Daughertymoss9830

Current evidence on the natural course from BQ exposure to cancer occurrence and development provides information for developing primary, secondary, and tertiary prevention strategies against BQ-associated cancer at clinical or translational levels. Fourier Transform Infrared Spectroscopy (FTIR) has been largely employed by scientific researchers to improve diagnosis and treatment of cancer, using various biofluids and tissues. The technology has proved to be easy to use, rapid and cost-effective for analysis on human blood serum to discriminate between cancer versus healthy control samples. The high sensitivity and specificity achievable during samples classification aided by machine learning algorithms, offers an opportunity to transform cancer referral pathways, as it has been demonstrated in a unique and recent prospective clinical validation study on brain tumours. We herein highlight the importance of early detection in cancer research using FTIR, discussing the technique, the suitability of serum for analysis and previous studies, with special focus on pre-clinical factors and clinical translation requirements and development. Medulloblastoma (MB) is the most frequent malignant brain tumour in children with a poor outcome. Divided into four molecular subgroups, MB of the Sonic hedgehog (SHH) subgroup accounts for approximately 25% of the cases and is driven by mutations within components of the SHH pathway, such as its receptors PTCH1 or SMO. A fraction of these cases additionally harbour PIK3CA mutations, the relevance of which is so far unknown. To unravel the role of Pik3ca mutations alone or in combination with a constitutively activated SHH signalling pathway, transgenic mice were used. These mice show mutated variants within Smo, Ptch1 or Pik3ca genes in cerebellar granule neuron precursors, which represent the cellular origin of SHH MB. Our results show that Pik3ca mutations alone are insufficient to cause developmental alterations or to initiate MB. However, they significantly accelerate the growth of Shh MB, induce tumour spread throughout the cerebrospinal fluid, and result in lower survival rates of mice with a double Pik3caH1047R/SmoM2 or Pik3caH1047R/Ptch1 mutation. Therefore, PIK3CA mutations in SHH MB may represent a therapeutic target for first and second line combination treatments. ETHNOPHARMACOLOGICAL RELEVANCE Panax ginseng C.A. Mey. (Korean ginseng) has been widely used in traditional medicine to treat diabetes mellitus for thousands of years. It also plays a key role in health maintenance owing to its anti-oxidant and anti-fatigue properties, and is quite popular as a dietary supplement. AIM OF THE STUDY This study was designed to offer a complementary and alternative medicine to manage the diabetic kidney disease (DKD), which causes long-term damage to the renal structure. We also investigated the regulation of the autophagy mechanism, which is the underlying the pathogenesis of DKD. MATERIALS AND METHODS The effect of Korean red ginseng (KRG) on DKD was evaluated using human kidney proximal tubular cells and streptozotocin (STZ)-treated Sprague-Dawley rat models. In vitro experiments were conducted to evaluate the proteins related to fibrosis and autophagy. This was followed by in vivo experiments involving rats treated with single intraperitoneal administration of STZ (60 mg/kg) rosis by blocking TGF-β1 activation and can induce cellular autophagy. Therefore, this study strongly suggests that KRG exhibits a renoprotective effect against the STZ-induced DKD. ETHNO-PHARMACOLOGICAL RELEVANCE Tagetes patula L. an important medicinal plant of Asteraceae family is worldwide distributed and reported for its folkloric use in various disorders like skin, eye problems, injury and stomach issues by different communities of China, Nepal, India, Bangladesh and Pakistan. AIM OF THIS REVIEW The present review has focused the ethnomedicinal and traditional uses of T. patula with special reference to Asian countries. Chemical constituents and pharmacological aspects of T. patula was explored. After reading the review the researchers may able to find new insights to further investigate this plant. REVISION OF LITERATURE Google scholar, PubMed, and Science direct, were the major search engines used to get relevant information based on articles and books. RESULTS and Discussion The ethno-botanical aspects were recorded, the pharmacological aspects like antioxidant, anti-inflammatory, antimicrobial, anti-parasitic and anti-diabetic potentials evaluated both in vivo and in vitro is described. The toxicity or allergic manifestation with the use of the plant is also a section in the article. It is a rich source for thiophene derivatives, flavonoids, carotenoids, terpenes and terpenoids. Various gaps were pointed out for researchers that need to be investigated. CONCLUSION Various traditional uses have been reported in Asian countries that need to be scientifically investigated in depth and several pharmacological activities have been reported for the T. patula but more detailed and mechanism-based studies linked to a particular lead compound need to be targeted in future. ETHNOPHARMACOLOGICAL RELEVANCE Piper umbellatum L. leaves, commonly found in the Amazon, Cerrado and Atlantic rain forest regions of Brazil, are widely used as a traditional medicine to treat gastrointestinal disorders and inflammation, among others diseases. Also, previous scientific studies demonstrated that P. umbellatum has gastroprotective and anti-inflammatory activity. AIM To investigate the phytochemical profiles and the intestinal anti-inflammatory effect of the hydroethanolic extract of P. umbellatum (HEPu) leaf on ulcerative colitis in rats. MATERIALS AND METHODS In this study, the chemical composition of HEPu was analyzed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography coupled to mass spectrometry (LC/MS). mTOR inhibitor Also, this work studied the effects of HEPu on ulcerative colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS, 30 mg/mL in 20% ethanol) by intrarectal administration in rats. Simultaneously, animals were pre-treated orally with HEPu (30, 100 and 300 mg/kg), mesll infiltration, ulceration and necrosis (p  less then  0.001). Furthermore, HEPu (30, 100, and 300 mg/kg, p.o) inhibited the levels of oxidative parameters, such as MPO (49%, 53%, and 62%, p  less then  0.001), NO (20%, 19%, 22%, p  less then  0.01), and MDA (75%, 83%, 70%, p  less then  0.001), whereas increased the antioxidant activities such as SOD (208%, 192%, 64%, p  less then  0.001), GSH (94%, 75%, 49%, p  less then  0.01), and CAT (92%, 69%, 108%, p  less then  0.01). The extract also inhibited the pro-inflammatory cytokines TNF-α (81%, 85%, 85%, p  less then  0.001) and IL-1β (95%, 79%, 89%, p  less then  0.001) levels. CONCLUSION Together, these results revealed that P. umbellatum L. is a promising source of metabolites to be used in the treatment of inflammatory bowel disease. Supercritical impregnation technology was applied to load acrylic intraocular lenses (IOLs) with methotrexate to produce a sustained drug delivery device to mitigate posterior capsule opacification. Drug release kinetics were studied in vitro and used to determine the drug loading. Loaded IOLs and control IOLs treated under the same operating conditions, but without drug, were implanted ex vivo in human donor capsular bags. The typical cell growth was observed and immunofluorescence staining of three common fibrosis markers, fibronectin, F-actin and α-smooth muscle actin was carried out. Transparent IOLs presenting a sustained release of methotrexate for more than 80 days were produced. Drug loading varying between 0.43 and 0.75 ± 0.03 µgdrug·mg-1IOL were obtained when varying the supercritical impregnation pressure (8 and 25 MPa) and duration (30 and 240 min) at 308 K. The use of ethanol (5 mol%) as a co-solvent did not influence the impregnation efficiency and was even unfavorable at certain conditions. Even if the implantation of methotrexate loaded IOLs did not lead to a statistically significant variation in the duration required for a full cell coverage of the posterior capsule in the human capsular bag model, it was shown to reduce fibrosis by inhibiting epithelial-mesenchymal transformation. The innovative application presented has the potential to gain clinical relevance. While nanoparticulate drugs for deep lung delivery hold promise for particular disease treatments, their size-related physical instability and tendency of being exhaled during breathing remain major challenges to their inhaled formulation development. Here we report a viable method for converting drug nanosuspensions into inhalable, stable and redispersible nano-agglomerates through combined in-situ thermal gelation and spray drying. Itraconazole (ITZ) nanosuspensions were prepared by flash nanoprecipitation, and co-spray dried with two different grades of the gel-forming polymer, methylcellulose (MC M20 and MC M450) as protectants. MC M20 was found superior in protecting ITZ nanoparticles against thermal stress (through nanoparticle entrapment within its gel network structure) during spray drying. In terms of redispersibility, an Sf/Si ratio (i.e., ratio of nanoparticle sizes after and before spray drying) of unity (1.02 ± 0.03), reflecting full particle size preservation, was achieved by optimizing the suspending medium content and spray drying parameters. Formulation components, nanosuspension concentration and spray drying parameters all showed a significant impact on the aerosol performance of the resulting agglomerates, but an absence of defined trends or correlations. Overall, the MC-protected nano-agglomerates displayed excellent in-vitro aerosol performance with fine particle fractions higher than 50% and mass median aerodynamic diameters within the 2-3 µm range, which are ideal for deep lung delivery. Two ibuprofen suspension formulations were investigated for their dissolution in various bicarbonate, phosphate and acetate buffers. Phosphate and acetate gave faster release than bicarbonate at comparable molarities. Nevertheless, mass transport modelling using the reversible non-equilibrium (RNE) approach enabled the calculation of phosphate molarities that gave good matches to physiological bicarbonate in terms of ibuprofen dissolution. This shows that developing surrogate buffers for bicarbonate that are devoid of the technical difficulties associated with the bicarbonate-CO2 systems is possible. In addition, the intestinal dissolution kinetics of the tested suspensions were determined by applying compartmental pharmacokinetic modelling to plasma profiles that were previously obtained for these suspensions in an in vivo study performed on healthy human volunteers. The in vitro dissolution profiles in bicarbonate compared reasonably well with the profiles representing the in vivo intestinal dissolution kinetics of the tested suspensions when applied to healthy human volunteers in a pharmacokinetic study. This shows the possible potential toward extending biowaivers so that they include BCS class IIa compounds. Multidrug resistance (MDR) and the spread of cancer cells (metastasis) are major causes leading to failure of cancer treatment. MDR can develop in two main ways, with differences in their mechanisms for drug resistance, first drug-selected MDR developing after chemotherapeutic treatment, and metastasis-associated MDR acquired by cellular adaptation to microenvironmental changes during metastasis. This study aims to use a nanoparticle-mediated photodynamic therapy (NPs/PDT) approach to overcome both types of MDR. A photosensitizer, 5,10,15,20-Tetrakis(4-hydroxy-phenyl)-21H,23H-porphine (pTHPP) was loaded into poly(D,L-lactide-co-glycolide) (PLGA)-lipid hybrid nanoparticles. The photocytotoxic effect of the nanoparticles was evaluated using two different MDR models established from one cell line, A549 human lung adenocarcinoma, including (1) A549RT-eto, a MDR cell line derived from A549 cells by drug-selection, and (2) detachment-induced MDR acquired by A549 cells when cultured as floating cells under non-adherent conditions, which mimic metastasizing cancer cells in the blood/lymphatic circulation.