LINKED CONTENT This article is linked to Bansal et al. papers. To view these articles, visit https://doi.org/10.1111/apt.17930 and https://doi.org/10.1111/apt.18124 .
Patients who are chronically infected with hepatitis C virus (HCV) and who do not have a sustained virologic response after treatment with regimens containing direct-acting antiviral agents (DAAs) ...have limited retreatment options.
We conducted two phase 3 trials involving patients who had been previously treated with a DAA-containing regimen. In POLARIS-1, patients with HCV genotype 1 infection who had previously received a regimen containing an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive either the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the protease inhibitor voxilaprevir (150 patients) or matching placebo (150 patients) once daily for 12 weeks. Patients who were infected with HCV of other genotypes (114 patients) were enrolled in the sofosbuvir-velpatasvir-voxilaprevir group. In POLARIS-4, patients with HCV genotype 1, 2, or 3 infection who had previously received a DAA regimen but not an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir-voxilaprevir (163 patients) or sofosbuvir-velpatasvir (151 patients) for 12 weeks. An additional 19 patients with HCV genotype 4 infection were enrolled in the sofosbuvir-velpatasvir-voxilaprevir group.
In the three active-treatment groups, 46% of the patients had compensated cirrhosis. In POLARIS-1, the rate of sustained virologic response was 96% with sofosbuvir-velpatasvir-voxilaprevir, as compared with 0% with placebo. In POLARIS-4, the rate of response was 98% with sofosbuvir-velpatasvir-voxilaprevir and 90% with sofosbuvir-velpatasvir. The most common adverse events were headache, fatigue, diarrhea, and nausea. In the active-treatment groups in both trials, the percentage of patients who discontinued treatment owing to adverse events was 1% or lower.
Sofosbuvir-velpatasvir-voxilaprevir taken for 12 weeks provided high rates of sustained virologic response among patients across HCV genotypes in whom treatment with a DAA regimen had previously failed. (Funded by Gilead Sciences; POLARIS-1 and POLARIS-4 ClinicalTrials.gov numbers, NCT02607735 and NCT02639247 .).
Summary
Spermatogenesis, a highly coordinated process, is prone to environmental insults which may lead to impaired spermatogenesis or, at worst, infertility. Bisphenol A (BPA) is a well‐known global ...environmental toxicant and a ubiquitous oestrogenic chemical. This study evaluated the role of selenium (0.5 ppm sodium selenite/kg diet) on spermatogenesis after BPA treatment in different groups of male BALB/c mice: control, selenium, BPA and selenium+BPA. Markers of oxidative stress and apoptosis were evaluated in testis after BPA treatment. Significant decrease in sperm concentration and motility and increased reactive oxygen species(ROS) and LPO levels were seen in BPA group. Histopathological changes revealed extensive vacuolisation, lumen devoid of spermatozoa and decreased germ cell count, confirmed by testicular germ cell count studies. TUNEL assay for apoptosis showed increased number of TUNEL‐positive germ cells in BPA group with increased percentage apoptotic index. However, in Se+BPA group, histopathological studies revealed systematic array of all germ cells, preserved basement membrane with relatively less vacuolisation, improved sperm parameters and ROS and LPO levels and decreased number of TUNEL‐positive germ cells. These results clearly demonstrate the role of selenium in ameliorating oxidative stress and apoptosis induced upon BPA treatment in mice and can be further used as therapeutic target in male infertility.
The most promising way to achieve the smooth, flexible and sustainable bioeconomy is the utilization of renewable lignocellulosic biomass as a feedstock for the production of fuels, chemicals, ...enzymes and high-valued products. Cellulolytic enzymes are indispensable for the maintenance of global carbon cycle, since they catalyze the degradation of cellulose. Therefore for solving the forthcoming waste management and energy issues of mankind, cellulase production technology plays significant and vital role. Cellulases are industrial enzymes and have extensive application in various process industries. Its relatively high cost of production has hindered the wider industrial application. Significant cost reduction is required to enhance the commercial viability of cellulase production technology. Utilization of novel and cheap lignocellulosic renewable resources as substrate for enzyme fermentation process is a promising way of efficient and low cost cellulases production. The present paper reveals, a review on cellulase production through various microorganisms employing economical, abundantly available renewable lignocellulosic biomass as carbon source. It also deals with the recent approaches used at microbial as well as feedstock level, making more efficient, flexible and cost effective fermentation process.
Graphic Abstract
Summary
This study evaluated the role of selenium (0.5 ppm selenium/kg diet) and vitamin E (200 mg alpha‐tocopherol/kg diet) on spermatogenesis after scrotal hyperthermia (42 °C, 30 min) in six ...different groups of male Balb/c mice; Control, Heat shock, Selenium, Selenium+heat shock, Vitamin E and Vitamin E+heat shock. Markers of the stress responses, hypoxia and oxidative stress, were evaluated in testis after the hyperthermic shock. Hyperthermia caused an elevated mRNA expression of hypoxia‐inducible factor‐1 alpha, haem oxygenase‐1 (HMOX‐1) and also glutathione peroxidase activity and reactive oxygen species (ROS). Apoptosis was evaluated by TUNEL assay and further by mRNA expression of Bcl‐2, caspase 3, 8, 9, bid and AKT. TUNEL assay showed significant increase in apoptotic index of spermatogenic cells, whereas decrease in mRNA expression of Bcl‐2, AKT and increase in caspase 3, 8, 9 and Bid in heat‐shock group were observed. A significant decrease in sperm motility was also seen in heat‐shock group in comparison with control group. These observations clearly indicate the development of oxidative stress and apoptosis after hyperthermia. Further analysis in Selenium+heat shock and Vitamin E+heat shock groups showed protective behaviour as compared to effects in heat‐shock group which could be of therapeutic interest in future studies.
Aegilops umbellulata, a non‐progenitor diploid species, is an excellent source of resistance to various wheat diseases. Leaf rust and stripe rust resistance genes from A. umbellulata were transferred ...to the susceptible wheat cultivar WL711 through induced homoeologous pairing. A doubly resistant introgression line IL 393‐4 was crossed with wheat cultivar PBW343 to develop a mapping population. Tests on BC2F7 RILs indicated monogenic inheritance of seedling leaf rust and stripe rust resistance in IL 393‐4 and the respective co‐segregating genes were tentatively named LrUmb and YrUmb. Bulked segregant analysis placed LrUmb and YrUmb in chromosome 5DS, 7.6 cM distal to gwm190. Aegilops geniculata‐derived and completely linked leaf rust and stripe rust resistance genes Lr57 and Yr40 were previously located in chromosome 5DS. STS marker Lr57/Yr40MAS‐CAPS16 (Lr57/Yr40‐CAPS16), linked with Lr57/Yr40 (T756) also co‐segregated with LrUmb/YrUmb. Seedling infection types differentiated LrUmb from Lr57. Absence of leaf rust‐susceptible segregants among F3 families of the intercross (IL 393‐4/T756) indicated repulsion linkage between LrUmb and Lr57. YrUmb expressed a consistently low seedling response under greenhouse conditions, whereas Yr40 expressed a higher seedling response. Based on the origin of LrUmb/YrUmb from the U genome and Lr57/Yr40 from the M genome, as well as phenotypic differences, LrUmb and YrUmb were formally named Lr76 and Yr70, respectively. These genes have been transferred to Indian wheat cultivars PBW343 and PBW550, and advanced breeding lines are being tested in state and national trials.
Hyperextension injuries of lumbar spine resulting in lumbosacral dislocation are a rare entity. We report a case of a 60-year-old male who presented to us in outpatient department with history of ...trivial fall from bicycle with fracture through the pedicles extending from L2 to L5 with lumbosacral dislocation with free floating posterior elements with intact neurology. This is the first case report of 4 level extension compression injury with lumbosacral dislocation leading to floating lumbar spine to the best of author’s knowledge. Treatment consists of reduction of the lumbosacral dislocation first and fusion of the disc space followed by reduction of the other fractures proximally. These injuries may present with a trivial trauma in spondylotic spine in elderly patients. MRI and CT scan should be done early to identify it, reduce and fix it, as in many cases with trivial trauma there may be no neural deficit.
In the utilization of lignocellulosic biomass, the hydrolysis of lignocellulose is playing a vital role because it decides the amount of glucose that is used for fermentation. Lignin present in ...lignocellulosic biomass is a major barrier to the effective utilization of their carbohydrate content. Pretreatment of biomass is an essential processing step for making efficient lignocellulose utilization. Polymeric sugars like cellulose and hemicellulose are converted to their corresponding monomers by chemical, physicochemical, and biological methods. Alkaline pretreatment is believed to cleave hydrolyzable linkages in lignin and glycosidic bonds of polysaccharides, which causes a reduction in the degree of polymerization, swelling of the fibers, as well as disruption of the lignin structure. The present paper describes the comparative view on the potential ability of untreated and alkali-treated wheat straw, bagasse, and groundnut shell waste in cellulase production. Application of XRD and FTIR analysis has also been used to compare the potentiality of lignocellulosic biomass. Higher FPase (1.29 ± 0.05 IU/mL) and CMCase (8.64 ± 0.15 IIU/mL) were observed with alkali-treated groundnut shell waste by
Aspergillus
strain. Alkali-treated raw materials were found quite effective for cellulase production as compared to untreated.
Selenium has been linked to cell survival and apoptosis. Apoptosis plays an important role in spermatogenesis. Evidence suggests that reactive oxygen species induce apoptotic pathways. Although the ...mechanism by which oxidants mediate apoptosis is not well defined, the mitogen-activated protein kinase (MAPK) and caspase pathways have been implicated in apoptosis. Thus, this study was designed, keeping in view the critical balance between cell proliferation and apoptosis for normal spermatogenesis, and the requirement of selenium for the maintenance of male fertility. The intracellular selenium status was modulated by feeding selenium-deficient and -excess diet for 8 weeks. Involvement of p38 MAPK and ROS was monitored. Apoptotic factors like caspases and Bcl-2 were also analyzed. It was observed that the selenium levels were altered along with an increase in ROS generation and lipid peroxidation. mRNA expression of p38, caspases 3, and 8 increased, whereas that for Bcl-2 decreased. Western immunoblot analysis and immunohistochemical localization studies for p38 showed a similar increase. Integrity of DNA was altered in the form of apoptotic cells. Thus, the results presented in this study suggest that sodium selenite causes apoptosis and the toxicity of selenite is mediated by increase in ROS. Morevoer, ROS generation is associated with increased expression of p38, caspases 3 and 8, and decreased Bcl-2 expression. Our data indicate that p38 participates in testicular apoptosis and that selenium is required for maintenance of the critical balance between cell death and proliferation.
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