Paintable Decellularized-ECM Hydrogel for Preventing Cardiac Tissue Damage.

The tissue-specific heart decellularized extracellular matrix (hdECM) demonstrates a variety of therapeutic advantages, including fibrosis reduction and angiogenesis. Consequently, recent research for myocardial infarction (MI) therapy has utilized hdECM with various delivery techniques, such as injection or patch implantation. In this study, a novel approach for hdECM delivery using a wet adhesive paintable hydrogel is proposed. The hdECM-containing paintable hydrogel (pdHA_t) is simply applied, with no theoretical limit to the size or shape, making it highly beneficial for scale-up. Additionally, pdHA_t exhibits robust adhesion to the epicardium, with a minimal swelling ratio and sufficient adhesion strength for MI treatment when applied to the rat MI model. Moreover, the adhesiveness of pdHA_t can be easily washed off to prevent undesired adhesion with nearby organs, such as the rib cages and lungs, which can result in stenosis. During the 28 days of in vivo analysis, the pdHA_t not only facilitates functional regeneration by reducing ventricular wall thinning but also promotes neo-vascularization in the MI region. In conclusion, the pdHA_t presents a promising strategy for MI treatment and cardiac tissue regeneration, offering the potential for improved patient outcomes and enhanced cardiac function post-MI.

A Biofloc-Based Aquaculture System Bio-augmented with Probiotic Bacteria Bacillus tequilensis AP BFT3 Improves Culture Environment, Production Performances, and Proteomic Changes in Penaeus vannamei.

Experiments were conducted to evaluate the probiotic effect of bio-augmented Bacillus tequilensis AP BFT3 on improving production, immune response, and proteomic changes of Penaeus vannamei reared in a biofloc system. Penaeus vannamei larvae (PL13) were stocked in 100-L tanks at a rate of 100 no per tank to study the effect of B. tequilensis AP BFT3 with and without biofloc (BFT-PRO and PRO). Control tanks devoid of probiotic strain were maintained in a clear water system. The growth and survival considerably increased in probiotic added biofloc reared shrimp than probiotic added clear water reared ones and control. Water quality significantly improved in probiotic added (PRO) and biofloc-probiotics (BFT-PRO) system than control. Microbiological investigations indicate increased heterotrophic bacterial load in BFT-PRO compared to the PRO and control. The quality of the isolated microbes was analyzed in terms of enzyme production, and an abundance of enzyme-producing bacterial population was observed in BFT-PRO shrimp. Immune-related genes were significantly upregulated in BFT-PRO shrimp, followed by the PRO and control. The proteomic data (2D gel electrophoresis and MALDI-TOF) of muscle tissue from the experimental animals identified 11 differentially expressed proteins. The Daxx OS and Lit v 1 tropomyosin was found upregulated in BFT-PRO shrimps. Downregulation of Na+/K+ATPase was observed in biofloc with probiotic-supplied groups. The findings revealed that the BFT system's efficacy could be improved through the addition of probiotics. The addition of B. tequilensis AP BFT3 as a probiotic in biofloc induced the expression of essential proteins, reducing contracting diseases during culture.

Cellular and molecular immune response and production performance of Indian white shrimp Penaeus indicus (H. Milne-Edwards, 1837), reared in a biofloc-based system with different protein levels of feed.

The present study focuses on the immunity and growth of Penaeus indicus fed with varying protein levels (25%, 30%, and 35%) in a biofloc based rearing system. A 120 days growth trial was carried out using juvenile Penaeus indicus (0.71 ± 0.01) with dietary protein level, 25% (LP), 30% (MP), and 35% (HP), and a control diet-fed with 35% acted as control group resulting in 4 treatments each with four replicates and were randomly assigned 16 tank units (7500 L each). A combination of different carbon sources (molasses, wheat flour, and rice bran in 2:1:1 ratio), yeast and a probiotic (Bacillus sp.) consortium were used for the development of biofloc. At the end of the trial, the growth parameters of shrimps viz., initial weight, feed conversion ratio (FCR), and daily growth coefficient (DGC) were computed. The results indicated that shrimp fed with medium (30%) protein (MP) diet recorded significantly (P < 0.05) improved growth performance compared to high protein fed group (35%) and low protein (25%) fed group (LP) in a biofloc system and control group (35%). The immunological parameters such as hemagglutination activity (HA) assay, serum protein, lysozyme, phenol oxidase (PO), and inhibition of superoxide dismutase (SOD) activity were observed in serum, plasma, and hemocyte lysate supernatant (HLS). The HA activity, PO activity in plasma was found to be higher in high protein fed animals, whereas medium protein resulted in enhanced PO activity in serum. Similarly, lysozyme and SOD were inhibited well in high protein fed animals compared to the low protein fed group. The vital immune genes's mRNA profiling showed a potential rise in the expressional pattern in MP and HP treatments compared to LP and control. BGBP (beta-1,3-glucan binding protein) and hemocyanin mRNA transcript levels were highly upregulated in the HP (5 fold) and moderately expressed in MP (2 fold) and LP (1-2 fold). The transcripts of peroxinectin, antimicrobial peptides like crustin showed significant upregulation in HP followed by in MP and LP and control. Likewise, other immune genes, such as SOD, prophenoloxidase (proPO), showed a similar trend in a marginal way, indicating immunomodulation in the biofloc groups. This study suggested that biofloc with high protein (35%) supplementation can substantially enhance the immune response of shrimps, although medium protein level (30%) is optimum for improving the survival, growth, and in turn economic return in Indian white shrimp.

Chrysin inhibits propagation of HeLa cells by attenuating cell survival and inducing apoptotic pathways.

OBJECTIVE: Chrysin, one of the main active constituents of flavonoids, is known for demonstrating protective effects against various types of cancer including cervical cancer. The aim of this study was to determine apoptosis induction and antiproliferative action of chrysin on human cervical cancer cells. MATERIALS AND METHODS: In this study, attempts have been made to establish anticancer role of chrysin on HeLa cells. MTT, mitochondrial potential, DNA fragmentation, annexin V/propidium iodide assays, qPCR and protein profiling were performed. RESULTS: Chrysin treated HeLa cells showed time and dose dependent decrease in cell viability and demonstrated profound effects on nuclear morphology and DNA fragmentation. Chrysin treatment increased the expression of proapoptotic genes BAD, BAX, BID, BOK and APAF1, TNF, FASL, FAS, FADD and caspases (like caspase 3, caspase 7, caspase 8 and caspase 9), whereas it decreased the expression level of antiapoptotic genes MCL-1, NAIP, XIAP and Bcl-2 and cell cycle regulatory genes CCNB1, CCNB2, CCND1, CCND2, CCND3, CCNE2, CDK4 and CDK2 at transcript level. Furthermore, chrysin significantly upregulated pro-apoptotic proteins, like TRAILR2/DR5, TRAILR1/DR4, Fas/TNFRSF6/CD95, phosphoP53(S15), BAD, BAX, cleaved caspase 3, procaspase 3, HTRA2/Omi and SMAC/Diablo, while downregulated anti-apoptotic proteins like BCL-X, BCL2, XIAP and CIAPs that support chrysin mediated apoptosis in HeLa cells. Remarkably, chrysin downregulated the phosphorylated AKT pathway proteins, (p-473) AKT, (p-Ser 2448) mTOR, (p-Ser241) PDK1, (p-Ser112) BAD, and upregulated (p-Ser21) GSK3b, (p-Thr172) AMPKa, P27 (p-Thr198) and (p-Ser15) P53, which endorses chrysin mediated apoptosis. CONCLUSIONS: Chrysin significantly inhibited proliferation and induced apoptosis by modulation of various apoptotic genes and AKT/MAPK pathway genes.

Vasoconstrictor and coagulation activator entrapped chitosan based composite hydrogel for rapid bleeding control.

Chitosan (Cs) as a hemostatic agent has been in use to control hemorrage. Composite hydrogel formed by entrapment of vasoconstrictor-potassium aluminium sulfate (0.25 %PA) and coagulation activator-calcium chloride (0.25 %Ca) into Cs (2 %) hydrogel would enhance the hemostatic property of Cs. In this work, the prepared composite hydrogel was injectable, shear thinning, cyto and hemocompatible. The 2 %Cs-0.25 %PA-0.25 %Ca composite hydrogel caused rapid blood clotting by accelerating RBC/platelet aggregation and activation of the coagulation cascade. Further, in vivo studies on rat liver and femoral artery hemorrage model showed the efficiency of 2 %Cs-0.25 %PA-0.25 %Ca composite hydrogel to achieve hemostasis in a shorter time (20 ± 10 s, 105 ± 31 s) than commercial hemostatic agents-Fibrin sealant (77 ± 26 s, 204 ± 58 s) and Floseal (76 ± 15 s, 218 ± 46 s). In in vivo toxicological study, composite hydrogel showed material retention even after 8 weeks post-surgery, therefore excess hydrogel should be irrigated from site of application. This prepared composite hydrogel based hemostatic agent has potential application in low pressure bleeding sites.

Phytochemicals induce apoptosis by modulation of nitric oxide signaling pathway in cervical cancer cells.

OBJECTIVE: Nitric Oxide (NO) is produced by NO synthases (NOS) and is a key signaling molecule that regulates tumorigenesis, both aiding and alleviating it. Elevated NO levels are cytotoxic to cancer cells, making NOS an important target for cancer treatment. In the present study, the modulatory effects of the phytochemicals, quercetin, sulforaphane, genistein, and epigallocatechin-3-gallate on NO pathway and apoptosis were shown in HeLa cervical cancer cells. MATERIALS AND METHODS: Fluorescent microscopy and flow cytometry were used to assess apoptosis. A Griess assay was used to quantitatively measure NO, quantitative PCR array was used to assess the expression levels of genes involved in the NO signaling pathway, and immunocytochemistry was used to determine NOS protein expression. The functional association among the modulated genes was evaluated using network biology analysis, gene set enrichment, and KEGG pathway analysis. RESULTS: Treatment with the phytochemicals elevated NO levels in HeLa cells and modulated various genes involved in nitric oxide biosynthesis, superoxide metabolism, and oxidative stress, including NOS1, NOS2, NOS3, ALOX12, and SOD2, with a concomitant increase in NOS2 and NOS3 protein expression levels; also, the phytochemicals were found to induce apoptosis. CONCLUSIONS: These results suggest that the phytochemical-induced cell death is partially attributed to the activation of the NO pathway and upregulation of pro-oxidant ROS generators. Further experimental studies are required to explore this mechanistic association of NO signaling pathway activation and induction of apoptosis in other types of cancer.

Injectable chitosan-nano bioglass composite hemostatic hydrogel for effective bleeding control.

Effective bleeding control is a major concern in trauma and major surgeries. Chitosan (Ch) as hemostatic agent has been widely used and when applied at the site of injury it acts by aggregating blood cells and forming a plug. Our prime interest is to improve the blood clotting property of Ch hydrogel. Incorporation of nanobioglass (nBG) with silica (activate coagulation factor XII), calcium (activate intrinsic pathway) and phosphate (initiates extrinsic pathway) ions into Ch hydrogel (protonated NH2 group) would act at the same time and bring about rapid blood clot formation. Sol-gel method was followed to synthesize nBG particles and its particle size was found to be 14 ±â€¯3 nm. 2%Ch-5%nBG hydrogel was then prepared and studied using SEM and FTIR. The prepared hydrogel was injecable and was also cytocompatible with HUVEC. In in vitro blood clotting study and in vivo major organ injury model, 2%Ch-5%nBG hydrogel formed rapid blood clot than 2%Ch hydrogel. Hence, 2%Ch-5%nBG hydrogel might have great potential to achieve effective bleeding control during critical situations.

Chitosan hydrogel scaffold reinforced with twisted poly(l lactic acid) aligned microfibrous bundle to mimic tendon extracellular matrix.

Regeneration of tendon requires construct that provides necessary structural support closely mimicking the native architecture. To recreate this complex architecture a construct made of heat-treated, twisted poly(L lactic acid) (PLLA) microfibers coated with chitosan gel and surrounded by PLLA micro-fibrous layer was developed. The developed construct characterized using SEM showed the macroporous nature of gel coating around four distinct PLLA twisted fibrous bundle and a thin fiber layer surrounding the construct. FTIR analysis confirmed the presence of PLLA and chitosan construct. Mechanical strength increased with increasing number of strips. Protein adsorption was significantly low on the construct with outer covering that could retard cell adhesion to the outer layer. The developed construct showed good cell attachment and proliferation of tenocytes. These results indicate that the construct would find application for tendon tissue engineering.

Carbohydrate sources deferentially influence growth performances, microbial dynamics and immunomodulation in Pacific white shrimp (Litopenaeus vannamei) under biofloc system.

This study aims to evaluate the influence of different carbohydrate sources on water quality, growth performance and immunomodulation in pacific white shrimp and to find an alternate for molasses in biofloc system. The experiment consists of 8 biofloc treatments with different carbon sources, C1 (maida flour), C2 (wheat flour), C3 (gram flour), C4 (millet flour), C5 (rice flour), C6 (corn flour), C7 (molasses), C8 (multigrain flour) and un-supplemented control C0 was conducted in 200 L tank system for 120 days. Shrimp juveniles of average weight 1 g were stocked at the rate of 300 nos/m3. Shrimp reared in C8, C7 and C4 treatments had similar growth, survival rate, and disease resistance and were significantly higher (P < 0.05) than other treatments including control. Immune parameters like total hemocyte count (THC) and prophenoloxidase (ProPO) activity showed significantly higher (P < 0.05) levels in biofloc treatment groups. The genes targeting the proPO cascade (PX, BGBP) and antioxidant defense systems (SOD, MnSOD, CAT) revealed significant upregulation in the transcript levels indicating an enhancement in the immune-regulatory functions in the BFT groups. The results suggest that millets and multigrain flour can effectively replace molasses as the carbohydrate source for biofloc system and the biofloc system offers higher growth, survival, and immunomodulation than control.

Bioengineered Braided Micro-Nano (Multiscale) Fibrous Scaffolds for Tendon Reconstruction.

A braided multiscale fibrous scaffold consisting of aligned PCL micro/collagen-bFGFnano fibers was fabricated (mPCL-nCol-bFGF) to mimic native tendon tissue architecture which was further coated with alginate to aid in prevention of peritendinous adhesion. The bFGF release kinetics showed a sustained release of growth factors for a period of 20 days. Further, in vitro cell viability, attachment, and proliferation were performed using rabbit tenocytes under static and dynamic conditions. mPCL-nCol-bFGF showed a higher cell proliferation and enhanced expression of tenogenic markers compared to mPCL-nCol (braided scaffold without bFGF). When subjected to dynamic stimulation in a bioreactor, mPCL-nCol-bFGF-DS (braided scaffold with bFGF after dynamic stimulation) showed enhanced cellular proliferation and tenogenic marker expression, compared to mPCL-nCol-bFGF. The in vivo studies of the cell seeded scaffold after dynamic stimulation in Achilles tendon defect model showed tendon tissue regeneration with aligned collagen morphology within 12 weeks of implantation.

Carbon: Nitrogen (C:N) ratio level variation influences microbial community of the system and growth as well as immunity of shrimp (Litopenaeus vannamei) in biofloc based culture system.

Biofloc technology (BFT) is a novel modern aquaculture farming technique used to reduce toxic nitrogen concentration, act as in situ food source and eradicate pollutants using carbon and therefore to control C:N ratio in an aquaculture system. In this study, effect of different C:N ratios of a biofloc based system on water quality such as the level of Total ammonia nitrogen (TAN) nitrite-nitrogen (NO2--N) and nitrate nitrogen (NO3--N) were explored. Further, the growth and immunity status of shrimp L. vannamei under the influence of different C:N ratios were evaluated. Two of the C:N ratios (15 and 20) could significantly (P < 0.05) reduce TAN, NO2-N and NO3-N levels (0.456 ±â€¯0.01, 0.145 ±â€¯0.09, and 0.102 ±â€¯0.02 ppm) compared to control (1.45 ±â€¯0.1, 0.749 ±â€¯0.14 and 0.675 ±â€¯0.16 ppm). Large variations in the frequency distribution of operational taxonomic units (OTUs) for the bacterial community in water with different C:N ration (BFT) and control were observed. Vibrios often considered as opportunistic pathogens, where the most dominant bacterial flora of water in control (79%) and C:N5 (37%) group. In C:N10, Thauera (62%) was most represented genus. Similarly, Attheyaceae (56%), followed by Peridiniaceae (30%) were the most dominant groups in C:N15 treatment. The diversity of bacterial flora was more spread in C:N20 treatments with Psychrobacter (26%), Proteobacteria (25%) and Peridiniaceae (20%) as the major groups. The trend of Vibrio dominance decreased with the increase in C:N ratios and thus confirming the dominance of heterotrophic bacteria in high C:N ratio groups. Upon challenge with pathogens, shrimps from C:N10, C:N15 and C:N20 groups showed significantly higher survival (P < 0.05) compared to the C:N5 and control group. Similarly, better growth rate was also observed in BFT tanks compared to control both during the culture and at harvest. Comparatively higher expression of four immune-related genes (ras-related nuclear gene (RAN), serine proteinase gene (SP), prophenoloxidase activating enzyme (PPAE), and crustin were observed in different C:N ratio ponds than control and these were in increasing trend with the C:N ratio. Gene expression analysis showed that the transcripts of those immune genes were significantly increased among all C:N treatments than that of control. Overall, these findings demonstrated that with optimum C:N ratio, BFT can be used to optimize the bacterial community composition for both optimal water quality and optimal shrimp health. This study thus indicates the possibility of obtaining better performance of L. vannamei culture with proper adjustment of C:N ratio in a biofloc based system.

Engineering poly(hydroxy butyrate-co-hydroxy valerate) based vascular scaffolds to mimic native artery.

Electrospun tri-layered fibrous scaffold incorporating VEGF and Platelet Factor Concentrate (PFC) in multiple layers having different layer architectures was designed to mimic native artery. The scaffold consisted of longitudinally aligned poly(hydroxy butyrate-co-hydroxy valerate) (PHBV) and poly(vinyl alcohol) (PVA) nanofibers (inner layer), radially aligned PHBV-elastin nanofibers (middle layer) to provide the bi-directional alignment and combination of longitudinally aligned PHBV-elastin and random PHBV/PVA multiscale fibers (peripheral layer). Tubular constructs of diameter <6 mm were developed. The developed electrospun fibers were characterised by Scanning Electron Microscope (SEM), Fourier Transform Infrared Spectroscopy and Tensile tests. Further the burst strength, compliance and stiffness index of tri-layered tubular scaffold was evaluated. SEM images of fibrous layers showed the typical longitudinal and radial alignment of fibers in the tubular construct. SEM images showed that the prepared PHBV nanofibers were in the range of 500-800 nm and PHBV microfibers were of 1-2 µm in diameter in the tri-layered electrospun membrane. PVA nanofibers were of size 200-250 nm. The tensile strength, percentage compliance and stiffness index of tri-layered membrane was in accordance with that of native small blood vessels. The developed tri-layered membrane was blood compatible, with hemolysis degree 0.85 ±â€¯0.21% and did not activate platelets. Controlled release of VEGF and PFC was observed from the scaffold. The biocompatibility of the tri-layered scaffold was evaluated using HUVECs, SMCs and MSCs and SMCs infiltration from the outer layer was also evaluated. Specific protein expression for the HUVECs and SMCs was evaluated by flow cytometry and immunocytochemistry. HUVECs and SMCs exhibited good elongation and alignment along the direction of fibers and was found to maintain its CD31, VE-Cadherin and αSMA expression respectively. The results highlight the importance of bi-directional fiber alignment on the tri-layered electrospun scaffold as a suitable architectural prototype for vascular scaffolds to mimic the native arteries.

Dispersion of Ni2+ ions via acetate precursor in the preparation of NaNiPO4 nanoparticles: effect of acetate vs. nitrate on the capacitive energy storage properties.

The influence of the precursors on the dispersion of Ni2+ ions and the presence of several other functional groups was investigated in the preparation of sodium nickel phosphate (NaNiPO4) cathode for a supercapacitor study. The dispersion of nickel phases, in the form of nanosheets, is influenced by the type of precursors used in the synthesis. XPS based spectroscopic information on the surface functional groups on NaNiPO4 show differences between the precursors (i.e.) acetate- and nitrate-derived materials. The benefits of using acetate as an alternative to nitrate are explored by using the NaNiPO4 nanoparticles as a cathode for supercapacitor applications. The acetate-derived material exhibits improved electrochemical properties possessing both redox behaviour and double-layer capacitance. The results indicate that the metal acetates are homogenously distributed. Acetate functionalization resulted in an improved capacitance of 90 F g-1 compared with that obtained from the nitrate precursor derived material (58 F g-1). Capacitance retention and high rate capability were also a feature of the acetate-derived material. The sodium nickel phosphate cathode material has provided useful insights on the precursor chemistry in storing renewable energy have been reported for the first time.

Epidemiologic Investigation of Highly Pathogenic H5N2 Avian Influenza Among Upper Midwest U.S. Turkey Farms, 2015.

In 2015, an outbreak of H5N2 highly pathogenic avian influenza (HPAI) occurred in the United States, severely impacting the turkey industry in the upper midwestern United States. Industry, government, and academic partners worked together to conduct a case-control investigation of the outbreak on turkey farms in the Upper Midwest. Case farms were confirmed to have HPAI-infected flocks, and control farms were farms with noninfected turkey flocks at a similar stage of production. Both case and control farms were affiliated with a large integrated turkey company. A questionnaire administered to farm managers and supervisors assessed farm biosecurity, litter handling, dead bird disposal, farm visitor and worker practices, and presence of wild birds on operations during the 2 wk prior to HPAI confirmation on case premises and the corresponding time frame for control premises. Sixty-three farms, including 37 case farms and 26 control farms were included in the analysis. We identified several factors significantly associated with the odds of H5N2 case farm status and that may have contributed to H5N2 transmission to and from operations. Factors associated with increased risk included close proximity to other turkey operations, soil disruption (e.g., tilling) in a nearby field within 14 days prior to the outbreak, and rendering of dead birds. Observation of wild mammals near turkey barns was associated with reduced risk. When analyses focused on farms identified with H5N2 infection before April 22 (Period 1), associations with H5N2-positive farm status included soil disruption in a nearby field within 14 days prior to the outbreak and a high level of visitor biosecurity. High level of worker biosecurity had a protective effect. During the study period after April 22 (Period 2), factors associated with HPAI-positive farm status included nonasphalt roads leading to the farm and use of a vehicle wash station or spray area. Presence of wild birds near dead bird disposal areas was associated with reduced risk. Study results indicated that the initial introduction and spread of H5N2 virus likely occurred by both environmental and between-farm pathways. Transmission dynamics appeared to change with progression of the outbreak. Despite enhanced biosecurity protocols, H5N2 transmission continued, highlighting the need to review geographic/topologic factors such as farm proximity and potential dust or air transmission associated with soil disruption. It is likely that biosecurity improvements will reduce the extent and speed of spread of future outbreaks, but our results suggest that environmental factors may also play a significant role in farms becoming infected with HPAI.

Layered chitosan-collagen hydrogel/aligned PLLA nanofiber construct for flexor tendon regeneration.

The aim of our study was to develop a tendon construct of electrospun aligned poly (l-lactic acid) (PLLA) nanofibers, to mimic the aligned collagen fiber bundles and layering PLLA fibers with chitosan-collagen hydrogel, to mimic the glycosaminoglycans of sheath ECM for tendon regeneration. The hydrogel coated electrospun membrane was rolled and an outer coating of alginate gel was given to prevent peritendinous adhesion. The developed constructs were characterized by SEM, FT-IR and tensile testing. Protein adsorption studies showed lower protein adsorption on coated scaffolds compared to uncoated scaffolds. The samples were proven to be non-toxic to tenocytes. The chitosan-collagen/PLLA uncoated scaffolds and alginate gel coated chitosan-collagen/PLLA scaffolds showed good cell proliferation. The tenocytes showed good attachment and spreading on the scaffolds. This study indicated that the developed chitosan-collagen/PLLA/alginate scaffold would be suitable for flexor tendon regeneration.

Bilayered construct for simultaneous regeneration of alveolar bone and periodontal ligament.

Periodontitis is an inflammatory disease that causes destruction of tooth-supporting tissues and if left untreated leads to tooth loss. Current treatments have shown limited potential for simultaneous regeneration of the tooth-supporting tissues. To recreate the complex architecture of the periodontium, we developed a bilayered construct consisting of poly(caprolactone) (PCL) multiscale electrospun membrane (to mimic and regenerate periodontal ligament, PDL) and a chitosan/2wt % CaSO4 scaffold (to mimic and regenerate alveolar bone). Scanning electron microscopy results showed the porous nature of the scaffold and formation of beadless electrospun multiscale fibers. The fiber diameter of microfiber and nanofibers was in the range of 10 ± 3 µm and 377 ± 3 nm, respectively. The bilayered construct showed better protein adsorption compared to the control. Osteoblastic differentiation of human dental follicle stem cells (hDFCs) on chitosan/2wt % CaSO4 scaffold showed maximum alkaline phosphatase at seventh day followed by a decline thereafter when compared to chitosan control scaffold. Fibroblastic differentiation of hDFCs was confirmed by the expression of PLAP-1 and COL-1 proteins which were more prominent on PCL multiscale membrane in comparison to control membranes. Overall these results show that the developed bilayered construct might serve as a good candidate for the simultaneous regeneration of the alveolar bone and PDL.

HiSCR (Hidradenitis Suppurativa Clinical Response): a novel clinical endpoint to evaluate therapeutic outcomes in patients with hidradenitis suppurativa from the placebo-controlled portion of a phase 2 adalimumab study.

BACKGROUND: Determining treatment response for patients with hidradenitis suppurativa (HS) can be challenging due to limitations of current disease activity evaluations. OBJECTIVE: Evaluate the novel, validated endpoint, Hidradenitis Suppurativa Clinical Response (HiSCR) and its utility as an outcome measure. METHODS: Patients with baseline total abscess and inflammatory nodule count (AN count) of at least three and draining fistula count of 20 or fewer comprised the post hoc subpopulation analysed. HiSCR (at least a 50% reduction in total AN count, with no increase in abscess count, and no increase in draining fistula count relative to baseline) and HS-PGA Response [Hidradenitis Suppurativa-Physician's Global Assessment score of clear, minimal, or mild, with at least a 2-grade improvement from baseline] were used to evaluate patient response after adalimumab treatment weekly, every other week, or placebo (1 : 1 : 1). RESULTS: The subpopulation included 132 (85.7%) patients; 70.5% women and 73.5% white. At week 16, HiSCR was achieved by 54.5% receiving weekly adalimumab, 33.3% every other week, and 25.6% placebo and HS-PGA Response was achieved by 20.5% receiving weekly adalimumab, 6.7% every other week and 2.3% placebo. CONCLUSION: HiSCR was more responsive to change than HS-PGA Response in this subpopulation.

Propensity of crocin to offset Vipera russelli venom induced oxidative stress mediated neutrophil apoptosis: a biochemical insight.

Viper envenomation results in inflammation at the bitten site as well as target organs. Neutrophils and other polymorphonuclear leukocytes execute inflammation resolving mechanism and will undergo apoptosis after completing the task. However, the target specific toxins induce neutrophil apoptosis at the bitten site and in circulation prior to their function, thus reducing their number. Circulating activated neutrophils are major source of inflammatory cytokines and leakage of reactive oxygen species (ROS)/other toxic intermediates resulting in aggravation of inflammatory response at the bitten/target site. Therefore, neutralization of venom induced neutrophil apoptosis reduces inflammation besides increasing the functional neutrophil population. Therefore, the present study investigates the venom induced perturbances in isolated human neutrophils and its neutralization by crocin (Crocus sativus) a potent antioxidant carotenoid. Human neutrophils on treatment with venom resulted in altered ROS generation, intracellular Ca(2+) mobilization, mitochondrial membrane depolarization, cyt-c translocation, caspase activation, phosphatidylserine externalization and DNA damage. On the other hand significant protection against oxidative stress and apoptosis were evidenced in crocin pre-treated groups. In conclusion the viper venom induces neutrophil apoptosis and results in aggravation of inflammation and tissue damage. The present study demands the necessity of an auxiliary therapy in addition to antivenin therapy to treat secondary/overlooked complications of envenomation.

Inflammation and oxidative stress in viper bite: an insight within and beyond.

Though systemic and local manifestations of snakebite are considered serious, the relevance of oxidative stress in viper bite pathology is largely denied. However, over the past decade, studies have provided substantial evidence for the presence of persistent oxidative stress in viper bite victims. This review aims at highlighting the disturbances in redox homeostasis soon after viper envenomation and its implications in the pathomechanism of secondary/long term complications including thrombocytopenia, hypopituitarism, infertility, renal abnormalities and persistent local tissue degradation. Both enzymatic and non-enzymatic components of viper venom play a pivotal role in bringing redox turbulence in victims. Venom-induced hemorrhage and necrosis with subsequent release of damage associated molecular pattern (DAMPs) molecules also contribute to sustained oxidative stress and inflammation. Studies have demonstrated that along with anti-venom therapy an antioxidant treatment during the early stages of viper bite and also long term treatment could help to reduce the occurrence of secondary/long term complications. Further, proper knowledge regarding the pathophysiology will allow for exploration of new avenues in the treatment of viper bite.

Adalimumab retreatment successfully restores clinical response and health-related quality of life in patients with moderate to severe psoriasis who undergo therapy interruption.

BACKGROUND: Published evaluations of skin disease signs and health-related quality of life (HRQoL) upon therapy withdrawal and retreatment in psoriatic patients are limited to results of drug withdrawal after short-term treatment. Analyses are lacking that evaluate patients' response to retreatment for patients treated successfully long-term. OBJECTIVE: To study the efficacy and safety of adalimumab in patients with long-term clinical responses to adalimumab who then discontinue therapy and are retreated with the same dosing regimen as the initial course. Skin disease signs and patients' HRQoL are evaluated. METHODS: This post hoc analysis of an open-label study (NCT00195676) included patients who had responded favourably to adalimumab during initial treatment (≥75% improvement in Psoriasis Area and Severity Index [PASI 75 response]) and had maintained good clinical response for an extended period (up to 252 weeks); patients had Physician's Global Assessment (PGA) 0 or 1 before treatment interruption. Following drug withdrawal (up to 40 weeks), all patients were retreated with adalimumab 80 mg initial dose, followed by 40 mg every-other-week for 16 weeks. PASI response and HRQoL were evaluated. RESULTS: Of the 133 patients in this analysis, 24 (18%) relapsed during therapy withdrawal. After 16 weeks of retreatment, 75% who relapsed and 89.9% who did not relapse, had a PASI 75 response; 89.5% achieved European Consensus Programme treatment goals after 16 weeks of retreatment. During drug withdrawal, HRQoL disproportionally worsened compared to skin disease signs; HROoL also considerably worsened for patients who did not relapse. Patients regained HRQoL upon retreatment with adalimumab. No new safety signals were identified in this study. CONCLUSION: Retreatment with adalimumab was successful in improving psoriasis skin signs and HRQoL in this subgroup with initial and extended responses to therapy followed by relapse after treatment withdrawal. Patient's HRQoL should be considered, as it may substantially worsen during therapy interruption.