Pricing of hospital services: evidence from a thematic review.

The management implications of pricing healthcare services, especially hospitals, have received insufficient scholarly attention. Additionally, disciplinary overlaps have led to scattered academic efforts in this domain. This study performs a thematic synthesis of the literature and applies retrospective analysis to hospital service pricing articles to address these issues. The study's inputs were sourced from well-known online repositories, using a structured search string and PRISMA flow chart to select the pertinent documents. Our thematic analysis of pricing literature encompasses: (a) comprehension of hospital service pricing nature; (b) pricing objectives, strategies and practices differentiation; (c) presentation of factors impacting hospital service pricing. We observe that hospital pricing is an intricate and unclear matter. The terms 'pricing strategies' and 'pricing practices' are often used interchangeably in academic literature. Hospital service pricing is influenced by costs, demand and supply factors, market structure, pricing regulation and third-party reimbursements. The study's findings provide policy implications for service pricing in hospitals, in addition to suggesting avenues for future research on hospital pricing.

An In Situ Fabricated Hydrogel Polymer - Palladium Nanocomposite Electrocatalyst for the HER: Critical Role of the Polymer in Realizing High Efficiency and Stability.

Development of general and simple designs of catalytic electrodes for the hydrogen evolution reaction (HER) is critical. The present work demonstrates the multiple roles played by a hydrogel polymer in the fabrication and activity enhancement of the nanoelectrocatalyst. A nanocomposite thin film of Pd with the insulating hydrogel, poly(2-hydroxyethyl methacrylate) (PHEMA), is fabricated through a facile in situ process, the polymer itself functioning as the reducing/stabilizing agent in the formation of Pd nanoparticles. Pd-PHEMA on Ni foam enables efficient HER in alkaline medium with a low overpotential; the polymer enables the electrocatalysis by its swelling and confinement of the electrolyte. Most significantly, when the electrode is subjected to an optimized cycling protocol, the overpotential decreases steadily, reaching an impressively low value of 36 mV (@10 mA cm-2 ). A low Tafel slope (68 mV dec-1 ), high exchange current density, Faradaic efficiency and TOF (3.27 mA cm-2 , 99 %, 122.7 h-1 ), and extended stability are achieved. Detailed investigations reveal the active role of the polymer in the evolution of the nanocatalyst, itself undergoing favorable morphological changes. The study illustrates the widened scope for developing efficient and stable catalytic electrodes with hydrogel polymers and unique features that promote the generation of green hydrogen.

Effectiveness of interventions to contain out-of-pocket-expenditure in lower-middle income countries: A systematic review and synthesis.

The extant literature on myriad interventional strategies to contain the adverse financial impacts of soaring out-of-pocket expenditures commands systematic auditing and knowledge synthesis. The purpose of this study is to answer these specific questions. What are the interventions present in lower-middle-income countries? How effective are those interventions in reducing the household's out-of-pocket expenditure? Are the studies suffering from any methodological bias? The imprints for this systematic review are obtained from Scopus, PubMed, Web of Science, ProQuest and CINAHL. These manuscripts are identified in full compliance with PRISMA guidelines. The documents identified have undergone quality assessment checks using the 'Effective Public Health Practice Project'. The review identified Interventions that are found to reduce out-of-pocket expenditure are patient educational programs, a combination of financial assistance, healthcare facility quality upgrade measures, and early disease detection strategies. However, these reductions represented marginal changes in the total health expenditure of patients. The role of non-health insurance interventions and the combination of health insurance and non-health insurance measures are highlighted. This review concludes by emphasising the need for further research to fill the knowledge gap by building on the suggestions put forward.

Electrospun polysaccharide scaffolds: wound healing and stem cell differentiation.

Irrespective of the labyrinth of fastidiously woven artificial scaffolds, the lack of biocompatibility hampers effective clinical translation, which is the definitive purpose of any biomedical system or device. Hence, the current exploration deals with the fabrication of scaffolds with enhanced bioactivities for wound healing. The methodology used for the fabrication of the scaffolds was electrospinning of the polysaccharide, which is isolated from tamarind seed kernel using the electrospinning process. To improve the antimicrobial activity of the scaffolds, in-house synthesized silver nanoparticles were added to the scaffolds. Wound healing and antimicrobial efficiency of the scaffolds were established in murine models. An insight into the wound healing mechanism was also analyzed using differentiation screening of stem cells grown on scaffolds. The results showed that newly synthesized scaffolds presented excellent wound healing ability along with antimicrobial activity. Furthermore, detailed toxicological evaluations through the histopathology and collagen staining wound sections, the probability of any off-target effects were also ruled out. Differentiation screening showed that adipogenesis was more prominent in cells attached to the scaffolds and markers of adipogenesis were strongly expressed in fluorescent microscopy. Thus we hope that the scaffolds mediate stem cell differentiation in wounds and promote a progressive healing response. Results thus obtained were encouraging and further studies need to embark on to establish the combined role in all aspects studied here.

Randomized, Comparative, Clinical Trial to Evaluate Efficacy and Safety of PNB001 in Moderate COVID-19 Patients

ABSTARCTO_ST_ABSObjectiveC_ST_ABSTo evaluate the efficacy and safety of PNB001 a CCK-A agonist and CCK-B antagonist, a new chemical entity with anti-inflammatory and immune stimulation properties, along with Standard of Care (SOC) in patients with moderate COVID-19 infection. DesignMulti-center, randomized, parallel group, comparative, open label study. SettingTwo tertiary-care hospitals in India. ParticipantsPatients with laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) within 2 days of randomization, having pneumonia with no signs of severe disease (severe disease means SpO2[≤]94% on room air), and any two of the following signs or symptoms suggestive of COVID-19: fever, cough, dyspnea, or hypoxia. InterventionsPatients were randomized 1:1 to receive PNB001 at an oral dose of 100 mg three times daily for 14 days with Standard of Care (PNB001+SOC) or only SOC. Main outcome measuresThe primary endpoints were mean change in the 8-point WHO Ordinal Scale score from baseline by Day 14 and mortality rate by Day 28. The key secondary endpoints were percentage of patients showing change in clinical status using the ordinal scale, improvement in inflammatory segments in X-ray chest, reduction of days of hospitalization, duration of supplemental oxygen use, days to negative PCR for COVID-19 and change in inflammation markers Interlukin-6 (IL6) and C-reactive protein (CRP) from baseline by Day 14. ResultsA total of 40 (20 in PNB 001+SOC arm and 20 in SOC arm) patients were randomized and received treatment. The primary endpoint showed significant clinical improvement from baseline to Day 14 with PNB001+SOC (0.22 Vs 1.12; P=0.0421). One patient in PNB001+SOC arm and two patients in SOC arm died (1 Vs 2; HR: 2.0 [95%CI=0.18, 22.05]; P=0.5637) by Day 28. At the end of the treatment by Day 14, more patients achieved zero ordinal scale in PNB001+SOC arm (17 Vs 12; P=0.0766). In the PNB001+SOC arm, change in mean chest X-ray score showed significant improvement (2.05 Vs 1.16; P=0.0321), and more patients quickly showed complete improvement (10 Vs 7; HR: 1.48 [95%CI=0.64, 3.44]; P=0.4309). In the PNB001+SOC arm, patients needed shorter duration of hospitalization in days (9.45 Vs 9.80) and more patients attained earlier discharge from the hospital (19 Vs 15; P=0.0486) with respect to days. The mean duration of supplemental oxygen requirement in days was shorter (5.45 Vs 7.10) and complete withdrawal from supplemental oxygen was more frequent with PNB001+SOC compared to SOC by Day 14 (17 Vs 13; P=0.1441). All patients in both the arms had negative PCR by the end of the study (18 Vs 17; P=0.6265) by similar time (7.6 Vs 7.0). Exploratory analysis done for IL-6, CRP, Neutrophil-Lymphocyte-Ratio (NLR), Platelet-Lymphocyte-Ratio (PLR) and Erythrocyte Sedimentation Rate (ESR) showed statistically significant reduction by Day 14 demonstrating PNB001s anti-inflammatory and immunomodulatory properties. Lymphocyte and neutrophil counts also improved by Day 14. 11 adverse events (AE) in 8 patients were observed with PNB001+SOC compared to 13 AEs in 10 patients with SOC; none of the AEs in PNB001+SOC arm were related to PNB001. The most common AE were tachycardia and acute respiratory distress syndrome; there were isolated cases of hepatic enzyme elevation and hyperglycemia. Overall, safety profile was similar between PNB001+SOC and SOC arms. ConclusionsPNB001 with standard of care showed significant clinical improvement in moderate COVID-19 patients when compared to standard of care and was well tolerated by moderate COVID-19 patients. Trial RegistrationCTRI/2020/10/028423

A novel treatment of bromelain and acetylcysteine (BromAc) in patients with peritoneal mucinous tumours: A phase I first in man study.

BACKGROUND: Bromelain (Brom) and Acetylcysteine (Ac) have synergistic activity resulting in dissolution of tumour-produced mucin both in vitro and in vivo. The aim of this study was to determine whether treatment of mucinous peritoneal tumour with BromAc can be performed with an acceptable safety profile and to conduct a preliminary assessment of efficacy in a clinical setting. METHODS: Under radiological guidance, a drain was inserted into the tumour mass or intraperitoneally. Each patient could have more than one tumour site treated. Brom 20-60 mg and Ac 1·5-2 g was administered in 5% glucose. At 24 h, the patient was assessed for symptoms including treatment-related adverse events (AEs) and the drain was aspirated. The volume of tumour removed was measured. A repeat dose via the drain was given in most patients. All patients that received at least one dose of BromAc were included in the safety and response analysis. FINDINGS: Between March 2018 and July 2019, 20 patients with mucinous tumours were treated with BromAc. Seventeen (85%) of patients had at least one treatment-emergent AE. The most frequent treatment-related AEs were CRP rise (n = 16, 80%), WCC rise (n = 11, 55%), fever (n = 7, 35%, grade I) and pain (n = 6, 30%, grade II/III). Serious treatment-related AEs accounted for 12·5% of all AEs. There were no anaphylactic reactions. There were no deaths due to treatment-related AEs. An objective response to treatment was seen in 73·2% of treated sites. CONCLUSION: Based on these preliminary results and our preclinical data, injection of BromAc into mucinous tumours had a manageable safety profile. Considerable mucolytic activity was seen by volume of mucin extracted and radiological appearance. These results support further investigation of BromAC for patients with inoperable mucinous tumours and may provide a new and minimally invasive treatment for these patients.

A biocompatible glycol-capped nano-delivery system with stimuli-responsive drug release kinetics abrogates cancer cell survival.

An eco-friendly polysaccharide (PSP001) isolated from the fruit rind of Punica granatum is a biodegradable polymer with immunostimulatory and anticancer properties. PSP001 was employed for the stimuli-responsive targeted delivery of antineoplastic agent doxorubicin (Dox) by the fabrication of Dox-holding PSP nanoparticles (DPN). The galactose moieties of PSP001 were occupied as an effective tumor-targeted motif against the over-expressed asialoglycoprotein and galectin receptors of cancers. DPN followed a pH-sensitive cargo release kinetics, competent cancer cell internalization profile, and appealing biocompatibility towards peripheral red blood cells. The selective execution of caspase-mediated programmed cell death by the DPN on cancer cells was confirmed with multiple apoptosis studies. Extensive toxicity profiling on BALB/c mice rules out any palpable signs of abnormality with DPN administration while bare Dox produced vital signs of toxicity. Studies on syngraft solid tumor-bearing mice uncovered the tumor homing nature of DPN with the subsequent release of the entrapped drug which further translated in the direction of a significant reduction in the tumor payload and enhanced survival benefits, thus offering a robust approach towards endurable cancer management.

Causes of Under-5 Mortality Among Brazil, the Russian Federation, India, China, and South Africa Nations: A Comparative Study.

OBJECTIVES: The coverage of the study extends over BRICS nations. This study aims to identify the major causes of under-5 mortality across the selected nations of Brazil, the Russian Federation, India, China, and South Africa (BRICS). METHODS: Secondary data served as inputs to the survey. Relevant data were obtained from the World Bank data repository, the United Nations Development Program, and the World Health Organization's (WHO's) official online repository between the years 2000 and 2015. Descriptive and inferential statistical tools, such as trend analysis, analysis of variance (ANOVA), and multivariate analysis of variance (MANOVA), were used to make sense of the relationship between the macro, community, and individual level variables on under-5 mortality. RESULTS: The results indicated a decreasing pattern in deaths from all the disease conditions affecting the under-5 age group for all 5 countries. CONCLUSION: The outcome of the study provides insights on disease transitions over time across the regions, which may have policy-related and educational implications.

Semi-interpenetrating nanosilver doped polysaccharide hydrogel scaffolds for cutaneous wound healing.

The extensive advancement with novel wound dressing materials functionalized with desirable properties, often touted as a panacea for cuts and burns afflicting various pathologies. However, it would indeed be a hard task to isolate any such material which perfectly fits the needs of any biomedical issue at hand. Biocompatibility, biodegradability as well as non-toxicity of natural polysaccharide served as a versatile and tunable platform for designing natural polysaccharide based scaffolds as an attractive tool in tissue engineering with a greater degree of acceptability. In this regard, we aimed to fabricate a semi interpenetrating hydrogel via exploiting the nontoxic and immune-stimulatory nature of galacto-xyloglucan (PST001) which was further doped with silver nanoparticles to formulate SNP@PST. The wound healing potential of SNP@PST was then studied both with in vitro and preclinical mice models. The current study gives a formulation for cost effective preparation of polysaccharide hydrogels using acrylamide crosslinking with improved biocompatibility and degradability. Wound healing studies in mice proved the efficiency of gels for the clinical application wherein the incorporation of nanosilver greatly enhanced the antimicrobial activity.

Immunostimulatory plant polysaccharides impede cancer progression and metastasis by avoiding off-target effects.

An unexploited homo-polysaccharide (PSM001) isolated from the seed kernel of Kottukonam variety of Mangifera indica, demonstrated selective cytotoxicity against cancer cells both in vitro and in murine models while maintaining the immunostimulatory potential. Galactoxyloglucan (PST001) isolated from the seeds of Tamarindus indica, was previously established to be an effective anticancer and immunomodulatory agent. Cancer metastasis, with key features including invasion, migration, increased angiogenesis and colony formation is only likely to accentuate in the coming decades, considering the ground realities of the modern lifestyle and environmental factors and hence both the polysaccharides were tested towards the management of malignancy. It was a startling observation with both the biopolymers in inhibiting various processes involved in the metastatic cascade. A quick perusal of the issue at hand would throw up the promising ability of both PSM001 and PST001 to inhibit lung metastatic nodules of C57BL/6 mice wherein the combinatorial treatment of these polysaccharides with vincristine delivered superior therapeutic output. Later, vascular endothelial growth factor and multiple matrix metalloproteinases were found to be the lead players in the polysaccharide mediated metastatic inhibition. Having considered the complexities associated with the chemotherapy in metastatic cancer in terms of palpable immunosuppression, the aftermaths with the co-administration of an immunostimulatory agent which itself possess unique anticancer and anti-metastatic potentials with a potent chemotherapeutic agent will be enormously consequential.

Serotonergic mechanisms in the 6-Hz psychomotor seizures in mice.

Serotonin (5-hydroxytrytamine (5-HT)) plays an important role in experimental seizures. Recently, we reported the depletion of 5-HT by parachlorophynylalanine (PCPA) in whole brain to enhance 6-Hz psychomotor seizures in mice. In the present work, we investigated the effect of 5-HT depletion in cortex and hippocampus, brain regions relevant for epilepsy, on behavioral and ultra-structural changes following 6-Hz psychomotor seizures in mice. In addition, we studied the effect of sodium valproate (SVP) on behavioral, biochemical, and ultra-structural effects induced by 6 Hz. Behavioral changes induced by 6 Hz stimulation were characterized as the increased duration of Straub's tail, stun position, twitching of vibrissae, forelimb clonus, and increased rearing and grooming. PCPA administration further enhanced while SVP reduced these behaviors in mice. The 6-Hz psychomotor seizure induced ultra-structural changes in both cortex and hippocampus in mice treated with PCPA. Furthermore, PCPA administrations followed by 6Hz-induced seizures were accompanied by reduced hippocampal and cortical 5-HT. SVP attenuated the PCPA-induced ultra-structural changes and alterations of 5-HT content in the mouse brain. The study suggests the involvement of 5-HT in the 6 Hz psychomotor seizures and in the mechanisms of action of SVP against such seizures in mice.

Surfactant structural effects on mediated electrocatalytic dechlorination: Links between the micellar enhancement of dechlorination reactions and micellar properties.

Electrocatalytic dechlorination mediated by micelle-solubilized electrocatalysts has attracted considerable current interest for pollutant degradation. Aggregation in micellar assemblies and their interactions with the additives in solution are affected by the surfactant structure. By choosing appropriate surfactant molecules, the system properties may be altered to achieve enhanced dechlorination efficiency. Cetyltrimethylammonium bromide-based surfactants with different hydrocarbon lengths and headgroup structures were studied for their structural effects on [Co(I)(bipyridine)3]+-mediated dechlorination reactions. A widely used pollutants allyl chloride derivatives were studied as the substrates. The performance of the surfactants towards various dechlorination reactions was evaluated by cyclic voltammetry (CV) based on the catalytic efficiency. Key micellar parameters were determined by CV and rotating disc electrode using [Co(II)(bipyridine)3]2+ as the micelle-solubilized redox probe. The surfactants affected the dechlorination reaction to different extents, correlating well with their structure. The catalytic efficiency was explained by the interactions of the Co(II)/Co(I) with the surfactant hydrophobic tail and headgroup. This is the first report quantitatively linking the performance of the surfactants in dechlorination reactions with their molecular structure, showing that is possible to use variant surfactant structures to tune the micellar properties for their application towards the enhanced dechlorination of organic pollutants. Substrate structure-susceptibility to reduction relationships were also discussed.

Computational and mechanistic studies on the effect of galactoxyloglucan: Imatinib nanoconjugate in imatinib resistant K562 cells.

Imatinib mesylate, a BCR/ABL fusion protein inhibitor, is the first-line treatment against chronic myelogenous leukemia. In spite of its advantageous viewpoints, imatinib still has genuine impediments like undesirable side effects and tumor resistance during chemotherapy. Nanoparticles with sustainable release profile will help in targeted delivery of anticancer drugs while minimizing deleterious side effects and drug resistance. The use of biopolymers like galactoxyloglucan (PST001) for the fabrication of imatinib mesylate nanoparticles could impart its use in overcoming multidrug resistance in chronic myelogenous leukemia patients with minimal side effects. This study involved in the synthesis of PST-Imatinib nanoconjugates with appreciable drug payload and excellent cytotoxicity against drug-resistant chronic myelogenous leukemia cell line (K562) in comparison with free drug. The use of bioinformatics tool revealed better binding affinity for the drug-polysaccharide complex than the drug alone with three proteins: 3QX3 (Topoisomerase), 1M17 (EGFR tyrosine kinase domain), and 3QRJ (ABL1 kinase domain). Assessment of the biochemical, hematological, and histopathological parameters in mice upheld the security and adequacy of the nanoconjugate compared to free drug. Although perspective investigations are warranted, in a condition like drug resistance in leukemia, this nanoconjugate would display a productive approach in cancer therapeutics.

Studies on Effective Generation of Mediators Simultaneously at Both Half-Cells for VOC Degradation by Mediated Electroreduction and Mediated Electrooxidation.

Of the several electrochemical methods for pollutant degradation, the mediated electrooxidation (MEO) process is widely used. However, the MEO process utilizes only one (anodic) compartment toward pollutant degradation. To effectively utilize the full electrochemical cell, an improved electrolytic cell producing both oxidant and reductant mediators at their respective half-cells, which can be employed for treating two pollutants simultaneously, was investigated. The cathodic half-cell was studied first toward maximum [CoI(CN)5]4- (Co+) generation (21%) from a [CoII(CN)6]3- precursor by optimizing several experimental factors such as the electrolyte, cathode material, and orientation of the Nafion324 membrane. The anodic half-cell was optimized similarly for higher Co3(SO4)2 (Co3+) yields (41%) from a CoIISO4 precursor. The practical utility of the newly developed full cell setup, combining the optimized cathodic half-cell and optimized anodic half-cell, was demonstrated by electroscrubbing experiments with simultaneous dichloromethane removal by Co+ via the mediated electroreduction process and phenol removal by Co3+ via the MEO process, showing not only utilization of the full electrochemical cell, but also degradation of two different pollutants by the same applied current that was used in the conventional cell to remove only one pollutant.

Effect of piperine on pharmacokinetics of sodium valproate in plasma samples of rats using gas chromatography-mass spectrometry method.

UNLABELLED: Piperine (PIP) is used as anticonvulsant in traditional Chinese medicine. Co-administration of low-dose sodium valproate with PIP has been regarded to have potential anticonvulsant activity. AIM: This study was intended to investigate the effect of PIP on the pharmacokinetics of sodium valproate (SVP) in the plasma samples of rats using gas chromatography-mass spectrometry (GC-MS) method. MATERIALS AND METHODS: The plasma samples obtained after oral administration of SVP, 150 mg/kg and SVP, 150 mg/kg + PIP, and 5 mg/kg to male Wistar rats were used to quantify the concentrations in plasma using GC-MS method. RESULTS: A simple and accurate method developed in-house was applied for the analysis of plasma samples of Wistar rats after oral administration of SVP and PIP + sodium valproate, respectively. The pharmacokinetic parameters reported 14.8-fold increase in plasma concentration (maximum observed concentration in the concentration-time profile), 4.6-fold increase in area under the curve and slightly prolonged time to reach that concentration (1 h) of SVP in presence of PIP. CONCLUSION: The study reaffirms the bioenhancing effect of PIP suggesting possibility of dose reduction of SVP while co-adminstering with PIP.

The Effect of Subchronic Dosing of Ciproxifan and Clobenpropit on Dopamine and Histamine Levels in Rats.

The present study was designed to investigate the effect of once daily for 7-day (subchronic treatment) dosing of histamine H3 receptor antagonists, ciproxifan (CPX) (3 mg/kg, i.p.), and clobenpropit (CBP) (15 mg/kg, i.p), including clozapine (CLZ) (3.0 mg/kg, i.p.) and chlorpromazine (CPZ) (3.0 mg/kg, i.p.), the atypical and typical antipsychotic, respectively, on MK-801(0.2 mg/kg, i.p.)-induced locomotor activity, and dopamine and histamine levels in rats. Dopamine and histamine levels were measured in striatum and hypothalamus, respectively, of rat brain. Atypical and typical antipsychotics were used to serve as clinically relevant reference agents to compare the effects of the H3 receptor antagonists. MK-801-induced increase of horizontal activity was reduced with CPX and CBP. The attenuation of MK-801-induced locomotor hyperactivity produced by CPX and CBP was comparable to CLZ and CPZ. MK-801 raised dopamine levels in the striatum, which was reduced in rats pretreated with CPX and CBP. CPZ also lowered striatal dopamine levels, though the decrease was less robust compared to CLZ, CPX and CBP. MK-801 increased histamine content although to a lesser degree. Subchronic treatment with CPX and CBP exhibited further increase in histamine levels in the hypothalamus compared to the MK-801 treatment alone. Histamine H3 receptor agonist, R-α methylhistamine (10 mg/kg, i.p.) counteracted the effects of CPX and CBP. In conclusion, the subchronic dosing of CPX/CBP suggests some antipsychotic-like activities as CPX/CBP counteracts the modulatory effects of MK-801 on dopamine and histamine levels and prevents MK-801-induced hyperlocomotor behaviors.

Anticancer activity of galactoxyloglucan polysaccharide-conjugated doxorubicin nanoparticles: Mechanistic insights and interactome analysis.

Toxicity associated with chemotherapeutic drugs such as doxorubicin (Dox), is one of the major obstacles that is currently affecting patients. PST-Dox (Galactoxyloglucan, PST001-conjugated Dox) nanoparticles were synthesized by encapsulating Dox with polysaccharide PST001, isolated from Tamarindus indica (Ti) by ionic gelation with tripolyphosphate (TPP). Herein, we demonstrate a detailed mechanistic and interactome network analysis that is specific to PST-Dox action in cancer cells and normal lymphocytes. Our results show that PST-Dox is superior to its parental counterparts, exhibiting a greater cytotoxicity by the induction of apoptosis against a wide variety of cancers by enhanced cellular uptake of Dox from the nanoparticle conjugates. Also, PST-Dox nanoparticles were non-toxic to normal lymphocytes with limited immunostimulatory effects up to certain doses. Elucidation of molecular mechanism by whole genome microarray in cancer cells and lymphocytes revealed that a large number of genes were dysregulated specifically in cancer cells. Specifically, a unique target gene EGR1, contextually determined translational activation of P53 in the cancerous and non-cancerous cells. Most of the key downregulated genes were tyrosine kinases, indicating the potential inhibitory action of PST-Dox on tyrosine kinase oncogenic pathways. Western blotting of proteins corresponding to the genes that were altered at the genomic level was very well correlated in the majority of them, except in a few that demonstrated post-transcriptional modifications. The important findings and highly disciplined approaches highlighted in the present study will speed up the therapeutic potential of this augmented nanoparticle formulation for more robust clinical studies and testing in several cancers.

Resveratrol chemosensitizes HER-2-overexpressing breast cancer cells to docetaxel chemoresistance by inhibiting docetaxel-mediated activation of HER-2-Akt axis.

As breast cancer cells often develop chemoresistance, better therapeutic options are in search to circumvent it. Here we demonstrate that human epidermal growth factor receptor-2 (HER-2)-overexpressing breast cancer cells resist docetaxel-induced cytotoxicity by upregulating HER-2 and its activity downstream, through Akt and mitogen-activated protein kinase (MAPK) pathways. We observed that introducing resveratrol as a chemosensitizer in docetaxel chemotherapy blocks upregulation and activation of HER-2 in addition to blocking downstream signaling pathways such as Akt. Resveratrol and docetaxel combination results in the synergistic induction of cell death in HER-2-overexpressing SK-BR-3 cells, whereas introduction of wild-type HER-2 in MDA-MD-231 cells increased the resistance to docetaxel. Dominant-negative HER-2 sensitizes SK-BR-3 cells to docetaxel. Our study identified a new synergistic therapeutic combination that targets HER-2-induced breast cancer resistance and might help to overcome therapeutic resistance during breast cancer therapy. The synergism of docetaxel and resveratrol was maximum in SK-BR-3, which is unique among the cell lines studied, due to its high expression status of HER-2, a receptor known to dictate the signaling environment of breast cancer cells. Docetaxel could further induce HER-2 activity in these cells, which was downregulated on resveratrol treatment. Transfection of DN-HER-2 in SK-BR-3 cells inhibits the synergism as the transfection itself sensitizes these cells to docetaxel, leaving no role for resveratrol, whereas ectopic expression of HER-2 introduces the synergism in MDA-MB-231, the triple-negative cell line, in which the synergism was minimum, attesting the crucial role of HER-2 in suppressing the sensitivity to docetaxel. Single-agent docetaxel induced HER-2-mediated resistance to cell death, which was blocked by resveratrol. Resveratrol also downregulated docetaxel-induced activation of MAPK and Akt, survival signaling pathways downstream of HER-2. In short, this study, for the first time, establishes the role of HER-2-Akt signaling axis in regulating the synergistic effect of docetaxel and resveratrol in breast cancer cells overexpressing HER-2.

Inhibitory effect of Careya arborea on inflammatory biomarkers in carrageenan-induced inflammation.

CONTEXT: Careya arborea Roxb. (Lecythidaceae) has multiple applications in traditional medicine; it exhibits analgesic, antibacterial, anti-inflammatory, antiulcer, and protective effects. However, the effect of C. arborea on biochemical and immmunological inflammatory mediators has not been explored. OBJECTIVE: The present study investigates the anti-inflammatory potential of the methanol extract of C. arborea stem bark and further assesses its possible mechanism on the modulation of inflammatory biomarkers. MATERIALS AND METHODS: Anti-inflammatory activity of C. arborea methanol extract (CAME) was evaluated (100 and 200 mg/kg, p.o) using indomethacin (10 mg/kg, p.o) as the standard drug in Wistar albino rats. Inflammation was induced by injecting 0.1 ml carrageenan (1% w/v) into the left hind paw. The anti-inflammatory mechanism was studied by measuring malondialdehyde (MDA), C-reactive protein (CRP), nitric oxide (NO), myeloperoxidase (MPO), TNF-α, and IL-1ß levels in both control and treated groups. A protocol has also been established to quantify quercetin and betulinic acid content in CAME using HPTLC fingerprint. RESULTS: Careya arborea significantly (p < 0.001) decreased carrageenan-induced paw edema, showed a reduction of 48.87 and 65.53% at doses of 100 and 200 mg/kg, respectively. Moreover, CAME significantly decreased the MDA, CRP, NO, and MPO levels, elevated by carrageenan induced inflammation. CAME also markedly down-regulated serum TNF-α and IL-1ß levels. These findings were further supported by the histological study. The content of quercetin and betulinic acid in CAME was found to be 0.177 and 3.14%, respectively. CONCLUSION: Several mechanisms, including the inhibition of pro-inflammatory cytokines, enzymes and mediators release, appear to account for the anti-inflammatory potential of C. arborea.

Fine needle aspiration cytology of thyroid lesions and its correlation with histopathology in a series of 248 patients.

Thyroid swellings are a significant clinical problem in the general population but majority of them are nonneoplastic and do not require surgery. The initial screening procedures include ultrasonography, fine needle aspiration cytology (FNAC) and radionucleotide scan. An initial screening test which will diagnose thyroid lesions accurately will help to avoid surgery in nonneoplastic conditions. The aim of the present study is to correlate the cytology findings with final histopathology. Two hundred and forty-eight cases of thyroid nodules which underwent FNAC followed by surgery were included in this study. The cytology diagnoses were classified into nondiagnostic/unsatisfactory, benign, atypia of undetermined significance/follicular lesion of undetermined significance, follicular neoplasm/suspicious for a follicular neoplasm, suspicious for malignancy and malignant. The fine needle aspiration diagnosis was compared with the histopathology diagnosis. In majority of cases the FNA diagnosis was in concordance with final histopathology. A high incidence of follicular variant of papillary carcinoma thyroid was detected in this study. The awareness of this entity and the search for fine nuclear details of papillary carcinoma can lead to proper identification of this category of tumors and thus help to avoid false negative and equivocal results. Fine needle aspiration cytology is a simple, cost effective, rapid to perform procedure with high degree of accuracy and is recommended as the first line investigation for the diagnosis of thyroid lesions.