained tissues were evaluated by immunohistochemical staining. The immunoreactivity of the investigated proteins in the brainstem heart and lung tissues of rats with chronic PTZ administration was significantly increased. Recurrent seizures led to accumulation of inflammatory cells in tissues, hemorrhage, vasodilation, and apoptosis. Following TUDCA administration, expression of NF-κB p65, TNF-α and Kir6.2 was significantly reduced in all tissues (except the atrium of the heart) compared to control rats. HIF-1α levels were significantly suppressed in ventricular and lung tissues of epileptic rats given TUDCA. However, TUDCA pretreatment improved histopathological changes due to chronic seizures and partially reduced apoptosis. We showed that epileptic seizures may cause tissue damage with the development of inflammatory and hypoxic conditions in the brainstem and organs that represent the autonomic network. TUDCA therapy could be an effective agent in the treatment of cardiac and respiratory problems associated with seizures.

Characterization and bioactivities of M. arvensis, V. officinalis and P. glabrum: In-silico modeling of V. officinalis as a potential drug source.

In current study the pharmaceutically active herbs was used against coccidiosis, caused by a protozoan: Eimeria, lead to $ 3 billion loss annually. The aqueous and methanolic extracts of whole plants were applied in-vitro to assess sporulation inhibition (spi) assay and calculated the inhibitory concentration (IC50). For in-vivo study 9 groups of 14 day old broiler chicks were infected with Eimeria tenella and three groups were treated different concentrations of methanolic extracts of Verbena officinalis and Polygonum glabrum post infection. The mean weight gain, oocyst count, diarrhea, biochemical tests, hematology, and histopathology of all groups were analyzed. The herbs were characterized by antioxidant assay, phytochemical screening, Fourier transmission and infrared (FT-IR), Ultra Violet-visible (UV-Vis) spectroscopy and Gas chromatography and mass spectroscopy (GC-MS). The GC-MS identified phyto-compounds of V. officinalis were docked with S-Adenosyl methionine (SAM) synthetase. The in-vitro study revealed that V. officinalis and P. glabrum have minimum IC50 of 0.14 and 12 mg/ml respectively. The in-vivo experiment showed that V. officinalis had significantly high anticoccidial potential with significant hematological profile like drug treated controls. The histology of treated chicks also showed recovery in the studied tissues. The antioxidant assay showed that V. officinalis have 4.19U/mg Superoxide dismutase (SOD) and 33.96 µM/mg Glutathione (GSH) quantities. The chemical characterization confirmed the presence of large number of organic compounds, however Flavonoids found only in V. officinalis, which suggests the anticoccidial potential of V. officinalis because flavonoids as antagonist of thiamine (Prinzo, 1999), because it promotes the carbohydrate synthesis required. Strychane, 1-acetyl-20a-hydroxy-16-methylene has best binding of with target protein with lowest binding score (-6.4 Kcal/mol), suggests its anticoccidial potential in poultry.

Apoptotic and antiproliferative effects of silk protein sericin conjugated-AgNO3 nanoparticles in human breast cancer cells.

Bombyx mori silk sericin is a globular-like protein that is used as an antioxidant, antibacterial, and antitumor agent. In this current research, we isolated sericin by degumming process and formation of sericin-AgNO3 NPs confirmed by UV-vis spectra, SEM, EDX, FTIR, and XRD patterns. The sericin and sericin-AgNO3 NPs mediated changes in human breast cancer cells were determined. The antiproliferative activity of sericin-AgNO3 NPs was analyzed by MTT dye reduction assay. Alterations at molecular levels were investigated by qRT-PCR, while apoptotic effects were studied by nuclear DNA staining. After 72 h treatment, sericin and sericin-AgNO3 NPs showed significant antiproliferative effects in MDA-MB-231 (26 %) and MCF-7 (41 %) cells. Expression modification showed prominent stimulation of cell cycle arrest and stress related genes such as cyclin-dependent kinase inhibitors (CDKN1A, CDKN1B), and GADD family genes. RT-PCR results of the GADD family include GADD45A, B, G, 34, 153 and cyclin-dependent kinase inhibitors (CDKN1A, 1B) showed pronounced induction of 3.1 to 19.8-folds in MCF-7 cell line while induction in MDA-MB-231 cell line was 2.5 to 34.3-folds. Nuclear DAPI staining showed significant induction of apoptosis and nuclear fragmentation in MDA-MB-231 cells at a concentration of 1 mg/mL for both sericin and sericin-AgNO3 NPs. Meanwhile, in case of MCF-7 cells, after treatment with sericin and sericin-AgNO3 NPs (1 mg/mL), the cells changed into a round shape and lost their original spindle outlook in dose-dependent manners. We concluded that sericin-AgNO3 NPs have significant antiproliferative, apoptosis, and genetic profiling effects in both breast cancer cell lines at the highest concentration.

Biocidal action, characterization, and molecular docking of Mentha piperita (Lamiaceae) leaves extract against Culex quinquefasciatus (Diptera: Culicidae) larvae.

Mosquitoes are found in tropical and subtropical areas and are the carriers of a variety of diseases that are harmful to people's health. e.g., malaria, filariasis, chikungunya, dengue fever, etc. Although several insecticides are available, however, due to insect resistance and environmental hazards, more eco-friendly chemicals are needed for insect control. So, the current research was planned to explore the prospective of Mentha piperita to be used for the formulation of larvicides against mosquito Culex quinquefasciatus. The ethanolic and water extracts of M. piperita leaves were prepared using the soxhlet apparatus. The extracts were dried and subjected to prepare five concentrations multiple of 80 ppm. Each concentration was applied for its larvicidal efficacy setting an experiment (in triplicate) in plastic containers of 1000 ml with extracts, 30 larvae of all four instars separately, and fed with dog biscuits along with controls. Observations were taken after each 12 hrs. till 72 hrs. The antioxidant perspective of M. piperita was determined by DPPH radical scavenging, total antioxidant capacity, and ferric reducing power assays. Using brine shrimp lethality bioactivity, the cytotoxic study was perceived. Standard techniques were used to classify the M. piperita extract using preliminary qualitative and quantitative phytochemicals, UV-Vis spectroscopy, FT-IR, and GC-MS analysis. M. piperita ethanolic leaves extract after 24 hrs. of exposure in 400 ppm showed 93% (LC50 = 208.976 ppm) mortality in ethanolic extract and 80% (LC90 = 246.900 ppm) in the water extract. In treated larvae, biochemical examination revealed a substantial (P<0.05) decrease in proteins, carbohydrates, and fat contents. The ethanol extract of M. piperita was the most efficient, killing brine shrimp nauplii in 50% to 90% of cases. TAC (125.4 3.5gAAE/mg DW) and FRP (378.1 1.0gAAE/mg DW) were highest in the ethanolic extract of M. piperita. The presence of medicinally active components such as alkaloids, carbohydrates, flavonoids, and others in M. piperita leaves extract in ethanol was discovered. The UV-Vis spectrum showed two peaks at 209.509 and 282.814 nm with the absorption of 2.338 and 0.796 respectively. The FT-IR consequences exhibited the occurrence of alcohols, alkanes, aldehyde, aromatic rings, ether linkage, ester, and halo- compounds. The GC-MS analysis according to peak (%) area and retention time showed ten phytochemicals consisting of six major and four minor compounds. Among all the compounds, 1, 2-benzene dicarboxylic acid, and 3-ethyl-5, 5-dimethyl -6-phenyl bound well to the NS3 protease domain with PDB ID: 2FOM. Hence, for the prevention of health hazards and mosquito control, M. Piperita is a potential source of chemicals for insecticide formulation.

Role of DNA Methyltransferases (DNMTs) in metastasis.

The DNA methyltransferase (DNMT) family constitutes a conserved set of DNA-modifying enzymes which have essential functions in the modulation of epigenetics. The fundamental role of epigenetic changes in carcinogenesis and metastasis is increasingly being appreciated. DNMTs (DNMT1, DNMT3A and DNMT3B) have been shown to drive metastasis. Epigenetic machinery is installed at the target sites for the regulation of a wide variety of genes. Moreover, microRNAs, long non-coding RNAs and circular RNAs also shape the epigenetic landscape during metastasis. In this review, we have provided a snapshot of the quintessential role of DNMTs in metastasis. We also summarize how lncRNAs and circRNAs play roles in the epigenetic regulation of a myriad of genes.

Minocycline-Derived Silver Nanoparticles for Assessment of Their Antidiabetic Potential against Alloxan-Induced Diabetic Mice.

Diabetes is a life-threatening disease, and chronic diabetes affects parts of the body including the liver, kidney, and pancreas. The root cause of diabetes is mainly associated with oxidative stress produced by reactive oxygen species. Minocycline is a drug with a multi-substituted phenol ring and has shown excellent antioxidant activities. The objective of the present study was to investigate the antidiabetic potential of minocycline-modified silver nanoparticles (mino/AgNPs) against alloxan-induced diabetic mice. The mino/AgNPs were synthesized using minocycline as reducing and stabilizing agents. UV-visible, FT-IR, X-ray diffraction (XRD), and transmission electron microscopy (TEM) were applied for the characterization of mino/AgNPs. A 2,2-diphenyl-1-picrylhydrazyl free radical scavenging assay was conducted to determine the antioxidant potential of newly synthesized mino/AgNPs. The results revealed that the mino/AgNPs showed higher radical scavenging activity (IC50 = 19.7 µg/mL) compared to the minocycline (IC50 = 26.0 µg/mL) and ascorbic acid (IC50 = 25.2 µg/mL). Further, mino/AgNPs were successfully employed to examine their antidiabetic potential against alloxan-induced diabetic mice. Hematological results showed that the mice treated with mino/AgNPs demonstrated a significant decrease in fasting blood glucose level and lipid profile compared to the untreated diabetic group. A histopathological examination confirmed that the diabetic mice treated with mino/AgNPs showed significant recovery and revival of the histo-morphology of the kidney, central vein of the liver, and islet cells of the pancreas compared to the untreated diabetic mice. Hence, mino/AgNPs have good antidiabetic potential and could be an appropriate nanomedicine to prevent the development of diabetes.

Drug-Based Gold Nanoparticles Overgrowth for Enhanced SPR Biosensing of Doxycycline.

In clinical chemistry, frequent monitoring of drug levels in patients has gained considerable importance because of the benefits of drug monitoring on human health, such as the avoidance of high risk of over dosage or increased therapeutic efficacy. In this work, we demonstrate that the drug doxycycline can act as an Au nanoparticle (doxy-AuNP) growth and capping agent to enhance the response of a surface plasmon resonance (SPR) biosensor for this drug. SPR analysis revealed the high sensitivity of doxy-AuNPs towards the detection of free doxycycline. More specifically, doxy-AuNPs bound with protease-activated receptor-1 (PAR-1) immobilized on the SPR sensing surface yield the response in SPR, which was enhanced following the addition of free doxy (analyte) to the solution of doxy-AuNPs. This biosensor allowed for doxycycline detection at concentrations as low as 7 pM. The study also examined the role of colloidal stability and growth of doxy-AuNPs in relation to the response-enhancement strategy based on doxy-AuNPs. Thus, the doxy-AuNPs-based SPR biosensor is an excellent platform for the detection of doxycycline and demonstrates a new biosensing scheme where the analyte can provide enhancement.

Molecular epidemiological survey of cutaneous leishmaniasis from Azad Jammu and Kashmir, Pakistan.

Cutaneous leishmaniasis (CL) is an emerging neglected tropical disease in Azad Jammu and Kashmir which is an underdeveloped area. Prevalence and parasite species identification are the key factors to control disease in a particular population, which were the objectives of the present study. Due to a lack of previous data, we performed a district-based active CL surveillance in 2018. The data of CL, suspected (n = 20,000) cases were analyzed statistically and identified the parasite species in microscopic positive cases by ITS1-PCR RFLP and also obtained accession numbers MN891719-28 from gene Bank. The phylogenetic tree was constructed using MEGA6 software. Out of 20,000 CL, suspected cases the highest rate of 4.02% (135/3360) of CL in Mirpur and the lowest 1.58% (8/505) in Neelum was reported. The slide positivity rate, annual parasite incidence rate and annual blood examination rate were 2.27 per 1000 population, 0.08 and 0.34%. The males were more infected 58.12% (297/511) than females 41.88% (214/511) and the age group of 1-20 years were found highly infected 82.78% (423/511) than 21-40 years 13.89% (71/511) and 41-60 years 3.33% (17/511) in the studied population. The patients 56.36% (288/511) had a single lesion whereas 29.35% (150/511) had two, only 10.76% (31/288) and 8% (12/150) were using bed nets. The patients 14.29% (73/511) had three or more lesions were not using bed nets. Only 27.98% (143/511) patients had received treatment, while 72.02% (368/511) didn't. Microscopically positive cases were found to be 2.56% (511/20,000) and ITS1-PCR positive cases were found to be 91.39% (467/511). The RFLP assay confirmed the presence of Leishmania tropica in 467 samples.

Regulation of signaling pathways by Ampelopsin (Dihydromyricetin) in different cancers: exploring the highways and byways less travelled.

Ampelopsin or Dihydromyricetin is gradually emerging as a high-quality natural product because of its ability to modulate wide-ranging signaling pathways. Ampelopsin (Dihydromyricetin) has been reported to effectively modulate growth factor receptor (VEGFR2 and PDGFRß) mediated signaling,  TRAIL/TRAIL-R pathway, JAK/STAT and mTOR-driven signaling in different cancers. Ampelopsin (Dihydromyricetin) has also been shown to exert inhibitory effects on the versatile regulators which trigger EMT (Epithelial-to-Mesenchymal Transition). Findings obtained from in-vitro studies are encouraging and there is a need to comprehensively analyze how Ampelopsin (Dihydromyricetin) inhibits tumor growth in different cancer models. Better knowledge of efficacy of Ampelopsin (Dihydromyricetin) in tumor bearing mice will be helpful in maximizing its translational potential.

In Vitro Drug Release and Biocatalysis from pH-Responsive Gold Nanoparticles Synthesized Using Doxycycline.

pH-sensitive doxycycline gold nanoparticles (doxy-AuNPs) are reported here to act as effective drug nanocarriers and as biocatalysts. The AuNPs were synthesized with doxy as the reducing and capping agent. Various parameters were optimized to find the best conditions for the synthesis of doxy-AuNPs, and these were characterized with UV-vis, X-ray diffraction (XRD), FTIR, and transmission electron microscopy (TEM). Doxy-AuNPs were then loaded with the anticancer drug doxorubicin (DOX), where 70% of the initially available drug was loaded within 24 h. Furthermore, pH-dependent drug release was measured at 60% with in vitro measurements in phosphate-buffered saline (PBS). In addition, the doxy-AuNPs were applied as a biocatalyst. Oxidation of dopamine was taken as a model reaction to determine the catalytic activity of doxy-AuNPs. Almost complete oxidation of dopamine occurred in 5 min, which indicates the fast response of synthesized doxy-AuNPs as a biocatalyst. Hence, doxy-AuNPs are a versatile platform for drug loading and biocatalyst.

MicroRNA-143 as a new weapon against cancer: overview of the mechanistic insights and long non-coding RNA mediated regulation of miRNA-143 in different cancers.

Central dogma of molecular biology, a term coined by Francis Crick in 1958 was considered to be the cornerstone of molecular biology unless molecular biologists challenged the idea after ground-breaking discovery of non-coding RNAs. Discovery of microRNAs marked a new era and revolutionized our understanding related to puzzling mysteries about intermediate steps between transcription and translation. Technological advancements have spawned a multitude of platforms for profiling of long-noncoding RNAs and miRNAs in different cancers. Detailed investigation of mRNA targets of miRNAs has enabled high-order analyses of interconnected networks and revealed affected pathways in different cancers. miR-143 has emerged as a multi-talented tumor suppressor microRNA having considerable ability to inhibit and prevent cancer via regulation of myriad of oncogenes. In this review, we will summarize most recent evidence related to characteristically unique ability of miR-143 to target different oncogenic mRNAs in different cancers. We will also comprehensively discuss how scientists have identified multiple long non-coding RNAs reportedly involved in promoting the expression of oncogenes by interfering with miR-143 mediated targeting of these oncogenes. Because of excellent ability of miR-143 to effectively target oncogenic mRNAs, researchers have started to focus on use of miR-143 mimics to restore expression of miR-143 in various cancers.

Role of mTORC1 and mTORC2 in Breast Cancer: Therapeutic Targeting of mTOR and Its Partners to Overcome Metastasis and Drug Resistance.

Based on the insights gleaned from decades of research, it seems clear that mechanistic target of rapamycin (mTOR) is an essential signaling node that integrates environmental clues for regulation of cell survival, metabolism and proliferation of the cells. However, overwhelmingly increasing scientific evidence has added a new layer of intricacy to already complicated and versatile signaling pathway of mTOR. Deregulation of spatio-temporally controlled mTOR-driven pathway played contributory role in breast cancer development and progression. Pharmacologists and molecular biologists have specifically emphasized on the identification and development of mTOR-pathway inhibitors. In this chapter we have attempted to provide an overview of the most recent findings related to therapeutic targeting of mTOR-associated mTORC1 and mTORC2 in breast cancer. We have also comprehensively summarized regulation of mTOR and its partners by microRNAs in breast cancer.

NEDD4 Family of E3 Ubiquitin Ligases in Breast Cancer: Spotlight on SMURFs, WWPs and NEDD4.

Massively parallel sequencing, genomic and proteomic technologies have provided near complete resolution of signaling landscape of breast cancer (BCa). NEDD4 family of E3-ubiquitin ligases comprises a large family of proteins particularly, SMURFs (SMURF1, SMURF2), WWPs and NEDD4 which are ideal candidates for targeted therapy. However, it is becoming progressively more understandable that SMURFs and NEDD4 have "split-personalities". These molecules behave dualistically in breast cancer and future studies must converge on detailed identification of context specific role of these proteins in BCa. Finally, we provide scattered clues of regulation of SMURF2 by oncogenic miRNAs, specifically considering longstanding questions related to regulation of SMURF1 and WWPs by miRNAs in BCa. SMURFS, WWPs and NEDD4 are versatile regulators and represent a fast-growing field in cancer research and better understanding of the underlying mechanisms will be helpful in transition of our knowledge from a segmented view to a more conceptual continuum.

Regulation of Cell Signaling Pathways by Berberine in Different Cancers: Searching for Missing Pieces of an Incomplete Jig-Saw Puzzle for an Effective Cancer Therapy.

There has been a renewed interest in the identification of natural products having premium pharmacological properties and minimum off-target effects. In accordance with this approach, natural product research has experienced an exponential growth in the past two decades and has yielded a stream of preclinical and clinical insights which have deeply improved our knowledge related to the multifaceted nature of cancer and strategies to therapeutically target deregulated signaling pathways in different cancers. In this review, we have set the spotlight on the scientifically proven ability of berberine to effectively target a myriad of deregulated pathways.

Focusing on the brighter side of Sevoflurane: Realizing true potential of an anesthetic agent as a regulator of cell signaling pathways and microRNAs in different cancers.

Reconceptualization of different anesthetics as anticancer agents has opened new horizons for a better and sharper analysis of true potential of Sevoflurane as a promising and frontline candidate in the pipeline of anticancer agents. Sevoflurane mediated regulation of cell signaling pathways and non-coding RNAs has leveraged our understanding to another level. There have been remarkable advancements in unraveling mechanistic insights related to the ability of sevoflurane to modulate microRNAs in different cancers. Astonishingly, sevoflurane mediated regulation of miRNAs and long non-coding RNAs have been more comprehensively addressed in ischemia-reperfusion injuries. However, researchers yet have to gather missing pieces of premium research-work to uncover mechanistic regulation of long non-coding RNAs by sevoflurane in various cancers. Sevoflurane modulated control of miRNAs have been reported in glioma, colorectal cancer, breast cancer and hepatocellular carcinoma. In this review we have attempted to summarize most recent cutting edge and high-impact experimental researches which have elucidated myriad of underlying mechanisms modulated by sevoflurane to inhibit cancer development and progression. Despite some of the amazing pharmacological properties of sevoflurane, it has been shown to possess darker side because of its involvement in positive regulation of metastasis.  In accordance with this notion we have also summarized how sevoflurane enhanced migratory potential of different cancer cells in a separate section. Therefore, these aspects have to be tested in better designed experimental models to identify most relevant types of cancers which can be therapeutically targeted by sevoflurane.

Piperlongumine as anticancer agent: The story so far about killing many birds with one stone.

Piperlongumine is a biologically and pharmacologically active constituent of the plant Piper longum. This compound is gradually gaining attention because of its ability to inhibit/prevent different cancers. Modern era of molecular oncology is incomplete without ground-breaking discoveries made in the field of cell signaling pathways. High-throughput technologies have considerably improved our understanding about wide ranging signal transduction cascades which play crucial role in cancer development and progression. It is exciting to note that piperlongumine has been shown to pleiotropically modulate different oncogenic signaling pathways. We partition this multi-component review into discrete sections and categorically summarize key findings related to excellent ability of piperlongumine to therapeutically target JAK-STAT, NF-kB and PI3K/AKT/mTOR pathways. We also set spotlight on regulation of TRAIL pathway and autophagy by piperlongumine in different cancers. On the basis of the current understanding of piperlongumine, molecular biologists and pharmacologists will develop the next generation of translational studies, which will prove to be helpful in improving the clinical outcome and getting a step closer to personalized medicine.

Ionic liquid coated iron nanoparticles are promising peroxidase mimics for optical determination of H2O2.

Ionic liquid coated nanoparticles (IL-NPs) consisting of zero-valent iron are shown to display intrinsic peroxidase-like activity with enhanced potential to catalyze the oxidation of the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide. This results in the formation of a blue green colored product that can be detected with bare eyes and quantified by photometry at 652 nm. The IL-NPs were further doped with bismuth to enhance its catalytic properties. The Bi-doped IL-NPs were characterized by FTIR, X-ray diffraction and scanning electron microscopy. A colorimetric assay was worked out for hydrogen peroxide that is simple, sensitive and selective. Response is linear in the 30-300 µM H2O2 concentration range, and the detection limit is 0.15 µM. Graphical abstract Schematic of ionic liquid coated iron nanoparticles that display intrinsic peroxidase-like activity. They are capable of oxidizing the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide. This catalytic oxidation generated blue-green color can be measured by colorimetry. Response is linear in the range of 30-300 µM H2O2 concentration, and the detection limit is 0.15 µM.

Exosome biogenesis, bioactivities and functions as new delivery systems of natural compounds.

A rapidly growing body of experimental evidence has begun to shed light on the wide ranging molecular mechanisms which modulate intra- and inter-cellular communications. A substantial quantity of the available knowledge has only been uncovered in recent years, and we are learning that donor cells release nanovesicles, known as exosomes, which regulate the cellular behavior of recipient cells following uptake. Based on the impressive capacity of exosomes in delivering their "payload", different therapeutic agents, are currently being tested using this delivery method for more effective therapy. This review summarizes the most recent developments in exosome bioactivities and discusses the biochemical nature of exosomes and their biogenesis. It also summarizes the use of exosomes as delivery vehicles for drugs and natural compounds to the targeted site.