Iron nanoparticles as a promising compound for food fortification in iron deficiency anemia: a review.

Abstract: Iron deficiency anemia (IDA) is a global health concern that is affecting all age groups significantly. Among many of the existing methods, the fortification of foods with iron salts is the best and most cost-effective strategy for targeting large-scale populations to provide nutritional security. The fortification of foods with iron salts is a challenging task because most iron complexes (ferrous sulfate, ferrous chloride) used in fortification are highly water-soluble, which impart unacceptable organoleptic changes in food vehicles and also causes gastrointestinal problems. However, insoluble iron salts (ferric pyrophosphate) do not cause unacceptable taste or color in food vehicles but low bioavailable. Nanosized iron salts can overcome these concerns. The particle size of iron salts has been reported to play an important role in the absorption of iron. Reduction in the particle size of iron compounds increases its surface area, which in turn improves its solubility in the gastric juice leading to higher absorption. Nanosized iron compound produces minimal organoleptic changes in food vehicles compared to water-soluble iron complexes. Thus nanosized iron salts find potential applications in food fortification to reduce IDA. This paper focuses on providing a complete review of the various iron salts used in IDA, including their bioavailability, the challenges to food fortification, the effects of nanosized iron salts on IDA, and their applications in food fortification. Graphic abstract: Fortification of foods with water-soluble Fe salts imparts unacceptable organoleptic changes in food vehicle and adverse impact on health. However, insoluble iron salts do not cause unacceptable taste or color in food vehicles but low bioavailable. Using Nano-sized iron compound produces minimal organoleptic changes in food vehicles compared to changes produced by water-soluble iron complexes, improves Fe absorption in the gastrointestinal tract and does not cause any health issues.

Formulation and evaluation of novel functional snack bar with amaranth, rolled oat, and unripened banana peel powder.

The present pandemic situation has increased demand for functional foods that enhance all aged groups' people immunity against COVID-19. This factor has led to innovation in snack market because healthy and good quality snack products are lacking. In this study, attempt has been made to develop functional snack bar that is beneficial for malnourished population from various combinations of amaranth grain, oat, and banana peel powder. Among various combinations amaranth grain (60%), oats (25%) and banana peel powder (15%) was found better than other combinations in respect to organoleptic and nutritional quality. Oat and banana peel powder addition increased the contents of protein, mineral, ß-glucan, dietary fibre, essential amino acid, phenolic, and antioxidant activity of functional snack bar. TGA analysis shows that active components present in it were stable even at high temperature which adds benefit to its functional property. Microbial studies of FSB revealed it could be stored up to 60 days without microbial contamination and acceptable by consumer. The cost of a functional snack bar was 9.57 per bar, which was less than market snack bar. This study showed that developed functional snack bar snack increases market's revenue and enables snack market to develop new type snack bar.

Production of beetroot (Beta vulgaris L.) wine using different Saccharomyces strains and study of physicochemical and sensorial characteristics.

The present study investigated the effect of different wine strains and inoculum size on the physicochemical, bioactive, and sensorial attributes of wine prepared from beetroot with varying TSS content (18 and 20°Brix) and inoculum sizes (5% (v/v) and 10% (v/v)). The beetroot wine produced by fermenting the must for 0-14 days and standard protocols adopted to analyze the wine properties. It was noticed that the acidity of wine increased and pH was found to be decreased as the fermentation days increased. In addition, alcohol content was significantly enhanced (> 10% by volume) in T5, which was higher than the other trials. In general, results of sensory and physicochemical analysis of different trials showed that T5 (TSS 18°Brix and inoculum size of 5% (v/v)) produced the wine of acceptable quality using Saccharomyces cerevisiae. The color properties revealed that the L* value increased as fermentation progressed. Wine prepared from T5 possessed TSS of 6.55°Brix, 3.96 pH, 0.35% titratable acidity, reducing sugar of 26.75 µg ml-1, 30.03% of DPPH free radical scavenging activity, phenol content (104.20 µg ml-1) and betalain content of 10.85 mg 100 g-1. There were significant differences in the taste, flavor, and overall acceptability of beetroot wines fermented for 14 days. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05136-y.

Development of water spinach powder and its characterization.

The study was performed on water spinach (Ipomea aquatica), a hidden gem with lots of nutritional attributes and medicinal properties. To check its feasibility as an ingredient in other food products and to know its nutritional attributes, powders were made by drying the leaves and stems of the plant using different drying techniques such as sun drying, freeze-drying, and tray drying. The physicochemical analysis of powder was done to get a comparative result, in which the freeze-dried powder showed the most significant result. The physicochemical analysis revealed that lyophilized water spinach powder has a good amount of carbohydrates (58.15%), ash (12.39%), protein (4.01%), and fat (4.46%) content. The powder also possessed a high antioxidant property of 77.25% and a total phenolic content of 32 µg/ ml. SEM and XRD results showed that the water spinach powder was amorphous in nature.

Antimicrobial potential of the food-grade additive carvacrol against uropathogenic E. coli based on membrane depolarization, reactive oxygen species generation, and molecular docking analysis.

The antibiotic resistance of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli has increased drastically in recent years. In our study, we determined the principle mechanisms of action for the food-grade additive carvacrol against ESBL E. coli isolated from the blood of patients with a urinary tract infection. Carvacrol, which has a minimum inhibitory concentration of 150 µg/ml and a minimum bactericidal concentration of 300 µg/ml, reduced E. coli cell counts in a time-dependent manner. After treatment with carvacrol, the E. coli killing time was found to be 120 min. Fluorescent staining confirmed an increase in bacterial cell death, greater membrane depolarization, and an elevated oxidative burst in carvacrol-treated E. coli. Carvacrol also induced the release of cellular DNA, proteins, and potassium ions from bacterial cells and reduced both the number of E. coli in invasion assays against macrophages and the levels of the inflammatory proteins TNF-α and COX-2. In addition, carvacrol was found to inhibit ß-lactamase enzyme activity (in vitro), which was supported by in silico results. Moreover, carvacrol inhibited motility, and protected against bacterial invasion. Overall, the findings suggest that carvacrol has significant antimicrobial potential against ESBL E. coli.

Sensory acceptability of value added cookies incorporated with Tinospora cordifolia (TC) stem powder; improvement in nutritional properties and antioxidant potential.

Tinospora cordifolia (TC) is regarded nature's treasure as it is salutary in various ways to the human health in ayurvedic and vedic scriptures. The TC stem creeping on neem tree (Azadirachta indica) are considered best for medicinal use. Present study was carried out to develop functional food as cookies by incorporating the TC stem powder. Functional cookies were prepared by incorporating 2%, 4%, 8%, 10% and 12% of TC stem powder and admissibility was decided on the basis of sensory evaluation to get the optimized cookies (TCC). Further physical parameters (L*, a* and b* color value and spread ratio) were analyzed. TC, TCC and control cookies without TC were evaluated for nutritional composition and antioxidant potential [antioxidant assays: 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing power (FRAP) and nitric oxide (NO), total polyphenolic content and total flavonoid content]. Results showed that with increase in TC addition from 0 to 12% in cookies there was decreases in the sensory parameters and maximum admissible concentration was up to 8% of TC, hence optimized at this level. Incorporation of TC in cookies resulted in increase in b* value, protein, moisture, total ash, iron, copper, zinc and antioxidant potential, whereas the fat content decreases. Developed cookies proved to be better than standard control cookies with respect to functional properties.

Isorhamnetin Has Potential for the Treatment of Escherichia coli-Induced Sepsis.

Isorhamnetin is a flavonoid that is abundant in the fruit of Hippophae rhamnoides L. It is widely studied for its ability to modulate inflammatory responses. In this study, we evaluated the potential of isorhamnetin to prevent gram-negative sepsis. We investigated its efficacy using an Escherichia coli-induced sepsis model. Our study reveals that isorhamnetin treatment significantly enhances survival and reduces proinflammatory cytokine levels in the serum and lung tissue of E. coli-infected mice. Further, isorhamnetin treatment also significantly reduces the levels of aspartate aminotransferase, alanine amino transferase and blood urea nitrogen, suggesting that it can improve liver and kidney function in infected mice. Docking studies reveal that isorhamnetin binds deep in the hydrophobic binding pocket of MD-2 via extensive hydrophobic interactions and hydrogen bonding with Tyr102, preventing TLR4/MD-2 dimerization. Notably, binding and secreted alkaline phosphatase reporter gene assays show that isorhamnetin can interact directly with the TLR4/MD-2 complex, thus inhibiting the TLR4 cascade, which eventually causes systemic inflammation, resulting in death due to cytokine storms. We therefore presume that isorhamnetin could be a suitable therapeutic candidate to treat bacterial sepsis.

RIP1-dependent reactive oxygen species production executes artesunate-induced cell death in renal carcinoma Caki cells.

Artesunate is a well-known anti-malarial drug originated from artemisinin as a Chinese herb and has been reported to have anti-cancer potential in many cancer cells. In the present study, we examined the efficacy of artesunate against the renal carcinoma Caki cells and explored its mechanism of cytotoxicity. A steep decline in cell viability within 18 h was recorded upon artesunate exposure, but pretreatment of z-VAD-FMK had no effect on the loss of the cell viability by artesunate. On the other hand, necrostatin-1 pretreatment and knockdown of RIP-1 significantly reduced the cytotoxicity of artesunate against Caki cell. Moreover, the generation of mitochondrial ROS prompted by artesunate was found to be the principle mechanism of cell death. Pretreatment with necrostatin-1 or knockdown of RIP-1 inhibited the generation of ROS by artesunate, resulting in the protection of the cells from artesunate toxicity. Moreover, the similar results were observed in the case of other renal carcinoma cell lines (ACHN and A498). The results suggest that artesunate induces the generation of ROS and cell death in RIP1-dependent manner. Therefore, our data suggest that artesunate could induce RIP1-dependent cell death in human renal carcinoma.

Medicinal and therapeutic properties of garlic, garlic essential oil, and garlic-based snack food: An updated review.

Garlic (Allium sativum) is an edible tuber belonging to the family Liliaceae. It has been used since ancient times as a spice to enhance the sensory characteristics of food and as a household remedy for the treatment of a variety of ailments. Garlic has been studied for its medicinal and therapeutic effects in the treatment of various human diseases for a long time. Health benefits associated with the consumption of garlic are attributed to the various sulfur compounds present in it such as allicin, ajoene, vinyl-dithiin, and other volatile organosulfur compounds which are all metabolized from alliin. Several researches in the literature have shown evidence that garlic exhibits antioxidant, antiviral, anti-microbial, anti-fungal, antihypertensive, anti-anemic, anti-hyperlipidemic, anticarcinogenic, antiaggregant, and immunomodulatory properties. The present review identifies and discusses the various health benefits associated with the consumption of garlic, its essential oil, and bioactive constituents, along with exploring the various snack-food products developed by incorporating garlic.

Correlation of perceived stress with monthly cyclical changes in the female body.

Background: Women are liable to stress-related disorders as female sex hormone, estrogen has been indicated to be protective against stress disorders. The hormone level varies with different phases of menstrual cycle. Moreover, postmenopausal women are at risk for stress-related disorders. So this study was done to correlate the different phases of menstrual cycle with the perceived stress in different phases of monthly cycle. Methods: This study was conducted in the Department of Physiology, Shri Guru Ram Rai Institute of Medical and Health Sciences (SGRRIMHS), Dehradun. Four hundred girls in the age group of 18-26 years were selected for the study. The Perceived Stress Scale (PSS) questionnaire was circulated via Google forms after briefing them about the study. Informed consent was also taken. The menstrual history of the subjects was enquired by one-to-one interaction. The participants completed the PSS questionnaire twice in the same cycle. Data collected were statistically analyzed, using Independent t-test and Chi-square test and point biserial correlation test. Result: The analysis showed strong statistical association of PSS with two phases of menstrual cycle. The PSS score was higher in the late luteal and menstrual phase, while it was less in the late follicular phase (P < 0.05). Conclusion: The decreased oestrogen levels in the late luteal & menstrual phase are strongly associated with perceived stress in our study. Hormonal changes in the monthly cycles are related with stress, behavioral shift and many other physical changes in females. This information to the family physicians would be beneficial in counseling the females regarding various changes occurring during the menstrual cycle.

Psychobiotics for Mitigation of Neuro-Degenerative Diseases: Recent Advancements.

Ageing is inevitable and poses a universal challenge for all living organisms, including humans. The human body experiences rapid cell division and metabolism until approximately 25 years of age, after which the accumulation of metabolic by-products and cellular damage leads to age-related diseases. Neurodegenerative diseases are of concern due to their irreversible nature, lack of effective treatment, and impact on society and the economy. Researchers are interested in finding drugs that can effectively alleviate ageing and age-related diseases without side-effects. Psychobiotics are a novel class of probiotic organisms and prebiotic interventions that confer mental health benefits to the host when taken appropriately. Psychobiotic strains affect functions related to the central nervous system (CNS) and behaviors mediated by the Gut-Brain-Axis (GBA) through various pathways. There is an increasing interest in researchers of these microbial-based psychopharmaceuticals. Psychobiotics have been reported to reduce neuronal ageing, inflammation, oxidative stress, and cortisol levels; increase synaptic plasticity and levels of neurotransmitters and antioxidants. The present review focuses on the manifestation of elderly neurodegenerative and mental disorders, particularly Alzheimer's disease (AD), Parkinson's disease (PD), and depression, and the current status of their potential alleviation through psychobiotic interventions, highlighting their possible mechanisms of action.

Fumonisin B1 induces poly (ADP-ribose) (PAR) polymer-mediated cell death (parthanatos) in neuroblastoma.

Fumonisin B1 (FB1) is a well-known mycotoxin produced by Fusarium spp. and has a wide range of dose-dependent toxic effects, including nephrotoxicity, hepatotoxicity, and neurotoxicity. This research illustrated that FB1 exerts its toxicity in the neuroblastoma cell line through a distinct cell-death pathway called parthanatos. FB1 can cause excessive DNA strand breaks, leading to poly (ADP-ribose) polymerase-1 (PARP-1) overactivation and cell death. In this study, we used 50 µM FB1-treated SH-SY5Y neuroblastoma cells to elucidate the signaling pathway of FB1-induced parthanatos. We observed that FB1-induced cell death is caspase-independent and accompanied by rapid activation of PARP-1, c-Jun N-terminal kinase activation, reactive oxygen species (ROS) generation, and intracellular calcium increase. FB1 treatment also increased endoplasmic reticulum stress due to the rapid increase of calcium ions and ROS levels. In addition, FB1 induced massive DNA damage and chromatin decondensation. We also observed that apoptosis-inducing factor nuclear translocation and PAR accumulation were associated with the necroptosis signal.

Synthesis of 2,5-furandicarboxylic acid-enriched-chitosan for anti-inflammatory and metal ion uptake.

The main aim of the present study is to synthesize a hitherto unreported polymer of chitosan (CS) and 2,5-furandicarboxylic acid (FDCA) derived from renewable biomass resources. For this purpose, CS was chosen which had -NH2 groups as abundant active sites. Synthesis of 2,5-furandicarboxylic acid-enriched-chitosan polymer (CS-FDCA) was carried out by reaction involving EDC-NHS coupling reagents. The structure of CS-FDCA polymer was confirmed by various characterization techniques such as Fourier-transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H NMR), X-ray powder diffraction (XRD), high resolution-field emission scanning electron microscope (HR-FESEM), and thermogravimetric analysis (TGA). Moreover, CS and CS-FDCA were scrutinized to examine their efficacies towards ameliorate inflammation via detection of lipopolysaccharide (LPS) induced nitric oxide (NO) production. As compared to CS, CS-FDCA with low concentration (1.0 µM) exhibited the better efficacy to reduce the NO production. Furthermore, CS-FDCA polymer showed high as 12.6% of Cu2+ ion uptake while CS showed 9.2% of Cu2+ ion uptake. Overall, it can be inferred that CS-FDCA polymer is expected to be used for biomedical application and for the removal of metal contaminants from industrial wastewater.

Inhibitory insights of strawberry (Fragaria × ananassa var. Seolhyang) root extract on tyrosinase activity using computational and in vitro analysis.

The strawberry (Fragaria × ananassa var. seolhyang) is commonly used as fruit but medicinal importance for the non-edible roots which contained a pool of bioactive compounds are not yet studied against tyrosinase inhibition. This study demonstrates the potential of bioactive compounds in root and rhizome of strawberry against tyrosinase inhibition using in silico and in vitro approaches. ADMET profiling and molecular docking analysis show druglikeness for the major bioactive compounds in strawberry root extract (SRE), i.e. procyanidin, procyanidin trimer, kaempferol 3-O-(4-O-p-coumaroyl)-glucoside, neochlorogenic acid, procyanidin tetramer, and quercetin-3-O-pentoside, and docking score between -7.8 to -6.3 kcal/mol with tyrosinase, respectively. Also, these docked complexes exhibit substantial stability contributed by strong hydrogen bonding, hydrophobic interactions, and polar interactions in 100 ns molecular dynamics simulation; further supported by essential dynamics and dynamic cross-correlation matrix analysis. Also, in vitro functional assays support in silico predicted results in terms of substantial cytoprotective and cellular antioxidant potential in Raw 264.7 macrophages challenged by H2O2 as well as non-significant toxicity in zebrafish. SRE exhibits the lowest (5.8%) and highest (42.8%) inhibition of tyrosinase at 100 and 500 µg/ml concentrations, respectively. These results advocated functional properties and tyrosinase inhibition potential of SRE; and hence, SRE can be used in medicinal or cosmetic applications.

Effects of C-Terminal Residues of 12-Mer Peptides on Antibacterial Efficacy and Mechanism.

The development of new antimicrobial agents is essential for the effective treatment of diseases such as sepsis. We previously developed a new short peptide, Pap12-6, using the 12 N-terminal residues of papiliocin, which showed potent and effective antimicrobial activity against multidrug-resistant Gram-negative bacteria. Here, we investigated the antimicrobial mechanism of Pap12-6 and a newly designed peptide, Pap12-7, in which the 12th Trp residue of Pap12-6 was replaced with Val to develop a potent peptide with high bacterial selectivity and a different antibacterial mechanism. Both peptides showed high antimicrobial activity against Gram-negative bacteria, including multidrug-resistant Gram-negative bacteria. In addition, the two peptides showed similar anti-inflammatory activity against lipopolysaccharide-stimulated RAW 264.7 cells, but Pap12-7 showed very low toxicities against sheep red blood cells and mammalian cells compared to that showed by Pap12-6. A calcein dye leakage assay, membrane depolarization, and confocal microscopy observations revealed that the two peptides with one single amino acid change have different mechanisms of antibacterial action: Pap12-6 directly targets the bacterial cell membrane, whereas Pap12-7 appears to penetrate the bacterial cell membrane and exert its activities in the cell. The therapeutic efficacy of Pap12-7 was further examined in a mouse model of sepsis, which increased the survival rate of septic mice. For the first time, we showed that both peptides showed anti-septic activity by reducing the infiltration of neutrophils and the production of inflammatory factors. Overall, these results indicate Pap12-7 as a novel non-toxic peptide with potent antibacterial and anti-septic activities via penetrating the cell membrane.

α-Ecdysone suppresses inflammatory responses via the Nrf2 pathway in lipopolysaccharide-stimulated RAW 264.7 cells.

The search for new biologically active compounds is a topic of current research because of their ubiquitous availability and low toxicity. Plants of the Silene genus contain secondary metabolites known as phytoecdysteroids that reportedly have various biological activities. α-Ecdysone is a phytoecdysteroid with biological activity that has not been thoroughly investigated to date. Therefore, we investigated the immunomodulatory and anti-inflammatory effects of α-ecdysone on LPS-treated RAW264.7macrophage cells and in a zebrafish model. To explore these activities, RAW264.7 cells were pretreated with α-ecdysone (0.1-10 µM) for 24 h and then with LPS to induce inflammation. We assayed membrane fluidity, lysosomal enzyme activity, and superoxide generation to determine the immunomodulatory activity. Using ELISA, we examined the levels of the pro-inflammatory cytokines prostaglandin (PGE2) and interleukin-1ß (IL-1ß), as well as the protein expression of cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α) and heme­oxygenase-1 (HO-1) by immunoblotting. We also investigated the subcellular localization of the nuclear transcription factor (NF-κB) subunits and expression of the mitogen-activated protein kinase (MAPK) pathway. We found that α-ecdysone is a potent immunostimulator that enhances membrane fluidity and lysosomal enzyme activity and generates superoxide anions. Simultaneously, α-ecdysone inhibited nitric oxide levels and suppressed the levels of pro-inflammatory mediators and cytokines. Furthermore, α-ecdysone increased HO-1 and nuclear factor erythroid 2-related factor (Nrf2) production, mitigated NF-κB subunit proteins in the nucleus and decreased MAPKs and Akt activation. These results suggest that α-ecdysone is a good immunostimulator with anti-inflammatory effects that occur via inhibition of pro-inflammatory mediators and cytokines through stimulation of HO-1 and Nrf-2 production.

Morin hydrate ameliorates cisplatin-induced ER stress, inflammation and autophagy in HEK-293 cells and mice kidney via PARP-1 regulation.

The present study assessed the possible therapeutic potential of a natural flavonoid morin hydrate (MH), against cisplatin (CP) induced toxicity in HEK-293 cells and mice kidney. Herein, we observed that exposure of HEK-293 cells to CP (20 µM, 24 h) reduced the cell viability, and increased the intracellular ROS generation, nuclear DNA damage, Ca++ release, and accumulation of acidic vacuoles. Concomitantly, acute exposure of CP (30 mg/kg, 72 h) to male ICR mice induced histopathological changes in kidney tissue, and alterations in serum creatinine and blood urea nitrogen (BUN) levels. Oxidative stress mediated ER-stress was evidenced by the reduced expression of antioxidant enzymes such as SOD-1, SOD-2, GR, and Trx, and increased expression levels of CytP450, IRE1-α, PERK, and CHOP. The expression levels of major inflammatory response markers such as NF-κB, TNF-α, IL-1ß, COX-2 and iNOS were significantly increased in the HEK-293 cells and mice kidney. Temporal up-regulation of p-AMPK and LC3I/II, and down regulation of mTOR was also noticed after CP treatment. CP-induced DNA damage led to activation of PARP-1, which plays a crucial role in inflammation, apoptosis and autophagy activation. Concurrently, co-treatment of CP-MH and CP-ANI (PARP-1 inhibitor) significantly attenuated the expression level of PARP-1, reduced cellular death, alleviated inflammatory responses, and inhibited autophagy stimulation in HEK-293 cells and mice kidney. On the basis of above findings, we suggest MH as a potential therapeutic agent against CP-induced nephrotoxicity.

Thymol Elicits HCT-116 Colorectal Carcinoma Cell Death Through Induction of Oxidative Stress.

BACKGROUND: Colon cancer is one of the most deadly and common carcinomas occurring worldwide and there have been many attempts to treat this cancer. The present work was designed in order to evaluate thymol as a potent drug against colon cancer. MATERIALS AND METHODS: Cytotoxicity of thymol at different concentrations was evaluated against a human colon carcinoma cell line (HCT-116 cells). Fluorescent staining was carried out to evaluate the level of ROS as well as mitochondrial and DNA fragmentation and immunoblot analysis were performed to confirm apoptosis and mitoptosis. RESULTS AND CONCLUSION: Results of the study demonstrated that thymol efficiently created an oxidative stress environment inside HCT-116 cells, a colorectal carcinoma cell line, through induction of ROS production along with intense damage to DNA and mitochondria, as observed through Hoechst and rhodamine 123 staining, respectively. Moreover, expression of PARP-1, p-JNK, cytochrome-C and caspase-3 proteins was up-regulated, suggesting HCT-116 cells underwent mitoptotic cell death. Therefore, thymol could be used as a potent drug against colon cancer due to its lower toxicity and prevalence in natural medicinal plants.

Differential expression patterns of the short and long isoform of cFLIP on FasL­mediated apoptosis.

cFLIP is a key regulator of the anti­apoptotic mechanism and its association with FAS­mediated apoptosis has been widely studied and well documented. However, the equipoise between its two isoforms i.e. the long isoform cFLIP(L) and the short isoform cFLIP(S) during FAS­mediated apoptosis remains to be revealed. Therefore, the present study aimed to investigate the regulatory effect of these isoforms on FasL­mediated apoptosis in renal carcinoma. Our results revealed that FasL treatment to Caki cells induced the expression of cFLIP(S) and downregulated the expression of cFLIP(L) in a concentration­ and time­dependent manner. Furthermore, our results indicated that cell death receptor­mediated apoptosis inducers such as TNF­α and TRAIL, induced apoptosis in Caki cells along with downregulation of cFLIP(L), however, they had no effect on the expression of cFLIP(S). In addition, FasL­mediated cFLIP(L) downregulation was prevented by pan­caspase inhibitor (z­VAD­fmk), however pan­caspase inhibitor did not have an effect on FasL­induced cFLIP(S) upregulation. Furthermore, FasL induced upregulation of the expression of cFLIP(S) at the post­translational level. Furthermore, pretreatment of Caki cells with ROS scavengers (N­acetylcysteine and glutathione) prevented the downregulation of cFLIP(L), the upregulation of cFLIP(S) and apoptosis induced by FasL. Collectively, these data indicated that a novel pathway of cFLIP(L)/(S) differential expression pattern was associated with FasL­induced apoptosis and modulated by ROS generation.

Synthesis of novel Chlorin e6-curcumin conjugates as photosensitizers for photodynamic therapy against pancreatic carcinoma.

Curcumin (cur) has been comprehensively studied for its various biological properties, more precisely for its antitumor potential and it has shown the promising results as well. On the other hand, Chlorin e6 (Ce6) has mostly been used as a photosensitizer in photodynamic therapy (PDT) against a variety of carcinomas. In the present study, we have synthesized a series of Chlorin e6-curcumin (Ce6-cur) conjugates and investigated their photosensitizing potential against pancreatic cancer cell lines. All the synthesized compounds were characterized by UV, 1H NMR, 13C NMR and LC-MS. These Ce6-cur conjugates showed better physicochemical properties and higher singlet oxygen generation capability. The cellular uptake was studied in AsPC-1 cells using fluorescence-activated cell sorting (FACS). Compound 17 was rapidly internalized within 30 min and sustained for 24 h. Compound 17 showed excellent PDT efficacy with IC50 of 40, 35 and 41 nM against AsPC-1, MIA PaCa-2 and PANC-1 respectively with exceptional dark/phototoxicity ratio in the range of 2371-7500. Moreover, the treatment of compound 17 upregulated the expression of BAX, Cytochrome-C and cleaved caspase 9 while downregulating the Bcl-2 expression an anti-apoptotic protein marker. These results demonstrate outstanding capability of compound 17 as a potent photosensitizer which could improve the PDT efficacy in pancreatic cancer patients.