X-ray photoelectron spectroscopy and tunable photoluminescence study of gold nanoparticles embedded in PVA films.

This article reports the systematic photoluminescence study of the various contents of gold nanocomposites in polyvinyl alcohol (PVA) films. The variations in the gold content in PVA film were 0.2, 0.5, 1.0, and 1.5 wt%. All the samples were excited at two selected wavelengths; those are at 400 nm and 532 nm. On exciting the gold-PVA nanocomposite films at 400 nm the photoluminescence was observed in the region of 430-500 nm in comparison to pure PVA films that show an emission at 400 nm. However, on exciting the gold-PVA nanocomposites at 532 nm, the emission was observed at 560-650 nm with a long tail till 700 nm that is unlike the pure PVA films that do not show any emission peak in this region. This suggests that emission between 430 and 500 nm regions is due to the coordination of PVA with gold nanoparticles because PVA has an emission at 400 nm. However, the emission peak between 560 and 650 nm is entirely due to the gold nanocomposite particle. The peak also shows a smaller red-shift that is usually with the increasing nanoparticles size with the increasing content in the PVA films. The formation of gold nanoparticles was justified by X-ray diffraction (XRD) analysis which is further supported by X-ray photoelectron spectroscopy (XPS) analysis.

Vinpocetine mitigates DMH-induce pre-neoplastic colon damage in rats through inhibition of pro-inflammatory cytokines.

Colorectal cancer (CRC) is currently recognized as the third most prevalent cancer worldwide. Vinpocetine is a synthetic derivative of the vinca alkaloid vincamine. It has been found effective in ameliorating the growth and progression of cancerous cells. However, its pharmacological effect on colon damage remains elusive. Hence, in this study, we have shown the role of vinpocetine in DMH-induced colon carcinogenesis. At first, male albino Wistar rats were administered with DMH consistently for four weeks to induce pre-neoplastic colon damage. Afterward, animals were treated with vinpocetine (4.2 and 8.4 mg/kg/day p.o.) for 15 days. Serum samples were collected to assess the physiological parameters, including ELISA and NMR metabolomics. Colon from all the groups was collected and processed separately for histopathology and western blot analysis. Vinpocetine attenuated the altered plasma parameters; lipid profile and showed anti-proliferative action as evidenced by suppressed COX-2 stimulation and decreased levels of IL-1ß, IL-2, IL-6, and IL-10. Vinpocetine is significantly effective in preventing CRC which may be associated with its anti-inflammatory and antioxidant potential. Accordingly, vinpocetine could serve as a potential anticancer agent for CRC treatment and thus be considered for future clinical and therapeutic research.

A Comprehensive Review on PCSK9 as Mechanistic Target Approach in Cancer Therapy.

PCSK9 is a strongly expressed protein in the liver and brain that binds to the LDLR and regulates cholesterol in the liver effectively. Other receptors with which it interacts include VLDLR, LRP1, ApoER2, and OLR1. PCSK9 gain-of-function results in lysosomal degradation of these receptors, which may result in hyperlipidemia. PCSK9 deficiency results in a lower amount of cholesterol, which reduces cholesterol's accessibility to cancer cells. PCSK9 regulates several proteins and signaling pathways in cancer, including JNK, NF-κВ, and the mitochondrial-mediated apoptotic pathway. In the liver, breast, lungs, and colon tissue, PCSK9 initiates and facilitates cancer development, while in prostate cancer cells, it induces apoptosis. PCSK9 has a significant impact on brain cancer, promoting cancer cell survival by manipulating the mitochondrial apoptotic pathway and exhibiting apoptotic activity in neurons by influencing the NF-κВ, JNK, and caspase-dependent pathways. The PCSK9 impact in cancer at different organs is explored in this study, as well as the targeted signaling mechanisms involved in cancer growth. As a result, these signaling mechanisms may be aimed for the development and exploration of anti-cancer drugs in the immediate future.

Synthesis and appraisal of dalbergin-loaded PLGA nanoparticles modified with galactose against hepatocellular carcinoma: In-vitro, pharmacokinetic, and in-silico studies.

Hepatocellular carcinoma (HCC) is a common malignancy which affects a substantial number of individuals all over the globe. It is the third primary cause of death among persons with neoplasm and has the fifth largest mortality rate among men and the seventh highest mortality rate among women. Dalbergin (DL) is described to be effective in breast cancer via changing mRNA levels of apoptosis-related proteins. DL belongs to neoflavonoids, a drug category with low solubility and poor bioavailability. We created a synthetic version of this naturally occurring chemical, DL, and then analyzed it using 1H-NMR, 13C-NMR, and LC-MS. We also made PLGA nanoparticles and then coated them with galactose. The design of experiment software was used to optimize DL-loaded galactose-modified PLGA nanoparticles. The optimized DL-nanoformulations (DLF) and DL-modified nanoformulations (DLMF) were analyzed for particle size, polydispersity index, shape, and potential interactions. In-vitro experiments on liver cancer cell lines (HepG2) are used to validate the anti-proliferative efficacy of the modified DLMF. The in-vitro research on HepG2 cell lines also demonstrated cellular accumulation of DLF and DLMF by FITC level. The in-vitro result suggested that DLMF has high therapeutic effectiveness against HCC. In-vivo pharmacokinetics and bio-distribution experiments revealed that DLMF excelled pristine DL in terms of pharmacokinetic performance and targeted delivery, which is related to galactose's targeting activity on the asialoglycoprotein receptor (ASGPR) in hepatic cells. Additionally, we performed an in-silico study of DL on caspase 3 and 9 proteins, and the results were found to be -6.7 kcal/mol and -6.6 kcal/mol, respectively. Our in-silico analysis revealed that the DL had strong apoptotic properties against HCC.

Ameliorative effect of fluvoxamine against colon carcinogenesis via COX-2 blockade with oxidative and metabolic stress reduction at the cellular, molecular and metabolic levels.

Fluvoxamine's (FLX's) anticancer potential was investigated in pre-clinical research utilizing a DMH-induced colorectal cancer (CRC) rat model. qRT-PCR and immunoblotting validated the mechanistic investigation. The CRC condition was induced in response to COX-2 and IL-6, however, following FLX therapy, the condition returned to normal. FLX's anti-CRC potential may be attributable to COX-2 inhibition since this molecular activity was more apparent for COX-2 than IL-6. FLX repaired the altered metabolites linked to CRC rats, according to 1H-NMR analysis. FLX was shown to be similar to 5-FU in terms of tumor protection, which may be useful in future medication development.

ECM Mimicking Biodegradable Nanofibrous Scaffold Enriched with Curcumin/ZnO to Accelerate Diabetic Wound Healing via Multifunctional Bioactivity.

Introduction: Foot ulceration is one of the most severe and debilitating complications of diabetes, which leads to the cause of non-traumatic lower-extremity amputation in 15-24% of affected individuals. The healing of diabetic foot (DF) is a significant therapeutic problem due to complications from the multifactorial healing process. Electrospun nanofibrous scaffold loaded with various wound dressing materials has excellent wound healing properties due to its multifunctional action. Purpose: This work aimed to develop and characterize chitosan (CS)-polyvinyl alcohol (PVA) blended electrospun multifunctional nanofiber loaded with curcumin (CUR) and zinc oxide (ZnO) to accelerate diabetic wound healing in STZ-induced diabetic rats. Results: In-vitro characterization results revealed that nanofiber was fabricated successfully using the electrospinning technique. SEM results confirmed the smooth surface with web-like fiber nanostructure diameter ranging from 200 - 250 nm. An in-vitro release study confirmed the sustained release of CUR and ZnO for a prolonged time. In-vitro cell-line studies demonstrated significantly low cytotoxicity of nanofiber in HaCaT cells. Anti-bacterial studies demonstrated good anti-bacterial and anti-biofilm activities of nanofiber. In-vivo animal studies demonstrated an excellent wound-healing efficiency of the nanofibers in STZ-induced diabetic rats. Furthermore, the ELISA assay revealed that the optimized nanofiber membrane terminated the inflammatory phases successfully by downregulating the pro-inflammatory cytokines (TNF-α, MMP-2, and MMP-9) in wound healing. In-vitro and in-vivo studies conclude that the developed nanofiber loaded with bioactive material can promote diabetic wound healing efficiently via multifunction action such as the sustained release of bioactive molecules for a prolonged time of duration, proving anti-bacterial/anti-biofilm properties and acceleration of cell migration and proliferation process during the wound healing. Discussion: CUR-ZnO electrospun nanofibers could be a promising drug delivery platform with the potential to be scaled up to treat diabetic foot ulcers effectively.

Mechanistic exploration of the activities of poly(lactic-co-glycolic acid)-loaded nanoparticles of betulinic acid against hepatocellular carcinoma at cellular and molecular levels.

The effectiveness of betulinic acid (B) and PLGA loaded nanoparticles of B (Bnp) against hepatocellular carcinoma (HCC) was established and reported earlier. In continuation of our previous report, the present study described the molecular mechanisms of their antineoplastic responses. In this context, the antineoplastic properties of both B and Bnp were evaluated on DEN-induced HCC rat model. The quantitative real-time polymerase chain reaction and western blot analyses revealed that HCC was developed through lower expressions of e-NOS, BAX, BAD, Cyt C and higher expressions of i-NOS, Bcl-xl, Bcl-2. B and Bnp normalised the expressions of these apoptogenic markers. Particularly, both activated i-NOS and e-NOS mediated Bcl-2 family proteins→CytC→Caspase 3 and 9 signalling cascades. The 1H-NMR-based metabolomics study also demonstrated that the perturbed metabolites in DEN-induced rat serum restored to the normal level following both treatments. Moreover, the antineoplastic potential of Bnp was found to be comparable with the marketed product, 5-flurouracil.

New Scope of Targeted Therapies in Lung Carcinoma.

Lung Cancer (LC) is the leading cause of cancer deaths worldwide. Recent research has also shown LC as a genomic disease, causing somatic mutations in the patients. Tests related to mutational analysis and genome profiles have lately expanded significantly in the genetics/genomics field of LC. This review summarizes the current knowledge about different signalling pathways of LC based on the clinical impact of molecular targets. It describes the main molecular pathways and changes involved in the development, progression, and cellular breakdown of LC and molecular changes. This review focuses on approved and targeted experimental therapies such as immunotherapy and clinical trials that examine the different targeted approaches to treating LC. We aim to clarify the differences in the extent of various genetic mutations in DNA for LC patients. Targeted molecular therapies for LC can be continued with advanced racial differences in genetic changes, which have a significant impact on the choice of drug treatment and our understanding of the profile of drug susceptibility/ resistance. The most relevant genes described in this review are EGFR, KRAS, MET, BRAF, PIK3CA, STK11, ERBB3, PTEN, and RB1. Combined research efforts in this field are required to understand the genetic difference in LC outcomes in the future.

Blood pressure normalizing effect of Talahridaya marma therapy: A case report.

Ancient Ayurvedic literature described 107 vital regions of the body and considered them as a seat of prana (life force) and collectively termed them as marma. The applied aspect of this concept, marma chikitsa or marma therapy, is gaining popularity as it is being practiced by many clinicians in which these marma are stimulated in different ways to treat different diseases. Hypertension is one of the major disorders affecting majority of the world population. Inspite of available antihypertensive therapies, the hypertensive population of not only the older age group, but also of that of young adults is increasing. Blood pressure normalising effect of marma therapy is observed by clinicians practicing marma therapy due to its holistic effect on the body. Clinical data regarding efficacy of this therapy is very sparse and hence, its application in different diseases remained unexplored till date. This case report is of a young hypertensive male whose blood pressure significantly improved with Talahridaya marma therapy. This patient was detected with raised blood pressure on repetitive examinations. The volunteer was subjected to Talahridayamarma therapy where his classical Talahridaya marma point on left upper limb was physically stimulated in controlled way for 10 days and the patient was also taught to perform the therapy on himself. The blood pressure was recorded, both before and after giving the therapy on each day. The volunteer showed significant improvement in his blood pressure recordings.

Assessments of in vitro and in vivo antineoplastic potentials of ß-sitosterol-loaded PEGylated niosomes against hepatocellular carcinoma.

ß-sitosterol (BS), a phytosterol, exhibits ameliorative effects on hepatocellular carcinoma (HCC) due to its antioxidant activities. However, its poor aqueous solubility and negotiated bioavailability and short elimination half-life is a huge limitation for its therapeutic applications. To overcome these two shortcomings, BS-loaded niosomes were made to via, film hydration method and process parameters were optimized using a three-factor Box-Behnken design. The optimized formulation (BSF) was further surface-modified with polyethylene glycol (PEG). The resulting niosomes (BSMF) have spherical shapes, particle sizes, 219.6 ± 1.98 nm with polydispersity index (PDI) and zeta potential of 0.078 ± 0.04 and -19.54 ± 0.19 mV, respectively. The drug loading, entrapment efficiency, and drug release at 24 h of the BSMF were found to be 16.72 ± 0.09%, 78.04 ± 0.92%, and 75.10 ± 3.06%, respectively. Moreover, BSMF showed significantly greater cytotoxic potentials on Hep G2 cells with an enhanced cellular uptake relative to pure BS and BSF. The BSMF also displayed potentially improved curative property of HCC in albino wistar rat. Thus, the BSMF could be one of the promising therapeutic modalities for HCC treatment in terms of targeting potential resulting in enhanced therapeutic efficacy.

Preclinical Evaluation of Dimethyl Itaconate Against Hepatocellular Carcinoma via Activation of the e/iNOS-Mediated NF-κB-Dependent Apoptotic Pathway.

Hepatocellular carcinoma (HCC) is one of the most common tumors affecting a large population worldwide, with the fifth and seventh greatest mortality rates among men and women, respectively, and the third prime cause of mortality among cancer victims. Dimethyl itaconate (DI) has been reported to be efficacious in colorectal cancer by decreasing IL-1ß release from intestinal epithelial cells. In this study, diethylnitrosamine (DEN)-induced HCC in male albino Wistar rats was treated with DI as an anticancer drug. The function and molecular mechanism of DI against HCC in vivo were assessed using histopathology, enzyme-linked immunosorbent assay (ELISA), and Western blot studies. Metabolomics using 1H-NMR was used to investigate metabolic profiles. As per molecular insights, DI has the ability to trigger mitochondrial apoptosis through iNOS- and eNOS-induced activation of the NF-κB/Bcl-2 family of proteins, CytC, caspase-3, and caspase-9 signaling cascade. Serum metabolomics investigations using 1H-NMR revealed that aberrant metabolites in DEN-induced HCC rats were restored to normal following DI therapy. Furthermore, our data revealed that the DI worked as an anti-HCC agent. The anticancer activity of DI was shown to be equivalent to that of the commercial chemotherapeutic drug 5-fluorouracil.

Antineoplastic properties of zafirlukast against hepatocellular carcinoma via activation of mitochondrial mediated apoptosis.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwideand haslimited treatment options. In view of this, zafirlukast (ZAF) was administered orally to DEN-induced HCC rats to evaluate its antineoplastic properties. ELISA, qRT-PCR and Western blot were used to determine the molecular mechanism associated with ZAF therapy for HCC. We found that HCC developed as a result of lower expression of caspases 3 and 9, but their levels returned to normal when the expression of eNOS, BAX, BAD, and Cyt C was decreased and when the expression of iNOS, Bcl-xl, and Bcl-2 was increased. Again, ZAF (80 mg/kg dose) treatment normalized the expression of caspase-mediated apoptotic factors, i.e. BAX and Bcl-2 proteins, as established through Western blot analysis. Later, 1H NMR-based serum metabolomics study revealed that levels of perturbed metabolites in DEN-induced rat serum returned to normal after ZAF administration. Altogether, the antineoplastic potential of ZAF was found to be comparable, and to some degree better, than the marketed chemotherapeutic 5-flurouracil, which may be beneficial for anti-HCC treatment from a future drug design perspective.

Oleylamine as a reducing agent in syntheses of magic-size clusters and monodisperse quantum dots: optical and photoconductivity studies.

Separation of magic size clusters (MSCs) from monodisperse quantum dots (QDs) has generally been a difficult task while employing the commonly used synthesis procedure, where for preparation of PbSe QDs, Se-TOP (TOP = trioctylphosphine) is injected into Pb-oleate in 1-octadecene medium. In this study, we report for the first time a simple method to prepare MSCs, QDs and particles close to the bulk of PbSe using oleylamine (OAM) as the reducing agent, where the individual entities are efficiently separated. The chemical yield is found to be 95%. Studies on optical properties revealed the absorption and emission peaks of MSCs at fixed positions of 600 and 780 nm, respectively, while QDs exhibit significant shift to longer wavelengths for both the cases, depending on the particle size. Shift of the emission peak position for QDs is observed to be larger for initial stages of the waiting time as compared to those for longer waiting times. This can be attributed to two factors: faster growth in particle size is favoured kinetically in the initial stages, while thermodynamic stability occurs in the later stages, and reduction in surface to core contribution with increase of waiting time. QDs were found to emit at only one particular wavelength while they absorbed at two or more wavelengths. The quantum yields (QYs) of particles of sizes 4.1 and 5.1 nm are found to be 80 and 30%, respectively. The lifetime values are found to be 1.0-1.3 µs for QDs having an emission peak in the range of 1300-1500 nm. The hybrid device of PbSe (5 nm size) and MEHPPV (2-methoxy-5-(2'-ethyl-hexyloxy)-1,4-phenylene vinylene) shows increased conductivity both in the dark and in light, due to absorption in the region of NIR photons in the former and additionally in the visible region in the latter.

Synthesis of nanoparticles, their biocompatibility, and toxicity behavior for biomedical applications.

Nanomaterials research has in part been focused on their use in biomedical applications for more than several decades. However, in recent years this field has been developing to a much more advanced stage by carefully controlling the size, shape, and surface-modification of nanoparticles. This review provides an overview of two classes of nanoparticles, namely iron oxide and NaLnF4, and synthesis methods, characterization techniques, study of biocompatibility, toxicity behavior, and applications of iron oxide nanoparticles and NaLnF4 nanoparticles as contrast agents in magnetic resonance imaging. Their optical properties will only briefly be mentioned. Iron oxide nanoparticles show a saturation of magnetization at low field, therefore, the focus will be MLnF4 (Ln = Dy3+, Ho3+, and Gd3+) paramagnetic nanoparticles as alternative contrast agents which can sustain their magnetization at high field. The reason is that more potent contrast agents are needed at magnetic fields higher than 7 T, where most animal MRI is being done these days. Furthermore we observe that the extent of cytotoxicity is not fully understood at present, in part because it is dependent on the size, capping materials, dose of nanoparticles, and surface chemistry, and thus needs optimization of the multidimensional phenomenon. Therefore, it needs further careful investigation before being used in clinical applications.

Synthesis of InN@SiO2 nanostructures and fabrication of blue LED devices.

We synthesized InN@SiO(2) nanostructures (i.e., nanoparticles and nanowires) by varying the annealing temperature and nitridation conditions of In(2)O(3)@SiO(2) nanoparticles in the presence of ammonia. The In(2)O(3)@SiO(2) nanoparticles were synthesized using a urea-based homogeneous precipitation of indium hydroxide on the surface of the SiO(2) (15 nm) nanoparticles, followed by annealing at 600 °C in air. Subsequently, nitridation of In(2)O(3)@SiO(2) nanoparticles in ammonia at 600 °C for 2 h resulted in InN@SiO(2) nanoparticles. The sizes of InN nanoparticles are ∼5 nm on the silica surface. Nitridation at the same temperature for 3-5 h gave InN nanoparticles of size ∼20 nm. Furthermore, on annealing above 650 °C the InN nanoparticles grew in the form of nanowires. The nanowires are 4-5 µm in length and have a diameter of 100 nm. The photoluminescence peak of both InN@SiO(2) nanoparticles and nanowires is centered at 442 nm (λ(exi) = 325 nm). Subsequently, the surface of InN@SiO(2) nanoparticles was modified by reacting with dodecyltriethoxysilane at 80 °C, which enabled them to be dispersible in toluene. The surface-modified InN@SiO(2) nanoparticles were used to fabricate blue electroluminescence devices which showed blue electroluminescence peak centered at 442 nm. The Commission Internationale de I'Eclairage (CIE) coordinates of InN@SiO(2) nanoparticles are X = 0.15 and Y = 0.13, which is well within the blue region and commercially appropriate.