Lipid-Based Nanocarriers in the Treatment of Glioblastoma Multiforme (GBM): Challenges and Opportunities.

Glioblastoma multiforme (also known as glioblastoma; GBM) is one of the most malignant types of brain tumors that occurs in the CNS. Treatment strategies for glioblastoma are majorly comprised of surgical resection, radiotherapy, and chemotherapy along with combination therapy. Treatment of GBM is itself a tedious task but the involved barriers in GBM are one of the main impediments to move one step closer to the treatment of GBM. Basically, two of the barriers are of utmost importance in this regard, namely blood brain barrier (BBB) and blood brain tumor barrier (BBTB). This review will address different challenges and barriers in the treatment of GBM along with their etiology. The role and recent progress of lipid-based nanocarriers like liposomes, solid lipid nanocarriers (SLNs), nanostructured lipid carriers (NLCs), lipoplexes, and lipid hybrid carriers in the effective management of GBM will be discussed in detail.

Caveolin-1 as a critical component in the pathogenesis of lung fibrosis of different etiology: Evidences and mechanisms.

Caveolin is a structural protein of flask-shaped invaginations of the plasma membrane termed as caveolae and is widely expressed on the endothelial cells, smooth muscle cells and fibroblasts in the different parts of the body including the lung tissues. The expression of caveolin-1 in the lung tissues is important to prevent the fibrogenic actions of TGF-ß1 in lung fibrosis of different etiology including idiopathic pulmonary fibrosis, systemic sclerosis-associated interstitial lung disease and allergen-induced airway remodeling. Caveolin-1-mediated internalization and degradation of TGF-ß1 receptors may possibly account for the decreased actions of TGF-ß1. Studies have shown that the deficiency of caveolin-1 is very important in inducing lung fibrosis and its upregulation is reported to prevent lung fibrosis. The biological actions of caveolin-1 involve signaling pathways including JNK signaling, IL-4, STAT-3, miR199a-5p, CXCR4+ and CXCL12. The present review discusses the key role of caveolin and associated signaling pathways in the pathogenesis of lung fibrosis of different etiology.

Uptake, translocation and impact of green synthesized nanoceria on growth and antioxidant enzymes activity of Solanum lycopersicum L.

Cerium oxide nanoparticles (nanoceria) were synthesized by a novel, simple green chemistry procedure using Elaeagnus angustifolia leaf extract as a reducing and capping agent. The crystalline nature of nanoceria was confirmed by XRD analysis. FTIR analysis revealed that phytochemicals are present on the surface of nanoceria. SEM and TEM images revealed that the nanoceria are well dispersed, spherical in shape with a particle size range in between 30 and 75 nm. Thereafter, the effects of various concentrations of cerium oxide (CeO2) and green synthesized nanoceria on growth and metabolism of Solanum lycopersicum (tomato) were investigated. The bio-accumulation of Ce in tomato seedlings was found to be dose dependent and the results showed that with the increase in exposure concentrations, the accumulation of Ce contents in both root and shoots augmented. However, unlike nanoceria treated seedlings, Ce contents in the roots with CeO2 treatments were negligible than that in the shoots at lower concentrations and this suggested the immobilization of Ce in CeO2 treatment at lower concentrations. Nanoceria at 500 and 1000 mg/L resulted in inhibitory effect on growth of test plant as compared to CeO2 component. The exposure of plants to nanoceria and CeO2 has resulted in significant reduction in pigment content, increased LP, EL and H2O2 content. The activities of antioxidant enzymes viz. SOD, CAT, APX and GPX were significantly up regulated on exposure of nanoceria and CeO2. It is concluded that plant exposure with nanoceria at concentrations of 20 and 100 mg/L were more beneficial for growth and metabolism of tomato plants than that of CeO2 at equivalent concentrations.

Green synthesis of nanoparticles and its potential application.

Nanotechnology is a new and emerging technology with wealth of applications. It involves the synthesis and application of materials having one of the dimensions in the range of 1-100 nm. A wide variety of physico-chemical approaches are being used these days for the synthesis of nanoparticles (NPs). However, biogenic reduction of metal precursors to produce corresponding NPs is eco-friendly, less expensive, free of chemical contaminants for medical and biological applications where purity of NPs is of major concern. Biogenic reduction is a "Bottom Up" approach similar to chemical reduction where a reducing agent is replaced by extract of a natural products with inherent stabilizing, growth terminating and capping properties. Furthermore, the nature of biological entities in different concentrations in combination with reducing organic agents influence the size and shape of NPs. Present review focuses on microbes or plants based green synthesis of Ag, Au, Cu, Fe, Pd, Ru, PbS, CdS, CuO, CeO2, Fe3O4, TiO2, and ZnO NPs and their potential applications.

Comparative histologic and immunologic evaluation of 1,4-butanediol diglycidyl ether crosslinked versus noncrosslinked acellular swim bladder matrix for healing of full-thickness skin wounds in rabbits.

BACKGROUND: Collagen-rich extracellular matrix from land-based mammalian tissues is increasingly used in regenerative medicine. However, its uses are associated with risk of disease transfer and may carry an ethnocultural stigma. In the present study, collagen-rich acellular swim bladder matrix (ASBM) from Rohu fish was prepared using sodium deoxycholate and crosslinked with 1,4-butanediol diglycidyl ether (BDDGE). Wound healing potential of ASBM and ASBM-BDDGE was compared in full-thickness skin wounds in rabbits. MATERIALS AND METHODS: Four full-thickness skin wounds (20 × 20 mm(2) each) were created on the dorsum of 18 rabbits and randomly divided into three equal groups. Wounds were left open, repaired with ASBM and ASBM-BDDGE in groups sham (I), ASBM (II), and ASBM-BDDGE (III), respectively. Planimetry, contracture, immunologic, and histologic observations were carried out to evaluate wound healing. RESULTS: Significantly (P < 0.05) lesser wound contraction was observed in ASBM (II) and ASBM-BDDGE (III) groups compared with sham (I) group. Total immunoglobulin G response in rabbit sera was decreased significantly (P < 0.05) in the ASBM-BDDGE (III) group compared with ASBM (II) group by enzyme-linked immunosorbent assay. Stimulation index of peripheral blood lymphocytes was decreased significantly (P < 0.05) in the ASBM-BDDGE (III) group compared with ASBM (II) group by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Histologically, improved epithelialization, neovascularization, fibroplasia, and best arranged collagen fibers were observed in ASBM (II) and ASBM-BDDGE (III) groups as early as on postimplantation day 21. CONCLUSIONS: Findings of this study indicate that BDDGE crosslinked ASBM derived from Rohu fish has potential for the clinical applications. Furthermore, it is expected that their clinical applications will not be limited by ethnocultural stigma.

Activity of MMP-9 after repair of abdominal wall defects with acellular and crosslinked bovine pericardium in rabbit.

This study was undertaken for the identification of matrix metalloproteinases (MMPs) in extracts obtained from native, acellular and crosslinked bovine pericardium (in vitro), as well as in the plasma after implantation of these biomaterials in rabbits (in vivo). Native pericardium (NP) expressed a 72 kDa (MMP-2) band; whereas, in acellular pericardium (AP) two bands (10 kDa and 92 kDa) of MMPs were observed of which, 92 kDa band was very faint. AP crosslinked with glutaraldehyde did not show any gelatinase activity and thus reflects the creation of new additional chemical bonds between the collagen molecules which has been effectively removed. Gelatin zymography showed only one major band of 92 kDa in all the implanted and untreated rabbit plasma, but the relative amount of 92 kDa was 1-2 times higher in acellular bovine pericardium implanted rabbits as compared to crosslinked and native groups. In NP group, the 92 kDa band was the dullest among the three groups. This indicated that the level of MMP-9 corresponds to the degree of collagen degradation.

Antioxidant and antiproliferative activities of phenolics isolated from fruits of Himalayan yellow raspberry (Rubus ellipticus).

Yellow Himalayan raspberry, a wild edible fruit, was analyzed for phenolic contents, and antioxidant, antibacterial and antiproliferative activities. Phenolics were extracted using 80 % aqueous solvents containing methanol, acidic methanol, acetone and acidic acetone. Our analysis revealed that the acidic acetone extracts recovered the highest level of total phenolics (899 mg GAE/100 g FW) and flavonoids (433.5 mg CE/100 g FW). Free radical scavenging activities (DPPH, ABTS, superoxide and linoleate hydroperoxide radicals) and ferric reducing activity were highest in the acetone and acidic acetone extracts. No metal chelating or antibacterial activity was detected in any of the extracts. Acetone and methanol extracts showed potent antiproliferative activity against human cervical cancer cells (C33A) with an EC50 of inhibition at 5.04 and 4. 9 mg/ml fruit concentration respectively, while showing no cytotoxicity to normal PBMCs cells. Therefore, the present study concluded that the yellow Himalayan raspberry is a potent source of phytochemicals having super antioxidant and potent antiproliferative activities.

A Reversible Cause of Cutaneous Rash in a Patient With Alcohol Consumption.

The most common cutaneous manifestations of alcoholism include urticarial reaction, flushing, porphyria cutanea tarda, psoriasis, rosacea, seborrheic dermatitis, and pruritus. Here, we present a case of a young male with a history of alcohol abuse who presented with non-blanching, petechial, and perifollicular macular rash secondary to vitamin C deficiency in view of poor oral intake. The rash improved significantly with vitamin C supplementation. Although rare in developed countries, clinicians should keep vitamin C deficiency as a differential diagnosis for skin rash in alcohol consumers.

Modulation of inflammatory and oxidative stress biomarkers due to dexamethasone exposure in chicken splenocytes.

Dexamethasone (DEXA) is a potent corticosteroid, commonly used for treating inflammatory, hypersensitive and allergic conditions. It is administered to birds with tumours. Many studies were conducted on its immunosuppressive effects; however none of the similar study is available employing chicken splenocytes culture system. The present study was conducted to assess DEXA induced alterations in inflammatory and oxidative stress biomarkers in chicken splenocytes due to its in vitro exposure. The maximum non-cytotoxic dose (MNCD) was evaluated and was further used for conducting lymphocytes proliferation assay (LPA), antioxidant assays (lipid peroxidation, GSH, superoxide dismutase and nitric oxide assays) and assessment of mRNA levels of various genes (IL-1ß, IL-6, IL-10, LITAF, iNOS, NF-κB1, Nrf-2, Caspase-3 and -9) through qPCR. The MNCD was determined to be 30 ng/ml in chicken splenocytes culture system. DEXA caused reduction in B and T lymphocytes proliferation indicating its immunosuppressive effects, however improved the antioxidant status of the exposed splenocytes. The expression levels of IL-1ß, IL-6, iNOS, LITAF and NF-κB1 were significantly reduced while IL-10 was enhanced, which signify potent anti-inflammatory potential of DEXA. NF-κB is a major transcription factor that regulates genes responsible for both, innate and adaptive immune responses and elicits inflammation. The nuclear factor erythroid 2-related factor 2 (Nrf-2) level was found to be up-regulated. Nrf-2 plays important role in combating the oxidant stress and its increased expression could be the reason of improved antioxidant status of DEXA exposed cells. Present findings indicated that DEXA exhibited modulation in anti-inflammatory, immunomodulatory and antioxidant mediators in chicken splenocytes.

Implant abutment using hand drivers versus torque wrench.

The most frequent instrument used to begin tightening screws is a manually regulated screwdriver. Regarding manually regulated screwdrivers, predicted margins of error vary between fifteen percent to forty eight percent. Mechanical Torque restricting devices can consistently produce the requisite torques. As a result, devices like wrenches are needed to achieve the desirable values of torque. Hence, the present study was designed to evaluate the torque difference between handheld drivers and torque wrench and thereby its effect on the internal threads of implant surface.120 blocks was prepared from an autopolymerizing type of acrylic material each with a dimension of 1 inch. The centre of each block was affixed with analogue of dental impalnts with dimensions of 3.5 mm width and 13 mm length. With 60 specimens each, these models were split into two categories: hand torque specimens category and torque wrench specimens category. A stereomicroscope was used to look at the implant analog's internal threading architecture at a magnification of 100. At the bottom and top, four threads were spaced apart by a certain amount. Biowizard software was used for the assessment, and the results were recorded. Threads on the internal surface of dental implants were produced once more following torquing the implant's impression, and the stereomicroscope was used to quantify the separation between the 4 threads. Statistics were used to correlate the readings. All study participants' hand torque as well as torque wrench measurements were documented and statistical analysis was performed on them. When there was statistical analysis of the measurements then it was observed that mean values of torque in specimens included category of manual torque application was found out to be 33.6 ± 6.510 Ncm. On the other hand the mean values of torque in specimens included in category of torque application by torque wrench were found out to be 33.57 ± 3.472 Ncm. The outcome showed operator heterogeneity for both categories and operator variance when using a manual driver to generate torque. One independent - sample t test was used to contrast the mean data between the two categories, and P< 0.05 was chosen to determine whether the intergroup difference was meaningful. Because the torque values obtained with hand tightening were uneven, it may be concluded that different levels of hand torquing skill caused the torque to fluctuate. The torque wrench device displayed the desired torque data in the range that the manufacturer had advised. However, utilising manual drivers and a mechanical torque instrument did not cause any modifications to thread on the internal surface, and it rarely underwent significant deformation during the preliminary tightening torque readings. Thus, given that manually hand regulated drivers create a range of torques, it may be inferred that the employment of mechanical torque restricting instruments should be required.

Submassive Pulmonary Embolism Treated With Catheter-Directed Thrombolysis in Resource-Limited Setting: A Case Report and Review of Literature.

We describe a case of a young male who presented with acute onset progressively worsening shortness of breath for four days duration. He used to smoke cigarettes, and his profession required prolonged periods of standing. He underwent a two-dimensional echocardiogram showing right ventricular (RV) strain and computed tomography (CT) showing thrombus in the left major pulmonary artery. His pulmonary embolism severity index (PESI) score was high, predicting higher short-term mortality. Treatment options including risks and benefits were discussed with the patient, and he underwent catheter-directed thrombolysis (CDT) with rapid resolution of symptoms, oxygen saturation, and pulmonary artery pressures (PAP). He was discharged home safely after successful treatment of his condition.

A Rare Case Report of Impacted Foreign Body (Sewing Needle) in Upper Neck.

The Rationale: A 19-year-old female presented to the Otorhinolaryngology Department. Patient Concerns: Pain over the right side of the neck below the angle of the mandible following a fall on a pin cushion after a fight with her brother. She reported that the wound might have been caused by a sewing needle lodged in the pin cushion. Diagnosis: X-ray soft-tissue neck lateral view revealed a radiopaque linear shadow on the right side of the neck at the level of the C1-C2 vertebrae. On contrast-enhanced computed tomography, a linear (needle-like) foreign body at the level of C1-C2 was approximately 1.6 cm deep from the skin. The internal jugular vein seemed to be compressed between the needle and vertebrae. Treatment: Foreign body was explored and removed under general anaesthesia by an open lateral cervical approach. Outcomes: The patient's postoperative recovery was uneventful. Take-away Lesson: Due to early diagnosis, management, and a team of experienced surgeons, anaesthesiologists, and support staff, any morbidity or mortality was avoided.

Theranostic Applications of Nanomaterials in the Field of Cardiovascular Diseases.

A large percentage of people are being exposed to mortality due to cardiovascular diseases. Convention approaches have not provided satisfactory outcomes in the management of these diseases. To overcome the limitations of conventional approaches, nanomaterials like nanoparticles, nanotubes, micelles, lipid-based nanocarriers, dendrimers, and carbon-based nanoformulations represent the new aspect of diagnosis and treatment of cardiovascular diseases. The unique inherent properties of the nanomaterials are the major reasons for their rapidly growing demand in the field of medicine. Profound knowledge in the field of nanotechnology and biomedicine is needed for the notable translation of nanomaterials into theranostic cardiovascular applications. In this review, the authors have summarized different nanomaterials which are being extensively used to diagnose and treat the diseases, such as coronary heart disease, myocardial infarction, atherosclerosis, stroke and thrombosis.

Effect of biologically synthesized copper oxide nanoparticles on metabolism and antioxidant activity to the crop plants Solanum lycopersicum and Brassica oleracea var. botrytis.

Study on the ecological effect of metal oxide nanomaterials (NMs) has quickly amplified over the precedent years because it is assumed that these NMs will sooner or later be released into the environment. The present study deals with biologically oriented process for the green synthesis of copper oxide nanoparticles (CuO NPs) by using Morus alba leaf extract as reducing agent. Powder X-ray diffraction (XRD) and transmission electron microscope (TEM) analysis revealed the monoclinic phase and 20-40nm size respectively. The presence of reducing and capping agents revealed by Fourier transform infrared (FTIR) spectroscopy. The seedlings of Brassica oleracea var. botrytis and Solanum lycopersicum were exposed to 10, 50, 100, and 500mgL-1 concentrations of CuO NPs in the sand medium. Bioaccumulation of Cu was also investigated by atomic absorption spectroscopy (AAS). Plant exposure to 100 and 500mgL-1 of CuO NPs has resulted in significant reduction of total chlorophyll and sugar content in the two test plants while 10mgL-1 of NPs slightly increased the pigment and sugar content in tomato plants only. Augmentation of lipid peroxidation, electrolyte leakage, and antioxidant enzyme activity was observed in a dose dependent manner upon plants exposure to CuO NPs. Deposition of lignin in roots of both plants treated with the highest concentration of CuO NPs was observed. Histochemical analysis of leaves of treated plant with nitroblue tetrazolium and 3'3' diaminobenzidine showed a concentration dependent increase in superoxide and hydrogen peroxide formation in leaves. The green synthesis of CuO NPs was carried out by using Morus alba leaf extract. Accumulation of NPs more actively by tomato plants as compared to cauliflower was possibly due to the difference in root morphology. The histochemical visualization highlights the spatial organization of oxidant biochemistry occurring in response to metal stress.

Classification, Source, and Effect of Environmental Pollutants and Their Biodegradation.

Any foreign chemical substance that is unusually present within an organism or is unexpectedly found in the environment at a higher concentration than the permissible limits can be termed a xenobiotic or a pollutant. Such substances include carcinogens, drugs, food additives, hydrocarbons, dioxins, polychlorinated biphenyls, pesticides or even some natural compounds. Pollutants are known for their higher persistence and pervasiveness, and along with their transformed products, they can remain in and interact with the environment for prolonged periods. In this article, the classification of such substances based on their nature, use, physical state, pathophysiological effects, and sources is discussed. The effects of pollutants on the environment, their biotransformation in terms of bioaccumulation, and the different types of remediation such as in situ and ex situ remediation, are also presented.

Green synthesis of nano zinc oxide and evaluation of its impact on germination and metabolic activity of Solanum lycopersicum.

In the present study, zinc oxide nanoparticles (ZnO NPs) were rapidly synthesized at room temperature by treating zinc acetate dihydrate with the flower extract of Elaeagnus angustifolia (Russian olive). The formation of ZnO NPs was primarily confirmed by UV-visible absorption spectrum in the range of 250-700nm. XRD analysis and DLS particle size analyzer revealed the size of ZnO NPs. The FTIR spectrum revealed the presence of phytochemicals in the flower extract mediated ZnO NPs. Moreover, the morphology of the ZnO NPs was determined using SEM. Seeds of Solanum lycopersicum (tomato) were separately treated with different concentrations of synthesized ZnO NPs and zinc sulphate (ZnSO4) salt suspensions (common zinc supplement). The effect of these treatments on seed germination, seedling vigor, chlorophyll, protein and sugar contents as well as on the activities of lipid peroxidation and antioxidant enzyme were studied. Leaves of plants treated with 6.1mM concentration of ZnO NPs recorded maximum reflectance while it was minimum in plants treated with 1.2mM concentration of NPs. The effect of synthesized ZnO NPs on seedling vigor, pigment, protein and sugar content was found affirmative at lower concentrations contrary to control and ZnSO4 salt. The inhibitory effect at higher concentration of NPs indicated importance in the precise application of NPs, in Zn deficient system, where plant response varies with concentration. To the best of our knowledge this is the first report on Elaeagnus angustifolia mediated synthesis of ZnO NPs and their effects on germination and physiological activity of tomato.

Frequency of Helicobacter pylori and CagA antibody in patients with gastric neoplasms and controls: the Indian enigma.

BACKGROUND: Despite association between H. pylori and gastric neoplasm (GN) from the developed world, studies from India, where infection is more common and acquired early, are scant and contradictory. METHODS: Two hundred and seventy-nine patients with GN from two northern and one eastern Indian centers during the period 1997-2005, 101 non-ulcer dyspepsia (NUD), and 355 healthy volunteers (HV) were evaluated for H. pylori [rapid urease test (RUT), histology and anti-H. pylori, and CagA IgG serology]. RESULTS: Patients with GN [263 gastric carcinoma and 16 (6%) primary gastric lymphoma, 208 male] were older than HV (n = 355, 188 male) and NUD (n = 101, 54 male) patients (53 +/- 12 versus 44 +/- 17 and 43 +/- 13 years, respectively; P < 0.001). Eastern Indian patients with GN (n = 145) were younger than those from northern India (n = 134; 52 +/- 12 versus 55 +/- 12 years; P < 0.007, t-test). In GN and NUD patients H. pylori positivity by RUT [86/225 (38%) versus 46/101 (46%)], anti-H. pylori IgG [154/198 (78%) versus 85/101 (84%)], and histology [136/213 (64%) versus 55/101 (55%)] were comparable (chi(2)-test). Serum IgG anti-H. pylori antibody was more common among HV than among GN patients [300/355 (85%) versus 154/198 (78%); P = 0.04, chi(2)-test]. Intestinal metaplasia was more common in GN than in NUD patients [101/252 (40%) versus 2/98 (2%), P < 0.000, chi(2)-test]. CagAIgG was more common in GN than in NUD patients [124/163 (76%) versus 64/101 (63%)] but comparable to that in HV patients [87/98 (89%), P = NS]. CONCLUSION: Frequency of H. pylori as detected using endoscopy and serology-based tests is not higher among patients with GN as compared with controls in India.