Conectar
by Sukanya G. Gakare, Jay M. Bhatt, Kishore Kumar S. Narasimhan, Shashank M. Dravid
In this study, we investigated the role of glutamate delta 1 receptor (GluD1) in oligodendrocyte progenitor cell (OPC)-mediated myelination during basal (development) and pathophysiological (cuprizone-induced demyelination) conditions. Initially, we sought to determine the expression pattern of GluD1 in OPCs and found a significant colocalization of GluD1 puncta with neuron-glial antigen 2 (NG2, OPC marker) in the motor cortex and dorsal striatum. Importantly, we found that the ablation of GluD1 led to an increase in the number of myelin-associated glycoprotein (MAG+) cells in the corpus callosum and motor cortex at P40 without affecting the number of NG2+ OPCs, suggesting that GluD1 loss selectively facilitates OPC differentiation rather than proliferation. Further, deletion of GluD1 enhanced myelination in the corpus callosum and motor cortex, as indicated by increased myelin basic protein (MBP) staining at P40, suggesting that GluD1 may play an essential role in the developmental regulation of myelination during the critical window period. In contrast, in cuprizone-induced demyelination, we observed reduced MBP staining in the corpus callosum of GluD1 KO mice. Furthermore, cuprizone-fed GluD1 KO mice showed more robust motor deficits. Collectively, our results demonstrate that GluD1 plays a critical role in OPC regulation and myelination in normal and demyelinating conditions.by Farhana Boby, Md. Nurul Huda Bhuiyan, Barun Kanti Saha, Subarna Sandhani Dey, Anik Kumar Saha, Md Jahidul Islam, Mahci Al Bashera, Shyama Prosad Moulick, Farhana Jahan, Md. Asad Uz Zaman, Sanjana Fatema Chowdhury, Showti Raheel Naser, Md. Salim Khan, Md. Murshed Hasan Sarkar
The raising concern of drug resistance, having substantial impacts on public health, has instigated the search of new natural compounds with substantial medicinal activity. In order to find out a natural solution, the current study has utilized prodigiosin, a linear tripyrrole red pigment, as an active ingredient to control bacterial proliferation and prevent cellular oxidation caused by ROS (Reactive Oxygen Species). A prodigiosin-producing bacterium BRL41 was isolated from the ancient Barhind soil of BCSIR Rajshahi Laboratories, Bangladesh, and its morphological and biochemical characteristics were investigated. Whole genome sequencing data of the isolate revealed its identity as Serratia sp. and conferred the presence of prodigiosin gene cluster in the bacterial genome. “Prodigiosin NRPS”, among the 10 analyzed gene clusters, showed 100% similarity with query sequences where pigC, pigH, pigI, and pigJ were identified as fundamental genes for prodigiosin biosynthesis. Some other prominent clusters for synthesis of ririwpeptides, yersinopine, trichrysobactin were also found in the chromosome of BRL41, whilst the rest displayed less similarity with query sequences. Except some first-generation beta-lactam resistance genes, no virulence and resistance genes were found in the genome of BRL41. Structural illumination of the extracted red pigment by spectrophotometric scanning, Thin-Layer Chromatography (TLC), Fourier Transform Infrared Spectroscopy (FTIR), and change of color at different pH solutions verified the identity of the isolated compound as prodigiosin. Serratia sp. BRL41 attained its maximum productivity 564.74 units/cell at temperature 30˚C and pH 7.5 in two-fold diluted nutrient broth medium. The compound exhibited promising antibacterial activity against Gram-positive and Gram-negative bacteria with MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values ranged from 3.9 to15.62 μg/mL and 7.81 to 31.25 μg/mL respectively. At concentration 500 μg/mL, except in Salmonella enterica ATCC-10708, prodigiosin significantly diminished biofilm formed by Listeria monocytogens ATCC-3193, Pseudomonas aeruginosa ATCC-9027, Escherichia coli (environmental isolate), Staphylococcus aureus (environmental isolate). Cellular glutathione level (GSH) was elevated upon application of 250 and 500 μg/mL pigment where 125 μg/mL failed to show any free radical scavenging activity. Additionally, release of cellular components in growth media of both Gram-positive and Gram-negative bacteria were facilitated by the extract that might be associated with cell membrane destabilization. Therefore, the overall findings of antimicrobial, antibiofilm and antioxidant activities suggest that in time to come prodigiosin might be a potential natural source to treat various diseases and infections.by Kamonwan Chamchoy, Sirapapha Sudsumrit, Jutamas Wongwigkan, Songsak Petmitr, Duantida Songdej, Emily R. Adams, Thomas Edwards, Ubolsree Leartsakulpanich, Usa Boonyuen
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymopathy caused by mutations in the G6PD gene. A medical concern associated with G6PD deficiency is acute hemolytic anemia induced by certain foods, drugs, and infections. Although phenotypic tests can correctly identify hemizygous males, as well as homozygous and compound heterozygous females, heterozygous females with a wide range of G6PD activity may be misclassified as normal. This study aimed to develop multiplex high-resolution melting (HRM) analyses to enable the accurate detection of G6PD mutations, especially among females with heterozygous deficiency. Multiplex HRM assays were developed to detect six G6PD variants, i.e., G6PD Gaohe (c.95A>G), G6PD Chinese-4 (c.392G>T), G6PD Mahidol (c.487G>A), G6PD Viangchan (c.871G>A), G6PD Chinese-5 (c.1024C>T), and G6PD Union (c.1360C>T) in two reactions. The assays were validated and then applied to genotype G6PD mutations in 248 Thai females. The sensitivity of the HRM assays developed was 100% [95% confidence interval (CI): 94.40%–100%] with a specificity of 100% (95% CI: 88.78%–100%) for detecting these six mutations. The prevalence of G6PD deficiency was estimated as 3.63% (9/248) for G6PD deficiency and 31.05% (77/248) for intermediate deficiency by phenotypic assay. The developed HRM assays identified three participants with normal enzyme activity as heterozygous for G6PD Viangchan. Interestingly, a deletion in intron 5 nucleotide position 637/638 (c.486-34delT) was also detected by the developed HRM assays. G6PD genotyping revealed a total of 12 G6PD genotypes, with a high prevalence of intronic variants. Our results suggested that HRM analysis-based genotyping is a simple and reliable approach for detecting G6PD mutations, and could be used to prevent the misdiagnosis of heterozygous females by phenotypic assay. This study also sheds light on the possibility of overlooking intronic variants, which could affect G6PD expression and contribute to enzyme deficiency.by Jihun Ahn, HyeYon Yu, Seung-Woon Rha, Byoung Geol Choi, Dong Oh Kang, Cheol Ung Choi, Sangho Park, Jon Seo, Kichang Kim, Minung Kim, Yong Hoon Kim, Yong Seong Seo
This prospective, multicenter, randomized study aimed to compare the 1-year clinical outcomes after primary stenting with self-expanding bare metal nitinol stent (SENS) and plain old balloon angioplasty (POBA) in patients with critical limb ischemia (CLI) and below-the-knee (BTK) lesions. Overall, 119 patients with CLI and BTK lesions were randomized to POBA alone (POBA group, 61 patients) or primary stenting with SENS (stenting group, 58 patients) after achieving acceptable POBA results in target BTK lesions. Clinical outcomes including amputation and revascularization rates were prospectively compared for 1 year. After 1 year, similar incidence rates of individual clinical endpoints, including cardiac death (6.5% vs. 5.1%, p > 0.999), myocardial infarction (1.6% vs. 0.0%, p > 0.999), repeat revascularization (19.6% vs. 18.9%, p = 0.922), target lesion revascularization (13.1% vs. 17.2%, p = 0.530), and amputation (4.9% vs. 0.0%, p = 0.244), were observed. POBA appeared to have acceptable treatment outcomes compared with primary stenting with SENS after 1 year in CLI patients with BTK lesions undergoing percutaneous transluminal angioplasty (PTA).by Philipp Kanzow, Katharina Mielke, Franziska Haupt, Susanne Wiegand, Henning Schliephake, Dirk Beutner, Annette Wiegand
Oral health might not only act as risk factor for head and neck squamous cell carcinoma (HNSCC), but might also have a predictive value for the patients’ survival. Currently, information on the effect of oral health on survival of patients with different sites of HNSCC is lacking. This single-center retrospective study aimed to compare oral health in patients with different sites of HNSCC and to analyse whether oral health is associated with survival in the different subsets of HNSCC patients. Dental records of HNSCC patients referred for dental assessment prior to radio(chemo)therapy were included. Patient-related parameters (age at time of diagnosis, sex, tobacco exposure, alcohol consumption, HPV status), treatment data (primary treatment, intent), performance status, tumor demographics (anatomical site, TNM staging), and oral health parameters (DMFT, periodontal health, teeth with/without root canal treatment and with/without periodontitis apicalis) were obtained. Oral health parameters were compared between different anatomical sites. Survival of all HNSCC patients and of individual subsets was assessed using Kaplan-Meier statistics, and the effect of tumor demographics, patient-related parameters, and oral health on survival was analysed by cox regression analyses (α = 5%). 371 patients with HNSCC (oral: n = 86, oropharyngeal: n = 174, hypopharyngeal: n = 59, laryngeal: n = 15, other: n = 37) were included. Oral health parameters did not differ between subsets (padj.≥0.199). Five-year cumulative survival of HNSCC patients amounted to 78.6%. Only for HNSCC originating in the oral cavity and oropharynx, survival was associated with the treatment intent (p = 0.015) or performance status (p = 0.007) in the multivariable analyses, respectively. Within the limitations of this study, oral health was not different between different subsets and had no significant effect on survival of HNSCC patients.
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