Te4+ and Er3+ doped ZrO2 nanoparticles with enhanced photocatalytic, antibacterial activity and dielectric properties: A next generation of multifunctional material.

Amid rising water contamination from industrial sources, tackling toxic dyes and pathogens is critical. Photocatalysis offers a cost-effective and eco-friendly solution to this pressing challenges. Herein, we synthesized Te4+ and Er3+ doped ZrO2 photocatalysts through hydrothermal method and investigated their efficacy in degrading Congo red (CR) and pathogens under visible light. XRD and Raman Spectroscopy confirm monoclinic and tetragonal mixed-phases without any impurities. Doping-induced defects, reduced crystalline diameter, high surface area, modified bandgap (2.95 eV), photoluminescence quenching, coupled with interfacial polarization, contribute to EZO's excellent dielectric response (1.149 × 106), for achieving remarkable photocatalytic activity, verified by photoelectrochemical measurements, LC-MS and phytotoxicity analysis. Under optimal conditions, EZO achieves 99% CR degradation within 100 min (TOC 79.9%), surpassing ZO (77%) and TZO (84%). Catalyst dosages, dye concentrations, and solution pH effect on EZO's photocatalytic performance are systematically assessed. Scavenging experiment emphasized the pivotal role of · OH in CR degradation with 96.4% efficiency after 4 cycles, affirming its remarkable stability. Moreover, EZO demonstrates ROS-mediated antibacterial activity against E. faecalis and E. coli bacteria under visible light, achieving >97% and >94% inhibition rate with an inhibition zone > 3 mm. Hence, the nanoparticle's dual action offers a practical solution for treating contaminated wastewater, ensuring safe irrigation.

Optimization of microbial fuel cell process using a novel consortium for aromatic hydrocarbon bioremediation and bioelectricity generation.

Microbial Fuel Cell (MFC) is an innovative bio-electrochemical approach which converts biochemical energy inherent in wastewater into electrical energy, thus contributing to circular economy. Five electrogenic bacteria, Kocuria rosea (GTPAS76), two strains of Bacillus circulans (GTPO28 and GTPAS54), and two strains of Corynebacterium vitaeruminis (GTPO38 and GTPO42) were isolated from a common effluent treatment plant (CETP) and were used individually as well as in consortium form to run double chambered "H" type microbial fuel cell. Individually they could produce voltage in the range of 0.4-0.7 V in the MFC systems. Consortium developed using GTPO28, GTPO38, GTPAS54 and GTPAS76 were capable of producing voltage output of 0.8 V with 81.81 % and 64 % COD and BOD reduction, respectively. The EPS production capacity and electricity generation by the isolated bacteria correlated significantly (r = 0.72). Various parameters like, effect of preformed biofilm, length of salt bridge and its reuse, aeration, substrate concentration and external resistance were studied in detail. The study emphasizes on improving the commercialization aspect of MFC with repeated use of salt bridge and improving wastewater treatment potential after optimization of MFC system. Polarization curve and power density trends were studied in optimized MFC. A maximum power density and current density achieved were 18.15 mW/m2 and 370.37 mA/m2, respectively using 5 mM sodium benzoate. This study reports the use of sodium benzoate as a substrate along with reusing of the salt bridge in MFC study with promising results for BOD and COD reduction, proving it to be futuristic technology for bio-based circular ecosystem development.

Acute and sub-chronic oral toxicity studies of hesperidin isolated from orange peel extract in Sprague Dawley rats.

Citrus sinensis contains glycoside hesperetin-7-rhamnoglucoside (hesperidin) which harbor an array of therapeutic potentials including antioxidant, anticancer, and anti-inflammatory. However, a systematic examination of safety is needed before its utilization. Hence, the present investigation is aimed to evaluate acute and sub-chronic toxicity of hesperidin isolated from the citrus fruit. Hesperidin (73%) was isolated from a methanolic extract of dried peel of the citrus fruit, characterized using FTIR, and standardized by HPLC. Its acute oral toxicity (AOT) and sub-chronic toxicity studies were carried out in Sprague-Dawley rats. Hesperidin (5000 mg/kg) showed 10% mortality in AOT. In sub-chronic toxicity study, hesperidin (250 and 500 mg/kg) did not induce any abnormalities in body weight, food consumption, clinical signs, ophthalmological and neurological observations, urine analysis, hematology, clinical chemistry, organ weights, and gross pathology. However, hesperidin (1000 mg/kg) showed significant (p < 0.05) alterations in body and organ weights, hematology, clinical chemistry, and tissue histopathology. To conclude, hesperidin has median lethal dose (LD50) of 4837.5 mg/kg, and Low Observed Adverse Effect Level (LOAEL) at 1000 mg/kg for both male and female Sprague-Dawley rats. Thus, hesperidin isolated from citrus fruit showed a good safety profile in animal study.

Development of fluorescent protein-based biosensing strains: A new tool for the detection of aromatic hydrocarbon pollutants in the environment.

The major sources for release of hydrocarbons into the environment include the effluents generated from chemical processing industries and ports. The introduction of such hazardous compounds into natural water bodies creates considerable disturbances in aquatic life and causes a threat to humans. Thus, it is essential to detect and quantify pollutants at various stages of the wastewater generation and treatment before they reach natural aquatic environments and contaminate them. This study reports the development of "biosensing strains" by cloning hydrocarbon recognizing promoter-operator and a reporter gene in bacterial strains for sensing the presence of pollutants at their lowest possible concentration. So far, various biosensing strains have been constructed with a fused promoter-operator region of the hydrocarbon degrading operons, but most of them use luxAB as a reporter gene. A novel approach in the present study aimed at constructing strains harboring two different fluorescent protein (FP)-based reporter genes for the quantification of multiple pollutants at a time. Two vectors were designed with a fusion of tbuT-gfp and phnR-cfp for the quantification of mono- and poly-aromatic hydrocarbons, respectively. The designed vectors were transformed into E. coli DH5α, and these strains were designated as E. coli DH5α 2296-gfp (containing pPROBE-Tbut-RBS-gfp-npt) and E. coli DH5α 2301-cfp (containing pPROBE-phn-RBS-cfp-npt). Both the developed recombinant strains were capable of successfully detecting mono- and poly-aromatic hydrocarbons in the range of 1-100 µM. The sensing capacity of recombinant strains was successfully validated with actual wastewater samples against available physico-chemical analytical techniques. The development of such recombinant microbial strains indicates the future for online contaminant detection, treatment quality monitoring and protection of aquatic flora and fauna.

Evaluation of health-related quality of life in hemolytic uraemic syndrome patients treated with eculizumab: a systematic evaluation on basis of EMPRO.

BACKGROUND: Hemolytic uraemic syndrome (HUS) is progressive renal failure disease and determination of their quality of life (QoL) on the basis of patient-reported outcomes (PROs) are becoming increasingly important in the economic evaluations for its treatment with eculizumab (ECU). AIM: To perform the systematic evaluation of QoL in HUS patients treated with ECU on the basis of Evaluating Measures of Patient Reported Outcomes (EMPRO) tool. MATERIALS AND METHODS: A systematic review was conducted in PubMed, EMBASE, the Cochrane Library, CINAHL and Google Scholar till September 2016 by two independent researchers. Each identified instrument was evaluated for its quality of performance by using the EMPRO tool for its overall score and seven attribute specific scores (range 0-100, worst to best). RESULTS: Five different PROs instruments were identified from 10 articles (n = 112) which showed eculizumab significantly improves health-related quality of life (HRQOL) in atypical HUS (aHUS) patients. Amongst five instruments viz. EuroQol five dimensions questionnaire (EQ-5 D), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Headache Impact Test-6 (HIT-6), 36-Item Short Form Health Survey (SF-36) and Visual Analogue Scale (VAS), the overall EMPRO score was higher for VAS (73.83) and EQ-5 D (73.81). Whereas, FACIT-F and HIT- 6 were just able to meet the minimal threshold of EMPRO scoring (50.24 and 59.09, respectively). CONCLUSIONS: Evidence from present investigation support that eculizumab significantly improves HRQoL in patients with aHUS furthermore, EQ-5 D and VAS instrument should be recommended for assessing HRQoL in them. However, selection of PRO instrument for determination of QoL in HUS entirely depend upon the study requirements.

Influence of charge traps in carbon nanodots on gas interaction.

The nonlinear electrical characteristic of carbon nanodots (CNDs) has revealed important physical phenomena of charge trapping playing a dominant role in surface interactions. Functional groups on the surface of CNDs attract ambient water molecules which in turn act as charge traps and give rise to electrical hysteresis that plays a dominant role in understanding charge transport in CNDs on surface interactions. Hysteresis in the current-voltage response is further utilized to study the interaction of the CNDs with nitrogen dioxide gas as an external stimuli. The hysteresis area is observed to be dependent on the time of gas interaction with the CNDs, therefore revealing the interaction mechanism of the CNDs with the gas.

An investigation of the association of genetic susceptibility risk with somatic mutation burden in breast cancer.

BACKGROUND: Genome-wide association studies have reported nearly 100 common germline susceptibility loci associated with the risk for breast cancer. Tumour sequencing studies have characterised somatic mutation profiles in breast cancer patients. The relationship between breast cancer susceptibility loci and somatic mutation patterns in breast cancer remains largely unexplored. METHODS: We used single-nucleotide polymorphism (SNP) genotyping array data and tumour exome sequencing data available from 638 breast cancer patients of European ancestry from The Cancer Genome Atlas (TCGA) project. We analysed both genotype data and, when necessary, imputed genotypes for 90 known breast cancer susceptibility loci. We performed linear regression models to investigate possible associations between germline risk variants with total somatic mutation count (TSMC), as well as specific mutation types. We examined individual SNP genotypes, as well as a multi-SNP polygenic risk score (PRS). Models were statistically adjusted for age at diagnosis, stage, oestrogen-receptor (ER) and progesterone-receptor (PR) status of breast cancer. We also performed stratified analyses by ER and PR status. RESULTS: We observed a significant inverse association (P=8.75 × 10(-6); FDR=0.001) between the risk allele in rs2588809 of the gene RAD51B and TSMC across all breast cancer patients, for both ER(+) and ER(-) tumours. This association was also evident for different types of mutations. The PRS analysis for all patients, with or without rs2588809, showed a significant inverse association (P=0.01 and 0.04, respectively) with TSMC. This inverse association was significant in ER(+) patients with the ER(+)-specific PRS (P=0.02), but not among ER(-) patients for the ER(-)-specific PRS (P=0.39). CONCLUSIONS: We observed an inverse association between common germline risk variants and TSMC, which, if confirmed, could provide new insights into how germline variation informs our understanding of somatic mutation patterns in breast cancer.

Sandwiched assembly of ZnO nanowires between graphene layers for a self-powered and fast responsive ultraviolet photodetector.

A heterostructure of graphene and zinc oxide (ZnO) nanowires (NWs) is fabricated by sandwiching an array of ZnO NWs between two graphene layers for an ultraviolet (UV) photodetector. This unique structure allows NWs to be in direct contact with the graphene layers, minimizing the effect of the substrate or metal electrodes. In this device, graphene layers act as highly conducting electrodes with a high mobility of the generated charge carriers. An excellent sensitivity is demonstrated towards UV illumination, with a reversible photoresponse even for a short period of UV illumination. Response and recovery times of a few milliseconds demonstrated a much faster photoresponse than most of the conventional ZnO nanostructure-based photodetectors. It is shown that the generation of a built-in electric field between the interface of graphene and ZnO NWs effectively contributes to the separation of photogenerated electron-hole pairs for photocurrent generation without applying any external bias. Upon application of external bias voltage, the electric field further increases the drift velocity of photogenerated electrons by reducing the charge recombination rates, and results in an enhancement of the photocurrent. Therefore, the graphene-based heterostructure (G/ZnO NW/G) opens avenues to constructing a novel heterostructure with a combination of two functionally dissimilar materials.

Few-layer graphene/ZnO nanowires based high performance UV photodetector.

A graphene and zinc oxide nanowires (G/ZnO NWs) based ultraviolet (UV) photodetector presents excellent responsivity and photocurrent gain with detectivity. Graphene due to higher charge carrier transport mobility induces faster response to UV illumination at the interface between ZnO and graphene with improved response and decay times as compared to a ZnO NWs device alone. A linear increase is revealed for both the responsivity and photocurrent gain of the G/ZnO NWs device with the applied bias. These results suggest that the G/ZnO NWs device exhibits great promise for highly efficient UV photodetectors.

Graphene based multifunctional flame sensor.

Recently, graphene has attracted much attention due to its unique electrical and thermal properties along with its high surface area, and hence presents an ideal sensing material. We report a novel configuration of a graphene based flame sensor by exploiting the response of few layer graphene to a flame along two different directions, where flame detection results from a difference in heat transfer mechanisms. A complete sensor module was developed with a signal conditioning circuit that compensates for any drift in the baseline of the sensor, along with a flame detection algorithm implemented in a microcontroller to detect the flame. A pre-defined threshold for either of the sensors is tunable, which can be varied based on the nature of the flame, hence presenting a system that can be used for detection of any kind of flame. This finding also presents a scalable method that opens avenues to modify complicated sensing schemes.

Control of TiO2 grain size and positioning in three-dimensionally ordered macroporous TiO2/C composite anodes for lithium ion batteries.

After several high-profile incidents that raised concerns about the hazards posed by lithium ion batteries, research has accelerated in the development of safer electrodes and electrolytes. One anode material, titanium dioxide (TiO2), offers a distinct safety advantage in comparison to commercialized graphite anodes, since TiO2 has a higher potential for lithium intercalation. In this article, we present two routes for the facile, robust synthesis of nanostructured TiO2/carbon composites for use as lithium ion battery anodes. These materials are made using a combination of colloidal crystal templating and surfactant templating, leading to the first report of a three-dimensionally ordered macroporous TiO2/C composite with mesoporous walls. Control over the size and location of the TiO2 crystallites in the composite (an often difficult task) has been achieved by changing the chelating agent in the precursor. Adjustment of the pyrolysis temperature has also allowed us to strike a balance between the size of the TiO2 crystallites and the degree of carbonization. Using these pathways to optimize electrochemical performance, the primarily macroporous TiO2/C composites can attain a capacity of 171 mAh/g at a rate of 1 C. Additionally, the carbon in these composites can function as a secondary template for high-surface-area, macroporous TiO2 with disordered mesoporous voids. Combining the advantages of a nanocrystalline framework and significant open porosity, the macroporous TiO2 delivers a stable capacity (>170 mAh/g at a rate of C/2) over 100 cycles.

The role of inflammatory mediators and matrix metalloproteinases (MMPs) in the progression of osteoarthritis.

Osteoarthritis (OA) is a chronic musculoskeletal disorder characterized by an imbalance between (synthesis) and catabolism (degradation) in altered homeostasis of articular cartilage mediated primarily by the innate immune system. OA degenerates the joints resulting in synovial hyperplasia, degradation of articular cartilage with damage of the structural and functional integrity of the cartilage extracellular matrix, subchondral sclerosis, osteophyte formation, and is characterized by chronic pain, stiffness, and loss of function. Inflammation triggered by factors like biomechanical stress is involved in the development of osteoarthritis. In OA apart from catabolic effects, anti-inflammatory anabolic processes also occur continually. There is also an underlying chronic inflammation present, not only in cartilage tissue but also within the synovium, which perpetuates tissue destruction of the OA joint. The consideration of inflammation in OA considers synovitis and/or other cellular and molecular events in the synovium during the progression of OA. In this review, we have presented the progression of joint degradation that results in OA. The critical role of inflammation in the pathogenesis of OA is discussed in detail along with the dysregulation within the cytokine networks composed of inflammatory and anti-inflammatory cytokines that drive catabolic pathways, inhibit matrix synthesis, and promote cellular apoptosis. OA pathogenesis, fluctuation of synovitis, and its clinical impact on disease progression are presented here along with the role of synovial macrophages in promoting inflammatory and destructive responses in OA. The role of interplay between different cytokines, structure, and function of their receptors in the inter-cellular signaling pathway is further explored. The effect of cytokines in the increased synthesis and release of matrix-decomposing proteolytic enzymes, such as matrix metalloproteinase (MMPs) and a disintegrin-like and metalloproteinase with thrombospondin motif (ADAMTS), is elaborated emphasizing the potential impact of MMPs on the chondrocytes, synovial cells, articular and periarticular tissues, and other immune system cells migrating to the site of inflammation. We also shed light on the pathogenesis of OA via oxidative damage particularly due to nitric oxide (NO) via its angiogenic response to inflammation. We concluded by presenting the current knowledge about the tissue inhibitors of metalloproteinases (TIMPs). Synthetic MMP inhibitors include zinc binding group (ZBG), non-ZBG, and mechanism-based inhibitors, all of which have the potential to be therapeutically beneficial in the treatment of osteoarthritis. Improving our understanding of the signaling pathways and molecular mechanisms that regulate the MMP gene expression, may open up new avenues for the creation of therapies that can stop the joint damage associated with OA.

Absence of BTK, BCL2, and PLCG2 Mutations in Chronic Lymphocytic Leukemia Relapsing after First-Line Treatment with Fixed-Duration Ibrutinib plus Venetoclax.

PURPOSE: Mutations in BTK, PLCG2, and BCL2 have been reported in patients with progressive disease (PD) on continuous single-agent BTK or BCL2 inhibitor treatment. We tested for these mutations in samples from patients with PD after completion of first-line treatment with fixed-duration ibrutinib plus venetoclax for chronic lymphocytic leukemia (CLL) in the phase II CAPTIVATE study. PATIENTS AND METHODS: A total of 191 patients completed fixed-duration ibrutinib plus venetoclax (three cycles of ibrutinib then 12-13 cycles of ibrutinib plus venetoclax). Genomic risk features [del(11q), del(13q), del(17p), trisomy 12, complex karyotype, unmutated IGHV, TP53 mutated] and mutations in genes recurrently mutated in CLL (ATM, BIRC3, BRAF, CHD2, EZH2, FBXW7, MYD88, NOTCH1, POT1, RPS15, SF3B1, XPO1) were assessed at baseline in patients with and without PD at data cutoff; gene variants and resistance-associated mutations in BTK, PLCG2, or BCL2 were evaluated at PD. RESULTS: Of 191 patients completing fixed-duration ibrutinib plus venetoclax, with median follow-up of 38.9 months, 29 (15%) developed PD. No baseline risk feature or gene mutation was significantly associated with development of PD. No previously reported resistance-associated mutations in BTK, PLCG2, or BCL2 were detected at PD in 25 patients with available samples. Of the 29 patients with PD, 19 have required retreatment (single-agent ibrutinib, n = 16, or ibrutinib plus venetoclax, n = 3); 17 achieved partial response or better, 1 achieved stable disease, and 1 is pending response assessment. CONCLUSIONS: First-line fixed-duration combination treatment with ibrutinib plus venetoclax may mitigate development of resistance mechanisms associated with continuous single-agent targeted therapies, allowing for effective retreatment. See related commentary by Al-Sawaf and Davids, p. 471.

Selective Sensing of Volatile Organic Compounds Using an Electrostatically Formed Nanowire Sensor Based on Automatic Machine Learning.

With the development of Internet of Things technology, various sensors are under intense development. Electrostatically formed nanowire (EFN) gas sensors are multigate Si sensors based on CMOS technology and have the unique advantages of ultralow power consumption and very large-scale integration (VLSI) compatibility for mass production. In order to achieve selectivity, machine learning is required to accurately identify the detected gas. In this work, we introduce automatic learning technology, by which the common algorithms are sorted and applied to the EFN gas sensor. The advantages and disadvantages of the top four tree-based model algorithms are discussed, and the unilateral training models are ensembled to further improve the accuracy of the algorithm. The analyses of two groups of experiments show that the CatBoost algorithm has the highest evaluation index. In addition, the feature importance of the classification is analyzed from the physical meaning of electrostatically formed nanowire dimensions, paving the way for model fusion and mechanism exploration.

STROVE: spatial data infrastructure enabled cloud-fog-edge computing framework for combating COVID-19 pandemic.

The outbreak of 2019 novel coronavirus (COVID-19) has triggered unprecedented challenges and put the whole world in a parlous condition. The impacts of COVID-19 is a matter of grave concern in terms of fatality rate, socio-economical condition, health infrastructure. It is obvious that only pharmaceutical solutions (vaccine) cannot eradicate this pandemic completely, and effective strategies regarding lockdown measures, restricted mobility, emergency services to users-in brief data-driven decision system is of utmost importance. This necessitates an efficient data analytics framework, data infrastructure to store, manage pandemic related information, and distributed computing platform to support such data-driven operations. In the past few decades, Internet of Things-based devices and applications have emerged significantly in various sectors including healthcare and time-critical applications. To be specific, health-sensors help to accumulate health-related parameters at different time-instances of a day, the movement sensors keep track of mobility traces of the user, and helps to assist them in varied conditions. The smartphones are equipped with several such sensors and the ability of low-cost connected sensors to cover large areas makes it the most useful component to combat pandemics such as COVID-19. However, analysing and managing the huge amount of data generated by these sensors is a big challenge. In this paper we have proposed a unified framework which has three major components: (i) Spatial Data Infrastructure to manage, store, analyse and share spatio-temporal information with stakeholders efficiently, (ii) Cloud-Fog-Edge-based hierarchical architecture to support preliminary diagnosis, monitoring patients' mobility, health parameters and activities while they are in quarantine or home-based treatment, and (iii) Assisting users in varied emergency situation leveraging efficient data-driven techniques at low-latency and energy consumption. The mobility data analytics along with SDI is required to interpret the movement dynamics of the region and correlate with COVID-19 hotspots. Further, Cloud-Fog-Edge-based system architecture is required to provision healthcare services efficiently and in timely manner. The proposed framework yields encouraging results in taking decisions based on the COVID-19 context and assisting users effectively by enhancing accuracy of detecting suspected infected people by ∼ 24% and reducing delay by ∼ 55% compared to cloud-only system.

Impact of rituximab on anthropometric indices among childhood steroid-dependent nephrotic syndromes.

BACKGROUND: There is scarcity of data on impact of rituximab on anthropometrical parameters (weight, height and body mass index i.e. BMI SD score (SDS)) among children with steroid-dependent nephrotic syndromes (SDNS). METHODS: Multicentre retrospective review. RESULTS: 102 children with SDNS (male: 63%; n=64), median age 7 (IQR: 4.3-9.6) years, received a total of 217 rituximab infusions (total 110 cycles). At median follow-up of 2.1 (IQR: 1.3-2.8) years, 58 (57%) children were off steroids and a significant fall in steroid threshold for relapse was noted (median 0.6; IQR 0.4-0.9 to median 0.3; IQR 0.12 - 0.5 mg/kg/alternate day, p=0.005). Anthropometric parameters (BMI SDS: 0.92±1.8 to 0.25±1.47, p=0.003; weight SDS: 0.20±1.6 to -0.11±1.3, p=0.01; and height SDS: -0.93±1.88 to -0.45±1.54, p=0.04) as well as obesity (38% to 20%, p=0.003) and short stature (11% to 3%, p=0.02) improved. Results remained significant even when analysis was restricted to children ≤12 years (n=88), (BMI SDS: 0.97±1.98 to 0.25±1.5, p=0.001; weight SDS: 0.33±1.6 to 0.02±1.2, p=0.01; and height SDS: -0.67±1.84 to -0.186±1.42, p=0.001). CONCLUSIONS: Use of rituximab resulted in significant steroid sparing effect with an improvement in both growth and obesity parameters.

Therapeutic Potential of Morin in Ovalbumin-induced Allergic Asthma Via Modulation of SUMF2/IL-13 and BLT2/NF-kB Signaling Pathway.

BACKGROUND: Allergic asthma is a chronic immune-inflammatory disorder, characterized by airway inflammation and airway hyperresponsiveness (AHR). Morin is a natural flavonoid reported to exhibit inhibitory action against IgE-mediated allergic response. AIM: To determine the efficacy of murine model of ovalbumin (OVA)-induced AHR inhibition by morin and decipher the molecular mechanism involved. MATERIALS AND METHODS: Sprague-Dawley rats were sensitized and challenged with OVA to induce AHR. Rats received treatment with morin (10, 30 and 100 mg/kg, p.o.) for the next 28 days. RESULTS: Morin (30 and 100 mg/kg) significantly and dose-dependently attenuated (p < 0.01 and p < 0.001) OVA-induced alterations in pulse oxy and lung function test, increased bronchoalveolar lavage fluid cell counts, elevated total protein and albumin levels in serum, BALF, and lungs, increased serum total and OVA-specific IgE levels and, elevated oxidative stress levels in the lung. RT-PCR analysis revealed that morin treatment (30 and 100 mg/kg) significantly (p < 0.001) up-regulated SUMF2 mRNA expression in lungs whereas mRNA expressions of BLT2, NF-κB, and Th2-cytokine (TNF-α, IL-1ß, IL-4, IL-6, and IL-13) were down-regulated significantly and dose-dependently (p < 0.01 and p < 0.001). Also, histologic and ultrastructural studies showed that morin significantly inhibited (p < 0.001) OVAinduced perivascular and peribranchial inflammatory infiltration and interstitial fibrosis. CONCLUSION: Morin exhibited inhibitory effect against OVA-induced allergic asthma by activation of SUMF2 which impeded IL-13 expression and in turn attenuated Th2-cytokines, BLT2, NF-κB, and IgE levels to ameliorate AHR. Thus, our findings suggested that morin could be considered as a potential alternative therapeutic agent for the management of allergic asthma.

Alpha-synuclein, Proteotoxicity and Parkinson's Disease: Search for Neuroprotective Therapy.

BACKGROUND: There is a growing body of evidence in animal and cell based models of Parkinson's disease (PD) to suggest that overexpression and / or abnormal accumulation and aggregation of α-synuclein can trigger neuronal death. This important role of α-synuclein in PD pathogenesis is supported by the fact that duplication, triplication and mutations of α-synuclein gene cause familial forms of PD. METHODS: A review of literature was performed by searching PubMed and Google Scholar for relevant articles highlighting the pathogenic role of α-synuclein and the potential therapeutic implications of targeting various pathways related to this protein. RESULTS: The overexpression and accumulation of α-synuclein within neurons may involve both transcriptional and post-transcriptional mechanisms including a decreased degradation of the protein through proteasomal or autophagic processes. The mechanisms of monomeric α-synuclein aggregating to oligomers and fibrils have been investigated intensively, but it is still not certain which form of this natively unfolded protein is responsible for toxicity. Likewise the proteotoxic pathways induced by α- synuclein leading to neuronal death are not elucidated completely but mitochondrial dysfunction, endoplasmic reticulum (ER) stress and altered ER-golgi transport may play crucial roles in this process. At the molecular level, the ability of α-synuclein to form pores in biomembranes or to interact with specific proteins of the cell organelles and the cytosol could be determining factors in the toxicity of this protein. CONCLUSION: Despite many limitations in our present knowledge of physiological and pathological functions of α-synuclein, it appears that this protein may be a target for the development of neuroprotective drugs against PD. This review has discussed many such potential drugs which prevent the expression, accumulation and aggregation of α-synuclein or its interactions with mitochondria or ER and thereby effectively abolish α-synuclein mediated toxicity in different experimental models.

Hesperidin, a plant flavonoid accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats: Role of TGF-ß/Smads and Ang-1/Tie-2 signaling pathways.

Background: Delayed wound healing is a diverse, multifactorial, complex and inter-related complication of diabetes resulting in significant clinical morbidity. Hesperidin possesses potent antidiabetic and wound healing activity. Aim: To evaluate the potential of hesperidin against experimentally induced diabetes foot ulcers. Methods: Diabetes was induced experimentally by streptozotocin (STZ, 55 mg/kg, i.p.) in Sprague Dawley rats (180-220 g) and wounds were created on the dorsal surface of the hind paw of rats. Hesperidin (25, 50 and 100 mg/kg, p.o.) was administered for 21 days after wound stabilization. Various biochemical, molecular and histopathological parameters were evaluated in wound tissue. Results: STZ-induced decrease in body weight and increase in blood glucose, food, and water intake was significantly (p < 0.05) inhibited by hesperidin (50 and 100 mg/kg) treatment. It showed a significant increase (p < 0.05) in percent wound closure and serum insulin level. The STZ-induced decrease in SOD and GSH level, as well as elevated MDA and NO levels, were significantly (p < 0.05) attenuated by hesperidin (50 and 100 mg/kg) treatment. Intraperitoneal administration of STZ caused significant down-regulation in VEGF-c, Ang-1, Tie-2, TGF-ß and Smad 2/3 mRNA expression in wound tissues whereas hesperidin (50 and 100 mg/kg) treatment showed significant up-regulation in these mRNA expressions. STZ-induced alteration in would architecture was also attenuated by hesperidin (50 and 100 mg/kg) treatment. Conclusion: Together, treatment with hesperidin accelerate angiogenesis and vasculogenesis via up-regulation of VEGF-c, Ang-1/Tie-2, TGF-ß and Smad-2/3 mRNA expression to enhance wound healing in chronic diabetic foot ulcers.

Neuroprotective effect of Azadirachta indica standardized extract in partial sciatic nerve injury in rats: Evidence from anti-inflammatory, antioxidant and anti-apoptotic studies.

Chronic neuropathic pain is a common and widely recognized pain syndrome for patients and difficult to manage for physicians. Azadirachta indica (AI) possesses analgesic, anti-inflammatory, and antioxidant properties. To evaluate the neuroprotective effect of AI standardized extract in an animal model of peripheral neuropathy induced by partial sciatic nerve ligation (PSNL). PSNL was induced in male Wistar rats (180-200 g) with tight ligation of the nerve. Rats received treatment with either vehicle i.e. distilled water (PSNL control), Pyridoxine (100 mg/kg, p.o.) or AI (100, 200 and 400 mg/kg, p.o.) for 28 days. Various behavioral parameters, biochemical, molecular and histological parameters were evaluated. PSNL resulted in a significant decrease (p < 0.05) in allodynia, hyperalgesia, motor coordination and motor nerve conduction velocity (MNCV) whereas chronic treatment with AI (200 and 400 mg/kg) significantly attenuated (p < 0.05) these behavioral changes. Enhanced activity of oxidative-nitrosative stress, inflammatory mediators (TNF-α, IL-1ß, and NF-κB) as well as mRNA expression of Bax, Caspase-3, and iNOs were significantly attenuated (p < 0.05) by AI treatment. It also significantly increased (p < 0.05) peripheral blood oxygen content and Bcl-2 mRNA expression. The flow cytometric analysis revealed that AI (200 and 400 mg/kg) treatment significantly attenuated neural apoptosis and reactive oxygen species levels. PSNL induced histological aberrations were also decreased by AI treatment. Azadirachta indica exerts its neuroprotection against PSNL induced neuropathic pain via inhibition of oxidative-nitrosative stress, the release of pro-inflammatory cytokines and apoptosis to improve MNCV (graphical abstract, Figure 1(Fig. 1)).